ML20099J500

Applicant Exhibit A-147,consisting of Undated Photocopies of Pages 85,200,498 & 499 of Effects of Ionizing Radiation

ML20099J500
Person / Time
Site:	Limerick
Issue date:	05/22/1984
From:	AFFILIATION NOT ASSIGNED
To:
References
OL-A-147, NUDOCS 8411290084
Download: ML20099J500 (6)

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,f increase TABLE IV-2 Genetic Effects of an Average Population Exposure of 6 i will bear - 1 Rem per 30-Yr Generation f3 mutation y D/\

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tal to the ;g: Typeof Genetic per Mion Uset>orn i %;

1 Disorder

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in heterozygotes incrLase

}ullibrium f accounted for in l top row Q our adop-( Chmm s mal 6.000 Feu er than 10e Increases Q j 8-250 rem) h aberrations / only n-p slightly e; th,is was -

t 7 44 ge is most

• includes disorders and traits that cause serious handicap at some time during lifetime. A g'

, 6 Estimated directly from measured phenotypic damage or from observed cytogenetic effects. ,.

w ? Estimated by the relative-mutation-risk method. a .  ;

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$r dNo first generation estimate available for X-linked disorders; the expectation is that it }{I u and um- $e ,would Some be relatively estimates havesmall.

been rounded off to eliminate impression of considerable precision.

Ion-caused flncludes only aberrations expressed as congenital malformations. resulting from un- p t is in close k(, balanced segregation products of translocations and from numerical aberration. ,

4 8 Maj rity of Subcommittee feels that it is considerably closer to zero. but one member feels

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that it could be as much as 20.

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estimated i( slowly,recessive traitsandwould anybe effect ofaan spread over veryincreased large number of mutation generations. rate on the incidence of The population survey in British Columbia reported that at least 9% of

$q nt for only type is ex-g; g.all liveborn humans will be seriously handicapped at some time during j autosomal n their lifetimes by genetic disorders of complex etiology, manifested as con- M oduced by f genital malformations, anomalies expressed later, or constitutional and S (

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$ egenerative diseases. This, the larges- category of genetic disorder listed matter, see hin Table IV-2, we refer to as " irregularly inherited" disorders. The muta-y@

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498 Tus smCTs OF IONIZING RADIATION .,(- 8omatic s,,,.,.

spermatocyte is relatively radioresistant, in comparison with its progenitor ^

E W cells. Single acute doses of SD0 rads or less cause significant cellular '

"##"## 88M i damage in the testis; these changes are dose dependent, with complete Populations >

recovery after doses of 600 rads or less, and with the time until recovery ; proliferating sperd also dose-dependent, extending up to 5 yr. below 400 rads (

the spermatogo '

I*iIctous epit Atomic-Bomb Survivors and proliferating

- Information on impairment of fertility in man is available from the study much greater tha of atomic-bomb survivors and from Marshallese and Japanese who were '%

- inadvertently exposed to fallout during atomic-bomb testing in the f atImpairmen't the testisofcould f l

Pacific.l5." 06 # 8# The data lack precision, but demonstrate the follow- j, ovary in the range .

ing: Relatively low doses can decrease production of sperm cells, but ef. 'Q but this depends,is fects on spermatogenesis are transient; the sterilizing dose in the male is that women appro$

probably much greater than about 400-500 rads, i.e., it probably exceeds I of fertility or q the mean lethal dose to the whole body. Fertility is impaired in the oocyte g sient infertility ass population only after moderately high doses-200-400 rads. Little is ]; associated, in part,I

[- known regarding the delayed effects of radiation on fertility in these ex- g physiologic atresia posed populations, nor is there information on the extent of impairment, 7 if any, in the male and female populations exposed in utero and in thei F ' i

populations of exposed parents. sas.ie Followup studie; of the Japanese J CATARACTS atomic bomb survivors and the Marshallese women exposed to tellout g- .j have failed to demonstrate any long-term effect on fecundity.6. 5. 4.12 A causal involveme h,k the germinative zon;,

been proved. How Radiotherapy Patients and Victims of Nuclear-Reactor Accidents kg strongly suggests thi Clinical data are available on male radiotherapy patients and men ex.4 affected cells into at posed during criticality accidents at nuclear-reactor installations.#.12 $ the appearance of I s

Careful sperm-count studies after limited partial-body radiation exposure % epithelial cells into' f' have indicated that, if sterility occurs, normal sperm counts can return in '1) cells in the posterior j about 1 yr after doses of 100 rads and even in 3 yr after exposures in the resulting in a loss of g near-lethal range."12 Acute whole-body exposure has not been shown to ;,, opacification depent cause permanent sterility in males.12 The sterilizing dose therefore ex. zone. The sigmoid c. I ceeds the lethal whole-body dose for acute radiation. Similarly, steriliza. i of partiallens shield radiation cataractog g

tion of the human testis has never been shown to result from continuous or fractionated (protracted) low-dose exposure.30.w.i44. 4a g( The available data In women, radiotherapy experience has suggested that acute doses of Q apparent threshold !

