ML20141J126
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NUCLEAR REGULATORY COMMISSION WASHINGTON. D.C. 90st44mt o% ****/ March 12, 1990 HEMORANDUM 10: Hugh L. Thompson, Jr., Deputy Executive Director for Nuclear Materials Safety, Safeguards and Operations Support -
Office of the Exocutive Director for Operctions FROM: David L. Morrison, Director
- Office of Nuclear Regulatory Research / 'l
SUBJECT:
REVISED FINAL RULEMAKING PACKAGE - CRITERIA FOR THE RELEASE Of INDIVIDVAI.S ADMINISTERED RADIOACTIVE MATERIALS (PARTS 20 AND 35)
Attached is the Commission paper and its attachments on tha subject final-rulemaking. TheRegulatoryAnalysis(RA)hasbeenrevisedinaccordancewith the recent ch- ges to the RA guidelines. Conforming changes have also been made to the ; ul Register Notice (FRN) and the Environmental Assessment (EA). There on the first p a,noand changes in the staff paper, except for adding a footnote other attachments. i i
i in the revised RA, the staff used $2,000 per person-rem instead of $1,000. In addition, the. staff used effective half-life instead of physical half-life.
Since effective half-life includes biological elimination, its use results in more realistic estimates of exposures to the patient's family members. In j fact, these ex)osures are now astimated to result in a collective dose which is about one t1ird of that previously estimated.
Specifically, as compared to the status quo, the savings in hospital costs was estimated at $14 million, whereas the collective dose would be increased by j about 2,700 person > rem which corresponds to a cost of about $5 million based on $2,000 per person-rem.
The revised cost-benafit analysis indicates that almost all patients who receive radiopharmaceutical therapy may be released from the hospital immediately if the physic 11:n elected to perform a case-specific calculation to show compliance with the dose-based release criteria. Any individual associated with the patient's family would be unlikely to receive a dose of ;
500 mrem within a year.
Marked up sheets of the FRN, RA, and EA showing significant changes are attached under " BACKGROUND."
i Attachments:
- 1. Commissior. paper w/atts & disk
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4 fQB: 1he Commissioners l
[RQM: James M. Taylor Executive Director for Operations SUBJECT': FINAL AMENbMENTS TO 10 CFR PARTS 20 AND 35 ON CRITERIA FOR THE RELFASE OF INDIVIDUALS ADMINISTERED RADIOACTIVE HATERIAL PURPOSE:
To obtain Commission approval to publish a notice of final rulemaking in the fedeyal e Register.
BACKGROUND':
On May 21,1991 (56 FR 23360), the NRC published a final rule that amended 10 CFR Part 20, " Standards for Protection Against Radiation." The rule, contained a dose limit of 1 millisievert (0.1 rem) total effective dose equivalent for members of the public in 10 CFR 20.1301(a). When 10 CFR Part 20 was issued, there was no discussion in the supplemental information or, whether or how the provisions of 10 CfR 20.1301 were intended to apply to the release of patients.
' The subject paper was submitted to the Commission on November 30, 1995 (SECY 95-286). Subsequently, the staff requestad withdrawal of the paper to revise the regulatory analysis (RA) to conform with the new RA guidelines. In a Staff Requirements Memorandum dated December 21, 1995, the Commission granted the request. The staff revised the RA (a summary of major changes is attached to the RA) and made conforming changes to the federel Register Notice (FRN) and _
the Environmental Assessment (EA). These revisions did not affect the content of this staff paper except in items 1 and 5 of the DISCUSSION in which the staff mentioned the expanded discussions of breast-feeding women in the RA.
CON 1 ACTS:
Stewart Schneider, RES 415-6225 Stephen A. McGuire, RES 415-6204
.m.
The Commissioners 2 NRC's current patient release criteria are contained in 10 CfR 35.75, " Release of patients or human research subjects containing radiopharmaceuticals or f permanent implants." That section states: "(a) A licensee may not authorize i
release from confinement for medical care any patient or human research sebject administered a radiopharmaceutical untti either: (1) 1he measured dose rate from the patient or human research subject is less than 5 millirems per hour at e distance of 1 metart or (2) The activity in the patient or human research subject is less than-30 n..ill;ca.;est (b) A licensee may not authorize release from confinement for medical care of any patient nr human research subject administered a permanent implant until the measured dose rate from the patient or the human research subject is less than 5 millirems per hour at a dittance of I meter.'
Some licensees were uncertain about the effect that the revised 10 CFR Part 20 would have on patient release criteria, and three petitions for rulemaking were received on the issue ' To resolve this uncertainty, two steps were taken.
The short-term resolution was to inform licensees of the NRC's position that 10 CfR 35.75 governed patient release. The Commission was informed in SECY-94-01 of the staff's recommendation that 10 CFR 35.75 governs patient release. Information Notice No. 94-09 was issued on February 3, 1994, to inform licensees of this position in accordance with a Staff Requirements Memorandum (SRM) dated January 28, 1994.
The longer term resolution was to address this issue through rulemaking, and a proposed rule was published for comment on June 15, 1994 (59 FR 30724). The proposed rule was transmitted to the Commission in SECY-94-054 and responses to questions raised by the Office of the inspector General are contained in SECY-94-054A.
EjSCUSSION:
The final rule (Attachment 1) takes into consideration the recommendations of the Agreement States, as well as the comment letters received on the proposed rule and the petitions, in all, 232 comment letters were received on the three petitions, and 63 comment letters were received on the proposed rule.
1he rule was also discussed with the Advisory Committee on Medical Uses of Isotopes (ACMUI) at several public meetings, the last on October 18 and 19, 1995.
The following summarizes the main features of the amendments:
' One commenter raised an issue abt,ut contacts allegedly relating to this rulemaking petween one of the petitioners and the Office of the Chairman. The staff notes that the final rule is based on the public record associated with the rulemaking and that the NRC decision maker with whom contact was made is no longer with the Commission. The staff has not included any further comment with respect to this issue in the final rulemaking package.
The Commissior. ors 3
- 1. The major changes to the final rulemaking are: (1) significant expansion of the discussion on breast-feeding in the Statement of Considerations and the regulatory analysis and (2) explicit use of the term " breast-feeding" in the final rule text to make it clear that breast-feeding women are a class of patients requiring additional '
records and instructions to limit the dose to the breast-feeding child.
The subject of brce.t-fteding was mentioned in the Statement of Considerations to the proposed rule but not in the proposed rule text.
- 2. The amendments make it clear that patient release is governed by 10 CFR 35.75 rather than by 10 CFR 20.1301(a). There was very broad agreement with this position in the comment letters, with ACMul, and with :he Agreement States. i
- 3. The amendments revise the criteria for release of patients administered radioactive material for medical use under 10 CfR 35.75 to permit a maximum likely total effective dose equivalent of 5 millisieverts !
(0.5 rem), excluding background or any occupational exposure, to en individual exposed to the patient. ,
S)ecifying the release criterion in terms of radiation dose requires t1at the NRC provide an acceptable method that relates the quantity of radioactivity administered to that dose. That relationship will be included in a regulatory guide. A working draft of that guide is attached (Attachment 2); the staff is still reviewing the guide, but will publish it in final form before the final rule becomes effective.
The guide presents two methods to relate dose to quantity of
-radioactivity administered. The first method is the use of a default table of release quantities and release dose rates based on conservative assumptions. for the radioactive material of greatest significance, iodine-131, the default table is essentially equivalent to the release criteria in the current regulations. The staff anticipates that nearly all patients will be released based on the default table of activities.
The second method is to perform a case-specific dose calculation using the method described in the guide. The case-specific method can be less conservative than the default table because it permits a more realistic estimate of how quickly the radioactive material leaves the patient's body. Thus, use of this method would, in some cases, permit the release of patients containing several times more radioactive material than the current regulations permit or allowed with use of the default table.
The authorization to release a patient is based on the licensee's determination that the tutal effective dose equivalent to an individual from the released patient is not likely to exceed 5 millisieverts (0.5 rem). The dose to the breast-feeding child from breast-feeding is not necessarily a criterion for release since it can be controlled by giving the woman guidance on the interruption of breast-feeding, as required by the amendments (see No. 5).
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! , 4 1he Commissioners 4 Overall, a substantial majority of all comments supported an explicit ,
dose limit of 5 millisieverts (0.5 rem) for individuals exposed to patients released with radioactive material in their bodies, in addition, ACMUI and the Agreement States sup>orted the criterion based on a dose limit. A few commenters who thoug1t that the present criteria ;
were working well and were adequate, opposed allowing the release of patie..t. it. quantities of radioactive material greater than that permitted under the current regulations.
- 4. The proposed rule would have required licensees to maintain, for 3 years, a record of the basis for the patient's release and the total effective dose equivalent if any individual is likely to receive a dose in excess of 1 mil 11 sievert (0.1 rem) in a year from a single administration. This requirement was proposed so that records would be available to calculate the dose if a patient received multiple administrations in a year.
This proposed recordkeeping requirement met a great deal of opposition.
Commenters were especially concerned about having to retrieve records of previous administrations, sometimes from another medical facility. Upon reconsideration, it was decided to delete this requirement because a review of nuclear medicine procedures indicated that there was no significant itkelihood of exceeding a 5-millisievert (0.5-rem) annual dose because of multiple administrations. '
In place of the deleted recordkeeping requirement, the final rule contains requirements to maintain: (1) a record for the basis of the release for a limited number of certain radiopharmaceutical administrations (e.g., therapeutic administrations of iodine-131) and (2) a record that instructions were provided to a breast-feeding woman if the administered activity could result in a total effective dose equivalent to the breast-feeding child exceeding 5 millisieverts (0.5 rem) if the woman did not interrupt breast-feeding. The requirements'(in 10 CFR 35.75(c) and (d)) would af feet about 20,000 of the 8 to 9 million administrations done annually.
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- 5. The amendments require that the patient be given instructions, including written instructions, on how to maintain doses to others as low as is reasonably achievable if the dose to an individual is likely to exceed I mill 1 sievert (0.1 rem). In general, most commenters agreed with this ,
requirement, although a few did not think that instructions should '
necessarily have to be written, l The proposed rule had a requirement to provide instructions which would l include guidance on breast-feeding children, but some commenters wanted information on when instruction would_have to be given and what the instructions should say about interruption or cessation of breast .
feeding. The final rule requires that guidance regarding interruption l of breast-feeding and consequences be provided if the released i individual may be breast-feeding an infant or child and the total i effective dose equivalent is likely to exceed I millisievert (0.1 rem).
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l The Comissioners 5 lhe regulatory guide will contain interruption periods that keep the, dose from breast-feeding to 'ess than 1 millistevert (0.1 rem). The purpose of describing the consequences is so that women will understand that breast-feeding after an administration of certain radionuclides could cause harm in other cases, the g(e.g., iodine-131 uidance cculd could sim)1y harmavoidance address the child'softhyroid),
any
. r ecessary radiation exposure to tie child from breast-feeding. The regulatory analysis indicates the basis for selecting the option of i
enhancing communications and instructions to breasting-feeding women.
6.
The amendments make it clear that the limit on dose in unrestricted areas ) resented in 10 CFR 20.1301(a)(2) does not include dose contriautions from patients administered radioactive material and released in accordance with 10 CFR 35.75. The purpose of this change is to clarify that licensees are not responsible for doses outside of their restricted areas from radiation sources not under their control. The comments supported this pcsition.
The final amendments represent a partial granting of the regulatory relief requested by the petitioners. The request to delete 10 CFR 20.1301(d), was denied because the reference to the Environmental Protection Agency's regulations in 10 CFR 20.1301(d) has nothing to do with the patient release issue. Also, the request to permit licensees to authorize release from hospitalization any patient administered a radiopharmaceutical regardless of the activity in the patient by defining " confinement" to include not only confinement in a hospital, but also confinement in a private residence was denied. The staff considers it inadvisable to use a patient's home for the purpose of confinement when the activity in the patient is expected to result in a dose exceeding 5 millisieverts (0.5 rem) to another individual.
At its last meeting, held on October 18 and 19, 1995, the ACMU1 passed several motions suggesting changes to three aspects of the rule, first, the ACMUI suggested using the term " rationale" instead of
" consequences" in the requirement, under 10 CFR 35.75(b), to provide " guidance on the interruption of breast feeding, and information on the consequences of failure to follow the guidance" for cases where failure to follow the
-instructions could result in a dose to the infant exceeding 1 millistevert (0.1 rem). Since most of the administrations that would be affected by this requirement are technetium-99m administrations, the ACMUI suggested the change because there was concern that the consequences of low doses of radiation cannot always be explained to the patient without causing unjustified alarm.
Also, there was concern that physicians cannot explain with certainty the effects of low doses of radiation, such as would be caused by diagnostic administrations of technetium-99m. The staff did not change the rule in response to the ACHUI comment, because the requirement to provide information on the consequences is included to primarily protect the breast-feeding infant from therapeutic administrations of radiotodine, which could cause serious thyroid damage. Regulatory Guide 8.39 will contain guidance on the types of information, including expected consequences, to be provided to patients to meet this requirement.
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The Commissioners 6 Second, the ACHUI suggested using the phrase "the retained activity rather than the activity administered" instead of "an activity other than the activity administered" in the requirement under 10 CFR 35.75(c), to maintain a record of the basis for authorizing the release of an individual, if the total effective dose equivalent is calculated. The ACHUI was concerned that the meaning was not clear, and in addition, the requirement was already implicit In the remainder of the recordkeeping requirements in 10 CFR 35.75(c). The staff changed the rule in response to the ACHUI comment. This information would be needed for cases where a patient would be held for some time period prior to release. Such cases would not be covered in the default release table that a) pears in the regulatory guide. In this case, a record is needed to confirm t1at the licensee has released the individual in accordance with the limit in Part 35. Regulatory Guide 8.39 will provide guidance on cases where such records will be needed for release.
Third, the ACMUI suggested that the term
- discontinuation" should be used in
, conjunction with " interruption" in the requirement to )rovide " guidance on the interruption of breast-feeding" if failure to follow tie instructions could result in a dose to the infant exceeding 1 mil 11 sievert (0.1 rem). The ACHUI suggested the change because they said that there is a distinct difference between the two terms. The staff changed the rule in response to the ACMui comment. As stated in the Federal Register notice, "the instructions must include guidance on the interruption period for breast-feeding." Table 2 in the guide gives interruption periods for various radiopharmaceuticals which can be temporary (48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br /> or less) in some cases, or discontinuation (no resumption) when necessary.
Finally, the ACMUI recommended that the Commission proceed with the rule as promptly as possible.
RESOURCES:
Resources needed to conduct and implement this rulemaking are included in the FY 1995-1999 Five-Year plan.
C0 ORDINATION:
The Office of the General Counsel has no legal objection to this paper.
RECOMMENDATION:
That the Commission:
- 1. 6pprove the notice of final rulemaking for publication (Attachment 1).
- 2. Certify that this rule will not have a significant economic impact on a substantial number of small entities; such certification will satisfy requirements of the Regulatory Flexibility Act, 5 U.S.C. 605(b).
The Commissioners 7
- 3. Notes:
- a. The final rule will become effective 120 days af ter publication in the Federal Reaister.
- b. A final regulatory guide will be published, for use, befen tho final rule becomes effective (Attachment 2). I
- c. A final regulatory analysis will be available in the Public 1 Document Room (Attachment 3). !
- d. A final environmental assessment and a finding of no significant I impact have been prepared (Attachment 4),
- e. The Chief Counsel for Advocacy of the Small-Business Administration will be informed of the certification-regarding economic impact on small entities and the reasons for it as required by the Regulatory Flexibility Act.
- f. The ap)ropriate Congressional Committees will be informed (Attac1 ment 5);-
g.- A public announcement will be issued (Attachment 6).
- h. The rule contains information collection requirements that are subject to review by the Office of Management and Budget. Upon Commission approval, the OMB supporting statement (Attachment 7) will be submitted to OMB for approval,
- i. Copies of the Federal Reaister notice of final rt.lemaking and the associated regulatory guide will be distributed to all NRC medical licensees and each Agreement State. The notice will be sent to other interested parties upon request.
James M. Taylor Executive Director for Operations Attachments:. As Stated (7) 4
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The Commissioners 7
- 3. t{o h : ,
- a. The finai rule will become effective 120 days after publication in the [Idfral Reaister.
- b. A final regulatory guide will be publisl.cd, fo use, before the final rule becomes effective (Attachment 2),
- c. A final regulatory analysis will be available in the Public Document Room (Attachment 3),
- d. A final environm 1tal assessment and a finding of no significant Impact have been prepared (Attachment 4).
- e. The Chief Counsel for Advocacy of the Small Business Administration will be informed of the certification regarding economic impact on small entities and the reasons for it as required by the Regulatory Flexibility Act,
- f. The appropriate Congressional Committees will be informed (Attachment 5);
9 A public announcement will be issued (Attachment 6),
- b. The rule contains information collection requirements that are subject to review by the Office of Management and Budget. Upon Commission approval, the OMB supporting statement (Attachment 7) will be submitted to OMB for approval,
- i. Copics of the federal Reatster notice of Gnal rulemaking and the associated regulatory guide will be distributed to all NRC medical licensees and each Agreement State. The notice will be sent to other interested parties upon request, James M. Taylor Executive Director for Operations Attachments: As Stated (7)
RECORD N01[: A draft of sne final rule was sent to OlG for information on May 31, 1995.
- see previous to c1 Offc: RP RA iP A RPHEB:0RA 0:0RA: #M . ADM Name: IMder F duit cdlllGlenn BMorri C#a,/96'riep [ D:SP RBangart WO11u Date: 3 1/96 3/11/96 )3/119 g 3/ll/96 3pu 6/13/95* 6/05/95*
Offc: 0:IRM OC 0:0E 0:RES E00 Name: GLranford PScroggins Sire y JLeiberman DMorrisTn JMTaylor Date: 6/07/95* 6/08/95* 3/11/96 6/06/95* 3/11/96 / /96 OfflCIAL RECORD COPY RES FILE NO. 3A-3
1he Commissioners 7
- d. A final environmental assessment and a finding of n'o significant impact have been prepared,(Attachment 4),
- e. The Chief Counsel for Advocacy of the Small Business
. Administration will be informed of the certification regarding
. . . economic impact on smail enuttes and the reasons for it as required by the Regulatory Flexibility Act.
- f. The appropriate Congressional Committees will be informed (Attachment 5);
l 9 A pubile announcement will be issued (Attachment 6).
- h. The rule conthins information collection requirements that are l subject to review by the Office of Management and Budget. Upon Commission approval, the OMB supporting statement (Attachment 7) will be submitted to OMB for approval.
- i. Copies. of the [ederal Reatster notice of final rulemaking and the associated regulatory guide will be distributed to all NRC medical
. itcensees and encl- Agreement State. Tho' notice will be sent to other interested parties upon request.
Original Signed By Hugh L. Thompson, Jr.
for James H. Taylor Executive Director for Operations Attachments: As Stated (7)
RECORD NOTE: A draf t of the final rule was sent to OlG for information on May 31, 1995.
- see previous concurrence Offe: RPHEB:0RA RPHED:0RA RPHED:0RA 0:0RA:RES 0:NHSS 0:SP ADM Name: SSchneider SMcGuire JGlenn BMorris CPaperiello RBangart WO11u Date: 6/08/95* 6/08/95* 6/09/95* 6/14/95* 6/13/95* 6/13/95* 6/05/95*
Offc: 0: IRM - OC OGC 0:0E 0:RES E00 Name: GCranford pScroggins MMaisch JLieberman 0Morrison JMTaylor Date: 6/07/95* 6/08/95* 6/08/95* 6/06/95* 6/14/95* H /h /95 0FFICIAL RECORD COPY RES IILE N0.3A 3
4 e
lhe Commissioners 5 1
- b. A final regulatory analysis will be available in the Public Document Room (Attachment 3);
- c. A final environmentas assessment and a finding of no significant impact have been prepared (Attachment 4)i
- d. The Chief Counsel for Advocacy of the Small Business Administration will be informed o Lhe certification regarding economic impact on small entiti and the reasons for it as required by the Regulatory flex 111ty Act;
- e. Therulecontainsinformati collection requirements that are subjecttoreviewbyOMB./UponCommissionapproval,theOMB supporting statement (Attachment 7) will be submitted to OMB for approval.
- f. The ap)ropriate Congressional Committees will be informed (Attarament 5); /
- g. A public annouptement will be issued (Attachment 6); and
- h. Copies of tpc Federal Register Notice of final rulemaking and the associate 4/ regulatory guide will be distributed to all Commission medical , licensees and each Agreement State. The notice will be sentto/otherinterestedpartiesuponrequest.
/
/
/ James M. Taylor
/ Executive Director
/ for Operations Attachd ts: As Stated (7)
/
/
RECORDNpTE: A draft of the final rule was sent to 0!G for information on May 31, 1995.
dJud a Offe tl DRA R{. ( DRA 0:0RA:@WKN 0:SPM 0:NMSS CPapertello RBangart ADM dL M Name: SSchpeider SMc ire i n BMorrt W0liu % hlod Date:
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[//3/95 6//f/95 (, g/95 Of fc: 0:lRM OCh'/fd&OGCb'EP 0:0E 47b Jtieberman DMorrionI JMTaylor Di i E00 Name: GCranford _PScroggins MMalsch Date: 6 / 7 /95 /3/f/95 (; /i /95 ' / (, / 95 f /pf 95 / /95 gbhtd
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l ATTACHMENT - I FEDERAL REGISTER NOTICE
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NUCLEAR REGULATORY COMMISSION 10 CFR Parts 20 and 35 RIN 3150-AE41 Criteria for the Release of Individuals Administered Radioactive Material AGENCY: Nuclear Regulatory Commission.
ACTION: Final rule.
SUMMARY
- The Nuclear Regulatory Commission (NRC) is amending its regulations concerning the criteria for the release of patients administered radioactive material. The new criteria for patient release are based on the potential dose to other individuals exposed to the patient. The new criteria are consistent with the iecommendations of the National Council on Radiation Protection and Measurements (NCRP) and the international Commission on Radiological Protection (ICRP). This final rule requires the licensee to provide written instructions to patients on how to maintain the doses to others as low as is reasonably achievable if the total effective dose equivalent to any other individual exposed to the released patient is likely to exceed 1 millistevert (0.1 rem). This final rule responds to three petitions for rulemaking regarding the criteria for release of patients ,
administered radioactive material.
EFFECTIVE DATE: (120 days following publication in the Federal Register).
1 ADDRESSES: Copies of Regulatory Guide 8.39, " Release of Patients Administered
. Radioactive Materials"; the final regulatory analysis, NUREG-1492, " Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material" (1996); Revision 2 of NUREG/BR-0058, " Regulatory Analysis Guidelines of the U.S. Nuclear Regulatory Commission" (1996); and the public co.wents received on the proposed rule may be examined and copied for a fee-in the Commission's Public Document Room at 2120 L Street NW. (Lower Level),
Washington, DC. Sir.gle copies of Regulatory Guide 8.39 may be obtained free-of charge by writing the Office of Administration, Attn: Distribution and Services Section.- USNRC, Washington, DC 20555, or by fax at -(301) 415-2260.
Single copies of NUREG-1492 and NUREG/8R-0058 may be purchased at current rates from the U.S. Government Printing Office, P.O. Box 37082, Washington, DC 20402-9328 (telephone (202) 512-1800); or from the National Technical Information Service at G285 Port Royal Road, Springfield, VA 22161.
FOR FURTHER INFORMATION CONTACT: Stewart Schneider or Stephen A. McGuire, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission.
Washington, DC 20555, telephone (301) 415-6225.
- l. Background Each year in the United States, radioactive pharmaceuticals or compounds or. radioactive implants are administered to approximately 8 to 9 million individuals for the' diagnosis or treatment of disease or for human research.
lhese individuals to whom radioactive materials have been administered are 2
hereinafter referred to as " patients.* These patients can expose others around them to radiation until the radioactive material has been excreted from their bodies or the radioactivity has decayed away.
t NRC's current patient release criteria in 10 CFR 35.75, " Release of patients or human research subjects containing radiopharmaceuticals or permanent implants," are as follows:
"(a) A licensee may not authorize release from confinement for medical care any patient or human research subject administered a radiopharmaceutical until either: (1) The measured dose rate from the patient or human research subject is less than 5 millirems per hour at a distance of 1 meter; or (2) The activity in the patient or human research subjact is less than 30 millicuries; (b) A licensee may not authorize release from confinement for medical care of any patient or human research subject administered a permanent implant until the measured dose rate from the patient or human research subject is less than 5 millirems per hour at a distance of 1 meter."
On May 21,1991 (56 FR 23360), the NRC published a final rule that amended 10 CFR part 20, " Standards for Protection Against Radiation." The rule contained limits on the radiation dose for members of the public in 10 CFR 20.1301. However, when 10 CFR part 20 was issued, there was no discussion in the supplementary information on whether or how the provisions of 10 CFR 20.1301 were intended to apply to the release of patients.
Some licensees were uncertain about what effect the_ revised 10 CFR part 20 would have on patient release criteria, and two petitions for rulemaking were received on the issue. On June 12, 1991 (56 FR 26945), the NRC published in the Federal Register a notice of receipt of, and request for 3
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comment on, a petition for rulemaking (PRM-20-20) from Dr. Carol S. Marcus, in addition, Dr. Marcus submitted a letter dated June 12, 1992, further characterizing her position.
On March 9,1992 (57 FR 8282), the NRC published a notice of receipt and request for comment in the Federal Register on another petition for rulemaking (PRM-35-10)_on patient release criteria from the American College of Nuclear Medicine (ACNM). On May 18, 1992 (57 FR 21043), the NRC published in the Federal. Register notice of an amendment submitted by the ACNM-to its original petition (PRM-35-10A).
In addition, a third petition (PRM-35-11) dealing, in part, with these same issues was submitted by the American Medical Association (AMA). That petition was noticed in the-Federal Register on July 26, 1994 (59 FR 37950).
The main point raised in the petition was that the radiation dose limits in 10 CFR part 20 should not apply to individuals exposed to the patient and that the dose limit to the individuals should be 500 millirems per year. The AMA believed that 10 CFR 20.1301 would have an adverse impact on the availability and the cost of treatment of thyroid disease, .which would outweigh the advantages of reduced radiation exposure to the public. The AMA stated that treatment of up.to 10,000 cancer patients annually for thyroid carcinoma would I require the hospitalization of the patients under the revised regulation
-(10 CFR 20;1301), reducing both early release of patients and the treatment of 4 patients at home.
- 11. publication of the Proposed Rule On June 15, 1994 (59 FR 30724), the NRC published a proposed rule on criteria for the release of patients administered radioactive material in response to the first two petitions. The proposed rule discussed the public I comment letters received on the first two petitions.. Three additional comment letters were received on the third petition (PRM-35-ll). These letters each supported the petition but did not contain any additional information not covered by the letters on the first two petitions.
The NRC proposed to amend 10 CFR 20.1301(a)(1) tn specifically state that the dose to individual members of the public from a licensed operation does not include doses received by individuals exposed to patients who were released by the licensed operation under the provisions of 10 CFR 35.75. This was to clarify that the Commission's policy is that patient release is governed by 10 CFR 35.75, not 10 CFR 20.1301.
The NRC proposed to amend 10 CFR 20.1301(a)(2) to specifically state that the limit on dose-in unrestricted areas does not include dose contributions from patients administered radioactive material and released in accordance with 10 CFR 35.75. The purpose was to clarify that licensees would not be required to centrol areas (such as waiting rooms) simply because of the presence of a patient released pursuant-to 10 CFR 35.75, if a patient has
' been released from licensee control pursuant to 10 CFR 35.75, licensees would not be required to limit the radiation dose from a patient to members of the pubite (e.g., visitors in a waiting room) to 0,02 millistevert (2 millirems) in any I hour. Patient waiting rooms or hospital rooms would need only be 5
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controlled for those patients not meeting the release criteria in 10 CfR part 35.
The NRC proposed to adopt a new 10 CFR 35.75(a) to change the patient
! release criteria from 1,110 megabecquerels (30 millicuries) of activity in.a i
patient or a dose rate of 0.05 millisievert (5 millirems) per hour at 1 meter from a pattent to a total effective dose equivalent not to exceed 5 millisieverts (0.5 rem) in any 1 year to an individual from exposure to a j released patient. A dose-based limit provides a single limit that could be :
used to provide an equivalent level of risks from all radionuclides. Also, the proposed changes were supported by the recommendations of the ICRP and the NCRP that an individual could be allowed to receive an annual dose up to 5 millisieverts (0.5 rem) in temporary situations when exposure to radiation is not expected to result in annual doses above 1 millisievert (0.1 rem) for long periods of time.
The NRC proposed to adopt a new 10 CFR 35.75(b)(1) to require that the licensee proside released patients with written instructions on how to maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any individual other than the released patient is likely to exceed 1 millisievert (0.1 rem) in any 1 year. A requirement to give instructions to certain patients was already contained in 10 CfR 35.315(a)(6) and 35.415(a)(5), but the proposed requirement would also require instructions for an additional 50,000 individuals who are administered iodine-131 for the treatment of hyperthyroidism and anotht-r 27,000 individuals who are breast-feeding and administered various diagnostic and therapeutic radioactive materials. The purpose of the instructions is to maintain doses to individuals expt ad to patients as low as is reasonably achievable.
6 4
)
l i
lhe NRC proposed to adopt a new 10 CfR 35.75(b)(2) to require that licensees maintain, for 3 years, a record of the released patient and the i calculated total effective dose equivalent to the individual likely to receive the highest dose if the total effective dose equivalent to any individual other than the released patient is likely to exceed I mil 11 sievert (0.1 rem) in a year from a single administration. The major purpose was to provide a record to allow licensees to assess the need to limit the dose to individuals exposed to a patient who may receive more than one administration in a year.
Finally, the NRC proposed to amend its requirements on instructions in 10 CFR 35.315(a)(6) and 35.415(a)(5). These regulations already required instructions (not necessarily written) in certain cases, but the phrase "if required by i 35.75(b)" was added to each. The purpose of this change was to make Part 35 consistent as to when instructions must be given, in addition, the NRC concurrently issued an associated draft regulatory guide and supporting draft regulatory analysis for public comment. The draft regulatory guide, DG-8015, " Release of Patients Administered Radioactive Materials," proposed guidance on determining the potential doses to an individual likely to receive the highest dose from exposure to a patient and established appropriate activities and dose rates for release of a patient.
The draft guide also proposed guidelines on instructions for patients on how to maintain doses to other individuals as low as is reasonably achievable and it described recordkeeping requirements, The draft regulatory analysis, NUREG-1492, " Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material" (May 1994), examined the benefits and impacts of the proposed rule considered by the NRC.
7
t I -
111. Public Comments on the proposed Rule A total of 63 comment letters were received on the proposed rule, the draf t regulatory guide, and the draf t regulatory analysis. A majority of the comment letters were f rom medical practitioners and medical organizations, but
f there were also connent letters from private individuals, public-interest i
groups, and regulatory agencies in Agreement States. Overall, the majority of comment letters supported a dose limit of 5 millisieverts (0.5 rem) for individuals exposed to patients released with radioactive material. However, about one-fourth of the comment letters opposed the proposed recordkeeping requirement. The significant comments are discussed below, arranged by subject.
EXCLUSION Of pAllENT RELEASE FROM i 20.1301(a)
All the commenters except one supported governing patient release by the regulations in 10 CFR 35.75 and excluding the dose to individuals exposed to a released patient from 10 CFR 20.1301(a).
Comment. One commenter, representing a public-interest group, objected to any exposure of a member of the general public who has not consented freely to the dosage. They said that such exposure would lead to widespread morbidity and mortality.
Response, in its revision of 10 CFR part 20 (56 FR 23360; May 21, 1991), the NRC determined that, while doses should be maintained as l
low as is reasonably achievable, a dose limit of 1 mil 11 sievert (0.1 rem), or 1 8
4
a dose limit of 5 millisteverts (0.5 rem) in certain special circumstances, provides adequate protection. The revised Part 20 is based, in part, upon the recommendations of the International Commission on Radiological Protection (ICRP) and the recommendations of the National Council on Radiation Protection and Measurements (NCRP). The NCRP recommends public dose limits of -
1 millisievert (0.1 rem) for continuous or frequent exposure and 5 millisieverts (0.5 rem) for infrequent exposure.
The ICRP recommends that the limit for public exposure should be expressed as an effectivo dose of 1 mil 11 sievert (0.1 rem) in a year, except that.-in special circumstances, the dose could be higher in a single year provided the average over 5 years does not exceed 1 millisievert (0.1 rem) per year. In ICRP Publication 60, in defining medical exposure, ICRP stated that medical exposure includes " exposures (other than occupational) incurred knowingly and willingly by individuals helping in the support and comfort of patients undergoing diagnosis or treatment." Furthermore, in explaining dose limits in medical exposure, the ICRP stated in the same publication that the Commission therefore recommends that dose limits should not be applied to medical exposures." Thus, in ICRP's opinion, family members who are helping in the support and comfort of patients would not be restricted under the dose limit stated above.
The revision of Part 20 incorporated the long-term objective as the dose limit and included a provision (i 20.1301(c)) to allow for alternative limits on an occasional basis. Section 20.1301(c) provides that an annual dose of up to 5 millisieverts (0.5 rem) is acceptable if there is a need for it and if steps are taken to red' ice the dose to as low as is reasonably achievable. The NRC reaffirms that previous detcrmination in this rulemakir.g.
9 5
in the case of released patients, it would be unlikely for a single individual exposed to a patient to receive a dose in a year of over 1 millisievert (0.1 rem) because large therapeutic doses (greater than 3,700 megabecquerels (100 millicuries)) are rarely adm_inistered more than once to the same patient in a given year. ' -
Coswent. One commenter said that the NRC should change the 0.1 rem dose limit for the public in 10 CFR 20.1301(a)(1) to 0.5 rem for all licensed activities because a dose limit of 0.5 rem offers adequate protection and is a dose that has no proven effects.
Response. This issue of the general public dose limit is outside the scope of this rulemaking. The issue was dealt with when 10 CFR part 20 was recently revised (56 FR 23360; May 21, 1991). That rulemaking explained the NRC's rationale for adopting the 1-millisievert (0.1-rem) dose limit in 10 CFR 20.130)(a)(1).
ACTIVITY-BASED VS. DOSE-BASED RELEASE LIMIT The issue is whether to retain the current patient release limit in 10 CFR 35.75, which is expressed as an activity limit together with an alternative but approximately equivalent limit on dose rate at 1 meter, or to express the release limit as a dose to an individual exposed to the patient.
The majority of commenters supported the dose-based limit. However, some commenters opposed the dose-based approach.
10 y
\
Comment. A nnmber of commenters said that 10 CFR 35.75 should not be changed and that the 30 millicurie or 5 millirem per hour release criteria should be retained because they are working well. Some commenters said that a dose-based release limit as proposed would.cause confusion and potential problems. One commenter said that the Part 20 revision: was not intended to alter the status quo for patient release. Commenters objected to the dose-based release limit because they thought the dose estimates to the public would be very inaccurate as these estimates are based on the unreliable method of predicting the anticipated time and proximity to others. Commenters also said that dose estimation and the subsequent recordkeeping would be time consuming and would add to the cost of treatment without a probable significant decrease in radiation exposure.
