Position Document 1
(U.S.) Environmental Protection Agency
Arlington, VA
17 Jan Y?
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NOTICE
THJS DOCUMENT HAS BEEN REPRODUCED
FROM THE BEST COPY FURNISHED US BY
THE SPONSORING AGENCY. ALTHOUGH IT
IS RECOGNIZED THAT CERTAIN PORTIONS
ARE ILLEGIBLE, IT IS BEING RELEASED
IN THE INTEREST OF MAKING AVAILABLE
AS MUCH INFORMATION AS POSSIBLE.
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Lindane: Position Document 1
Lindane Wording Group
U.S. Environmental Protection Agsncy
1 7 JAN 1S77
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50772• )Q ) — -
REPORT DOCUMENTATION 2. PEPORT NO. 2. 3. Rsclplents *c e. on i c
PAGE ___E?A/SP D -8O/I 3___ PB 80 2138, 1
4. Title end Subtitle S. Roped 0.1.
1/17/77
Lindane: POSITION E U? . 1T I —____
7. Author(t) - 8.Perfonning Orga&z. liop RopiNo — —
9. Performing Orgenization Name end Addrn. 10. Proiect/TeekIWork Unit No.
Special Pesticide REview Division ______
ENvironmental Protection Agency ii. ConrractC or GriiittG No.
Crystal Mall 2 IC)
Arlington, VP (C)
22. Sponeor.ng Organization Nima end Addm; 13. Type of Report & Period Cowered
Eniironmental Protection Agency
401 M St. S.W. I ___
Washington, 1?.C. 20460
IS. Supplementary Notes
IS. Ab tr.cl (Limit 700 word I)
Preliminary Risk Assessment: Examination of possible unreasonable
risks associated with uses of pesticide and a gathering of all available
information to determine whether or not this or any othef risk does
exist. Initiates literature search and evaluatns risk data. Limited
infermation on exposure to forecast extent of risk.
11. Document &n.i).i.C • De crfpto,.
O5O1 ,o6o6,oTo3
b. ldcntirierelOpen Fndod Teren
C. COSATI field/Group
t•. . “-burly Stalcm.n ]ic. Security Cizie (TP.. Report) 21. No of Page.
Release Un1im ed UncJassifi .d _____
20. S curlt dais (lbs P.30) 22. Price
UneIassif ed I
(S.. ANS 1—239 13) 5.. inotruction. on R. e,,o OPTIONAl. FORU 172 (4—77)
(formr ly N iS-35)
Department of Commerce
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Liadane: Po LtLon Document I
C0UTE 1T
P at a
S ummar . . . ..... . . . . . . . . . . . . . . . . •..... . . . . . .. . . . . . . . . . I
t. Background...... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
A. Eav iron ieacal. Chemistry.. ..................... 2
C l) Geaor L.................................... 2
(2) Ras1duns....... ........................... 3
(a) Vater.................................. 3
(b) Air. ................................. 3
Cc) Soil................................... 4
(4) Plants andAaima1s............. ....... 4
Ce) Tood..................... •........., •. 7
(f) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
3 • letaboiism..................................... 9
C. Studies en the lsoe&ertza:ion of Camma—8RC
to the Alpha and Beta Lsomers.................. 10
D. Regulatory Eistory. . . . . •• • • • .. ••s•S•• s . •. • .. . . 12
£. aegisto d Uses and Production................. 15
U. Summary of Scientific Evidence to Support
Rebizttab La resump t ion... .. . . . ... .. . . .. •......... 17
. Chronic Toxicitv....... 5 •...................... 17
(1) Oucoganic Effects Li Test AnimaLs.......... 17
(a) Sttidies La Which Dicta y CammA—BRC
produced Oncogeaic Changes La
Rodeats................................ 19
(b) Studieij Reporting Io Obeeeved
Oncogenic Eflec ts... . .. . ... . ..... ...... 20
(1) Mouse Studies..................... 20
(ii) Za t S t ud I as. . . . . • . . . . . . • . . . . . . . . . . 21
(2) Reproductive and Fetatoxic Effects La
}lammaltan Species. ......... . s...... ...... 21
(a) Gr ieh, faturatLou, and Reproductive
(b) Reproductive Capacity, eracogenesi.s,
and Stillbirths LaDogs................ 24
3. Acute ToxicIty: aazards to ZL.Ldi.ife........... 26
(1) Aq’iatjc Species......................... .. 26
(2) Lv Spec les............................. 30
L I I. Other ReL i ant Any er e ffects................... 30
utagean ....... ....•.......... ... ..
3. Ee otoxLc .ffec:s 31
(1) Sload Dyscrasias AssocIated it:h
Exposure to 32
(a) Aplastlc Anemia and Llypopiastic 3one
.... •.. ......... .. .. 32
(b) Other 3lood Dyscras ias................ . 3
4.
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Pa e
(2) Cas s InvoL’,L g £zposuze to Linda s i
C05bLLstioft vith Oe zer Cheiai ais.......... 34
ta) Aplastie Ano ia sad Hypoplaseie Boas
••••.............. 34
(b) Othar BLood D’scrasias.,....,...,..... 34
(3) Zpid aioLo ica1 Coasiderations............ 35
C. Ae zto Hazards o Humans and Do ostic Aninais... 36
0. Papu.Lation Rednetion La ontargst Or aei ns.... 37
(1) Liadane Residues in Birda................ 38
(2) e.fEec t an Roproduccive ‘..apacity........... 39
List o &i ferences.......... .......................... 41.
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POSITION DOCUMENT, 1
Tec mic L Lindans is at Least 99 gamma—aaC, the
ràmainder being other C isomers.Thu £nsecctctd L proper—
tics of benzeaa bexachioride (!UC) were discovered and
d we1oped for ca5mercial. use in pest control in 1942. Zhen
I .e was found that virtually all, the iasoctt24a1 activity of
BRC resided in the gamma isomer, major devslopmenc of the
latter as the insecticide called Lindace was ra,Ld. t.in 1an.e
h4s had. major use in insect control in domestic and co i r—
cial settings, in numerous agrieui.cure and silvacuicure
applications, and as dips, sprays, and dusts for LLvestoci
and pets. There are currently 557 federal registratLons foi
pesticide products containing L. .ndane and 87 for er1y
state—registered produ:ts containing tiadane for which
federal registration has been requested.
In 1969, the Departnenc of Reaith, Educac ou, rind
Welfare (aE’J) recommended in the Report of the Secrecary’s
Commission on ?esticidas and Their ReLationship o Eovi:onnr.-
tal Raalch ( rak Report), that the usage of Li darte aloug
with that of other named persistent pesticides, be restrictcci
to specific essential uses which create no hazard to human
health ar to the quality of the environment and which are
mmanimously approved by the Secretaries of the Depart tencs
of eaLth, Education, and Welfare; Agriculture; and Interior
(1). It was noted that these pesticides cause or cart cause
contamination of the environment and damage to vaiious
speci4s within it.
anicoring data show that 1in t, ne occurred in 0.77,
1.56, and 0.56 of sanpies coLlected during the years 1970,
1973 and 1974, respectively. The geometric mean Level of
Lindane in the adipose tissue of the general population
for the years 1910 to L9l i less than 0.1. p m on a
lipid. basis.
Residues between 0.1 and 16.2 ng/n 3 were faunA a ambient
air samplies .a 5 U.S. cities Ln 1976. Lindane residues
have been found in ra nvacer ani drInking water. ResLdues
detected in the REW—USDA arkec 3asket Survey of foodstuffs
have been veil under the average daily .ncako Level deemed
acceptable by the rood and AgrIcultural. 0r anL:atIon of the
World ealth OrZanLzatioa.
The possLbility exists that Lsonertzation o llndane,
ganna—BEC, to other isomers cahas place under certain
cond t ons
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Lindane accu ’zlaees in tissues, although not to the
same extent as many other eh.Lortnated hydrocarbon insecticides.
Upon cessation of feeding much of the lindane appears to be
eLiminated from the bodies of laboratory rodents in the forn
âf substances of relatively 1u toxicity.
Administrative actions resulting in canceLlation
have been taken against the registration of lindane products
for certain uses including “continuous” vaporizers, use on
certain agricultural crops and dairy cattle, and in dairy
brns and milk roams. The use of “one—shot” lindane vapor-
izers is still registered.
Adaqu be scientific evidence exists to initiate
the rsbuc:abi.e presumption againit the registrarion of aLl
pesticide products containing lindane on the basis of
onc genicity, chronic reproductIve and fetocoxic, effects,
and acute effects on aquatic orgaatsms.
A number of humafl pestIcide accidents Lovolvtng Lindace
save been reported. Renotoxic effects in humans and possible
reproductIve effects in noatarget avian species have been
noted and are described in thls.position document. These
effects have not been used to initiate the rt buttabte
resuupcLoa, but additional. data viii be solIcited in the
Rebuttable Presumption Against Registration Pederni Register
etice. (See Sections IU. S., C., and D.)
