ML19308B791

Forwards Recommendations of Surgeon General Re Thyroid Blocking.Concurs W/Recommendations.Public Health Svc 790403 Request Encl

ML19308B791
Person / Time
Site:	Crane
Issue date:	04/03/1979
From:	Califano J HEALTH & HUMAN SERVICES, DEPT. OF
To:	Watson J PRESIDENT OF U.S. & EXECUTIVE OFFICES
References
TASK-TF, TASK-TMR NUDOCS 8001170313
Download: ML19308B791 (8)

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T H E S EC R E T A n y o r H E A LT H. E D U C AT IO N, A N D W E L F A R E

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April 3, 1979 MEMORANDUM FOR THE HONORABLE JACK WATSON Enclosed are recommendations of the Surgeon General with respect to thyroid blocking.

Both the Director of the National Institutes of Health, and the Director of the-National Cancer Institute, and the Commissioner of the Food and Drug Administration support these recommendations.

These recommendations are:

1) Have workers in the plant and others on the island begin taking blocking doses now.

2) Have potassium iodide now personally available to all persons whose proximity to the site is such (perhaps up to ten miles distant) that they vill not have 6

as much as 30 minutes advance warning

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of Il31 exposure.

3) Have potassium iodide available at convenient distribution points for e'

distribution to other persons who may be exposed, such that they can have the medication at least 30 to 60 minutes in advance of possible exposure.

4) Accompany all distribution with notifica-tion to the effect that:

All persons may take potassium iodide safely for a short time.

All persons who:

a) have goiter or known thyroid disease, or b) are pregnant or c) are breast-feeding a child should notify their physician when they start taking iodide and after they have stopped.

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5) Preparations must be made for reducing the iodide dose after two weeks of administra-tion of the amount on the labels.

We will help you devise instructions for this if you wish.

6) Those in immediate touch with the local situation should assess these recommendations in light of knowledge about current risks and about the likelihood of advance warning of releases.

I also concur in these recommendations and urge that you provide this information to the state authori-ties as the basis for their action.

Joseph A.

Califano, Jr.

Enclosure

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' MEMORANDUM DEPARTMENT OF lidLEALWJ, MLc0tDAcK\\W9M, AkWED \\MELFARM PUBLIC IIEALTil SERVICE Food AND DRUc ADMINISTRATION

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APR 3 1979 TC*

The Secretary DATE:

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ES Assistant Secretary Dr Health FRoM :

and Sucgeon General SunJECT: Request for a Federal Advim on Thyroid Blocking On April 2 we were asked by Gene Eidenberg to provide guidance from Federal health officials for the Governor's staff in Pennsylvania on the advisability of providing precautionary iodine blocking for residents of the Three Mile Island area. The following is based upon consultation with Dr. Donald Frederickson, Director, NIH, and three of his staff (Drs. Rall, Robbins, and Wolff, NIAMDD) and Comissioner, FDA, his staff (Dr. Richard Crout, Dr. Jerome Halperin and Dr. Paula Botstein, Bureau of Drugs) and Dr. Arthur Upton, Director, NCI.

Dr. Frederickson had already consulted with his cun advisory group on the norning of April 2.

The reamnendation of the group is that workers in the plant and others on the island begin receiving blocking doses ncw.

Persons farther from the facility, perhaps up to 10 miles distant, should g

1 have the solution made personally accessible and be given instruc-tio, for its use, but should not receive precautionary doses as long as the dose can be given at least 30 minutes before a significant exposure to Il31 becomes probable.

Persons at greater distances should have the solution available at convenient distri-bution points that can be reached within a tine adequate to allow

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blocking doses to be ahtered at least 30 minutes before sig-nificant exposure.

It is not possible for us to give recomen-a dations in terns of precise distances from the facility, because the logistics of distribution and the probability of release affect

'those determinations.

Our advice is based upon the following considerations:

Blocking Effectiveness and Kinetics.

Guidance on these subjects nas been provided by the National Council on Radiation Protection and Measumnent, Ad Hoc Comnittee on Thyroid Blocking, Report #55, recently published in the Federal Register (Dec. 15, 1978; copy attached).

