ML20070B196

Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material.Draft Report for Comment

ML20070B196
Person / Time
Issue date:	05/31/1994
From:	Behling K, Behling U, Goldin D, Mcguire S, Stewart Schneider NRC OFFICE OF NUCLEAR REGULATORY RESEARCH (RES), S. COHEN & ASSOCIATES, INC.
To:
References
NUREG-1492, NUREG-1492-DFC, NUREG-1492-DRFT, NUREG-1492-DRFT-FC, NUDOCS 9406290327
Download: ML20070B196 (78)

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,

NUREG-1492 Regulatory Analysis on Criteria

'or t:ae Release 0:? Patients Acministerec Racioac-ive Ma~:eria Draft Report for Comment U.S. Nuclear Regulatory Commission Office of Nuclear Regulatory Research S. Schneider. S. A. McGuire/NRC U. It Behling, K. Behling. D. Goldin/S. C&A. Inc.

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AVAILABILITY NOTICE Availability of Reference Materiais Cited in NRC Publications Most documents cited in NRC publications will be available from one of the following sources:

1.

The NRC Public Document Room. 2120 L Street, NW., Lower Level Washington, DC 20555-0001 2.

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NUREG-1492 Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material Draft Report for Comment Manuscript Completed: March 1994 Date Published: May 1994 S. Schneider, S. A. McGuire U. II. Ilehling*, K. Ilchling*, D. Goldin*

Division of Regulatory Applications OfHee of Nuclear Regulatory Research U.S. Nuclear Regulatory Commission Washington, DC 20555-0001 p

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• S. Cohen & Associates, Inc.

1355 Ileverly Itoad, Suite 250 McLean, VA 22101

i ABSTRACT The Nuclear Regulatory Commission (NRC) has limit of 5 millisieverts (0.5 rem) for patient received two petitions to amend its regulations in release. The evaluation demonstrates that, except 10 CFR Parts 20 and 35 as they apply to deses for a few diagnostic procedures using iodine-131, received by members of the public exposed to diagnostic procedures are unaffected by the choice patients released from a hospital after they have of alternative. Only some therapeutic administra-been administered radioactive material. While the tions of radioactive material could be affected by two petitions are not identical, they both request the choice of alternative. The evaluation indicates that the NRC establish a dose limit of 5 milli-that Alternative 1 would cause a prohibitively sicverts (0.5 rem) per year for individuals exposed large increase in the national health care cost to patients who have been administered from retaining patients in a hospital longer and radioactive materials. This Regulatory Analysis would cause significant personal and psychological evaluates three alternatives. Alternative 1 is for costs to patients and their families. The choice of the NRC to amend its patient release criteria in Alternatives 2 or 3 would affect only thyroid 10 CFR 35.75 to use the more stringent dose limit cancer patients treated with iodine-131. For those of 1 millisievert (0.1 rem) per year in patients, Alternative 3 would result in less 10 CFR 20.1301(a) for its patient release criteria.

hospitalization than Alternative 2. Alternative 3 Alternative 2 is for the NRC to continue using the has a potential decrease in national health care existing patient release criteria in 10 CFR 35.75 of cost of $30,000,000 per year but would increase 1,110 megabecquerels (30 millicuries) of activity the potential collective dose from released therapy or a dose rate at one meter from the patient of patients by about 2,700 person-rem per year, 0.05 millisievert (5 millirems) per hour, mainly to family members. Alternative 3 would Alternative 3 is for the NRC to amend the patient also have personal and psychological benefits for release criteria in 10 CFR 35.75 to specify a dose the patients and their families.

iii NUREG-1492

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CONTENTS ABSTRACT............

.....................................iii ACKNOWLEDG EM ENTS..................................................... vii 1 STATEMENT O F TH E PROBLEM........................................

1 2 OBJECTIVES OF THE RULEMAKING....

1 3 ALTE RNATIVES........................................................... 2 4 CONSEOUENCES....

............................... 2 4.1 Current Uses of Radiopharmaceuticals........................................ 2 4.1.1 Diagnostic Uses of Radiopharmaceuticals................................... 3 4.1.2 Therapeutic Administrations............................................ 4 4.1.2.1 Radiopharmaceuticals Used in Therapy............................... 6 4.1.2.2 Radioactive Materials Used in Permanent Implants (Brachytherapy).......

10 4.1.23 Summary of Therapeutic Administrations............................. 11 4.2 Assessment of Doses to Individuals Exposed to Patients Administered Radioactive Materials 11 4.2.1 Methodology for Calculating Direct Gamma Dose............................. 12 4.2.2 Screening Calculations 13 4.23 Estimate of Maximum Likely Dose to Indidduals Exposed to Patients...

15 4.23.1 Exposure Factor............

15 4.23.2 Iodine Retention by the Thyroid.................................... 15 4.233 Internal Exposure..

17 4.23.4 Self-Shielding for Permanent Implants................................ 18 4.23.5 Summary of Maximum Likely Doses 19 4.2.4 Collective Dose............................................

19 43 Value Impact Analysis.

.....................................22 i

43.1 Estimates of the Potential Costs.......................................... 22 43.1.1 Estimater of the Direct Costs of Patient Retention....................

22 43.1.2 Derivation of Indirect Costs.....................................

24 43.13 Evaluation of Psychological Costs........................

24 43.2 Cost Comparison of Alternatives.....

25 4.4 Evaluation Of The Alternatives With Respect to Accepted Radiation Protection Principles

......................................25 5 DECISION R/T!ONALE 25 v

NUREG-1492

6 IMPLEMENTATION....

26 REFERENCES.....

27 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 4.3 Age and Sex Distribution of Patients Having Nuclear Medicine Examinations............. 6 4.4 Radiopharmaceuticals for Radiotherapy.

7 4.5 Data Relevant to Radionuclides Used in Brachytherapy Permanent Implants...

11 4.6 Number of Annual Therapeutic Administrations in the U. S. (significant gamma-emitting radionuclides only) 12 4.7 Specific Gamma-Ray Constants and Dose Rates at 1 Meter......

13 4.8 Screening Calculation of Total Gaama Dose to Decay at 1 Meter Due to Administrations of Radioactive Materials......

14 4.9 Family Doses from Patients Treated for Thyroid Carcinoma.

16 4.10 Parameters for Use in Estimating Iodine-131 Retention.

18 4.11 Maximum Likely Doses to Exposed Individuals from Therapeutic Procedures.....

20 4.12 Estimates of Collective Dose from Therapeutic Radiciodine Procedures for Alternative 1:

Annual Limit of 1 millislevert (0.1 rem) 21 4.13 Estimates of Collective Dose from Therapeutic Radioiodine Procedures for Akernative 2:

Limit of 1,110 megabecquerels (30 millicuries) or 0.05 millisievert (5 millirems)/hr.

21 4.14 Estimates of Collective Dose from Therapeutic Radiciodine Procedures for Alternative 3:

Annual Limit of 5 millisievert (0.5 rem).............

22 4.15 Duration of Retention per Therapeutic Procedure (to the nearest day)............

23 4.16 Costs of Alternatives 1, 2, and 3.........

25 i

l NUREG.1492 si

ACKNOWLEDGEMENTS Much of the statistical and technicalinformation R. Nath, PhD, Professor of Yale University, required for this analysis is not available in the School of Medicine, and President of the open literature, in such instances, information American Association of Nuclear Physics, was obtaiaed directly from technical experts. The New Haven, CT following individuals are acknowledged for their cooperation and contribution of technical M.P. Nunno, PhD, CHP, Cooper Hospital.

information and data.

University Medical Center, Camden, NJ R. Atcher, PhD, Staff Consultant to the P. Paras, PhD, Food and Drug Society of Nuclear Medicine, Argonne Administration, Center for Desices and National Laboratory, Argonne, IL Radiology Health, Rockville, MD D. Flynn, M.D., Massachusetts General M. Polycove, M.D., Visiting Medical Fellow, Hospital (NRC Advisory Committee on U.S. Nuclear Regulatory Commission, Medical Use of Isotopes), Boston, MA Rockville, MD W.R. Hendee, PhD, Dean of Research, M. Rosenstein, PhD, Food and Drug Medical College of Wisconsin, Milwaukee, Administration, Center for Devices and WI Radiology Health, Rockville, MD C. Jacobs, President, Theragenics, J. St.Germain, Radiation Safety Officer, Norcross, GA Memorial Sloan Kettering, New York City, NY F.A. Mettler, M.D., Department of Radiology, University of New Mexico, D. Steidley, PhD, CHP, Medical Health School of Medicine, Albuquerque, NM Physicist, Department of Oncology, St.

Barnabas Medical Center, Livingston, NJ K. L. Miller, CHP, Professor of Radiology and Director, Division of Health Physics, K. Suphanpharian, PhD, President, Best Milton Hershey Medical Center, Hershey, Industries, Springfield, VA PA i

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1 STATEMENT OF THE (2) Amend 10 CFR 35.75(a)(2) to retain the PROBLEM 1,11 -megabecquerel (30-millicurie) limit for iodine-131 (1-131), but provide an activity limit for other radionuclides consistent with the calculational methodology employed in Each year in the U.S., radioactive pharmaceuticals the National Council on Radiation Protection or radioactive implants are administered to and Measurements (NCRP) Report No. 37, roughly 8 to 9 million patients for the diagnosis or

" Precautions in the Management of Patients treatment of disease. These people can expose Who Have Received Therapeutic Amounts of others around them to radiation until the Radionuclides" (NCRP70).

radioactive material has been excreted from their bodies or has decayed away.

(3) Delete 10 CFR 20.1301(d) which requires licensees to comply with provisions of EPA's NRC's patient release criteria in 10 CFR 35.75, environmental regulations in 40 CFR Part 190

" Release of patients containing radiopharma-in addition to complying with the require-ceuticals or permanent implants," are as follows:

ments of 10 CFR Part 20.

"(a) A licensee may not authorize release from confinement for medical care any patient The second petition, submitted by the American administered a radiopharmaceutical until either:

College of Nuclear Medicine (ACNM)

(1) The measured dose rate from the patient is (PRM-35-10,57 FR 8282, as revised by l

less than 5 millirems per hour at a distance of PRM-35-10A,57 FR 21043), requests that the 1 meter; or (2) The activity in the patient is less NRC:

than 30 millicuries; (b) A licensee may authorize i

the release of a patient administered a permanent (1) Ad pt a dose limit of 5 millisieverts (0.5 rem)

[

implant only if "the measured dose rate is less f r indhiduals exposed to patients who have than 5 millirems per hour at a distance of been administered radiopharmaceuticals.

I meter."

(2) Permit licensees to authorize release from On May 21,1991, the NRC published a final rule hospitalization any patient administered a that amended 10 CFR Part 20," Standards for radiopharmaceutical 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 l

for members of the public in 10 CFR 20.1301.

include confinement in a private residence.

However, when 10 CFR Part 20 was issued, there was no discussion in the supplemental information Since the petitions submitted by Dr. Marcus and on whether or how the provisions of the ACNM both address the patient release

^

10 CFR 20.1301 were intended to apply to the criteria in 10 CFR 35.75, the NRC has decided to i

release of patients, thereby creating the need to resolve these petitions in a single rulemaking.

address this issue.

Because some licensees were uncertain what effect the revised 10 CFR Part 20 would have on 2 OBJECTIVES OF THE patient release criteria, two petitions for rule-RULEMAKING making were received on this issue. The first petition, submitted by Dr. Carol S. Marcus (PRM-20-20,56 FR 26945), requests that the NRC:

The objective of this rulemaking is to respond to.

l the two petitions for rulemaking by amending, as t

(1) Raise the annual radiation dose limit in deemed appropriate, the patient release criteria in

(

10 CFR 20.1301(a) for individuals exposed to 10 CFR 35.75.

radiation from patients receiving radiophar-i

- maceuticals for diagnosis or therapy from i

1 millisievert (0.1 rem) to 5 millisieverts (0.5 rem).

1 NUREG-1492 i

3 ALTERNATIVES 4 CONSEQUENCES I

e As the petitions and the public comments that To evaluate the impacts cf the three alternatives, were submitted to the Commission on the it is necessary to determine which current petitions make clear, some licensees were procedures invohing the administration of uncertain about whether dose limits imposed by radiopharmaceuticals or permanent implants 10 CFR 20.1301(a) or the patient release criteria might be affected by the imposition of a 1-milli-established by 10 CFR 35.75 govern patient sievert (0.1-rem) total effective dose equivalent release. In the Commission's view,10 CFR 35.75 per year dose limit for individuals exposed to governs patient release as explained in the Notice released patients. For convenience, procedures of Proposed Rulemaking associated with this invohing the administration of radioactive analysis. The public comments received on the materials to patients may be classified as:

two petitions also make it clear that the majority

1) diagnostic procedures invohing administration of commenters favor an annual dose limit of of radiopharmaceuticals to obtain information 5 millisieverts (0.5 rem). Given that about normal and pathological processes in the 10 CFR Part 35 is deemed to be the controlling patient; or,2) therapeutic procedures involving regulation, the Commission is faced with the administration of radiopharmaceuticals or decision regarding the regulatory approach to be implantation of a radioactive source to destroy i

pursued in 10 CFR 35.75. To evaluate the issues diseased tissue in the patient.

raised by the petitioners and those who commented on the requests made by the petitioners, the NRC has determined that the 4.1 Current Uses of follow' g alternatives should be evaluated:

Radiopharmaceuticals m

e Alternative 1: 1 millisievert (0.1 rem)hr total effective dose couivalent Radiopharmaceuticals can be defined as ' drugs" that are radioactive and because of this property In this alternative, a 1 millisievert (0.1 rem) are used to (1) obtain information about normal per year dose limit is evaluated as the and pathological processes in human organisms or controlling criteria for determining when a (2) destroy tissue. The first group of compounds patient may be released from the licensee's represents diagnostic and the latter therapeutic control.

radiopharmaceuticals. Although radiopharma-f ceuticals may be classified as drugs,it should be

,Ahernative 2: < 1,110 megabecauerels noted that neither the diagnostic nor therapeutic e

(30 millicuries) or < 0.05 millisievert radiopharmaceuticals are given for the purpose of (5 millirems)/hr at 1 meter exerting a pharmacological action.

In this alternative, the current patient release Radiopharmaceuticals are generated from two criteria in 10 CFR 35.75 is evaluated as the sources: nuclear reactors and accelerators.

controlling requirement for determining when Nuclear reactors can produce radionuclides i

a patient may be released from the licensee's through neutron capture reactions (e.g., (n, y),

control.

(n, p), and (n, a), as well as by nuclear fission j

(n, f)). Other radiopharmaceuticals are o Alternative 3: 5 millisieverts (0.5 rem)hr accelerator produced, in which a highly pure total effective dose eauivalent) target material is bombarded with p, d, or a t

particles Many have relatively short half-lives.

I This alternative evaluates a dose limit of Some radiopharmaceuticals may be produced by 5 millisieverts (0.5 rem) per year to an either reactor or accelerator (e.g., palladium-103, indhidual exposed to a patient as the limiting iodine-125). The choice in production method is t

factor for determining when a patient may be dictated by cost considerations and vendor access l

released from the licensce's control, to a high neutron flux reactor facility. While most

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iodine-125 has in the past and continues to be

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NUREG-1492

.2 F

produced by reactors, the production of All of the studies mentioned above are palladium-103 has shifted from reactor to summarized in Table 4.1 and represent hospital accelerator (personal communication, C. Jacobs, data only. However, the exclusion of non-hospital August 1993).

facilities should not significantly affect the accu-racy of estimates since less than 1 percent of all 4.1.1 Diagnostic Uses of nuclear medicine pracedures are performed out-Radiopharmaceuticals side hospitals (JO83). Inspection of Table 4.1 reveals severalimportant trends. While the total Estimates regarding the frequency and total number of diagnostic procedures has shown a number of diagnostic nuclear medicine procedures general increase, the number of specific proce-have been reported over the years in several dures has in some cases dramatical y increased or studies reviewed and analyzed by Mettler, et al.

decreased. By 1982, there were fewer radionu-(ME85). Among the earliest data reported was a clide brain imaging examinations than in 1972, study supported by the American College of undoubtedly due to replacement by computerized Radiology (ACR75), which reflects data collected I m graphy (ME85). For the same period, liver in 1972 by J. Lloyd Johnson Associates. Addition-imaging increased tenfold. The largest percent al data for the years 1973 and 1975 were obtained increase involves cardiovascular imaging, which in a similar fashion and also published in the increased from an estimated 25,000 procedures in American College of Radiology Manpower Survey 1972 to about 950,000 in 1982. Other procedures (ACR82),

such as renal, lung, and tumor imaging have experienced only modest increases in numbers.

In 1975, the Bureau of Radiological Health (BRH; now the Center for Medical Devices and A search of the open literature revealed no recent Radiological Health, CDRH) of the U.S. Food comprehensive studies to assess more current U.S.

and Drug Administration initiated a pilot study use of radiopharmaceuticals. It is generally that surveyed information reported by six hospitals thought, however, that the frequency and usage of to the Medically Oriented Data System (MODS).

radiopharmaceuticals have stabilized because of This project was later expanded to include 26 the competing and/or complementary technol-S es of computerized tomography, magnetic i

stratified hospitals that provided data for 1977 and.

1978 (FDA85).

resonance imaging, and gray-scale ultrasound (personal communication, F. A. Mettler, March Comprehensive data on 1980 diagnostic imaging 1993). For this report, the most recent RED 2 procedures were obtained by J. Lloyd Johnson frequency distribution and the cumulative frequen-Associates by mail questionnaire using a stratified cy f 32 diagnostic nuclear medicine procedures nc-thousand population will be used to esti-rr random sample of general hospitals and selected office practices in the U.S. (JO83). The sample 5"te current usage. Table 4.2 provides frequency included 6,109 hospitals and was estimated to estimates of diagnostic procedures adjusted to reflect about 90 percent of the total diagnostic reflect the 1993 U.S. population, which is imaging examinations. Additional studies were projected at 256,466,000 by the U.S. Bureau of the

Census, conducted by the BRH for the years 1980,1981, and 1982. The hospital. based survey was called the Radiation Experience Data (RED 1 and RED The identity, chemical form, and average quantity 2 studies) (ME85). The RED 1 study examined of radionuclides used for diagnostic in4ivo the computer billing records of 81 hospitals. Data procedures are cited in Table 4.2 and reflect for the subsequent RED 2 study reflect informa.

values cited by Mettler (ME85). It can be tion obtained by mail survey from 500 hospitals.

assumed that the average quantity per examina-tion has not significantly changed since the time of Data for 1982 were also provided by Parker, et al.

riginal publication (personal communication, (PA84) in which a randomized sample of 10 per-F. A. Mettler, March 1993).

cent of the U.S. hospitals was surveyed. Although his survey was specifically directed to thyroid As the results in Table 4.2 indicate, there are examinations, survey data also provided estimates approximately 8.2 million diagnostic examinations of total examinations.

employing radiopharmaceuticals performed annu-ally in the U.S. Of these, more than 85 percent 3

NUREG-1492

Table 4.1 Estimated Number of Diagnostic Radiopharmaceutical Procedures Performed in the U.S.

between 1972 and 1982 Year 1972 1973 1975 1978 1980 1980 1981 1982 1982 Source Examination gype ACR ACR ACR MODS Johnson RED 1 RED 2 RED 2 Parker Brain 1260*

1510 2120 1546 870 1176 1038 812 liepatobiliary 26 109 179 Liver 455 535 676 1302 1180 1399 1445 1424 Bone 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 Urinary 108 122 154 205 200 164 402 236 Tumor 10 14 22 166 130 125 121 Cardiovascular 25 33 49 160 580 558 708 950 Other 686 294 338 120 120 368 Total 3339 3510 4803 6411 5830 6374 7199 7401 7690 (16)m (17)

(22)

(29)

(26)

(28)

(31)

(32)

(33)

Source: M E85.

"' Numbers not in parenthesis indicate number of examinations x 1,000.