Registrants of lLclame products viii be directed
F° certify to the Agency their determinatIon as to uhether
the fornulatious registered for use meat or exceed the acute
.rmaL a d inhalation criteria of 162.ll(a)(3)(i)(A).
t. 8AC GROU
A. nvironmer.tal Cbenistrv
(1) GeneraL
Lindane is the gamma isomer of the insecticidal
chemical benezene hexachioride, BRC. Technical lindane
must contain at Least 99 gamna—BRC, the remainder beIng
other 3HC isomers. End—use LnsectIc!.d p oduets contain
varying percencs.gas of active .ngre4ient.
Ssnzene hexachioride (3!C) is the ounou cane used to -
desi nace the nized isomers of .,2,3,4,5,6—hexachioro—
cycLohexane, although l,2,3,4,.5,5—hexachioroc’ ciohexaue is
the proper tarn for these isoceric cocp. unds. 3 C (:echnicai.
gra4e) is a mixture of the eight possible Lsom r which
constitute the different spatiaL orIentations of the six
chlorine atoms on the chair forn of the rclohexane ring.
—2—
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Its co ositton approzimates 65 alpha, IL beta, 13—L4Z
&am*a, 8—9 4etta and 3—5Z other i ers. Technical B C is
coz.only prepared by phocochiorination of ben ene. Produc—
tioti of the ga tt a isomer for lindane is achieved by selective
extraction (2).
(2) ! csidues
The presence of tindane in sites far removed from any
aaplication suggests that this chemical has world—wide
dis tribut ion.
!.Lndznc residues have been found, for example, in
rainwater samples from several countries (see Section
I.A.(2)(t’)), in birds, penguins, skuas, and cormoranes;
fish, foeat eria p.; and planktonie krill in Antarctica
(3); and i.n seals and an arctic fax in Greenland (4).
(a) Water
Lindane, which is soluble in water at 10 ppm, is one of
the most solub la of the chlorinated hydrocarbon insecticides.
Tram February l 75 through June 1976, the TationaL Water
onicarisg Program’s survey of unfiltered water samples
detected Lindana in OmIT C single sampLe from Eavaii at a
level of U.OL ug/liter. About 850 water and 425 bottom
sodiranc samples coLLected from sites throughout the nation
have been analyzed for lin4ans since the start of th .s
survey (5).
Laboratory eXamination of drinking water from various
sources across the nieed States by EPA’s Water Supply
Program revealed that, of 684 samples tested far pesticide
residues, lindane Levels of <0.001 tag/Liter were found at 37
sites, (0.100 tag/liter at 16 sites, 0.160 tag/liter at I
site, 0.200 ug/licar at 1. site, and 0.900 tag/liter at 1 site
(6).
(b) Air
Lindane has a vapor pressure of 9.4 X 106 mm
at 20° C and is more volatile than msc of the commonly
occurring organochLori2e pesticides. During the years
1970 to 1972 Lindane resi.dues were found in 68 of :,479
ambient air samples from l to 16 seLected states. The
arithmetic mean for all samples was 0.6 mg/n 3 , and the
mean far positive samples was 0.9 mg/m 3 . In 1976, how-
ever, lindane was present at higher levels in ambient
a ir samples La some regions of the country. lelativety
high residue levels of aLpha—saC ere also found. Alpha
isomer residues are reLevant to our concern about liadane—
use if is.me:iz.ation of lindane is taking place in nature
a
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(see Section t.A.(2) and t.C .). Tbe levels detected far
alpIia—3EC and far Lindane (ganna—3KC) were, respectively,
2.6 and 2.2 ngln 3 ia Miani, florida; 13.9 and 0.3 ig/n 3 in
Port Collins, Colorado; 2.9 and 0.5 in Lafayette,
Indiana; 3.3 and 16.2 ug/n 3 in Jacksou, tisotssippL; nd
4.3 and 0.4 in aarrisburg, PennsyLvania (7).
Lindane has also been detected in rairtvater in several.
countries. Lindane residues were Zo’.&nd in rainwater in
the British Isles aver a 12—nonth period with a nun of
44 parts per i0 water (8). Lindane at levels of 46 to i oz
nano rans per L Iter of rainwater was sresent in all of 12
anpLas of rainwater taken over the pity of Berlin Dablee,
Iesr Gernany duria a 1—year perIod, June 1970 to 1tay 1971
ç9).
Traces of BRC were found La 34 of 90 rainwater
aawples fran 3 Ohio sites (l0 . This study noted that
recent evidence had shown that report.&d pesticide con—
contratious La rainwater were Low, p arhaps by a factor of
2, because the nethod used to collect sanples resulted L a
ineonpláte renew cry.
Ce) Soil
Lindans is elininated fton soil at faster races than
nose other chlorinated hydrocarbon insecticides but is
persistent when conparud vit i other classes of pesticIdes.
Soil, treated with lLadans and analyzed over a 15—year
period showed 0.22 of the lindanc renaming at the end of
that tine (11). 4 siniLar east in the Uethurlands shoved 3
to 32 of the Liadane renamed in soiL test areas after 13
years (12,. kvailabl .e data indicate, hawev.er, that lindaeo
residues La soil, are Lw. EPAs TatLona1 Soils oaitoriag
Pr gran has reported that Lindane has seldon been detected
in soils sanpLod. t 1969, O.9 of the 1,729 cropland sites
sanpiad had decectab e lindace residues. Levels found were
between 0.1 and 0.035 ppn. Ia 1970, the per entage of
cropland sites with. detectable lLndane residues fell, to 0.4
of 1,306 cropland sites sanpted, and lindane residues vas.ed
between 0.01 and 0.15 ppn. The prcgran was not •3perated i
1971. In .‘72 and 1913 no residues were derocr . d (13).
Cd) Plants & AnImals
Results fran .1.indane residue surveys i dicate that
low l e vels of lindana are present in sane plant and artinal
populations. The anount found i plants depends upon narty
factors LnciurL ng the crop and t soil typ .
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LLndauo residues have been found in natural bird
pop ijationa. Watson and Mor an (14) reperted the foLl.oving
Lindane r isidues in the carcass of a golden cagl.e found in
Scotland in 1963: 0.03 ppn in brain, 0.14 ppm i. fat, 0.66
ppm is, nu ci.e, and 0.02 pp La liver. Birds of prey and
owls ound dead or dying in the Netherlands during 1964 bad
considerably higher Lindano r uid’.&ee than isuai1y reported
in these bLrc i (2). t.acele found were: Liver, 0.3 to 28.6
ppm; brain, 3.2 o 17.7 ppn; breast vssc’s, 1.6 to 18.4 ppu;
and mesenteri.iJ. ac, 11.0 to 89 3 pp . !.iader and Dahigren
(2.3) analyzed Lindane levels in the eggs and adult tissues
of wild pheasants collected in eastern South Dakota between
1964 and. 1969. In this stu iy it vas found that eggs taken
from three different areas at two different periods (early
May and late .Iuna)had levels of L ndan. ranging from
0.02. to 0.04 ppm but Lindane residues were detected in traco
amountS (<0.05) in the tissue f only 2 of 100 birds exaisined.
Over seventy—five percent of tire grouse and pheasants
analyaed in the central portiqn of South Dakota between 1965
and 1967 had 0.01 ppm Lindane residues or Lass, and the
remainder bad less than 0.20 ppm (21). Greichtas cC si. (16)
found lindane reaLda es of 0.07 ppm in zuscl.n and 2.8 ppm in
fat of pelicans and carmorants which were part of the food
C : . ‘f a freshwater lake.
Starlings collected fran 128 sites throughout the
U.S. during 1967 and 1968 h d lS .ndane residues between, zero
and 1.25 ppm. Moat residues were below 0.02 ppm, and only
two ware over 1 ppm (20).
Analyses of wings of black ducks and mallards taken
along all ea ar U.S. f1yvay have shown an increase in
lindaue residues in recent years. During tha 1965—1966
buntLng season, trace amounts of lindane were found only in
some of the bird i killed in Sashi gtoa and Iichi an (17).
During the 1969—1970 season, no Llndane residues were
detected (18). In thu 1972—1973 hunting season, however, 75
of all bLack. ducks and sai.lards taken had Lindane present in
trace amounts in their wings (19).
tindane residues have also beeu found in birds
and their e;gs following laboratory feeding. Liska at si.
(23) sprayed a grass—covered range with 0.1: lindane
emulsion at a :ate of 0.3 lb/acre and assayed lindane
residues in groups of turkeys placed on the range at d 1far—
ant intervals after the pestLcide was applied. Lindane was
found at 2.1 ppm in the fat of turkeys pJ.aceci on the range
tmmedi.atei.y after spraying, at 1.0 ppm in turkeys placed on
the range one week after spraying, and at 0.7 ppm in turkeys
placed on the range weeks after spraying. S.Lsilarly,
Stadelnan at aL. (24) reported chat fe.edl g turkey hens t .1
to 0.13 ppm L ndane—t:eated seed for 14 days resulted .n
only transient traces of lindane .n. t±ssues, but that “hen
10 to 15 ppm lindane vas supplied in the feed for 3 days,
lindane residues were found in body fat and eggs for 13
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weeks. St dc1nan (23) revLe .d studies publ.tshed betwe:n
196. and 1972 which reporr.ad the occur ence of lindane
residues La avtae tissues and. eggs.
In another experiaentat study, Ash md ‘ ay1or (26)
assayed. lindane residues in pneasanc eggs atid adult tLaauos.