Response. The NRC is adopting a dose-based limit rather than an activity-based limit because the dose-based limit better expresses the NRC's primary concern for the public's health and safety. A single activity requirement was not retained because different radionuclides with the same activity can give very different doses under identical exposure conditions.
'ikewise, a single dose rate requirement for all radionuclides was not retained because different radionuclides with the same dose rate, at the time of releast. can give very different doses depending upon the half-life of the radionuclide. The total dose depends on the effective half-life of the radioactive material in the body of the patient and other factors that var 3 for different materials. For these reasons, the NRC is establishing a dose limit rather than an activity or dose rate limit.
11 4
5 I
1ho NRC is establishing a dose limit of 5 millisteverts (0.5 rem) total effective dose equivalent to an individual from exposure to the released patient for each patient release. This dose limit is consistent with the underlying risk, basis of the current 10 CFR 35.75 (50 FR 30627; July 26, 1985), the recommendations of the #003 ..d -tl.e ICRP, and the provisions in 10 CFR 20.1301(c) pertaining to temporary situations in which there is
. justification for a dose limit higher than 1 mil 11 sievert (0.1 rem).
The NRC believes that the dose-based release limit can and will work j well because the associated Regulatory Guide 8.39, " Release of Patients 1
. Administered Radioactive Materials," can be used to relate the dose to the quantity of activity in the patient. The guide provides conservative estimates of activities for commonly used radionuclides and their corresponding dose rates with which a patient may be released in compliance with the dose limits ir '3:: ft: 1 rule. The approach used in the regulatory guide is based on NCRP Report No. 37, ')recrutions in the Management of Patients Who llave Received 1herapeutic Amounts of Radionuclides."' In the case of iodine-131, the most significant radionuclide, the release quantity based on the standard conservative assumptions is 1,221 megabecquerels (33 millicuries), which is essentially the same as the current release quantity.
NUREG-1492 contains a detailed extmination of the benefits and impacts of the final rule that includes dose est :ation, recordkeeping, and radiation exposure. Single copies of the final regulatory analysis and Regulatory Guide 8.39, " Release of Patients Administered Radioactive Materials," are available as indicated in the ADDRESSES heading.
e ' National Council on Radiation Protection and Measurements (NCRP),
" Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides," NCRP Report No. 37 (October 1, 1970). (Available for sale from the NCRP, 7910 Woodmont Avenue, Suite 800, Bethesda, MD 20814-3095.)
12
1 3
i i
Comment. A commenter said that the calculational approach in the rule l would require the physician to ask many personal questions of the patient.
- esponse. The commenter is incorrect in believing that the dose-based ;
+
i
. approach will generally require personal information from the patient. The .!
l
! NRC anticipatesi that nearly all patients will be released based on default assumptions which do not require any personal information from the patient. ;
A table of releaso quantities, based on standard conservative assumptions, is l provided in Regulatory Guide 8.39,
- Release of Patients Administered Radioactive Materials." However, the rule does allow the physician to ,
calculate patient-specific dose estimates to allow early release of a patient i not otherwise subject to release under the default values in Regulatory Guide 8.39. Personal information may be necessary for such patient-specific i
Cases. 7 Comment. One commenter said that it should continue to be acceptable to release patients based on the dose' rate at 1 meter.
. Response. The rule authorizes release of patients based on the dose in ,
a year. However, release quantities based on dose rate and conservative assumptions can be calculated. The table of release quantities in Regulatory Guide 8.39, " Release of Patients Administered Radioactive Materials,"- .
~
specifies the dose rate at 1 meter of commonly used radionuclides that allow licensees to authorize patient release. ,
[
3.
I 13
=
I e , - _ . . . . . . .,__._m_.-.__...m.. . _ . . , -..e - . _ _ . . , , . _ _ . , . .m.mm.., -.m, , , ~ , , . . . . , . . , . _ _ - , . , , . .
RELEASE QUANTITIES ,
Using a dose-based system based on a dose to the most highly exposed individual of 5 millisieverts (0.5 rem) would, in some circumstances, allow release of a pelittisi'with more than 1.110 megabecquerels _(30 millicuries) of I activity. Some commenters were opposed to allowing releases with higher . l
-activities than are-now permitted.
-comment. Several commenters said that the release of patients with more than 30 millicuries of iodine-131 should not-be permitted because of concerns about the risk of internal exposure. One commenter said that doses to family =
members from the patie'it vomiting were not adequately considered. The.same commenter also said that a study indicated that in-home contamination by
. patients dosed with I-131 could double family members' risk of developing thyroid cancer.
Response. The concern over contamination.is not justified by the radiation doses that'are likely to be caused by the removal of radionuclides from the patient's body by the pathwayr of exhaled air, feces, saliva, sweat, urine, and vomit. Measurements from_several studies, as discussed in the supporting regulatory analysis, have shown that a relatively small proportion-of. the radioactive material administered will appear ~ as contamination. 00ses to family members-exposed to contamination from'living in-close contact with released patients have been measured in several studies and.in every case were less than 10 percent of the 5-mil 11 sievert (0.5-rem). total effective dose equivalent 11mit and.were most often less then_1 percent of the 5-mil 11 sievert (0.5-rem) limit. In addition, the internal doses resulting from contamination 14 4
l were always less and generally far less than the external dese, meaning that l contamination was the less impertant source of radiation exposure. These .
1 measurements show that even if the family members repeatedly touched household items touched by the patient, contamination does not cause unacceptably high ooses. ~ihese findings were true even in the case of a British study where cleven patients volunteered to disregard special precautions against contamination and minimizing spousal and family exposure. These measurements
- are discussed in NUREG-1492. Also, the NCRP recently addressed the risk of intake of radionuclides from patients' secretions and excreta in NCRP Commentary No. II, " Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients," and ccncluded that, "... a contamination incident that could lead to a significant intake of radioactive material is very unlikely."'
In general, the physical reactions (e.g., vomiting) that a patient may experience from the administration of any radiopharmaceutical are rare.
Vomiting is seldom an important elimination route for radiopharmaceuticals after the patient has left the medical facility lince orally administered radiopharmaceuticals such as iodine-131 are rapidly absorbed, within a half hour, by the gastrointestinal system.
Regarding the comment on the doubling of risk of developing thyroid cancer, there is no scientific consensus by the United Nations Scientific Committee on the Effects of Atomic Radiation, ICRP, or NCRP to support the suggested increased risk of thyroid cancer following ingestion of iodine-131.
' National Council on Radiation Protection and Measurements, " Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients," NCRP Commentary No. 11 (February 28, 1995). (Available for sale from the NCRP, 7910 Woodmont Avenue, Suite 800, Bethesda, MD 20814-3095.)
15
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-i l
Based on the information currently available, the Commission continues to !
l conclude that the benefits outweigh the potential of small increased risks associated with this rule, i
t Coasent. One commenter noted that hospitals now make great efforts to !
control contamination from patients who are now hospitalized because they !
contain more than 30 millicuries of iodine-131. This commenter stated that it would not be possible to' maintain the same level of contamination control at .
these patients' homes if these patients were released with more than 30 milliceries of iodine-131.
' Response. The NRC agrees that, even though released patients are given instructions'on how to limit the hazard from contamination, contamination control in a hospital can be more effective than contamination control out of the hospital. Howevers the two situations are not really comparable. In the ,
case of the released patient at home, therapeutic administrations almost never r
-occur more than once in a year and only rarely occur more,than'ence in a lifetime; but in the case of a hospital, large therapeutic administrations are done repeatedly on many patients. Therefore, areas in hospitals have the ,
potential for cnntamination from many'patienW, and people who frequent the hospital-(e.g., clergy or a hospital orderly) have the potential to be exposed i to contami. nation from many patients, in addition, the 5-millisievert (0.5-rem) limit that is applied to household members exposed to a patient is a-special-limit that is appropriate for only occasihnal use and for use where-there is.a definite need. This special limit fits the case of doses received -i t
by the household _ members of a released patient, but does not fit the case of ,
people who frequent a-hospital on a routine basis. Lastly, in limiting doses, ,
the NRC considers what is-reasonably achievable. The mere fact that a home
- 16 ,
. _ . . . . . . _ _ . _ _ _ s__ . . ~ . - , _ _ _ , _ _ . . - . _ . , . .__.a,. ;_,_.___.-_.._
cannot control contamination as well as a hospital does not mean that the contamination control achieved in homes is not adequat.e. Actual measurements of doses to household members from contamination, as discussed in NUREG-1492, show that the doses from contamination are low, demonstrating that the degree of contamination control that was achieved is adequate. _,
Comment. One commenter said that the proposed rule did nut adequately address the concerns that the Agreement States expressed on the petitions for rulemaking concerning releasing patients with qua,itities of iodine-131 in excess of 30 millicuries.
Response. In commenting on the petitions, a number of States expressed concerns about releasing patients administered 14.8 gigabecquerels (400 mil 11 curies) of iodine-131, which one of the petitioners had requested.
However, the States that commented were generally favoraole to the proposed rule limiting the-dose to the most exposed individual to 5 millisieverts (0.S rem), and none of the States indicated that their concerns were misrepresented. In fact, one Agreement State commenteJ that it was pleased that the NRC had considered the comments made by the Agreement States at various meetings with the NRC. The dose-based limit would generally permit releases if the dose to another individual would not be likely to exceed 5 millisteverts (0.5 rem). For example, if a licensee uses the def ault table of release quantities provided in tho regulatory guide as the basir r release, a patient administered 1,221 megabecquerels (33 millicuries) or less
" iodine-131 could be immediately released and no record of release is requi..i. However, if the licensee wishes to release a patient with an activity that is greater thari the _value in the default table, the licensee 17-
must do a dose calculation using case-specific factors to demonstrate compliance with the release criteria. Furthermore, if the table is used_ as
~the bas s for release but the administered activity exceeds the value in the
]
1 table, the licensee must hold the patient until the time at which the retained I
activity is no greater than the quantity in the table or the dose rate at 1 meter is no greater than the value'in the table. When the administered activity is greater than the value in the default table, a record of the basis for-the release must be maintained for NRC review during inspection.
Regardless of the method used by-the licensee to authorize release, the dose limit of 5 millisieverts (0.5 rem) in the revised 10 CFR 35.75 applies. By
-identifying more than one method-for calculating the release of a patient in - ;
accordance with 10 CFR 35.75,'the NRC provides greater flexibility for I
licensees to achieve compliance with the new requirtment while still providing adequate protection of public health and safety..
i Comment. One commenter said that in some cases.it should be permissible
-to authorize the release of a patient even if the dose to e. family member.
- might exceed 0.5 rem because the release might be beneficial and acceptable to family members. Another commenter said that a dose of 0.5 rem to an
-individual exposed to a patient .has so little hazard that the NRC should not be concerned with it.
Response. The NRC does not believe that individuals' exposed to a
- patient- should, in-general, receive doses in excess of 5 millisteverts (0.51 rem). This is consistent with the recommendations of the ICRP_in ICRP 18
4 Publication 60,' *1990 Recommendations of the International Commission on Radiological Protection"; and the recommendations of the NCRP in NCRP Report No.116,* " Limitation of Exposure to lonizing Radiation." Each of these recomendations provides a basis for allowing individuals to receive annual doses up to 5 millisteverts (0.5 rem) under certain circumstances. Both the ICRP and the NCRP recommend that an individual can receive a dose up to 5 millisieverts (0.5 rem) in a given year in situations when exposure to radiation is not expected to result in doses above 1 millistevert (0.1 rem) per year for a long period of time, as would be the case for doses from released patients. In NCRP Comentary No.11. " Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients,"' the NCRP recommended a dose limit of 5 millisieverts (0.5 rem) annually for members of I the patient's family. However, on the recomendation of the treating physician, the NCRP considered it acce able that members of the patient's family be permitted to receive doses as high as 50 millisteverts (5 rems).
The NRC does not agree that the latter NCRP recomendation should apply in general. The NRC believes that if the dose to another individual is likely to exceed 5 millisieverts (0.5 rem), the patient should remain under the control of the licensee. Licensee control is necessary to provide adequate protection to the individuals exposed to the patient.
' International Commission on Radiological Protection (ICRP), "1990 Recommendations of the International Commission on Radiological Protection,"
1 ICRP publication No. 60 (November 1990). Available for sale from Pergamon Press, Inc., Elmsford, NY 10523.
' National Council on Radiation Protection and Measurements, " Limitation of Exposure to lonizing Radiation," NCRP Report No.116 (March 31,1993).
Available for sale from the _NCRP, 7910 Woodmont Avenue, Suite 800, Bethesda, MD 20814-3095.
19
RECORDKEEPING 4
6 The strongest opposition to the proposed rule was to the proposed requirement to maintain a record of the released patient and the calculated total effective dose equivalent to the individual likely to receive the '
{
highest dose if the dose to that person is likely to exceed 1 millisievert (0.1 rem). Under the proposed rule, if a patient had or might have had one or more administrations within the same year, the licensee would use the records to determine the dose from the previous administrations so that the total dose to an individual exposed to a patient from all administrations would not exceed 5 millisieverts (0.5 rem).
Comment. Many commenters indicated that this requirement would cause excessive costs in time, effort, and money to track down records of previous administrations, to perform calculations, and to keep records of all the work .
and asked that the requirements to make calculations and keep records be removed. The commenters believed that the work would not produce an increased level of safety, that the NRC greatly underestimated the cost, and that the recordkeeping would be unnecessary, inappropriate, and impractical. Some commenters said that multiple administrations that would result in a total effective dose cquivalent greater than 1 millisievert (0.1 rem) are not done to the same patient routinely. Other commenters said that there nave been decades of experience unencumbered by any paperwork burden at all with no evidence that a lack of paperwork has resulted in any additional problems.
One commenter said that if 0.5 rem is acceptably safe, why have the documentation required at the 0.1 rem level.
20
Another commenter said that it cannot be a licensee's responsibility to know the details of a radionuclide therapy performed by another licensee in terms of which members of the public received the most radiation dose from that other licensee's therapy procedure.
One commenter said that the excessive recordkeeping cost would be a nonreimbursable cost, and the burden will cause many physicians to stop offering iodine therapy, which would force patients to travel to large medical facilities in cities and cause problems with patient access in sparsely populated areas.
Response. Upon reconsideration, the NRC has decided to delete the requirement to keep records when the dose to the most highly exposed individual is likely to exceed 1 millisievert (0.1 rem). The requirement was proposed so that it would be possible to account for the dose from multiple l-
. administrations in the same year to ensure that the total dose to an individual exposed to the patient did not exceed 5 millisieverts (0.5 rem).
The NRC has an advisory committee, the Advisory Committee on the Medical Uses of Isotopes, or "ACMUI," which advises the NRC on rulemakings and other initiatives related to the medical use of byproduct materials. The NRC also has a visiting medical fellows program that recruits selected physicians or pharmacists to work for the NRC for a period of 1 to 2 years. Both the ACMUI and the current Visiting Medical Fellow, Myron Pollycove, M.D., provided advice to the NRC during the development'ot'this rule. In addition, Barry A. Siegel, M.D., Chairman of the ACMUI, reviewed the' patient records at his medical facility for the 1-year period from July 1, 1993, to June 30, 1994 (Mallinckrodt Institute of Radiology, St. Louis, Missouri). Drs. Siegel and Pollycove concluded that no routine nuclear medicine practice, be it 21 l
diagnostic, therapeutic,-or a combination of the two, results in multiple
--large administrations that would be likely to cause the 5-millistevert
--(0.5-rem) dose limit to be exceeded because of multiple administrations in a year.
While the proposed 'iequirement to maintain a record of the dose to L another individual if the dose is likely to exceed 1 millisievert (0.1 rem).
u has been deleted, a recordkeeping requirement with a reduced impact has been retained as discussed under the heading, " Discussion of Text of Final Rule,"
Comment. Several commenters said that those who pay for health care will put great pressure on physicians to optimize calculations to reduce. ;
in-patient days and to justify out-patient treatments.
Response. There is no obiection to optimizing calculations to-reduce
' in-patient days as long as the calculations are realistic and the-5-millisievert (0.5-rem) limit in 10 CFR 35.75 is met. Regulatory Guide 8.39,
" Release of Patients Administered Radioactive Materials," describes examples of. calculations- that are acceptable to the NRC.
WRITTEN INSTRUCTIONS TO PATIENTS In general, there was little objection to providing instructions to rpatients on how to minimize the dose to others, but there was significant-opposition to-the proposed requirement that the instructions would have to be written.
22
Comment. One commenter said that the Statement of Considorations for ,
the proposed rule was in error in-stating-that the existing regulations -
already required that-the instructions to patients be written.
Response. _ The_ commenter is correct. The Statement of Considerations 1
was in' error on usaP point. The existing regulations do not specify that instructions have to be in written form.
l Comment. A number of commenters said that instructions should not need to be written and that oral instructions should be permissible. Some of these commenters said that oral instructions are more effective and that how the instructions should be given is within the province of-the doctor-patient relationship and that the NRC and its regulations should not interfere with that relationship. One commenter said that the physical condition of the patient could lessen the patient's ability to follow the instructions.
Another commenter said that the standard written instructions require too much time explaining how each patient varied from the standard instruction-sheet.
However,-one Agreement State and a major health maintenance organization strongly supported the~ requirement that the instructions be written.
Response. The NRC believes that providing written instructions has a significant value because_ often patients will' not remember all of the instructions given orally. In addition, written-instructions can be read by other family members or care givers. The requirement to provide the instructions'in written form was also supported by the_ACMUI. !
This regulation allows the licensee to determine the form of the written instructions. The NRC believes that for the majority of releases requiring written instructions, the written instructions can be prepared in a generic 23
form. for example, the Society of Nuclear Medicine has-preparhd a brief pamphlet; " Guidelines for Patients Receiving Radiotodine Treatment," which can be--given to patients at nominal cost-(less than $1 per patient). However,
' oral instructions may also be provided in all cases.
Consent. Several commenters said that dictating to a physician how and ;
~
what he or. she must tell a patient is not the-purview, mandate, or competence ,
of. the NRC and interferes with an essential part of medical practice, which is
-communication between physician and patient.
Response. In a' policy statement published on February 9,1979
-(44 FR 8242),l entitled " Regulation of the Medical Uses of-Radioisotopes; Statement of General Policy," the NRC made three specific statements. The third statement of the policy is "The NRC will minimize intrusion into medical judgments affecting patients and into other areas traditionally considered to be a part of the-practice-of medicine." The final rule -is consistent with this statement because it does-not dictate the choice of medical:treatmentior diagnosis,-does not specify the details _of what the physician must say or must include in the contents of the written-instructions, and is directed at
- minimizing the risk to the patient's family who have no doctor-patient relations to the prescribing or administering personnel. However, Regulatory Guide-8.39, " Release of Patients Administered Radioactive Materials,"
recommends contents of the written instructions.
Further discussion of the 1979 Medical Policy Statement is presented under the heading, "VIII. Consistency with<1979 Medical Policy Statement."
24
- i. .
Comment. Several commenters asked whether written instructions were appropriate if the patient was blind, illiterate, or did not read English.
Another commenter said that the instructions should be both written and oral and should be in the primary language of the patient.
Response. The NRC believes that written instructions are useful and should be required. If the patient is blind, illiterate, or does not read English, it is likely that someone else will be able to read the instructions for the patient. NRC considers it too much of a burden to require that the instructions be given in the primary language of the patient, although the regulations do not preclude foreign language written instructions if the licensee chooses to provide them. In most situations, it will be possible to find someone who can translate for the patient if necessary. The requirement that written instructions be given to the patient does not preclude additional oral instructions.
Comment. Several commenters asked how the NRC would enforce implementation of the-instructions given to the patient. Another commenter asked how the licensee could verify that the instructions are followed.
Another commenter said that a sizable fraction of patients may not follow radiation safety instructions to protect spouses and may be even less careful about protecting total strangers. This commenter also asked whether it is reasonable to exnect that released patients will alter their behavior and limit their activities for the protection of others.
Response. The NRC does not intend to enforce patient compliance with the instructions nor is it the licensee's responsibility. However, it is the responsibility of licensees to provide instructions to the patients.
25 4
n -
Following the instructions is normally the responsibility of the patient.
However,-American medical practice routinely depends on patients following
- instructions, such as instructions on when and how to-take' medications.
With regard to; compliance witht 'he instructions, surveys of patients and ,
their spouses, as discussed in the supporting regulatory analysis, indicate-that most will attempt to' follow the instructions faithfully, especially with regard to protecting their children,.although some patients and their-spouses
' indicated that they might not keep physically distant.from their spouse for prolonged periods of time.-
Comment. One commenter said that instructions should be given for all administrations of radioactive material, regardless of the quantity administered..
I.
-Response. The NRC does not agree. In some cases, particularly in'the large number of diagnostic administrations, the potential doses are so small
- that the burden of:-requiring instructions cannot be justified. Under the final-rule,- if the dose to any individual exposed to the patient is not likely to exceed 1-millisievert (0.1 rem), instructions are not required but'the physician could give any instructions that he or she considers desirable, CONFINEMENT OF PATIENTS
. Comment. -Two commenters said that-patients cannot be! confined against their~ wishes and that the rule provides no penalty for the patient who leaves.
confinement in the. hospital "against medical advice." Another commenter said 26
+.
that the rule seems to require that the licensee have control of the patient's activities after release. -
Response. The NRC recognizes that patients cannot be held against their will. The rule deals with the conditions under which the licensee may autt.orize release. The NRC would not penalize a licensee for the activities '
of the patient after release or if the patient were to leave "against medical advice."
Comment. One commenter asked whether a pr.tient who was releasable but was still hospitalized for other reasons would still be considered under the licensee's control.
Response. Once the licensee has authorized the release of the patient, there is no need to keep the patient under licensee control for radiation protection purposes if the patient remains hospitalized for other reasons. '
However, good health physics practice would be to continue to make efforts to maintain doses to people at the facility as low as is reasonably achievable.
Comment. Commenters also asked how a patient can be confined to his or her house.
Response. These commenters misunderstood the concept of confinement.
As explained in the Statement of Considerations for the proposed rule (59 FR 30724), the term " confinement" no longer applies to the revision to 10 CFR 35.75. Instead, the text of the rule uses the phrase " licensee control" to more clearly raflect the NRC's intent.
The NRC believes that there is a distinct difference between a patient being under licensee control in a hospital or other licensee facility (e.g., a 27 i
T a
hospice or nursing home):and being at home, in a hospital or other area or address of use111sted on the NRC license, the licensee has control over access to the patient as well-as having trained'personne'l and instrumentation available for making radiation measurements not typically available at the l
-patient's home. In addition, while_ under licensee control a licensee has l' control over the dose by limiting the ' amount of time that individuals are. in
{
close proximity to the patient. A patient who goes home is released from licensee control.
Comment. One commenter thought that the rule'should define the term
" release."
Response. The term " release from licensee control," when read in context, refers to radiation protection considerations and is sufficiently-clear that there is no need to define the term.
MISCELLANEOUS COMMENTS ON THE RULE Comment. Several commenters said that the rule st lid not be a matter of Agreement State compatibility =at-any level.
Response. The NRC does not agree. :The NRC conducts an-assessment of each proposed requirement or rule t'o determine what level of compatibility (will be . assigned to the rule.- These case-by-case assessments are based, for the most part, Lon protect'.ng public health and safety. NRC has evaluated the
- final rule and assigned compatibility designations ranging from level 1 (full
- compatibility required) to level 3 (uniformity not required)Las detailed later in th'is Federal Register notice.
_ =_
28
1
?
Comment. Several commenters said-that a breast-feeding infant should .
not be considered as an-individual exposed to the patient for the purposes of ,
determining whether patient release may be authorized.. These commenters said j .that consideration of the breast-feeding infant should be under the
- jurisdicti_on of the physician, that the' issue is a medical issue rather a regulatory issue, and that the NRC should not interfere in medical issues.
i Response. The NRC-does not agree. The NRC has a responsibility to protect the public health and safety, and that_ responsibility extends to all individuals exposed to a patient administered licensed radioactive materials, ,
including 1 breast-feeding children. When the release is authorized, it is based on the licensee's determination that the total effective dose equivalent '
to an individual from the released patient is not likely to exceed 5 millisieverts (0.5 rem). The dose to the breast-feeding child from breast-feeding is a criterion-for release but it can be controlled.by giving the woman guidance on the interruption or discontinuation of oreast-feeding, as required by the new 10 CFR 35.75. However, the release could be based on
-the default table of release activities in the regulatory guide or-a
. patient-specific-calculation', as required by the new 10 CFR 35.75. The issue of the dose to the breast-feeding child is discussed in NUREG-1492 and Regulatory Guide 8.39, " Release of Patients Administered Radioactive
~
Materials."
Comment. One commenter said that the proposed rule.did not accuaately
. represent the position of the Advisory Committee on Medical-use of Isotopes.
Response. A review of the transcript for the ACMul meeting in May 4992 shows that the Federal Register Notice provided an accurate description of tr a 29
2 ACMui position. The final-rule was discussed with the ACMut on October 18,
-1995, and the ACMUI,- in: general, supported the rule. (For ACMUI's comments
. and NRC's responses,-see V. Coordination with-the ACMUI.)
i Comment. One commenter said that its facility treated many foreign patients with therapeutic pharmaceuticals.' These patients frequently may leave the hospital and-immediately board a plane to return home.- Thus, there is a limit to-the-amount of control that a licensee has over the patient.
Response. The NRC recognizes that the licensee has no control over the patient after the-patient has been released. =The quantities-for release listed in Table 1 of Regulatory Guide 8.39, " Release-of Patients Administered
- Radioactive Materials," were calculated using conservative assumptions (for example, by using the physical half-life of the radioactive material rather than the more realistic effective half-life). Thus, the NRC considers it
~
_unlikely that-_the dose to-an individual--in-real circumstances would approach 5 millisieverts (0.5 rem).
In special situations, such as when a released patient would.immediately board an airplane and would therefore be in close. contact with one or more individuals it may be necessary to base the release on e. more realistic case-specific calculation. Once the patient is' released, the responsibility for following the instructions is entirely the patient's,-not the licensee's.
4 i
30 n
COMMENTS ON THE DRAFT REGULATORY GUl0E-
~
Comments were also requested on Draft Regulatory Guide, DG-8015,
" Release of Patients Administered Radioactive Materials," associated with this rulemaking. Because the guide is_ associated with the rule, the comments received on the draft guide are discussed here. Most of the comments concerned the method and the assumptions used to calculate the dose to the i individual likely to receive the highest dose.
Comment. Several commenters said-that the calculational methodology in
'the draftLguide is too complex and that the assumptions are too conservative.
As- an' example,- several commenters said that the assumed 24-hour nonvoiding assumption used in~ calculating doses is too conservative. As evidence that
_ theLcalculations are too conservative, several commenters said that the doses- i measured using dosimeters were much lower than doses _ calculated using the models in the draft guide.
- Response. The NRC has revised the guide to use a phased approach for determining when release can-be authorized. While the calculations can sometimes be complex, the results of calculations that use conservative assumptions are-given in a table of- release quantities in Regulatory Guide 8.39, " Release of Patients Administered Radioactive Materials." Of the 8 to 9 million administrations performed' annually, in all except about 10,000 cases' (radiciodine therapy- for thyroid cancer),' release-can be authorized based on conservative-assumptions and using Table 1 with no
- calculational effort on the part of the-licensee and no additional recordkeeping beyond what is already required. For permanent implants, the 31-
4 l
guide provider, dose rates at I meter from the patient at which release may be authorized. Thus, for implants, there would be no calculational effort needed. In addition, the guide provides information on iodine therapy for thyroid cancer that can be used for determining releas? based on retention and elimination. This additional information in the guide will allow the licensee to perform the calculation with relatively little effort.
With regard to the comments that the methodology is too conservative and that measured values are lower than calculated by the methodology,-the methodology in the table giving default release quantities is intended to be conservative. The NRC believes it is appropriate and prudent to be conservative when providing generally applicable release quantities that may be used with little consideration of the specific details of a particular patient's release. A review of published information, as described in the regulatory analysis, NUREG-1492, " Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material" (1995), finds that measured doses are generally well below those predicted by the methodology used to calculate the table of default release quantities. Thus, the default release quantities are conservative as the NRC intended. However, the licensee is given the option of using case-specific calculations that may be less conservative.
Nevertheless, the NRC agrees that the assumption used in the draft guide of 24-hour nonvoiding in the thyroid canger example was overly conservative.
The revised example uses an excretion half-life of 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> as recommended by 32
the ICRP in ICRP Publicatiori 53, " Radiation Oose to Patients from Radiopharmaceuticals."'
Comment. One commenter said that the occupancy factor (generally assumed to be 0.25 at I meter) should not be left to the discretioc ef-th; licensee because low occupancy factors could easily be justified by providing strict safety instructions without any verification that the instructions will be followed. Another commenter liked the flexibility provided by being able to adjust the occupancy factor, but wanted to know if other considerations are allowed and if it is acceptable to use values lower than 0.125.
Response. Oraft Regulatory Guide 8.39 discussed situations in which it might be permissible to lower the occupancy factor from 0.25 to 0.125, but did not recommend occupancy factors less than 0.125. Occupancy factors less than 0.125 may be difficult to justify because it is generally not realistic to assume that the patient can avoid all contact with others. However, lower values for the occupancy factor are not prohibited by the regulation, but they must be justified in the record of the calculation, as the record will be subject to inspection. '
Comment. Several commenters said that the iodine-131 retention fraction of 0.3 used in the draft guide for treatment of thyroid cancer is too large and that the correct value should be 0.05 or less. Another commenter said that the biological half-life of extrathyroidal iodine should be 0.5 day for both the euthyroid and hyperthyroid condition. One commenter said that the
' International Commission on Radiological Protection (ICRP), " Radiation Dose to Patients from Radiopharmaceuticals," ICRP Publication No. 53 (March 1987). Available for sale from Pergamon Press, Inc., Elmsford, NY 105?3.
33
biological half-lives from ICRP Publication No. 53 should be used for thyroid cancer.
Response. The NRC agrees that the commenters raised valid points. In Regulatory Guide 8.39, the iodine retention fraction for thyroid cancer was changed to 0.05. The biological half-life for the enr uhyr oidal fraction was changed to 0.33 day. In addition, the biological half-lives from ICRP Publication No. 53 were used for the thyroid cancer case.
Coment . One commenter said the table of release quantities in the draft guide should be expanded to include beta emitters such as strontium-89 and phosphorous-32. Another commenter said that the table should be expanded to include chromium-51, selenium-75, ytterbium-90, tin-ll7m, and iridium-192.
Response. Values for the beta emitters strontium-89 and phosphorous-32 have been added to the table of release quantities in Regulatory Guide 8.39.
The table of release quantities was also expanded to add values for chromium-51, selenium-75, ytterbium-90, tin-117m,,and iridium-192.
Coment. The table of release quantities in the draft regulatory guide should be expanded to include accelerator-produced radioactive materials as an aid to Agreement States.
Response. Several accelerator-produced materials were added to Regulatory Guide 8.39 as an aid to the States and to medical facilities. The NRC has no regulatory authority over the release of patients administered accelerator-produced materials and would not inspect the release of patients administered accelerator-produced materials.
34
~
__.-7_..
Consent. .One commenter said that the regulatory-guide should have a- ,
table of release quantities based on biological half-life rather than only the ;
. physical half-life.
. Response. Regulatory Guide 8.39_ now provides more-information on
- release quantities for iodine-IS. based unu' iviugical half-lives. -
l Consent. One connenter said that the factor of 10" used.in the draft-i- guide to estimate internal dose is not well supported for nonoccupational exposures. Another commenter said that the calculation of dose to individuals exposed to the patient ignores the potential of radiation dose from the excretion of. radioactive material from the patient, and this could present a
, significa".; radiological hazard to family members.
Response. It is true that there is not'a great deal of information on the use of the factor in nonoccupational settings, but measurements (described'
- in NUREG-1492) have=been made_in which-iodine uptake was measured in people exposed to'a-patient. These data suggest that the fractional uptake of_ the administered activity will be on the order of 10" -Since iodine is among the most soluble .and volatile radiopharmaceuticals, it can be expected that the transfer to others of less soluble and less volatile radiopharmaceuticals
- would be less than that of iodine.
In addition, the NCRP_ recently concluded that,-for individuals exposed
- to radionuclide~ therapy patients,.the. risks of external irradiation and-
- potential contamination:are' minor from a public health viewpoint; therefore a significant intake from a contamination incident is very unlikely.'
35 t s' !- m - erw+ w- 1- ,y- , -ee-r-.-,e-r. -ie-w r . -
- -r m s- i mv
Comment. A medical organization commented that the draft guide is not complete and does not provide sufficient comprehensive examples to assist licensees in complying with the rule.
Response. The NRC has expanded the guide to include information and I further examples on the biologic.i eliniination of iodine-131 and on when guidance on the interruption or discontinuation of breast-feeding should be given. Expanded examples are now given in Regulatory Guide 8.39, " Release of Patients Administered Radioactive Materials." The example on thyroid cancer was revised to include more realistic assumptions, and an additional example on hyperthyroidism was added. The NRC believes that the examples provided illustrate the techniques sufficient to perform the whole range of potential calculations.
Comment. One commenter said that the draft regulatory guide did not provide enough information on when and for how long breast-feeding of infants should be interrupted.
Response. Regulatory Guide 8.39 has been greatly expanded with respect to information on the breast-feeding child, including a table on recommendations for the interruption or discontinuation of breast-feeding for specific radiopharmaceuticals.
Comment. One commenter said that the sample instructions in the draft guide concerning implants should include a picture of an implant seed.
Response. The sample instructions were not expanded to include this because of graphics limitations, but licensees may add photos if desired.
36 7
I-Coment . Several commenters asked whether multiple individual calculations have to be done or if a generally applicable calculation could be done once and used for many patients.
p Response. The NRC believes that there may be some situations for which a case-specific calculdion tuuld be done for a class of patients. The record for a particular patient's release could then reference the calculation done for the class of patients. However, depending on a patient's individual status (e.g., lower occupancy factor), there may be cases when the calculation-will be done for a specific individual.
Coment . One commenter said that the discussion on radiolabeled antibodies in the draft guide was wrong because antibodies labeled with iodine-131 will be deiodinated in the body and the iodine will behave like other iodine. None of the radiolabeled antibodies now being developed or planned for the future snould have an internal dose hazard for the general public.
Response. The NRC agrees with this comment. Statements in Regulatory
-Guide 8.39 are now modified.
COMMENTS ON THE DRAFT REGULATORY ANALYSIS (DRAFT NUREG-1492)
Comen t . One commenter said that the value of a person-rem should be
$40 rather than $1,000 as used in the draf t regulatory analysis for the purpose of evaluating the costs and benefits of the rule. The commenter cited a 1993 Health Physics Society position paper as a reason that the value should be $40 per person-rem.