The blocking effect de p ds upon the action of non-radioactive iodine, provided as a saturated solution of potassium iodide (SSDI) at an adult dose of about 100 mg/ day in ampctitively 1

displacing 131 in the uptake nechanism of the thyroid.

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experinents in which the interval between pulses of I 31 and g

of KI was varied, blocking was fairly coaplete when the

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blocking dose and the radioactive iodine were given simul-taneously. About 50% blocking was seen when the KI follcued the radioactive dose by 3-4 hours. Of course in real situ-ations the exposure to radioactive iodine is cantinuous and the thyroid steadily accumulates it, so the blockingfo#ss&p solution is effective even if doses of the KIuc L:

Aw11%* gIcormenced and cantinued even a]. the exposure has begun A, hours or even davs before. The kinetics of this inter-action do argue?~ - --, that the largest effect will be obtained if the KI solution is administered before the radioactive dose.

If, however, the thyroid has been exposed to elevated levels of iodine by the administration of KI over several days - as would be likely in a continuous precautionary dosage regimen - there may be " escape" from protection against a subsequent dose of radioactive iodine.

Possible Side Effects. The possible side effects of continuous administration of KI at high dose levels include sone skin rashes (not serious), or '(in a few cases per 100,000 popula-tion) hypothyroidism or hyperthyroidism. The latter effect, which is treatable, is. especially likely in persons with goiter - a condition detectable in nore extreme cases by bisible swelling of the neck. Persons with this condition should be advised to consult their physicians while taking and advised KI dosages, and to continue consultation after the regimen has been discontinued. Pregnant and lactating

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tinued KI administration.

Like those persons with thyroid warren also may be subject to scrre elevated risk from con-disease, pregnant and nursing women shauld take KI when the rest of the population is advised to do so, but should consult their physicians during and after the regimen.

Other Risks and Benefits. The psychological effects on the population that Iray associated with an official program of protective nedication are difficult to assess, but obviously should not be ignored.

To sone it may appear that hitherto unrevealed difficulties 3now foreseen by the authorities.

On the other hand, a successful program might well provide sone reassurance that those responsible are displaying foresight and solicitude.

It may also generate scrre positive sense of control on the part of residents over a situation in which they have been relatively pcwerless to affective out-i cones up to ncw.

We believe that only those directly in touch with the behavior and nood of the population at risk can make such judgments - and then only with difficulty.

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It should also be pointed out that the decision depds critically upon infonration about the likelihood of a loss of containnent at the site, about the nature of the accidents that might be anticipated, and about the intervals by which warnings might be expected to preceed significant exposure at varying distances frcxn the site.

We believe that the benefits of protective dosing clearly outaeigh the risks close to the site, where sufficient time to anticipate the exposure does not exist. Whether this zone extends to 2 miles or to five miles we cannot say.

We would enphasize that instructions will also need to be given to the population receiving blocking doses about hoa to discontinue the reginen after the need for it has passed.

The dose must be tapered, presumably by a progmmed decrease in the frequency of taking the nedication.

It is our understanding that Dr. Neil Wald of the University of Pittsburgh is consulting with State health officials on this matter.

Dr. Wald is highly kroaledgeable in this area, and has been in regnbr commmication with nenbers of the NCRPM subconmittee and other eph.

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l'A* W htM N NMuwe EDUC4TICN, AND WELFARE plans are to include the prophylactic r:Id-blocking egents c.t cppropriate us2 cf drugs that would reduce the rc.

cuticts for ease of distribution in the f d ead D,vg Ad=lal:esH*a diation dos 2 ta specific organs due to event their use is necessary in a radi.

the sudden ralease into the environ. r.tlon emergency. The report con-erxxktt No.18D-03t31 mint of large quantitles of radioactiv. cludes, however, that the details cf..; %

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DtDE A5 A THYROID-StocKlH 3 ity that might include several radioac. stockpiling, if this method is to be.., Jf.

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, A R ADIATION EMERGENCY tive Isotopes of lodine.

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termined best at the State and local./.E.,,

awest f.e 5.b=1.1.as of New Drus APPW BACKCRoUND g

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p.as and N&e of Avail bil ty of Leben g The GSA notice of December 24, N Ana:.ysts f' *"". :

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• r eedingly low probability that incl.