Twenty —fo ur birds were fed li.darxa’dreósed oed for 32. days.
Lindane levels on the seed ranged frog 52 to 117 ppe. Tht
a t.tors cati ated that each bird consusod appr ’zisateLy 0.5
g lindano er day &nd that the 430 eggs Laid during the
poriaeutal period contained an average of 1.0.7 ppu ndane
indicating that soie of the die ry pesticIde was e crets4
via the egg. Within 9 days, 2/3 of the initial L.,d aa
residues had been excreted.
A tent. (27) in which pheasants were fed as I.%ch
14 C—Liadane treated seed as hay would eat in one day (an
esttmatad 9.OC to 14.15 sg of lindane per bird) esuLeed
in liedans residue levels of 1.1.2 and. 2.48. ppe La nuscis aac
Liver, respectively, one day later. These l,,els, however,
decreased very rapidly, and no residue cou d be detected
after 1.4 days. The ingentLou of less lindane— (525 to 860
seeds) than hoptac1 3.ar—creaced seed (590 to L24O. seeds) was
believed duo to less palatability of the Liadanè—treated
seed.
This rosul.t was aL o noted. in the Ash ar’ ay1 . “td)
(26) which de ionstrated ttat pheasants a n v * .eL. . c;nc to
eat liadaae—e:eatad grain. I this Labor: . ory test. p?laasant’
would ingest lLndane —trea ed seed on ly after they ware
gradually condLt oued Co eat Larger amounts of pesttcLde in
their diet, and then only when the application r was
reduced to 1/3 the nornal dose. These pheasants still
con uasd 14 less seed than the controls.
Same research suggests that birds nay be killed by.
lLadauo but that detected restdne levels nay not reflect he
cause. Trench and Jsffertes (Z8), for example, denonscracad
that durtng the first. 24 hours after death degrada: c’r’ of
Lindane occurs rapidly in the liyer of tabaratary pigeons
force—fed gelatin capsules coata. . iag i.indaoe. aesidues ere
found in the Livers of 3 pigc aes killed :fter being fed 0
ag/kg liadane for 72 hours and 2 pigeons which died after
being fed 225 ng/’tg lindane for 1.44 hours. !ai tal LLver
residues after death Lu one of the high dosage bir3s was 153
pm. 3y the end of 630 hours, the residue Level fell, to 2
ppa. Lindane residues in the L.i.’,er of the second hL h
dosage bird, which ware not neasured at death, were ;p a
430 hours. aapid degradation of Iladane residues also took
place in the Livers of the low dosage pigeons. aes .dues
‘neasured one day after death had fallen oalnoat ai.f of
the Ln ctai. level neasured Ln edLatej7 after death and
continued to decline thereafter (ZS).
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The 1972—1973 resutt.q cf the fish ouitorLng progran
conducted by the Fish and J 1.d1i±a Zanies, USD1, iadLcaced
c ac SEC. includIng Lindana, ias in the group of p*sttcidas
vbjc b vets found in 3 or Less of the sampLes taken during
those cvo years (29). A study by Ga.kstactor and ‘Jeisa (30)
t potte4 that vich n 2 days after being pLaced in clear
vatar the initial. lindans cnstduas had been aJ.ininaced by 2
sp eiez of fish, bluagilLs and oLdfLah, exposed to water
contaIning 0.03 pp Lin(auc for 32 days.
Trot October 1968 to ZuLy 1970, shellfish fton 10
estuaries in T oug Island, 1.T.. were collected nonchly and
examined for C orinacad hydrocarbons as part of a cancinuiig
uationv .do urvey conducted by the aciocaL Marine Fisheries
Service of tho .S. Departnenc of Commerce. o lindane
residues were found (31).
There are fey 1inda e rssLdue scud Los in naeals
in nature. T4:dans resL uos becvesn 0.1 and 0.08 ppn were
found La 17 of 47 large game aninai.s taken in South Da oca
(32). I c was macad th. c thcr was only limited use of
lindane L a South skoca.
T4mdane residues have a so been found in the adipose
tissue of arctic animals kIlled in 1972 on the vest coast
of Greenland (4). Lindane w s detected in 5 bearded seals,
0.007 to 0.64 ppm, 2 ringed seals, 0.002 and 0.025 ppm,
1 hooded seaL, 0.317 ppm, and an arctic fox, 0.010 ppm.
In general, Lindane storage in the fat, milk, and
eggs of animals Li Lass than, chat of ocher chlorInated
hydrocarbon insectIcides.
Ce) Food
The VorId ffaalth Organization (TJEO) and the Food
and Ag:Lculcur L 0’ganizacion (TAO) of Lha United acions
have sac an a.csptabla daIly tacake (A I) for Liadane of
I.2 I L0 :g per kg body weight. The ADI is a dosage
(as determined by 0/FAO) vhIcr , LZ ingested dai!.y for
the LifetIme of an individual., is assumed to be without
appreciable rLsk. SEW’s “ 1a ,rkuc 3asker. Survey,” conducted
by the Food and r .ag Administration La cooperation with
the Department of Agriculture, monitors cecain pesticIde
residues In the sample dail7 diec of an average L6—co—L9—yea:—
old. Amet’.can male in various regionr ..f the country.
!.i dane residues in the dLe: as measured under these arke:
3asket Surieys have been con iderabl7 Lo r than the 1!O/FA0
acäeptabla Levels. Far the five—year period from L96i . to
L9 9, the average daIi.y dietary intake o Lindane was 5.0 X
L0 5 mg/k; accordIflg to the F A 1arkec 3áskec Su ey. Zn
general, the hL; est residues La f Qd Lnc nded far human
c nsumptIoa appeared, in descend±ag order, in neat, grain
and cereals, daI: ,rodue:z, eggs, and pou.L:r,.
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The incidence and the amount of lindane residues
in foad tuffs varied. Oul.y trace amounts, <0.005 ppm,
found as an average in raw products of most food groups
durtng the 3—year par 4 .od. Levels above trace amounts in
these ray products were found in the fat of imported dairy
products, 0.02 ppm; in iamestic tree nuts, 0.01 ppm; audin
domestic and impor; moat La 1968—].969 only, 0.01. ppm (LL4).
The average if sost Lindsue residues found La samples
of ready a—ear foods from the major food groups were below
0.001 ppm, but the average for vine and ear craps was 0.002
ppm; far the grains sod cereaLs group, 0.006 ppm; and for
meat fat for 1968—1969, 0.1. ppm (114).
It must be remembered that these fLguros represent an
average which imd1.vtdu.aL samples exceeded and that risk of
ingesting LLndaa may be dIfferent for certain segments of
the popui.atlou because of such factors as diet and susceptt—
biliry. In 196a, far e aspLe, lindane was present In
poml.try meat at Levels of 0.01 to 3.0 ppm in L0.6 of 2,679
samples; in 1971, Ilodane levels of 0.01. to 0.5 ppm were
reported La 51 of 1, 904 sampLes. ThLs represeo:ed a
rsducrLan in the Lindane level. cod in the proportion of
samples i.tth resid.ue during this 3—year p rtod (1C9).
— —...Xore recently, lindane residue Levels in food have
dropped (33). In L973, although detectable amounts were
found to 10.8: o cli samples, oniy 2.22 1 L0 4 mg/day v s
present La the diet of an average 15-ta—19 —year—oLd male.
This La equivalent to 0.32 1 LO” a 1k body weLghr per day,
vbi.ch is Less than the 3.0 1 L0 mg/kg/day found during
1966 to 1969. In 1974, Lindane residues were found in 16.4
of al.. FDA arkac 3askat samples. These food residues
resulted In a humnn consumption rate of 0.84 1 LO /‘&;/c .ay.
Ce) Humans
In addition rs food sources, the total. human body
burden may be increased by residues to household dust,
La fish and other seafood caught by the consumer, In game
animals, in driniclog iater, to vegetables from the home
ardea, and. rom tnhalacion.
1onLtortmg data, collected by ?A’s ac onal Ruman
Xonitoring ? ‘ogran, show that Lindane in human adipose
tissues occurred In 3.77, 1.56, and 0.56: of sampLes collactod
during the years 1970, 1973, and 197e, espact. veJ.y. The
-------
geouettic nean level of 1 Lrsdarae etecte4 L a adipose tissue
from tao ;eaera]. population for the years 1.970 to 1974 vas
lass than 0.1 ppa on a Lipid basis (34),
3. Metaboi.ts
Lindane can be found in the body organs and tLssues
of eamnaJ.isa, avian, and acuacic species with the greatest
storage La body L a :. It has been established that Lindane
is deposited in body l Ipids at the sane concan :rac ou
as that found La the diet (33).
tindane is, however, eventually netabolized in
various erganisas to auth Less COXit water soluble products
which are then e crered in the urine. (The available data
vdrs siaaari:ed by Ieu:ie (36), (37)).
Mannalias biocransfornation of 311C isoners involves
the fornation of chiorophenols (trLch.Loro—, rachloro—,
and pentachioro—) which are excreted free and as conjugates
of sulfuric and Lucuronic acIds (38), (39). The eliminated
products, the free and conjugated c lorophnaois, are of nuch
lower toxicity than the parent isoners, and some are being
considered separately as cancanI ants in water.