• Numbers in parenthesis indicate number of examinations /1,000 population.

use technetium-99m (Tc-99m) as the label, about 4.1.2 Therapeutic Administrations 5 percent use xenon-133 (Xe-133), about 5 per-cent use thallium-201 (T1-201), about 3 percent Therapeutic use of radioactive materials involves use iodine-131 or iodine-123 (I-123), and about two distinct approaches. The first involves the 2 percent use gallium-67 (Ga-67).

oral, intravenous, or intracavity administration of a radiopharmaceutical that may subsequently be Age and Sex Distribution of Patients distributed, concentrated, retained, and eliminated by physical, chemical, and metabolic actions The age and sex distribution of the U.S.

occurring within the body. The second approach population that underwent nuclear medicine involves the implantation of radioactive sources examinations in 1980 is shown in Table 4.3. For (i.e., seeds) directly into a solid tumor. While the period of observation, more than three-fourths both temporary and permanent implants are of all nuclear medicine examinations were performed, all patients receiving temporary performed on persons over the age of 45; nearly implants are hospitalized until the implants are 40 percent of these patients were 64 years and removed. Thus, only permanent implants are older. With the exception of the youngest age potentially affected by this rulemaking.

category, the percentage of females exceeded males.

NUREG-1492 4

Table 4.2 Estimated Radiopharmaceutical Use for Diagnostic Procedures in the U.S. In 1993")

Average Activity Total No. of Examination Type per Examination Exair.inations (Radiopharmaceutical)

(MBq (mCl))

(x 1,000)

Brain

- Tc-99m DTPAS 740 (20) 450

- Tc-99m 0 740 (20) 450 4

Hepatobiliary

- Tc-99m IDAS 185 (5) 198 Liver

- Tc-99m sulfur colloid 185 (5) 1,578 Bone

- Tc-99m phosphate 740 (20) 2,007 Luna Perfusion Tc-99m MAAm 185 (5) 871 Lune Ventilation

- Xe-133 370 (10) 449 Thyroid

- Tc-99m O, 185 (5) 600

- I-131 3.7 (0.1) 75

- I-123 11.1 (03) 75 Renal

- Tc-99m DTPA 740 (20) 157

- I-131 hippuran 9.3 (0.25) 105 Cardiovascular

- Tc-99m RBCS 740 (20) 421

- TI-201 chloride 111 (3) 421

- Tc-99m phosphate 740 (20) 211 Tumor

- Ga-67 citrate 111 (3) 134 Total 8,202

'" Based on ME85; and personal communication, F. A. Mettler, March 1993, but adjusted for the 1993 U.S.

population.

• DTPA is diethylene-triamine pentacetic acid; IDA is imino discetic acid; MAA is macro-aggregated albumin, and RBC is red blood cells.

l 5

NUREG-1492 l

l 1

Table 4.3 Age and Sex Distribution of Patients llaving Nuclear Medicine Examinations Male Female.

Total Age

(%)

(%)

(%)

< 15 0.9 0.7 1.6 15 - 29 3.3 4.9 8.2 30 - 44 5.2 8.7 15.9 45 - 64 15.8 21.6 37.4

> 64 17.0 21.9 38.9 Source: ME86.

4.1.2.1 Radiopharmaceuticals Used in Therapy of occurrence and treatment must be inferred.

Incidence of hyperthyroidism is reported at 3 per The in-vivo use of radiopharmaceuticals in therapy 10,000 adults per year, with peak incidence is based on the ability to differentially deliver occurring between 30 and 50 years of age (DG79).

lethal radiation doses to the selected target tissue.

From the most recent data (1990) available from The choice of radionuclides is based on specific the U.S. Bureau of the Census,it can be assumed physical characteristics. Most desirable are beta that about 75 percent of the U.S. population emitters that can deliver intense irradiation of (approximately 191,500,000 persons) is 18 years of target cells while sparing the surrounding tissues, age or older. Thus, it can be estimated that about in contrast to diagnostic procedures for which the 57,500 individuals per year require medical gamma emission is essential, the emission of treatment for hyperthyroidism, energetic gammas is undesirable for therapeutic purposes since it results in unwanted irradiation of Although medical treatment may in some cases surrounding healthy tissues and doses to involve the use of anti-thyroid drugs or surgery, it individuals in close proximity to the patient. In may be assumed that about 85 percent of the recent review articles, Verbruggen (VE90) and cases of hyperthyroidism are treated with lloefnagel (11091) identified a list of available therapeutic doses of iodine-131 (personal tumor-seeking radiopharmaceuticals (Table 4.4).

communication, M. Polycove, November 1993).

The more significant therapeutic applications are The resulting estimate is about 50,000 treatments described below, per year.

liyperthyroidism In the past, therapeutic quantities of iodine-131 for treatment of hyperthyroidism tended to be of 11yperthyroidism is characterized by an increased a magnitude that would reduce the hormone production of thyroid hormone. Ilyperthyroidism production of the hyperactive thyroid gland to is most commonly associated with Graves' normal levels. liowever, experience demonstrated Disease. Graves' Discase is an autoimmune that over a period of years the therapy-induced disease in which the body's own immune system is euthyroidal (normal or healthy thyroid) condition directed against cellular and secretary products of deteriorated to one of hypothyroidism requiring the thyroid gland.11yperthyroidism can also be thyroid hormone replacement therapy. As a the result of excessive hormone production by a result, hyperthyroid therapy today involves single " toxic" nodule, thyroid carcinomas, and ablation of the thyroid using doses of iodine-131 medications inclusive of potassium iodide.

in the range of 550 to 1,100 megabecquerels i

(15 to 30 millicuries). Such doses quickly result in rlyperthyroidism is not a condition reportable to the total loss of thyroid function and the patient is public health agencies. As a result, data on rates given hormone replacement therapy from the NUREG.1492 6

Table 4.4 Radiopharmaceuticals for Radiotherapy

}

Site / Mechanism Radiophannaceutical Application Intracellular DNA incorpolation 251-lUdR Chorioncarcinoma l

Metabolic

"'I. iodide Differentiated thyroid carcinoma l

"'l/'251-MIBG Neural crest tumors

'2P-phosphate Polycythaemia vera "I-Rose Bengal liepatoblastoma

"'l-iodide Oncocytoma Steroid receptor

• Br-estrogens Breast carcinoma i 'l-tamoxifen Breast carcinoma Non-specific

'"Rc(V)-DMSA Medullary thyroid carcinoma Cell surface llormone receptor

"'l-$MS analog Neuroendocrine tumors Immunologic

" l-anti CEA Colon / medullary thyroid carcinoma "il-B72.3 Colon / ovarian carcinoma

" I-IIMFG 1 + 2 Ovarian carcinoma

"'I/*Y-OC 125 Ovarian carcinoma

"'l-Lym-1 Leukemia /lymphoma l

"'l-anti pan B Lymphoma l

"'l/*Y-antiferritin IICC/Ilodgkin's disease

"'l-anti p97 Melanoma

" l-3F8/UJ31A Neuroblastoma Extracellular Adsorption

' P-phosphate Bone metastases "Sr/Sr-chloride Bone met /osteosarcoma

'"Re-Sn-llEDP Bonc metastases

"'Sm-EDTM P Bone met /osteosarcoma

"'l-BDP3 Bonc metastases "Y-citrate /EDTMP Bonc metastases Cells

"*"In-A31 cells Lymphoma intracapillary

"'l-lipiodol Liver tumors 52P-resin microspheres Liver tumors "Y-glass microspheres Liver tumors / sarcoma "Y-resin particles Liver tumors / sarcoma intracavitary

' P/*Y/'"Re-colloids Astrocytoma / cystic craniopharyngioma

'2P-colloids Malignant effusions "Au/32P-colloid ALL intrathecal therapy

"'I/*Y-antibodies Malignant effusions

'"Au-colloid Synoviorthesis "Y-citrate / silicate Synoviorthesis

Dy-FliMA Synoviorthesis "Re-colloid Synoviorthesis

'"Er-citrate Synoviorthesis Sources: 1109); VE90, j

7 NUREG-1472 l

_ -____u

t onset (personal communication, F. A. Mettler, Census Bureau's population projections for 1992.

March 1993).

The ACS's estimate of new thyroid cancers in 1992, is 12,500 (ACS93). This report assumes that nyroid Nodules about 10,000 cases per year will be treated with therapeutic doses of iodine-131.

Single or multiple nodules of sufficient size may cause obvious enlargement of the thyroid. A The quantities of iodine-131 used in thyroid nodule (s) refers to a replacement of the normal cancer therapy depend upon the type of cancer, homogeneous cytostructure of the thyroid with a the status of the cancer, and the degree of uptake histologic pattern ranging from colloid-filled cysts and retention of iodine-131 by residual cancerous and colloid adenomas to follicular adenomas.

thyroid tissue. As a result, current therapeutic Since the incidence is 4 to 5 times as great in doses range from 1,850 to 11,100 megabecquerels women as in men, and since it develops and (50 to 300 millicuries) (personal communications, progressively increases in size during life, it is F. A. Mettler and K. L. Miller, March 1993).

most frequently found in temales 50 to 70 years of age. It is not uncommon for nodules to remain nerapy for Polyc3themia Vera undetected until a post-mcrtem examination.

Since the introduction of radiophosphorus in 1936, Small nodules in cuthyroid subjects require no patients with polycythemia vera (PV) have been therapy. If the gland is grossly enlarged and treated successfully with this radioisotope te causes a cosmetic problem or tracheal control rather than cure this disease. Polycy-compression, treatment may be indicated along themia vera is a relatively rare disease that is with thyroid hormone replacement therapy.

characterized by an autonornous proliferation of marrow cells leading to an over production of red A small percentage of thyroid nodules tend to blood cells and white blood cells. Typically, produce thyroid hormones uncontrollably and in phosphorous-32 (P-32) is administered intra-l excess (i.e., the nodule is not under the regulatory venously in doses of 110 to 185 megabecquerels control of the pituitary gland and is clinically (3 to 5 millicuries) per treatment over a period of referred to as toxic nodular goiter). The presence time with average cumulative quantities of of these autonomously functioning thyroid nodules 740 megabecquerels (20 millicuries) per patient leads to hyperthyroidism (thyrotoxicosis).

(MO65). Since phosphorous-32 is a pure beta emitter, treatments using phosphorous-32 would Toxic nodular goiter, like Graves' Disease, may be not be affected by the rulemaking and need not treated surgically (thyroidectomy) or by be considered further in this analysis.

therapeutic dose (s) with radioactive iodine.

Estimates of the frequency of radioactive iodine Bone Therapy treatment for this condition are included under the estimates for hyperthyroid treatment above.

Since the use of radioactive strontium for the treatment of bone metastases was first described nyroid Cancer in early 1942 (PE42), bone therapy has included other radionuclides. Bone therapy may involve There is no nationwide cancer registry that the treatment of primary bone tumors such as accurately defines the number of new cases of osteosucoma (BL87) in which bone-seeking cancer diagnosed each year. Ilowever, the radiopharmaceuticals are in fact tumor seeking.

American Cancer Society (ACS) annually Bone therapy may also be the treatment of painful publishes data on cancer incidence and patient skeletal metastases, which may be palliated by survival based on information provided by the bone-seeking radionuclides. Although the National Cancer Institute's Surveillance, literature references the palliative and tumor Epidemiology, and End Results (SEER) program.

therapeutic use of these radionuclides (phosphorous-32: Cil80, RO77; strontium-89 The ACS estimates of U.S. cancer cases (Sr-89): BIE8, KL87, S185, RO87, ROE 90; diagnosed for the most recent year,1992, are rhenium-186 (Re-186): KE87, MA88, SC90; i

based on age-specific incidence rates from the samarium-153 (Sm-153): TU89, LA90), there are SEER program for 1986-1988 applied to the no data bases and no studies have been NUREG-1492 8

l performed that would a!!ow quantitative estimates initially, gold-198 colloids were used, but regarding the number of patients given bone phosphorous-32 is now preferred due to its longer therapy with radiopharmaceuticals. As stated half-life, more energetic beta particles, and the previously, phosphorous-32 need not be absence of gamma radiation. Intracavitary considered and the other therapies are performed radionuclide tl erapy with phosphorous-32 in so seldom that they have negligible impact in quantities of 185 to 370 megabecquerels (5 to comparison with the radiciodines.

10 millicuries) has been applied to malignancies involving the pleural, pericardial, and peritoneal Therapy with Radiolabelled Cells cavitics (JA81; MA78; KA81).

For lymphoid cell malignancies, the tumor cells More recently, iodine-131-or yttrium-90-labelled j

(i.e., lymphocytes) may retain their ability to tumor-associated monoclonal antibodies have migrate and recirculate into the lymphorcticular been used in intracavitary therapy (PE86; F189; tissues (i.e., spleen, liver, bone marrow, and lymph R190) in doses of 740 to 2,220 megabecquerels nodes). The harvesting, labelling, and reinjection (20 to 60 millicuries). Superiority of monoclonal of lymphocytes has been demonstrated to deliver antibodies aver colloids is expected due to the therapeutic levels of radiation doses to tumors of enhanced affinity of the labelled antibody for the the lymphoreticular system (CO87). Indium-114-target cells. At present, these therapies are rarely labelled lymphocytes have a potential therapeutic used and thus have no impact in comparison with role in the management of lymphoma, and clinical radioiodines.

studies are underway. Because use of this new therapy is not widespread, its impact may be Radioimmunotherapy omitted in the analysis, but it should be noted that use of a dose-based methodology provides a Radioimmunotherapy involves the use of radio-means to determine the quantities for which labelled antibodies directed against tumor-specific release may be authorized.

antigens such as the carcinoembryonic antigen (CEA) and ferritin. Only a very limited number Intra-Arterial Therapy of cancer patients have been treated experimen-tally with radiolabelled antibodies in combination Some primary tumors as well as metastatic lesions with chemotherapy and external beam irradiation.

are highly vascularized. Direct arterial injection Among cancers treated are hepatomas, Hodgkin's with insoluble radiolabelled particulates that lodge disease, and non-Hodgkin's lymphoma (OR85; in arterioles and capillaries of the tumor is the LE85; NE90). In the past, radioimmunotherapy basis of this form of therapy (Zl84; EH87).

involved the use of iodine-131-and yttrium Insoluble carriers of radionuclides that have been labelled polyclonal antibodies raised against clinically tested include iodine-131-labelled oil tumor-associated antigens in a variety of animal contrast medium, iodine-131 tipoidal or -ethiodol species. Based on avidity of tumor cells and (PA87), yttrium-90-glass microspheres (HE88),

exposure considerations of the bone marrow, and yttrium-90 (Y-90) resin particles (ROE 90).

single doses of 370 to 1,110 megabecquerels Since these therapies are so seldom used, &ir (10 to 30 millicuries) have been used.

impact may be ignored in this analysis.

The development of the hybridoma technique by Intracavitary Tumor Therapy Kohler and Milstein (KO75) has caused significant shift in radioimmunotherapy. The hybridoma For tumors that are sp ead over the serosal technique allows the development of monoclonal linings of the body canties or for ascites tumors, antibodies against tumor-associated antigens. At one approach to delivering therapeutic doses of this time, however, the use of radiolabelled mono-radiation is to inject the rediopharmaceutical clonal antibodies for therapeutic applications has directly into the body cavity. For this approach, been limited to experimental treatments. At colloids, chelates, and, more recently, monoclonal present, these therapies are rarely used and thus antibodies labelled with gold-198 (Au-198),

have no impact in comparison with radiciodines.

phosphorous-32, yttrium-90, or iodine-131 can be used.

l 9

NUREG-1492

l 4.1.2.2 Radioactive Materials Used in Permanent Although iodine-125 implants are most commonly i

Implants (Brachytherapy) used to treat cancer of the prostate (FU91, MOS8, DE86, HE82, WH88, PR92), they have In. situ radiotherapy may involve permanent also been used on a very limited basis for brain implants or brachytherapy. Brachytherapy has tumors (AG92, SC92, OS92), carcinomas of the l

been around almost since the discovery of X rays.

pancreas (MO92), non-oat cell lung carcinomas j

Brachytherapy can be divided into temporary (FL92), breast cancers (RU92), and tumors of the implantation using high activity sources or per-head, neck, and eye.

manent brachytherapy using the interstitial implantation of 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 kev is lower than iodine-125, but, i

Currently, iridium-192 is the radionuclide of given its shorter 17 day half-life, it has a higher choice for temporary implantation. For tempo-initial dose rate. Recently, palladium-103 seeds rary implantation, patients may be retained in the have been developed with the same physical hospital for reasons that are independent of parameters as iodine-125 seeds to ensure radiological considerations. Radionuclides used compatibility 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 kev 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). However, its use as a permanent implant of their decay deliver a lethal dose of radiation to is nomin d due to the presence of a small (less tumor cells within a short distance of the implant.

than 3 percent) average photon peak at 300 kev, The major advantage of brachytherapy over that can significantly impact radiation doses to external irradiation in the treatment of solid individuals in proximity to the patient.

tumors is the favorable ratio of dose delivered to tumor cells versus normal tissue. This is particu-Gold-198 implants have been used in a few larly true of prostate cancer where the surround-instances of prostate c:mcer (FR88, CA88). The ing normal tissue includes the bladder, rectum, potential advantage of delivering a high dose and urethra. The presence of these normal within a relatively short ti ne, however, is offset by tissues limits the dose of external beam radiation its energetic gamma emissions, which has caused therapy that can be administered safely to the its use in recent years to fall into disfavor and be prostate to approximately 7,000 rads (PO93).

used only rarely (CA87).

1 The radionuclides primarily used in permanent Table 4.5 lists information on radionuclides used implants are iodine-125 (1-125) and palladium-103 in brachytherapy permanent implants relative to (Pd-103). Less frequently used radionuclides factors that affect the external dose rates of include gold-198 and ytterbium-169 (Yb-169).

implants.

The most frequently used radionuclide in A thorough scarch of the literature and personal perman-nt implants is iodine-125, which has the communications with several prominent members advantage of an extremely low energy (27 kev) of the medical and scientific community (see photon and a half-life of 60 days. Besides Acknowledgements) indicates that there is no minimizing dose to surrounding healthy tissue, the published data available to quantify the annual i

low photon energy also limits doses to hospital number of cancer patients receiving permanent

+

personnel and others when compared to implants.

temporary implants with iridium-192 (Ir-102) or permanent implants with gold-198 (Cl29, RU92).

NUREG-1492 10 l

i

Table 4.5 Data Relevant to Radionuclides Used in Brach therapy Pernunent Implants 3

External Exposure Parameters EITective Italf-Photon Attenuat.

7-ray Dose Rate at Radio-life Energy Coeff.

IIV11" Constant rm 1 Meter nuclide (days)

(lev)

(cm )

(cm)

(R/mCl-h at I cm)

(mrem /h-mCl) d 1-125 60 27 0.387 1.8 2.00 0.20 Yb-169 32 93 0.143 4.8 2.38 0.24 Pd.103 17 21 0.770 0.9 1.68 0.17 Au-198 2.7 412 0.104 6.7 2.13 0.21 source: PO93.

"' Values are given for soft tissue.

• Values do not include shielding by the implant capsule.

l The scientific literature and consensus opinion activities ranging from 2,775 to 4,625 mega-among the experts identified in the acknowledg-becquerels (75 to 125 millicuries).

ments to this report does, however, support the following:

4.1.2.3 summary of'Iherapeutic Administrations 1.

permanent implants are currently considered an appropriate treatment for only a few sites Table 4.6 summarizes the estimates of the of solid tumors; quantities of gamma-emitting radioactive materials used in therapeutic administrations and the 2.

among the cancer sites for which permanent numbers of each therapy currently perfotmed implants are currently employed, prostate annually.

cancer represents the overwhelming majority; 3.

among the 132,000 annual new cases of 4.2 Assessment of Doses to prostate cancer (ACS93), only a small Ind.. duals Exposed to IVi fraction is treated with permanent implants;

and, Patients Administered 4.

for the purposes of this analysis, implants invohing gold-198 (largely discontinued) and ytterbium-169 (isolated use only) may be To identify the potential impacts associated with cach of the alternatives, it is necessary to know ignored.

the magnitude of doses that could be received by In the absence of documented clinical data, an individual exposed to a patient who has been administered radioactive materials. While information was sought from the implant vendors on numbers of administrations and typical exposure can occur via any of the elimination activities of radioactive material used per pathways by which radionuclides are removed administration. Currently, there are only three fr m the body (e.g., urine, feces, sweat, saliva, vendor sources. Vendor supplied data suggests exhalation), experience indicates that for that approximately 2,000 implants invohing iodine-131 and other gamma emitters, these iodine-125 are performed annually, at activities pathways will generally be insignificant in relation to the doses that can result from exposure to the ranging from 1,110 to 1,850 megabecquerels (30 to 50 millicuries). For palladium-103, approx-direct gamma radiation from the patient.

imately 1,500 implants are performed annually, at 11 NUREG-1492 I

. =

Table 4.6 Number of Annual'Rerapeutic Administrations in the U.S. (significant gamma-emitting radionnclides only)

Activity per Estimated No. of Therapeutic Radionucilde Administration Administrations Procedure Employed (MBq (mCl))

(per year)

Thyroid Ablation for 1-131 555 - 1,110 (15 - 30) 50,000 Hyperthyroidism Thyroid Cancer 1-131 1,850 - 11,100 (50 - 300) 10,000 Permanent implant I-125 1,110 - 1,850 (30 - 50) 2,000 Permanent implant Pd-103 2,775 - 4,625 (75 - 125) 1,500 Total 63,500 This section of the report assesses the dose to After a single administration q, of a radionuclide, individuals exposed to patients who have been the body content q(t) at time t diminishes with administered radioactive materials. For time according to the equation (LO56):

cxpediency, a two-tiered approach is employed.

dq(t) = - E(t) - A q,,

(1)

The first tier serves as a baseline and may be dt viewed as a screening method. Consequently, this first screening tier employs conservative where E(t) = the amount (mci) of radionuclide assumptions and represents upper-bound values.

excreted per unit time at time t, Therefore, procedures invohing quantities of radionuclides that are less than those defined by A = the radioactive decay constant.

the screening calculation can be eliminated from further consideration. Procedures employing The rate of radionuclide excretion may be quantities in excess of the first tier screening complex if more than one biological compartment quantities are subsequently assessed using is involved. For such instances, variation of q(t) parameters that are more realistic.

follows the exponential decay relationship characterized by the physical half-life T, and 4.2.1 Methodology for Calculating biological half-life T, of the radionuclide for each Direct Gamma Dose compartment.