37
Response. The Commission recently adopted a value of $2,000 per person-rem as explained in Revision 2 of NUREG/BR-0058, " Regulatory Analysis Guidelines of the U.S. Nuclear Regulatory Commission (November 1995),"
Section 4.3.3, " Evaluation of Values and Impacts." (Single copies of NUREG/BR-0GSG ofe .vailable as indicated in the ADDRESSES heading.) The draft regulatory analysis, which was prepared utilizing $1,000 per person-rem, i
employed a simple computational model using the physical half-life only of radiopharmaceuticals. The regulatory analysis has been revised to include use of $2,000 per person-rem, as well as a more realistic dose model based on biological retention and elimination of the radiopharmaceuticals. The more realistic model with a value of $2,000 continues to demonstrate the cost-effectiveness of the dose-based limit. Specifically, the savings in f hospital costs under the earlier release time allowed are estimated at
$14 million, whereas the collective dose of 2,740 person-rem (at a value of
$2,000 per person-rem) corresponds to a cost of about $5 million.
NUREG-1492 contains a detailed discussion of the model and the benefits and impacts of the dose-based limit. Single copies of the final _ regulatory analysis are available as indicated in the ADDRESSES heading.
Comment. One commenter said that the benefits of the rule were overestimated because the length of time that a thyroid patient would have to remain in the hospital was overestimated and the cost of a hospital room was overestimated, being $450 per day rather than $1,000 per day as assumed in the draf t regulatory analysis.
Response. The commenter is correct that the benefits of the rule were overestimated. The estimates in the draft regulatory analysis of days of hospitalization required did not include biological elimination of the radioactive material; only radioactive decay was considered. As a 38
consequence, the draft regulatory analysis, in some cases, overestimated the:
time that patients would need to be retained under licensee control, and therefore the~ costs of patient retention were too high. The-final regulatory analysis corrects the estimates.
The NRC believes that the current cost of $1,000 per day for a iioipital
-room'is not an overestimate. Under 10 CFR-35.315(a)(1), licensees are required to provide a private room with a private sanitary facility for each patient -receiving radiopharmaceutical therapy and hospitalized for compliance with 10 CFR 35.75. Considering this NRC requirement and the recent reference cited in the final regulatory analysis on-the cost of hospitalization, $1,000 per dayifor a hospital room is a reasonable estimate.
o Comment. One commenter said that the description of the measured doses received by family members was not consistent with the reference cited.
Response. The commenter is correct. An incorrect reference was given.
The final regulatory analysis provides the correct reference.
IV. Coordination with NRC Agreement-States The NRC staff discussed the status of this rulemaking effort at two public meetings: the Agreement State-Managers Workshop held on July 12-14, 1994,-and at the All Agreement States Meeting held on October 24-25, 1994.
The Agreement States expressed no objections to the approach-in this~ rule.
V. Coordination with the Advisory Committee on Medical Uses of Isotopes The Advisory Committee on Medical Uses of Isotopes (ACMUI) is an-advisory body established to= advise the NRC staff on matters that involve the administration of radioactive material and radiation from radioactive material. The NRC staff presented a summary of the comments on the proposed 39
rule to the ACMUI during a public neeting held in Rockville, Maryland, on November 17 and 18, 1994. ,
Drafts of the final rule and regulatory guide were discussed with ACMui in Rockville, Maryland, on October 18 and 19,1995. The ACMUI supported the approach in this rule but suggested some clarifying dian9es. The NRC staff
^
made all but one of the suggested changes. The ACHUI suggested using the term
" rationale" instead of " consequences" in the requirement under the revised 35.75(b), to provide " guidance on the interruption or discontinuation of breast-feeding, and information on the consequences of failure to follow the guidance" for cases where failure to follow the instructions could result in a dose to the infant exceeding 1 millisievert (0.1 rem). Since most of the administrations that would be affected by this requirement are technetium-99m administrations, the ACHUI suggested the change because there was concern that the consequences of low doses of radiation cannot always be explained to the patient without causing unjustified alarm. Also, there was concern that physicians cannot explain with certainty the effects of low doses of radiation, such as would be caused by diagnostic administrations of !
technetium-99m. The staff did not change the rule in response to the ACMUI comment. The requirement to provide information on the consequences is included to primarily protect the breast-feeding infant-from therapeutic administrations of radiciodine, which could cause serious thyroid damage.
Regulatory Guide 8.39 rill contain guidance on the types of information, including expected consequences, to be provided to patients to meet this requirement. Transcripts of the meetings have been placed in and are available for examination at the NRC Public Document Room, 2120 L Street NW,
.(Lower Level), Washington, DC.
40
- VI.' Discussion of Text of Final Rule-This section' summarizes-the final rule. The NRC is amending 10 CFR 20.1301(a)(1) to-state specifically that the dose to individual members of the public from a licensed operation uoes" nut include doses received by
~
individuals exposed to patients who were released by the licensed operation under the provisions of 10 CFR 35.75. -This is not a substantive change. it'
'is a clarifying change to make clear that the Commission's. policy is that patient release is governed by-10 CFR 35.75,_not 10 CFR 20.1301.
For the sake of consistency and clarity, the same words are used in i 20.1002 " Scope"; in i 20.1003, " Definitions" (in the definitions of_both l public dose and occupational dose); and in i 20.1301, " Dose limitsL for individual members of the public." Also for consistency and clarity, the exclusion of dose from background radiation and from voluntary participation -
in medical research programs that are now included.in il 20.1002 and 20.1003 are added to i 20.1301(a)'. In addition, the definition of " member'of the public,":as published in 60 FR 36038 on July 13, 1995, is revised by removing the footnote which read,'"Except as delineated in other parts _of 10 CFR -
Chapter 1." With the publication of this rule that footnote is no longer needed.
_The NRC'is-amending 10 CFR 20.1301(a)(2) to state specifically that the limit on dose in unrestricted areas does not-include dose contributions from
-individuals administered radioactive material and released in accordance with 10 CFR 35.75. The purpose of this. change is to clarify that after a patient
-has been released under 10 CFR 35.:'5, licensees are no longer required to control radiation from the patient. The regulation uses the' term " individual" to refer to the individual to whom the radioactive material has been -
administered rather.than " patient" to clarify that the regulation refers to -
anyone: receiving a medical' administration.
41
__.__________m_.._.___m_-_______-_.-.._-_-----:_m---_u.--_----_-m-_
~~ _
The NRC is-ame,iding-10 CFR 20.1903(b) to use the term " licensee control" rather than " confinement" because the ,latter term no longer applies to 10 CFR 35.75. The conforming change is necessary since th'e term " licensee control" more ' clearly reflects the NRC's intent-in 10 CFR 35.75.
The-NRC is adopting a new'fu CFR 35.75(a) to change the patient release criteria from 30 millicuries of activity in a patient or a dose rate of 5 millirems per hour at 1 meter from a patient to a dose limit of 5 millisteverts (0.5 rem) total- effective dose equivalent to an individual from exposure to a released patient. (The dose from the radionuclide' involved is taken to be the dose to total decay.) A dose-based limit provides a single '
limit that can be used to provide an equivalent level of protection from.rlsks from all radionuclides. Also, the changes.are supported by the recommeadations of the-ICRP and NCRP that an individual can receive an annual dose up to 5 millisieverts (0.5 rem) in temporary situations where exposure to radiation is not expected to result in annual doses above 1 millisievert (0.1 rem)~ for many years. Usually, the only individuals likely to exceed a dose of 1 m1111 sievert (0.1 rem) will be those who are aware of the patient's-condition such 'as the primary care-giver, a fartily member, or any other-individual who spends significant time close to the patient' .
This dose-based rule would, in some instances, permit the release of-
' patients with activities greater than currently allowed.- This is especially _
true when case-specific factors are evaluated to more accurately assess the dose to other. individuals. The individuals exposed to the patient could receive higher doses.than if the patient had-been hospitalized longer. These ;
higher-doses are balanced by shorter hospital stays and thus lower health care costs. -In addition, shorter hospital stays may provide emotional benefits to-patients. and their families. Allowing earlier reunion of families can improve ,
the patient's'_ state of mind, which in itself may improve the outcome of the treatment-and lead to the delivery of more effective health care.
42
The release criteria in 10 CFR 35.75(a) could prevent a woman from being released because of the pote,ntial transmission of radioactive materials in breast milk. The dose to the breast-feeding child is controlled by giving the woman guidance, as required by 10 CFR 35.75(b), on the interruption or discontinuation vi breast-feeding and information on the consequences of failure to follow the guidance. The expectation is that the woman would follow the instructions and would interrupt or discontinue breast-feeding.
Finally,10 CFR 35.75(a) includes a footnote to inform licensees that the NRC has made available guidance on rule implementation. The footnote states that Regulatory Guide 8.39, " Release of Patients Administered Radioactive Material," contains tables of activities not likely to cause doses exceeding 5 millisieverts (0.5 rem) and describes methods for calculating doses to other individuals.
The NRC is adopting a new 10 CFR 35.75(b) to require that the licensee provide released patients with instructions, including written instructions, on how to maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any individual other than the released patient is likely to exceed 1 mil 11 sievert (0.1 rem). This also requires giving instructions to breast-feeding women if the dose to the child could exceed 1 millisievert (0.1 rem) assuming there were no interruption of breast-feeding. The instructions must include guidance on discontinuation or the interruption period for breast-feeding and the consequences of failing to follow the recommendation. Regulatory Guide 8.39 contains tables that show temporary interruption periods for various radiopharmaceuticals or discontinuation. The temporary interruption periods were calculated based on the determination that the dose to a child from breast-feeding is unlikely to exceed 1 millisievert (0.1 rem). However, the physician may use discretion in the recommendation, increasing or decreasing the duration of interruption somewhat depending on the woman's concerns about radioactivity or interruption of breast-feeding.
43 l
The purpose of describing the consequences is so that women will t
understand that br. east-feeding af ter an administration of certain radionuclides could cause harm (e.g., iodine-131 could harm the child's thyroid), in other cases, the guidance could simply address avoidance of any Lr.r.ec 33s , radiation exposure to the child from breast-feeding.
A requirement for instructions for certain patients was already contained in 10 CFR 35.315(a)(6) and 35.415(a)(5), but the modified ,
requirement for written instructions adds approximately (a) 50,000 patients y per year who are administered iodine-131 for the treatment of hyperthyroidism and (b) 27,000 patients per year, among about 8 million administered radiopharmaceuticals, who may be breast-feeding to whom additional written instructions be given. The purpose of the written instructions is to maintain ;
doses to individuals exposed to patients as low as is reasonably achievable.
The instructions may be either written only or written plus oral. The NRC believes that written instructions are necessary so that the patient and the patient's family and friends will have a document to refer to rather than having to rely solely on the patient's memory and understanding of the instructions.
The requirement of 10 CFR 35.75(b), requiring a licensee to provide guidance on discontinuation or the interruption period for breast-feeding and the consequences of failing to follow the recommendation, presumes that the licensee will make appropriate inquiry regarding the breast-feeding status of the patient. For breast-feeding women where the dose to the child is likely to exceed 1 millisievert (0.1 rem), the NRC requires that the patient be provided with specific instructions, as described in 10 CFR 35.75(b). There is no specific requirement to maintain a record indicating that breast-feeding status was determined prior to tee release of the patient.
The NRC is adopting a no.10 CFR 35.75(c) to require that the licensee maintain a record of the basis for authorizing the release for 3 years if the calculation of the total effective dose equivalent to other individuals uses 44
i .
the retained activity rather than the activity administered, an occupancy f actor, less than 0.25 at 1 meter, the biological or ef f ective half-lif e of the radionuclide. or shielding of radiation by the patient's tissue. lhus, records of release are required when the default assumptions are not used as discussed in Regulatcry Guide 8.39. Measurements made in se,'eral studies indicate that the default assumptions should generally overpredict the dose even when instructions are not given or are not strictly followed, if a licensee administers an activity no greater than the value in the default table of release quantities provided in the regulatory guide as the basis for release, no record of release is required, t.icensees are aircady required by 10 CFR 35.53 te etain records of the measurement of the activity of each dosage of radioactive material administered to a patient; these records are typically maintained in a patient dose 109 In addition, 10 CFR 35.32 requires licensees to retain a written directive and a record of cach administered radiation dose or radiopharmaceutical dosage for therapeutic administrations and diagnostic administrations of iodine-125 or iodine-131 sodium iodide greater than 30 microcuries. These records can be used in conjunction with Regulatory Guide 8.39 to demonstrate that patient releases meet the requirements of 10 CFR 35.75(a) when no record is auired by 10 CFR 35.75(c). When the licensee determines that the patient must be held to allow the reduction of radioactivity and then released, the licensee will need a record of release time to demonstrate that the release criteria have been met. A licensee may use any existing record to establish the release time. if biological elimination of radioiodine is a basis for release and the licensee uses the information in Regulatory Guide 8.39, a record of the thyroid uptake may be necessary as part of the basis for release because it is one of the nonstandard conservative assumptions listed in 10 CFR 35.75(c). If other case-specific factors are used as the basis for patient release that are in addition to, or modify, the standard conservative assumptions, a record of the 45
i i
. basis for the release,-including the assumpt;ons used for the calculations,
, must also be maintained.
This recordkeeping requirement is a modification of the proposed rule.
-The proposed rule would have required that a record be maintained of the basis for the patient's release, including all calculations performed, if the total effective dose equivalent to any individual other than the released patient is likely to' exceed 1 mil 11 sievert (0.1 rem)_.in a year from a single i administration. Under the proposed rule, the major purpose of the record was to provide the basis for limiting the dose to 5 millisieverts (0.5 rem) to l
individuals exposed to a patient who may receive more than one administration in a year. Upon reconsideration, based on public comments and consultation ;
with the ACMUI, an NRC medical consultant, and the NRC Visiting Medical i
-Fellow, the NRC has decided to delete this requirement. A review of medical treatment practices revealed no routine practice that would result in doses exceeding the 5 mil 11 sievert (0.5-rem) limit because of multiple administrations in the same year to the same patient. Without the need to account for the dose from multiple administrations, maintaining records for the many tens of thousands of patients released when their dose to an individual is_likely to exceed 1 mil 11 sievert (0.1 mil 11 sievert) becomes an unnecessary burden. The requirement'to retain these records has therefore been deleted. Each patient release is to be treated as a separate _ event upon which licensee knowledge of previous administrations is unnecessary.
The NRC is also adopting a new 10 CFR.35.75(d) to require that the-licenseo maintain a record that instructions were provided to a breast-feeding woman-if the administered activity could result in a total effective dose
-equivalent-to the breast-feeding child exceeding 5 millisieverts (0.5 rem) if the mother did not interrupt or discontinue breast-feeding. Thus, the NRC is requiring records for certain radiopharmaceutical administrations (e.g.,
therapeutic administrations of iodine-131). The activities of 46 h
radiopharmaceuticals that > quire this record are described in Regulatory Guide 8.39.
Finally, the NRC is delettig its requirements on written instructions in 10 CfR 35.315(a)(6) and 35.415(a)(5) because those paragraphs are redundant now that 10 CTR 35.75 has requirements for instructions. In addition, 10 CFR 35.415(a) and a(1) are reworded to clarify the original intent of the paragraphs, which was to limit the dose rate at 1 meter from the patient. The ambiguity was introduced when Part 20 was revised and a conforming change was made in 10 CFR 35.415. The conforming change that was made was not fully consistent with the original intended meaning of 10 CFR 35.415(a) and (a)(1).
Vll. Disposition of the Petitions for Rulemaking '
1he three petitions for rulemaking submitted by Dr. Marcus (PRM-20-20),
the ACNM (PRM-35-10 and PRM-35-10A), and the AMA (PRM-35-ll) requested that the NRC auend the revised 10 CFR part 20 and 10 CFR part 35. These requests and their disposition by this rulemaking are discussed below.
The requests made by Dr. Marcus and their disposition may be summarized as follows:
(1) Raise the annual radiation dose limit in 10 CFR 20.1301(a) for individuals exposed to radiation from patients receiving radiopharmaceuticals for diagnosis or therapy from 1 millistevert (0.1 rem) to 5 millisieverts (0.5 rem). The final rule grants this request.
(2) Amend 10 CFR 35.75(a)(2) to retain the 1,110-megabecquerel (30-niillicurie) limit for iodine-131, but provide an activity limit for other radionuclides consistent with the calculational methodology employed in the National Council on Radiation Protection and Measurements (NCRP) Report No. 37, " Precautions in the Management of Patients Who Have Received l Therapeutic Amounts of Radionuclides."' The final rule does not contain l activity limits, but Regulatory Guide 8.39 uses a calculational methodology 47 l
l
based on NCRP Report No. 37 to relate the dose to the quantity of activity in the patient. Therefore, the wish of the petitioner to have an easy method to determine when the patient may be released is granted in Regulatory Guide 8.39.
1 (3) Delete 10 CfR 20.1301(d), which requires licensees to comply with
~
provisions of the Environmental Protection Agency's environmental regulations in 40 CFR part 190 in addition to complying with the requirements of 10 CFR part 20. The EPA regulations referenced in 10 CfR 20.130)(d) are contained in 40 CFR part 190, which deals only with doses and airborne emissions from uranium fuel cycle facilities. Part 190 of Title 40 of the Code of Federal Regulations dc9s not apply to hospitals or to the release of patients.
Furthermore, 10 CFR 20.1301(d) does not incorporate the EPA's Clean Air Act standards in 40 CFR part 61 that applies to hospitals. The NRC is separately pursuing actions with the EPA to minimize the impact of dual regulation under the Clean Air Act and to take agreed upon actions that will lead to EPA recision of 40 CFR part 61 for NRC and Agreement State licensees.
Because the reference to EPA regulations in 10 CFR 20.1301(d) has nothing to do with the patient release issue, and therefore is outside the scope of this rulemaking, the final rule denies this request.
The requests made by the ACNM and their disposition may be summarized as follows:
(1) Adopt a dose limit of 5 millisieverts (0.5 rem) for individuals exposed to patients who have been administered radiopharmaceuticals. The final rule grants this request.
(2) Permit licensees to authorize release from hospitalization any
- patient administered a radiopharmaceutical regardless of the activity in tha patient by defining " confinement" to include not only confinement in a hospital, but also confinement in a private residence. The final rule denies this request for the reasons described in the discussion on this issue.
48
c--_--- - _ - - - - - - _ _ _ _ _ ___
Finally, the requests made by the AMA did not all pertain to the issue of patient release. The final rule grants the request pertaining to patient release, i.e., that the radiation dose limits in 10 CFR 20.1301 should not apply to individuals exposed to the patient and that the dose limit to the individuals should be 500 millirems. The request to change the term
' hospitalized" in 10 CFR 35.310(a) and 35.315(a) to the term " confined" was denied for the reasons discussed above. The request not related to the subject of patient release (that it should be clear in Part 20 that Part 20 does not limit the intentional exposure of patients to radiation for the purpose of medical diagnosis or therapy) was addressed in another rulemaking,
" Medical Administration of Radiation and Radioactive Materials," which was published as a final rule on September 20, 1995 (60 FR 48623), and became effective on October 20, 1995.
Vill. Consistency with 1979 Medical Policy Statement on February 9, 1979 (44 FR 8242), the NRC published a Statement of General Policy on the Regulation of the Medical Uses of Radioisotopes. The first statement of the policy reads "The NRC will continue to regulate the medical uses of radioisotopes as necessary to provide for the radiation safety of workers and the general public." The rule is consistent with this statement because its purpose is to provide for the safety of individual members of the public exposed to patients administered radioactive materials.
The second statement of the policy is 'The NRC will regulate the radiation safety of patients where justified by the risk to patients and where voluntary standards, or compliance with these standards, are inadequate."
This statement is not relevant to the rule because the rule does not affect the safety of patients themselves. The rule instead affects the safety of individuals exposed to patients.
49
I The third statement of the policy reads "The NRC will minimize intrusion l
into medical judgments affecting patients and into other areas traditionally l
considered to be a part of the practice of medicine." The rule is consistent with this statement because it places no requirements on the administration of radioactive materials to patients and because the release of patients administered radioactive materials has long been considered a matter of regulatory concern to protect members of the public rather than solely a matter of medical judgment.
{ Thus, the final rule is considered to be consistent with the 1979 medical policy statement.
L IX. Issue of Compatibility for Agreement States The NRC considers the definitions contained in i 20.1003 and the text in i 20.1301(a) that are modified by this rulemaking are Division I levels of compatibility. The definitions and text in these sections must be the same for all NRC and Agreement State licensees so that national consistency can be maintained.
Section 20.1002, " Scope," is a Division 3 level of compatibility because this section by nature is not a regulatory requirement and many States are prohibited by their administrative procedures act from including such sections in their rules. The scope section is a general statement of scope of the rule and does not contain specific requirements that are not presented in other sections of Part 20. Rules at the Division 3 level would be appropriate for Agreement States to adopt, but they do not require any degree of uniformity between NRC and State rules, Additionally, 6 35.75(a) and (b) are a Division 2 level of compatibility because the patient release triteria required by the rule are the minimum requirements necessary to ensure adequate protection of the public health and safety. The Agreement States will be allowed to establish requirements that 50
are more stringent than the NRC's requirements, but not less stringent. The recordkeeping requirements in i 35.75(c) and (d) are a Division 3 level of compatibility because uniformity in recordkeeping is not considered essential for this rule. t' X. Finding of No Significant Environmental lepact: Availability The NRC has determined under the National Environmental Policy Act of 1969, as amended, and the Conaission's regulations in Subpart A of 10 CFR part S1, that the amendments are not a major Federal action significantly affecting the quality of the human environment, and therefore an environmental impact statement is not required. The final amendments clarify the pertinent regulatory language to reflect explicitly the relationship between 10 CFR part 20 and part 35 with respect to release of patients, and the amendments revise the release criteria for patients receiving radioactive material for medical use from an activity-based standard to a dose basis. It is expected that there will be relatively little change in radiation dose to the public or to the environment as a result of the revised regulation.
The final environmental assessment and finding of no significant. impact on which this determination is based is available for inspection at the NRC Public Document Room, 2120 L Street NW, (Lower Level), Washington, DC. Single copies of the environmental assessment and the finding of no significant impact are available as indicated in the FOR FURTHER INFORMATION CONTACT heading.
51 1
- .. ~. , , - _- . , , , . - . , ,
XI. Paperwork Reduction Act Statement
, lhls final rule amends information collection requirements that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.).
These requirements were approved by the Office of Management'ano Budgec, approval number 3150-0010.
l The pubile reporting burden for this collection of information is estimated to average 13 hours1.50463e-4 days <br />0.00361 hours <br />2.149471e-5 weeks <br />4.9465e-6 months <br /> per licensee per year, including the time for ;
reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments on any aspect of this collection of information, including suggestions for reducing the burden, to the Information and Records Management Branch (T-6 F33), U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by Internet electronic mail at BJS10NRC. GOV; and to the Desk Officer, Office of Information and Regulatory Affairs, NE0B-10202, (3150-0010), Office of Management and Budget, Washington, DC 20503.
Xil. Regulatory Analysis The NRC has prepared a final regulatory analysis (NUREG-1492) on this regulation. The analysis examines the benefits and impacts considered by the NRC. The NRC has received public comments regarding the draft regulatory analysis and has addressed the comments (see Comments on the Draft Regulatory Analysis in 111. Public Comments on the Proposed Rule). The final regulatory analysis is available for inspection at the NRC Public Document Room at 2120 L Street NW. (Lower level), Washington, DC. Single copies are available as indicated in the ADDRESSES heading.
52 4
if
Xill. Regulatory flexibility certification As required by the Regulatory flexibility Act of 1980, 5 U.S.C. 605(b),
the NRC certifies that this rule will not have a significant economic impact on a substantial number of small entitles. This rule arrects medical use of byproduct material licensees. The impact of the final rule will not be significant because the final rule basically represents a continuation of current practice.
XIV. Backfit Analysis ,
1 The NRC has determined that the backfit rule, 10 CFR 50.109, does not apply to this rule, and therefore, that a backfit analysis is not required for j this rule, because these amendments do not involve any provisions that impose backfits as defined in 10 CFR 50.109(a)(1).
List of Subjects 10 CFR part 20 Byproduct material, Licensed material, Nuclear materials, Nuclear power plants and reattors, Occupational safety and health, Packaging and containers, Penalty, Radiation protection, Reporting and recordkeeping requirements, Special nuclear material, Source material, Waste treatment and disposal.
i List of Subjects 10 CFR part 35 Byproduct material, Criminal penalty, Drugs, Health facilities, Health professions, incorporation by reference, Medical devices, Nuclear materials, Occupational safety and health, Penalty, Radiation protection, Reporting and recordkeeping requirements.
53
-v
For the reasons set out in the preamble and under the authority of the Atomic Energy Act of 1954, as amended; the Energy Reorganization Act of 1974, as amended; and 5 U.S.C. 552 and $53; the NRC is adopting the following amendments to 10 CFR parts 20 and 35.
PART 20--STANDARDS FOR PROTECTION AGAINST RADIATION l
l
- 1. The authority citation for part 20 continues to read as follows:
Authorityi Secs. $3, 63, 65, 81, 103, 104, 161, 182, 186, 68 Stat. 930, 933, 935, 936, 937, 948, 953, 955, as amended, sec. 1701, 106 Stat. 2951, 2952, 2953 (42 U.S.C. 2073, 2093, 2095, 2111, 2133, 2134, 2201, 2232, 2236, 2297f), secs. 201, as amended. 202, 206, 88 Stat. 1242, as amended, 1244, 1246 (42 U.S.C. 5841, 5842, 5846).
- 2. Section 20.1002 is revised to read as follows: >
l 20.1002 Scope.
The regulations in this part apply to persons licensed by the Commission to receive, possess, use, transfer, or dispose of byproduct, source, or special nuclear material or to operate a production or utilization facility under parts 30 through 35, 39, 40, 50, 60, 61, 70, or 72 of this chapter. The limits in this part do not apply to doses due to background radiation, to exposure of patients to radiation for the purpose of medical diagnosis or therapy, to exposure from individcals administered radioactive material and released in accordance with 5 35.75, or to exposure from voluntary participation in medical research programs.
54 Y
a
l i
- 3. Section 20.1003, the footnote to the definition of member of the pubile is removed and the definitions of occupational dose and pubile dose are revised to read as follows:
i 20.1003 Definitions.' .
Occupational dose means the dose received by an individual in the course of employment in which the individual's assigned duties involve exposure to radiation or to radioactive material from licensed and unlicensed sources of radiation, whether in the possession of the licensee or other person.
Occupational dose does not include dose received from background radiation, from any medical administration the individual has received, from exposure to individuals administered radioactive material and released in accordance with i 35.75, from voluntary participation in medical research programs, or as a member of the public.
Public dose means the dose received by a member of the public from exposure to radiation or radioactive material released by a licensee, or to any other source of radiation under the control of a licensee. Public dose does not include occupational dose or doses received from background radiation, from any medical administration the individual has received, from exposure to individuals administered radioactive material and released in accordance with i 35.75, or from voluntary participation in medical research programs.
- 4. Section 20.1301, paragraph (a) is revised to read as follows:
1 20.1301 Dose limits for individual members of the public.
55 4
j (a) Each licensee shall conduct operations so that--
(1)= 1he total effective dose equivalent to individual members of the public from the licensed operation does not exceed 0.1 rem (1 millistevert) in a year, exclusive of the dose contributions from background radiation, from any medical adiiiin,inseiun the individual has received, from exposure to individuals admintstered radioactive material and released in accordance with 5 35.75, from voluntary participation in medical research programs, and from the licensee's disposal of radioactive material into sanitary sewerage in accordance with 6 20.2003, and (2) The dose in any unrestricted area from external sources, exclusive of the dose contributions from patients administered radioactive material and j released in accordance with i 35.75, does not exceed 0.002 rem (0.02 millistevert) in any one hour.
- 5. Section 20.1903, paragraph (b) is revised to read as follows:
6 20.1903 Exceptions to posting requirements.
(b) Rooms or other areas in hospitals that are occupied by patients are not required to be posted with caution signs pursuant to i 20.1902 provided that the patient could be released from licensee control pursuant to i 35.75 of this chapter.
PART 35--ME01 CAL USE OF BYPRODUCT MATERIAL
- 6. The authority citation for part 35 continues to read as follows:
56
I l
l l .
Authority: Secs. 81, 161, 182, 183, 68 Stat. 935, 948, 953, 954, as amended (42 U.S.C. 2111, 2201, 2232, 2233); sec. 201, 88 Stat. 1242, as ,
amended (42 U.S.C. 5841).
/. ,'bettion 35.8, paragraph (b) is revised to read as follows:
i 35.8 Information collection requirements: OMB approval.
(b) The approved information collection requirements contained in this part appear in il 35.12, 35.13, 35.14, 35.21, 35.22, 35.23, 35.27, 35.29, 35.13, 35.50, 35.51, 35.53, 35.59, 35 60, 35.61, 35.70, 35.75, 35.80, 35.92, 35.204, 35.205, 35.310, 35.315, 35.404, 35.406, 35.410, 35.415, 35.606, 35.610, 35.615, 35.630, 35.632, 35.634, 35.636, 35.641, 35.643, 35.645, and 35.647.
- 8. Section 35.75 is revised to read as follows:
5 35.75 Release of individuals containing radiopharmaceuticals ur permanent implants.
(a) The licensee may authorize the release from its control of any individual who has been administered radiopharmaceuticals or permanent implants containing radioactive material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 millisieverts (0.5 rem).'
(b) The licensee shall provide the released individual with instructions, including written instructions, on actions recommended to
' Regulatory Guide 8.39, " Release of Patients Administered Radioactive Materials" (1996), describes methods for calculating doses to other individuals and contains tables of activities not likely to cause doses exceeding 5 millisteverts (0.5' rem).
57
4 maintain doses to other individuals as low as is reasonably achievable if the total effective dose equivalent to any other individual is likely to exceed 1 mil 11 sievert (0.1 rem). If the dose to a breast-feeding infant or child could exceed 1 millisievert (0.1 rem) assuming there were no interruption of ureast-feeding, the instructions shall also include (1) guidance on the interruption or discontinuation of breast-feeding and (2) information on the consequences of failure to follow the guidance.
(c) The licensee shall maintain a record of the basis for authorizing l I
the release of an individual, for 3 years after the date of release, if the total effective dose equivalent is calculated (1) using the retained activity rather than the activity administered (2) using an occupancy factor less than 0.25 at I meter, (3) using the biological or effective half-life, or (4) considering the shielding by tissue.
(d) The licensee shall maintain a record, for 3 years after the date of release, that instructions were provided to a breast-feeding woman if the radiation dose to the infant or child from continued breast-feeding could result in a total effective dose equivalent exceeding 5 millisteverts (0.5 rem).
5 35.315 (Amended]
- 9. In 5 35.315, paragraph (a)(6) is removed and reserved.
.6 35.315 Safety precautions.
(a) * * *
(6) (Reserved]
58 4
- 10. Section 35.415, the introductory text to paragraph (a) and paragraph (a)(1)arerevisedandparagraph(a)(5)isremoved.
5 35.415 Safety precautions.
(a) For each patient receiving implant therapy and not released from licensee control pursuant to i 35.75 of this part, a licensee shall:
(1) Not quarter the patient or the human research subject in the same room as an individual who is not receiving radiation therapy.
Dated at Rockville, Maryland, this day of , 1996, for the Nuclear Regulatory Commission.
John C. Hoyle, Secretary of the Commission.
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1 i
l . 1 ATTACINENT - 2 ORAFT REGULATORY GUIDE 8.39
.c=
NOTE TO COMMIS$10N-This guide is a working. draft rather than a final draft, it does'not-have Office concurrence, and it has not yet undergone final editing. =lt.
is thus subject to change before publication, but it is expected that the changes will be relatively-minor, 'There should be no difficulty lin' publishing the final guide before the' final rule is effective.
REGULATORY GUIDE 8.39 (Draft was issued as DG-8015)
RELEASE OF PATIENTS kDMINISTERED RADI0 ACTIVE MATERIALS A. INTRODULIIDH Section 35.75, " Release of individuals containing radiopharmaceuticals or permanent implents," of 10 CFR Part 35, " Medical Use of Byproduct Material," permits licensees to ' authorize the release from its control of any individual who has been administered radiopharmaceuticals or permanent implants containing radioactive material if the total effective dose equivalent to any other individual from exposure to the released individual is not liKely to exceed 5 millisteverts (0.5 rem)."
in addition,10 CFR 35.75(b) requires that the licensee " provide the released individual with instructions, including written instructions, on ORAfl: October 13, 1995
I actions recommended to maintain doses to other individuals as low as reasonably achievable if the total ef fective dose equivalent to any other l
individual is likply to exceed I millistevert (0.1 rem)."
Section 35.75(c) requires that the licenseo maintain "a record of the basis for authorizing the release of a individual for 3 years after the date ,
of release, if the total effective dose equivalent is calculated (1) using an activity less than the activity administered, (2) using an occupancy factor less than 0.25 at I meter, (3) using the biological or effective half-life, or (4) considering the shielding by tissue."
Section 35.75(d) requires that the licensee malnatin a record "that instructions were provided to a breast-feeding woman if the radiation dose to the infant or child from continued breast-feeding could result in a total effective dose equivalent exceeding 5 millisteverts (0.5 rem)."
Hereafter in this guide the individual to whom the radioactive material has been administered will be called the patient.
This guide provides guidance on determining when a licensee may authorize the release of a patient and when instructions must be given and records kept. The guide lists activities for commonly used radionuclides and their corresponding dose rates with which a patient may be released in compliance with the dose limits in 10 CFR 35.75.
The information collections contained in this regulatory guide are covered by the requirements in 10 CFR 35.75, which have been approved by the Office of Management and Budget, Approval No. 3150-0010.
B. DISCUSSION The activities were calculated by using, as a starting point, the method discussed in National Council on Radiation Protection and Measurements (NCRP)
Report No. 37, " Precautions in the Management of Patients Who Have neceived Therapeutic Amounts of Radionuclides."'
' National Council on Radiation Protection and Measurements, " Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides," Report No. 37, 1970.
DRAfi: October 13, 1995 2
I NCRP Report No. 37 uses the following equation to calculate the exposure until time t at a distance r from the patient:
1 3 4. 6 0 0,1, ( 1-e'""4) )
O(t) - (Equation 1) )
r' l l
Where O(t) - accumulated exposure at time t, in roentgens. . i 34.6 - conversion factor of 24 hrs / day times the total integration of decay (1.44),
f- specific gamma ray constant for a point source, R/mC1 h at I cm, 0, - initial activity of the point source in millicuries, at the time of the release, T, e physical half-life in days, r- distance from the point source to the point of interest in centimeters, t- exposure time in days.
This guide uses the NCRP equation (Equation 1) in the following manner to calculate the activities at which patients may be released.
- The dose to an individual likely to receive the highest doso from exposure to the patient is taken to be the dose to total decay.
Therefore, (1-e'""4) is set equal to 1.
- It is assumed that I roentgen is equal to I rem.