Uaity netaboiltes of.Lindaae have been reported in
the Literature nw jawed by the Uerkiag Group. Sane of tho
netaboiLtes were chlorophenol and chionobeezene compounds
which appeared La the 1914 edition ol azrs toxic S .ibstaacc r
L.Lsr (11.0).
In ecenber 1975, EPA ’s OffLcc of ToxIc Substances
submitted to Congress a prelininary assessment of suspe :ed
carcinogens La dni .Lng water. There vera 233 orZaaic
chemicals, nest not Laplicated as carcinogens in that
publication, vnlch have been-found in drtnkLng water sanpLc
is. this country (110).
Several. chl.orophenols and o—Dichloroben:eee ere
tbe only 1 ndane necabolites of those identIfied in the
Literature reviewed S7 the Working Group which appeared in
the above List of substances found in drinking water. It
was observed, however, that because of LLni:ed saupLing and
the restrictIve nature of anaLytIcal sy cens, the drinking
water LLst was not defInItive nor indicatIve of contInuous
occurnence. The highest reported Level for these netaboli:es
was for 2,i—0IchLorop anoL at a concentratIon of 36 u per
LIter of water V.10). thIs high LeveL at one sLte is no:
sur?nising as chiorophenols ore readily rod ce4 by the
addi : on of chlorine to wacar contaIning phenol (LU).
-9—
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The po stSiiity of the at ence of Ltadaria necab
elites as :ba result of other it aral and human—influenced
ehenical prOcoeses in water and ocher edia coaplicaces
assenent of the role of lindaue in any hazard fran
‘these substances. An appra ied health unit for ltndane
of 0.006 ng/Ltcer of drinking water has bean set by
SPAs ‘Jator SuppLy Division (1.1.1).
0
The r.Lndane orkLng Gra . p has not as yet thoroughly
astigated the evi onnencal. and h nan health hazards
free lindane necabolites. Data vjfl be r v Loved by the
Working Group during the Rcbuttable Presunpcian Process to
dter ina if any of the known Llndane neesbolites can be
shown to add substantially to the ha:ards associ tad with
the use of products concainLn lindane. Anong the data to
be rw,teved, if available, v i i. !. be a study by the laeionaL
Acad ny of Sciences which is bni g condLzctnd to provide
háalth data for setting na inun cantaninant Lev’el for
d inking water. This study was aranged by EPA’s Office of
Tozie—Substances (111), and is now scheduled far conpiation
in arch. 1977.
C. StudLes on the Iso rt:acio of G nna—3RCeo the
Ai na and 3eea socer
Separate- scient !Lc studies indicate :h;c the alpha
and beta isoners of BIiC are oncogen .c in rodents and that th
ganna Lsaner zay isceetize to the alpha ann beta farms. hi
suggests that in additton to the adverse propart es
erenc La the ganna isaner, ].iadane nay also have additiou•-
a l adverse effects based on the alpha and beta isoners,
n y be fatned £3 sanerization products of the parent
g na isoner.
The relative th odyn.ani.c scabilitLes of the four
najar S C Lsoners in order of increasing cher iodynan c
stability are as follows: gannacalphacdel:a
-------
L.O . Becauac aeration Lnflue edc o’reactiou rates, the
investigators ‘ssu ed ice i nsti atLori proceeded ehrai gb a
biol.ogic l. nachi nisn; the responsible o aniens Vera no
isolated or identified.
Studies by enuazet and :1nevun ra (41) on the fate
of the ganma isuDler in aquatic sadinenca indicate that
the alpha Lso ev La present in. o ce a of the Levels ihich
VQulct b expected if ganea-4iC rere not converted to the
alpha form ny L ao rL:ation. In a bsequout study 1at—
su ura at aL. (42) isoLated a noil organism, Pseudoaonas
outlda , which Lsomertzos the g xna isama: and La ibLquitous
in Lak.a, sail, and sedi eots. a ada (63) seperatuly
administered the alpha, gamma, and delta Laomer of BHC to
rats by L ubaeion 0 Subsequent analysis of the rat tissues
rev eled acct mu1.actou of aLpha- .B IC and beta—BaC, indicae ng
that Lsoeer tend. to aanvert to 1pha and beta.
Studies indicating that gamma—BRC nay Lsomeri:e
to the alpna. and beta isomers sake the data which establish
that the alpha and beta Laoners are oncogenic and fatotoxic
to rodents relevant to assessment of Lindane#s toxic proper—
ties. These studIes report chat the alpha and beta isomers
of EC induce atacistLcally sL n.i ficanc cacogenie changes
in. 7 dLffarnnt rat and nause strains. IARC ha evaluated
these studies and concluded chat “(t)echnlcai 31(C, its pure
alpha, beta and gamma isomers and the mixture of delta pLus
zpsilou isomers are carcinogenic in nLce, producLng LIver—
cell tumors fol .Loutn oral. adnLoLstratio&’ (4 ). Tha
3tu4LC3 formed the basis for the issuance of a rebut-
table prasumpc2cia against re.regLacration of 30C In part an
grounds of the attcogenieity of 3HC and. its alpha and beta
isomers. They are summarized a chat notice and the accom-
panying position document.
Llehougb the IJorking Group is aware that there are
degradation and metabol.Lam studies which nave neither
detected isamerizacion of gamma— I1C nor found unidsatLfied
products, we believe that the posi:Lve studies aever:helesff
prnvtde a basis for concern chat Liadane ay possess sone of
th. toxic properties of the alpha and beta isomers. The
Agency is presonUy examining monitortng data which show
unexplained and unantictpated high levels of al;ha—3i .C in
ambient air (See Section I(A)(2)b) and beta— C in adL;ose
tissue; these data may be supportive of studIes indIcating
isonerinatlon. ?urther stu4Ls on the extent of Ln v :o and
environaental Isomeri a:i .aa as well as additIonal con .:acor;’
b nalytical cesc nay be necessary.
LI ar.Chaawtnac,, an scientIst vhO has done esearnr.
on’ invLvo netaboLlam a Llndane, auesticnad the technlnues
and conclusions arrived at In Canadas im’ ’ Isomerizat .on
study (44), (43).
—Li—
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• i tUi Qrv Rtstørv
In 1969, aE r oaeer.ded in the trak Report (1.) that
the usage of 1. iradans, along with that of ocher naeed persia—
tone pesticides, be rQstrictsd to specific essential. uses
vbicb. eate o hazard to hut ;o health or to the quality of
the enitronteenc and wh eh are unanisously approved by the
S.c? :arie3 oi the Depart ssnta of Roai.th, Educacion, and
Ielfare; Agr cuL:nro; and £tterior. I: was noted that these
pesticides cause or can cause ccnta ioaeion of the environ—
ecnt and. da aga to various species within it.
In April 1969, pnrsuant to a General £ccou_.._ag Off co
(GAO) raporc to Congress, the Deparc ent of Agrtculcure,
aSDA, cancelled the registration of lindane insecticide
products intended for vaporization. Questions regard ag the
safety of these products had been raised repeatedly since
the first regIstrations were ada in the early 1950s, but
prior to the cancellatIon decision USDA had condiude4 that
there was little evidence either to support definitive proof
of safety or to do ons:raca a genuine hazard fron the
producca when used as directed.
Under recoeuendacioa,s of the General AccountIng
Office, the Secretary of Agriculture appointed a edicaL
Advisory Panel. to revtev USDAs previous cancellation
decisIon. The panel caref iL1y considered the association of
blood dyscrasias with lindane vaporIzer S, the abLiLey of
Lindane vapor to penetrate and persist In foods Cun.Less they
were *ea.].ed in netal or glass), and the availabLlity of Less
persistent but equally effective insecticides. The Medical
£dv sory Panel. confirnud the orIginaL decision. concluding
chat the use of Lindane by auconatic vaporization tschnIque
should be discontinued because it creates a potential hazard
to human health. USDA thereupon reaffirned its original.
cancellatIon decision. Sa u re istranes tnen requested that
&n;independeut advisory camnitcee consider the relatIve
hazard of these products. This advisory comnittea was
convened and recounended on July 2, 1970, that the cancel.a—
tian be aintaLaed.
At the request of acne registrants, publLc hearings
ware held June 23 through 29, 1971. Separate hearings
were held to consider the cancellation of “conti uOus”
vaporizers ann of “one—shoe” vaporizers. In both cases the
Reartag Ezaniner reconnnnded .that the cancellations be
withdrawn, but the EPA JudIcIal. OffIcer issued an order
whIch disagreed with t ose reconnendacions. One coni. itious
vaporizer produce was Inn diately cancelled. Others vote
restrIcted en connerclal use with labels nodlfied acc rdi L7.
One—shot vaporIzer Labels were anended :o prohibL: use in
areas where food is prepared, scored, sold, proäessed, or
otherwise hand .ed.