) 300-400 rads or slightly higher doses given in two or three fractions result % rays and gamma ray in permanent sterility.2.is.45.53.ie If fractionation is protracted over a 2-wk T rads, whereas the thi

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period, much larger doses (possibly 1,000-2,000 rads) are required for '.f is around 1,000 rad:

T sterilization, depending on the age of the woman.2.is.45.ie The ovaries of y vivors of Hiroshima

{ The subjective natur f younger women are much less radiosensitive; permanent sterility is more p likely as the menopause is approached. t vestigators involved i c

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cis or sonizzuc nronrrn Somatic Effects: Effects Other Than Cancer 499 ,

WParison with its progenitorg , Conclusions p e er 7gnificant cellular % "

ode :nt, with complete .i Populations of mature spermatozoa in the human testis are maintained by eith the time until recovery X , Proliferating spermatogonial stem cells. Provided that the dose remains Q below 400 rads (low-trT radiation, acute exposure), radiation depletion of u j 3A

• the spermatogonial-cell population is only temporary, and the seminiferous epithelium is repopulated and regenerates from surviving 4: and proliferating spermatogonial cells in the damaged tissue. Exposure i is available from the study ?,i .

much greater than this (perhaps by an order of magnitude) directed only ese and Japanese who wereg'- 4 .

at the testis could probably result in permanent sterility.

omic bomb testing in the Impairment of fertility can result from absorbed doses to the human but demonstrate the follow. ovary in the range of 300-400 rads (Iow-tzr radiation, acute exposure), ,

" tion of sperm cells, but ef. but this depends, in part, on age. Radiotherapeutic experience has shown trilizing dose in the male is that women approaching the menopause may have long term impairment l ds, i.e., it probably exceeds M - of fertility or permanent sterility, whereas in younger women only tran- .y iity is imptired in the oocyte M sient infertility associated with amenorrhea may result. This may be i s - 200-400 rads. Little is ; associated, in part, with oocyte populations, which decrease primarily by b

. ion on fertility in these ex ' ' Physiologic atresia (and to a much lesser extent by ovulation) with age.

, a the extent of impairment, >

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, >osed in utero and in the F

.up studies of the Japanese CATARACTS ' I women exposed to fallout

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t on fecundity.6.is. 4a.i65 % A causal involvement of radiation-induced damage of epithelial cells in @

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the germinative zone of the lens in radiation cataractogenesis has not yet ' h] (.M %

-Reactor Accidents  ;

f been proved. However, the available evidence from animal studies strongly suggests this mechanism, on the basis of the differentiation of the l

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' N$h g, rapy patients and men ex affected cells into abnormal lens fibers and the time coincidence between r- q installations.90 865 g the appearance of lens opacification and the rate of migration of lens

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!i - a ia bdiation exposure" sperm counts can return in ePi thelial cells into the posterior lens cortex. Accumulation of aberrant cells in the posterior cortex causes alteration in the lens cytoarchitecture,

' fjg 3 yr after exposures in the h resulting in a loss of transparency. " There is no direct evidence that lens W isure has not been shown to g. 0 Pacification depends on the killing of epithelial cells in the germinative . .-

erilizing dose therefore ex. Y zone. The sigmoid cataract dose-response curves and the protective effect  ;

listioni. Similarly, steriliza- j of artial P lens shielding provide evidence that other fac'c rs are involved in ( ^? y 2 *) result from continuous y radiation cataractogenesis in addition to cell-killing. .

, 3a.go.i44. i4s y '

The available data suggest a sigmoid dose response re ationship with an hgested that acute doses of 7 apparent threshold for lens opacification. Threshold doses in man for x rays and gamma rays delivert.d in a single exposure vary from 200 to 500 wo or three fractions result M 2n is protracted over a 2-wt ;- rads, whereas the threshold for doses fractionated over periods of months ' []

000 rads) are required for i is around 1,000 rads.' Continuing observations of lens changes in sur-san.2.isas.i65 The ovaries of P '

vivors of Hiroshima and Nagasaki have been reported.n4s.saa2.s4.ioo.iei permanent sterility is more The subjective nature of the lens assay techniques used by the several in-

, vestigators involved in these studies, as well as the limited dose informa-g n

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