- The doses are calculated using the physical half-life of the radionuclides given in Appendix A and do not account for the biological half-life of the radionuclide.
- The gamma ray constants and half lives for radionuclides typically used in nuclear medicine and brachytherapy procedures are given in Appendix A to this guide.
DRVT: October 13, 1995 3
e for radionuclides with half-lives greater than 1 day, it is assumed that the individual likely to receive the highest dose
, from exposure to the patient would receive a dose of 25 percent of the dose to total decay (0.25 in Equation 2) at a distance of
-100 centimeters. Selection of 25 percent of the dose to total decay for estimating the dose is based on measurements indicatin; that the dose calculated using the factor is conservative in most -
normal situations.-
e for radionuclides with half-lives no greater than 1 day, the factor of 0.25 used in Equation 2 is replaced with a factor of 1.0 to give Equation 3. The factor of 0.25 may not be valid when relatively long-term averaging of behavior cannot be assumed.
Thus, for radionuclides with a half-life greater than 1 day:
34.6 0Q T,(0.25) I D(m) = (Equation 2)
(100 cm)'
for radionuclides with a half-life no greater than 1 day:
34.6r0.T, D(=) = _-(Equation 3)
(100 cm)'
Equations 2 and 3 calculate the dose from external exposure to gamma radiation. The equations do-not explicitly include dose from internal intake by household members and members of the public because the dose from intake by other individuals is expected to be _small for most radiopharmaceuticals (less than a few percent) relative to the gamma dose (see Section 3.2 of Appendix B). furiner, the equations above do not apply to the dose to breast =
feeding children who continue to breast-feed. Breast-feeding must be considered separately as described below.
DRAFT: October 13, 1995- 4
1 C. REGULATORY POSITION
- 1. RELEASE CRITERIA 1.1 Activities for Release of Patients Licensees may demonstrate corapliance with the dose limit in -
10 CFR 35.75(a) for release of patients from licensee control if the activity administered is no greater than the activity in Column 1 of Table 1. In this case, no record of the release is required. If the activity administered exceeds the activity in Column 1 of Table 1, the licensee may hold the patient until the activity in the patient's body is no greater than Column 1 of Table 1 and then authorize release. In this case a record is required by 10-CFR 35.75(c) because the release is based on an activity less than the activity administered.
1.2 Dose Rates for Release of Patients Licensees may also demonstrate compliance with the dose -limit in 10 CFR 35.75(a) for release of patients from licensee control if the dose rate at 1 meter (from the patient-centerline) is no greater than-the value-in Column 2 of Table 1 for that radionuclide, if the release is based on the dose rate at _1 meter, a record of the measured dose rate is required by 10 CFR 35.75(c) because the measurement includes shielding by tissue.
1.3 Releases Based on Case-Soecific Factors
. Licensees may calculate the maximum likely dose to an individual exposed to the patient on a case-by-case basis to account for factors specific to a patient. In such cases, licensees may be able to release-a patient with radioactive material in excess of the activity listed in Table 1 and still
. demonstrate con.pliance with the annual dose limit. Licensees may take into account-the effective half-life of the radioactive material and other factors that may be relevant to the particular case.
DRAFT: .0ctober 13, 1995 5
Appendix B contains procedures for performing case-specific dose calculations, and it describes how various factors may be considered in the calculations.
1.4 Special Consideration for Breast Feedino Women 1he release quantities in Table 1 do not includ: c:r.:idor: tion of the dose te a breast-feeding infant from ingestion of radiopharmaceuticals i
contained in a woman's breast milk. If the patient is a breast-feeding woman it may be necessary to give instructions as described in Section C.2.3 as a condition for release because the activities in Table 1 could cause a dose I exceeding 5 millisteverts (0.5 rem) to the breast-feeding infant if there were no interruption of breast-feeding.
draft: October 13, 1995 6
Table 1. Activities and Dose Rates for Authorizing Patient Release and Giving Instructions' Column 1 Column 2 Column 3 Column 4 Dose Rate At Activity At Or 1 meter At Requiring Requiring Below Which Or Below Instructions If Instructions Patients May Which Activity Is If Dose Rates Be Released Patients May Greater Than at 1 meter Is Be Released Greater Than Radio-nuclide (mci) (GBq) (mrom/hr) (mci) (Gbq) (aram/hr) >
Ag-ll! 500 20 8 100 4 2 Au-198 90 3 20 20 0.7 4 Cr-51 100 4 2 20 0.8 0.4 Cu-64 200 9 30 40 2 5 Ga-67 200 9 20 40 2 4 1-123 160 6 20 30 1 4 1-125 8.7 0.32 1 1.7 0.06 0.2 (implant) 1-125 7 0.2 1 1.4 0.5 0.2 1-131 30 1.2 7 6 0.24 1.4 In-ll! 60 2 20 10 0.4 4 Ir-192 1.6 0.06 0.8 0.3 0.01 0.1 P-32 100 4 NA 20 0.8 NA Pd-103 40 1.5 3 7.9- 0.29 0.7 implants Re-186 900 30 10 200 7 2 Re-188 600 20 20 100 4 4 Sc-47 300 10 10 50 2 3 Se-75 2 0.07 .5 .4 0.01 0.1 Sm-153 700 30 30 100 5 6 Sn-117m 30 1 4 6 0.2 0.8 Sr-80 100 4 NA 20 0.8 NA Tc-99m 700 30 50 100 6 10 T1-201 400 10 20 80 2 4
- Values rounded to one significant figure, except-in a few instances where it:was considered appropriate to use two significant figures. The details of the calculations are shown in NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material,1995.
DRAF1: October. 13, 1995 7
J Y-90 100 4 14A 20 0.8 f1A Yb-169 10 0.4 2 2 0.07 0.4
-l DRAFT: October 13, 1995 8
. = :_
- 2. .Lt1SJMCJ 1045 2.1 Activities Rgguirina Instructions if the total effective dose equivalent to an individua'i exposed to a patient is likely to excced 1 Mllisievert (0.1 rem),10 CFR 35.75(b) requires that the released patient be given instructions, including written instructions, on how to maintain doses to other individuals as low as reasonably achievable.
l.icensees may use the values in Column 3 or Column 4 of Table 1 to determine when instructions must be given to patients who are not breast-feeding. Column 3 provides activities above which an individual could receive a dose of 1 mil 11 sievert (0.1 rem) or more. Column 4 provides corresponding dose rates at 1 meter, based on the activities in Column 3.
If the reletsed patient is a woman who will be breast-feeding after release, licensees may also use Table 2 to determine when additional instructions on the interruption of breast-feeding must be given to the patient to meet the requirements in 10 CFR 35.75(b).
2.2 Content of Initructions The instructions should be specific to the type of treatment given, such as permanent implants or radiciodine for hyperthyroidism or thyroid carcinoma, or they may include additional information for individual situations. The instructions should include a contact and phone number in case the patient has any questions. The instructions should include, as appropriate
- Maintaining distance from other persons, including separate sleeping arrangements, o Minimizing time in public places (e.g., public transportation, grocery stores, shopping centers, theaters, restauranti, and sporting events).
- Precautions to reduce the spread of radioactive contamination, and DRAFT: October 13, 1995 9
- 1he length of time precautions should be in effect. i The Society of Nuclear Medicine published a pamphlet in 1987 that ,
provides information for patients receiving treatment with radiciodine.'
This pamphlet was prepared jointly by the Society of Nuclear Medicine and the NRC., The NRC considers the instructions in this pamphlet to be acceptable instructier.$ fer.pctients, provided specific information is given to patients regarding any case-specific factors. However, licensees may develop their own instructions, addressing the items discussed above as appropriate.
Sample instructions for patients who have _ received permanent implants '
are given in Appendix C.
I 2.3 additional Instructions for Release of Women Who Could be Breast-Feedino after Release lf the patient to be released is a woman who could be breast-feeding after release Table 2 provides information and instructions on the interruption of breast-feeding for the radiopharmaceuticals commonly used in medical diagnosis and treatment. In order to use this table it will be necessary to determine the breast-feeding status of women patients receiving some administrations.
The purpose of describing the consequences is so.that women will understand that breast-feeding after an administration of certain
-radionuclides could cause harm (e.g., iodine-131 could harm the child's thyroid), in other cases, the guidance could simply address avoidance of any unnecessary radiation exposure to the child from breast-feeding.
- " Guidelines for Patients: Receiving Radioiodine Treatment," Society of Nuclear Medicire, 1987. This pamphlet may be obtained from the Society of Nuclear Medicine, 136 Madison Avenue, New-York, NY 10016-6760.
~0 RAFT: October 13, 1995 10
__ ~
Table 2. Activities of Radiopharmaceuticals Administered to Breast-Feeding Women Requiring Instructions and Records Requiring Requiring Recommended Instructions if Records If Duration of Adm. Activity Adm. Actlytty Interruption
- Radio- Is Greater Than Is Greater Than pharmaceutical (mci) (met) 1-131 Na! 0.0004 0.002 Complete cessation l to avoid damage to thyroid 1-123 Na! 0.6 3 NA 1-123 OlH 4 20 NA l-123 mlBG 2 10 24 hr for 10 mci 12 hr for 4 mci 1-125 OlH 0.08 0.4 NA 1-131 OlH 0.34 1.7 NA Tc-99m DTPA 30 150 NA Tc-99m MAA 1.3 6.5 6 hr for 4 mci l
Tc-99m 3 15 24 hr for 30 mci pertechnetate 12 hr for 12 mci Tc-99m DISlDA 30 150 NA Tc-99m 30 150 NA gluccheptonate Tc-99m HAM 10 50 NA Tc-99m MIBl 34 170 NA Tc-99m MDP 30 150 NA Tc-99m PYP 25 125 NA Tc-99m RBC's in 10 50 6 hr for 20 mci vivo labeling Tc-99m RBC's in 30 150 NA vitro labeling Tc-99m sulfur 7 35 6 hr for 12 mci colloid Tc-99m 01PA 30 150 NA aerosol Tc-99m MAG 3 30 150 NA DRAfl: October 13, 1995 11
Ic-99m WBC's 3 15 24 hr for 30 mci 12 hr for 12 mci Ga-67 citrate 0.04 0.2 Complete cessation Cr-51 EDTA 1.6 8 NA In-ll! WBC's 0.3 1.5 6 hr for 0.5 mci
'~
T1-201 1 5 Complete cessation for 3 mci 48 hr for 1.5 101
- NA, reanin9 *not applicable," is used if the administered activity requiring instructions exceeds the maximum activity normally administered.
ORAFT: October 13, 1995 12 j
3, Rf[0RDS 3.1- Records of Release ,
There is no recordkeeping requirement- for immediate release of patients based on Table 1. However, if the release of the patient is based on factors
- other than the standard conservative assur.ptions on which Table 1 is based, 10 CFR 35 <5(c) requires that the licensee maintain, for 3 -years, a record of the= basis for the release. For example, when the licensee releases a patient Ewith an activity that is greater'than the value in the default table, a record of-the basis for the release must be ma6ntained for NRC review during inspection.
Records should-include (1) the patient's name, (2) the radioactive material, (3) the administered activity.-(4) the'date and time of administration, (5) the date and time of the patient's release, (6) the
-case-specific factors that were used in calculating the dose to the j individual, and (7) the estimated dose to an individual exposed to the patient, in those instances for which a case-specific calculation applies to more-than one patient release, the calculation need not be performed again.
.The record for a particular patient's release could reference the calculation done for the- class of patients.
3.2- Records of Instructions A record that instructions were provided is required by 10 CFR 35.75(d)
.if a woman is breast-feeding and failure to interrupt breast-feeding could result in a dose to'the beast-feeding child in excess of 5 millisieverts 1(0.5 rem)-
D'. lHPLEMENTATION
.The pu'rpose of this section is to provide information about the NRC
- taff s plans for using this regulatory guide.
ORAFT: October 13, 1995 13
4 Except in tnose cases in which a licensee uses an acceptable alternative method for complying with 10 CFR 35.75, the method described in this guide will be used in the evaluation of a licensee,'s compliance with 10 CFR 35.75.
i I
I DRAFT: October 13, 1995 14
APPENDIX A Table A-1. Half-Lives and Expc*ure Rate Constants of Radionuclides Used in Medicine Half- Exposure Half- Exposure Radio- Life Rate Constant' Radio- Life Rate nuclide (days)' -
(R ca'/ mci h) nuclide (days)' Constant' (R cm*/ mci h
)
Ag-lll 7.45 0.150 Pd-103 16.97 0.86*
(implants)
Au-198 2.696 2.36 Re-186 3.777 0.168 Cr-51 27.704 0.177 Re-188 0.7075 0.337 Cu-64 0.5292 1.10 Sc-47 3.351 0.626 Ga-67 3.261 0.753 Se-75 119.8 2.60 1-123 0.55 1.61 Sm-153 1.9458 0.425 I-125 60,14 1.42 Sn-ll7m 13.61 1.48 I-125 60,14 1.11* Sr-89 50.5 NA' (implants)
_I-131 8.040 2.20 Tc-99m 0.2508 0.756 In-lll 2.83 3.15 T1-201' 3.044- 0.447 Ir-192 74.02 4.69 Y-90 0.1329 NA' P-3 2 - 14.29 NA' Yb-169 32.01 1.83_
' Keith F. Eckerman, Anthony B. Wolbarst, and Allan C. B. Richardson, Federal Guidance ReDort No -11. Limitina Values of Radionuclide Intake and Air i Concentration and Dose Conversion Factors for Inhalation. Submersion. and Inaestion, Report # EPA-520/1-88-020, Office of Radiation Programs, U. S.
Environmental Protection Agency, Washington, DC,1988.
- The exposure rate factor includes gamma rays and x-rays with an energy above 11.3 kev. The ll.3 kev cutoff is the one used in NCRP Report No. 41,
" Specification of Gamma-Ray Brachytherapy Sources," 1974. The exposure rate constant was calculated from the following equation:
F mci
- * hr
- (1.332 x 10" mci hr )(4rr (100 cm)* ) E f,E,( p gm cmx )
9*'* erg
( 87.6 erg)(1.6 x 10.. MeV)
DRAFT: October 13, 1995 A-1 1
Where E, - the energy of the gamma ray or x-ray i in Mev, f f, - the probability of decay of gamma rays or x-rays with energy E, per disintegration. Values for E, and f, were taken from:
Bernard Shleien, The Health Physics arid Radioloaical Health l' Handbook, Revised Edition, Scinta, Inc., 1992,-pages 294-334. For Re-186, Re-188, and Sn-ll7m the values for E, and f, were taken from: 1.aurie M. Unger and D. K. Trubey, " Specific Gamma-Ray Dose L . Constants for Nuclides Important to Dosimetry and Radioluvit.di Assessment,." 0P.N!/PS L A5/R1, 1982,
- p. , . - the-linear energy absorption coefficient in air of photons of energy E., taken from Radioloaical Health Handbook, U. S.
Department of Health, Education, and Welfare, 1970, page 135.
p- the density of air at standard temperature and pressure, taken to be 0.0012929 gm/cm'.
The details of the calculation of the exposure rate factors are shown in Table A-2, Appendix A to NUREG-1492.
- R. Nath, A.S. Meigooni, and J.A. Heli, " Dosimetry on Transverse Axes of '"I and '"Ir Interstitial Brachytherapy Sources," Medical Physics, Volume 17, Number 6, November / December 1990. The exposure rate constant given is a measured value averaged for several source models and taking into account the n
- attenuation-of gamma rays within the implant capsule itself.
- Ravinder Nath, Yale University School of Medicine, letter to Dr. U. Hans Behling dated March 31, 1993. The exposure rate constant given is a measured value that- takes into account the attenuation of gamma rays within the implant capsule itself.
- Not applicable (NA) because release quantities based on beta emission.rather Lthan gamma emission.
DRAFT: October 13, 1995 A-2
APPEN0!X B PROCEDURES FOR CALCULATING DOSES BASED ON CASE-SPECIFIC FACTORS .
-In certain d tuetions, a licensee may release a patient with an activity
- higher than the values listed in Table 1 for a specific radionuclide.
Licensees e.ay calcuhte-the potential doses to individuals exposed to patients receiving treatment with radioactive material on a case-by-case basis to account for certain factors specific to an individual.
According to 10 CFR 35.75(b), a record must be kept for 3 years of the-basis for the release of the patient if the release of the patient is based on ,
other than standard conservative assumptions. For example,-a licensee may use assumptions-other than the standard conservative ones, i.e., (1) biological elimination rather than j'at the physical half-life of the radionuclide, (2) an occupancy factor less than 0.25 at one meter, or (3) the attenuation of radiation by body tissue of the released individual.
The following equation is generally used to calculate doses:
34.6 FQ,T,E 0(t)'= (Equation B-1)-
(r)'
Where 0(t) - dose to total decay, 34.6 - conversion-factor of 24 hrs / day times the total integration of decay (1.44),
f= exposure rate constant, Q, -- initial activity at the start of the time interval,
- T, - physical half-life, E- exposure factor that accounts for the different occupancy times and distances when an individual is around a patient. This value is typically 0.25 when the distance is 100 cm. .
r - -distance. This value is- typically 100 cm.
- 1. EFFECTIVE HALF-LIFE _ _
DRAFT: October 13, 1995 B-1
- - - _ _ = _ . _
l
'd 1
A licensee may_ take into account the effective half-life of-the
, ~ radioactive material to demonstrate compliance with the dose limits to members of the-public stated in 10 CFR 35.75. The effective half-life is defined as:
T,, , -
(Equation B-2)
T, + T, .. t j.
Where T, - biological half-life of the radionuclide, T, - phys scal half-life of the radionuclide.
Using' the effective half-life, Equation B-1 becomes:
34.6 FQ,T ,,E 0(t) = .(EquationB-3)
} with the factors defined as above, T.,, is the effective half-life.
For radioiodine, the effective half-life comprises the effective half-life of extrathyroidal iodide (i.e., existing outside of the thyroid) and
= the effective half-life of iodide following uptake by the thyroid. The effective half-life for the extrathyroidal and thyroidal fractions (i.e., F i and F,, respectively) can be calculated with the following equations:
Ti .,, = (Equation B-4)
T,3 + T, T,,,, =
(Equation B-5)
T , + T, Where: T , -_ biological half-life for extrathyroidal iodide, T., biological half-life of iodide following uptake by the thyroid, T, - physical half-life of iodine-131.
ORAFT: October 13, 1995 B-2
_ _ . . . _ . . _ . - _ _ > _ . _ . ~ . _ _ _ - . _ - - _ _ . _ _ _ . _ . . ~ _ . __
Thyroid Cancer Examplg: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 100 millicuries (3,700 megabecquerels) of iodine-131, 3 to 4 weeks after thyroid, cancer j surgery, for the treatment of thyroid remnants and metastases. The occupancy factor is 0.25'at.1 meter. .
-. .. Solution: In_ th_is example, we will account. for the elimination 'of iodine-131 from the body by using the biological half-lives appropriate for thyroid ;
cancer to_ calculate the dose. - It is generally recognized that, after surgical removal of the thyroid,-the uptake of iodine-131 by the thyroidal remnants and metastases does not exceed 5 percent of. the administration. -It will be necessary to consider the different biological half-lives for thyroidal and extrathyroidal iodine. The following assumptions are made in this example:
'10 DINE-131 PARAMETERS FOR THYROID CANCER EXAMPLE Physical half-life of iodine-131. T, . . . . . . . . . . . . . . . 8.0 days Extrathyroidal fraction F .i . . . . . . . . . . . . . . . . . . . . . . - 0.95 2 Biological half-life of extrathyroidal fraction, T,i . . . . . . ._0.33 day
- Effectivs half-life of extrathyroidal fraction, T .,, . . . . . . . i ._0.3 day
- Thyroidal fraction, F, ................_.......,.._.0.05' Biological half-life of thyroidal fraction, T., . -. . . . . . . . . 80 days' Ef fective hal f-life of thyroidal fraction, T,,,, . . . . . . . . . . 7.3 days
-Specific-gamma ray constant, f . . . . .-, . . . ._. . . . 2.2 R cm'/ mci h
- ' Personal communication, M. Pollycove, ~ M.D., Visiting Medical Fellow, U.S.
- Nuclear Regulatory Commission, Rockville, MD, April 1995.
' International Commission on Radiological Protection (ICRP), " Radiation Oose to Patients'from-Radiopharmaceuticals," ICRP Publication No. 53, March 1987. -
DRAFT: _ October 13, 1995- B-3
The' total dose comprises the doses from the-extrathyroidal ant. ' Syroidal fractions. _The equation is: -;
34.6 r F Q T .,,(0,25) (l-e "''8'")
3 D(t).= + (Equation B-6)
(100cm)'
34.b 1 t, Q,T,,,, ( 0. 2 5) ( 1-e * "*")
(100 cm)'
l- Substituting the values from above, the dose to total decay is ,
34.6(2.2 R cm'/ mci h)(0.95)(100 mC1)(0.3 d)(0.25)
D(=) =
(100 cm)*
34.6(2.2 R cm'/ mci h)(0.05)(100 mC1)(7.3 d)(0.25)-
(100 cm)'
D(=) = 0.054 + 0.069 0(=) = 0.124 rem (1.24 mSv)
Therefore, thyroid cancer patients administered 100 millicuries
~(3,700 megabecquerels) of iodine-131 or less would not have to remain under
' licensee-control and could be released under:10 CFR 35.75, assuming that the foregoing assumptions can be justified for the individual-patient's case and
'the patient is given instructions.
In the example above, the thyroidal fraction, F, = 0.05, is a conservative assumption. For those individuals who have had surgery to remove
- thyroidal tissue, F, is_ typically smaller and, in some cases, F, is known for a specific individual.
H_YDerthyroidism Example: Calculate the' maximum likely. dose to an individual' exposed to a: patient who has been administered 33 millicuries (1,200 megabecquerels) of iodine-131 for the treatment of hyperthyroidism
-(i.e., thyroid ablation). The occupancy factor is 0.25 at 1 meter.
DRAFT: October 13, 1995 B-4
-Solution: In this example, we will account for elimination of iodine-131 from the' body by using the biological half-lives appropriate for hyperthyroidism to calculate the dose. It will be necessary to consider the different biological half _-lives for- thyroidal and extrathyroidal iodine. The following assumptions are made in this example:
10 DINE-131 PARAMETERS FOR HYPERTHYROIDISM EXAMPLE -
Physical half-life of iodine-131, T, ............... 8.0 days Extrathyroidal fraction, F_i.....................0.45' Biological: half-life of extrathyroidal fraction, T,i - ...... 0.33 day' '
Effective half-life of extrathyroidal fraction, T .,, i . . . . . . . 0.3 day Thyroidal - fraction, F. ........................0.55' Biological-half-life of thyroidal fraction, T,, .......... 21 days' Effective half-life of thyroidal fraction, T,,,, . . . . , . . . . 5.8 ' days' Specific gamma ray constant, f . . . . . . . . . . . . . . 2.2 R cm'/ mci h
' Personal communication, M, Pollycove, M.D., Visiting Medical Fellow, U.S.
Nuclear Regulatory Commission, Rockville, MD, April 1995.
' International Commission c '.adiological Protection (ICRP), " Radiation Dose to Patients from Radiopharmaceuticals," ICRP Publication No. 53 (March 1987).
The total dose comprises the doses from the extrathyroidal and thyroidal- fractions. The equation is:
- 34. 6 f F Q,T .,, (0. 25) (1-e "" '")
3 i D(t) -- + (Equation B-6)
- 34. 6 iF,Q,T,,,, (0. 25) (1-e * """)
(100 cm)'
Substituting the values from above, the dose to total decay is 34.6(2.2R cm'/ mci h)(0.45)(33 mci)(0.3 d)(0.25)
(100 cm)*
DRAFT: October 13, 1995 B-5
_ _ _ _ _ _ = _ _ - - _---_-__-_ -__ ___-__________ ___ _ ___ . _ _ _ _ _
34.6(2.2R cm'/ mci h)(0.55)(33 mci)(5.8 d)(0.25)
(100 cm)* -
0(*) - 0.008 + 0'.200 0(=) = 0.208 rem (2.08 mSv)
Therefore, hyperthyroid patients administered 33 millicuries (1,200 megabecquerels) of iodine-131 or less would not have to remain under licensee control and could be released under 10 CFR 35.75.
Release Time Example:
l Using Equation B-6, it is possible to calculate doses from which release times can be estimated using a graphical method. This is shown in Table B-1 for the maximum quantities normally administered. The values for hyperthyroidism and thyroid ablation are given for various thyroid retention fractions. The licensee's record required by 10 CFR 35.75(b) should indicate the reason for using the assumed thyroid retention fraction.
DRAFT: October 13, 1995 B-6
t 4
i 3
3 1
i
-t Table 3-1.. Release Times Post. Administration for Therapeutic Iodine-131 Procedures Based on- l Biological Retention and Elimination 'I h
5
~
t (To be prepared) .;
f f
P P
i
.}
l i
! t I
l
.i i
'i DRAFT: October..13, 1995 B-7 l
'l .
I
- 2. EXPOSURE FACTOR 4 i
,The distance and the time that other individuals'will spend in t proximity of the patient may occasionally be taken into account when determining the dose to an individual. If the patient is living alone, will i l~ have few if any visits by family or friends, will not be returning to work immediately, and will be generally isolated from other people, the exposure factor can be decreased by a factor of 2 (for example, from the general value j of 0.25 to 0.125). ' This would allow an individual to be released with an activity that is higher than that specified in Table 1 in the regulatory guide. On the other hand, if the patient _needs exter,sive care at home, the exposure factor may have to be increased to account for the increased exp'osure of the individual caring for the patient.
In general, the NRC does not believe that the exposure factors less than -
0.125 can be easily justified because it is not possible to avoid someone I
being exposed to the patient at all times. Lower values for the exposure factor are not specifically prohibited by the regulation, but must be explicitly justified in the record of the calculation, as the record will be subject to inspection.
Example: Calculate the maximum likely dose to an individual exposed to a patient who has received 40 millicuries (1,480 megabecquerels) of iodine-131.
The patient lives alone:and will not be working.
Solution: The dose is calculated using Equation B-1:
34.6 00,T, E D(t)_.=
r' u Since the patient lives alone and will not be returning to work, and therefore will not be around the public,-the exposure factor can be reduced-to 0.125:
-0(t) - 34.6(2.22 R cm'/ mci hr)(40 mC1)(8.05 d)(0.125)
(100cm)'
DRAFT: October 13, 1995 B-8
D= 0.31 rem (3.1 mSv)
, .Since the dose is no greater than 5 millisievert (0.5 rem), the patient may be released but instructions to the patient are required. Because an occupancy factor less than 0.25 at 1 meter was used, a record of the calculation must be maintained pursuant to 10 CFR 35.75(c).
Example: Calculate the maximum likely dose to an individual exposed to a patient who has received 40 millicuries (1,480 megabecquerels) of iodine-131.
- The patient requires extensive care because of other medical conditions.
Solution: Since the patient needs extensive care, the exposure factor will have to be increased to account for the increased time the primary caregiver will spend near .the patient. An exposure factor of 0.5 is used in this example:
0- 34.6(2.2 R cm'/ mci hr)(40 mC1)(8.04 d)(0.5)
(100 cm)'
0- 1.22 rem (12.2 mSv)
Since the dose exceeds 5 millisievert (0.5 rem), the licensee may not
-authorize release. However;. when the patient is releasable,10.CFR 35.75(c) ~
, requires a record of.the release and 10 CFR-35.75(b) requires instructions to'
-the patient if the dose to an individual from the released patient is likely to exceed 1 millisievert (0.1. rem).
-3. DIHER FACTORS 3.1 Attenuation of the Radiation in the Body Licensees may take into account attenuation of the-radiation-by the
. patient. .The fraction of the dose that results after attenuation by the body may be calculated using the following equation:
DRAFT: October 13, 1995 B-9
D= Do e*' (Equation B-8)
{
1 Where 0 - dose after attenuation, 0, - dose before attenuation, p - linear attenuation coefficient of tissue, x - thickness of tissue covering the implant. .
, Also, the dose before attenuation is, from Equation 2 in the guide:
l 34.6 FQ T,(0.25)
D- (Equation B-9) i (100 cm)*
Substituting Equation B-9 for D, in Equation B-8, the dose after attenuation becomes 34.6 0Q,T,(0.25) (e'"')
D= (Equation B-10)
(100 cm)"
Exampl e. Calculate the maximum likely dose to an individual exposed to a patient who has received a permanent implant of 60 millicuries -
(2,220 megabecquerels) of iodine-125. The following factors apply:
F - 1.11 R cm*/ mci hr, T, = 60.2 days, y = 0.387/cm (Ref. B-1),
5 HVLs - 9 cm (assume 5 Half Value Layers in soft tissue; 1 Half Value Layer for iodine-125 = 1.8 cm).
There is a significant reduction in the exposure rate from the shielding effects of the source capsule. The f of 1.11 R.cm*/ mci h for iodine-125 already accounts for the reduction in exposure rate from attenuation by the source capsule.
DRAFT: October 13, 1995 B-10
Based on empirical assessment involving patients with implants, soft tissue shielding for iodine-125 is likely to exceed 5 or more half value layers (Ref. B-1).
Lolution: The dose is calculaten using Equation B-10:
0- 34.6(1.11 R cm'/ mci hr)(60 mCl)(60.2 d)(0.25)(e"' **'/""' "))' '
(100 cm)*
D- 0.107 rem (1.07 mSv)
Therefore, a patient who has received a permanent implant of 60 millicuries (2,220 megabecquerels) of iodine-125 may still be authorized for release. To meet the requirements of 10 CFR 35.75(b), the licensee must provide the patient with instructions and to meet the requirements of 10 CFR 35.75(c), the licensee must maintain a record of the calculation.
Although a correction for attenuation may be calculated, it will usually be simpler to measure the dose rate at 1 meter. If the dose rate is no greater than the rate in column 2 of Table 1, the patient may be released and the record of the survey would serve as the record required by 10 CFR 35.75(c).
3.2 Internal Dose Internal dose may be a consideration with certain radiopharmaceuticals now being developed, such as radiolabeled antibodies, or those that are developed in the future. Some of the radionuclides used in radiolabeled antibodies are predominantly beta or alpha emitters, which emit few gammas.
A rough estimate of the maximum likely committed effective dose equivalent from internal exposure can then be calculated from the following equation:
0, = Q
- 10
- DCF (Equation B-ll)
Where 0, - the maximum likely internal committed effective dose equivalent to the individual exposed to the patient in rems, ORAFT: October 13, 1995 B-ll
Q = the activity administered to the patient in microcuries, l
10 = the assumed fractional intake.
DCf - the dose conversion factor to convert an intake in i
millicuries to an internal committed effective dose !
equivalent (such as tabulated in Reference B-6),
Equation B-ll uses a value of 10 as the fraction of the activity administered to the patient that would be taken in by"the individual exposed f
to the patient. A common rule of thumb is to assume that no more than one 1-millionth of the activity being handled will become an intake to an individual working with the material. This rule of thumb was developed in Reference B-2 for cases of worker intakes during normal workplace operations, worker intakes from accidental exposures, and public intakes from accidental airborne releases from a f acility, but it does not specifically apply for However, two studies cases of intake by an individual exposed to a patient.
(Refs. B-3 and B-4) regarding the intakes of individuals exposed to patients administered iodine-131 indicated that intakes were generally of the magnitude of one 1-millionth of the activity administered to the patient and that To account for the most highly internal doses were f ar below external doses.
exposed individual and to add a degree of conservatism to the calculations, a fractional transfer of 10 has been assumed.
As an example of the use of Equation B-ll, assume that 30 millicuries of iodine-131 was administered to a patient. The dose conversion factor DCF for the ingestion pathway is 53 rems /millicurie from Table 2.2 of Reference B-6, The ingestion pathway was selected since it is likely that most of the intake would be through the mouth or through the skin, which is most closely approximated by the ingestion pathway. Thus, the maximum internal dose to the In this case, the internal individual D, would be calculated to be 0.016 rem.
dose would be about 3 percent of the assumed 5 millisieverts (0.5 rem) external gamma dose. Internal doses may be ignored in the calculations if they are likely to be less than 10 percent of the external dose since the internal dose would be significantly less than the uncertainty in the external dose.
The _ conclusion that internal contamination is relatively unimportant in The NCRP addressed the case of patient release was also reached by the NCRP.
DRAFT: October 13, 1995 B-12
the risk of intake of radionuclides from patients' secretions and excreta in NCRP Commentary No, ll, " Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients." The NCRP concluded that, "Thus, a contamination incident that could lead to a significant intake of radioactive material is very unlikely."(B-5). For additional discussion on the subject, see Reference B-1.
DRAFT: October 13. 1995 B-13
REFERENCES FOR APPENDIX B .
I B-1. Stewart Schneider and Stephen A. McGuire, " Regulatory Analysis on l
Criteria for the Release of Patients Administered Radioactive Material," j
! NUREG-1492 (Final Report), NRC,1995.*
B-2. A. Brodsky, "Resu:p:n:i:r.-Factors and Probabilities of Intake of Material in Process (Or 'Is 10 a Magic Number in Health Physics?'),"
i Health Physics, Volume 39, Number 6, 1980.
B-3. R.C.T. Buchanan and J.M. Brindle, "Radiciodine Therapy to Out-patients -
The Contamination Hazard," British Journal of Radioloav, Volume 43, 1970.
B-4. A.P. Jacobson, P.A. Plato, and D. Toeroek, " Contamination of the Home Environment by Patients Treated with Iodine-131," American Journal of Public Health, Volume 68, Number 3, 1978.
B-5. National Council on Radiation Protection and Measurements, " Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients," Commentary No. 11, February 28, 1995.
B-6 Keith F. Eckerman, Anthony B. Wolbarst, and Allan C. B. Richardson, limitina Values of Radiottuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation. Submersion, and Inaestion, Federal Guidance Report N.11, U. S. Environmental Protection Agency, Washington, 1988.
- Requests for single copies of drafts should be made in writing to the U.S. Nuclear Regulatory Commission, Washington, DC 20555, Attention:
Distribution and Mail Services Section. Requests for drafts will be filled as long as supplies last. Copies of drafts are also available for inspection and copying for a fee from the NRC Public Document Room at 2120 L Street NW.
(Lower Level), Washington, DC. The POR's mailing address is Mail Stop LL-6,
. Washington, DC 20555; telephone (202)634-3273; fax (202)634-3343.
DRAFT: October 13, 1995 B-14
l l
APPEN0 LLC J SAMPLE-INSTRUCTIONS FOR PATIENTS RECE!VING PERMANENT IMPLANTS .
1 A small radioactive source has' been placed (implanted) .inside your body. The source is actually many small metallic pellets .or seeds, which are about 1/3 _
to 1/4 of ar. inch 1:r.;, similar in size and shape to a grain of rice. To-minimize exposure to radiation to others from the source inside your body and to yourself if the source falls out or comes out, you should do the following for days:
- ~ Stay at a distance of feet from .
- Maintain separate sleeping arrangements. e
- Minimize time with children and pregnant women.