—12--
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App4ala by,rhe registraneri r ulted it, stays of
each order by U.S. Courts of Appeal ptnçit2g futthQr dLrectioii
from be curt , On May 11, 1972, the U.S. Court of Appeals
far the 7th Circuit ruled in favor of Continental Chomisee
Company, the sole registrant for o—o; vaporizers, and
sales of th ree- h company’ .L, ice .rproduccs were
allowed to,’cp.z .ut?!itthaut labej.c ros cciona. (46]. F. 24
33]. (7tt’C . L 972.’)$ These products Ir stIll Suing
prodiicod and sold. On December 6, 1972, the U.S. Court of
Appeals for the 8th Circuit upheld the JudiciaL Officers
order with regard to the two “continuous” lindane vaporizer
products.
Another lindane household product, treated shelf
paper, was first cancelled after USDA Ag czl tural Lesearch
azv ice tests indicated chat continuous use of 1.t:daae or
chiordame treated shelf paper may produce residues in
hale-secored food, and the Food and Drug Administration
recommended against further usc of these products. USDA
then cancelled the registrations of all. lindane and chlor4au
impregnated shelf papâr c m fo’iember 18. 1.969. Ac that
tine, USDA beliceed that label restrictions were inadequate
to p euc use in food-storage areas. 3ovever, upon recommen-
dation of an internal Eazard.ous aeerials Advisory Committee,
EPA, which had assumed the pesticid. regulatory function
frOm USDA, Later withdrew the original order and pe L:ted
use. with certain labeling requirements.
Tolerances of 0.01 to 7 ppm for lindane k.ave been see
on a variety of forage crops. dairy products, poultry, and
raw moat from domestic amiaals including cattle, sheep,
hogs, and chickens. Some of tho original tolerances were
reduced, primarily so they would comply with the policy that
residues should be no higher that. the amount reasonably
expected to result whom dIrections for use are followed
(46).
The Food and Drug Aduiniscracioa enforces “actio
levels” for pestIcIde resIdues on raw agricultural. commodi-
ties a’ .id processed foods for which formal tolerances have
not been granted. These action levels represent residue
l e1s at which legal action can be ta sn to prohibit sale
oruse of the commodity; the FDA nay take actioft at lower
residue levels 1.! there is evIdence of pesticide misuSe or
if some other factor appears Co warrant such action. The
followIng action Levels hav been estabLIshed for Llndane:
4.0 ppm for poul .er;’ fat, 0.5 ppm for eggs and some frui s
and egetables, O. 3 ppm (on a fat basis) for butter, raw
unpascaurlzed ilk, and all. anufaccured dairy produces
including pastaurt:ed or otherwise processed ni1 . and 0.1
ppm for grains (47).
—13—
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On February 1, 196 3, all regtstered uses of ltndane
on the following cvops, v .Lcb had been assigned a zero
LLadans residue toLorao e as a safe Level., were cancelled by
USDA: blueberrtes , btrdsfooc trefoil, buckwheat, currants,
endive, gooseberries, pJsi. ira and range srass, Lespedeta,
pecans, sweet potat ns, pineutoes, and walnuts. En addition
all registurot Lindane uses, except seed treatnent, ware
cancelled on the following praduct : alfalfa, clover,
cotton, flax, oats, rye, sorghun, soybeans, sugar beets, and
wheat. In the event that any crops had been left out e
this category, the notice also specifted that all. Lindane
uses except seed treatment on all, field, forage, fiber, and
grain crops were cancelled (48). The registered uses on
dairy cattle, dairy barns, and eilk rooi s which were
cancelled by tuZ.s no .ice were extended on January 19,
1970. by a renporary axenption fron cancetlatton. On
Uareh 12, 1971, these uses were cancelled ( 9). Fo1Lovin
FD A . cancellation of tolerances for lindane and 3aC on bear.s
citrus, corn, and peas, TISDA cancelled the registration of
these insecticides on February 26, 1970, for those uses and
for the post—harvest application of Llndane vapor to lenons
in storage (50).
On. tl rch 18, 1971, the Adoi Lstratar announced that
EPA. had begun an extensive Luter l review of three persis-
tent pesticides (3 IC, Ltudane, and endr n) to deternine Lf
any uses of these. eonpot.tnds.preseuted a subitantial. question
of safety. Accordingly, an EPA SpecLal ?escLcide aeview
Group conducted a review of the bazar Ls associated with the
use of lindane, campLe:Lng a-report in August 1973. This
report was prinarily a LLteratu:e review and coepLiation of
currant research; no recomne tdatioss were nade at that tine
regarding continued regLscra ion. there was, however, a
brtef discussion of relative rtsks and bfznefits resuittug
from broad usage patterns. To regulatory a tion resulted.
On N e ber 27, 1974, the Cri eria and Evaluation
Divtstou (CEO), using iaforxatian de:Lved in the 973 revLaw,
recomnendod that the use of lLadane in feed bins be cancelled
because of the potentiaL for producing residues in. nil . 1o
other l.indane uses were recoenended for cancellation.
aowever, gradual. phaseout was recoenended for all uses of-
3gC.
This recomseudation observed that, .n general,
studIes reviewed indicated :har “ Lgh levels of I .ndane a’
be expected. to present a careLnogeuic ha:ard to nan when
used as a ;est ci.da on food crops.” t was furt ter observed
that Lindane is nor occurrin; as resLdues La nan, hIs
food or his e rii:ocnenc n anounts suffIcIent to war:anc
concern. The use of shelf paper in accor aace th EPA
reconnended Label changes was beLieved not likel7 to result
La excessIve :esLdues.
—L4—
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A notice of Latent to cancel all BHC uses ad the
use of Lindaae in cattle. food bias was drafted but not Sent
tetbe Adnintscrator (31).
On December 1, 1973. the Ecaith Research Group
(ERG) petitioned the ? dninia:raror to cake imnediate
action against all Lindarie aerosol producrs by issuing a
tLce of suspension arid cancellation and by req irLag a
recaki and seizure of existing stocks (32). Consuner
cànfustau arid, potential. hazard due to the Labeling of
ot e egistraat’s lindane produces were primarily at fault.
The virtually identical Labeli ng of Lou percentage Lindane
aerosoL cream, Lotion, and shampoo for control of lice on
humans and of the same manufacturer’s higher percentage
lindane aerosol product for use on Laznuiate objects pre—
seated the possibLlity of accidents. tri response to thc RR(
the Registration OLvision, 0!?, directed the
registrant to chaige its product label which would, La
effect, reduce accidental exposure to hunans. The aaalch
Research Group subsequently withdrew its petition.
E. Reeiseered uses and Production
Pesticides containing Lindarte have been federally
registered since the early 1950s although the iriseccLctdal
properties of Liodane were known before that time. Curre te
registrations include uses for hone and garden; seed treat—
merit; foliat arid soil applications to fruit and vegetable
crops, órnanontalz, Lawn and turf; bGrer controL in fruit
and erns iaacal trees; eoncril of pests on Livestock arid
pets; and control of hunrin parasites. The rocords in the
Registration Dtviston, 0??, show registrations for 337
lindaun products distrLbuted among 257 federal registrants.
There were 87 applications for federal :egiscracion of
formerly intrastate reg st:atioris by 48 compaties.
Liadane products are fornulated as wettable powdets,
eriulstfiable concentrates, dry powders, ltquids, and
pressurized products, including t one shot” vaporizers and
aerosols. Hooker Chemicals an ?Lastics Corporation of
Hiagara Pails, New York, was the sole domestic manufacturer
of Lindane. In ay 1976,. however, Hooker teriporarily halted
production of Lindarie, arid iii nanufac:uring—use LLndarie has
been iportad since that tine.
Section 7(c) of I L requLres manufacturers arid
formulators to submit to PA LaformatLon on produttton,
sales, and distribution. tnder FIZ3A sections 7(c) and 10
chLs infor at on nay riot be made ava labLa to the pubLic.
confidential memorandum coc:ai irig this i ornation ha been
seat to the Deputy Assistant AdnLalstra:or for ?est cides
(53).
-15—
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Curreoc EPA records L dLcate char 242 re iscracirs
of lLndane products reported produc eLo . aud distriburiou
to chi Agency. 1Lthia this group less than 23 Lb of
actu,a3. lindan. vas formulated for each of 39 end—usa pro—
ducts, and 40 products vere oar produced at aLL. Of the 555
re isrsrod products co aining Lindane, the farmu’.ators
for 3 3 products did nor report production anc distribu—
tion data. Mast products in this group are co Longer being
produced.
A8ricultural end—use data vas obtained fr,m the
? atiunaL Study of Agricultural, Gavern entat, and Industrial.
Uses of Pesticides conducted by thts Agency (54). These data
tLdtcatad the folloving uses of Lindane in the united Stace
tn 1974:
Lb acCLve lindane I total
Crop ‘ aoo1. ed a ricu1rure
cucu bers 68,250 18.26
cattle 61,275 16.39
squash 33,025 14.19
swine 11,660 3.17.
pineappLes 7,274 1.95
ornanentals 6,244
nursery 2,310 0.67
âorn 1,241 0.60
sheep 1,632 0.44
?egetables (nisc. 1,000
principally cucu bera)
seed tXaat eut 158,538 42.44
(peas, a1 a1fa,
vacermtijoi , wheat,
barley, oats, sorghus,
to rn)
eushrao 50
turf 8
safflower 2
esri aced total
use in gricu1ture
for 1974 373,809 100
—16—
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Tn addition, this survey reported that 3,127 lb of
actIve Lindane vera used by federal and stats ag acies and
11,098 Lb by industry.
t should b noted that tha o totals represoer the
ieinunt anmuat of Lindano uscd an tho listed sites. The
protocol for piov oneieg this study required that the
pesticide uses an the swien Lcad±u craps in each state be
identified, and the esti Gtes vera developod frau chL point.