A basic calculation in gamma-ray dosimetry is the The gamma-ray dose rate constant P commonly radiation distribution around a point source. In expresses the dose rate per hour at 1 cm in air for air, the absorption of even low-energy photons is a 37-megabecquerel (1-millicuric) point source of small and can, therefore, be neglected for small a given radionuclide. The gamma dose rate distances from the source. As a result, the dose constant P may be measured directly if the dis-around a point source follows the inverse square integratian rate is accurately known or it may be law. If a point source is placed at the center of calculated from known physical constants.

an imaginary sphere, the same number of gamma Table 4.7 identifies the specific gamma-ray rays pass through the surface independent of the constants and corresponding dose rates at 1 meter sphere's radius r. Since the surface area is for principal radiopharmaceuticals employed in proportional to r, the number of quanta passing diagnostic and therapeutic procedurcs.

2 2

2 I cm of surface area is proportional to 1/r,

Therefore, if the dose rate is known at I cm from Thus, for an initial acthity q, (in megabecquerels the point source, it can be easily determined at or millicuries), the external dose rate R,(t) of a any distance, given radionuclide point source is defined as follows (LO56):

NUREG-1492 12

i Table 4.7 Specific Gamma-Ray Constants and Dose Rates at 1 Meter Exposure Rate at flatf-Life Specific y-Ray Constant r 1 Meter per mci Radionuclide (days)

(R/ mci-h at I cm)

(mR/ mci-h)

Ga-67 3.25 1.1 0.11 1-123 0.55 0.7 0.07 I-125 60.2 2.0 0.20

)

1-131 8.04 2.2 0.22 l

Pd-103 17.0 1.7 0.17 Tc-99m 0.25 0.7 0.07 j

TI-201 3.08 0.9 0.09 sources: NCRP70, personal communication, R. Nath, March 1993).

J Vg,T'I omt R,(t) =

• e (2)

D,(=) = 1.44 (7) r where 4.2.2 Screening Calculations (3)

To determine which, if any, of the diagnostic and T,f =

T, + T, therapeutic procedures involving administration of radioactive materials would be affected by the alternatives under consideration, a series of The total dose D,(t) at any time t is found by screening calculations were performed using integrating the dose rate R,(t) from time t, to the Eq. (7) to calculate the total gamma dose to time t. The total dose for a given time interval is decay at 1 meter that would be delivered by the therefore:

radionuclide modeled as a point source in air.

The screening calculations used the physical D,(t) = (R,(t)dt.

(4) half-lives of the radionuclides and did not consider biological elimination. In other words, the physical half-life was used in Eq. (7) in place of Using Eq.(2) the effective half-life. The physical characteristics of the radionuclides are given in Table 4.7.

D,(t) =

'e

1. dt, (5) summarized in Table 4.8. Table 4.8 indicates that, except for a few procedures using iodine-131 to from which it follows that detect thyroid cancer, none of the other diagnostic procedures currently being performed have the D,(t) = 1.44Pqo,f(1 -e r, ).

(6) potential to deliver a 1 millisievert (0.1 rem) dose T

to an individual exposed to a patient. Ilowever, based on the screening procedure, additional consideration must be given to the therapeutic For a time period in which total decay takes procedures and the diagnostic use ofiodine-131.

place, Eq. (6) is simplified and the total dose is defined by D,(oo) as follows:

13 NUREG-1492 i

1

Table 4.8 Screening Calculation of Total Gamma Dose to Decay at 1 Meter Due to Administrations of Radioactive Materials Activity per Total Gamma Dose Examination Type Examinationm To Decay at 1 Meter *

(Radiopharmaceutical)

(MBq (mci))

(mSv (rem))

Diagnostic Procedures Brain

- Tc-99m DTPAS 740 (20) 0.1 (0.01)

- Tc-99m 0 740 (20) 0.1 (0.01) 4 Hepatobiliary

- Tc-99m IDAS 185 (5) 0.03 (0.003)

Liver

- Tc-99m sulfur colloid 185 (5) 0.03 (0.003)

Bone

- Tc-99m phosphate 740 (20) 0.01 (0.01)

Lune Perfusion l

- Tc-99m MAAS 185 (5) 0.03 (0.003)

Thyroid

- Tc-99m O.

185 (5) 0.03 (0.003) 131 3.7 (0.1) 0.06 (0.006)

- I-131 (maximum)"'

370 (10) 6 (0.6)

Cardiovascular

- Tc-99m RBC*

740 (20) 0.1 (0.01) f

. Tc-99m phosphate 740 (20) 0.1 (0.01)

Renal

- Tc-99m DTPA 740 (20) 0.1 (0.01)

- I-131 hippuran 9.3 (0.25) 0.15 (0.015)

Therapeutic Procedures Thyroid Ablation (Hvnerthyroidism)

- I-131 1110 (30) 18.5 (1.85)

Thyroid Cancer

- I-131 11,100 (300) 185 (18.5)

Permanent Implant

- I.125 1,850 (50) 118 (11.8)

- Pd-103 4,625 (125) 63 (63) r

"' For diagnostic procedures, the activity is the average per administration (see Table 4.2). The maximum diagnostic activity of I-131 is shown because it yields gamma doses exceeding the 1-millisievert (0.1-rem) screening value. For therapeutic procedures, the activity is the maximum per administration (see Table 4.6).

• Calculations assume no biological elimination and no attenuation of gamma rays in air, body of patient, or source capsule.

+

• DTPA is diethylene-trimmine pentscetic acid, IDA is imino diacetic acid, MAA is macro-aggregated albumin, and RBC is red blood ce!!s.

l NUREG-1492 14

4.2.3 Estimate of Maximum Likely time close to the patient as possible are given.

Doses to Individuals Exposed to The value is also supported by empirical data.

Patients Harbert and Wells (HA74) monitored family members of three patients for external exposure.

ey parameters of padent summa s

To determine the potential magnitude of the treatments and associated measured doses to impacts on therapeutic administrations, consid-etably more realistic assessments were made of family members. The last column of Table 4.9 the doses that could result from exposure to a ProMes dow esfunates eat wouM haw been patient treated with each of the radionuclides used predicted based on the 25 percent Reference m therapy.

Dose Model adopted in th,s report.

i

"" " ' " " I '

4.2.3.1 Exposure Fnctor The release of a patient with radiopharmaceuticals For therapeutic administrations of iodine-131, the has the potential for exposing other individuals taal ganuna dose to & cay at 1 meter $as calcu-who are near that patient. As such, essentially all 1 {cd based upon specific uptake, retention, and members of society are to a varying extent at risk "I'""". tmn rams for hype @Toid and euthyroid to exposure whether at home, work, or in a public c nditions. For thyroid ablat,on, the patient is i

facility (e.g. public transportation, restaurant, mnsidered hyperthyroid; for thyroid cancer, the theater, store, sporting event, etc.). Doses among patient is conservatively considered euthyroid or individuals who may come in contact with a having normal thyroid function. For nodme-125 released patient are highly variable and reflect the and pana&umE unplads, k taal gamma hw t decay at 1 meter was calcdated consMer, g m

crucial, but difficult to define, parameters of time, auenuat, n h tb source capsuk and de m

distance, and shielding. Based on time and distance considerations, it is reasonable to surr unding tissues.

conclude that for the overwhelming majority of released patients, the maximally exposed lodide is concurrently removed from the blood by mdividual is likely to be the primary care-both the thyroid and by the kidneys. The concurrent removal of free iodide from the blood provider, the family, or any other mdividual wh spends sigmficant time close to the patient.

by thyroid uptake and urinary excretion yields a biological half-life of blood iodide of about 5 to Based on t.ime, distance, and shielding factors, 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> (ST88). This implies that about 95 per-which describe normal lifestyles of the U.S.

cent of iodide (and therefore radiciodide) is cleared from the blood in the first 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> population, it is highly unlikely that doses equal t spending 100 percent of time at a distance of following an oral or i.v. administration. The 1 meter from a patient would result to any kinetics of these two competing removal s of iodide from the blood forms the mdividualincluding a patient s spouse. As a standard medical practice, patients undergoing basis of the iodide uptake fraction from the blood therapeutic treatments with radiopharmaceuticals by the thyroid.

are given firm instructions, both verbally and in writmg, regardmg basic prmciples on how to Organ Uptake Fraction minimize doses to other individuals.

The fraction of iodide taken up from the blood by Given all considerations, a realistic estimate of the the thyroid varies widely among indidduals maximal likely dose to an individual exposed to a because of differences m dietary modine levels and metabolic factors that are age and sex related.

patient is 25 percent of the

• Reference Dose" (.i.e.,

dose-to-total decay at a distance of 1 meter).

For heahby adult (cuthyroid) h:dh; duals in the U.S. with an average daily dietarf intake of iodide, The selection of 25 percent of the *Referenc the daily thyroidal uptake of about 60 to 100 g of Dose" for estimating maximal likely exposure is an iodide represents a 9 to 30 percent fractional mtuitive judgment based on the authors judgment uptake, with an average fractional intake of of tune-distance combinations that are beheved 17 percent. Under conditions of hyperthyroidism, likely to occur when mstructions to spend as little the fractional uptake is considerably higher and j

15 NUREG-1492 l

Table 4.9 Family Doses from Patients Treated for Hyroid Carcinome Pndicted Measured Dose Based on Total Body Hurden Doses to 25% of Activity at Time of Family Reference Administered Discharge Member Dose Patient (mCl)

(mCl)

(mrem)

(mrem) 1 20 25.2 146,128,55 176 2

is1 26.4 91,36,36 184 3

209 18.4 146,73 128 Source liA74.

may reach levels as high as 75 to 80 percent (8)

(ST88).

+Fe R(t) = F,e 2

Since elemental mdine is heavily concentrated in the thyroid gland, iodine-131, a beta-gamma where F + F = 1.0 ; and where F, and F i

2 2

emitter, has found extensive applications in represent the extrathyroidal and diagnostic and therapeutic procedures invohing thyroidal fraction of iodide, the thyroid. Owing to its physical, chemical, and respectively, biological characteristics, iodine-131 is the most frequently used therapeutic radiopharmaceutical T., = biological half-life of and thus of primary concern in a discussion of extrathyroidal iodide, regulatory release criteria.

T., = biological half-life of iodide Biological IIalf-Life following uptake by the thyroid, The biological half-life of cicmental iodide is t = time after administration of primarily governed by metabolic utilization and iodide.

retention of organified iodide. For euthyroid conditions, the thyroid releases approximately 60 Because radioactive nuclides of iodine are also to 100 g of hormonaliodide daily. Empirical lost by radioactive decay, the retention equation studies by Dunning and Schwarz (DU81) show Eq. (8) must be modified accordingly:

that the climination of iodide from the thyroid among individuals may vary with biological half-(9) lives of 21 days to over 300 days. Under condi-R(t) = F e r2 ' + F ' r'#

3 2

tions of extreme hyperthyroidism (e.g., Graves' disease), enhanced elimination of iodide may where reach biological half-life values as short as 7 days (ST88).

61 P

(10)

T' d = T, + T,'

s The Quantitative Assessment of the Uptake, Retention, and Excretion of Iodine-131 x T, k33) 62 T'#

=

There is general agreement that retention of 7 + T,

• 62 stable iodide introduced into the blood stream declines with time according to a two-term exponential equation (ICRP79):

and T, = the physical half-life of iodine-131.

NUREG-1492 16

Empirical measurements of the fractional uptake life will equal the physical half-life of iodine-131.

following a single administration have been For the time interval of 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> to infinity, the reported by many investigators. For North effective half. life will assume the value 5.7 days.

American adults with daily dietary intakes of 100 to 300 pg of iodide, the F value generally applied For purposes of quantifying average body and 2

to adults is 0.3 (ICRP79). Empirical measure-thyroid burdens in thyroid cancer patients, a ments also indicate that representative values for practical approach is to assume that (1) the 7, and T., vary between 4 to 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> and 50 to residual cancerous tissue is normal (i.e.,

3 100 days, respectively. Values of 5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> and euthyroid) and (2) the iodine-131 is metabolized 68 days represent average values for T, and T,,

in a manner that conforms with a normal and will be used for computational purposes in euthyroid condition. The total dose D,(m) is this report (LOS6). Table 4.10 identifies established in an analgous manner to that appropriate values that may be used to calculate described for hyperthyroidism above.

the total retention of iodine-131 under euthyroid and hyperthyroid conditions.

4.2.3.3 Inernal Exposure Substituting appropriate values from Table 4.10 Upon oral administration or direct injection into into Eq. (9) yields the following retention the circulating blood, the normal processes of equations:

absorption, distribution, and excretion take place.

Removal of radionuclides from the body may Euthyroid Condition:

follow the pathways of urine, feces, sweat, saliva,

""d '*h"1"d "i

R(t) = 0.7 c -8 "' + 0.3 r *'

(12)

Urine. Radionuclide excretion in the urine is the Ilyperthyroid Condition:

dominant and almost universal elimination E

• I' R(t) = 0.4 em2' + 0.6e -o me (13)

Feces. Radiopharmaceuticals retained or Eqs. (12) and (13) reveal that in the first 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> catabolized by the liver may be secreted into nearly all of the F, fraction has been eliminated the gastrointestinal lumen via the bile. Biliary (the F, fraction is that quantity which is not taken secretion of a radionuclide may be followed by up by the thyroid and is largely eliminated by intestinal reabsorption.

urinary excretion at discrete intervals over the first 24-hour period under normal conditions) and that Sweat. Radionuclides present in the extracellular post-24 hours the body burden of iodine-131 is in fluid will tend to be excreted in the sweat in essence defined by the F, fraction or thyroid accordance with the fraction that is unbound in burden. While these equations describe the the plasma.

retention in the body they do not include the iodide contained in the urine in the bladder. That Saliva. Salivary excretion of radionuclides is also iodide can be significant in the early hours af:er proportional to the unbound or diffusible fraction administration.

in the plasma. However, salivary excretion is seldom an important climination route, since For hyperthyroidism, due to the complexities nearly all saliva is swallowed rather than associated with the geometric distribution, uptake expectorated.

and biological climination of iodide, a simple, conservative model assumes that (1) the F, Milk. Radionuclide excretion via the mammary fraction is eliminated by a single urinary voiding gland constitutes a potential exposure pathway to at r equals 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> and (2) in the first 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br />, the breast-fed infant or child. This can be a very all of the iodide is concentrated in the body as a important pathway after the administration of point source (e.g., bladder). The total dose radiciodines. Relatively small administrations of D,(m) may, therefore, be established by adding radiciodine to a breast-feeding mother can cause the doses for two discrete time intervals: (1) O to very large doses to the thyroid of the infant.

24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> and (2) 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> to infmity. For the first Thus, precautions must be taken against breast-24 hours after administration, the effective half.

feeding after the administration of radiciodines.

17 NUREG-1492 d

Table 4.10 Parameters for Use in Estimating Iodine-131 Retection T,

Tu T

Tu Tag g

(days)

(days)

(days)

(days)

(days)

F F

i 2

Euthyroid (adult) 8.0 0.21 0.20 68 7.2 0.7 0.3 1

Hyperthyroid (adult) 8.0 0.063 0.062 20 5.7 0.4 0.6 i

Exhaled Air. Exhalation is the principal pathway monitored for external radiation exposure, thyroid for the elimination of radioactive gases such as dose equivalents may be assumed to be equal or xenon-133, which is used for lung ventilation tests.

less than the corresponding whole body exposures Through passive diffusion, unbound iodide in the from external radiation.

circulating blood may also be exhaled.

In a 1978 study by Jacobson, et.al. (JA78), seven i

The potential for contamination by patients families were studied in which one family member treated with radiciodine which may serve as a had been treated with iodine-131 doses ranging source for internal exposures to others have been from 2% to 5,500 megabecquerels (8 to assessed for various excreta pathways (BL71, 150 milicuries). Non-patient family members MA73, N180). Levels of iodine in urine, perspira-were assessed for external exposures by means of tion, saliva, and exhaled air are proportional to thermoluminescent dosimeters (TLDs) worn at l

the blood levels of free or unbound iodide. Thus, the wrist for the full duration of exposure.

maximum excretion rates are observed shortly Internal exposure (i.e., thyroid burden) was after an administered dose. Excretion rates determined at discrete time intervals by means of decline rapidly thereafter due to renal clearance a pair of 30-inch Nal crystals. Although all family and thyroidal uptake. While contamination members proximal to the patient had measurable through urinary excretion may be readily thyroid burdens, dose estimates in nearly all cases controlled by cautious but reasonable hygiene indicate that external exposures substantially practices, contaminatior by other pathways exceeded intemal thyroid dose equivalents.

inclusive of saliva, salis a spray (i.e., sneering and Moreover, the investigators also concluded that it coughing), perspiratioa, and breathing are more

"... appears certain from our study of these difficult to mitigate. In a thorough study of two subjects that for spouses, there is a relation patients treated for thyroid carcinomas, Nishizawa, between thyroid activity and intimacy. Of the 12 et.al. (NIS0) observed maximum excretion rates of husbands and wives questioned,.. none were iodine in exhalation, perspiration, and saliva of willing to adjust living habits with their spouses 4

4 4

3.2 x 10 /hr,2.4 x 10 /hr, and 63 x 10 /hr of the because of the radiation therapy. Most, however, administered dose, respectively.

are concerned for their children and are willing to listen to suggestions which minimize exposure to Buchanan and Bridle (BU70) estimated thyroid their children."

radioiodine activity in 39 subjects who, as family members, were associated with patients treated Ahhough the number of studies and associated for hyperthyroidism. Administered quantities data regarding internal exposures are limited, ranged from 148 to 740 megabecquerels (4 to existing information suggests that internal doses 20 millicuries) per patient. Of the 39 patients,28 from intake of contamination are likely to be were instructed to take precautionary measures to much less than external doses.

minimize exposure to family members. Eleven patients volunteered to disregard special 4.23.4 Self-Shielding for Permanent Implants precautions against contamination and minimizing spousal and family exposure. On the basis of one The modeling of doses from patients with measurement per family, subject thyroid burdens implants is relatively simple because the ranged from less than 37 to 1,110 becquerels (1 to encapsulated activity is not subject to the complex 30 nanocuries) with an average of 259 becquerels uptake and climination of in-vivo administered (7 nanocuries). Although the subjects were not radionuclides. Dose and dose rates, as a function NUREG 1492 18

of time, are therefore governed exclusively by the and may, therefore, be exempted from physical decay of the radionuclide. Table 4.5 consideration in the cost-benefit analysis.

provided dose rates at a distance of 1 meter for point sources in air having activities within the 4.2.3.5 Summary of Maximum Likely Doses range of therapeutic implants. In Table 4.5, no attenuation of gamma rays within the source Table 4.11 provides the maximum likely dos,s to capsule or the patient's tissue was assumed.

individuals from current therapeutic procedures.