- Do not hold or cuddle children.
- Avoid public transportation.
- - Examine any bandages or linens that come into contact with the implant ,
site for. any pellets or seeds that may have come out of the implant site.
- Take the following action if you find a seed or pellet:.
- _Oo not handle it with your. fingers. Use something like a spoon or tweezers to place it in a jar or other container that you can close with a lid.-
- Place the container with_ the seed / pellet in a location-away from people.
- Notify one of the individuals listed below.
If you have any questions, contact the following individual (s):
Name Phone' number Beeper' number-
' Name. Phone _ number Beeper number e
. DRAFT: October 13, 1995 C-1 4
- - , .e-- -
3 -- . , - - , ,,e , ,.-v-.s, r
REGULATORY ANALYSIS
]
" Regulatory Analysis on Criteria for the Release of Patients ,
Administered Radioactive Material" (NUREG-1492, S. Schneider et al., 1995),
provides the regulatory basis for this guide and examines the costs and benefits. A copy of NUREG-1492 is available for inspection and copying for a f:0 at the NRC Public Document Room, 2120 L Street NW., Washington, DC.
ORAFT: October 13, 1995 RA-1
. .. . . . . . . , . . . ...n
..,.,.... , , ,ggg e-agmy g 9
G
+
ATTACHMENT - 3 REGULATORY ANALYSIS /NUREG-1492 4
i _ _ . - . - _ _ _
-4
SUMMARY
OF MAJOR CHANGES TO REGULATORY ANALYS11
- l (CRITERIA FOR THE RELEASE OF PATIENTS ADMINISTERED RADICACTIVE MATERIAL) l 1. Costs ner man-rts l
Original RA: Used $1,000 per' person-rem.
Revised RA: Used $2,000 per person-rem.
-2. Half-lives of radionharmaceuticals in body-
- Original RA: Used physical half-life.
For- I-131, T,=8.04 days.
Revised RA: Used effective half-life (biological and physical).
For I-131 in thyroid,~ T,-20 days-(approximate, it varies slightly with uptake fraction);-T,-5.73 days.
For I-131 in whole body _ (other than thyroid), T,=0.33 '
days; T,-0.32 days. _
- 3. -Votake fraction for thyroid and the whole body fother than-thyroid)
Original RA: Since physical half-life was used,_ the use of uptake j fraction was not necessary.
Revised RA: For thyroid ablation, four uptake fractions for thyroid and for whole body are used. An average dose is estimated by averaging four doses calculated by each uptake fraction.
' For thyroid cancer, uptake fractions for thyroid of.
O.95 and for whole body of 0.05 are used.
- 4. Impact on breast-feedina wom3n and infant (section 4.2.4.3) 4 Original RA: Some discussion.
Revised RA: Expanded discussion.
- 5. Chanaes in Cost and benefit estimates increase in Collective Dose Decrease in Hospital Cost person-rem $1,000 $2,000 Original RA:
Using physical 9,000 $9M $18M $8M Tu,.and $1000 per person-rem Revised RA*:
Using physical 2,700 $2.7M $5M $14M and BIOLOGICAL Tu, and $2000 per person-rem The revised cost-benefit analysis indicates that almost all patients who receive radiopharmaceutical therapy may be released from the hospital immediately if the physician elects to perform a case-specific calculation to show compliance with the dose-based release criteria. Any individual associated with the patient's family would be unlikely to receive a dose of 500 mrem within a year.
i s
l l Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material Final Report Prepared by:
Stewart Schneider and Stephen A. McGuire Office of Nuclear Regulatory Research U.S. Nuclear Regulatory Commission Washington, D.C. 20555 April 10,1996 w
~
SJ 4
w._ ,
L ABSTRACT The Nuclear Regulatory Commission (NRC) has The evaluation demonstrates that diagnostic received three petitions to amend its regulations procedures are unaffected by the choice of in 10 CFR Parts 20 and 35 as they apply to doses alternative. Only some therapeutic received by members of the public exposed to administrations of radioactive material could be patients released from a hospital after they have affected by the choice of alternative. The been administered radioactive material. While the evaluation indicates that Alternative 1 would cause three petitions are not identical, they all request a large increase in the national health care cost that the NRC establish a dose limit of 5 millisienrts from retaining patients in a hopital longer and (0.5 rem) pei year for individuals exposed to would cause significant personal and psychological patients who have been administered radioactive costs to patients and their families. The choice of materials. This Regulatory Analysis evaluates Alternatives 2 or 3 veould affect only thyroid three alternatives. Alternative 1 is for the NRC cancer patients and some hyperthyroid patients
- to amend its patient release criteria in 10 CFR 35.75 treated with iodine-131. For those patients, to use the more stringent dose limit of 1 millislevert Alternative 3 would result in less hospitalization (0.1 rem) per year in 10 CFR 20.1301(a) for its than Alternative 2. Alternative 3 has a potential patient release criteria. Alternatie 2 is for the decrease in national health care cost of NRC to continue using the existing patient release $13,700,000 per year but would ' t
- case the criteria in 10 CFR 35.75 of 1,110 megabecquerels potential collective dose from released therapy (30 millicuries) of activity or a dose rate at patients by about 2,740 person-rem per year, 1 meter from the patient of 0.05 millislevert mainly to family members. Alternative 3 would (5 millirems) per hour. Altetaative 3 is for the also have personal and psychological benefits for NRC to amend the patient release criteria in th: patients and their families.
10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) for patient release.
iii NUREG 1492 s
CONTENTS ABSTRACT.. ... ... .. .. . . . . . . . . iii ACKNOWLEDGEMENTS .... . .. .. . . . ..., . . .. . . . . ix 1 STATEMENT OF TIIE PROBLEM . . ... ... . . .. . ... . . ... . 1 2 OBJECTIVES OF Tile RULEMAKING . ...... ... ... .. .. ...... . .. 2 3 ALTERNATIVES . . . . . . . . . . . . . . ... . ... .. ....... ..... ,, ... . ... .. 2 4 CONSEQUENCES ..... .. ...... .. ... .... .... ..... ..... ...... . 2 4.1 Current Uses of Radiopharmaceuticals . . .... . .......... .. ............. .2 4.1.1 Diagnostic Administrations . . . ... ... .......... . . . .. ... . ...3
( 4.1.1.1 Estimates of the Number of Diagnostic Procedures Performed . .3 4.1.1.2 Age and Sex Distribution of Patients . . .. . . .. . .. . 4 4.1.2 Therapeutic Administrations . . . . .. ... . . .. . . . . 6 4.1.2.1 Radiopharmaceuticals Used in Therapy . . . . . . ... ... . . 6 4.1.2.2 Radioactive Materials Used in Permanent Implants (Brachytherapy) . , . .9 4.1.2.3 Summary of Therapeutic Administrations .. . . .... ... . . .. .. 10 4.2 Assessment of Doses to Individuals Exposed to l'atients Administered Radioactive Materials .. . ... .. ... ... . .. .. , ,. . ,, . . . ... 10 4.2.1 Methodology for Calculating External Gamma Dose ... , ,. . . . ... ,, 10 4.2.1.1 Occupancy Factor . . . ... .. .. ... . .. . 11 4.2.1.2 Exposure Rate Constant . ... ... ... .. . . . . 13 4.2.13 Biological Retention and Elimination . . .. ... . . . . .. 13 4.2.1.4 Tissue Shielding for Permanent implants . . . .. . . . . 14 4.2.2 Assessment of Internal Exposure . . ... .. . . . 14 4.2.2.1 Internal Exposure Pathways . . .... .. . . . 14 4.2.2.2 Measurements of Internal Exposure . . 15 4.2.3 Estimate of Maximum Likely Doses to Indhiduals Exposed to Patients . 16 4.23.1 Diagnostic Procedures . . . .. . . 16 4.2.3.2 Therapeutic Procedures . . . ... , 16 4.2,4 Assessment of Doses to Breast-Feeding Infants .. 16 4.2.4.1 Internal Dose . , .
19 4.2.4.2 External Dose . 19 4.2.43 lodine 131 Sodium lodide 19 4.2.4.4 Summary of Doses to Breast-Feeding infants 20 v NUREG 1492 v
4.2.5 Collmive Dose . . ...... ... .. . ....... .... ............. . ... 21 4.2.5.1 Collective Dose to Individuals . . . . . . . ....... ... . . . .... 21
. 4.2.5.2 Collective Dose to Breast Feeding infants . . . . . . . .. .... . . . . . 24 43 Value impact Analysis . . . . . . . . . . . . . . . . . ......... ....... . ............ , , 24 43.1 Estimates of the Potential Costs . . . . . . .................. ................ 24 43.1.1 Estimates of the Direct Costs of Patient Retention . .................... 24 43.1.2 Derivation of Indirect Costs . . . . . . . . . . . . . . . . . . . . .................. 26 43.13 Evaluation of Psychological Costs . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . 27 -
43.2 Costs and Benefits of Alternatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 4.4 Evaluation of the Alternatives With Respect to Accepted Radiation Protection Pr in cip les . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
~ 5 - DECISION RATIONALE . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...., ................ 28 6 IM PLEM ENTATI O N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , 29
? REFERENCES. . . . . . . . . . . . . . . . . . . . . ...................... ...... ......... 30 APPENDIX A . Parameters and Calculations for Determining Release Ouantities and Dose Rates for Radionuclides Used in Medicine . . . . . . ... ............ . A.1 APPENDIX B . Parameters and Calculations for Determining Instructions to Breast. Feeding Women.........,........................................... . . . B.1
' B.1 Calculational Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. ............ . . . B.1 B.2 Results .. ... .. . . .. ..... .............. . ... ... . . . . . . B .2 B.2.1 Biokinetic Data for Excretion of Radiopharmaceuticals in Breast Milk . . ........ . B.2 B.2.2 Radiation Dose Estimates . . . . . . . . . . . . . . .... . .......... .... ,.......B3 B3 References . . .. . . ........ . ............ . . . ... ...... B.25 Tables 4.1 Estimated Number of Diagnostic Radiopharmaceutical Procedures Performed in the U.S.
Between 1972 and 1982 . .. .... . . ...... .... ....... .... . . . 4 4.2 Estimated Radiopharmaceutical Use for Diagnostic Procedures in the U.S. in 1993 .. .. .5 43 Age and Sex Distribution of Patients Having Nuclear Medicine Examinations . . .... 6 4.4 Number of Annual Therapeutic Administrations in the U.S. (significant gamma emitting
- radionuclides only) .. . . . ... . . . . . 11 NUREG.1492 vi x
4.5 Family Doses from Patients Treated with lodine.131 for Thyroid Carcinoma . . .. . . 12 ~f 46 lodinc.131 Biological Retention and Elimination Parameters for llyperthyroidism, Thyroid Ablation, and Thyroid Cancer . . . . . . . . . .. .. .. . .. .. . ...... 14 1
1 4.7 - Maximum Likely Doses to Total Decay to Exposed Individuals from Diagnostic Procedurcs . . 17 4.8 Maximum Likely Doses to Total Decay to Exposed Individuals from Therapeutic Procedures
~~
Assuming No llospitalization . . . . . . . . . . . . . . .......... ..... ................ 18 4.9 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 1:
Annual Limit of 1 millisievert (0.1 rem) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 4.10 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Alternative 2.:
Limit of 1,110 megabecquerels (30 millicuries) or 0.05 millisievert (5 millirems)/hr . . . . . . . . 22 4.11 Estimates of Collective Dose from Therapeutic Radiciodine Procedures for Alternative 3:
Annual Limit of 5 millisieverts (0.5 rem) . . . . . . . . . . . . . . . . . . . . . .. . .,........., 23 l 4.12 Duration of Retention per Therapeutic Procedure . ......... ... .............. 25 1
4.13 Annual Attributes of Alternatives 1,2, and 3 . ........ ... ............. ...... 27 4.14 Annual Costs and Benefits of Alternatives 1 and 3 Compared to Alternative 2 (The Status Ouo) . .............. . .. . ... .. ...... ..... . 28 A.1 Half Lives and Exposure Rate Constants of Radionuclides Used in Medicine . . . . . . . . . . . . . A.1 A.2 Calculations of Exposure Rate Factors, Release Quantities, and Release Dose Rates . . . . .A3 B.1 Effective Dose Equivalents to Newborns and One. Year. Olds from Infant's lutake of Radiopharmaceuticals . . . . .. . .......... , ....... ................. B.4 B.2 Excretion Fractions and Biological Half. Lives for Radiopharmaceuticals Excieted in Breast Milk . . . . . . . . . . . . . . . .. . . ... .................. . . B.5 B3 Biological and Physical Pr.rameters Used to Calculate the Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals in Breast Milk . . B.8 B.4 Total Activity Ingested and Internal Radiation Doses Received from the intake of Radiopharmaceuticals iu Breast Milk Under Different Interruption Schedules . . B.10 B.5 Potential Doses to Breast-Feeding infants from Radiopharmaceuticals Administered to a Woman if No Interruption of Breast. Feeding and Recommendations on Interruption of Breast. Feeding . . . . ........ . . . . . .. . . B.23 vii NUREG.1492 5
D ACKNOWLEDGEMENTS Mmh of the statistical and technicalinformation P. Paras, Ph.D., Food and Drug required for this analysis is not ava table in the Administration, Center for Desices and open literature. In such instances, information Radiology IIcalth, Rockville, MD was obtained directly itora technical expests. The following individuals are acknowledged for their M. Pollycove, M.D., Visiting MedWI cooperation and contribution of technical Fellow, U.S. Nuclear Reculatory information and data. Commission, Wa's hington, DC '
R. Atcher, Ph.D., Radiation and Cellular Oncology Department., University of G.E. Powers, Ph.D., Office of Nuclear Chicago, Chicago,IL Regulatory Research, U.S. Nuclear 7 Regulatory Commission, Washington, DC K. Ilciding, S. Cohen and Associates, McLean, VA M. Rosenstein, Ph.D., Food and Drug Administration, Center for Devices and U. II. Ilehling, S. Cohen and Associates, Radiology llealth, Rockville, MD Mclean, VA J. St.Germain, Radiation Safety Officer, D. Flynn, M.D., (NRC Advisory Committee Memorial Sloan Kettering, New York City, NY on Medical Use of Isotopes) Massachusetts General llospital, Iloston, MA B A Siegel, M.D., (Chairman, NRC D. Goldin, S. Cohen and Associates, Advisory Committee $m Medical Use of McLean, VA Isotopes) Director, Dmsmn of Nuclear Medicine, Mallinckrodt Institute of
" '"EY' W.R. llendee, Ph.D., Dean of Research, "". E'" " * I * #"'
Medical College of Wisconsin, Milwaukee, WI ' # ' ' ***
P. Ilolahan, Ph.D., U.S. Nuclear Regulatory M.G. Stabin, Ph.D., CilP, Radiation Commission, Washington, DC Internal Dose information Center, Oak Ridge Institute for Science and Education, C. Jacobs, President, Theragenics, Oak Ridge, TN Norcross, G A D. Steidley, Ph.D., CllP, Medical l{calth FA Mettler, M.D., Department of Physicist, Department of Oncology, St.
Radiology, University of New Mexico, Barnabas Medical Center, Livingston, NJ School of Medicine, Albuquerque, NM J. Stubbs, Ph.D., Radiation Internal Dose
- K.L Miller, CHP, Professor of Rcdiology information Center, Oak Ridge institute for and Director, Dmsion of Ilealth Physics, Science and Education, Oak Ridge, TN Milton tiershey Medical Center, liershey, FA R. Nath, Ph D., Professor of Yale K. Suphanpharian, Ph.D., President, Best University, School of Medicine, and Industries, Springfield, VA Preslient of the American Association of Nuch at Physics, New Ilaven. CT R.E. Toohey, Ph D., CllP, Director, Radiation Internal Dose information M P. Nunno, Ph.D., CllP, Cooper llospital, Center, Oak Ridge Institute for Science and University Medical Center, Camden, NJ Education, Oak Ridge. TN is NURliG 1492
i 1 STATEMENT OF Tile (1) Rahe the aaaual radiation dose limit in pj{()l,gM 10 CFR 20.lT01(a) for individuals exposed to radiation ftom patients receiing adiopharma. (cuticals for diagnosis or therapy from I milli. sievert (0.1 rem) to 5 millisieverts (0.5 rem). Each year in the UK, radioactive pharmaceuticals (2) Amend 10 CFR 35.75(a)(2) to retain the or compounds or radioactive implants are 1,110 megabecquerel (30-millicurie) limit for administered to rougHy H to 9 million patients for iodine.131 (1 131), but p ue ml achity the diagnosis or treatment of disease. These limit fc. at'.a . 4a.. dides consistent with people can expose others around them to the calculational methodology employed in radiation until the radioactive material has been the National Council on Radiation Protection excreted from their bodies or has decayed away, and Measurements (NCRP) Report No. 37,
- Precautions in the Management of Patients NRC's patient release criteria in 10 CFR 35.75, Who llave Received Therapeutie Amounts of
- Release of patients or human research subjects Radionuclides * (NCRP70),
containing radiopharmaceuticals or permanent implants,* are as followe *(a) A licensee rnay not (3) Delete 10 CFR 201301(d) which requires authorire release from confinement for medical licensees to comply with provisions of EPA's care any patient or human research subject etnironmental regulations in 40 CFR Part 190 administered a radiopharmaceutical until either: in addition to complying with the requirements (1) The measured dose rate from the: patient or of 10 CFR Part 20. the human research subject is less than 5 millirems per hour at i distance of 1 meter; or The second petition, submitted by the American (2) The activity in thr patient or the human College of Nuticar Medicine (ACul)(PRM.3510, research subject is less than 30 millicuries; 57 FR 8282, as revised by PRM 35-10A, (b) A licensee may not authorire release from 57 FR 21043), requested that the NRC: confinement for medical care of any patient or human tscarch subject administered a penaanent (1) Adopt a dose limit of 5 millisleverts (0.5 rem) implant i . .il the measured dose rate from the for indhiduals exposed to patients who have patient or the human research subject is less been administered radiopharmaceuticals. than 5 millirems per hour at a distance of 1 meter." (2) Permit licensees to authorire release from On May 21,1991, the NRC published a final rule hospitaliation any patient administered a that amended 10 CFR Part 20,' Standards for radiopharmacentical even if the activity in the Protection Against Radiation" (56 FR 23360), patient is greater than 1,110 megabecquerels The rule contained limits on the radiation dose (30 millicuries) by defining " confinement
- to for members of the public in 10 CFR 20.1301, include confinement in a private residence.
Ilowever, when 10 CFR Part 20 was issued, there was no discussion in the supplemental infu mation A third petition (PRM 3511,59 FR 37950) on whether or how the prosisions of 10 CFR 20.1301 dealing, in part, with these same issues a submitted were intended to apply to the release of patients, by the American Medical Association (AMA). thereby creating the need to address this issue. The main point of the petition is that the radiation dose limits in 10 CFR 20.1301 should llecause some licensees were uncertain what effect not apply to indhiauals exposed to the patient, the revised 10 CFR Part 20 would have on patient release criteria, three petitions for rulemaking Since the petitions submitted by Dr. Marcus, the were received on this issue. 'lhe first petition, ACNM, and the AMA all address the patient submitted by Dr. Carol S. Marcus (PRM.20-20, release criterii. in 10 CIR 35.75, the NRC decided 56 FR 2t#45), requested that the NRC: to resolve these petitions in a single rulemaking. I NURihl492 t
2 OB.lECTIVES OF Tile controlling requirements for determining when a RULEMAKING D'"' "' h con t rol."' 'Y * ' * '* *
- d "" * ""
e Mternative 3: 5 millisieverts (0 5 rem) total The objective of this tulemaking is to respond to effective dose couivalent) the three petitions for rulemaking by amend:rg, as deemed appropriate, the patient release criteria in This alternative evaluates a dose limit of 10 CFR 33.75. 5 milli.icart. (0.J nm) to an individual
- p ::d to a patient as the limiting factor for determining when a patient may be released from the licersee's control.
3 ALTERNATIVES 4 CONSEQUENCES As the petitious and the public comments that were submitted to the Commission on the petitions made clear, some licensees were To evaluate the impacts of the three alternatives. w.tain about whether dose limits imposed by it is necessary to determine which current 10 CFR 20.1301(a) or the patient release criteria procedures invohing the administration of established by 10 CFR 35.75 govern patient radiopharmaceuticals or permanent implants release, in the Commission's view,10 CFR 35.75 might be affected by the imposition of a governs patient release as explained in the Notice of proposed Rulemaking (59 FR 30724). The 1.millislevert (0.1 rem) total effective dose equivalent dose limit for individuals exposed to public comments reecived on the three petitions released patients. For convenience, procedures and the Notice of Proposed Rulemaking also invohing the administration cf radioactive made it clear that the majority of commenters materials to patients may be classified as: favored an annual dose limit of 5 millisieverts (1) diagnostic procedures involving admitustration (0.5 rem). Given that 10 CFR Part 35 was of radiopharmaceuticals to obtain information deemed to be the controlling regulation, the about normal and pathological processes in the Commission was faced with the decision regardag patient; or, (2) therapeutic procedures invoking the regulatory approach to be pursued in administration of radiophtrmaceuticals or 10 CFR 3535. To evaluate the issues raised by
. the petitioners and those who commented on the implantation of a radioactive source to destsoy diseased tissue in the patient.
tequests made by the petitioners and the Notice of Proposed Rulemaking, the NRC determined that the following alternatives should be evaluated: 4.1 Current uses or e Alternative 1: 1 millislevert f0.1 rem) total Radiopharmaceuticals effective dose cauivalent Radiopharmaceuticals can be defined as ' drugs" This alternative evaluates a dose limit of that are radioactive. Although radiopharma-1 millisievert (0.1 rem) to an individual ceuticals, diagnostic or therapeutic, may be exposed to a patient as the limiting factor for classified as drugs,it should be noted that determining when a patient may be released radiopharmaceuticals are not given for the from the licensee's control. purpose to exert any pharmacological action. e Alternative 2: < 1.110 mecabecauerels Radiopharmaceuticab are generated from two 00 millicuries) or e 0.05 millisievelt sourc(s: nuclear reactors and accelerators. (5 milPrems)/hr at 1 meter Nuclear reactors can produce radionuclides through neutron capture reactions (e.g.,(n, y), in this iternative, the current patient release (n, p), and (n, a)), as well as by nuclear Ihsion criteria in 10 CFR 3535 are evaluated as the (n. f). Other radiopharmaceuticata are accelerator NURIIG 1492 2
. _ =
l l
)
produced,in which a highly pure target material is RiiD 2 studies)(ME85). The RiiD 1 study bombarded with protons, demerons, or alpha esamined the computer billing rewrds of particles. Many have relatively short half thes. 81 hospitals. Data for the subsequent RED 2 Some radiopharmaceuticah may be produced by study reflect information obtained by mail survey either reactor or accelesator (e g., palladium 103 from 500 hospitals. ; (Pd 103) and iodine 125 (1125)). The choice in production method is dictated by w$t Data for 1982 were also provided by Parker, et al. considctations and vendor access to a high (PAB4) in ,vhich a randomized sample of neutron flux reactor facility, While most 80 giercent of the U.S. hospitals was surveyed. lodme 125 has in the past and contmues to be . Although his survey was specifically directed to produced by reactors, the productmo of palladium 103 has shifted from reactor to thyroid examinations, survey data aho provided estimates of total examinations. accelerator (personal communication, C. Jacobs, August 1993), All of the studies mentioned above are I 4.1.1 Diagnostic Administrations summasized in Table 4.1 and represent hospital data only. Ilowever, the exclusion of non hospital 4.1.1,1 Estimates of the Number of Diagnostle facilities should not significantly affect the Proceduits Performed accuracy of estimates since less than 1 percent of all nuclear medicme procedures are performed Estimates reg rding the frequency and total utside hospitals (J083). Inspection of Table 4.1 number of diagnostic nuclear medicine procedures reveals severalimportant trends. While the total have been reported over the years in several number of diagnostic procedures has shown a studies reviewed and analyred by Mettler, et al. general increase, t number of specM, c (ME85). Among the earliest data reported was a procedures has in some cases dramatically study supported by the American College of '"#85d r decreased. By 1982, there were Radiology (ACR75), which reflects data collected fewer rad.ionuclide brain imaging examinations in 1972 by J.1loyd Johnson Associates, than in 1972, undoubtedly due to replacement by Additional data for the years 1973 and 1975 were c mputedzeq tomography (ME85). For the same obtained in a simile fashion and also published in period, liver unag,mg increased tenfold. The the American College of Radiology Manpower largest percent increase mvolves cardiovascular Survey (ACR82), imaging, which mereased from an estimated 25,000 procedures m 1972 to about 950,000,m In 197.% tha Hureau of Radiologicallicalth 1982. Other procedures such as renal, lung, and (BRil; now the Center for Medical Devices and }um t unagmg have expenenced only modest Radiological llealth, CDRil) of the U.S. Food increases in numbers. and Drug Administration initiated a pilot study that surveyed information reported by six hospitals A search of the open hterature revealed no recent to the Medically Oriented Data System (MODS), comprehensive studies to assess more current U.S. This project was later expanded to include use of radiophrmaceuticals, it is generally 26 stratified hospitals that provided data for 1977 thought, however, that the frequency and usage of and 1978 (FDA85). radiopharmaceuticals have stabillied because of the competing technologies of computerized Comprehensive data on 1980 diagnostic imaging tomography, magnetic resonance imaging, and procedures were obtained by J. L.loyd Johnson gray scale ultrasound (personal communication, Associates by mail questionnaire using a stratified F.A. Mettler, March 1993). For this report, the random sample of general hospitals and selected most recent RED 2 frequency distribution and the office practices in the U.S. (1083). The sample cumulative frequency of 16 diagnostic nuclear included 6,109 hospitals and was estimated to medicine procedures per one-thousand population reflect about 90 percent of the total diagnostic will be used to estimate current usage. Table 4.2 imaging examinations. Additional studies were provides frequency estimates of diagnostic conducted by the llRil for the years 1980, 1981, procedures adjusted to reflect the 1993 U.S. and 1982. The hospital based survey was called population, which is projected at 256,4%000 by the Radiation IIxperience Data (RED 1 and the U.S. Iluteau of the Census. 3 NUREG 1492
Table 4.1 Estimated Number of Diagnostic Radiopharmaceutical Procedures Pe formed in the U.S. lictween 1972 and 1982
%.e. al 1972 1973 1975 1978 1980 1980 1981 1982 1982 Enutte Esamination Tn, ACR ACH ACH MODS Johnson RED 1 RED 2 Rf D 2 Parker 11 rain 12W" 1510 2120 1546 870 1176 1038 812 ~
liepatobiliary 26 - - -~ --- -- 109 179 - 1.lver 455 535 676 1302 1180 1399 1445 1424 -- l lione 81 125 220 1160 1270 1307 1613 1811 --- Respiratory 332 417 597 1053 830 898 1095 1191 -- , Thyroid 356 460 627 699 650 506 664 677 533 I Urinary 108 122 154 205 200 164 402 236 - Tumor 10 14 22 166 130 -- 125 121 - Cardiovascular 25 33 49 160 5s0 558 708 950 -- Other 686 294 338 120 120 368 - - -- Total 3339 3510 4803 6411 5830 6374 7199 7401 7690 (16)* (17) (22) (29) (26) (28) (31) (32) (33) Source: MI'8 5.
"* Numbers sua la parenthuis indicate number of eneminations a 1,000.
- Numbm in parendweis indwaie numt.or of esaminations/1.000 population.
The identity, chemical form, and typical quantity 3 percent use iodine 131 or iodine-123 (1123), administered of radionuclides used for diagnostic and about 2 percent use gallium-67 (Ga-67). inaivo procedures are cited in Table 4.2 and tellect values cited by Mettler, et al. (MFM). 4.1.1.2 Age end Sex Distribution of Patients it can be assumed that the typical quantity per examination has not significantly changed since the time of original publication (personal The age and sex distribution of the U.S. communication, F.A. Mettler, March 1993). population that underwent nuclear medicine examinations in 1980, as cited by Mettler, et al. As the results in Table 4.2 indicate, there are (ME86), is shown in Table 4.3. For the period of approximately 8.2 million diagnostic examinations observation, more than three fourths of all nuclear employing radiopharmaceuticals performed medicine examinations were performed on annually in the U.S. Of these, more than persons over the age of 45; nearly 40 percent of 85 percent use technetium 99m (Tc 99m) as the these patients were 64 years and older. With the label, about 5 percent use xenon 133 (Xc 133), exception of the youngest age category, the about 5 percent use thallium-201 (TI-201). about percentage of females exceeded males. NilREG1492 4 l l I
l . Table 4.2 Estimated Radiopharmaceutical Use for Diagnostic Procedures in the U S, l In 1993"' T)pleal Actisity Number or . I Examination 'lype per Esamination Examinations I (Radiophar unceutical) (Milq) (mCl) (s 1,tXHI) Ilrain TvT,.a LTPA 740 (20) 450 Tc 99m O. (Pertechnetate) 740 (20) 450 litriatobiliary Tc 99m IDA 185 (5) 198 Liver Tc 99m Sulfur Colloid 185 (5) 1,578 lione Tc 99m Phosphate 740 (20) 2,007 Lunc Perfusion Tc 99m MAA 185 (5) 871 Jame Ventilation Xe 133 370 (10) 449 Tinroij Tc-90m O. (Pertechnetate) 185 (5) 600 I131 3.7 (0,1) 75 1123 11.1 (03) 75 Renal Tc 99m DTPA 740 (20) 157
- I 131 liippuran 93 (0.25) 105 C'ardiovascular
- Tc 99m R11C 740 (20) 421 Tc 99m Phosphate 740 (20) 211 TI 201 Chloride 111 (3) 421 Tum_pr Ga-67 Citrate til (3) 134 Total 8,202
"' lissed on Mi'86, and personal communication F, A. Menier, Merch 1993, t>ut adjusted for the 1993 U.S.
population. 5 NUREG-1492
Table 4.3 Age and Set Distribution of Patients llatinu Nudeur Medicine l'ssminations Male l'emale Total - Age (%) (%) (%)
< 15 0.9 0.7 1.6 15 29 3.3 4.9 8.2 30 44 5.2 8.7 13.9 45 64 15.8 21.6 37.4
> 64 17.0 21.9 38.9 Soune: M136.