Therefore, pesticides appiiad Ca minor crops in oe ch state
vera not !.dsctified, nor wore the ancunts used inclunod in
these ssti2atcs. aame and garden use of lindane w 5S not
reported.
Tho International Trade Commission reported that
63,805 Lb of Lindacte was imported ifltO the U.S. L 1966.
there was no veporced U.S. importation of Liudane botween
196? and 1971. In 1972, how . ier, importation totaled
1 .939 Lb but dropped to 5,737 Lb in 1973 and 3,525 lb in
1974 (55), C56).
It. SU !AR? OF SCI NTIYIC EVIDE(CE TO SUPPOR? R!3UTTA3LE
PRES tTht P TIC L
The foli.oving adverse effects of liadans have been
found to exceed the criterfa for issuance of a Rebuttable
Prasi&mp tion.
A. Chronic Toxicity
(1) Onco entc Effects in Test Aniisals
40 C7R Section L62.11(a)(3)(ii)(A) pr Ldes that
“a rebuttabLe presumption shALl arise iE a :dst ctdes
ingredient(s) . . . (L)odnces ancogenic effects La exper .nen—
tal mammalian species or in man as a result of oral, iahala—
c on, or dsrn l exposure. . . .“ Section ó2.3(bb) defines
the eor oncogenic as “the property of a substance or a
mi :ure of substances to ,raduco or induce benign or nalig—
nanc tumor fornat au in. Living animals.”
Although the 1969 HEW 1rak Report (1.) raconnended
s ere :estrict on of Llndane usage, LLadane was not among
the possible oncogenic agents .ted in that report. or as
lindane among the 120 compo .rnd tested earlier .n 1969 for
tunaro!eaIcity by the racionaL Cancer Institute. Lindane
was, however, lIsted as a suspected carcinogen in the more
recont Suspected. Carcinogens: Subfile or : e I0sE Toxic
Substances t.ist (57).
—17-
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The recent scientific Literature incLudes six subacute
studies (duration of ezpasure to a esticLde Less than
one—half the nornal. iS. aspen of the organisa) and four
Long—tern studies assessing the oncoganic ef ects of ganna—
B C in nice and rats. Three studios reported that Lindane..
feeding induced ben1 n tu 0rs, and one of those itudiei ,lsa
doserthed. notastatte invasion of the lungs fron cunar .
Seven studies reported that Lindane feedS.ng did not induce
oncoganic changes. In a 1973 report, the IatarnatLonal
Lgency for Research on Cancer (IA&C) WorkLng Croup on the
alueciou of the Carcinogenic Ris1 of Chenicals to Man
reviewed chase tudias and concluded that ganna—BUC was-
carcinogoni: in nice because it produced liver call eunurs
following oral. adeinisttatioa. This group also concluded
that the available feeding studies in rats were inconclusive
either eeausa dosages or su iv c i. races ware lay, or because
the published reports did not include sufficient infornacion
(45).
The Criteria and Evaluatton Division (C!D) of the
EPA ’s Office of Pesticide Prograns rev jawed several of these
studies (58), (59), (60) (61), and concluded that none of
the presented data was adequate to initiate an RPAR. th .s
conclusion was based on the reasoning that the studies were
Limited to 1ca, that the anl7 cunor type to :creasa was
hapatona, and that the toxtc effects evidenced by the high
early nortaiity race sug eated that the hepatonas resulted
fran non—specific toxin effects due to high workload on the
Liver (62).
There was, however, isunderseandS.ng at this tine as
:o CE ’s role. The proper functIon of CED L a the Rebuttable
Prmsunpcion procedures now established is to detar ine
whether the research conducted is scientifically valid, not
whether subnit:ed tests constitute adequate evIdence to
in tiata an PLR. The latter function La the role of the
Working Group for a particular pescLcide.
The EPA’s Carcinogen Assessnent Group (C. G) reviewed
this sane research and concluded that the rroceduras followed
were scientifically valid and that the resui.cs obtained
supported the research papers’ conclusions chat Lindane
induces oncogenic changes in nice as a result of oral
exposure. CAC based its conclusions (63) on the facts that
oncogenic changes were reported La several dLff ranc nousa
strains and chat cunors with. lung cetastases had been
reported by Thorpe and ‘. aLaer (.58).
—18—
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A othQr bioassay study on the oncogenic effects of
lindane has been parfor e4 by the NatLonal Cancer Institute
( iCI), as part of its SionatLcs—tt prograe for the e ’aiua—
tion of compounds suspected of carcinogenic activity. £ rat
study was com onced on September 7, 1971; aniuials were
acrifice4 after October 9. 1973. A nouse:-seudy was
con enced on January 4, L9t2; aniais ware sacrificed after
Sept h bar 23, 1973. UCI has not issued a final, report with
respect to these studies. however, preliainary data ‘ias
sub Ltte4 to EPA concerning these ntudies bearing the
notation “Inco pleta—aot verified.” ‘his preiiainary
data reflects, among other things, pathological, diagnoses of
tjsàue sections taken f ovz the aninals in the studies and
so a statLSticai analyses of the results. Because of the
ezistence of cospleted studies which provided an sufficient
ba sis for preauning agalast the registratiorzs of Lindane
products on the basis of oucogenic effect, the prelininary
rEsults of the :ici study were not submitted for formal
comment by either CED or CAG, and are not a basis for
issuance of a rebuttable 2resw!ptioo against registration i
this instance. however, EPA is interested in receiving
co5nenta fro’s registrants or other interested persons
concerning the significance which should be accQrded to the
prelininary data which have been recetved with respect to
this CI study. Tar this reason, the preliminary data are
attached (i. .3).
(a) Studies in rJbLch Dietary Camna—B C Produced
Oncoqenjc C anees tnaoder ts
LU Laboratory studies in which observed oncogenic
changes took place used mice as the test animals. Goto ec
al. (50) fed, 3—week—old male nice (strain IC —iCL) 300 or
600 ppm gamma—BMC far 26 weeks. Liver tumors were observed
in 30 of 10 animals ingesting 600 ppm gamma—3RC. Eisto1og —
cally, the nodules were classified as benign hepatomas.
Although the £nvestlgacors found no sàtastasis to lymph
nodes or other internal. organs, there was no indication that
the lungs had been serially sectIoned, the most reL ab1a
method of detecting mecastases. Another change associated
with gaua—aliC feeding was a two—fold increase in the ratio
of lIver vei 3 ht to body weight. Also, five treated animals
(23) didd earl: in the study. There was a nlcroscopic or
macroscgpic indicatIon of tumor d eLopment and no increase
in the lIver—to—body weIght ratIo for the an.Lnals ingesting
300 ppm ga a—3aC.
aaeada et al. (64) treated 6—week—old male and
female mIce (strain dd) t:h 100. 300, or 600 ppm ganna—B C
for 32 weeks; the axiials were :hen na scai ed art a basal
dIet for 6 weeks and sacrI ced 38 weeks after feeding
started. rumors were found in 4 of 7 fcnales and in 3 of
—19—
-------
males testing 600 ppm gamiea—3RC far a co &bined rat’o of 64Z
(7 of LL . Uene of the 29 controL animals, the 18 animals
ingesting -100 .ppu , nor the -16’ a in aU Lngestiag 300
ppm !ania—3UC bore tumors. Doses of 300 ppm gamma—a IC
produeed .atyptcaL proliferation of l Iver cells.
Thorpe and taLker (58) fed fo ar—vee —o1d male
and female mice (strain CT1} 400 ppt gamma—8HC far 52 to
1.10 weeks, they reported a tatistlcalLy sLgnifLcant
Lncrsaee L u the incidence of hepacic tumors as well as
metascases to the Lung in the ganma—BRC—fod aetmals rel .tLvc
to the controls: 96Z of the ma.oe bad tumors including LiZ
metastases, and 95Z of the females had bepatic tuners with
no metastases, Hepatic tuuaro were found in 24: of the
control. animaLs, but no ecascasos were ebsotwed in this
group.. .” Other obeetvations Included comic effects Leading
to death during the first three months of Iludene—feed ing
for approximately L5 of the animaLs. Further, for the
entire 110—week ezperimo,’caL ported, there was a SO total
fatsltty record for gamma—aRC—fed animals as compared to
68: for the control group.
(b) Studies ReoortLne :;o Obse ed Orteocenic Effects
Ci) Mouse Stu Lies
1agasakt at al. (61). fed 20 male mice (strain dd)
100, 250, or 500 ppm gamma-BRC for 24 weeks, and Ito en al.
(66) fed maLe nice straia dd) 100, 250, or ZOO ppm gamma—a) C
for 24 weeks. Toue of the cuntroi or gamma—aaC—fed anImals
developed tumors in either of these studies.