The estimates indicate that only the therapies and Calculated doses and dose-rate values of point a few diagnostic procedures invohing radiciodine sources in air, however, cannot be assumed to would be affected by any of the alternatives under represent implant conditions. A significant consideration.

reduction in dose rate and exposure doses must be anticipated from the shielding effects of the 4.2.4 Colketive Dose source capsule and the tissue surrounding the implant. The linear absorptica coefficient and To evaluate cach alternative, it is also necessary corresponding soft tssue half-value layer for the to estimate not only the dose to the maximally low energy photon of iodine-125 and exposed individual, but also the collective dose to palladium-103 were identified in Table 4.5. For a other individuals who may be exposed to patients prostate implant, tissues that serve to reduce administered radioactive materials. To calculate photon flux about the patient include the soft and precisely the collective dose that would be bone tissues of the thighs, pehis, buttocks, received under any of the alternatives would abdomen, etc.

require detailed information of a highly diverse group of patients relative to lifestyles, thing To assess the impact of tissue shielding by the arrangements, work environments, social activities, patient, the medical health physicist of the etc. This information does not exist and is l

Memorial Sloan Kettering Cancer Center was essentially impossible h precisely determine. In consulted (personal communication, J. St.

place of a precise estin. ate we have made a rough Germain, March 1993). Based on empirical estimate of the collective dose per procedure assessment invohing patients with implants, tissue which we believe is adequate for the purposes of shickling for iodine-125 is likely to exceed 5 or this rulemaking, more half-value layers (IIVLs), which would reduce the dose and dose rate by a factor of at Based on considerations of the written instructions least 32. For palladium-103 implants, in which the provided patients, the demographics of the patient ilVL in tissue is less than one centimeter, the population (see Table 4.3), and time, distance, shielding afforded by the patient's tissue is even and shielding factors, we estimate that the more extensive. For other implants invohing the collective dose per procedure is 3 times the lungs, brain, pancreas, etc., tissue shielding values maximal dose. This 3 times factor could occur in of similar magnitude can be assumed for an adult the following manner, based upon intuitive male and female. For certain implants invohing assumptions about a typical family and friends. In primary cancers of the neck and head, overlying addition to the person recching the maximal dose, tissues may provide less than 5 IIVLs of who is likely to be the primary care-provider, attenuation. In such instances, it is standard there could be 2 other people who will average practice to provide the patient with a small about half as much time near the patient. There portable " shield" which effectively attenuates all might also be about 4 other people who will emissions (personal communications, C. Jacobs, average about a quarter as much time near the August 1993, and R. Nath, J. St. Germain and patient as the maximally exposed individual. The K. Suphanpharian, March 1993). A shield consists sum of the collective dose to all these people is of a vinyl sheet impregnated with lead and molded 3 times the dose to the maximally exposed individ-to fit the anatomical surface over the implant.

ual. This situation could represent a typical family and friends. Of course some patients will Table 4.11 provides estimates of the maximal spend more time near other people, but other likely doses to an indhidual from implants. Even patients will spend less. A collective dose of for upper-bound aethitics of palladium-103, doses 3 times the dose to the maximally exposed are not likely to exceed 1 millisievert (0.1 rem) 19 NUREG-1492

Table 4.11 Maximum Likely Doses to Exposed Individuals frem nerapeutic Procedures m

Therapeutie Procedure Acthity Administered Maximum Likely Dose (Radionuclide)

(MBq (mCl))

(mSv (rem))

Thyroid Ablation (Hyperth>Toidism)

- iodine-131 555 (15) 1.05 (0.105) 833 (22.5) 1.58 (0.158) 1,110 (30) 2.1 (0.210)

Thyroid Cancer

- iodine-131 1,850 (50) 2.5 (0.250) 3,900 (100) 5.0 (0.500) 6,475 (175) 8.75 (0.875) 11,100 (300) 15.0 (1.500)

Permanent Implants

- iodine-125 1,110 (30) 0 96 (0.096) 1,480 (40) 1.28 (0.128) 1,850 (50) 1.60 (0.160)

- palladium-103 2,775 (75) 0.56 (0.056) 3,700 (100) 0.78 (0.078) 4,625 (125) 0.98 (0.098)

"' For iodino-125, tirne-integrated activities and curnulative doses are calculaced for a 1-year period which represents 98.5 percent of the dose-t& total decay.

• These values account for the 5 HVLa of tissue shielding by the pat:ent and, therefore, are equal to the point source dose in air divided by 32.

individual is thus a reasonable average the dose dropped to 1 millisievert (0.1 rem).

representation.

Thus, the dose to the most exposed individual would be 1 millisievert (0.1 rem). The collective Finally, as data are not available on the distri-dose per procedure is then assumed to be 3 times bution of the quantities of radionuclides adminis-the dose to the most exposed individual. In tered for each procedure, the estimates of Table 4.13, the collective dose per procedure was collective dose for each alternative are based on calculated in the following manner. For thyroid the mid-point values withic the ranges of the ablation, no hospitalization is required ecause the activities administered.

administered activity is less than 1,110 mega-becquerels (30 millicuries).

Tables 4.12,4.13, and 4.14 present the estimates of the collective doses for Alternatives 1,2, and 3, From Table 4.11, the dose to the most exposed respectively for therapeutic administrations that indhidual from an administration of 833 mega-could be affected by choice of alternative.

becquerels (22.5 millicuries) is 1.58 millisieverts implants using palladium-103 are not included (0.158 rem). The collective dose is 3 times the because doses to exposed individuals are always individual dose or 4.74 millisieverts (0.474 rem).

less than 1 millisievert (0.1 rem).

The collective dose per procedure for iodine-125 implants was calculated in the same manner In Table 4.12, the collective dose per procedure assuming no hospitalization. For thyroid cancer, was determined in the following manner. For all hospitalization is assumed until the activity types of procedures in the table, the average remaining in the patient's body is 1,110 mega-activity administered will cause a dose to the most becquerels (30 millicuries). The estimated annual highly exposed individual that may exceed total effective dose equivalent to the maximally 1 millisievert (0.1 rem). Therefore it was assumed exposed indhiduals from a patient containing that all patients would remain hospitalized until NUREG-1492 20

Table 4.12 Estimates of Collective Dose from Therapeutic Radiolodine Procedures for Alternative 1:

Annual Limit of 1 millislevert (0.1 rem)

Aserage Activity Collective Estimated Total Herapeutic Administered Dose / Procedure Procedures Collective Dose Procedure (MBq (mCl))

(mSv (rem))

per Year (person-Sv (rem))

Thyroid Ablation

- iodine-131 833 (22.5) 3 (0.3) 50,000 150 (15,000) l Thyroid Cancer

- iodine-131 6,475 (175) 3 (0.3) 10,000 30 (3,0(X))

Permanent Implant

)

- iodine-125 1,480 (40) 3 (0.3) 2,000 6

(600)

All Therapeutic Procedures 62,000 186 (18,600)

Table 4.13 Estimates of Collective Dose from Therapeutic Radiolodine Procedures for Alternative 2:

Limits of 1,110 megabecquerels (30 millicuries) or 0.05 millislevert (5 millirems)/hr Average Activity Collective Estimated Total Therapeutic Administered Dose / Procedure Procedures Collective Dose Procedure (MHg (mCl))

(mSv (rem))

per Year (person-Sv (rem))

Thyroid Ablation

- iodine-131 833 (22.5) 4.74 (0.474) 50,000 237 (23,700)

Thyroid Cancer

- iodine-131 6,475 (175) 12.3 (1.23) 10,000 123 (12,300)

Permanent implant iodine-125 1,480 (40) 3.84 (0.384) 2,000 7.68 (768)

All Therapeutic Procedures 62,000 368 (36,800) 21 NUREG-1492 l

Table 4.14 Estimates of Collective Dose from nerapeutic Radiolodine Procedures for Alternative 3:

Annual Limit of 5 millisleverts (0.5 rem)

Average Activity Collective Estimated Total Therapeutie Administered Dose / Procedure Procedurrs Collective Dose Procedure (MBq (mCl))

(mSv (rem))

per Year (person-Sv (rem))

Thyroid Ablatmn

- iodine-131 833 (22.5) 4.74 (0.474) 50,000 237 (23,700)

Thyroid Cancer

- iodine-131 6,475 (175) 15 (1.5) 10,000 150 (15,000)

Permanent implant

- iodine-125 1,480 (40) 3.84 (0384) 2,000 7.68 (768)

All Therapeutie Procedures 62,000 395 (39,500) 1,110 megabecquerels (30 millicuries) is estimated given to the psychological impact of retention on to be 4.1 millisieverts (0.41 rem).

the affected individual and family members.

Hospitalization will also cause an increase in the In Table 4.14, the collective dose per procedure dose to the hospital staff and other patients in the for thyroid cancer is estimated by assuming hospi-hospital. However, the increase in dose to the talization until the maximum dose to an individual hospital staff is expected to be low relative to a would be 5 millisieverts (0.5 rem). The collective patient going home earlier because of the precau-dose is therefore 15 millisieverts (1.5 rems), using tions taken during hospitalization; e.g., patients the previously described assumption that the are isolated and the hospital staff rarely enters the collective dose will be 3 times the dose to the patient's room.

maximally exposed indhidual.

In the analysis that follows, these costs arc calculated assuming that all retained patients will 4.3 Value Impact Analysis be hospitalized. While retention costs might be less for non-hospitallocations, no attempt is made 4.3.1 Estimates of the Pctential Costs 43.1.1 Estimates of the Direct Costs of Patient The analysis in Section 4.2 indicates that the Retention 1 millisievert (0.1 rem) per year dose limit imposed by Alternative 1 would result in the Durations of Patient Retention smallest collective dose to indisiduals exposed to released patients. The benefit of smaller doses Estimates of the periods of time that patients estimated for Alternative 1 will only be achieved if would need to be retained under licensee control the patients to whom the radioactive materials for each of the alternatives are presented in have been administered are retained under the Table 4.15. These estimates are based on the control of licensees for longer periods of time.

limits imposed by each alternative and employ the The impact of retaining patients must be assessed midpoint aethities used for a given medical in terms of the patient, family, and society as a procedure.

whole. At a minimum, the economic cost must consider the direct cost of medical resources Cost of Patient Rttention required to retain the patient in a hospital and the indirect cost resulting from the loss of human To estimate the annual dollar costs for these resources. Additional consideration should be periods of retention, one needs only multiply the NUREG-1492 22

Table 4.15 Duration of Retention per Therapeutic Procedure (to the nearest day)

Alternative 1 Alternative 2 Alternative 3 (days)

(days)

(days)

Midpoint Activity E

I E

Rerapeutic Administered per procedures per procedures per procedures Procedure (Milq (mCl))

procedure (x 1000) procedure (x 1000) procedure (x 1000)

Thyroid Ablation 1-131, 50,0(X) procedures / year 833 (22.5) 3 150 0

0 0

0 Thyroid Cancer 1 131, 10,000 procedures / year 6,475 (175) 21 210 6

60 3

30 Permanent Implant, 1 125, 2,000 procedures / year 1,480 (40) 21 42 0

0 0

0 Total for All Therapeutic 402 60 30 Procedures l

l l

l 23 NUREG-1492 i

1

number days required for each procedure by the al (e.g., domestic) work which must be performed number of procedures per year and the average by someone else at the expense of the patient.

cost per day of hospitalization. In 1990, the average cost per day in a community hospital The conversion of time lost from economic was $687 (SA92). Based on an 8 percent per year activities to equivalent dollars is most fairly increase (SA92), the per diem cost at the achieved by means of the gross national product beginning of 1993 would be estimated to be $800.

(GNP). The GNP is considered the most flowever, as the current regulations require that comprehensive measure of the country's economic patients who are hospitalized from a therapeutic activity and includes the market value of all goods administration of radiopharmaceuticals to be and senices that have been bought for final use placed in a private room, the $800 per day during a year. From the GNP of about estimate is adjusted to $1,000 per day. Using this

$5,600 billion in 1991, the gross average annual figure, the potential costs of retaining patients per capita income of about $22,000 is derived, under Alternative 1 are estimated to be $402 mil-The value of $22,000 per year corresponds to lion. Under Alternative 2, the estimated cost is

$60 per day and can be used to determine the

$60 million. And, under Alternative 3, the equivalent dollar value for the number of days lost estimated cost is $30 million.

due to retention of an individual. The value of the days lost is shown in Table 4.16.

Costs of Providing Recordkeeping 43.13 Evaluation of Psychological Costs The currently emisioned proposed rule associated with Alternative 3 imposes additional paperwork Retention of patients in a hospital by design and recordkeeping requirements on the estimated necessitates that the patient be " isolated" and that 1,350 licensees (NRC-and Agreement State-human contact, inclusive of family members,is licensed) that provide therapeutic administrations either avoided or minimized. Such isolation may of radiopharmaceuticals or permanent radioactive bring about numerous changes and impositions in implants. For therapeutic administrations where the lives of the patient and family members that the annual dose to an exposed individual could may in part be linked to, but are not reflected in, exceed 1 millisievert (0.1 rem) total effective dose the direct and indirect economic costs identified equivalent, licensees would be required to record above. The wide variety of deterioration in the the estimate of maximum annual total effective quality of life brought on by illness are frequently dose equivalent that is likely to be received by an referred to as psychological costs. For thyroid individual, and to retain the record for three cancer or dysfunction requiring therapeutic doses years.

of iodine-131 for example, a deterioration in the quality of life may be precipitated by the loss of it is estimated that approximately 62,000 thera-bodily function, a lifetime dependence on medica-peutic procedures per year would be subject to tion, hormonal insthility, uncertainty of normal these requirements. A cost of $33 per patient is life-expectancy, disruption of normal daily estimated. This results in an annual estimated routines, and reduced financial security related to cost of approximately $2.1 million.

employment, lost earnings, and medical expenses.

43.1.2 Derivation of Indirect Costs While some of these elements of psychological costs are the result of the disease itself, others Loss of Time such as disruption of normal routines, social isolation, and enhanced financial strain are clearly Indirect costs principally reflect the time and elements of psychological costs that are directly output lost or forfeited by the patient while related to patient retention. In characterizing retained in a controlled emironment. Indirect psychological costs, Thomas Hodgson (HO84) costs may also be incurred by indhiduals other chief economist for the Department of Heahh and than the patient who may forego economic Human Services' Offices of Analysis and activities to accommodate a family member's Epidemiology states: ".. The emironment hospital retention. Economic aethities include created by illness often induces anxiety, reduced occupational work that is lost to either the patient self-esteem and feelings of well-being, resentment, or his or her employer as well as non-occupation-and emotional problems that often require NUREG-1492 24

Table 4.16 Costs of Alternatives 1,2, and 3 Cost Estimates llospitalization Value of Record llospital cost lost time keeping Psychological Collecthe Dose Hetention cost Alternative (person rem)

(days)

(millions)

(millions)

(millions)

(relative) 1 18400 402,000 402 24.1 0

High 2

36,800 60,000 60 3.6 0

Moderate 3

39,500 30,000 30 1.8 1.2 Low psychotherapy. Problems of living arrangements allowing individuals to receive annual doses up to may develop, leading to family conflict, antisocial 5 millisieverts (0.5 rem) under certain circum-behavior and suicide.... The combination of stances. Both ICRP and NCRP recommend that financial strain and psychological problems can be an individual be allowed to receive a dose up to especially devastating."

5 millisieverts (0.5 rem) in a given year in temporary situations where exposure to radiation 4.3.2 Cost Comparison of Alternatives is not expected to result in doses above 1 milli-sievert (0.1 rem) for long periods of time. The Table 4.16 summarizes the most relevant data recommendations of the ICRP and NCRP are pertaining to the costs of the three alternatives based on their finding that annual doses in excess under consideration. Quantitative values are of 1 millisievert (0.1 rem) to a small group of based on the midpoint activity values of iodine-131 people, provided that they do not occur often to used in the therapeutic treatments of hyperthy-the same group, need not be regarded as roidism and thyroid neoplasms and iodine-125 especially hazardous. Although the risk is seeds which are used in permanent implants for potentially greater under Alternative 3, it is stid treatment of select solid tumors. Due to the within the range of acceptable risk for radiation subjective nature of psychological costs, exposure accepted by the NRC (as implemented comparison is provided on a relative scale.

under the revised 10 CFR Part 20).

4.4 Evaluation Of The 5 DECISION RATIONALE Alternatives Writh Respect To Accepted Radiation Protection Principles 1.

All of the Alternatives are acceptable according to generally accepted radiation Selection of the 5-millisieverts (0.5-rem) total protection principles, as those expressed by effective dose equivalent per year criterion is con-NRC, NCRP, and ICRP, as discussed in sistent with; the Commission's provision in Section 4.4.

10 CFR 20.1301(c) for authorizing a licensee to operate up to this limit; the recommendations of 2.

Alternative 1 is considerably more expensive the International Commission on Radiological to the public compared to Alternative 2 (the Protection (ICRP) in ICRP Publication 60, "1990 status quo) or Alternative 3. Even neglecting Recommendations of the International Commis-the psychological costs, which have not been sion on Radiological Protection;" and the recom-expressed in dollar terms, the incremental mendations of the NCRP in NCRP Report cost of Alternative 1 relative to Alternative 2 No.116," Limitation of Exposure to lonizing is about $363,000,000 per year, mostly in Radiation." Each of these provide a basis for increased national health care costs. The 25 NUREG-1492

value of the dose savings at a value of $1,000 where multiple administrations in a year of per person rem is $18,200,000 per year. In 1,110 millisieverts (30 millicuries) or less of view of this, Alternative 1 may be dismissed.

iodine-131 are now administered to a patient, it may be possible to give all of the activity in 3.

Alternative 3 relative to Alternative 2 has a a single administration. This would reduce value of $30/40,000 per year, mostly in lower the potentisi for repeated expost_es to health care costs at a collective dose cost of hospital statf and to those providing care to

$2,700,000 per year. Alternative 3 also has the released patient.

psychological benefits to patients and their families. Thus, Alternative 3 is cost effective Additionally, this would provide physicians in comparison with Alternative 2.

with the flexibility to no! have to fractionate doses to avoid hospitalization to meet the 4.

Basing the patient release criteris in current requirements, which may lead to a 10 CFR 35.75 on the dose to individuals more effective treatment.

cxposed to a patient prosides a consistent, scientific basis for such decisions that treats 6.

Shorter hospital stays provide emotional all radionuclides on a risk-equivalent basis.

benefits to patients and their families. Allow-The dose delivered by an initial activity of ing earlier reunion of families can improve 30 millicuries or a dose rate at 1 meter of the patient's state-of-mind, which in itself may 5 millirems per hour varies greatly from one improve the outcome of the treatment and radionuclide to another. Thus, while the lead to the delivery of more effective health values in the current 10 CFR 35.75 may be care.

appropriate for iodine-131, they are too high for some other radionuclides and too low for others. A dose-based rule, such as Alternative 3, provides a consistent approach 6 IMPLEMENTATION for regulating new therapies, such as radiolabelled antibodies, as was discussed in Section 4.1.2.1.

No impediments to implementation of the recom-5.

A dose-based rule no longer restricts patient mended alternative have been identified. The release to a specific activity, and therefore staff is preparing a Regulatory Guide for licensees would permit the release of patients with which will provide, in part, simple methods to aethities that are greater than currently evaluate the dose to the indhidual member of the allowed. This is especially true when case-public likely to receive the highest dose from the specific factors are evaluated to more released patient. This will enable licensees to accurately assess the dose to other determine when a patient may be released from indhiduals. As can be seen in Table 4.11 for their control, the case of thyroid cancer,in those cases NUREG-1492 26

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31 NUREG-1492 l

NRC FORM 335.

U.S. NUCLE AR REGUL ATORY COMMISSION

1. REPORT NUMBER (Assioned try NRC. Add Vol.. Supp, Rev.,

O 89)

NRCM 1102.

and Addendum humbers,if any )

nu. m BIBLIOGRAPHIC DATA SHEET rse, instruer,m on rn, mm,>

NUREG-1492 2, TITLE AND SUBTITLE Regulatory Analysis on Criteria for the Release of Pat tents Administered Radioactive Material 3

DATE REPORT PUBLISHED r

j MONTH vEAR D' aft Report for Comment May 1994

4. F IN OR GR ANT NUMBE R

5. AUTHOR (St

6. TYPE OF REPORT S. Schneider, S. A. McGuire, U. H. Behling*, K. Behling*,

D. Goldin*

Draft

7. PE R LOD COV E R E D Unclusove' Darro 8 PE R F O,R MING,,O,*RG,ANIZ AT GON - N AME AND ADDh ESS for Nac. oroe* Demson. O*roct or Freron. v.s Nucteer Reputarorv commossion. nnd m n.,r,..n

,. um ea Division of Regulatory Applications

• S.