4.1.2 Therapeutic Administrations is most commonly associated with Graves' Disease. Graves' Disease is an autoimmune Therapeutic use of radioactive materials involves disease in which the body's own immune system is two distinct approaches. The first involves the directed against cellular and secretary products of oral, intravenous, or intracavity administration of the thyroid gland. Ilyperthyroidism can also be a radiopharmaceutical that may subsequently be the result of excessive hormone production by a astributed, concentrated, retained, and climinated single ' toxic" nodule, thyroid carcinomas, and by physical, chemical, and metabolic actions medications inclusive of potassium iodide. occurring within the body. The second approach involves the implantation of radioactive sources liyperthyroidism is not a condition reportable to (i.e., seeds) directly into a solid tumor. While public health agencies. As a result, data on rates both temporary and permanent implants are of occurrence and treatment must be inferred. performed, all patients recei ing temporary incidence of hyperthyroidism is reported at 3 per implants are hospitalized until the implants are 10,000 adults per year, with peak incidence removed. Thus, only permanent implants are occurring between 30 and 50 years of age (DG79). potentially affected by this rulemaking. From the most recent data (1990) available from 4.1.2.1 l{adiopharmaceuticals Used in nerapy the U.S. Ilureau of the Census, it can be assumed that about 75 percent of the U.S. population The in vivo use of radiopharmaceuticals in therapy (approximately 191,500,000 persons) is 18 years of is based on the ability to differentially deliver age or older. Thus,it can be estimated that aboit lethal radiation doses to the selected target tissue. 57,500 indhiduals per year require medical Most desirable are beta emitters that can deliver treatment for hyperthyroidism, intense irradiation of target cells while sparing the surrounding tissues. In contrast to diagnostic Although medical treatment may in some cases procedures for which the gamma emission is involve the use of anti-thyroid drugs or surgery,it es*ential, the emission of energetic gammas is may be assumed that about 85 percent of the undesirable for therapeutic purposes since it cases of hyperthyroidism are treated with results in unwanted irradiation of surrounding therapeutic doses of iodine-131 (personal healthy tissues and doses to individurls in close communication, M. Pollycove, November 1993). proximity to the patient. The more significant The resulting estimate is about 50,000 treatments therapeutic applications are described below. per year. Ilyperth3roidism in the past, therapeutic quantities of iodine 131 for treatment of hyperthyroidism tended to be of Ilyperthyroidism is characterized by an increased a magnitude (185 to 550 megabecquerels production of thyroid hormone. Ilyperthpoidism (5 ta 15 millicuries)) that would reduce the NUltiin W2 6
hormone production of the hyperactive thyroid Estimates of the frequency of radioactive iodine gland to normal levels. Ilowever, experience treatment for this condition are included under demonstrated that over a period of years the the estimates for hyperthyroid treatment above. therapeutically induced cuthyroidal condition . (normal or healthy thyroid) deteriorated to one of Thyrold Cancer hypothyroidism requiring thyroid hormone replacement therapy. As a result, today There is no nationuide cancer registry that hyperthyroid therapy also involves the use of accurately defines the number of new cases of iodine 131 to ablate the thyroid. Approximately cancer diagnosed each year. Ilowever, the 50 percent of all hyperthyroid patients undergo American Cancer Society (ACS) annually ablation (personal communication, M. Pollycove, publishes data on cancer incidence and patient January 1996). Typically, activities in the range survival based on information provided by the itom 550 to 1,110 megabecquerels (15 to National Cancer Institute's Surveillance, 30 millicuries) are used but about 2 pcrcent of all Epidemiology, and End llesults (SEElt) program, patients require as much as 2,220 megabecquerels - (60 millicures), the maximum typically The ACS estimates of U.S. canccr cases administered. Such doses quickly result in the diagnosed for 1992, are based on age specific total loss of thyroid function and the patient is incidence rates from the SEElt program for 1986 given hormone replacement therapy from the to 1988 applied to the Census Iluteau's population onset (personal communications, P. A. Mettler, projections for 1992. The ACS's estimate of new March 1993 and M. Pollycove, January 1996). thyroid cancers in 1992, is 12,500 (ACS93). This report assumes that 100 percem of these cases Thyroid Nodules will be treated by the surgical removal of thyroid gland tissue (i.e., thyroidec*omy). Following Single or multiple nodules of sufficient size may surgery, about 20 percent of these cases will not cause obdous enlargement of the "Mroid. A require additional thyroid cancer therapy but nodule (s) refers to a replacement of the normal about 80 percent will require additional homogeneous cytostructure of the thyroid with a therapeutic administrations of iodine 131 to histologic pattern ranging from colloid-filled cysts eliminate residual thyroid cancer tissue (personal and colloid adenomas to follicular adenomas. communication, M. Pollycove, January 1996). lince the incidence is 4 to 5 times as great in Therefore, this report assumes that about women as in men, and since it develops and 10,000 cases per year will be treated with progressively increases in size during life, it is therapeutic doses of iodine 131. most frequently found in females 50 to 70 years of age. It is not uncommon for nodules to remain The quantities of iodine 131 used in thyroid undetected until a post. mortem examination. cancer therapy depend upon the type of cancer, the status of the cancer, and the degree of uptake Small nodules in cuthyroid subjects require no and retention of iodine 131 by residual cancerous therapy. If the gland is grossly enlarged and thyroid tissue. As a result, current therapeutic causes a cosmetic problem or tracheal quantities range from 1,850 to compression, treatment may be indicated along 11.100 megabecquerels (50 to 300 millicuries) with thyroid hormone replacemcot therapy. (personal communications, F.A. Mettler and K.1 Miller, March 1993). The typical quantity A small percentage of thyroid nodules tend to administered is 5,500 megabecquerels pn) duce thyroid hormones uncontrollably and in (150 millicuries) (personal communication, M. excess (i.e., the nodule is not under the regulatory Pollycove, January 1996). control of the pituitary gland and is clinically referred to as toxic nodular goiter).- The presence Therapy for Polyc)themia Vera of these autonomously functioning thyroid nodules leads to hyperthyroidism (i.e., thyrotoxicosis). Since the introduction of radiophosphorus in 1936, patients with polycythemia vera have been treated Toxic nodular goiter, like Graves' Disease, may be successfully with this radioisotope to control treated surgically (thyroidectomy) or by rather than cure this disease. Polycythemia vera therapeutic dose (s) with radioactive imline, is a relatively rare disease that is characterited by 7 NUllEG 1492
e I an autonomous prolifesation of marrow cells intra Arterial 1herapy l leading to an over production of red blood cells, white blood cells, and platelets. Typically, Some primary tumors as well as metastatic lesions phosphorous 32 (P 32) is administered , are highly vascularized. Direct arterial injection intravenwsly in (kises of li t to 185 megabecquerels with insoluble radiolabelled particulates that lodge (3 to 5 millicuries) per treatment over a period of in arterioles and capillaries of the tumor is the time with average cumulative quantities of basis of this form of therapy (Eli87, ZlS4). 740 megabecquerels (20 millicuries) per patient, insoluble carriers of radionuclides that have been clinically tested include iodine 131 labelled oil contrast medium, iodine 131 tipoidal or -ethiodol
"' EI (PA87), yttrium-90-glass microspheres (IIE88),
and yttrium-90 (Y 90) resin particles (ROE 90). Since the use of radioactive strontium for the Since these therapies are so seldom used, their treatment of bone metastases was first described impact may be ignored in this analysis, in early 1942 (PE42), bone therapy has included other radionuclides. Done therapy may involve intracavitary Tumor lherapy the treatment of primary bone tumors such as osteosarcoma (BL87) in which bone seeking For tumors that are spread over the serosal radiopharmaceuticals are in fact tumor seeking. linings of the body cavities or for ascites tumors,
!!one therapy may also be the treatment of painful one approach to delivering therapeutic doses of skeletal metastases, which may be palliated by radiation is to inject the radiopharmaceutical bone seeking radionuclides. Although the directly into the body cavity. For this approach, literature references the palliative and tumor colloids, chelates, and, more recently, monoclonal therapeutic use of these radionuclides antibodies labelled with gold 198 (Au 198),
(phosphorous 32: Cll80, RO77; strontium-89 phosphorous 32, yttrium 90, or iodine-131 can be (Sr-89): B128, KlE7, RO87, ROE 90, S185; used, rhenium 186 (Re 186): KE87, MA88, SC90; samarium 153 (Sm 153): lA90, TU89), there are initially, gold 198 colloids were used, but no databases and no studies have been performed phosphorous 32 is now preferred due to its longer that would allow quantitative estimates regarding half life, more energetic beta particles, and the the number erpatients given bone therapy with absence of gamma radiation. Intracavitary radiopharmaceuticals. These other therapies are radionuclide therapy with phosphorous 32 in performed so seldom that they have negligible quantities of 185 to 370 megabecquerels (5 to impact in comparison with the radiciodines. 10 millicuries) has been applied to malignancies invohing the pleural, pericardial, and peritoneal lherapy with Radiolabelled Cells ca es GA81, KA81, MA78). More recently, iodine 131- or yttrium 90 labelled For lymphoid cell malignancies, the tumor cells tumor associated monoclonal antibodies have (i.e., lymphocytes) may retain their abilit tr. been used in intracavitary therapy (F189, PE86, migrate and recirculate into the lymphora .olar R190) in doses of 740 to 2,220 megabecquerels tissues (i.e., spleen, liver, bone marrow, and lymph (20 to 60 millicuries). Superiority of monoclonal nodes). The harvesting, labelling, and reinjection antibodies over colloids is expected due to the of lymphocytes has been demonstrated to deliver enhanced affinity of the labelled antibody for the therapeutic levels of radiation doses to tumors of target calls. At present, these therapies are rarely the lymphoreticular system (COS7). Indium 114 used and thus have no impact in comparison with labelled lymphocytes have a potential therapeutic radiciodines, role in the management of lymphoma, and clinical studies are underway, Because use of this new Radioimmunotherapy therapy is not widespread, its impact may be omitted in this analysis, but it should be noted Radioimmunotherapy involves the use of that use of a dose based methodology provides a radiolabelled antibodies directed against means to determine the quantities for which tumor-specific antigens such as the relcase may be authorized. carcinoembryonic antigen (CEA) and ferritin. NUREG 1492 8
l l Only a very hmited number of cancer patients of their decay deliver a lethal dose of radiation to have been treated esperimentally with tunr i (cih within a short distance of the implant. radiolabelled antibodies in combination with - The major advantage of brachytherapy over chemotherapy and external beim irradiation. cxternal irradiation in the treatment of solid Among cancert treated are hepatomas, llodgkin's tumors is the favorable ratio of dose delivered to l disease, and non.Ilodgkin's lymphoma (LEh5, tumor cells versus normal tissue. This is ; NE90, OR85). In the past, radioimmunotherapy particularly true of prostate cancer where the involved the use of iodine 131. and yttrium 90- surrounding normal tinue includes the bladder, labelled polyclonal antibodies raised against rectum, and urethra. The presence of these tumor associated antigens in a variety of animal normal tissues limits the dose of external beam species. Ilased on avidity of tumor cells and radiation therapy that can be administered safely exposure considerations of the bone marrow, to the prostate. single doses of 370 to 1,110 megabecquerels (10 to 30 millicuries) have been used. The radionuclides primarily used in permanent implants are iodine 125 and palladium 103,1ess The development of the hybridorna technique by frequently used radionuclides include gold 198 and Kohler and Milstein (KO75) has caused significant f shift in radioimmunotherapy. The hybridoma ytterbium 169 (Yb-169). technique allows the development of monoclonal The most frequently used radionuclide in antibodies against tumor associated antigens. At permanent implants is iodine 125, which has the this time, however, the use of radiolabelled advantage of an extremely low energy (27 lev) monoclonal antibodies for therapeutic applications photon and ,i physical half life of 60 days. Ilesides has been limited to experimental treatments. At minimizing oose to surroimding healthy tissue, tb present, these therapies are rarely used and thus low photon energy also limits doses to hospital have no impact in comparison with the personnel and others when compared to radiolodines. temporary implants with iridium 192 or permanent implants with gold 198 (Cili 9, RU92). 4.1.2.2 Radioactive Materials Used la Permanent Although iodine 125 implants are most commonly implants (llruchytherapy) used to treat cancer of the prostate (DE86, FU91, ilE82, MOSS, PR92, Wil88), they have also been in situ radiotherapy may involve permanent used on a very limited basis for brain tumors implants or brachytherapy. Brachytherapy has (AG92, OS92, SC92), carcinomas of the pancreas been around almost since the discovery of X rays. (MO92), non-oat cell lung carcinomas (FL92), Brachytherapy can be divided into temporary breast cancers (RU92), and tumors of the head, implantation using high activity sources or neck, and eye. permanent brachytherapy using the interstitial implantation nf encapsulated radioactivity, in Palladium-103 seeds were developed for use in 1911, Pasteau reported the first treatment of brachytherapy to reduce some of the problems prostate cancer by brachytherapy using radium associated with iodine 125. Its average photon inserted through a urethral catheter (Pall). energy of 21 lev is lower than iodine 125, but, Currently, iridium 192 (Ir 192) is the radionuclide given its shorter 17 day half life, it has a higher of choice for temporary implantation. For initial dose rate. Recently, palladium 103 seeds temporary implantation, patients may be retained have been developed with the same physical in the hospital for reasons that are independent of pirameters as iodine 125 seeds to ensure radiological considere' ions. Radionuclides used cempatibility with the brachytherapy tubes and for temporary implants are, therefore, of no templates used for iodine implantation (ME90), concern to this report and will not be discussed further. Ytterbium 169 has been hailed as a replacement for iodine 125 in brachytherapy Compared to Over the past 20 years, several radionuclides have iodine-125 and palladium 103, it has a slightly been introduced to brachytherapy, allowing for the higher initial dose rate, and its average 93 lev permanent implantation of radioactive ' seeds!' beta energy allows for a more favorable dose Seeds are miniature capsules that are strategically distribution and negligible tissue self attenuation inserted within a solid tumor and over the period (pO90). Ilowever, its use as a permanent implant 9 N t IREG.1492
I i f .- is nominal due to the presence of a small(Icss annually, at activities ranging from 2,775 to
- than 3 perrent) average photon peak at 300 kev, 4,625 megabecquerels (75 to 125 millicuries).
that can significa:itly impact radiation doses to indhiduah in proximity to the patient- (1.L3 Summary of Therapeutic Gold.198 implants have been used in a few instances of prostate cancer (CARM, FR88), The Table u sumenariies the range of the acthit,e. s of potential advantage of 4clivering a high dose gamma emittmg radionuclides used in therapeutic within a relatively short time, however,is offset by administrat, ions and the esthr.ates of the numbers its energetic gamma emissions, which has caused , of each therapy currently performed annually, its use in recent years to fall into disfavor and be used only rarely (CA87). 4.2 Assessment of Doses to A thorough search of the literature and personal communications with several prominent members Individuals exposed to of the medical and scientific community (see Patients Administered Acknowledgements) indicates that there is no Radioactive Materials published data available to quantify the annual number of cancer patients receiving permanent implants, llowever, the scientific literature and To identify the potential impacts associated with consensus opinion among the experts identified in each of the alternatives, it is necessary to know the acknowledgments to this report does support the magnitude of doses that could be received by the following: an individual exposed to a patient who has been administered radioactivt. materials. While
- 1. permanent implants are currently considered exposure can ocem via any of the climination an appropriate treatment for only a few sites pathways by which radionuclides are removed of solid tumors; from the body (e.g., exhalation, feces, saliva, sweat, urine, and possibly vomh), experience
- 2. among the cancer sites for which permanent indicates that for lodine-131 and other gamma impluts are currently employed, prostate emitters, these pathways will generally be cancer represents the overwhelming majority; insignificant in relation to the doses that can result from exposure to the direct gamma
- 3. among the 132,000 annual new cases of radiation from the patient, with the exception of prostate cancer (ACS93), only a small intake from the milk in breast feeding infants, fraction is treated with permanent implants; This section of the report assesses the external and, and internal doses to indhiduals, including a breast feeding infant, exposed to patients who
, 4. for the purposes of this analysis, implants have been administered radioactive materials, invohing gold 198 (largely discontinued) and ytterbium.169 (isolated use only) may be 4.2.1 Methodology I'or Calculating ignored. External Gamma Dose in the absence of documented clinical data, information we sought from the implant vendors The methodology for calculating the external on numbers of administrations and typical gamma dose from exposure to the released acthitics of radioactive material used per patient is fully descr' bed in the associated administration. Currently, there are only three regulatory guide for the final rule (NRC96). The
. vendor sources. Vendor supplied data suggests methodology is based on the one employed in the that approximately 2,000 implants involving National Council on Radiation Protection and iodine-125 are performed annually, at aethities Measurements (NCRP) Report No. 37, ranging from 1,110 to 1,850 megabecquerels " Precautions in the Management of Patients Who (30 to 50 millicuries). For palladium.103, llave Received Therapeutic Amounts of approximately 1,500 implants are performed Radionuclides" (NCRI'70).
NURIIG 1492 10 I
Table 4.4 Number of Annual' therapeutic Adminhtrations in the U.S. (significant gamma emitting radionuclides only) Range of Attivities I:stimated No. of
'Iherapeutic Radionuclide Administered Administrations l Procedure I:mployed (Mitq) (mCl) (per year)
Thyroid Ablation and 1 131 370 2,220'" (10 60) 50,000 ilyperthyroidism Thyroid Cancer 1131 1,850 11,10F (50 300) 10,000 l Permanent Implant 1125 1,110 1,85(f* (30.$0) 2,000 ! Permanent implant Pd.103 2,773 4,625t* (75 125) 1,500 Total 63.500
'" Based on personal commurucatiom. F. A. Metder, Mmh 1993 and M. Pouycovo, January 1996.
- Bess,d on personal conunurutet,ona, F A. Metder and KL Miller, Mmk 1993.
,
- Based on infornudon supphed t,y 6mplant vendors, August 1993.
To calculate the dose to total decay D(ce), the when most of the dose is delivered in a relatively regulatory guide uses the following equations. short time. 7 For radionuclides with a half-life greater than 1 day Doses among individuals who may come in p(,,) , 34.6PO,T,(0.25) * (1) contact with a released patient are highly variable (100 cm)2 and reflect the crucial, but difficult to define, parameters of time, distance, and shielding. Ilased on time and distance considerations,it is and for radionuclides with a half life less than reasonable to conclude that for the overwhelming iday majority of released patients, the maximally exposed individual is likely to be the primary care-D(~) = (2) prodder, a family member, or any other individual (100 cm)2 , who spends significant time close to the patient. Ilased on time, distance, and shielding factors, where P = exposure rate constant for a which describe normallifestyles of the U.S. point source, R/ mci h at 1 cm, population, it is highly unlikely that doses equal to spending 100 percent of time at a distance of G, = initial activity of the point source in 1 meter from a patient would result to any millicuries, at the time of release, individual including a patient's spouse. As a standard medical practice, patients undergoing T, = physical half. life in days, therapeutic treatments with radiopharmaceuticals are given firm instructions, both verbally and in 4.2,1.1 Occupancy I'nctor wTiting, regarding basic principles on how to minimize doses to other individuals. liquation 1 assumes, for radionuclides with half lives greater than 1 day, that the individual G;ven all considerations, a reasonable estimate of likely to receive the highest dose from exposure to the maximal likely dose to an individual exposed the patient would receive a dose of 25 percent of to a patient is 25 percent of the dose to total the dose to total deca"(0.25 in IIquation 1) at a decay at a distance of I meter (except for the distance of 100 centimeters (1 meter) For short lived radionuclides). The selection of an radionuclides with half lives less than 1 day, the occupancy factor of 25 percent at 1 meter for factor 1.0 is used in I!quation 2 because the estimating maximal likely exposure is based on the assumption that the time that indhiduals will authors' professional judgment of time-distance spend near the patient will be limited is not valid combinations that are beliesed likely to occur 11 NU RIIG-lO2
Table 4.5 l'amily Doses from patients Treated with lodine.131 for Thyroid Carcinoma Measured Predicted Total flody llurden Doses to Dose liased on Aethity at Time of l'amily Occupancy factor of Administered Discharge Members 25% at I rneter Pa0ent (mCl) (mCl) (mrem) (mrern) 1 210 25.2 80,70,30 386
^
2 311 2A4 '50,20,20 404 3 2W 18.4 80,40 282 Source: ItA R when instructions to minimize time spent close to distance are not made doses can be higher thni the patient are given. predicted by Equation 1. The occupancy factor of 0.25 at I meter is also 11uchan and 11rindle (BU71) monitored the doses supported by empirical data. liarbert and Wells of 54 family members of patients who underwent (llA74) monitored the external dose of 8 l'amily iodine therapy for hyperthyroidism. This study is members of 3 patients treated for thyroid interesting because no instructions on minimizing carcinoma using iodinc.131. All doses to family dose were given. Thus, the results can be taken members were far below 5 millisieverts (0.5 rem) to represent the doses that would be received if as shown ,m Table 4.5. The last column of
, no instructions were given or if instructions were Table 4.5 provides dose estimates based on th totally disregarded. The highest measured dose to 25 percent occupancy factor m Equation 1. The a family member was 2.7 milh. .steverts (0.27 rem),
actual doses are far below the calculated doses for an occupancy factor of 25 percent, indicating that below the 5-millisievert (3.5. rem) limit. The the model generally provides a conservative effettive occupancy factor at 1 meter was less than estimate of the dose. or equal to 0.25 in 45 of the 54 cases (83 percent). Thus, even in the complete absence of liarbert and Wells (llA74) also measured the instructions, the occupancy factor at 1 meter was external doses to 11 family members of seven usually less than 0.25. hyperthyroid patients. All doses to family members were far below 5 millisieverts (0.5 rem). In conclusion, both empirieal measurements and in each case, the measured doses were at least a professional judgement support an occupancy factor of 10 below the doses predicted by Equation 1 factor of 0.25 at 1 meter as a generally using an occupancy factor of 0.25 at 1 meter. conservative value. Using this value in Equation 1 should generally overpredict the dose even if Jacobson et al. (JA78) measured the external instructions are not given or are not strictly doses to 10 family members of 7 iodine therapy followed. Ilowever, higher occupancy factors are patients. In each case execpt one, the external certainly possible in situations where instructions de to the family member was below that are disregarded and are not considered a problem predicted by Equation 1 using an occupancy factor for this rulemaking. The NRC's rulemaking of 0.25 at I meter and well below 5 millisieverts based on Alternative 3 provides an adequate level (0.5 rem). In the case of the exception, the family of protection with a significant margin of safety went on a extended vacation spending much of for those families that make a reasonable effort to the time together in an automobile. This follow the instructions. The NRC considers that demonstrates that if reasonabic efforts to maintain to be sufficient. NUREG 1492 12
4.2.1.2 Exposure Rate Constant both of which are dependent upon the physical condition of the patient. Table 4.6 prmides the
. The exposure rate constant P expreues the dose uptake fraction and biological half life for each rate per hour at I centimeter in air for a component with respect to patients being treated 37 megabecqueret (1 millicurie) point source of for hyperthyroidism (and thyroid ablation) and I a given radionuclide. The exposure rate constants thyroid cancer. The extrathyroidal and thyroidal l and the physical half lives of radionuclides used in uptake fractions for thyroid cancer assume medicine are shown in Table A.1 of Appendix A. surgical removal of the thyroid gland prior to For permanent implants, a significant reduction in I the dose and dose rate occurs from the shiciding To determine the total dose to an individual effects of the source capsule. For iodine 125 and exposed to a patient administered iodine 131, palladium 103 implants, the dose to total decay at considering biological retention and climination by 1 meter was calculated using an exposure rate - the patient, Equation 1 must be split into two constant corrected for capsule shielding as shown terms that separately represent the dose in Table A.1 of Appendix A. The physical contribution from the thyroidal and extrathyroidal characteristics of other radionuclides used in components. The following equation was used to permanent implants (e.g., gold 198 and calculate the total dose to complete decay ytterbium 169) are also given in Appendix A. assuming an occupancy factor of 0.25 at I meter:
4.2.1.3 Illological Retention and Elimination Tffectlie llalf Life q,,) , 34.6PQ,T,, F,(0.25) , (4) (100 cm)2 in Equations (1) and A (2) licensee with the effective mayhslfreplace T' life T,of the 3t6 PQ,T,, F,(0.25) radioactive material to demonstrate compliance (100 cm)2 with the dose limit in the revised 10 CFR 35.75. T,is characterized by 7, and the biological half life T, of the radionuclide (which accounts for where T,i = cffective half life of the extrathyroidal the biological retention and elimination of the. component in days (based on the radionuclide from the patient's body) according to biological half-life T., of the the equation thyroidal component), T, = T' # '. (3) F, = extrathyroidal uptake fraction, T,
- T, T,3 = cffective halflife of the thyroidal component in days (based on the Under the final rule a licensee could authorire on the biological half life T,3 of the release on a case by-case basis based on the thyroidal component),
biological half life rather than only the physical halflife of the radiopharmaceutical. F3 = thyroidal uptake fraction, Iliological Retention and Elimination of lodine 131 P = exposure rate constant for a point source, R/raci h at I cm, For iodine-131, biological retention and climination are characterized by the fractional O, = initial activity of the radionuclide in amounts that reside in the thyroid (i.e., thyroidal millicuries, at the time of release. component) and in the rest of the body (i,e., extrathyroidal component). Each component has This equation is only valid if the release occurs at 3 specific fractional uptake and biological half life, the time of administration. 13 NURIMi 1492
Table 44 lodine 131 lilological Retention and Elimination Parametrrn for II3perthyroidism, %)rold Ablation, and %) told Cancer'" Extrath>toldal %)roidal Component Component Uptake liiological Uptake filological fraction llalfLife Fraction llatfLife Disease F. T., (days) F, I,,(days) \ l Ilyperthyroidism and 0.10 033 0.90 10 Thyroid Ablation 0.20 033 0.80 15 030 033 0.70 20 0.40 033 0.00 20 0.50 033 0.50 25 040 033 0.40 40 0.70 033 030 65 Thyrold Cancet 0.95 033 0.05 80
"' Dets taken from ICRP I%htauons 30 OCRP7s),53 OCR)17), and $6 0CR119), and g eroonal communication, M. Pollycove, March 1996, be d on clinical experience.
}
. 21.4 Tissue Shiciding for Permanent implants the lungs, brain, pancreas, etc., tissue shielding values of similar magnitude can be assumed for in addition to the shielding effects of the source an adult male and female, llowever, for certain capsule (see 4.2.1.2 Exposure Rate Constant), a implants involdng primary cancers of the occk significant reduction in the dose and dose rate and head, overlying tissues may provide less than also occurs from the tissue surrounding the 5 llVla of attenuation. In such instances,it is implant. For a prostate implant, tissues that serve standard practice to provide the patient with a to reduce photoc flux about the patient include small portable ' shield" which effectively attenuates the soft and bone ti:ees of the thighs, pelvis, all emissions (personal communications, C. Jacobs, buttocks, abdomen, etc, The linear attenuation August 1993, and R. Nath, J, St. Germain and coefGcient and corresponding soft tissue half value K. Suphanpharian, htarch 1993). A shirld consists layer for the 27 kev photon of iodine-125 are of a vinyl sheet impregnated with lead and molded 4
0387 cm and 1.8 cm, and for the 21 lev photon to fit the anatomical surface over the implant. of palladium.103,0.770 cm4 and 0.9 cm, respectively (J01183). For the purposes of this analysis, implants will be evaluated considering shielding by tissue To assess the impact of tissue shielding by the equivalent to 5 half value layces. patient, the medical physicist of the hiemorial Sloan Kettering Cancer Center was consulted 4.2.2 Assessment of Internal Exposure (personal communication, J. St Germain, htarch 1993). Ilased on empirical assessment invohing 4.2.2.1 Internal Esposure Pathways paticats with prostate implants, tissue shielding for iodine 125 is likely to exceed 5 or more half value Upon oral administration or direct injection into layers (11VLs), which would reduce the dose and the circulating blood, the radiopharmaceutical dose rate by a factor of at least 32. For undergoes the normal processes of absorption, palladium 103 implant'., in which the llVL in distribution, and excretion. Removal of tissue is less than I centimeter, the shielding radionuclides from the patient's body may follow afforded by the patient's tissue is even more the pathways of breast milk, exhaled air, feces, extensive. For other implants involving saliva, sweat, urine and vomitus. NURl!G.1492 14
Itreast Milk. Itadionuclide escretion via the 4.2.2.2 Measurements nf Internal tiposure l mammary gland coru.titutes a potential exposure pathway to the breai.t. fed infant. This can be a 'Ibe potential for contamination by patients scry important pathway after the administration of treated with radiciodine which may serve as a radioiodines, itelatively small administrations of source for internal exposures to others have been radioiodine to a breast feeding women can cause auessed for various excreta pathways (111,7t. . very large doses to the thyroid of the infant. MA73, N180). Maximum excretion rates are Cessation of breast feeding for iodine observed shortly after an administered dose, l administrations avoids the potential for thyroid Excretlou rmes occunc rapidly thereafter due to ablation in the infant. . r;r.a! dearance and thyroidal uptake. Almost all the excreted activity is excreted in the urine. Eshaled Alr. Exhalation is the principal pathway Contamination through urinary excretion may be for the climination of radmactive gases such as readily controlled by cautious but reasonable menon.133, which is used for lung ventilation tests. hygiene practices. Through passive diffusion, unbound lodide in the circulating blood may also be exhaled. in a thorough study of two patients treated for thyroid carcinomas, Nishizawa, et al. (NIS0) l'eces. Itadiopharmaceuticals retained or observed maxlaum excretion rates of lodine in catabolized by the liver may be secreted into exhalation, perspiration, and saliva of the gastrointestinallumen via the bile. !!iliary 3.2 x 10*/hr,2A x 10*/hr, and 6.3 x 104/hr of the secretion of a radionuclide may be followed by administered dose, respectively. Thus, the intestinal reabsorption. amounts in exhalation and perspiration were very small. The amount in saliva is larger, but transfer Saliva. Salivary excretion of radionuclides is also of saliva to other people is likely to be limited. proportional to the unbound or diffusible fraction in the plasma. Ilowever, salivary excretion is A liritish study (11U70) estimated thyroid seldom an important elimination route, since radiohidine activity in 39 subjects who, as family nearly all saliva is swallowed rather than members, were associated with patients treated espectorated. for hyperthyroidism. Administered quantities ranged from 148 to 740 megabecquerels (4 to Sweat, Itadionuclides present in the extracellular 20 millicuries) per patient. Of the 39 patients,28 iluid will tend to be excreted in the sweat in were instructed to take precautionary measures to accordance with the fraction that is unbound in minimize exposure to family members. Eleven the plasma, patients volunteered to dbregard special precautions against contamination and minimizing Urine. Itadionuclide excretion in the urine is the spousal and family exposure. On the basis of one dominant and almost universM elimination measurement per family, subject thyroid burdens pathway, ranged from lets than 37 to 1,110 becquerels (1 to 30 nanocuries) with an average of 259 becquerels Vomitus. The occurrence of vomiting is not (7 nanocuries). Thus, the uptake of radioiodine related to the administration of iodine 131 or any by family members was only about 1 one. millionth other radiopharmaceutical(personal of the administered quantity, ar.d the dose from communication, M. Pollycove, August 1995). the uptake was less than 0.01 millisievert Furthermore, vomiting is seldom an important (1 millirem) committed effective dose equivalent. elimination route, since orally administered This internal dose is negligible compared to the radiopharmaceuticals such as iodine-131 are external dose. The authors concluded that rapidly absorbed, within a half hour, by the contamination is not important and "except where gastrc'.atestinal system. Ilowever, a significant young children are involved, precautions to portion of the administered radionuclide could be minimite contamination should be abandoned? excreted if vomiting occurs immediately following the admiestration. In this case the patient li, a 1978 study by Jacobson, et al, (JA78), seven typically would not have been released, and the Ianifies were studied in which one family member licensee would be able to limit exposure and citan had been treated with iodine 131 doses ranging up contamination. from 2% to 5,500 megabecquerels (8 to 15 NUltliG 1492
t 150 millicuries). Non patient family members Table 4.7 indicates that, except for some were assessed for external exposures by means of procedures using iodme.131 to detect thyroid thermolumincuent dosimeters (TLib) worn at can er, none of the other diagnostic procedures the wrist for the full duration of exposure. currently being performed have the potential to Internal expmure (i.e., thyroid burden) was deliver a 1 millisievert (0.1 rem) dose ta an determined at discrete time intervals by means of indhidual exposed to a patient. Ilowever,in the a pair of 30 inch Nal crystals. Although all family case of lodine 131, the effective half. life of the members proximal to the patient had measurable extrathroidal component is much shorter than the thyroid burdem, dose estimates in nearly all cases /,Ll. life w,ed to calculate doses. Therefore, indicate that internal committed eff;dce h.a the dose would be much lower than the value equivalents were always less than 10 percent of shown in Table 4.7. Since the doses in all cases the 5-millislevert (0.5-rem) dose limit, even when are much below 1 millisievert (0.1 rem), no precautions were taken, and the external dose diagnostic procedures will not be considered any substantially exceeded the internal dose. further in this analysis. The investigators also concluded that it * . . 4.2.3.2 "Iherapeutic Procedurea appears certain from our study of these subjects that for spouses, there la a relation between The results of the dose calculations for thyroid acthity and intimacy. Of the 12 husbands therapeutic procedures using the physical and and wives questioned. . . . none were willing to effective half lives (as applicable) are summarized adjust living habits with their spouses becau e of in Table 4.8. All calculations assume an the radiation therapy. Most, however, are concerned occupancy factor of 25 percent at a distance of for their childret. and are willing to listen to I meter and immediate release of the patient by suggestions which minimize exposure to their the licensee (i.e., no hospitalization). For children.' While the authors are vague about hyperthyroidieu (and thyroid ablation), doses what they mean by ' adjust thing habits,' it appears based on effective half. life have been calculated that couples are often unwilling to abstain from using the four thyroidal uptake fractions that brief periods of close intimate contact for prolonged characterize the majority of patients with this periods of time. This should not be a problem disease. Table 4.8 indicates that the model because the brief times will be too short to add considering biological retention and climination significant external dase and transfer of contamination prmides dose estimates that are significantly less is not a significant contributor to internal dose, than the model that considers physical half. life only. Thus, the studies on internal exposures suggest that internal doses from intake of contamination For the purposes of this analysis, the dose are likely to be much smaller than doses from estimates for iodine 131 based on the biological external radiation and much smaller than the model will be used because this model more public dose limit. Therefore, internal exposures closely reflects the behasior of iodine 131 in will not be considered in this analysis other thaa humans. For permanent implants, biological for the breast. feeding infant, modeling does not apply, in this case, this analysis uses the dose estimates based on the
'*' * #' "'" ** "E 4.2.3 Estimale of Maximum Likel}' radiomdine would be affected by any of the 1)oses to Individuals Exposed to alternatives under consideration.
Patients 4.2.4 Assessment of I)osts to lircast-Assessments were made of the doses that could Feeding Infants result from exposure to a patient treated with cava of the radionuclides used. If a radiopharmaceuticalis administered to a woman who is breast feeding, a fraction of the 4.2.3.1 Diagnostic Procedures quantity administered may be deposited in the breast milk and may be transfnred to the "t he results of the dose calculation for diagnostic breast feeding infant. In consid-ring the dose to piocedures are summarized ia Table 4.7. the indhidual likely to receive the highest dose NURiiG 1492 16 I
Table 4.7 hlasimum IJkely Doses to Total Decay to I:sposed Individuali from Diagnostic l'rocedures Arthily per I:samination Type l'samination'h Gamma Dose (2' (ltadiopharmaceutical) (hlligt (mCl) (m5h) (rem)
.!LfR}.0 Tc.99m DTPA 740 (20) 0.13 (0.013)
Tc.99m O. 740 (20) 0.13 (0.013) lierintobiliary Tc-99m IDA 185 (5) 0.03 (0.003) 1.iver Tc-99m Sulfur Colloid 185 (5) 0.03 (0.003)
.lh101 Tc 99m Phosphate 740 (20) 0.13 (0.0 13) 1.unn Perfusion
- Tc 99m MAA 185 (5) 0.03 (0.003) 1 hvioid Tc 99m O. 185 (5) 0.03 (0.003)
- l 131 3.7 (0.1) 0.02 (0.032)
- l 131 (maximum) 370 (10) 1.5 (0.15)
Cardiovascular T -99m itBC 740 (20) 0.13 (0.013)
- Tc-99m Phosphate 740 (20) 0.13 (0.013)
TI 201 Chloride 111 (3) OD4 (0.004) Ren.il Tc 99m DTPA 740 (20) 0.13 (0.0 13) I-131 ICppuran 9.3 (0.25) 0.04 (0.004)
'" The acuvity u the typical quantity admirustered per examination (see Table 4.2). The maximum diagnostic activity of I-131 is shown because it yields gamme doses exceeding i millisievert (0.1 rem).
"' Calculations asaume no biological elinunation, no attenuation of gamma rays in air or body of g suent, and occupaney factors of 100 percent at a distance of I meter for Ts-99m and 25 percent at a distance of I meter for 1131 and Tl 201.
17 NUltliG 1492 v
l 1 I l l l l lable 4.N Alasimum (JLely l)os s to Total Decay to thposed ludhiduals from lherapeutie Procedures Assuming No llospitalization j Gamma Dose Itased on l'.fictthe llatf 1.lfe'" + Gamma Dose f.:trathpoldal 7hyroldal lined on Component Component 1herapeutic Activity Physical Uptake Uptake Proerdure Admintittred llatf tJfe'" Fraction Fraction Dose Guid.vuutsides (h111q) (mCl) (mSv) (rem) r, F, (mSv) (rem)
- ilvoerthyroidism &
*[bvroid Ablation
- l iodine 131 370 (10) 1.5 (0.15) 0.40 0.60 0.67 (0.067) 0.50 0.50 0.61 (0.061) 0.60 0.40 0.58 (0.058) 0.70 0.30 0.45 (0.045) 1,110* (30) 4.6 (0.46) 0.40 0.60 2.01 (0.201) 0.50 0.50 1.83 (0.183) 0.60 0.40 1,74 (0.174) 0.70 0.30 135 (0.135) 2,220 (60) 9.2 (0.92) 0.40 0.60 4.02 (0.402) 0.50 0.50 3.66 (0366) 0.60 0.40 3.43 (0348) 0.70 030 2.70 (0.270)
Thyroid Can er iodine-131 1,850 (50) 7.6 (0.76) 0.95 0.05 0.62 (0 062) 1 5,550*(150) 22.9 (2.29) 0.95 0.05 1.86 (0.186) 7,400 (200) 30.6 (3.06) 0.95 0.05 2.48 (0.248) Permanent in.,)pjanf*
. iodine 125 1,110 (30) 0 54 (0.054) Effective llatf 1.ife Not Applicable to 1,480* (40) 0.72 (0.072) Permanent implants 1,850 (50) 0.90 (0.090)
- palladium 103 2,775 (75) 0.29 (0.029) 3,700* (100) 039 (0.039) 4,625 (125) 0.49 (0.049)
'" Matimum likely done bened on an occupancy factor of 25 percent at a distance of 1 meter.