Rerhot et al. (59) fLd i iai mice 12.5, 25, or 5
ppm gamma—aRC for 80 weeks, the authors reported benign
hepatomas to S of 195 control animals and in 4 of 292
lisdane—fed animals. Gamna—3HC feeding alone or in combina-
tion with polychlor.tn•aned biphenyis (?C3s) had no effect
in male mIce ingesting those compounds for 24 weeks.
11 Ia this study primary tumors were found at extrahepatic
sites, primary Lung and lymphatic tissue, in 32 of the
controL aetnals. A eompLlat .cn. and analysis of CTI mouse
tumor data by Sher (65) from several different studies
shoved that this st:aix has high spontaneous tumor race a
ex:rabepaetc st:es. The Sher com L1ation also showed that
in four dIfferent studies approx tely 75 of the spoutaneous .:
forming tumors were found in tIssues other ban lIver -and
that spontaneously far ing Liver tumors wore faund La
approximately 25 of the animals. The Thorpe and Walker
data are consistent with these date showing that the CTI
straIn has a spontaneous tumor race an ex: ahepacIc st:es
approximately three times greater than the rate tO lIver
tissue.
-------
(i L) Rat Ceudi e
S vaeal. studios reported that LL:daue—faciding did
nae cause co enie chau as. t a Lifatine exposure etudy
at si.. (67) fod ?3L areats S to 1,600 ppn Ltndaoe
far apprczi ately two years. .t donos of S to 800 ppu, no
sacroscopic or 3icr08009ic ebangos wore reported in ch
tiu_M- aui3ad; the or ns of aoe oxperi antaL animaLs
were not exsntnad uLtra a?icall.y. At 800 to 1,600 ppu
toxic e2fact eoduc d the Lifespan. of seue sniusis nd
Led to two—fold in oases in Liver veL ht and 1L ht” or
odoate” Liver taage such as enlarged Liver ceLls, fatty
degenerseton, and necrosis in the survLvors. tn. another
LLfetie stt 4 , rats LogestLn* 23, 50, or 100 ppu gaa ..3R
shaved no stiZicast cr1 5 50 La c uar incidence reiaci.ve
t controls (68).
tto at at. (59) fed naL. t?Lstar r*tz 500 ppv gauua—C
far 24- or 48 ve*ks. t$ver ceLl. r ro hy was observet
af tar 48 weeks, but no- tunars were foun3 La the 3UC -f ad
anixa.Ls. Ortega aL. (70) fed Sher iara rats 50 or 100 pp
Lindan. for 40 weeks. Liver call h7percrapby was reported.
for son. ani na1a., b -ut no t n ors va fuund.
(Z) Re oducr±ves Te oeo cieFffeets i !a 1i r
Saecies 1
4Q C?It 16Z.ll(a)(3)CLL)(3) prav-Ldes that “a reburra ..e
preauupciou sbal.i. arise i a. po icidci” ingrediQat. . .
(p)ra4i cas any other chronic or delayed toxic ef act in.
test aizixals at any dosage up t ’ a Level, as dotarinad hr
thu £4 aistratar, vh.Lch is substantially hLgher than
that to which huuau can reasonably be anticipated to be
exposed., caking into accounc aupte sargins of safoc .” Thi..
seecLon raf1oct concern that chronic. exposure t
uay result in injny to the reproductive systeu and/or- rh
fetus and provides that a rebuttabLe prasupcion 3 ai1 ar-i
if chtauic chuUcaL exposure in cost aninais produces such
results.
rouic reproducc vo effects La avL. n. species are d!. a
sad in Section tI. .(Z).
—21—
-------
Savital. studies, d.ca Le4 beLow, report that ozposu e
Ca Lindao n p?tor to or dueta; as taLiazi gc statio peoduced.
oiabryocaxi . or faeoeo ic. eE.fucts La test aais als. These
offsets L cludad r d eCioas La the zL:o of affspCin ,
daLa ’sd. and. retarded sci iaaL oat ratioo, and L c oased
fqusacies of stiLlbL:ths among the qffspriag of Lindane— .
•xpescd dar%s. La chose studiss aoee offsets wore observed
at. most desage Lwe.L i tested.,. b &t t e Louea dose at which
tke o effects aa ’ be obsoe’od . L. not rnown;. nor La
vtt eh,v the. I sv eL& w t:h. d .t ced.. fecoco.Lc effects th.
th a s act d.ias are. a &hstanc .. .z.LLy higher than those “to whL h
humans can reasanabL be a ic.ipated. to be • posed...” La the
abnence of an estahlL hed.. Lsve.L at which there was no
d .amaos:racct effect and. vttb. a. bseqnenc. Lac.h . of basis Lee
choice of an. “a p Is eargi.n of aLet ’, it m&y be prusunod
that crrnnc e. posurs is s ctenc to produce repro’tive
and. Letotazic. off accs l.a hwaaas.. A orriiagL , the 7arking
Group cas ond.r that a reOuttable presunprion be. iaitiats t.
pursuant ca Section i&Z.U( )(3) (ii)(3)..
(a) Growth. aeurzeian. anci ae,rcdue i’re , eit’r ta
3a cs
I!aLshtotn and. LOLbCLVL.cb.. CT !) doscr .bed. delayed
initiation of the first sst us in pubescent rats- and; langec
Lnrc%struus. perLods. in the oLf prtng of. fema..Lc. rats (noog:i L)
which had. been. fed 0.3 u J’a lindane for four mouths prier
te. eating ant pre aauc . Litdane—fed aninals avoesgecL 4.0/
eyci.as per antIz as compared ta 6.14. cyeLas l.a control
aninais (pc0.0 ), cast aniaais also averaged. a 4.8 daT
diestru s compared to L.. .9 eays for the control animaLs
(pcO.05). These. obsarv ationsLadLcacsd . that the. oifsprLn
of. I 4aae— fs* females have fewer e5t oiIs- cycles- during
their Lifotines and suggested that the reproductive capacity
of. the new generation vtLi. be! reduced. accordingly. reac—
neat with a ui turs of Llndane- (0.02 ng/lcg) and. 0 D (0.05
mg-/kg) and with DD alone! (0.02 . mg/kg) produced. siaii.ar
results, but c:eat ant with Low doses (0.05 ngI€g) of.
Li.adaue alone han no seacist .caLl)r signUicaut. eUeet.. he
authors .a:ed that. the. p sticide - eoncent atLons used La
these expe iacncs were sinilar :o chose GGCurr . g, La water,
food, and soil.
-------
a addition. this report included a grapb vhicti
shaved. that at tkto ase of one ianch the offspring of Liudane .
fed, iiothers vatg LGd 25 Less than the offspring of contro l
This g ecs that 3atsruai ezposurc to tindane
retardsr ovth o . fetal. and/or tevbotn. rats. The authors
nl.so starod that o pasure to Liudane .acreesed th n*anber of
stillbirths and reduced utsbility of the auriLwtng offspring.
The report. did oae include the &tu crtca1 data. ubich for ad
basis for these coucLns onsJ/
I ?nt:esctL • . al.. (73) i x Lned . the. effects of
Liáda.ne on th reproduc.tiva capacity of four stcces—
si- uueratLoua of ra .es; 327 rota La. the P. 7i.. FZ, ané
generations vers studied.. The Lava t.i;ar rs reported that
3. ,.. 1.0 or L. sg/’ Lin ane. in. the diet Lengthened. the
average ratton of preg aacy f rota 21. to ZZ daya in. the
c.ourroL al.s Co 21.. Ca 24. days La the ‘..indaae—f ad. aninais.
and that L a. the 1.5 ag/ks group there vas a d..c.reaaad ferti-
Lity Ludez (the nw3ber of births reLo: .ve to the nuabor of
aniaa.Ls in. the p raatai papu.Lat .oa) fro 100 births per
controL parental popu.Lation to 60 births per parental
popuLation La. the graur i gtsciag Lindane.. The repart also
teecribod dose opondant dolayed opening of t .vagina and
delayed Lni:tati ,n of the i:sr aet . us La. the offspring of
Liudan’ .fet na t rs,. an. veU. as Longw cycias. La the E2. and
T3 ganeracious. These. indications of ratar .cd sexual.
.aruracioa and. depressed.. sazuaL function suggest that
exposure to Lindane during- pregnancy reduces the reproduc—
tivo C5 5CiC7 ae Lindano—craated parents and. represses
sexuaL naturation. in. stabsequonc. geerariens.
L/ Dr.. K. .Djang e. Courtney-, an. tPL scLsntist has evaluated.
this. study. Dr, Courtney reported that the. itudy indicated
that. the increased. nas a. duration of the. escrous cycle was
prinarily due to increased intervaLs bretveen cycles. She
noted. Lt was difficui.r to dater iae fran. the numbers pre-
sented. whether or- nor the. incidence of stillbirths had
increased.
Dr.. Cour::ay also obser7-ed. that because o standard
daviatious- were presented and data was nor seporarea y
sax it is difficult to judge w char the griwrh race of
neonates was reduced L a. the high dosage z:o’ p (72).