Cohen and Associates, Inc.

Office of Nuclear Regulatory Research 1355 Beverly Road, Suite 250 US Nuclear Regulatory Commission McLean' VA 22101 Washington, DC 20555-0001

9. SPONSOR ING OP G ANtZ ATf ON - N AV E AND ADDR ESS tor NRc. twe 'same as ecove". ur onoros tor. provoce NRC Davosoon. Ortsce or negoon. u S. Nuctear vreousatory commism c

Ond MOA909 OD'Grena.$

Division of Regulatory Applications Of fice of Nuclear Regulatory Applications US Nuclear Regulatory Commission Washington, DC 20555-0001

10. SUPPLEME NT ARY NOTES

11. ABST R ACT (200 words or wt The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the pubhc exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical, they both request that the NRC establish a dose limit of 5 mithsieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millaievert (0.1 rem) per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels (30 millicuries) of activity or a dose rate at one meter from the patient of 0.05 millisievert (5 millirems) per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a donc limit of 5 millaieverts (0.5 rem) for patier.t release. The evaluation demonstrates that, except for a few diagnostic procedures using iodine-131, diagnostic procedures are unaffcced by the choice of alternative. Only some therapeutic administrations of radioactive material could be affected by the choice of alternative.."he evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members. Alternative 3 would also have personal and psychological benefits for the patients and their famihes.

t2. K E Y WOR DS/DE SCfrP10H S suas woras or parwa ener en suor rescerrners in sornung rne report.J 4 AV A@aWi Y M AiEMf NI 10 CFR 35.75 Unlimited Patient Release Criteria imcue uAsam Iodine-131 an,s,-

Therapeutic Administration Unclassified finn kenorv Unclassified Ib. NUMBER Of FAGt S

16. PRICE NRC 7oRV 3% (2491

i Printed on recycled paper Federal Recycling Program

NURECr1492 ' ~ ~

REGULATORY ANAIXSIS ON CRITERIA FOR Tile RELFASE OF PATIENTS MAY 1994 ADMINISTERED RADIOACTIVE MATERIAL UNITED STATES FIRST CLASS Matt NUCLEAR REGULATORY COMMISSION POSTAGE AND FEES PAID WASHINGTON, D.C. 20555-0001 USNRC PERMIT NO. G 67 OFFICIAL BUSINESS PENALTY FOR PRIVATE UsE, $300 l

30724 Federal Register / Vol. 59, No.114 / Wednesday. June 15, 1994 / Proposed Rules Document Room,2120 L Street NW.

(Lower Levell, Washington DC.

Obtain single copies of the environmental assessment and finding of no significant impact and the regulatory analysis (NUREG-1492) from:

Jayne McCausland, Offim of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission. Washington.

DC 20555, telephone: (301) 415-6219.

Obtain single copies of the draft regulatory guide," Release of Patients Administered Radioactive Material."

which is related to this rulemaking, by writing to: Distribution and Mail NUCLEAR REGULATORY Services Section, Offim af COMMISSION Administration, U. S. Nuclear 10 CFR Parts 20 and 35 kgulatory Commission, Washington.

DC 20555.

RIN 3150-AE41 FOR FORTHER INFORMATION CONTACT:

Stewart SchneMer, Mm omuclear Criterla for the Release of Patients Regulat ry Research. U.S. Nuclear Administered Radioactive Material Regulatory Commission, Washm, gton, AGENCY: Nuclear Regulatory DC 20555, telephone (301) 415-6225.

Commission.

SUPPLEMENTARY INFORMATION:

ACTION: Pmposed rule.

Table of Contents

SUMMARY

The Nuclear Regulatory

1 Background

Commission (NRC)is pmposing to it. Petitions for Rulemaking amend its regulations concerning the 111. Public Comn ents Received un the s

criteria for the release of patients Petitions administered radioactive material.The IV. Coordination with NRC Agreement States new criteria for patient release wotdd be V. Coordination with the Advisory dose-based rather than activity-based Committee on Medical Uses of Isotopes VI. lssues and Their Resolution and would be consistent with the

\\ IL Summary of the Proposed Changes recommendhtions of the International Vlil Consistency with 1979 Medical Policy Commission on Radiological Protection Statement (ICRP). The proposed rule would lx. lssue of Compatsbibty for Agrwment require the licenses to maintain a record States for 3 years if the quantity of radioactive X Finding of No Significant F.nvironmental materialis likely to result in an annual Impact: Availability total effective dose equivalent to an XL Paperwork Reducdon Ad Statement individual exposed to the patient that R gu y

,n exceeds 1 milhsievert (0.1 rem) from a x1V. tiackfit Analysis single admmistration. The proposed rule responds to two petitions for

1. Background

rulemaking reCarding the criteria for Each year in the United States, release of patients administered radioactive pharmaceuticals or radioactive material.

radioactive implants are admimstered to DATES: %e comment period expires approximately 8 to 9 million patients fer August 29.1994. Comments received the diagnosis or treatment of dis' ease after this date will be considemd if it is (hereinafter this group will be referred practicable to do so, but the to as patient (s)). These patients can Commission is able to assure expose others around them to radiation consideration only for comments until the radioactive material has been received on or lefore this date.

excreted from their bodies or has ADDRESSES: Send comments to:

decayed away. As discussed below.

Secretary, U.S. Nuclear Regulatory most of these exposures would be much Commission, Washington, DC 20555, less than 1 miP.isievert (0.1 rem) total Attn: Docketing and Service Uranch.

effective dose equivalent per year.

Iland deliver comments to 11555 NRC's current patient release criteria Rockville Pike Rockville, Maryland in 10 CFR 35.75, Release of patients hetween 7:45 a.m. and 4:15 p.m. Federal containing radiopharmaceuticals or workdays.

permanent implants." are as follows:

Examine comments received, the

"(a) A licensee may not authorize environmental assessment and finding release imm confinement for rnedical of no significant impact, and the care any patient administemd a regulatory analysis at: The NRC Public radiopharmaceutical until either: (1)

tMO Wem a ympsesegnes.w,,

M s

e W

1 i

r 1

l l

t 1

l l

I 1

1

l'ederal Register / Vol. 59 No.114 / Wednesday, June 15, 1994 / Proposed Rules 30725 The measurebose rate from the patient !!. Petitions for Rulemahing (1) Adopt a dose limit of 5 is less than 5 millirems per hour at a Because some licensees were rnillisieverts (0;5 rem) for individuals distance of one meter; or (2) The activity uncertain about what effect the revised

• • P.5".d to patients who have been adminisered radiopharmaceuticale.

in the patient is less than 30 millicunes; 10 CFR part 20 would have on patient (2) Permit licensees to authorire l

(b) A liwnsee may not authorize releas" release criteria, two petitions were yq fr m hospitalization any patient from confinement for medical care of rewived m the issue.

re

'""""""U'"

any patient administered a permanent On June 12,1M1 (56 FR 26945), the

'T"I Y *"

E""'"'

implant until the measured dose rate n.,

NRC published in the Federal Register by derming. confinement to mclude less than 5 millirems per hour at a a notice of recei it of, and re9uest for not only confinement m a hospital, but I

distance of one meter "

comment on, a petitm.n for rukmaung also confinement in a private residence.

On May 21,1991 (56 FR 23360), the (PRM-20-20) from Dr. Carol S. Marcus.

Because the petitions submitted by NRC published a final rule that In additmn Dr. Marcus submitted a Dr. Marcus and the ACNM both address arnended to CFR part 20," Standards for s letter dated June 12,1992, further the patient release criteria set forth in 10 Protection Against Radiation."The rule characterizing her position. Dr. Marcus CFR 35.75, the NRC has decided to l

contained limits on the radiation dose requested that the NRC amend the resolve both petitions with this single for members of the public in 10CFR f

20.1301. However, when 10 CFR part 20 revised 10 CFR part 20 and to CFR part rulemaking. The proposed actions, if 35t

• adopted in final form, would constitute was issued, there was no discussion in the supplementary information on

h. U.) Raise the annual radiation dose the partial granting of these petitions as mit m 10 CF-R 20.1301(a) for set forth in this notice. All other whether or how the provisions of 10 CFR 20.1301 were intended to apply to mdividuals exposed to radiation from portions of petitions PRM-20-20 and the release of patients, thereby creating patients receiving radiopharmaceuticals PRM-35-10 would be denied.

the need to address this issue.

for diagnosis or therapy from 1 To determine the potential number of rnilbsievert (0.1 rem) to 5 millisieverts Ill. Public Comments Received on the patients that could be affected by this (0.5 rem).

Petitions issue, the NRC performed a screening (2) Amend 10 CFR 35.75(a)(2) to There were 140 comment letters analysis to determine how many retain the 1,110-megabecquerel (30-recci"ed on PRM-20-20 and 88 patients administered radioauive millicuric) limit for iodine-131, but comment letters on PRM-35-10 and tr.aterials could cause the exposure of an provide an activity limit for other PRM-35-10A. Commenters represented individual to a dose exceeding 1 radionuchdes consistent with the hospitals and clinics, professional millisievert (0.1 rem) total ef fective dose calculational methodology employed in associations, citizens' groups, equivalent in a year if there were no the National Council on Radiation Agreement States and Government nestrictions on patient release. The Protection and Measurements (NCRP) agencies. State radiation advisory screening analysis indicated thai none Report No. 37," Precautions in the boards, universities, consulting brms, of the diagnostic administrations were Management of Patients Who llave public utihties, a utility association, and hkely to result in a dose to an Recewed Therapeutic Amounts of a labor union. The majority of the t

indwidual exposed to the patient Radionuclides."'

commenters were physicians who i

cuecdmg 1 milhsievert (o 1 rem),

(3) Delete 10 CFR 20.1301(d) which expressed concerns primarily related to except for a few diagnostic prm edures requires lic ensees to comply with the cost of hospitalization. Other using iodine-131. The therapeutic provisions of Environmental Prc tectmn commenters included health and administrations that the screening Agency's environmental regulations in medical physicists, pharmacists, nocIcar analysis indicated needed consideruic i 15 Ox part 190 in addition to medicine technicians, pmfessors, and were: (1) The treatment of complying with the requirements of to one former nuclear medicine patient.

hyperthyroidism with iodinc.131 CFR part 20-Overall, the majority of all comments (50,000 per year);(2) the treatment of On Man b 9,1992 (57 FR 8282), the supported a dose limit of 5 millisieserts thyroid cancer with iodinc.131 (10.000 NRC published a notice of receipt and (0.5 rem) for individuals exposed to per year); and (3) the treatment of a request for comment in the Federal patients released with radioactive s ariety of cancers (e g., prostate cancer)

Register on another petition for material with the pennanent implantation of rulemaking (PRM-35-10) on patient iodine-125 seeds (2,000 per 3 ear) Other release criieria frorn the American IV. Coordin at.mn with NRC Agreement Mates radionuclides may also wanant College of Nuclear Medicine ( ACNM).

consideration. For example, doses to On May 18,1992 (57 FR 21043), the The NRC conducted a public individuals exposed to a patient NRC published in the Federal Register workshop with representatises of the administered ytterbium-109 and gold-notice of an amendment submitted by Agreement States on July 15 and 16, tua for therapy might result in radiation the ACNM to its miginal petition (PRM-1992, to discuss a variety of medical exposures exceedmg 1 millisiesert (0.1 35-10A). In addition, the ACNM issues,includmg the proposals for rem) to individuals expowd to the submitted two letters dated September amending 10 CFR parts 20 and 35. The l

patient. However, these radionuclides 24,1991, and October 8,1991, on the workshop was held in Atlanta, Gemgia.

i are schlom used. In adddion.

issues in their petition. The ACNM Twenty-one of the Agreement States proc edures involving radio labeled requested (c onsidering the contents of were represented, as well as a antibodies might result in doses all four letteis) that the NRC revise 10 scpresentative from the City of New est eeding 1 mulisievert (0.1 rend, CFR part 35 to-York The major recommendations on ahbough no such procedures using the rule provided by the representatives byproduct material are yet apprused for

, % a con,aon na.amn %,,,,non a may be summarind as follows:

toutme use. (For further information see wwcmem N m.Tonunens m N (1) Revise 10 CFR part 20 to celude the regulatory analysis for the proposed Snarem* of huent' Who line kened doses to individuals ev. posed to patients rule Single dopics of the draft

[1ll,))'"(^p["M"$$d]$$ released under to CFR 35.75.

f (2) In 10 CFR 35.75, mtam the dote regulatory analysis are available as gy,m the NCRF. N m woodmom Ment.c. w,w am, indid ated in Ihe ADDRE SSES headmg.)

Dettesda. MD mu 4-309s }

rate limit of 0 05 millisievert (5

3072G Federal Register / Vol. 59, No.114 / Wednesday, }une 15, 1994 / Proposed Rules millirems) per hour at a distance of 1 The major ACMUI recommendations on commenters stated that a dose limit of meter and add a dose limit of 5 the proposed rule were to-5 millisieverts (0.5 rem) per year for millisleverts (0.5 rem) in 1 year for (1) Add a dose limit of 5 millisieverts individuals exposed to a patient is in individuals expowl to patients.

(0.5 rem)in 1 year for individuals line with the rocommendations of the (3) Retain the current 1,110 exposed to a patient released with K'.RP and the NCRP.

rnegabecepwrel (30-millicurie) activity radionuclidos.

Some commenters believed that the 5-limit for sodine-131 but provide activity (2) Retain both the 1.110-millisievert (0.5-rem) hmit is beneficial limits for other radionuclides based on megabecquerel (30-millicurie) activity to both the patient and the family the recommendations of NCRP Report limit and the maximum dose rate of 0.05 because patients are able to mturn home No. 37,"Pmcautions in the Management millisieverts (5 millirems) per hour for earlier than would be permitted if a 1-of Patients Who llave Received patient release in 10 CFR 35.75 because millisievert (0.1-rem) limit were used.

Therapeutic Amounts of they are a simple means to show One commenter believed that the case Radionuchdes."

compliance without assumptions or

% could be made that no limit should be (4) Do not define " confinement" in 10 calculations.

applied to the patient's family, just CFR part 35 because the present (3) Develop a regulatory guide that maintain doses as low as reasonably wording gives regulatory agencies the includes a set of standardized achievable, because there is a benefit to prerogative to confine patients by means calculations with factors (e.g.

the family from the patient's being other than hospitalization.

occupancy factor) for licensees to home. A physician commented that (5) Requite that written instructions determine compliance with patient many patients come from homes in on how to maintain doses to other release criteria on an individual basis.

which no member of the family is under individuals as low as reasonably Provide tabbs of acceptable release the age of 30, and therefore, contended achievable be given to the rehmsed activities that are radionuclide specific, that there was less risk from radiation patient and any individual likely to based on exposum at 1 meter for routine exposure. Other comments in favor spend significant time in close patient releases, with built-in safety included: (1) 11ospitalization can be a proximity with the patient.

factors to avoid doses to individuals distressing experience for many cancer The NRC staff presanted a status near the 5 millisievert (0 5 rem) limit.

patients; (2) patients can develop report on the requirements of the (4) Requim that written instructions hospital acquired infections if kept in pmposed rule to the Agreement States at on how to maintain doses to other the hospital too lone and (3) confining another public meeting in October 1W3 individuals as low as reasonably patients in a hospital until the release in Tempe, Arizona. The Agreement achievable be pmvided to the patient criteria are met increases the dose to States were generally supportive of the upon micase from confinement.

hospital personnel and other patients.

approadiin this proposed rule.

The NRC staff presented status reports Controlling the cost of medical care Transcripts of both meetings have been on the requirements of the proposed was one of the most cited reasons in placed in and are available for rule to the ACMUI at two other public favor of the 5-millisievert (0.5-rem) examination at the NRC Public meetings in May 1993, in Ilethesda, limit. Concern was expressed that the Document Room,2120 L Stumt NW.

Mar'yland, and in November 1993, in costs to all parties involved (i.e.,

(Lower Level). Washington, DC.

Reston, Virginia. The ACMUI was patients, hospitals, insurance in addition, in July 1993, the NRC generally supportive of the approach in companics, etc.) would dramatically rise requested the Agreement States to this proposed rule. Transcripts of all if a 1-millisievert (0.1-rem) limit were provide commcats on a previous meetings have been placed in and are used. Commenters said a 1-millisievert verslun of the proposed rule.OIthose available for examination at the NRC (01-rem) limit would require longer responding,14 Agreement States were Public Document Room,2120 L Street Periods of hospitalization,that many generally supportive of the approach in NW. (Lower Level), Washington, DC.

outpatients would become inpatients, and that this would be extremely this proposed rule. one was in VI. Issues and Their Resolution opposition, and one was uncertain ofits expensive, support without further study. The There am seven issues that arise in Comments from nuclear power Agreement State that opposed the responding to the two petitions. These utilities supported the 5-millisievert annual dose limit of 5 millisieverts10.5 issues and their resolution are discussed (0.5-rem) limit roquested by PRM rem) (total elfectivo dose equivalem) below.

20. These commenters stated further believed that instructions on how to issue 1: Should the limits in 10 CFR that if the limit for annual dose to the maintain doses as low as reasonably 35.75 or in 20.1301(a) govern patient public exposed to patients were 5 achievable to household members and release? The petitioners requested an millisievens (0.5 rem), then the dose other frxlividuals would not be annual dose limit of 5 millisieverts (0.5 limit should be 5 millisieverts (0.5 rem) followed, radioactive contamination rem) for individuals exposed to for all exposures to the public, would be a problem, and permanent radiation from a released patient.

including those from nuclear power plants, because no demonstrable health implants could dislodge.

Supporting Comments effects have been observed at chrome

{,.Coortlination With the Advisory The majority of commenters favored a exposure levels of 5 millisieverts (0.5 Committee on Medical Uses ofIsotopes dose limit of 5 millisieverts (0.5 rem) rem).

The NRC staff presented their per year far individuals exposed to suggestions for a proposed rule to the released patients rather than the 1 Opposing Comments Advisory Conunittee on Medical Uses of millisievert (0.1 rem) in 10 CFR A citizens' gmup commented that any Isotopes (ACMUI) during a public 20.1301(a). The representatives from amount of radiation, no matter how meeting held in Rockville. Maryland. on Agreement States who attended the small, carnes a risk to the recipient.

October 22 and 23,1992. The ACMUI is public meeting held in Attanta, Georgia. Thus, decisions that affect the public an advisory body established to advise on July 15 and 16,1992, and the ACMU1 health should be made strictly on the the NRC staff on matters ihat involve the public workshop held in October 1992 basis of health, not economic administration of radioactive material in Rockville. Maryland, also favored the considerations. A second citiwns' group and radiation frwn radioactive material. 5 millislevert (0.5-mm) limit. Some expressed similar concerns.

rederal Register / Vol. Sn. No.114 / Wednesday, June 15, 1994 / Proposed Eules 30727 A few r.ommenters stated that the patient release. This conclusion was supersede 10 CFR 35.75 criteria when lirensee already has the requested relief neither tied to nor designed to 10 CFR part 20 was amended. flecause because the Commission has inade implement the more pencral the NRC finalized to CFR 35.75 after pmvision in 10 CFR 20.1301(c) for considerations in the to CFR part 20 proposing revisions to 10 CFR part 20 in approval of a licensee's request to dose limits that had already been 1986, the NRC's silence should indicate incmase the annual dose hmit to 5 proposed when the conclusion of that it did not intend the revised millisieverts (0.5 rem) for individuals adequacy was reached.

standards for protection against Tbc NRC maintains that the public radiation to supersede either 10 CFR exposed to a patient.

health and safety judgement specific to 35.75 or the NRC's underlying adequacy liesponse patient release in 10 CFR part 35 should judgement.