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Drugs has analyzed the NCRP reportj$5,9; -

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dents will occur involving either the l

and the available scientific literature

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use of radforttive materials in fixed f 0N: 110tice.

nuclear facilities or the transportation about the possible prophylactic use of. $5l:*

(JMMARY: The Food and DruhAd. of those materials.Because of the pos.- drugs to reduce the radiation dose tot'h.f.,*,

,inistration (FDA). requests submts. sible increase in number of nuclear the thyrold gland in a radiation em r.;c.p..-

ons of new drug app!! cations (NDA's) power plants, however, several Federal gency. Although a varlety of chemicil y,*--

substances can block the accumulation.,. M.

er potassium todide in oral dosage agencies are identifying those possg.

prms for use as a thyrold. blocking bilities, however remote, that could of radiolodine in the thyroid gland,l.".c cent in a radiation emergency. The adversely affect the public, should an iodide in' the form of potassium lodide q.

pproval of oral dosage forms of potas-incident occur. One possibility is the appears to be most suitable for this

..,3 om todide as a thyroid.blocktng sudden release of large quantitles of purpose. A number of factors were gent for use in a radiation emergency radionuclides, which might include a considered in choosing lodide (and spe :,.g 7 ould be one step in meeting the re-number of isotopes of radiolodine, into cifically potassium lodide) over other...

aonslbtlities of the Department of the environment. When radiolodines blocking agents such as propylthloura-cil, methimazole, perchlorate, thlo-

ealth. Education, and Welfare are inhaled or. ingested, they rap!dly cyanate, or todate. These factors in-3 HEW) to State and local govem-accumulata in the thyrold gland and cluded the degree of the blocking,q,-

sents for radiological emergency re-are metabolized into organic lodine schleved, the rapidity on onset of the aonse planning. The agency encour-compounis. These compounds could blocking effect, the duration of the.,..

cs interested persons to subm!L reside in the thyroid gland long iDA's in the interest of the public enough to allow for local radiation blocking effect, and the safety of.the t,,-

tiety. The agency is also announcing d==ge, resulting in thyrolditis, hy-blocking agent. Although lodide acts,

on the thyroid gland in several ways, ae ava!! ability of labeling guidelines pothyroidism, or thyro!d neoplasta

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its use in this instance is primarily ir potassium iodide for such use.

with either benign or malignant char-predicated on its ability to, saturate

.DDRN Submit new drug applica. acteristics. Therefore, it is considered the lodide transport system, and thus * :. 4 l

ons to the Food and Drug Adminis in the public interest that State and effectively abolish entry of radiolodine 2 tion. Division of Metabolism and local authorities be prepared to take except for small arnounts that might effective measures to prevent or cur-ndocrine Drug Products (HFD-130),

tail markedly the accumulation of ra enter the gland by diffusion. Almost

m. If 5600 Fishers Lane, Rock.

complete- (greater than 90 percent)..

ille, Ip 157. Comments concerning diotodines by the thyroid gland, blocking of peak radioactive lodine

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should such an ine! dent occur. These.

1e lag guideline and requests for measures may include the use of a. uptake by the thyroid gland can be ob.

nples o. tne guideline should be sent tained by the oral administration of a the Hearing Clerk (HFA-305), Food thyrold blocking agent. -

100 milligrams (mg) of iodide (130 mg nd Drug Administration, Rm. 4-65 An ad hoc committee to the National of pott.ssium lodide) just before or at 600 Fishers Lane, Rockville, MD CouncU on Radiation Protection and the time of exposure. A smalleridose 0857.

Measurements (NCRP), which includ* (65 mg of potassium lodide) can be ed FDA representatives as consultants, used in infants under 1 year of age. A OR FURTHER INFORMATION studied the feasibility of using certain daily dose is required to maintain the

'ONTACT*

-- drug products as thyrold. blocking blocked state. The use of a blocking Edwin V.

Dutra, Jr., Bureau of agents to reduce radiation dose to the agent is not expected to exceed about Drugs (HFD-30). Food and Drug Ad-thyroid gland. The NCRP, located in 10 days ministration, Department of Health. Bethesda, Maryland, is a nonprofit

. Experiments designed to study the.