'" Doses have been calculated for the four thyroidal uptake fractions that characterue the majonty of patients treated
Typical actisity administered
- These dose values account for the $ llVl4 of tissue shielding by the patient and, thersfare, are equal to the poirt source done in air divided by 32 NUR.l!G 1492 18
r_-_________-____-- 0 i 1 from exposure to a patient who has been 20 centimeters as the distance between the infant administered a radiopharmaceutical,it is and the souice. Also, since only the physical necessary to consider both the internal and half hie is considered, the analysis h conservative. cxternal dose to the infant from breast feeding. The results are shown in column 4 of Table 0.5 assuming no interruption in breast feeding. 4.2.4.1 Internal Dose
- 4.2.4.3 lodine 131 Sodium lodide l The potential internal dose to the breast. feeding l infant was calculated for the maximum normally This final rule requires that,if the dose to a j
~auministered quantities of commonly used breast; feeding infant or child could exceed diagnostic and therapeutic radiopharmaceuticals. 1 mutisievert (0.1 rem) assuming there was no The results of the cateulations are shown in I"I*'.ruption of breast feeding, instructions must Appendix B. be given to the woman that mclude gu,idance on the laterruption or discontmustion of breast-feeding and information on the consequences of The doses can be represented as a range where the range covers the mmimum and the maximum failure to .ullow the guidance. When the guidance is followed, the dose to the infant or transfer of radioactive matgrial from published child from breast feeding would be a small data. The range is due to individual variability and measurement variability as mdicated by fraction of 1 millisievert (0.1 rem) concentrations measured in breast milk. Doses if the woman does not cease breast feeding after were calculated for newborn and one year old administration of millicurie quantities of mfanto since the doses for newborn infants are iodine 131 sodium iodide, the internal dose to the higher, those doses were used in the analysis.
breast feeding infant could be large enough to The dose ranges for commonly used
. cause the infant's thyroid to be surely damaged radiopharmaceuticals assuming no interruption of breast feeding are shown m column 3 of resultingin hypothyroidism. If hypothyroidism were undiagnosed in very young children, severe Table B.5 (see Appendix B). The radmnued.es in mental retardation may occur. However,if the the table that are not regulated by the NRC patient was provided instructions to discontinue (e.g., Ga47) are omitted from further breast feeding, as well as being advised of the considerat,on i in this analysis.
consequences of not following the instructions, the NRC believes that the probal-ility of a woman The final rule requires that instructions, including failing to cease breast feeding after being written instructions, on maintammg the doses to administered iodine 131 sodium iodide is small. other individuals as low as is reasonably For example, in 1990 an administered dosage of achievable be given to the released patient if the 185 megabecquerels (5 millicuries) of iodine 131 dose to another individual is likely to exceed sodium iodide to a patient resulted in her 1 millisievert (0.1 rem). If the dose or the breast fed infant receiving an unintended radiation maximum value of the dose range shown in dose of 300 grays (30,000 rads) to the infant's column 3 of Table U.5 exceeds 1 millislevert thyroid gland. This dose would result in ablation (0.1 rem), then instructions would be required. of the infant's thyroid. This situation was recognized in 2 days which allowed prompt action 4.2.4.2 Esternal Dose to be taken thereby reducing potential consequences such as mental retardation. The To determine a realistic estimate of the external NRC is aware of two other cases that occurred dose to total decay to the infant during breast durirr 1991 and 1995. In each of these cases, feeding, an occupancy factor must be selected that there was a breakdown in communications, rather specifically tellects the variables involved. It can than lack of intent to prevent breast-feeding. This be assumed that the average infant feeds for a rule might therefore be expected to provide a period lasting 30 minutes every 3 hours, resulting benefit by reducing the probability of a mother in an occupancy factor of 16 percent. Hrcast- breast-feeding after administration of large feeding requires close contact, the analysis uses quantitics of iodine-131. 19 N UlW G 1492
_ -. . - - - - - - ~ - - _ _ - - . - . It is estimated that approdmately 400* breast- be retained in a hospital for an average of 7 days feeding women could be administened millicurie at a cost of $1,000 per day. The estimated annual amounts of iodine 131 sodium iodide cach year cost for the extreme option is - for diagnosis and treatment of thyroid disease, in 400 x 7 x $1,000 ? $2.8 million. In addition, there some cases, instructions to interrupt or would be associated costs for providing women discontinue breasbfeeding may not be effectively with instructions and information as to the need communicated. To deal with this issue, the NRC for hospital retention. The circumstances of a considered a range of options which varied from woman choosing to ignore the warning that
- maintaining the status quo to the extreme option breast feeding would cause significant harm to the of confining a woman for a period of time after infant and to continue to breast feed are administration of millicuric quantites of I 131 considered to be very rare. As stated above, NRC sodiurn iodide to ensure here milk production has is not aware of any instance where this has stopped. Included within this range of options - occurred. Therefore, the extreme option was not was the option to enhanee communication b%wsen selected because of the negative psychological the licensee and woman regarding instructions to impact to both the woman and infant, as well as interrupt or discoritinue breast feeding before the the f 8gh annual dollar cost, woman is released from the hospital.
Regarding the preferred option to enhance The option of maintaining the status quo does not communication, although instructions to keep provide the assurance that instructions will be dosca to household members and the public as provided to a breastfeeding woman and could still low as is reasonably achievable are currently allow for a breakdown in communciations. As required for radiopharmaceutical therapy in indicated above, the NRC is aware of three cases 10 CFR 35.21: M)(6), there is no requirement of unintended exposure to a breast feeding child specific to the dose from breast feeding. To during the last five years. There would be no enhance communications, amended costs associated with this option. 10 CFR 35.75(b) will require licensees to provide guidance on the interruption or discontinuation of At the other end of the range, for the extreme breast feeding and information on the rationale option in a hospital, a woman would be retained for following the guidance. Compliance with the until she stopped producing milk. Ilowever, this regulation provides NRC with confidence that the option would result in psychological impacts to licensee will give the instrudions to breast feeding both the woman and breast feeding infant, by woman and it is expected that almost all women requiring them to be physically separated for will follow instructions to interrupt or discontinue some period of time, which are not quantified by breast feeding to protect their children from this analysis. This option was also considered to potentially harmful effects. The NRC is not be impractical as it would be difficilt for a aware of any instances where instructions were medical institution to separate a woman and given to the woman but she ignored the warning breast feeding child. That is, this option does not and continued breast feeding a child. Since the prevent the breastfed child from being brought estimated costs per patient for providing into the patient nor does it address the situation instructions and recordkeeping are $22 and $17, of the patient releasing herself against medical respectively (see 4.3.1.1, Estimates of the Direct advice. Also, to require cessation of breast. Cos'.s of Patient Retention), the estimated costs feeding after administration of iodine 131 sodium for this option would be about $16,000 per year, iodide by hospital retention, or prior to *Iterefore, the option to enhance communication administration (to avoid hospital retention), is selected as the preferred option, directly impacts the practice of medicine, since it would in effect dictate when a treatment could be ghen. If it is estimated that each woman would 4.2.4.4 Summary of Doses to Ilreast Feeding Infants
- 60,000 patients administered iodine 131 The dose to the breast feeding infant can be sodium iodide x 0.135 child bearing age x 0.05 controlled by ghing the woman instructions, as breast feeding - 405 patients administered iodine required by the revised 10 CFR 35.75, to who could be breast feeding. discontinue or to interrupt breast feeding as NUR tE 1492 20
appropriate. The dechion to require instructions about half as much time near the patient. There us shown in column 5 of Table 11.5 h based on might aho be about four other people who will both the external and internal dose to the nursing average about a quarter as much time near the infant. It can be seen from column 4 that for . patient as the maximally exposed indhidual. The some radiopharmaceuticals the external dose from sum of the collective dose to all these people is breast feeding can be a significant part of the total 3 times the dme to the maximally exposed indhidual, dose. The duration of the interruption shown in This situation could represent a 13pical family and column 6 is selected to reduce the maximum dose friends. Of course some patients will spend more to a newborn infant to less than 1 millisievert time near other people, but other patients will (0.1 rem). spend less. A collective dose of 3 times the dose to the maximally exposed individual is thus a l The actual doses that would bc acceived by most reasonable average representation. infants for the recommended interruption periods shown thould be a small fraction of 1 millislevert Finally, as data are not available on the (0.1 rem) due to the conservatism of the analysis. distribution of the quantities of radionuclides The conservative factors are based on: (1) the administered for each therapeutic procedure, the maximum measured level of activity in breast estimates of collective dose for each alternative milk, (2) the longest biological half life, and are based on the typical methities used within the (3) the lowest body weight (i.e., the newborn). ranges of methities administered and the These factors are explained in Appendix is. maximum aethity used for thyroid ablation. 4.2.5 Collecthe Dose Hy using the results from Table 4.8, Tables 4.9, 4.10, and 4.11 present the estimates of the To evaluate cach alternative,it is also necessary collective doses for Alternatives I,2, and 3, to estimate not only the dose to the maximally respectively, for therapeutic administrations that exposed i. lhidual, but aho the collective dose to could be affected by the choice of alternative. For other individuals who may be exposed to patients the typical administration of iodinc.131 for thyroid administered radioactive materials. To calculate ablation, this analysis uses 1,73 millisleverts precisely the collective dose that would be (0.173 rem) (the maximum likely dose to an received under any of the alternatives would indhidual exposed to a patient assuming no seguire detailed information of a highly diverse hospitalization) as the basis for estimating the group of patients relative to lifestyles, living collective doses. This value is the average of de arrangements, work enviromnents, social acthities, four doses calculated for the thyroidal uptake etc. This information does not exist and is fractions that characterize the majority of patients essentially impossible to precisely determine In undergoing thpoid ablation in a similar manner, place of a precise estimate we have made a rough the dose from the maximum quantity administered estimate of the collective dose per therapeutic (2,220 megabecquerels (60 millicuries)), was procedure which we believe is adequate for the deter,ained to be 3.47 millisleverts (0347 tr % purposes of this rulemaking. For thyroid cances, this analysis uses IE millisleverts (0.186 rem) (assuming i 4.2.5.1 Collecthc Done to Individuals hospitalization) as the basis for estimating the collective doses. Implants using iodine 125 are Based on considerations of the written instructions included because doses to exposed indhiduals provided patients, the demographics of the patient approach I millisievert (0.1 rem). Ilowever, population (see Table 43), and time, dhtance, palladium 103 implants are not included because and shielding factors, we estimate that the doses to exposed indhiduals are always less than collective dose per procedure is 3 times the 1 millisievert (0.1 rem), maximal dose (i.e., the dose to the most exposed indhidual). This 3 times factor could occur in the In Table 4.9 (Alternative 1), the collective dose following manner, based upon intuithc per procedure was determined in the following assumptions about a typical family and friends. In manner, it was assumed that all patients would addition to the person recching the maximal dose, remain hospitalized until the dose dropped to who is likely to be the primary carc. provider, I millhievett (0.1 rem). Thus, the dose to the there could be two other people who will average 21 NUIEG 1492
Talite 4.9 1:stimates of Collectlie Dose from *Iherapeutic Radiolodine l'rocedures for Alternatlie 1: Annual IJmit of I millisiciert (0.1 rem) Typical Atthity Collective Estimated Total
'lherapeutie Administe red Dose / Procedure Procedures Collectlic Dose Procedut e (hlliq) (mCD (mSv) (rem) per Year (person S$ (rem))
Thyroid Ablation iodine 131 1,110 (30) 3.0 (0.3) 49,GK) 147 (14,700) 2,2M" (60) 3.0 (0.3) 1,000 3 (300) l l . Thyroid Cancer iodine 131 5,550 (150) 3.0 (0.3) 10,010 30 (3,000) Permanent Implant iodine.125 1,480 (40) 22 (0.22) 2,MX) 4.4 (440) All Therapeutic Procedures 62,000 184.4 (18,440)
"' Maximum activity admirsatored, Die analysis assuem niet 98 ponent of the patients are typically administered 1,110 milhaievens (30 millicuries) and that 2 pman are a,: ministered the manimum quantity.
Table 4.10 Estimates of Collecthe Dose from
- therapeutic Radiolodine Procedures for Alternative 2:
Litnits of 1,110 megabecquerels (30 millicuries) nr 0.05 millislevert (5 millirems)/hr Typical Activity C<>llecthe Estimated Total Therapeutic Administered 1)ose/ Procedure Procedures Collective Dose Procedure (hllig) (mCl) (mSv) (rem) per Year (person Sv (rem)) Thyroid Ablation lodine 131 1,110 (30) 5.2 (0.52) 49,000 255 (25,500) 2,220'" (60) 9.0 (0.9) 1,000 9 (900) Thyroid Cancer
- iodine 131 5,550 (150) 3.0 (0.3) 10,000 33 (3,0m))
Permanent Implant
- iodine 125 1,480 (40) 2.2 (0.22) 2,000 4.4 (440)
All Therapeutic Procedures 62,000 298.4 (29,840)
"' Maximum activity administered his enelysis assumes that 98 percent of the patients are typically admimatened 1,110 mithsieverts (30 nullicuries) and that 2 percent are administered the meumum quantity.
NURi?G 1492 22
Table 4.11 1:stimates of Collecths Dose from 'lherapeutie ltadiolodine Procedurrs for Alternathe 3: AnnualIJmit of 5 ministescru (0.5 reno
, Typical Acthily Collecthe I:stimated Total Therapeutic Adminhtered Dose /Prmedure Prwedures Collecthe Dose Procedure (Milq) (mCl) (m'h) trem) per Year (person Sv (rem))
.T.hvrold Ablation iodine-131 1,110 (30) 5.2 49,000 255 (25,500)
(0.52) 2,220'" (60) 10.4 1,000 10.4 (1,040) (1.04) Thyroid CaneSI iodine-131 5,550 (150) 5.6 10,000 56 (0.56) ($/i00) permanent implant iodine 125 1,480 (40) 2.2 (0.22) 2,000 4.4 (440) All Therapeutic Procedures 62,000 325.8 (32,$80)
- Mesimum activity administered.
- e analysis assumes that 98 percerd of the patients are typicauy adnunistered 1,110 nullisievenu 00 miuicurin) and that 2 percent are administered cie mesimum quant ty, most exposed indhidual is 1 millislevert (0.1 rem). is 3 millisleverts (03 rem). The collective dose is For iodine 125 implants, the dose is already less 3 times the indhidual dose or 9 millisleverts thaa 1 millisievert (0.1 rem) so no hospitalizatica (0.9 rem). The collective dose per procedure for is required. The collective dose per procedure is iodine 125 implants was calculated similar to that then assumed to be 3 times the dose to the most for the typical activity administered for thyroid exposed indhidual. ablation. For thyroid cancer, an administration of 5,500 megabecquerels (150 millicuries) requires Under Alternative 1, patients administered the about I day of hospitalization to allow the typical and maximum quantities of iodine 131 for retained activity to reach the release limit Upon thyroid ablation require about 7 and 14 days of release, the estimated dose to the maximally hospitalization, respectively, before release can be exposed indhidual is 1 millisievert (0.1 rem).
authorized. Whereas, thyroid cancer patients Therefore, the collective dose is 3 millisieverts administered the typical quantity of iodine 131 (03 rems). require about 1.5 days of hospitalization. In Table 4.11 (Alternative 3), the collective dose in Table 4.10 (Alternative 2), the collective dose per procedure was determined in the following per procedure was evaluated in the following manner. For thyroid ablation, patients manner. For thyroid ablations using the typical administered the typical or maximum aethity can acthity of iodine-131, no hospitalization is required be released immediately because the dose from since the activity is equal to the release limit of each aethity is less than 5 millisieverts (0.5 rem). 1,110 megabecquerels (30 millicuries). The The indhidual doses from the typical and l collecthc dose is 3 times the indhidual dose (i.e., maximum aethities are 1.73 millisleverts 1.73 millisieverts (0.173 rem)) or 5.2 millisieverts (0.173 rem) and 3.47 millisieverts (0.347 rem), (0.52 rem). On the other hand, patients respectively. Thus, the collective dose is { administered the maximum aethity require about 5.2 millisieverts (0.52 rem) for the typical aethity i I day of hospitalization before release can be and 10.4 millisieverts (1.04 rem) for the maximum authorized. When released, the maximum dose aethity. The collective dose per procedure for from these patients will be greater than the dose iodine 125 implants was calculated in the same from a patient administered 1,110 megabecquerels manner assuming no hospitalization. For (30 millicuries) due to biological considerations. thyroidcancer, administrations of The estimated dose to the most exposed individual 5,500 megabecquerels (150 millicuries) ,equire no I i 23 NUREG 1492 i
< hospitalization because the dose to the masimally in the analysis that follows, these costs are l_ exposed individual is 1R millisieverts calculated assuming that all retained patients will ) (0.186 rem). The colle,ctive dose is be hospitaliicd. While retention costs might be - 5.6 millisieverts (0.56 rem). less for non hospital locations, no attempt is made I in this analysis to quantify the potential costs. j 4.2.5.2 Collecthe Dose to Itreast. feeding
- Infants 4.3.1.1 Dtimates of the Direct Costs of Patient
( The dose to the nursing infant from breast. Retention l feeding can be controlled to less than 1 milli-sicsett (0.1 rem) by giving the woman instructions Durations of Patient Retention to 4 case or to interrupt breast.feedmg (see Scolon 4.2.4 4) Summary of Doses to lircast- Estimates of the periods of hospitalization that: Pecding infants). The actual doses that would be patients would need to remain under licensee received by most infants after interruption should control for each alternative were discussed in be a small fraction of 1 millislevert (0.1 rem) or Section 4.2.5.1 Collective Dose to Individuals. nothing in the case of cessation. Consequently. Table 4.12 summarizes the duration of retention there is no reason to calculate the collective dose per therapeutic procedure. to nursing infants from breast. feeding since it does not ahect the choice of alternative. Cost of Patient Retention To estimate the annual dollar costs for these 4.3 Vsilue Impact Analysis Periods of retention, one needs only multiply the number of days required for each procedure by the number of procedures per year and the 4.3.1 Estlanates of the Potential Costs average cost per day of hospitalization in 1990, The analysis in Section 4.2 indicates that the the average cost per day in a community hospital 1 millisievert (0.1 rem) per year dose limit was $687 (SA92). The per diem cost at the imposed by Alternative I would result in the beginning of 1995 is estimated to be $800, smallest collective dose to individuals exposed to _ _llowever, as the current regulations require that released patients. The benefit of smaller doses patients who are hospitalized due to a therapeutic i estimated for Alternative 1 will only be achieved if administration of radiopharmaceuticals be placed the patients to whom the radioactive materlats in a private room, the $800 per day estimate is have been administered are retained under the - adjusted to $1,000 per day. Using this figure, the control of licensees for longer periods of time, potential cost of retaining patients under The impact of retaining patients must be assessed Alternative 1 is estimated to be $427 million, in terms of the patient, family, and society as a . Under Alternative 2, the estimated cost is whole. At a minimum, the economic cost must $16 million. And, under Alternative 3, there is no-consider the direct cost of medical resources related cost because hospitalization is not required to retain the patient in a hospital and the required. indirect cost resulting from the loss of human resources. Additional consideration should be Estimates of the Numbers of lircast Feeding given to the psychological impact of retention on % men Requiring Records and instructions the affected individual and family members. Under Alternative 3 -- llospitalization will also cause an increase in the dose to the hospital staff and other patients in the The rule associated with Alternative 3 establishes hospital liowever, the increase in dose to the additional requirements for recordkeeping and
- hospital staff is expected to be low relative to a providing instructions. Before one can determine patient going home earlier because of the the costs of these requirements, it is necessary to precautions taken during hospitalization; calculate the number of patient releases invohing
_e.g., patients are isolated and the hospital staff . breast. feeding women that apply to each rarely enters the patient's room. requirement. NUlWG.1492 24 n - =_= . _ _ .
t Table 4.12 Duration of Retention per lherapeutic Procedure Alternathe ! Alternathe 2 Alternative 3 (days) (days) (days) Typical Acthily hospital total laospital total E 1herapeutie Administered days per hospital da3s per hospital da3s per procedures Procedure (Milq) (mCl) procedure days procedurt days procedure (x 1000) Thyroid Ablation 1 131, 50,000 proceduies/ycar 1,110 (30) 7 343,000 0 0 0 0 2,220m (60) 14 14,000 1 1,000 0 0 Thyroid Cancer 1 131, 10,000 procedures / year 5,550 (150) 1.5 70,000 1,5S 15,000 0 0 Permanent Implant, 1 125, 2,000 procedures / year 1,480 (40) 0 0 0 0 0 0 Total for All Therapeutic 427,000 16,000 0 Procedures
"' Masimum activity admirustered. His analysis assumes that 98 percent of the patients are typicahy administered 1,110 millisieverts (30 nullitunes) amt that 2 percent are administered the maximum activity.
"' The analysis under Section 4.2.5.1 Conectivo Done to Individuals shows I day of hospitalization. Ilosever, patients are typically hospitahzad for i to 2 days, nus, the actual obaetved value is shown, 25 NUREG-1492
i l l l
'Ibe number of releases invohing breast. feeding imposes additional costs for providing instructions women that require instructions under including written instructions on the estimated Alternative 3 is calculated in the following 1,350 licensees. In the case in which the manner. First, the total number of administered activity could cause a dose from administrations potentially requiring instructions direct radbtion execeding 0.1 rem (1 millisievert),
for breast feeding, approximately 4 million, was instructions would have to be given to 62,000 determined by summing up the number of patients per year at a cost of $1.4 million per year, administrations for all of the radionuclides in in addition, instructions would have to be given to , Table 4.2 that would require instructions based on approximately 27,000 breast feeding women at a l Table 11.5. For radiopharmaceuticals not cost of $0.6 million per year. In both u.as, o a identified in Table 4.2 but listed in Table 11.5, the of $22 per patient is estimated. The total number of administrations was assumed to be estimated cost of instructions is $2 million per year. i negligible. Next, from Table 43 it was estimated that 13.5 percent of the radiopharmaceuticals ase Costs of Providing Recordkeeping ' administered to females of childbearing age and that 5 preent of them, based on information in Alternath>cs 1 and 2 have no recordkceping Statistical Abstracts of the United States (SA94), requirements, and therefore, have no related could be breast 4 ceding (assuming an everage costs, llowever, the rule associated with breast-feeding period of 1 year). To estimate the Alternative .$ imposes additional paperwork and r umber of releases that require instruction, one recordkeeping requirements ou the estimated needs only multiply 4 million by 13.5 percent, and 1,350 licensees (NRC. and Agreement State-then by 5 percent. Thus,27,000 releases of licensed) that prmide diagnostic and therapeutic breast feeding women require instructions, administrations of radiopharmaceuticals. For therapeutic adtninistrations where releases are not The number of patient releases invohing breast. based on the default table of activities and dose feeding women that require a record of rates in Regulatory Guide 839," Release of instructions under Alternative 3 was calculated in Patients Administered Radioactive Materials
- the following manner. Using Table 11.5, only the (NRC96), a record must be maintained for 3 years, radiopharmaceuticals resulting in a dose to the breast feeding infant exceeding 5 millisieverts Additionally,if the released patient is breae (0.5 rem) with no interruption were identified. Of feeding woman and the radiation dose to the the identified radiopharmaceuticals, only those nursing infant could result in a total effective dose with a significant number of administrations using equivalent exceeding 5 millislevert (0.5 rem) the data in Table 4.2 were considered. Ilased on assuming no interruption of breast-feeding, then a this analysis, the total number of administrations record must be maintained, for 3 years, that potentially requiring records for issuance of instructions were prcvided, la this case, both reast feeding instructions was estimated at diagnostic and therapeutic administrations of 1.06 million (i.e.,60,000 iodine 131 administrations radiopharmaceuticals could require a record.
for thyroid cancer and ablation plus 1 million technetium 99m pertechnetate administrations). It is estimated that approximately As discussed above,13.5 percent of the 17,200 procedures per year would be subject to radiopharmaceuticals are administered to females these requirements (i.e., (1) 10,000 patients of childbearing age and 5 percent of them could treated with iodine for thyroid cancer and be breast-feeding. To estimate the number of (2) 7,200 administrations to breast. feeding releases that require a record, one needs only women). A cost of $17 per patient is estimated, multiply 1E million by 13.5 percent, and then by This results in an annual estimated cost of 5 percent. Thus,7,200 releases of breast-feeding approximately 30.3 million. women require a record. 4.3.1.2 Derivation of Indirect Costs Costs of Prmiding instructions less of Time Alternatives 1 and 2 have no requirements for instructions, and therefore, have no related costs. Indirect costs principally reflect the time and flowever, the rule associated with Alternative 3 output lost or forfeited by the patient while NURIE 1492 2r>
Tabic 4.13 Annual Attributes of Alternathes I,2, and 3 Cost Estimates llospitallt.ation Value of Records & ilospital cost lost tirne Instructions Psychological Co!!ecthe Dose Retention $ $ $ cost Alternative (person rem) (days) (ruillions) (millions) (millions) (relathe) 1 18,400 427,000 427 2162 0 liigh 2 29,840 16,000 16 0 96 0 Moderate l 3 32,580 0 0 0 23 low retained in a controlled environment. Indirect the direct and indirect economic costs identified costs may also be incurred by individuals other above. The wide variety of deterioration in the than the patient who may forgo conomic quality of life brought on by illness is frequently activities to accommodate a family member's referred to as psychological costs. For thyroid hospital retention. Economic activities include cancer or dysfunction requiring therapeutic doses occupational work that is lost to either the patient of iodine 131 for example, a deterioration in the or his or her employer as well as non-occupation. quality of life may be precipitated by the loss of al (e.g., domestic) work which must be performed bodily function, a lifetime dependence on by someone else at the expense of the patient, medication, hormonal instability, uncertainty of normal life-expectancy, disruption of normal daily The conversion of time lost from economic routines, and reduced financial security related to activities to equivalent dollars is most fairly employment, lost earnings, and medical expenses. achieved by means of the gross national product (GNP). The GNP is considered the most While some of these elements of psychological comprehensive measure of the country's economic costs are the result of the disease itself, others activity and includes the market value of all goods such as disruption of normal routines, social and services that have been bought for final use isolation, and enhanced financial strain are clearly during a year. From the GNP of about elements of psychological costs that are directly
$5,600 billion in 1991, the gioss average annual related to patient retention. The conversion of per spita income of about $22,000 is derived, psychological cost from patient retention to The value of $22,000 per year corresponds to equivalent dollar; i complex such that an
$60 per day. To estimate the equivalent dollar evaluation is highly subjective and dependent upon value for the number of days Icst due to retention the individual situation. Instead, this analysis uses of an individual for a therapeutic procedure, one a qualitative and reasonable approach to scope need only multiply $60 by the days of retention the range of possible responses. As shown in for the procedure presented in Table 4.12. The Table 4.13, comparison is provided on a relative value of the days lost for each alternative is shown scale.
in Table 4.13. 4.3.2 Costs and Ilenefits of Alternatives 43.13 Evaluation of Psychological Costs Table 4.13 summarizes the data pertaining to the Retention of patients in a hospital by design annual attributes for each of the three alternatives necessitates that the patient be
- isolate # and that.
under consideration. To determine the preferred human contact, inclusive of family members, is alternative, the costs and benefits that result when either avoided or minimited. Such isolation may Alternatives 1 and 3 are each compared with bring about numerous changes and impositions in Alternative 2 (the status quo) were analped. Th: the lives of the patient and family members that results are shown in Table 4.14. A value of $2JXX) may in part be linked to, but are not reflected in, 27 NUREG-1492 5
f Table 4.14 Annual Costs and llenefits of Alternatises I and 3 Compared to Alternative 2 Clhe Status Quo) Collective Dosem Costs Assoelated llospitalization, Imt Time, Value Records and Instructions Net Itenefit Dose Averted $ $ $ Alternative (person rem) (millions) .sillions) (millions)
^
1 11,440 (savings) 23 (savings) 435 (cost) -412 (net cost) 2 0 0 0 0 - 3 -2,740 (cost) 5 (cost) -14 (savings) 9 (net savings)
"' A value of $2.000 per person-rern was used as the cwversion factor for does aven A i
a per person rem was used as the conversion factor above 1 millisievert (0.1 rem) for long periods of for dose averted (NRC95). time. The reccmmendations of thc ICRP and NCRP are based on their imding that annual Because the benefits and costs for al' alternatives doses in excess of 1 millisievert (0.1 rem) to a occur in t'ne same year, and remain tta: same each smal: group of people, provided that they do not year for tne therapeutic procedures discussed, a occur often to the same group, need not be discouated flow of the benefits and costs of this regarded as especially hazardous. Although the rulemaking is not required. risx is potentially greater under Alternative 3,it is still within the range of acceptable risk for radiation exposure accepted by the NRC (as 4A Evaluation of the Alternatives With Respect to Accepted Radiation Protection Principles 5 DECISION RATIONALE Selection of the 5-millisieverts (0.5-rem) total 1. All of the alternatives are acceptable effective dose equivalent per year criterma is according to generally accepted radiation consistent with: the Commission's provision in protection principles such as those expressed
'O CFR 20.1301(c) for authorizmg a licensee t by NRC, NCRP, and ICRP (see Section 4.4, operate up to this limit;. the recommendations of Evaluation of the Alternatives With Respect the International Commission on Radiological to Accepted Radiation Protection Principles).
Protection (ICRP) in ICRP Publication 60, "1090 Rcccmmemlations of the International Commission J- 2. Alternative 1 is considerably more expensive on Radiological Protection"; and the to the public compared to Alternative 2 (the recommendations of the NCRP in NCRP Report , , statw quo) or Alternative 3. Even neglecting No.116, " Limitation of Exposure to ' .nizmg thr. psychological costs, which have not been Radiation." Each of these provide a basis for expressed in dollar terms, the additional cost allowing mdividuals to receive annual doses up t of Alternative 1 relative to Alternative 2 is 5 millisieverts (0.5 rem) under certain about $412,000,000 per year, mostly due to cirenstances. Both ICRP and NCRI' increased national health care costs. In view recommend that an individual be allowed to of this, Altemove 1 may be Mmissed. eceive a dose up to 5 millisieverts (0.5 rem) ,ma t iven year in temporary situations where exposure
- 3. Alternative 3 reladve to Altei.iative 2 has a to radiation is not expected to result m doses
,et value of about $9,000,000 per war, mostly NUREG 1492 28 .x . -
due to lower health care costs. Also, to give all of the acthity in a single Alternative 3 has psychological benefits to administration. This would reduce the patients arid their families. Thus, potential for repeated exposures to hospital Alternative 3 is cost effective in comparison staff and to those providing care to the with Alternative 2. released patient. Additionally, this would 3 provide physicians with the Dexibility to not
- 4. !!asing the patient release criteria in have to fractionate doses to avoid 10 CFR 35.75 on the dose to individuals hospitalization to meet the current exposed to a patient provides a consistent, requirements, which may lead to a more scientific basis for such decisions that treats effective treatment.
~
all radionuclides on a risk equivalent basis. The dose delivered by an initial activity of 6. Shorter hospital stays provide emotional y_ 1,110 megabecquerele (30 millicunics) or a benefits to patients and their families. "? dose rate at 1 meter of 0.05 millisievert Allowing earlier reunion of families can (5 millirems) per hour varies greatly from one improve the patient's state of mind, which in radionuclide to another. Thus, while the itself may improve the outcome of the values in the current 10 CFR 35.75 may be treatment and lead to the delivery of more appropriate for iodine 131, they are too high effective health care, for some other radionuclides and too low for ) others. 1 3 5. A dose-based rule no longer restricts patient 6 IMPLEMENTATION release to a specific activity, and therefore would permit the release of patients with activities that are greater than currently No impediments to implementation of the allowed. This is especially true when case- recommended ahernative have been identified. specific factors are evaluated to more The staff has prepared a regulatory guide accurately assess the dose to other inoividuals. (NRC96) for licensees which provides, in part, For the case of thyroid cancer, in those simple methods to evaluate the dose to the occasional cases where multiple administrations individual member of the public likely to receive in a year of 1,110 megabecquerels the highest dose from the released patient. This (30 millicuries) or less of iodine.131 are now will enable licensees to determine when a patient administered to a patient,it may be possible may be released from their control. 29 NURiiG 1492
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Ohshima, IL Mackoshi, T. Orito, T. Watanabe,1980, ' Monitoring of PE86 Pectasides, D., S. Stewart, N. lodme Excretions and Used Courtenay Luck, R. Rampling, AJ, Materials of Patients Treated with Munro, T. Krausz, B. Dhokia, D. 1-131," llealth Physics 38(4):467. Snook, G, Ilooker, H. Durbin, J. Taylor.Papadimitriou, W.F. Bodmer, A.A. Epenetos,1986, ' Antibody-NRC96 U.S. Nuclear Regulatory Commission, Guided Irradiation of Malignant 1996, Regulatory Guide 8.39,
- Release Pleural and Pericardial Effusions,"
of Patients Administered Radioactive Br. J. Cancer 53:727. Merrials," Washington, DC. l _ PE42 Pecher, C.,1942, " Biological Investi-j NRC95 U.S. Nudear Regulatory Commission, gations with Radioactive Calcium and November 1995, NUREG/BR-0058, Strontium: Preliminary Report on the Revision 2," Regulatory Analysi, of Use of Radioactive Strontium in the the UE, Nuclear Regulatory Treatment of Metastatic Bone Cancer,' Commission," Final Report, Univ. Calif. Pub. Pharmacol.11:117. Washington, DC. PO93 Porter, A.T. and J.D. Forman,1993, OR85 Order, S.E., G.B. Stillwagon, " Prostate Brachpherapy. An Over-J.L Klein, P.K. Leichner, S.S. view,' Cancer 71 (3 Suppl):953. Siegelman, E.K. Fischman, D.S. Ettinger, T.11aulk, K. Kopher, PO90 1 orter, A.T., J. Battista, D. Mason, K. Finney, M. Surdyke, S. Sels, R. Barnett,1990, " Ytterbium-169; A S. Leibel,1985, " Iodine-131 Anti- Novel Brachgherapeutic Source," ferritine, A New Treatment Modality Clin. Invest. Med. Phys.13:198. in Hepatoma: A Radiation Therapy Oncology Group Study,' J. Clin. PR92 Priestly, J.B. Jr. and D.C. Beyer, Oncol. 3:1573. 1992," Guided B.achgherapy for Treatment of Confined Prostate OS92 Ostertag, C.B. and F.W. Kreth,1992,
" Iodine-125 Interstitial Irradiation RI90 Riva, P., S. Lazzari, M. Agostini, G.
for Cerebral Gliomas," Acta Sarti, G. Moscatelli, G. Franceschi, Neurochi (Austria) 119(14):53, A. Spinelli, G. Vecchietti, R. Tassini, Freiburg University, Federal D. Tirindelli,1990, " Intracavitary Republic of Germany. Radioimmunotherapy Trails in Systemic Gastrointestinal and PAS 7 Park, C.H., J.11. Suh, fl.S. Yoo, J.T. Ovarian Carcinomas: Pharmacokinetic, Lee, D.I. Kim, B.S. Kim,1987, Biologic and Dosimetric Problems,"
" Treatment of liepatocellular Car. In: Schmidt HAE, Chambron J.,
cinoma (HCC) with Radiolabeled Eds., Nuclear Medicine - Lipiodol: A Preliminary Report," Ouantitatise Analysis in Imaging and Nucl. Med. Commun. 8:1075. Function. Schattauer, Stuttgart, SM. 33 NU REG-1492
l ROS7 Robinson, R.G., J A. Spicer, D.F. Sl85 Silberstein, E.B., C. Williams,1985, Preston, A.V. Wegst, N.L. Martin, " Strontium.89 Therapy for the Pain 1987," Treatment of Metastatic Bone of Osseous Metastases," J. Nucl. Pain with Strontium.89," Nucl. Med. Med. 26:345. Biol.14:219. R O77 Roberts, DJ.,1977, ""P sodium ST88 Stanbury, J.B.,1988, "The Physio-Phosphate Treatment of Metastatic logical Basis for Blockade of Radio. Malignant Disease," Clin. I4d I.iod. - iodine Retention by lodine,"in 2:64. lodine Prophylaxis following Nuclear-Accidents, Proceedings of a Joint ROE 90 Roesler, H., J. Triller, L Geiger, WHO/ CEC Workshop, E. Rubery H.U. Baer, H.P. Beer, L Blumgart, and E. Smales, Eds., Pergamon 1990, Superselective 90Y-resia Press, NY. Embolization Therapy of Solid ; Tumors," Eur. J. Nucl. Med.16:439. TU89 Turner, J.H., P.G. Claringbold, RU92 Rustig, S.N., S.S. Hahn,1992, E.L Hetherington, P. Dorby, AA.