The NRC has determined that patient prevail over the mo e general 10 CFR As reflected in the above discussion, release should be governed by 10 CFR part 20.The criterion m the proposed to the NRC's finding of adequacy with 35.75, not to CFR 20.1301(a).10 CFR CFR part 35. 5 millisieverts (0.5 rem) respect to patient release criteria does 35.75 of the NRC's regulations adopted total effective dose equivalent per year.

not apply to or set a precedent for the in 1986 (51 FR 36932; October 16,1986) excluding bac) ground or any operations of nuclear power plants. The prohibits an NRC licensee from occupational exposure, is consistent basis for the limit for patient release is authorizing patient release until the with: The Commission's provision in 10 justified by the considerations that measured dose rate imm the patient is CFR 20.1301(c) for authorizing a specifically apply to patient release.

less than 0.05 millisievert (5 millimms) licensee to operate up to this limit for To codify the policy regarding the per hour at 1 meter or the activity in the limited periods of time; the issue of the applicability of 10 CFR patient is less than 1.110 recommendations of the International 20.1301 to patient release, the NRC is megabecquerels (30 millicuries).10 CFR Commission on Radiological Protection proposing to amend to CFR 20.1301(a) of the revised standards for (ICRP) in ICRP Publication 60? "1990 20.1301(a)(1) to explicitly exclude doses protection against radiation, adopted in Recommendations of the International to individuals exposed to released 1991 (56 FR 23360; May 21,1991),

Commission on Radiological patients. In addition 10 CFR requires a licensoe to limit the radiation Protection;" and the recommendations 20.1301(a)(2) would be amended by dose of any individual member of the of the National Council on Radiation adding the words " exclusive of the dose public from licem.ed activities to less Protection and Measurements (NCRPlin contributions from patients than 0.1 rem (1 millisievert) (total NCRP Report No.116.5 " Limitation of administered radioactive material and effective dose equivalent) in a year.

Exposure to lonizing Radiation." Each released in accordance with S 35.75" to The NRC's view that to CFR 35.75 of these pmvides a basis for allowing make it clear that the limit on dose in govems patient release represents a individuals to receive annual doses up unrestricted areas does not include dose reasonable interpmtation of the to 5 millisievertn (0.5 rem) under certain contributions from patients Commission's regulations on this circumstances. Both theICRP and NCRP administered radioactive material and subject. As a general rule, requirements recommend that an individualbe released in accordance with to CFR in to CFR part 35 are "in addition to."

allowed to receive a dose up to 5 35.75.

rather than "in substitution for "

millisieverts (0.5 rem)in a given year in issue 2: Should the patient release compliance with other NRC situations where exposure to radiation criteria in to CFR 35.75te expressed as requirements including to CFR part 20.

is ot expected to result in doses above a dose. based limit instead of being flowever,in this case, the dose limit of 1 millisievert (0.1 rem) per year for long expressed in terms of activity retained 10 CFR 20.1301(a), if it were interpreted periods of time, as would be the case for in the patient and dose rate at 1 meter to apnly to patient release. could require duses from released patients.The from the patient?

a license to continue confinement of a recommendations of the ICRP and NCRP patient whose release wmdd be are based on their findings that annual Supporting Comments l

permitted under to CFR 35.75. The NRC exposures in excess of 1 millisievert (0.1 While the choice of a dose-based vs will not adopt t is interpretation rem) to a small group of people, an activity-based limit was not h

because that would make 10 CFR 35 75 provided that they do not occur often to presented as an issue in the petitions, essentially meaningless.

the same group, need not be regarded as many commenters supported a dose-When the NRC proposed to CFR especially hazardous. Therapeutic base'd hmit of 5 millisieverts (0.5 rem).

35.75 (50 FR 30627; July 25.1985),it treatments with radioactive materials although those same commanters also l

said,"The Commission believes that are limited to a relatively small generally supported retaining an activity either limit li.e. 30 rudPr arias of proportion of the popuhition and are not limit. ~

activity or the a milliroentgen per houi often repeated for the same patient.

Some commenters and the ACNM exposure rate at'1 meter) provides an Although the NRC adopted 10 CFR discussed the inadequacy of the current adequate measure of safety for the 20.1301(a) after 10 CFR 35.75,it did not activitv. based limit in 10 CFR part 35 to general publicand that fuither intend to supersede 10 CFR 35.75.TLere deal with new techniques such as the

~

reductions in public exposure are not is no indication in the associated use of radiolabeled antibodies.

reasonably achievable considering the statements of consideration or response cost and lotential for detrimental effect to comments that NRC intended to S"PPorting Comments l

from an smnecessarily long hospital PRM-20-20 requested that patients confinement." Further, when it uniernaisonal caneniuion on Radiologirat given 1.110 megabecquerels (30 Proicuim Ocm>vmo h-nate of oc millicuries) ofiodine-131, or more, be approved 10 CPR 3515 in final fonn, the NRC again said,"The NRC believes

$7""$""$f7$$""n Noj,'o hospitalized and released In accordance ber that a 30-millicurie release limit 1990) avaaaue for sale from vergamon Preu. inc.

with the gu delines of NCRP Report No.

provides an adequate measure of public I:Imsford. N Y losn 37, and that the maximum activity that

' tational Counal on Radiation Protection and a patient can be released with for a houlth and safety." See 51 FR 36932.

The NRC's conclusion was based on an j,"[',"".$p'g"g',}"Qj"y,'l g"[*[f specific nuclide be consistent with the independent NRC public health and gy,a.si, go, w,m is, Negp, me wooamong calculations methodology of NCRP safety judgement that is specific to As enua..uite ano. rs rhesda.uu rosi+-so95.

Report No. 37. Many commenters and

[

307211 Federal Register / Vol. 59, No.114 / Wednesday, June 15, 1994 / Proposed Rules representatives from the Agreement requirement was not retained because the determining criteria, irrespective of States that attended the public the doses from a released patient are the amount of radioactive material workshop held in Atlanta. Georgia, on different for different radionuclides that administered or the potential pathways July 15 and 16,1992, also agreed with have the same activity. Likewise, a of exposure of individuals as a result of release criterion based on dose rate from contact with the patient. This is this regiuest.

the patient is not a uniform indicator of particularly important for proper control i

Opposing Comments dose because the total dose depends on of some types of materials, such as No comments opposing the the effective half. life of the radioactive strong beta emitters, which do not pose j

methodology in NCRP Report No. 37 materialin the body of the patient and a large externci dose hazard. In these were received.

other factors, which will differ for cases, dose through inhalation or different materials.

ingestion of contamination could be

Response

In most cases, the dose received by an significant pathways and must be i

The NRC agrees that the ulculational individual exposed to the patient will accounted for in a calculation for methodology of NCRP lieport No. 37 can be from external exposure. Ilowever,in compliance. To demonstrate compliance be used to calculate external doses from the case of a breast. feeding mother,the with the proposed rule in this situation, patients. Although NCRP Report No. 37 infant could be exposed following the optional calculationalinethod is dated, it still contains an appropriate ingestion of breast milk. In this case, the described in the draft regulatory guide method to calculate the integrated dose 5-millisievert (0.5-rem) limit applies to could be used, potentially resulting in at 1 meter from a patient following the infant as the individual likely to an earlier patient release than would administration of certain radionut lides. receive the, highest exposure.

otherwise have been allowed, while still This methodology is modified in the To halp hcensees casily determine if providing the specified level of l

draft regulatory guide to calculate they may authorize the release of a protection.

activities to meet the 5-millisievert (0.5 patient, a draft regulatory guide, Issue 3. Should the calculational rem) (total eifective dose equivalent) pt blished concurrently with this methodology in NCRP Report No. 37, l

limit.

proposed rule, contains a table that

" Precautions in the Management of specifies the activity of commonly used Patients Wno llave Received Opposing L,omments radionuclides with which a patient can Therapeutic Amounts of Several commenters, as well as be released in compliance with the Radionuclides," he an acceptabic means representatives from the Agreement proposed dose limit. The table in the to demonstrate compliance with the States and the ACMUI, noted that the draft guide provides a simple method to proposed rule?

1,110-megabecquerel (30-millicurie) demonstrate compliance that assumes issue 4. Should, as the ACNM activity limit is a simple method to no biological elimination of the requested, the word " confinement" be demonstrate compliance with NRC radioactive material. For example, in the defined to include confinement in a regulations and should be retained.

case of iodine-131, the value specified is private residence?

PRM-20-20 requested that the NRC 1.200 megabecquerels (33 millicuries).

"FP##"N " * * " " "

specify an activity for each specific The draft regulatory guide also offers radionuclide consistent with the guidance for the licensee who chooses The ACNM petitions stated that 10 calculational methodology of NCRP to calculate activities at which patient CFR 35.75 seems to mandate Report No. 37." Precautions in the release may be authorized based upon hospitalization as th,e only place of Management of Patients Who llave case specific information. Single copies (onfinement for patients receiving Receised Therapeutic Amounts of of the draft regulatory guide are radiopharmaceutical therapy for Radionuchdes."

available as indicated in the ADDRESSES compliance with 10 CFR 35.75. The heading.

ACNM petitions also stated that to CFR 1

1hponse The 0.05 millisievert (5 millirems) per 35.75 overlooks the merits of a The NRC's primary concern is the hour at 1 meter dose rate limit was not necessary option, temporary home public's health and safety. Doses are a retained in the regulation because. in confinement, for outpatient sneasure of degree of protection, essence, consideration of the dose rate radioph arrnaceutical therapy at levels whereas attimy of different is included in calculating the activity exceed tg 1.110 megabecquerels (30 radionutlides is not related in any for each of the radionuclides specified millicu es). This petition further stated consistent way to the level of protection. in the draft regulatory guide. In that pat. nts containint; quantities up to i

For this irason, the NRC proposes to addition, the draft regulatory guide now I voo megabecquerels (400 millicuries) l establish a dose limit as the only patient relates the dose rate with the relcam of iodine 131 could be confined in a release criterion in 10 Cl R 35.75. The criteria in the g3roposed to CFR 33.75 private residence, as justified by proposed dose limit is 5 millisieserts Newer techmques such as the published scientific papers that contend (0.5 rem) total effectwe dose equivalent therapeutic use of radiolabeled that home confinement of such patients in a year. This dose limit is consistent antibodies. involve the administration wouM not adversely affect public health,

with the underlying risk basis of the of perhaps as much as several and safety rurrent 10 CFR 35.75 (50 FR 30ti27).the gigabecquerels (hundreds of Another connuenter supported home recommendations of the ICRP, and the rnillicuries). These newer tec hniques

< onfinement because it would greatly provisions in 10 CFR 20130 tk ).

require that a patient' remain under the impmve patient comfort while reducmg pertaining to temporary situations in control of the lit ensee for a muc h longer medical expenditures by a considerable which there is requisi e justification for period of time before the current release amount, and that this can be

~

a dose limit higher than 1 millisievert criteria c,m be met. By thanging the accomplished without any significant (O. I rem).

basis for the release of patients in the risk to the public. Some commenters Unhke the current 10 Cl R 35.75, the proposed rule to an annuri dose limit, believed that patients confined at home pmposed to CFR 35.75 does not specify the activity or resulting dose rate are no with as much as 14.800 megabecquerels an at tivity or dose rate for authorizing longer the only limiting factors upon (400 millicuries) of iodine-131 would patient release. The 1,110-which a patient release is based. tinder not t reate a safety ha7ard to the puhhi megabecquerel (30.millit une) the propowd rule. the dose w onld be if simple precauf mns were followed i

Federal Re<,isier / Vol 59, No.114 / Wednesday, June 15, 1994 / Proposed Rules 30729

/

Several commenters beUcved that nu.terial. The licensee maintains contml Decause the reference to EPA they had been told by the NRC that the both from the location of patients and regulations in 10 CFR 20.1301(d) has use of the tenn confinement in 10 CFR by the actions the licensee takes to nothing to do with the patient release 3535 providnd for a nonhospital option. control doses. Although licensee control issue and has no impact on the A wuple of commenters suggested does not necessarily restrict a patient to petitioner, the NRC will not grant this that if a patient is rnedically capable of a hospital, the location of the patient request of the petitioner, t.cif <.are, informed and cooperative, must im listed as a place of use on the issue 6. Should the regulations release in amounts gmater than 1.110 license or a license amendment rnust be require that patients, upon release.

1 Inegahecquerels (30 milliruries) is issued pursuant to10 CFR 35.13(c).

receive written instructions on how to sensible.

Additional choices would be available maintain doses to other individuals as (e g, n.pic es or nursing homes) as long low as reasonably achievable?

Opposing CommeMs as the hcensee can demonstrate that it 1 he Conference of Radiation C4mtrol can control doses to other individuals as Supporting Comments Program thructors (CRCPD) commented well as the spread of radioactive PRM-20-20 recommended education that confinement should tot be defmed material.

of the patient and the care provider.

in 10 CFR part 35 Imcause the present The NRC believes that there is a Some commenters supported written wording already provides the optmn to distinct difference between a pat.ent instructions for the patient upon release.

confmc patients by means other than being " confined"in a hospital a nd Representatives from the Agreement hospitalir_ati<m.

" confined"in a home. In hosphal States who attended the public An Agreement State representative

( on hnement, the licensee has contml workshop held in Atlanta. Ocorgia. on remarked that it is not reahstic t over access to the patient as well as July 15 and 10,1992, and the ACMUI beheve that a person will go home and having trained personnel and public workshop held in October 1992 loc k themselves in a room for two to iwrumentation available for making in Rockville, Maryland, also agreed with three davs with limited contact with radiation measurements not typically this concept.

famdy and inends. Another Agreernent available at the patient's home. In Opposing Comments State iepreser,tative mamtained it is additim dile under licensee control.

difhrutt to mntrol actions of an a liansee has control over the dose by A physician stated that instructions ambulatory patient and difficult to limiting the amount of time that regarding patient activitiessignificantly rnsum that the patient has remained.m individuals are in close proximity to the increase apprehension needlessly.

confinement. This commenter als patient. Therefore, as a general practice.

N"E ""

i noted that the ACNM definition does the NRC does not want licensees to use not address transportntion to a confined a patient's home for the purpose of The NRC agrees that written area in a private residence that would

< onfining the patient.

instructions on how to maintain doses prohibit a patwnt imm using public issue 5. Should to CFR 20.1301(d) as low as reasonably achievable to r Ibophannaceutical therapy "'luim to pliance with Environmental people exposed to released patients f

Protection Agency (EPA) regulations?

should be provided. These written patsent opposed the changing of the PRM-20-20 stated that compliance with mstructions would specify what actions existing requirements. lie said that the EPA's Clean Air Act air effluent should or should not be taken by the r uttmg hospital costs by releasing standards would cost medical facilit, s released patients and by the individuals m

highly radioactive patients may afford

$10R000S00 per year,which would be potentially exposed. In fact, written shor1-term economic benefits for health added to natirmal health cam costs.

instructions are already required under rare I>roviders but it carries serious 10 CFR 35.315(al!G) and 35.415(a)(5).

heahh and safety risks to the farm.ly and S.upporting Comments Under the Proposed to CFR 35.75(b),

the public. lle also mdicated that some Most comments fmm physicians and when the total ef fect,ive do'se equivalent people would have a ddficuh time medical associations expressed concern to any individual other than the following the extensive advice that is over redundant NRC and EPA released patient is likely to exceed 1 given as to the precautions to he taken regulations contained m 40 CFR 61 millisievert (0.1 rem) from a single

- j tits expressed the msuhing fmm the EPA's limitation on administration, the licensee would lye c

rn air effluent imm NRC-licensed facilitics. required to pmvide wntten instruction-belief that wlease imm a hocpital with P8 " " * * * ' " ' * " "*

activities as high as 14E00 Opposing Comments as low as reasonably achievable to megabecquerels (400 millicuries) of houschold members and other iodine-131 is dangerous to public health No opposing comments were ny eived.

mdividuals. If the dose to any and safety individual exposed to the patient is not Unponse U"Pon" hkly to exceed 1 millisievert (0.1 rern).

'I he NRC has decided thnt the term The EPA regulations referenced in 10 instructions are not required but the

" confinement" should be deleted hom CFR 20.1301(dl are contained m 40 CFR physician could give any instructions the proposed revision to 10 CFR 3535.

part 190, w hich deals only with doses that he or she considers desirable.

Instead, the proposed rule language now and airborne emissions from uranium Written instructions provide an usec the phraso " licensee control." The fuel cycle facilities. 40 CFR part 190 available reference after the patient's NRC believes that the phrase " licensee does not apply to hospitals or to the release, if questions regarding patient control" more dearly reflects the NRC's release of patients. Furthermore,10 CFR care arise. Written instructions reduce intent.

20.1301(d) does not incorporate the the chance of misunderstandingthe The phrase " licensee control" refers EPA's Clean Air Act standards in 40 licensee's instructions as verbal to the ability of the licensee to CFR part 61 that apply to hospitals. The instructions may not be properly demonstrate that it can control dose:,to NRC is separately pursuing actions with conveyed to persons not present at the other individuals from the patient, as the EPA to minimire the impact of dual time of release. The NRC also believes well as the spread of radioactive regulation under the Clean Air Act.

that providing wdtten instructions will

30730 I?deral Register / Vol 59 No.114 / Nednesday, June 15, 1994 / Proposed Rules help relieve appn.hensions of the administrations requiring records Also, the proposed changes are patient primary c. arc-giver, and family.

involve iodine-131 therapeutic supported by the recommendations of The draft regulatory guide published administrations and a few diagnostic the ICFp and NCRp that an individual (oncurrently with this proposed rule procedures using iodine-131.

can be allowed to receive an annual includes recommended contents of the Recordkeeping would affect less them dose up to 5 millisieverts (0.5 rem)in written instructions. The instructions one percent of all administrations. (For temporary situations where exposure to v.hould be specific to the type of further information, see the regulatory radiation is not expected to result in ticatment given, such as radioiodine for analysis for the proposed rule. Single doses above 1 millisievert (0.1 rem) for hyperthyroidism or thyroid carcinoma.

copies of the draft regulatory analysis long periods of time.

or permanent implants;and may am available as indicated in the Doses among individuals who may include additional infonnation ADDRESSES heading.)

come in contact with a released patient regardingindividual situations 'ihe The proposed record retention period are highly variable atid reflect the instructions should include a contact of 3 years is consistent with similar crucial, but difficult to define, and phone number in case the patient recordkeeping requirements in 10 CFR parameters of time, distance, and has any questions. Written instructions pads 20 and 35.

shielding. Although all members of mkty have the potential for aposum should include, as appropriate; (1)

VII. Summary of the Proposed Changes to a released patient, based on time and mainta nmg distance from indmduals, including s!ceping arrangements and This section summarizes the distance considerations, it is reasonable the need to avoid public transportation; regulatwn changes that are being io conclude that for the overwhelming (2) the need to stop breast-feeding if proposed. The NRC proposes to amend nWority of released patients, the appropriate;(3) avoidance of public to CFR 20.1301(a)(1) to specifically maximally exposed individual is likely state that the dose to individual to be one who is aware of the patient's places (such as grocery stores, shopping centers, theaters, restaurants, and members of the public from a licensed i ondition such as the primary care-sporting events); (4) hygiene; and (5) t he operation does not include doses giver, a family meinber, or any other length of time pn cautions should be received by individuals exposed to individual who spends significant time taken. Not all of these precautions am patients who were released by the close to the patient.

nec essary for every patient; therefore, licensed operation under the provisions The NRC proposes to adopt a new to of to CFR 35.75.This is not a CFR 35 75(b)(1) to require that the patients should be given specific instruttions that are applicable to their substantive change but clarifies the NRC bcensee provide released patients with policy that patient release is governed written instructions on how to maintain situation.

Issue 7. Should records of patients by 10 CFR 35.75, not 10 CFR 20.1301, as low as reasonably achievable doses to released containing radioactive as discussed above under !ssue 1.

other individuals if the total effettive materials be required?

The NRC proposes to amend 10 CFR dose equivalent to any individual other Although the issue of records did not 20.1301(a)(2) to specifically state that than the released patient is likely to arise in the petitions or the comments the limit on dose in unrestricted areas exceed 1 millisievert (0.1 rem) in any on the petitions. proposed 10 CFR does not include dose contributions one year. A requirement for written 35.75lb) would require the licensen to from patients admini.stered radioactive instructions for certain patients was maintain a record of the basis for the material and reinased in accordam e already contained in to CFR patient's release and the calculations with 10 CFR 3535. The purpose of this 35.315'(a)(6) and 35 A 15(a)(5). The performed to determine the total change is to clarify that licensees are not proposed requirement would add ef fettive dose equivalent if an required to control areas, such as a approximately 50.000 patients per year individual is I kely to ret eive a dose in waiting room, simply because of the who are administered iodine.131 for the excess of 1 millisievert (0.1 rem) in a presence of a patient released pursuant treatment of hyperthyroidism.The year from a single administration 1:is to 10 CFR 35.75. If a patient is not '

purpose of the written instructions is to anthipated that this requirement will be required to be confined pursuant to 10 maintain as low as reasonably met by either a notation, such as a CFR 35.75, licensees are not required to achievable doses to individuals exposed reference to the Regulatory Guide, or limit the adiation dose to members of to patients, as discussed in more detail calculation (s) to be retained in the the public (e g., visitor in a waiting under issue 6.

patient's file. This record wonk! pros ide room) from a patient to 0.02 millismvert The NRC proposes to revisc 10 CFR a basis for assuring that the rnaximum (2 millirems) m any one hour. Patient 35.75(b)(2) to require that licensees dose to an individual exposed to the waiting rooms or hospital romus need maintain a record of the basis for the patient is below 5 millisieverts (0.5 rem) only be controlled for those patients not patient's release for three years. These for any single administration. This meetmg the release criteria in 10 CFR records inust include the calculations ret ont also provides the basis for 3535.

performed to determine the total ensuring that doses from multiple The NRC proposes to adopt a new 10 effective dose equivalent of the administrations greater than 1 CFR 35 75(a) to change the patient individual likely to receive the highest millisievert (0.1 rem) each do not total release criteria from 30 millicuries of dose if the total effective dose more than 5 millisieverts (0.5 rem)in activity in a patient or a dose rate of 5 equivalent to any individual other than millirems per hour at 1 meter from a ihe released patient is hkely to exceed any tear.