Education, and Welfare, 5600 Fish-corporation chartered by Congress in of onset of blocking have- * ~

• crs Lane, Rockville, MD 20857, 301-1964 to collect, analyze, develop, and ' rapidity shown that at a 100-mg dose of iodide, 443-6490.

disseminate information and recom* the onset of blocking is readily demon-

UPPLEMENTARY INFORMATION

mendations about radiation protec-strated 30 minutes after oral adminis-ly Frmrx4t. Rects+ca notice of Decem. tion. The NCRP is made up of 56 sci-tration. The decay of the blocking '

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er 24,1975 (40 FR 59494), the Gener. entific committees, composed of ex*

effect af ter cessation of lodide admin- '

1 Services Administration (GSA) out.

perts having detailed knowledge and 1stration is relatively slow, so that a ned the responsibilities of several competence in the particular area of daily dose of 100 mg of lodide (130 mg ' '.9 ' "

ederal agencies concerning certain the committee's interest. An NCRP of potnssium lodide) appears to main-mergency response planning guld. report published August 1,

1977 tain effective blocking. To have the' s '

nee that the arcncies should provide (NCRP Report No. 55, " Protection of greatest effect in decreasing the accu.

o State and local authorities.The De.

the Thyroid Gland in the Event of Re-mulation of radiolodine in the thyroid

.artment of Health Education, and lease of Radiolodine") discusses the gland, the thyroid olocking agent Velf are (DHEW) is responsible for as-safety and efficacy of thyrold. blocking should be administered immediately isting State and local authorities in agents and recommends that potas-before or af ter initial exposure. A sub-eveloping plans for preventing 1.d - slum lodide be considered for thyrold, stantial bene!!t (e.g., a block of 50 per-

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FIDER AL RECl5TER, VOL 43, NO. 242-FRtDAY, OEcEMBER 15, 1978 i ".

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~ctrcumstabtes 41o n;t' permit th dlathn cmmency under ceMn The imports.nce to the public of 5

mediate.adintnistrction Cf potaaslum ready and convenient E.ccess to this CD lodide: the initial cdministration will pr duct and the unlikelihood that it long t will be needed reinforce the Commis-be of some limited benefit even as long '

as 12 hours1.388889e-4 days <br />0.00333 hours <br />1.984127e-5 weeks <br />4.566e-6 months <br /> alter exposure.*WM "

'nc ence of side effects si ner's belief that potassium lodide as.

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• r'n'd!olodine and toxicities, in general, proportional a thyroid blocking agent in a radiation g

ttg tot taken up by[the thyrold directly to dose and duration of ther-emergency should be considered sutt-gl *.

. excreted in tne urine within apy. The risks from the short term use able for OTC use. The Commissioner

• 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />, the radiolodine that is taken of relatively low doses of potassium also believes that special labeling di-up by, and accumulatedjin; the thy-todtde in a radiation emergency are g

rold gland Inay be " leaked

• back into outwelched by the risks Involved from the immediate container of these OTC the general c!/ cub 00ns'ysti m as a exposure to rad'olodine. However, the ae tn i d!de h bee ed t

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at on to eluded on he suc an en o apr o t e-circulatin an r'ec!

g ta!ner label. if space permits, and if e may be en up by the thyrol permit the conclusion that the drug is the accompanying labeling is on file,.

g and (from -the circulatory system) genernUy recognized as safe and effee.

with the Hearing Clerk. FDA. The even though there are no radiciodines tive. Accordingly, it is regarded as a terna!ning in the environment. To pre-new drug requiring an approved new guideline sets forth specific language that would be acceptable to the vent 'or curtall the accumulation of ra-drug application as a condition of mar.

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diolodine by the thyrold gland from keting. Thus, the Commissioner will agency.

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any source, including chronic expo-accept new drug applic'ations rneeting The gu!deline is entitled " Guideline M

Labeling for Potassium Iodide for Use ~.- -

sure. a da!!y dose of a thyroid-blocking the requirements of I 314.1 (21 CFR agent is necessary for a period of time 314.1). Because of the publicly avalla. as a Thyrold-Blocking Agent in a Ra-f-

niter exposure. The duration of time ble safety and efficacy data document. diation Emergency."

that a blocking agent would be re-ing the drug's use, the safety and effl.