" Advantages of using High Activity Martindale,1989, "A Phase I Study 1 125 Seeds in Temporary Interstitial of Samarium-153 Ethylenedia-Breast Implants," Med. Dosim. minetetramethylene Phosphonate 17(4):217. Therapy for Disseminated Skeletal Metastases," J. Clin. Oncol. 7:19%.
SA94 - U.S. Bureau of the Census, Statistical Abstract of the United States: 1994 (114th edition.) WH88 Whitmore, W.F.,1988, " Interstitial Washington, DC. Implantation of the Prostate: 10 Year Results, Brachytherapy SC92 Scharfen, CS., P.K. Sneed, W.M. Update,1988," In: Proceedings of Wara, DA. Larson, T.L Phillips, the Memorial Sloan Kettering M.D. Prados, KA. Weaver, M. Cancer Center Course on Malec, P. Acord, K.R. Lamborn, Brachytherapy. B. Hilari , Ed. 1992,"High Activity lodine-125 Interstitialimplant for Gliomas," Int. J. Radiat. Oncol. Biol. Phys. 2 t(4):583. ZIS4 Ziessman, HA., J.H. Thrall, PJ. Yang, S.C. Walker, EA. Coni, J.E. SC90 Schroder, LE., H.R. Maxon,1990, Niederhuber, J.W. Gyves, W.D, "Re.186-HEDP Palliation of Painful Ensminger, M.C. Tuscan,1984, Skeletal Metastases," presented at " Hepatic Arterial Perfusion the European Association of Nuclear Scintigraphy with Tc-99m MAA," Medicine Congress, Amsterdam. Radiology 152:167. N UREG-1492 34 h ______-
APPENDIX A i PARAMETERS AND CALCULATIONS FOR DETERMINING RELEASE QUANTITIES AND DOSE RATES FOR RADIONUCLIDES USED IN MEDICINE Table A-1 Italf Uves and Exposure Rate Constants of Radlonuclides Used in Medicine. Exposure Exposure llatf Life Rate Constant' Italf Life Rate Constant' Radionuclide (days)* (R/mO-h at I cm) Radionuclide (days)* (R/ mci-h at I cm) i Ag-111 7.45 0.150 Pd-103 implant 16.97 1.48 " Au-198 2.6% 2.36 Re-186 3.777 0.168 l Cr-51 27.704 0.177 Re-188 0.7075 0337 i l Cu-64 0.5292 1.10 Sc-47 3351 0.626 Cu-67 2.5775 Se-75 119.8 2.60 Ga 67 3.261 0.753 Sm-153 1.9458 0.425 I123 0.55 1.61 Sn-117m 13.61 1,48 I125 60.14 1.42 Sr-89 50.5 NA" l 125 implant 60.14 1.1 l' Tc 99m 0.2508 0.756 I-131 8.040 2.20 TI-201 3.044 0.447 In 111 2.83 3.15 Y-90 0.1329 NA" Ir-192 implant 74.02 4.59' Yb-169 32.01 1.83 P-32 14.29 NA"
- Keith F. Eckerman, Anthony B. Wolbarst, and Allan C. B. Richardson, Federal Guidance Report No.11.
Limitine Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation. Submersion. and Incestion. Report No. EPA-520/1-88-020, Office of Radiation Programs, U. S. Environmental Protection Agency, Washington, DC,1988. A.1 NUREG 1492
. - ~. . . -. .. . -. ,- _ ' The exposure rate constant was calculated from the following equation (details of the calculation are shown in Table A.2):
mR cm2 dis ' 1 "', c m-' gm. m R erg
- l' =
(1.332 x 10
*nCi hr
. mci hr) ( 4r (100 cm)') E f,E' ( p gm cm' )( 87.6 erg )(1.6 x 10' MeV )
Where % = the energy of the ith gamma ray or x-ray i, MeV. f, m . 'he probability of decay of gamma rays or x-rays with energy % per disintegration. Values for % and f, were taken from: Bernard Shleien, The Health Physics and Radiolocical Health Handbook. Revised Edition, Scinta, Inc.,1992, pages 294-334. For Re-186, Re-188, and Sn-117m the values for 4 and f, were taken from: Laurie M. Unger and D. K. Trubey,
" Specific Gamma. Ray Dose Constants for Nuclides Im ur. ant to Dosimetry and Radiolocical Assessment.' U.S. Department of Energy, ORNL/RSIC-45/R1,1982.
, ,,,= the linear energy absorption coefficient in air of photons of energy %, taken from Radiolacical Health Handbook. U.S. Department of Heahh, Education, and Welfare,1970, page 135. p= the density of air at standard temperature and pressure, taken to be 0.0012929 gm/cm'. 8 R. Nath, A.S. Meigooni, and J.A. Meli, " Dosimetry on Transverse Axes of "31 and '"tr Interstitial Brachytherapy Sources," Medical Physics. Volume 17, Number 6, November / December 1990. The exposure rate constant given is a measured value averaged for several source models and takes into account the attenuation of gamma rays i. ' hin the implant capsule itself. -
" A. Meigooni, S. Sabnis, and R. Nath, " Dosimetry of Palladium-103 Brachytherapy Sources for Permanent implants," Endocurie eherapy Hyperthermia Oncolocv. Volume 6, April 1990. The exposure rate constant given is an
- apparent
- value (i.e., with respect to an apparcut source activity) and takes into account the attenuation of gamma rays within the implant capsule itself.
" Not applicable (NA) because the release quantity is not based on beta emissions.
i t I ) Y Pe C tAk/ t { [d. e 1 j' 0 's i l
,i l
, i - / r.
I i .
-)
/
NU REG-1492 A2
k 4 4 4 4 6 ATTACHMENT - 4 ENVIRONMENTAL ASSESSMENT ' ' ' ' ~ 3
e ENVIRONMENTAL ASSESSMENT AND FINDING OF NO SIGNIFICANT IMPACT s . ON AMENDMENTS _OF-10 CFR PARTS 20 AND 35 ON
" CRITERIA FOR T;lE RELEASE OF PATIENTS ADMINISTERED RADI0 ACTIVE MATERIAL" Stewart Schneider.and Stephen A. McGuire Office of Nuclear Regulatory Research U. -S. Nuclear Regulatory Commission April-1996
- 1. THE PROPOSED ACTION The Nuclear Regulatory Commission (NRC) .is amending its regulations in 10 CFR Parts 20 and 35 concerning criteria for the release'of patients administered radioactive material. The amendments permit licensees to authorize the release from licensee control of patients administered
{
-radiopharmaceuticals or permanent implants only if the dose.to total decay to
- an_ individual exposed to the released patient is not likely to exceed 5 millisteverts (0.5 rem),
II. NEED FOR_THE RULEMAKING ACTION This action is'necessary to respond _to three petitions for rulemaking. The petitions were submitted by Dr. Carol S. .Marcus by the American College of' Nuclear Medicine (ACNM), and by the _ American Medical: Association.(AMA). NRC's current-patient release criteria in 10;CFR 35.75, " Release of ; Patients or Human Subjects Containing Radiopharmaceuticals or Permanent
-Implants," are: as1follows: "(a) A licensee may not authorize' release from confinement for medical _ care any patient or humanLresearch subject administered a radiopharmaceutical'until either: (1) The measured dose rate from the patient _or human research subject.is less than.5 millirems per hour i
' atla. distance of one meter; or (2) The activity in the-patient' or human research subject-is less than 30 millicuries; (b) A licensee may not authorize
- release from confinement for medical care of any patient or-human research subject administered a permanent' implant--until the measured dose rate from the patientJ or the human research subject is less than 5 millirems per hour at a distance ofJone meter."'
-On May 2:1,;1991 (56 FR 23360), the NRC published a-final rule that amended 10 CFR PartL20, " Standards for Protection Against Radiation."_ The.
rule _ contained a dose . limit of 1 millisievert (0.1 rem)- (total effective dose equivalent) for members of the public in 10 CFR 20.1301(a). When 10 CFR part 20 was' issued, there was no discussion in the supplemental 1 J
information on whether or how the previsions of 10 CFR 20.1301 were intended to apply to the release of patients. Because some licensees were uncertain about what effect the revised 10 CFR Part 20 would have on patient release criteria, three petitions were received on the issue. On June 12, 1991 (56 FR 26945), the NRC published in I the Federal Register a notice of receipt of, and request for comment on, a I petition for rulemaking (PRM-20-20) from Dr. Carol S. Marcus. The petition requested the NRC to amend the revised Part 20 and 10 CFR 45.75 to raise the annual r'diation dose limits to members of the public from 1 millisievert (0.1 reni; to 5 millisieverts (0.5 rem) from patients administered radioactive materials. In addition, Dr. Marcus submitted a letter dated June 12, 1992, further characterizing her position. On March 9, 1992 (57 FR 8282), the NRC published a notice of receipt and request for comment in the Federal Register for a similar petition for rulemaking (PRM-35-10) from the American College of Nuclear Medicine (ACNM). On May 18,1992 (57 FR 21043), the NRC published in l the Federal Register notice of an amendment submitted by the ACNM to its l original petition (PRM-35-10A). In addition, the ACNM submitted two letters ! dated September 24, 1991, and October 8, 1991, on the issues in their petition. On July 26, 1994 (59 FR 37950) the NRC published in the Federal Register a petition from the American Medical Association requesting that , patient release be regulated by Part 35 rather than Part 20. r On June 15, 1994, the NRC published a proposed rule on criteria for the release of patients 4duinistered radioactive material in response to the petitions (59 FR 30724). The Federal Register Notice for the proposed rule discussed the public comment letters received on the first two petitions. Three comment letters, each supporting the petition, were received on the third petition (PRM-35-11), but these letters did not contain any additional information not covered by the letters on the first two petitions. The NRC proposed to amend 10 CFR 20.1301(a)(1) to specifically state that the dose to individual members of the public from a licensed operation does not include doses received by individuals exposed to patients who were released by the licensed operation under the provisions of 10 CFR 35.75. This was to clarify that the Commission's policy is that patient release is governed by 10 CFR 35.75, not 10 CFR 20.1301. Ill. ALTERNATIVES CONSIDERED To evaluate the issues raised by the petitioners and the members of the public who commented on the requests made by the petitioners and the proposed rule, the NRC has determined that the following alternatives merit evaluation: e Alternative 1: 1 millisievert (0.1 rem) total effective dose equivalent In this alternative, the 1 millisievert (0.1 rem) per year dose limit in 10 CFR 20.1301(a) is evaluated as the controlling criterion for determining when a patient may be released from the licensee's control. 2
I 1 l e Alternative 2: < l.110 megabecquerels (30 millicuries) or l
< 0.05 millistevert (5 millirems)/hr at I tieter '
In this alternative, the existing patient release criteria in 10 CFR 35.75 are v aluated at the controlling requirements for i determining when a patient may be released.
- Alternative 3: 5 millisieverts (0.5 rem) total effective dose l equivalent)
In this alternative, a dose limit of 5 millisieverts (0.5 rem) for , determining when a patient may be released is evaluated. ' The alternatives were evaiuated in the regulatory analysis done for the rulemaking (Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Hatericls, Final Report, Stewart Schneider and Stephen A. McGuire, NRC report NUREG-1492, 1996). The regulatory analysis found that there would be no need to retain patients because of any diagnostic procedure under any of the alternatives. Only about 62,000 therapeutic procedures per year, mostly using iodine-131, would be potentially affected. The costs of the alternatives for the affected therapeutic procedures are presented in Table 1. For details of how the results were calculated, the regulatory analysis should be consulted. Table 1 Annual Attributes of Attematives 1,2, and 3 Cost Estir .ates Hospitalization Value Records & Collective Hospital r ost lost time Instructions Psychological Dose Retention 4 4 $ cost Alternative (person tem) (aays) (millions) (millions) (millions) (relative) 1 18,400 427,000 427 25.62 0 High 2 29,840 16,000 16 0.96 0 Moderate 3 32,5PO O C 0 2.3 Low As set forth in more detail in the Regulatory Analysis, Alternative 3 is favored for the following reasons:
- 1. All of the Alternatives are acceptable according to generally accepted radiation protection principles, as those expressed by NRC, NCRP, and ICRP, as discussed in Section 4.4 of the Regulatory Analysis.
- 2. Alternative 1 is considerably more expensive to the public compared to Alternative 2 (the status quo) or Alternative 3. Even neglecting the psycheiogical costs, which have not been expressed in dollar terms, the additional cost of Alternative 1 relative to Alternative 2 is about 3
3
$412,000,000 per year, mostly because of increased national health care costs. In view of this, Alternative 1 may be dismissed.
- 3. Alternative 3 relative to Alternative 2 has a net value of about
$9,000,000 per year, mostly due to lower health care costs. Also, Alternative 3 has psychological benefits to patients and their families.
Thus, Alternative 3 ';s cost-effective in comparison with Alternative 2.
- 4. Basing the patient release erittitie in 10 CFR 35.75 en the dose to individuals exposed to a patient provides a consister.t, nis.t:fic basis for such decisions that treats all radionuclides on a risk-equiva.. tnt basis. The dose delivered by an initial activity of 30 millicuries or a dose rate at 1 meter of 5 millirems ptir hour varies greatly from one radionuclide to another. Thus, while the values in the current 10 CFR 35.75 may be appropriate for iodine-131, they are toa high for some other radionuclides and too low for others,
- 5. A dose-based rule no longer restricts patient release to a specific activity, and therefore would permit the release of patients with activities that are greater than currently allowed. This is especially true when case-specific factors re evaluated to more accurately assess the dose to other individuals. far the case of thyroid cancer, in those occasional cases where multiple administrations in a year of 1,110 millisieverts (30 millicuries) or less of iodine-131 are now administered to a patient, it may be possible to give all of the ;
activity in a single administration. This would reduce the potential for repeated exposures to hospital staff and to those providing care to the released patient. Additionally, this would provide physicians with f the flexibility to not have to fractionate doses to avoid hospitalization to meet the current requirements, which may lead to a more effective treatment.
- 6. Shorter hospital stays provide emotional benefits to patients and their families. Allowing earlier reunion of families can improve the patient's state of mind, which in itself may improve the outcome of the "
treatment and lead to the delivery of more effective health care. IV. ENVIRONMENTAL IMPACTS OF THE PROPOSED ACTION AND THE ALTERNATIVES Breast-feedina Infant The dose to the breast-feeding infant can be controlled by giving the woman instructions, as required by the revised 10 CFR 35.75, to discontinue or to interrupt breast-feeding as appropriate. The decision to require instructions as shown in column 5 of Table B.5 of the Regulatory Analysis (NLREG-1492) is based on both the external and internal dose to the nursing infant. It can be seen from column 4 that for some radiopharmaceuticals the external dose from breast-feeding can be a significant part of the total dose. 4 l l
+
a
lhe duration of the interruption shown in column 6 is selected to reduce the maximum dose to a newborn infant to less than 1 millisievert-(0.1 rem). The actual doses that would be received by most infants for the recommended ~ interruption periods shown should be a small fraction of 1 millisievert (0.1 rem) due to the conservatism of the analysis. The conservative factors are based on: (1) the maximum measured level'of activity in breast milk, (2) the longest biological half-life, and (3) the lowest body weight (i .e. , the newisorn). ' If the woman does not cease breast-feeding after administration of ' millicurie quantities of iodine-131 sodium iodide, the internal dose to the breast-feeding infant could be large enough to cause the infant's thyroid to be severely damaged resulting in hypothyroidism. If hypothyroidism were undiagnosed in very young children, severe mental retardation may occur. l However, if-the patient was provided instructions to discontinue breast-l= feeding, as well as being advised of the consequences of not following the instructions,-the NRC believes.that the probability of a woman failing to-cease breast-feeding after being; administered iodine-131 sodium lodide is small. For example, in 1990 an administered dosage of.185 megabecquerels (5 millicuries) of iodine-131 sodium iodide to a patient resulted in her breast-fed infant receiving an unintended radiation dose of 300 < .ys (30,000 rads) to the infant's thyroid gland. This dose would result in 4ation of _the infant's-thyroid. This situation was recognized in 2 days ch allowed-
. prompt action to be taken thereby reducing potentf C consequer such as.
mental retardation. The NRC is aware of two other cases that .urred during
-1991 and 1995. In each of these cases, there was a breakdown .n communications, rather than lack of intent to prevent breast feeding. This trule might therefore be expected to provide a henefit by reducing the probability of a mother breast-feeding af ter administration of large quantities of iodine-131.
It-is estimated that approximately 400* breast-feeding women could be . administered millicurie amounts of iodine-131 sodium iodide each year _for diagnosis and_ treatment of thyroid disease, in some cases, instructions to-interrupt or discontinue breast-feeding may not be effectively communicated. To deal with this issue, the NRC considered a range of options which varied from maintaining the status quo to the extreme option of confining a woman foi a period of time after administration of millicure quantites of I-131 sodium
;odide to ensure here milk production has stopped. Included within this range of options was the option to enhance communication between the licensee and
-woman regarding instructions to interrupt or discontinue breast feeding before the woman is released'from the hospital.
The option-of maintaining the status quo does not provide the assurance that instructions will'be provided tc a breastfeeding woman and could still allow
- 60,000 patients administered iodine-131 sodium iodide x 0.135 child bearing age x 0.05 breast-feeding = 405 patients administered iodine who could be breast-feeding.
5
i I 1 l i for a breakdown in communciations. As indicated above, the NRC is aware of three cases of unintended exposure to a breast-feeding child during the last five years. There would be no costs associated with this option. ! At the other end of the range, for the extreme option in a hospital, a woman would be retained until she stopped producing milk. However, this l option would result in psychological impacts to both the woman and breast-feeding infant, by requiring them to be physically separated for some period of time, whitir are not quantified by this analysis. This option was also considered to be impractical as it wcald k dificult for a medical institution to separate a woman and breast-feeding child. That is, this option does not prevent the breastfed child from being brought into the patient nor does it address the situation of the patient releasing herself against medical advice. Also, to require cessation of breast-feeding after administration of iodine-131 sodium iodide by hospital retention, or prior to administration (to avoid hospital retention), directly impacts the practice of given medicine,sinceitwouldineffectdict$tewhenatreitmentcouldbnahospitalforan. If it is estimated that each woman woul be retained average of 7 days at a cost of $1,000 per day. The estimated annual cost for the extreme option is 400 x 7 x $1,000 - $2.8 million. In addition, there would be associated costs for providing women with instructions and information as to the need for hospital retention. The circumstances of a woman choosing to ignore the warning that breast-feeding would cause significant harm to the infant and to continue to breast-feed are considered to be very rare. As stated above, NRC is not aware of any instance where this has occurred. Therefore, the extreme option was not selected because of the negative psychological impact to both the woman and infant, as well as the high annual dollar cost. Regarding the preferred option to enhance communication, although instructions to keep doses to household members and the public as low as is reasonably achievable are currently required for radiopharmaceutical therapy in 10 CFR 35.315(a)(6), there is no requirement specific to the dose from breast-feeding. To enhance communications, amended 10 CfR 35,75(b) will require licensees to provide guidance on the interruption or discontinuation j of breast-feeding and information on the rationale for following the guidance. Compliance with the regulation provides NRC with confidence that the licensee will give the instructions to breast-feeding woman and it is expected that almost all women will follow instructions to interrupt or discontinue breast-feeding to protect their children from potentially harmful effects. The NRC is not aware of any instances where instructions were given to the woman but she ignored the warning and continued breast-feeding a child. Since the estimated costs per patient for providing instructions and recordkeeping are
$22 and $17, respectively (see 4.3.1.1, Estimates of the Direct Costs of Patient Retention), the estimated costs for this option would be about $16,000 per year. Therefore, the option to enhance communication is selected as the preferred option.
It is expected that there will be no effect from breast-feeding on collective dose due to therapeutic administrations, although there may be a small effect from more infants having an opportunity to have contact with a woman sent home from hospital (i.e., cancer patients). However, instructions 6
providing guidance, such as to maintain distance from other persons, should '
. aid in minimizing this effect. In sum, the environmental impact is not censidered significant. -
- - In the case of diagnostic administrations of iodine-131 sodium iodide, it is currently normal practice to recommend interruption of breast-feeding.
Thus, this rule is expected to have little or no effect on collective dose due to diagnostic administrations. Other Family Members or Persons For the purpose of evaluating the environmental impact of the proposed action, the proposed action (Alternative 3) is compared to the impact of the existing patient release criteria, the status quo (Alternative 2). The impacts can be seen in Table 1 above. The estimated change in the collective ; dose when comparing Alternative 3 to Alternative 2 is an increase of 27 person-sievert (2,700 person-rem). Most of the increase, about 26 person-sievert (2,600 person-rem), is received by the primary care-providers and family members exposed-to released patients (about 10,000) administered iodine-131 sodium iodide for thyroid cancer (see Tables _4.10 and 4.11 of NUREG-1492); whereas, 1 person-sievert (100 person-rem) is associated with exposure to released patients (about 1,000) administered more than 1,110 megabecquerels (30 millicuries) of iodine-131 sodium for thyroid ablation-(see Tables 4.10 and 4.11 of NUREG-1492). Based on the assumption that each patient could expose about seven-family members and friends (including-the primary care-provider), the increase in dose to an affected individual in a year is about 0.00037 sievert (37 millirem) for thyroid cancer and about 0.00014 sievert (14 millirem) for thyroid ablation. The increase in-risk to the affected individual could vary from zero (if a dose threshold - exists) to 1.8x10 per year (if the linear no threshold hypotheses is valid and a risk factor of about 5x10" per person-rem is used). When compared with the incidence of cancer of 0.20 from natural causes, the potential- cancer- risk for a family member or other person rho has close contact with a thyroid cancer or. thyroid ablation patient is small. Thus, the environmental impact is not considered significant. V. FINDING 0F NO SIGNIFICANT IMPACT The Commission has determined under the National. Environmental Policy
- Act of 1969, as amended,-and the Commission's regulations- in Subpart A of 10 CFR Part 51, that the amendments are not a major Federal action significantly affecting the quality of the human environment, and therefore:an-environmental impact statement is not required. The amendments establish new criteria for patient release that are based on the potential radiation dose to other individuals exposed to the. patient. Furthermore, the amendments require the Itcensee to provide written instructions to patients on how to maintain
-the doses to others as low as is-reasonably achievable. It-is expected that there will be no significant impact to the environment.
7
VI. LIST OF AGENCIES AND PtRSONS CONSULTED The NRC has held public meetings concerning the release criteria for patients receiving radioactive material for medical use. Appropriate suggestions from the meetings have been incorporated in the proposed amendments. The following table lists the date, location, and the groups represented at each meeting. 1 Public Meetinos Held Date Location Group: Represented 07/15/92 Atlanta, GA Agreement States: AL, AR, AZ, CA, 00, FL, 07/16/92 GA, IL, KS, KY, LA, MD, NC, ND, NE, NH, NV, NY, OR, SC, TX, UT, WA, and NY City 10/24/92 Tempe, AZ Agreement States: AL, AR, AZ, CA, CO, FL, 10/25/92 GA, IA, IL, KY, LA, MD, MS, NC, ND, NE, i 10/26/92 NH, NV, OR, RI, SC, TN, TX, UT, WA, and 10/27/92 NY City 10/24/94 Portland, ME Agreement States: AL, AR, IL, KS, LA, NH, 10/25/94 NV, NY, PA, RI, TX, UT, WA, and NY City 10/22/92 Rockville, MD Advisory Committee on the Medical Uses of 10/23/92 1sotopes (ACMUI) 05/03/93 Bethesda, MD Advisoty Committee on the Medical Uses of 05/04/93 Isotopes (ACMUI) 11/01/93 Reston, VA Advisory Committee on the Medical Uses of Isotopes (ACMUI) 11/18/94 Rockville, MD Advisory Committee on the Medical Uses of - Isotopes (ACMUI). 05/12/95 Rockville, MD Advisory Committee on the Medical Uses of Isotopes (ACMul) 10/18/95 Rockville, MD Advisory Committee on the Medical Uses of 10/19/95 Isotopes (ACMUI) Much of the statistical and technical information required for this assessment is not available in the open literature. In such instances, information was obtained directly from technical experts. The following individuals-are acknowledged for their cooperaticn and contribution of technical information and data: R. Atcher, Ph.D., Radiation and Cellular Oncology Department, University of Chicago, Chicago, IL 8
K. Behling, S. Cohen and Associates, McLean, VA U. H. Behling, S. Cohen and Associates, McLean, VA D. Flynn, M.D. (NRC Advisory Committee on Medical Use of isotopes), Massachusetts General Hospital, Boston, MA D. Goldin,-S. Cohen and Associates, McLean, VA W.R. ller.Jee, Ph.D., Dean of Research, Medical College of Wisconsin, Milwaukee, WI P. Holahan, Ph.D., U.S. Nuclear Regulatory Commission, Washington, DC C. Jacobs, President, Theragenics, Norcross, GA F.A. Mettler, M.D., Department of Radiology, University of New Mexico, School of Medicine, Albuquerque, NM K.L. Miller, CHP, Professor of Radiology and Director, Division of Health Physice Milton Hershey Medical Center, Hershey, PA R. Nath, Ph. . /rofessor of Yale University, School of Medicine, and past President of .he American Association of Physicists in Medicine, New Haven, CT M.P. Nunno, Ph.D., CHP, Cooper Hospital, University Medical Center, Camden, NJ P. Paras, Ph.D., Food and Drug Administration, Center for Devices and Radiology Health, Rockville, MD M. Pollycove, M.D., Visiting Medical Fellow, U.S. Nuclear Regulatory Commission, Washington, DC G.E. Powers, Ph.D., Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC M. Rosenstein, Ph.D., Food and Drug Administration, Center for Devices and Radiology Health, Rockville, MD J. St.Germain, Radiation Safety Officer, Memorial Sloan Kettering, New York City, NY ' B. A. Siegel, M.D. (Chairman, NRC Advisory Committee on Medical Use of Isotopes), Director, Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, M0 M.G. Stabin, Ph.D., CHP, Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, TN 9
s D. Steidley, Ph.D., CHP, Medical Health Physicist, Department of Oncology, St. Barnabas Medical Center, Livingston, NJ J. Stubbs, Ph.D., Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, TN K. Suphanpharian, Ph.D., President, Best Industries, Springfield, VA R.E. Toohey, Ph.D., Director, Radiation Internal Dose Information Center, Oak Ridge Institute for Science and Education, Oak Ridge, TN i i 10
r--------.~.,-----, - , -- - - - - - - , - - - , - - , , . - - - - - - _ - - - - - - - , - - - --_____ - I' .,g .u. 4 0 6 e d 4 ATTACHMENT - 5 ORAFT CONGRESSIONAL LETTER O [/
! ORAFT CONGRESSIONAL LElTER 4 5
Dear Mr. Chairman:
Enclosed for the information of the Subcommittee are copies of a public announcement and a final amendment to 10 CFR Parts 20 and 35 dealing with criteria for the release of patients administered radioactive materials. Roughly 8 to 9 million medical diagnostic and therapeutic administrations of radioactive material are performed in the United States each year. The rule is largely in response to three petitions for rulemaking that were submitted by the medical community because of concerns that the NRC's recent amendments of its regulations in Part 20. " Standards for Protection Against Radiation," would require medically unnecessary hospitalization of patients administered radioactive materials for the treatment of disease and-would thus increase national health care costs. The rule makes it clear that the release of patients administered. radioactive materials continues to be regulated by the requirements in NRC's Part 35, " Medical Use of Byproduct Material." While the comments of the medical community on the proposed rule were generally supportive. they . objected strongly to one of the recordkeeping requirements contained in the proposed rule. Upon reconsideration, the NRC has deleted the recordkeeping requirement in question after concluding that the records were not necessary to provide for adequate protection of public health and safety. Sincerely, Dennis K. Rathbun, Director Office of Congressional Affairs
Enclosures:
I
- 1. Public Announcement
- 2. Federal Register Notice cc: Representative l
. Attachment 5
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9 9
$ b 4
- ATTACHMENT - 6 ORAFT PUBLIC ANNOVNCEMENT
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NRC REVISES REGULAT10N3 ON RELEASE 0F PATIENTS ADMINISTERED BYPRODUCT MATERIAL
' 't ,
The Nuclear Regulatory Commission is amending its regulations governing,_ the release of pt4ats f*om a hospital or other licensed medical facility
-after ti.;y have recened radioactive material for treatment or diagnostic purposes. The revisions respond to three petitions received on this subject.
Radioactive pharmaceuticals or radioactive implants are administered to approximately 8 to 9 million patients in the United States each year for diagnosis or treatment of disease. These patients can expose other persons Laround them to radiation until the radioactive material has been excreted from
- their bodies'or has become less intense due to radioactive decay.
Under the final rule, licensees may not authorize the release of patients if the estimated dose, to the individual likely to receive the
- highest dose from exposure to the patient, would' be greater than 500 millirems. (Typical natural background radiation in the United States is 300 millirems per year.) The new criteria are consistent with recommendations 4
of the international Commission on Radiological Protection and tha National Council on Radiation Protection and Measurements. Under current NRC medical use regulations, licensees are not permitted to authorize the release of patients to whom nuclear material has been administered until either (1) the measured dose rate from the patient is less
' than 5 millirems per hour at a distance of 1 meter or (2) the radiopharmaceutical content of'the patient is less than 30 millicuries.
The final rule amends the general radiation protection regulations in 10: CFR Part 20 to exclude doses to individuals exposed to released patients. y;5: 1 Attachment 6 4
j. l
.a-e ,: ~
Release o,f patients-containing radioactivity is instead governed by the more Lexplicit requirements of revised' medical use regulations, which include, in . ,
- addition' to the 500-millirem per year limit, a requirement that, if the annual dose to-an_ individual exposed to the patient is likely to exceed 100 millirems, cne-licensee must provide the patient with written instructions
-on how to maintain doses to other individuals as low as reasonably acnievaote'.
If the released individual may be breast-feeding an infant or child, the instructions must also include guidance on the1 interruption or discontinuation - of. breast-feeding and information on the-consequences of failure to follow the guidance. The revisions partially grant three petitions for rulemaking on criteria
-fort release of patients who have been administered radioactive material. On
- June 12, 1991, March 9,' 1992, May 18, 1992, and July 26, 1994, the NRC published Federal Register notices concerning receipt of the petitions from
- Or. Carol S Marcus, the American College of Nuclear Medicine and-the American Medical 1 Association.
A proposed rule on this subject was published in the Federal Register on
- June _15. 1994.7 The _ final rule reflects public comments received.
The. rule will be effective (120 days after publication of a Federal Register notice on. ). 5 2 Attachment 6 i
- , -~ - , , , - - , , . ,.,c, , , - , , . . . . , , --e - ,, - - - , ,
- a b-aa 4- o ._.r a. -
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4 ATTACHMENT - 7 FEDERAL REGISTER NOTICE AND SUPPORTING STATEMENT FOR OMB REVIEW
[7590-01] NUCLEAR REGULATORY COMMISSION Documents Containing Reoorting or Recordkeeping Requirements; Office of Management and Budget (OMB) Review AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of the OMB review of information collection.
SUMMARY
- The Nuclear Regulatory Commission has recently submitted to OMB for review the following proposal for collection of information under the provisions of the Paperwork Reduction Act of 1980 (44 U.S.C. Chapter 35).
- 1. Type of submission, new, revised, or extension: Revision.
- 2. The title of the information collection: Final amendments to 10 CFR 35.75, " Criteria for the Release of Individuals Administered Ra' ictive Material."
- 3. The form number if applicable: Not applicable.
1 Attachment 7
l
- 4. How often is the collection required: On occasion; when the ,
release of a patient is based on other than standard assumptions or tequires interruption or discontinuation of bec:.st feeding to meet the 5-millisievert (0.5-rem) dose limit.
- 5. Who will be required or asked to report: Medical licensees administering radiopharmaceuticals and permanent implants and releasing patients under the provisions of 10 CFR 35.75.
- 6. An astimate of the number of respondents: Approximately 1,350 NRC and Agreement State licensees.
- 7. An estimate of the number of hours annually needed to complete the requirement or request: 17,126 hours (includes NRC and Agreement State licensees).
- 8. The average annual burden per respondent: 13 hours.
- 9. An indication of whether Section 3504(h), Pub. L. 96- 511 applies: Applicable.
- 10. Abstract: The Nuclear Regulatory Commission (NRC) is amending the criteria for release of individuals administered radioactive material under 10 CFR Part 35. The amendment requires the licensee to provide the patient with 2 Attachment 7
written instructions on how to maintain doses to other , individuals as low as is reasonably achievable if the dose to an individual ' exposed to the patient is likely to exceed 0.1 rem. In those cases where the released individual may
~
be a breast-feeding woman, the instructions must also
/
include guidance on the interruption or discontinuation of breast-feeding and information on the consequences of - failure to follow the guidance. The amendment also requires the licensee to maintain a record of the basis for the release if the release is authorized using other than standard assumptions or that instructions were provided to a breast-feeding woman if the dose to the child from continued breast-feeding could result in a total effective done equivalent exceeding 0.5 rem. These requirements are necessary to ensure adequate protection of the public health and safety and that doses to other individuals are maintained as low as reasonably achievable. Copies of the submittal may be inspected or obtained for a fee from the NRC u Public Document Room, 2120 L Street NW. (Lower Level), Washington, DC. 3 Attachment 7
l l 1 Comments and questions can be directed by mail to the OMB reviewe,r: Peter Francis
-Office of In' formation and Regulatory Affairs
. (3150-0010)
~
NE0B-10202 Office of Management and Budget Washington, DC 20503 Comments may also be communicated by telephone at (202) 395-3084. The NRC Clearance Officer is Brenda Jo. Shelton, (301) 415-7230. Dated at Rockville, Maryland, this day o' , 1995. For the Nuclear Regulatory Commission. Gerald F. Cranford, Designated Senior Official for Information Resources Management. 4 Attachment 7 ,}}