'Flie 1 millisievert (0.1 rem) threshohl patient to a dose limit of 5 millisieverts 1 millisievert (0.1 rem)in a year from for recordkeeping is based on the public (0.5 rem)in any one year, excluding a single administration. It is anticipated dose limit of 1 millisievert (0.1 rem) bath,round or any occupational that this requirement will be met by specified in to CFR part 20. This exposure, to an individual from either a notation, such as a reference to threshold would not result in an undue exposure to a released patient. The the applicable regulatory guide or recordkeeping burden for the majority of reasons for this change were discussed calculation (s) to be retained in the diagnostic administrations because above under issue 2. In brief, a dose-patient's file.The major purpose of the these administrations are well below 1 based limit provides a single limit that change is to provide the basis for millisievert (0.1 rem). Based on the can be used to provide an equivalent controlling the oose to individuals regulatory analysis, the majority of level of risks from all radionuclides.

exposed to a patient who may receise

=

Federal Register / Vol. 59, No.,114 / Wodnesday, June 15c1994 / Proposed. Rules.

30731.

more than one administration in a year, safety. Ilowever, mpresentatives of the average 0.42 hours4.861111e-4 days <br />0.0117 hours <br />6.944444e-5 weeks <br />1.5981e-5 months <br /> per response, as discussed above under Issuo 7.

Agreement States who attended the including the time for reviewing Finally, the NRC proposes to amend public workshop held in Atlanta, instructions, searching existing data its requirements on written instructions Georgia, on July 15 and 16,1992, have sources, gathering and maintaining the in 10 CFR 35.315(a)(0) and 35.415(a)(5).

recommended that the pmposed data needed, and completing and These regulations already required changes to 10 CFR part 35 should not reviewing the collection of information, written instructions in certain cases, but be a matter of compatibility (i.e.,

Send comments regarding this burden the phrase "if requimd by $ 35.75(b)"

Division 3) for the Agreement States. In estimate or any other aspect of this was added. The purpose of this change addition, two Agreement States in their collection of information, including was to ensure internal consistency written comments on the draft rule suggestions for reducing this burden, to within 10 CFR part 35 on when written reviewed in July 1993 addressed the the Information and Records instructions must be provided issue of patient release under 10 CFR Management flranch (MNDB-7714),

Vill. C4msistency with 1979 Medi<.al part 35 as a Division 3 matter. Under U.S. Nuclear Regulatory Commission.

Division 2 status, the Agreement States Washmgton, DC 20555-0001; and to the Poh.cy Statement snust address the changes and may Desk Officer. Office of Information and On February 9,1979 (44 l'R 8242), the adopt more stringent requirements, but Regulatory Affairs, NEOB-3019 (3150-NRC published a Statement of General rnay not adopt less stringent provisions. 0010), Office of Management and Policy on the Regulation of the Medical Budget, Washington, DC 20503.

Uses of Radioisotopes. The first X. I.inding of No S..igmficant statement of this pohey states that. "Tho EnvinmmentalImpact: Availalility XII. Regulatory Analysis NRC will continue to regulate the The NRC has determined under the The NRC has prepared a reguiatory medical uses of radioisotopes as National Environmental Policy Act of analysis (NUREG-1492) for the necessary to provide for the radiation 1969, as amended, and the proposed amendment. The analysis safety of workers and the general Commission's regulations in Subpart A examines the benefits and impacts public." The proposed rule is consistent of 10 CFR part 51, that the proposed considered by the NRC. The regulatory with this statement because its purpose amendments,if adopted, would not be analysis is available for inspection at the is ta provide for the safety of a major Federal action significantly NRC Public Document Room at 2120 L individuals exposed to patients who are affecting the quality of the human Street NW. (Lower Level), Washington, administered radioactive materials.

environment and therefore, an DC. Single copics are available as

'Ibe $ccond statement of the policy environmental impact statement is not indicated under the FOR rURTHER states that, "The NRC will regulate the required. The proposed amendment INFORM ATION CONTACT heading.

radiation safety of patients where would clarify the pertinent regulatory XIll. Regulatory Flexibility l

Justified by the risk to patients and language to reflect explicitly the Certification l

w hem voluntary standards, or relationship between 10 CFR part 20 compliance with these standards, ans and part 35 with respect to releaso of As required by the Regulatory inadequata." This statement is not patients, and revise the release criteria Flexibility Act of 1980. 5 U.S.C. 605(b),

relevant to the proposed rule because for patients receiving radioactive the NRC certifies that,if adopted, this the proposed rule does not affect the material for medical use imm an proposed rule would not have a safety of patients themselves but affects activity-based standard to a dose basis.

significant economic impact on a the safety of individuals exposed to llocause the risk basis of the current substantial number of small entitles. As l

patients.

regulation remains unchanged. it is a result of the revised regulation, the Tim third statement of the policy espected that there would be no impact would not be significant because states that. "The NRC will minimize significant chango in radiation dose to the revised regulation basically intrusion into medical judgements the public as a result of the revised represents a continuation of curreni affecting patients and into other areas regulation.

pfDCllC"-

traditionally considered to be a part of The draft environmental assessment The NRC is seeking public cornment I

the practice of medicine."The proposed and finding of no significant impact on on the initial regulatory flexibility rule is consistent with this statement which this determination is based is certification. The NRC is particularly because it places no requirements on the available for inspection at the NRC seeking comment from small entities as adrmnistration of radioactive materials Public Document Room. 2120 L Street defined under the NRC's size standards to patients and because the release of NW. (Lower Level). Washington. DC.

published on November 6,1991 (50 FR patients administered radioactive Single copies of the draft environmental 56072), as to how the regulations will materials has long been considered a assessment and the finding of no affect them and how the regulations matter of regulatory concern rather than significant impact.are acallable as may be tiered or otherwise modibed to solely a matter of medical judrement.

indicated in the rOR rURTHER ampose less stringent requirements on Th'us, the proposed rule is considered INFOnMATION CONTACT heading small entities while'still adequately to be consistent with the 1979 medical protecting the public health and safety policy statement.

M. Paperw sk Reduction Act Any small entity subject to this Statement regulation who determines that, because IX. Issue of L,onipatibility for This proposed rule amends of its size, it is likely to bear a Agnement States information collection requirements that disproportionate adverse economic The NRC believes that the proposed are subject to the Paperwork Reduction impact should offer comments that modifications to 10 CFR 20.1301(a) and Act of 1980 (44 U.S C. 3501 et seq.).

sp(ecifically discuss the following items:

10 CFR 35.75 should be Division 1 and This rule has been submitted to the a) The licensee's size and how the 2 items of compatibility, respectively.

Office of Management and fludget for proposed regulation would result in a because the patient release criteria review and approval of the information significant economic burden or whether required by the rule are the minimum collection requirements.

the resources necessary to implement requirements necessary to ensum The public reporting burden for this this amendment could be more,

adequate protection of public health and collection ofinformation is estimated to effectively used la other ways to L_.

30732 Federal Register / Vcl. 59, No.114 / Wednesday, June 15, 1994 / Proposed Rules optimize public health and safety, as PART 20-STANDARDS FOR

$ 35.75 Fielease of patlents containing compared 1o the ecemomic burden on a PROTECTION AGAINST RADIATION radiopharmaceuticals or permanent larger lit crisee; impfants.

(b) flow the proposed regulation

1. The authority citation for pan 20 is (a) A licensee may authorize release could be rnodified to take into accoun, revised to read as follows:

from licenseo control any patient the licensee's differing needs or Authority: Secs. 53,63.65,81,103,104, administered radiopharmaceuticals or capabilities:

101,1n2,186, r,a Stat. rno.931, 935, 9 3r.,

permanent implants containing (c) The benefits that would accrue, or N 7, m.953,955,as anwnded (42 U.S C.

radioactive materialif the totaleffective if 2073,2093,209s,21:1,2133,2134,2201, the detriments that would be avoided"d dose equ, valent to an individual from i

2232, m>h sm 201, as amended,202,206, the proposed mgulation were modific at 42, as anendnt 12H.12#, M C.

exposum to b mleased patient is not as suggested by the licensee *.

SM 1,5842. 5846).

likely to exceed 5 mdhs.ieverts (0.5 rem)

(d)llow the proposed regulation, as I" "" Y """ } ""

modified, could mom closely equalize

2. In S 20.1301, paragraph (a) is the impact of NRC regulations or r.reate rmised to read as follows (b)If tho total effective dose equivalent to any individual other than mnre equal access to the benefits of g 20m Dose umas for individua' the released patient is'likely to exceed Federal programs as oppo:,ed to enembers of the public.

1 millisievert (0.1 rem)in a year from providing siw cial advantages to any individual or group; and (a) f:ach licensee shall conduct a single administration, upon release the fe) Ilow the proposed regulation, as operations so that-licensee shalb m<xlified, would still adequately protect (1)The total effective dose equivalent (1) Provide the patient with written thn public health and safety.

to imlividual members of the public instructions on how to maintain doses The umunents should be sent to the from the licem ml operation does not to other individuals as low as Secretary of the 0,mmission, U.S.

exceed 0.1 rern (1 mSv) in a year, reasonably achievable; and Nuclear Regulatory Commission, exclusive of the dose contributions from (2) Ma ntam, for three years, a record Washington, DC 20555. NrrN:

the licensee's disposal of radioactive of the wh'ased patient and the Docketing and Service Branch. Iland material into sanitary sewerage in calculated total effective dose deliver comments to 11555 Rockville accordance with S 20.2003 and frtun Pike. Rockville, Maryland, between 7 A5 patients administered radioactive equivalent to the individuallikely to a m. and 4:15 p m. Federal workdavs.

material and releawd in accordant e receive the highest dose.

w

. 5,and ti in S 35.315, paragraph (a)(6) is XIV H.nkfit Analysis (2)The dose in any unrestricted area revised to read as follows:

The NRC has detennined that the from esternal sources, culusive of the

$ 35.315 Safety precauens.

hxkfit rule,10 CFR 50.109, does not dose wntnbutions from patients apply to this proposed rule and, administemd radioactive material and (a) * *

• therefore, that a bar kfit analysis is not released in accordance with S 35 75,

.E """'

required for this proposed rule, because does not excm d 0.002 rem (0.02 mSV) safety guidance,if required by these amendments do not involve any in any one hour, S 35.75(b), that will help to keep provkions which would impose backfits radiation dose to household members as defined in 10 CFR 50.109h)(1).

and the public as low as reasonably PART 35-MEDICAL USE OF XV. List of Sub'et is ach,ievable beforo authorizing release of I

DYPRODUCT MATERIAL the patient.

10 CVil part 20

3. The authority citation for part 35 Hyproduct mateu. l. Lw.e nsed wmim.s to mad as follou a

matenal, Nuclear materials, Nuclear

7. In S 35.415, paragraph (a)(5) is

^ "d"*i!F S"'S "1.161 IR2.I'n.G3 Stat.

tevised to read as follows:

power plants and reactors, Occupational

'" 5' " " '

'M "5

"d"dH2l %

safety and heahh, Packaging and 2m. 2 201, 22 32. 22 m"'""et 201. M 9at.

$ 35.415 safety precautions.

s containers, Penalty, Radiation IN 2 at amended (42 (LS C SM t).

protection, Reporting and recordm.g (a) *.

gequirements. Special nuclear material.

4. In S 35 H, paryraph th)is revked t" (5) Provide the Iiatient with radiation oource material, Waste treatment and read as follows.

safety guidance,.f mquimd by i

dkpoU

$35.8 Information collection S 35.75(bl, that will help to keep 10 CFil par 135 requaements: OMO appn, a radiatinn dose to household members and the public as low as reasonably Hypunluct material, Criminal penalty, achievable before releasing the patient if (b) The approved intonnation Dro'gs. Ilealth facihties, licalth professions, incorporation by reference.

("IIrction requirements e ontained in the patient was administered a Medimi devices, Nuclear materials, this part appear in SS 35.12,35.13, permanent implant.

Occupational safety and health, Penalty, 35.14,35.21,35.22,35.23,35.27,35.29, a

Radiation protection, Reporting and 35.13,35.50,35.51,35.53,35.59,35.60, nan d at no, h in,. MD. this mh day of recordkeeping requirements.

35.61, 35.70. 35.75, 35.00, 3 5.92, n.204 June,19%.

35.205, 35.310, 35.315, 35 A 04, 35.400 For tM'm W Regulatory Commicion.

For the reasons set out in the preamble and ender the authority of the 35.410,35.415,35.606,35.610,35.615',lohn C Ifoyle*

3M30,3M32,3u30 35.634 au41 Atomic Energy Act of 1954, as amended'.

h@*WN bs*

au43,35ms, and 3Mn the,Enern Reorganfration Act of 1974

"I as amended; and 5 U.S.C. 553; the NRb is proposing to adopt the following

5. Section 35.75 is revied to read as amendments to 10 CFR parts 20 and 35.

follows:

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U.S. NUCLEAR REGULATORY COMMISSION June 1994 f'

0FFICE OF NUCLEAR REGULATORY RESEARCH Division 8 o

i Task DG-8015 i

DRAFT REGULATORY GUIDE

+.,*****/

Contact:

S. Schneider (301) 415-6225 DRAFT REGULATORY GUIDE DG-8015 RELEASE OF PATIENTS ADMINISTERED RADI0 ACTIVE MATERIALS A.

INTRODUCTION g

,j %

NRCisproposingtoamendthepatientreleasecriteridDi,nl@CFRPart35, n

" Medical Use of Byproduct Material." TheproposedSection;35d5readsas

[g k follows:

j% e kjgh (a) A licensee may authorize release from licensee control any

,xqy patientadministeredradiopharmaceuticals"or{pcrmanentimplants containing radioactive material if th,. total effective dose 3

(s equivalent to an individual fron agosure to the released patient is

\\

not likely to exceed 5 millisieverts"(0.5 rem) in any one year.

%rj -

(b)

If the total effectiY,e doseiequivalent to any individual other 3

thanthepatientisJikely'to; exceed 1millisievert(0.1 rem)ina year from a single administration, upon release the licensee shall:

~

W (1)

Provide the patient with written instructions on how to w.

maintainidoses to other individuals as low as reasonably achieNbid[and g

• k (2)yMa'Intain, for three years, a record of the released 4

sx

[N [ the individual likely to receive the highest dose.

g " patient and the calculated total effective dose equivalent to V

This regulatory guide is being issued in draft form to involve the public in the early stages of the develop-ment of a regulatory position in this area. It has not received complete staff review and does not represent an of ficial NRC staff position.

Public comments are being solicited on the draft guide (including any implementation schedule) and its assoc 1-ated regulatory analysis or value/ impact statement. Comments should be accompanied by appropriate supporting da ta.

Written comments may be submitted to the Regulatory Publications Branch. DFIPS. Office of Administra.

1 e

tion. U.S. Nuclear Regulatory Comission. Washington. DC 20555. Copies of comments received may be examined

/

at the NRC Public Document Room. 2120 L Street NW., Washington, DC. Comments will be most helpful if received

\\

by August 29, 1994 Requests for single copies of draft guides (which may be reproduced) or for placement on an automatic distri-bution list for single copies of future draft guides in specific divisions should be made in writing to the U.S. Nuclear Regulatory Commission. Washington, DC 20555. Attention: Office of Administration. Distribution and Mail Services Section.

This guide is being developed to provide guidance on determining the potential doses to an individual likely to receive the highest dose from exposure to the patient, to establish appropriate activities and dose rates for release, to provide guidance on instructions for patients on how to main-tain doses to other individuals as low as reasonably achievable, and to describe recordkeeping requirements.

For summaries, Table 1 lists the gamma ray constants and half-lives of commonly administered radionuclides, and Table 2 lists activities above which records and instructions should be prepared and the does rates below which patients may be released.

Regulatory guides are issued to describe and make available to the public such information as methods acceptable to the NRC staff for imple-

~

menting specific parts of the Commission's regulations, techniques used by the staff in evaluating specific problems or postulated accidents, and guidance to applicants.

Regulatory guides are not substitutes for regulations, and compliance with regulatory guides is not required.

Regulatory guides are issued in draft form for public comment to involve the public in the early l

stages of developing the regulatory positions.

Draft regulatory guides have l

not received complete staff review and do not represent official NRC staff positions.

The information collections contained in this draft regulatory guide are covered by the requirements in the proposed 10 CFR 35.75, which have been submitted to the Office of Management and Budget for review and approval.

B.

DISCUSSION This 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 the proposed Section 35.75.

The activities were calculated by using, as a starting point, the method discussed in National Council on Radiation Protection and Measurenents (NCRP)

Report No. 37, " Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides" (Ref. 1).

2 l

O Table 1 Gama Ray Constants and Half-Lives of Commonly Administered Radionuclides Specific Specific Half-Gama Ray Half-Gama Ray Radio-Life Constant Radio-Life Cor.stant nuclide (days)*

(R cm'/ mci h) nuclide (days)'

(R cm*/ mci h) 2 Ag-lll 7.5 0.2 Re-188 0.7 0.26' 8

Au-198 2.697 2.3 Sc-47 3.43 0.56' 2

Cu-64 0.53 1.2 Sm-153 1.95 0.447' I-125 60.2 1.11*

Sr-89 52.7 NA' 2

I-131 8.05 2.2 Tc-99m 0.25 0.607' Pd-103 17.

0.86' Yb-169 31.8 2.38' Re-186 3.7 0.2'

'From Reference 2.

'From Reference 3.

The constant given is a dose rate constant that takes into 4

account the attenuation of gamma rays within the implant capsule itself.

i

'From Reference 4.

The constant given is a dose rate constant that takes into account the attenuation of gamma rays within the implant capsule itself.

'From Reference 5.

i

' Calculated by Radiation Internal Dose Information Center, Oak Ridge Associated l

Universities, Oak Ridge, Tennessee.

l

'From Reference 2.

Not applicable (NA), 0.91 MeV gamma (0.009%, with Y-89m).

'From Reference 6.

'From Reference 7.

i A

3

---_--_---------------------------------------_-----------J

O Table 2 Activities for Which Records and Instructions should Be Prepared, and Dose Rates Below Which Patients May Be Released' Column l' Column 2' Column 3' Column 4*

Activity Below Dose Rate at Activity Above Dose Rate at Which Patients 1 meter at Which 1 meter May Be Released Which Instructions to Above Which Patients May Patients and Instructions Be Released Records should and Records Be Prepared Should Be Prepared i

Radio-nuclide mci GBq mrem /hr mci GBq mrem /hr Ag-111 390 14 8

77 2.9 2

Au-198 93 3.4 21 19 0.69 4

Cu-64 230 8.4 28 45 1.7 5

I-125 8.7 0.32 1

1.7 0.06 0.2 1-131 33 1.2 7

6.5 0.24 1

Pd-103 40 1.5 3

7.9 0.29 0.7 Re-186 780 29 16 160 5.8 3

Re-188 790 29 21 160 5.9 4

Sc-47 300 11 17 60 2.2 3

Sm-153 660 25 30 130 4.9 6

Tc-99m 960 36 58 190 7.1 11 Yb-169 7.6 0.28 2

1.5 0.06 0.4

'This table does not include radionuclides not regulated by NRC such as In-lll, T1-201, or Ga-67.

' Values have been rounded to two significant figures.

'Most values have been rounded to the nearest whole number.