The person responsible for maintain-quired is not expected to exceed about cacy requirements of I 314.1 rnay be Ing the guideline labeling is Jo Anne C.

10 days. A minimum of 3 to 7 days of met by citing the published literature Marrone. Food and Drug Administra-daily administration is anticipated in the List of Material Consulted tion. Division of Metabohsm and En-based on the biological events d e-(below) documenting its use. The docrine Drug P. cducts (HFD-130),

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scribed above and the effective half-Commissioner advises that it is unnec. Room 14B04,5600 Fishers Lane, Rock -

life of mI.

emry to submit (1) copies and re-ville MD 20857, 301-443-3520. Coples Potassium lodide has been used prints of the data cited in the List of of the guideline are available from the widely for many years in the treat. Material Consulted in this document. Hearing Clerk (address above).

ment of bronchial asthma and other and (2) copies and reprints contained IasT or 1

m. Consmm in the journals listed in 1 310.9 (21 pulmonary disorders. Dally oral doses CFR 310.9). Both the saiety and effl.

t. Adams, C. A. and J. A. Bonnell. " Admin-of potassium lodide ranging irom 300 cacy data upon which the Commis. 1stration of Stable lodide as a Means of Re-ducing Thyroid irradiation resulting from m ave n

en to asha-stoner bases the above conclusions and Inhalati n f nadioactive lodme," Realth tics over long periods of time. Daily NCRP Report No. 55, " Protection of Physica,7;127-149. 1962.

oral, '"es of potassium lodide of 100 the Thyroid Gland in,the Event of Re-

2. Blum. h!. and M. Elst.nbud " Reduction m/.

• ater have been adninistered 1 ase f Radiolodine, are on file ior of Thvrold Irradiation irois 131 I by Potas-in5 preparations to children. Al-public inspection in the office of the.stum Iodide." Journal of lac American Medi-thou.. a variety of adverse reactions Hearing Clerk. Food and Drug Admin-ca2 Association. 200:1035-1040.1967.

have been reported in connection with 1stration. The Commissioner invites

3. Ramsden. D., F. IL Passant. C. O. Pen-the use of potassium lodide, these re-appilcants to submit any other pertl.

body, and R. G. Speight. "Radiofodine Up-actions are considered in general, to nent studies and literature of which. takes in the Thyroid Studies of the Block-Ing and Subsment Recmry of the Gland be directly proportional to the dose they are aware

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and duration of therapy, and most The Commissioner also believes for n

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.13 6 3 646.19 toxicity has been related to chronic this specific use of. potassium lodide.

4. Johnson. A. E., "The Rate of Retum of administration (see pp. 38357-38358 of and at the dosages intended, that the Radiolodine Uptake by the Normal Thyroid the findings of the Advisory Review prescription-dispensing regulrements After Suppression by Pharmacological Panel on Over the-Counter (OTC) of section 503(b)(1) (21 U.S.C.

Doses of Stable lodine," Hen 2th PAysics.

353(bX11) of the Federal Food. Drug, 9:537-538.1963.

Cold. Cough Allergy, Drcnchodilator S. "Radlobiology 7brum on Radioiodine 3 and Cosmetic Act su unnecessary.

s,nd Antlasthmatic Drug Products Only the chronic administration of Coun 11 o ark res en n on published in the FrnautL Rtctstr.R o daily doses of potassium iodide far in

6. Cronquist. A., E E Pochtn. and B. D.

September 9,1976 (41 FR 38312)). In excess of those necessary for thyrold-Thompson. "The Speed of suppression by addition to its use in pulmonary disor-blocking in a radiation emergency lodate of Thyrold lodine Uptake," Ren2th

.ders. potassium lodide is used in daily have resulted in s!gnificant side ef fects Physics. 21:393-394.1971.

doses rancing from 250 to 300 mg in and toxicities. These problems should

7. It'in. L. A., G. V. Arkhangel'skaya, Yu.

patients for up to 3 weeks in connec-not occur from the short-term use of a O. Konstantinov, and I. A. Likhtarey. "Rn-dionctive lodine in the Problem of Radt.

tion w!th the diagnostic use of radio-relatively low daily dose of potasslum atton Safety. Translation series." USAEC pharTnkceutical drug products to block ' lodide. However* the Commissioner ad-TS36. published in Moscow 1972,1ssued 1974.

the uptake of radiolodine by the thy, vises that the conclusion that a poln-E. Cole.