O 4

NCRP Report No. 37 uses the following equation to calculate the exposure O

until time t at a distance r from the patient:

3 4. 6fQ,T, ( 1 -e-"'"""')

D(t) -

(Equation 1) r' Where D(t) - accumulated exposure at time t, in roentgens, f-specific gamma ray constant for a point source, R/ mci h

~

at I cm, Q, - initial activity of the point source in millicuries, at the time of the release, T, - 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.

e The dose to an individual likely to receive the highest dose from exposure to the patient is taken to be the dose to total decay.

Therefore, (1-e' """')

is set equal to 1.

It is assumed that I roentgen is equal to I rem.

Table 2 assumes, for radionuclides with half-lives greater than 1 day, that the individual likely to receive the highest dose from exposure to the patient would receive a dose of 25 percent of the l

total dose to decay (0.25 in Equation 2) at a distance of 100 centimeters.* For radionuclides with half-lives less than l

• Selection of 25 percent of the " reference dose" for estimating the maximal likely exposure is an intuitive judgment based on time-distance combinations believed to occur when instructions to spend as little time as possible to the patient are given. A study by Harbert and Wells (Ref. 8)

(O indicated that actual doses to family members of patients who had been treated for thyroid carcinoma was less than the predicted dose based on 25 percent of the reference dose.

5

1 day, the factor 1.0 is used in Equation 3 because the assumption that the time that individuals will spend near the patient will be limited is not valid when most of the dose is delivered in a relatively short time.

The doses are calculated using the physical half-life of the radionuclide as given in Table 1 and do not account for the biological half-life of the radionuclide.

For radionuclides with a half-life greater than 1 day:

34.6FQ,T,, (0.25)

D(m) =

(Equation 2)

(100 cm)*

For radionuclides with a half-life less than 1 day:

34. 6FQ,T, D(m) -

(Equation 3)

(100 cm)*

Equations 2 and 3 calculate the dose from external exposure to gamma radiation.

The equations do not account for internal intake by household members and members of the public because the dose from intake by other individuals is normally expected to be small (less than a few percent) relative to the gamma dose.**

Further, the table and the methods used do not apply to the release of breast-feeding mothers if they continue to breast-feed.

It should be noted that there could be a significant exposure to a breast-fed child.

l The gamma ray constants and half-lives for typical radionuclides used in nuclear medicine and brachytherapy procedures are given in Table 1.

The gamma ray constants used for iodine-125 (I-125) and palladium-103 (Pd-103) take into account attenuation of gamma rays within the implant capsule itself. All the l

• • There has been only a limited attempt to empirically measure the thyroid burden among family members associated with patients treated for hyperthyroidism or thyroid cancer.

Existing information suggests that thyroid doses from contamination leading to internal exposure are likely to be less than external exposures.

The addition of such a thyroid dose to the total effective dose equivalent (TEDE) by means of the thyroid weighting factor of 0.03 would, on the average, increase the TEDE by less than 3 percent.

6 l

l 1

other gamma ray constants in the table assume no attenuation of the gamma rays.

C.

REGULATORY POSITION 1.

ACTIVITY LEVELS 1.1 Activities for Release of Patients Licensees may demonstrate compliance with the dose limit in the proposed Section 35.75 for release of patients from licensee control if the amount of the specific radionuclide in the patient's body at the time of release is less than the value in Column 1 of Table 2 or if the dose rate at 1 meter is less than the value in Column 2 of Table 2 for that radionuclide.

If radioactive materials are to be administered to a mother who is currently breast-feeding, several alternatives are available.

First, the licensee may determine that the quantity and type of radionuclide administered is not likely to result in a dose to a breast-fed infant exceeding n

5 millisieverts (0.5 rem); this is unlikely to be the case for most administrations of radiciodine. A second alternative is for the mother to stop breast-feeding the infant for a predetermined period of time.

A third alternative is to postpone the administration until the mother has stopped breast-feeding.

References on the transfer of drugs and other chemicals into human milk and the cessation of breast-feeding after administration of radiopharmaceuticals to mothers can be used by licensees to determine whether it is necessary to stop breast-feeding (Refs. 9, 10, and 11).

The radionuclides currently used in medical diagnosis and treatment deliver the majority of their dose through an external dose pathway (e.g., radiation from the patient's body that exposes someone standing nearby).

If a radionuclide is, for example, a beta emitter, other pathways of exposure may need to be considered. The values in Table 2 do not take these i

other pathways into account, and licensees should refer to Regulatory Position 1.3 for further information.

OO 7

=

1.2 Activities Reauirino Instructions and Records Licensees may use the values in Column 3 or Column 4 of Table 2 to determine when instructions should be given to patients and when records should be kept in accordance with the proposed Section 35.75(b).

Column 3 provides activities above which an individual could receive a dose of 1 millisievert (0.1 rem) or more. Column 4 provides corresponding dose rates at 1 meter, based on the activities in Column 3.

1.3 Calculations 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 2 and still demonstrate compliance with the annual dose limit.

Licensees may take into t

account the effective half-life of the radioactive material and other factors that may be relevant to the particular case.

If the activity administered exceeds the activity listed in Table 2 for recordkeeping, but a case-specific calculation indicates a dose less than 1 millisievert (0.1 rem) that appears to not need a record, a record should still be maintained to ensure compliance with the proposed Section 35.75. The record should clearly identify the specific assumptions used in the calculation.

For case-specific calculations, written instructions should specifically address the case-specific factors that were assumed in calculating the dose to an individual.

Appendix A provides procedures for performing case-specific dose calculations, and it describes how various factors may be considered in the calculations.

1.4 Multiple Administrations To prevent a dose in excess of 5 millisieverts (0.5 rem) in any 1 year to an individual as a result of exposure to a patient containing radioactive material, licensees should sum the doses from all administrations of all l

B 1

o radionuclides to the patient in the year for which the record is maintained.

(The proposed Section 35.75(b) would require a record of the released patient if, for a single administration, the dose to any individual other than the released patient is likely to exceed 1 millisievert (0.1 rem) in a year.)

2.

INSTRUCTIONS FOR PATIENTS TO BE RELEASED If the total effective dose equivalent to an individual exposed to a patient is likely to exceed 1 millisievert (0.1 rem) in a year from a single administration, the proposed Section 35.75(b)(1) would require that the released patient be given instructions on how to maintain doses to other individuals as low as reasonably achievable.

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.

Instructions should include, as appropriate, the need for Maintaining distance from individuals, including sleeping arrangements and avoiding public transportation, Stopping breast-feeding if appropriate, Avoiding public places (e.g., grocery stores, shopping centers, I

theaters, restaurants, and sporting events),

Maintaining good hygiene, and The length of time precautions should be taken.

l 1

Not all these precautions are necessary for every patient; patients i

I should be given specific instructions that are applicable to their particular i

situation.

The Society of Nuclear Medicine published a pamphlet in 1987 that provides information for patients receiving treatment with radioiodine (Ref. 12). 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 instructions for patients, provided specific information is given to patients regarding any case-specific factors.

However, licensees may

(

9 l

develop their own instructions, addressing the items discussed in the above paragraph as appropriate.

Sample instructions for patients who have received permanent implants are given in Appendix B.

3.

RECORDS If the total effective dose equivalent from a single administration, upon the patient's release, to any individual other than the patient is likely to exceed 1 millisievert (0.1 rem) in a year, the licensee must maintain for 3 years a record of the releasad patient and the calculated total effective dose equivalent to the indivi'fual likely to receive the highest dose.

~

For example, if a patiert is administered 185 megabecquerels (5 millicuries) of iodine-131 (I-i31), the eximum dose to another individual is not likely to exceed 1 millisievert (0.1 rem).

Column 3 of Table 2 lists an activity of 240 megabecquerels (6.5 millicuries) or more as the activity corresponding to a dose at which a record should be kept and instructions should be given to the patient.

However, if the patient is administered 555 megabecquerels (15 millicuries) of iodine-131, the dose to another individual is considered likely to exceed 1 millisievert (0.1 rem).

In this case, the licensee is required to maintain a record of the dose and provide the patient with instructions.

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 release, (6) the estimated dose to an individual exposed to the patient, and (7) whether instructions were given to the patient.

If the dose to the individual most likely to receive the highest dose from exposure to the patient is determined t'/ asing Table 2 in this guide, the licensee should so state in the recor; and should state whether the

)

activity or the dose rate from the table was used.

If the dose was determined by a case-specific calculation, the licensee should maintain a record of the calculation, including the assumptions used in calculating the dose.

{

O 10

D.

IMPLEMENTATION The purpose of this section is to provide information about the NRC staff's plans for using this draft regulatory guide.

This draft guide has been released to encourage public participation in its development.

Except in those cases in which an applicant proposes an I

acceptable alternative method for complying with specified portions of the l

Commission's regulations, the method to be described in the active guide reflecting public comments will be used in the evaluation of a licensee's.

j compliance with Section 35.75.

[

i 1

J

'h i

j i

l 11 1

. ~..

l APPENDIX A PROCEDURES FOR CALCULATING DOSES BASED ON CASE-SPECIFIC FACTORS There may be situations in which a licensee may release a patient with an activity higher than the values listed in Table 2 for a specific radionuclide.

Licensees may calculate 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.

Such factors include (1) the effective half-life of the radioactive material, (2) exposure factors, and (3) other factors that may be relevant to the particular case.

]

The proposed Section 35.75 would require that a record of the release of the patient and the evaluation of the dose to an individual likely to receive the highest dose from a patient be maintained if the dose would exceed 1 millisieverts (0.1 rem).

The following equation may be used to calculate doses based on case-specific factors:

t 34.6rQ,T,E

\\

D(t) =

(Equation A-1)

(r)'

Where D(t) = dose to total decay, F=

specific gamma-ray 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 A licensee may take into account the effective half-life of the O

radioactive material to demonstrate compliance with the dose limits to members A-1

of the public stated in the proposed Section 35.75.

The effective half-life is defined as:

(Equation A-2)

T.,,

T, + T, Where T, - biological half-life of the radionuclide, T, - physical half-life of the radionuclide.

Using the effective half-life, Equation A-1 becomes:

34.6FQ,T.,, (E) 0(t) -

(Equation A-3) with the factors defined as above and T.,,

is the effective half-life.

For radiciodine, the effective half-life comprises the effective half-life of extrathyroidal iodide and the effective half-life of iodide following uptake by the thyroid.

The extrathyroidal and thyroidal fractions of iodide are F, and F,,

respectively. The effective half-life for F, and F, can be calculated with the following equations:

T,,,, =

(Equation A-4)

T,3 + T, T,,,, -

(Equation A-5)

T,, + T, Where T,3 - biological half-life for extrathyroidal iodide, T, - biological half-life of iodide following uptake by the thyroid, T,

- physical half-life of iodine-131.

Average values of 5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> and 68 days may be used for T,3 and T,,,

respectively, for radiciodine. A maximum daily thyroidal uptake of iodide of 9

A-2 l

l

30 percent may be used (Reference A-1).

Therefore, the extrathyroidal fraction of iodide is 70 percent.

Example: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 100 millicuries (3,700 megabecquerels) of iodine-131 for the treatment of thyroid cancer.

Solution:

In this example, we will account for elimination of iodine-131 from the body by using the biological half-lives appropriate for thyroid cancer 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:

Physical half-life of Iodine-131, T,,

8.0 days Extrathyroidal fraction, F 0.7 3

Biological half-life of extrathyroidal fraction, T,3 0.21 day Effective half-life of extrathyroidal fraction, T,,,,

0.2 day Thyroidal fraction, F, 0.3 Biological half-life of thyroidal fraction, T,,

68 days Effective half-life of thyroidal fraction, T,,,,

7.2 days Specific gamma ray constant, f 2.2 R cm'/ mci h For the first 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> after administration, the effective half-life, 1.,,, will equal the physical half-life because no correction has been made for loss of iodine from voiding of the bladder.

The dose for the first 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> is given by

34. 6FQo,,(0. 2 5) (1-e ""4)

T O(t) =

(Equation A-6)

(100 cm)'

Substituting the values from above gives 34.6(2.2R cm'/ mci h)(100 mci)(8d)(0.25)(1-e '""'**)

D(1 day) =

(100 cm)'

A-3

therefore, D(1 day) - 0.126 rem (1.26 mSv)

To calculate the dose from the end of the first day until total decay, it can be assumed that the extrathyroidal iodine has been totally voided and will not contribute to the dose. All the dose after the first day will come from the thyroidal iodine.

It is first necessary to calculate how much thyroidal iodine will be present at the end of the first day. The equation is:

Q(1 day) - Q,F,e -" '"' " "

(Equation A-7)

~

If t - 1 day and T,,,, - 7.2 days are substituted into Equation A-7, the activity is Q(1 day) - 100 mci (0.3)(0.91) 27.2 mci (1,006 Mdq)

The dose from the end of the first day to total decay can now be calculated using Equation A-6 [(1-e "'') is set equal to 1 since the dose is to total decay]:

(*

(

(*

D(Id e) -

(100 cm)*

D(Id e) - 0.373 rem (3.73 mSv)

Add ng the dose of 0.126 rem (1.26 millisieverts) from the first day to the dose of 0.373 rem (3.73 millisieverts) for day 1 to total decay yields a total dose of 0.499 rem (4.99 millisieverts). Thus, the maximum likely dose to an individual exposed to a thyroid cancer patient administered 100 millicuries (3,700 megabecquerels) of iodine-131 is about 0.5 rem (5 millisieverts). Therefore, thyroid cancer patients administered 100 millicuries (3,700 megabecquerels) of iodine-131 or less would not have to be confined and could be released under the proposed Section 35.75, assuming O

A-4 I

i

that there is documentation of the validity of the foregoing assumptions in the individual patient's case and that the patient is given instructions.

2.

EXPOSURE FACTOR The distance and the time that other individuals will spend in the proximity of the patient may occasionally be taken into account when determining the dose to an individual.

If the patient is living alone, will 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 two (for example, from the general value 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 2 in the regulatory guide. On the other hand, if the patient needs extensive care at home, the exposure factor will have to be increased to account for the increased exposure of the individual caring for the patient.

If this option is used in calculating the dose, the licensee should state in the record why a lower exposure factor was justified.

O Example: Calculate the maximum likely close to an individual exposed to a patient who has received 10 millicuries (370 megabecquerels) of iodine-131.

The patient lives alone and will not be working.

Solution: The dose is calculated using Equation A-1:

34. 6fQ,T,E D(t) -

(r)'

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:

(34.6) (2.22R cm*/ mci hr) (10 mci)(8.05d)(0.125)

D(t) -

(100 cm)*

D-0.077 rem (0.77 mSv)

A-5

Since the dose is less than 1 millisievert (0.1 rem), the patient may be released and instructions to the patient are not requiied.

Because the administered activity would indicate instructions and a record to be maintained based on the values in Table 2, it is recommended that a record of the calculation be maintained to ensure compliance with the dose limits in the proposed Section 35.75.

Example: Calculate the maximum likely dose to an individual exposed to a patient who has received 10 mil 11 curies (370 megabecquerels) of iodine-131.

g The patient requires extensive care because of other medical conditions.

SALuj;iol:

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:

(34.6) (2.2R cm*/ mci hr) (10 mci)(8.05d)(0.5) 0-(100 cm)*

D-0.304 rem (3.04 mSv)

Since the dose exceeds 1 millisievert (0.1 rem), the licensee must provide the patient with written instructions, and a record of the released patient is required.

3.

OTHER 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 M h ting equation:

O A-6

I O

D-Do -"

(Equation A-8) e 4

Where D - dose after attenuation, l

D, - dose before attenuation,

- linear attenuation coefficient of tissue, x - thickness of tissue covering the implant.

Also, the dose before attenuation is, from Equation 2 in the guide:

)

34.6FQ,T, (0.25)

]

Do (Equation A-9)

(100 cm)*

4 Substituting Equation A-9 for Do in Equation A-8, the dose after attenuation becomes 34.6rQ,T, (0.25)(e'")

I D

(Equation A-10)

(100 cm)*

O Example:

Calculate the maximum likely dose to an individual exposed to a patient who has received a permanent implant of 60 mil 11 curies (2,220 megabecquerels) of iodine-125. The following factors apply:

F - 1.11 R cm'/ mci br, T, - 60.2 days, p - 0.387/cm (Ref. A-1),

5 HVLs - 9 cm (assume 5 Half Value Layers; I 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 r of 1.11 R cm"/ mci h for iodine-125 already accounts for the reduction in exposure rate from attenuation by the source capsule.

Based on empirical assessment involving patients with implants, tissue shielding for iodine-125 is likely to exceed 5 or more half-value layers.

O A-7

Solution: The dose is calculated using Equation A-10:

34.6(1.11R cm'/ mci hr)(60 mci)(60.2d)(0.25)(e**/*""' *"))

g, (100 cm)"

D-107 rem (1.065 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.

The licensee must provide the patient with instructions and maintain a record that documents the validity of the foregoing assumptions in the individual patient's case.

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. Many of the radionuclides used in radiolabeled antibodies are predominantly beta or alpha emitters, which emit few gammas.

One way of evaluating the internal dose is to compare the internal dose with the annual limit on intake (ALI) value in 10 CFR Part 20.

A rule of thumb is to assume that the individual likely to receive the highest dose from exposure to the patient will receive an internal dose of 1-millionth of the activity that is in the patient. This rule of thumb was developed in Reference A-2 for cases of worker intakes during normal workplace operations, worker intakes from accidental exposures, and public intakes from accidental airborne releases from a facility, but it does not specifically apply for cases of intake by an individual exposed to a patient.

However, two studies (Refs. A-3 and A-4) regarding the intakes of individuals exposed to patients administered iodine-131 indicated that internal doses are negligible compared to external doses and that intakes were of the magnitude of one 1 'illionth of the quantity in the patient. For additional discussion on the subject, see Reference A-1.

O A-8

Thus, a rough estimate of the effective dose equivalent can be s

calculated from the following equation:

0 D,.

(Equation A-II)

ALI Where D, - the internal effective dose equivalent to the individual exposed to the patient in rems, Q = the activity in the patient at time of release in f

microcuries, ALI - the occupational inhalation annual limit on intake from Appendix B of Part 20, 5 rems - the dose from an intake of one ALI, 10

- the assumed fractional intake.

For example, assume that 30 millicuries (30,000 microcuries) iodine-131 was administered to a patient.

If 1-millionth of the administered activity is taken in by another individual, the activity would be 0.03 microcuries. The

[

stochastic ALI for iodine-131, 200 microcuries, corresponds to an effective dose equivalent of 50 millisieverts (5 rems). Thus, the individual would receive a dose of about 75 microsieverts (0.75 millirem).

In this case, the internal dose would be considerably less than 1 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 they would be significantly less than the uncertainty in l

the external dose.

t I

l 0

A-9

REFERENCES FOR APPENDIX A A-1.

S. Schneider et al., " Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material," NUREG-1492 (Draft report for comment), NRC, May 1994.*

A-2.

A. Brodsky, "Resuspension Factors and Probabilities of Intake of Material in Process (Or 'Is 10-' a Magic Number in Health Physics?'),"

Health Physics, Volume 39, Number 6, 1980.

A-3.

R.C.T. Buchanan and J.M. Brindle, "Radioiodine Therapy to Out-patients -

The Contamination Hazard," British Journal of Radioloav, Volume 43, 1970.

A-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.

O

• 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 PDR's mailing address is Mail Stop LL-6, Washington, DC 20555; telephone (202)634-3273; fax (202)634-3343.

A-10

J APPENDIX B i

SAMPLE INSTRUCTIONS FOR PATIENTS RECEIVING PERMANENT IMPLANTS i

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 l

to 1/4 of an inch long, similar in size and shape to a grain of rice.

To l

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:

l e

Stay at a distance of feet from t

for days / weeks.

f Minimize time with children and pregnant women for days / weeks.

e e

Do not hold or cuddle children for days / weeks.

s Avoid public transportation for days / weeks.

Examine any bandages or linens that come into contact with the implant e

site for any pellets or seeds that may have come out of the implant site.

O Take the following action if you find a seed or pellet:

o Do not handle it with your fingers. Use something like a e

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.

e Notify

, at (ohone number) for further instructions as soon as possible.

If you have any questions, contact the following individual (s):

Name Phone number Beeper number,

Name Phone number Beeper number O

B-1

---

e-c-

,w-u r3,---

y vt-wwr

REGULATORY ANALYSIS

" Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material" (NUREG-1492, S. Schneider et al.,1994),

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 fee at the NRC Public Document Room, 2120 L Street NW., Washington, DC.

l O'

Printed on recycled Paper Federal Recycling Program l

9 PA-1 t

-