R., " Inhalation of Radiolodine rold gland. The Comm!sslo I

nWare of reports of sign!!! Cant toxic y tured for use as a thyroid-blocking ures." Contract No. DAHC20-70-C-c381. De-with this use of potassium lodide.

agent in a radiation emergency is sult-rense Civil Preparedness Agency, o!! tee of f EDE RAL Rf-cl51ER. VOL. 43, NO. 242-f RIDAY, DECEMBER 15, 1978

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Swratsry's$ Dif enst. WasWngTEih - tl:n t.nd th2 Induction oil (2nusort.nyu IIcaring Clerk docket no. %@@JJW W

-2, cant Disease In the Humtn Thyrcid Oland.

63:957-978 the guideline labeling to the Hearing Saxent T.'-M.?e'; al. " Minim:1 Dosagt Amertctn Jaurnal of Medicine.

Clcrk (!!FA-305). Food and Drug Ad-

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podide Reo'utred to Suppress Upttke sf 4-65. 5600 Fishers

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1977.

16. Rtdiaurn. Associated Thyroid Carcino.

ministratJon. Rm.

.i ane431 by Normal Thytold. Science.

ma. Edited by 1. J. DeGroot with L A.

IAne Rockville. MD 20857. If, as a

• s. A. O. et al " Iodide-In-Prohman. E.1. Kaplan. and S. Refet.off; result of comments received on th.

.-:3 c430-431.1962.

& Vs:(

Icosts in Boston." #cto Eng-Grune and Stratton. Inc. publishers.1977.

guldellne labeling; the Commissloner

.:.g 4d The Nedicine. 287.523-527.1972.

17. Iengemann. P. W. and J. C. Thomp-determines that the labeling should be

-j d Jom$. Eafety Study-An Asses.sment Therapeuuc

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Measures for Radiolodine Contamination" revised

• a notice will be published in

• y*g o son. Jr " Prophylactic and 1."He h AccidInt Riska in U.S. Commeretal Nucle.

Power Pls.nts. Appendix VI. Calculauon #calth Physics. 91391-1397.1963.

the FEDERAL RECISTER announClng that

. a..:--Q 4 s,uch changes have been made.The Comm U.S.

Retetor Acetdent Consequences.

.18. Pochin. E. E. and C. P. Barnaby. '-The clett Re gulatory Commission. Report Effect of Pha.rmacological Doses of Non Ra.

dioactive lodide on the Course of Radiolo.that this document does not contain WQi 4

4SH-1400. NUREO 15/014 (1975).

2. N AtlIna) CounCU on Radladon Protec-dine Uptake by the Thyrold." #ccItA Phys.

an agenc9 action covered by $ 25.1(b) N' n Report No. 55. " Protection of the ThF-

19. Conard. R. A. et al., "A Twenty Year (21 CFR 25.l(b)) and, therefor'e. con.

icJ. 7:125-126.1962.

..e d Gland in the Event of Relesses of Ra*

elodina." National Council on Radlauon Review of Medica 3 Findings In a Marshal.

sideration by the agency of the need environnen,al -

otscuon anc Measurements. August 1.

lese Population Accidentally Exposed to Ra-for preparing an dioactive Pallout " Report BNir50424 Impact statement is not requireu.

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U.MJ,**d.,8"',(Qb 77.3. G1nera] Services Administrat!on P& Brookhaven National Laboratory. Upton.

Dated: December 8.1978.

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.g LL Rrr.tsm notice. 40 I R 59494, Decern-

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14. Talbot. J. M K. D. Fisher. and C. J.

20. Goodman. I. E. and A. Gilman. tac

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r 24.1975.

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Pharmacological Basts. of TAertapeutics.

ward Rsacdons to Jodine in Foods."

5th Ed., MacMllian Publishing Co, Inc.,

Commissioner of Food cnd Drugs.-.:M.

.tr, "A Restew of the Significance of Un.

s IPR Doc. 78-34843 Mled 12-14-78{8:45 aml,,g

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