-------
Tho study niso reported a progressive Lncriue La the
proportion of stillbirths vith each uccessiva generation.
the FL generation there was 1. stLfl.bLrtli per 1.04 births
La aaL ai .si Lnge ting 3, 10, or 1.5 g/kg Liadane sad o
stiLlbirths per 50 births in the control ani sa1.s. Ia the
P2 ge ratioa there were 23 LlLb rtiis per 64 births in
the LLndaae-’ fed groups, and I stilJ.birth per 43 births La the
controL aai a.Lz. ta the- P3 generation there were I stiLl
births per 6 births anoog tho survivors La the Liadans-fed
groups,. and no stillbirths per 36 births in the controls.
I addition, spastic paraplegia was observed in 17 of 119
P1 and 7 of 52. 12 animaLs but not La the parantal groups
(14- contra1s . 34 sxp.:.aencaLs) nor 1.: the- 12 and P3 ca’t—
trol. groups (32 and. 2.3 animaLs, respectively). These data
tad icated. that. ezposure of rats to Lindaae during pregnancy
increased the tacLdence of abnor a1 and scii.lborn
(b) &erradi, eive ‘a actev, eraeo enesLs, and.
StilLbirths in Does
EarL et at. (74.) reported. that dietary Lindane
ad srered during- prognaacy bad. no sLgnif caat adverse
fetotazic. or tnratogeaic. ef faets on beagle puppies (tabLe
1). !asticida feeding began on day- 1. or— day S of gcion
at. Lawels of 7.3 or ii mg/1c /dv y.. tindane—foeding had.
jnj gj. affects o 1itt r- size and. on. the incidence of
pregnancy,. resarptinas,- and. ratoganesis. 1!avevar, LLnd .ane—
feeding- did. increase the pr6pcveion of. stillborn animals.
The. incidence of stiLlbirths La. the controL group was
the- frequency of seillbi:ehs. increased to Level.s of
sppraz±atei.y- 18,. 23 , and. 30 La 3 groups of dogs ingascLag-
Lindano ar either 7.3 at U ng/kglday durLag pregnancy..
L/ r . . Cou:ney rev teved this study also and. concl.udsd
that the researchora’ findings were valid .ndicators of
Lis4aue - ’s adverse effects an. nornal reproduc:Lve functions.
She noted., however, that. not a ’1 details of the e perLaeaca1.
design were specified. and that this precluded. ccnnpleta
analysis of sane- dara. Despite the- reporting limitations,
Dr-.- Courtney concurred in the conclusion that Undane
sigtL ttantl7 affected. the. durarion of pregnancy and decrea-
sed. the fer: LL:y index. 1oraavcr, she stated. that there
was a progressive increase- in the- ocrralLcy rate i the
three- generations due to a fscotox c and/or reproductive
effect-. r. Courtney noted that the obeervat±ocs of parapLe—
Ln the TL and Fl generae±cns “was prababi.7 qui:e real”
(72).
-------
ab1e 1. TEC Of DtZL &T LI DA OW aE WDuC v . CaPACITY
I DOG
Par ecQr
P ot coi P .aiw
?uppi a/
R sar ,e±oca titt
Z Pupa
iLth
— Tersea
:
SCiUbort
-
Co tro1 87.5
5.1 6.8
L.O
2.0
7.5 Ik Id y
]Q •3
0 4.4
0
22.7
day 1.
7.5 gIk 1d ay
85.7
3.3 4.8
L6
30.5
dzv 5
LY /kg/dLy
£4.6
2.9- 6.L
Q
1.7.!
dac 5
Souxea. EarL e aL. (74).
-------
3. 4cizte To rLtitv: gararris o Utldlife
40 eTa Section. 162.11(a)(3)(t)(3) sets forth criteria
for vhicti a. rebuttable presueption ay arLso because of the
paaticides acuto cazicity to viLdLLfo. As discussed in thá
proaeblo to 40 CT3. Part 162 (40 TA 28262), pesticides vhich
ecet. or azcead the acute toxiciry criteria of Section
162.1l(s)(3)(L)(3) nuse be claeel.y scrutinized o determine
if the hazard presented by the pesticido’s acutetazicity
necessitates res:rietLons on oae, or denial or canceLi.atioa.
of the registrations..
CL) £auaeic Soociec
Section. L6Z.LL(a .) (3) C L) (3) ‘3) SPOCLfLes that a
rebuttable presnuption ehall a.ria against a pestitide use
La direct appl..Lca:ioc to vater if such use when app-Lied to
a. —Lach. Layer at water wouLd rosul.t in concentrations more
than 1/2. the cute far aquatic ar3anisu. LikeLy to
be ezpeeed Data Lnd.Lcata that. certain pesticide productsL’
containing Lindana Labeled fat use against mosquito- Lawae
meet or exceed the acute taricity cri.:eria far rspresontactvc
fish. and. cr staceaas.
1/ At. Least tue currenriT rgisrered prad’Lc !. ha o Label
directianm er use in aquatic environments a3ainet mosquito
Laro-ne (75). Zegistrants for these tvo products have reques:ed
deLetian of this use from their labeLs. Given the aunber of
Lindane re istratious, there is always the pasoibLlit of
£gaacy.campucer or record keeping errors. This requires the
initiation of a reburrabla presumption on this effect so
that. all. registered. ILadane product LabeLs with direct
water—use ma7- be acted.. tipen.. TormerLy, 1 iadaae was also
registerod far rico seed teatment in aquatic vironments.
—26—
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decetaiae uhethor LLldans—ILSQ in e5tuagjasf, erj3u
environments nee s :eb cv.able p e u pcion criteria, CED
ntjlLzed. the i 4Lcated LC 50 valuee for the foLlowing repre—
seetativ e mar/urine epv es.es:kI
s ,oeies Lindane 96—hour LC values
Pink shrtni 2/
renneus 4UOrZrU 0.1.lppb—
Grass shrizp
! 1.aoeonetos u 1 io 4..44ppb
ysid shri p
veidoosts bahia 6.Z8ppb
Sboepshead. minnowe
C e inoc on ‘.arLev ens 103.9ppb
?L f Lsb
taaodou rhonbeides 30.6ppb
.cuiamions besed. au these vaLues (76) iad icate
that anr appLicamtan of Lindanci to e uarine/navine waters
greater than. 0.Cj00 .LG Lb/scm would. e ezpeeeed to excoed
liz tho 96—ho’zr LC i a 6—inch Layer of water for p1ak
sh:L p, the spades with the Louese an ug represenma—
tive species.
1/ test. resuLts fran. Schinmek em. aL. (76).
7./ The L,C is here- ax?rssset as the concentration of
50
tozicaum. La the enviroaneac measured. in. ps:;s per bL.LLioa
(ppb) -
—27—
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To L i ormi vbe hu 1Lodaoi —u c jo frosk vator auvLron—
eots aeca reb tabLa p e$3utption c itor a, CZ u 1Uzed
tha tadi .ac d valuas for he following opresen a iva
frs5ll poCL83:L/
s eeio: Lindane 96—hour LC!O Vajua3
C aunoL ea fish 44ppb
Ictnlurtio punetatu .
8iack butlhorzd 64ppb
tetalurus eL _ zA
L3lppb
Caras i &s autat i
Ta haa4. innoi S7ppb
? i .vba1 s prcoelas
Carp 9Oppb
C!urLnus ear io
audear sunfish 83ppb
Le e is i rola hns
3Lu.agiLL 68ppb
Laoai t2v ae achLr’.zs
Large oueh bass 32ppb
ie o,teru sal aLde5
lainbow ouc- Zlppb
Sal rn air nert
!rawu c:ou Zppb
Sal o t ’ize z
Cohe ai.acu 4Lppb
Oueor1 chu5 k±sueeh
TsLlov parch 68ppb
? erta f1ave eetis
i. . pares per b .i.1 on; esc resuLts fon acek
and ‘.IcALlLsea: (75).
—23—
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Calc cioos bascd on these values (7 ) Lndicace that
any apptiéatian. of Lindano to fr ah wator greater than
0.00273 Lb/acre vcul.d be expected to exceed 1/2 the 96- hour
LC in a 6 inch Layer of vater foP? broun trout, the
species vith the Love LC 30 anoag pseutative species.
the foro oi data and catculatLcns establish that
t 1 e rocoirneuded appliczt ons far tindane products re istsred
car aquatic use. exceed the acute. toxicity criteria of
Section i.62.L1(a)(l)(S) for reprssoutat ve fresh and salt
vater species. Accordin 1y, a rebuttable prssuxption is
daclared against the re iscracion of Lindane p’?odtlcts
4bolad far this or any other di:ect appLic tian t vater
which ezce. 4s the 0.00273 Lb/acre rate.
While. there appear to be no other Lindane produces.
with re i ? rered acn4Uc uses, otherregisccred. non-aquatic
tz as uy result te. Linda —concanination of aquatic environ—
‘‘.ies: far example, drUe fro uses such as aeriaL applica—
in to control 2osquicoes , runoff into bodies of aeer,
appL. .cation. to far ani aLs. vhLc1t subsequentLy wade inte.
a. body of water. Further, aLthough the Agency i not aware
of any recent na ar fish kills artrihucabLc to direct-
Ltndane use, there. are P.E S reporrs.k’ a.iLe ing fish kilLs
resuLt n fron. uses of Lind.ane other than direct appLLcatioti
to water. E3 5. reports include Lindane—assaciated fIsh
ki.LLs caused by ri noff frog mushroou ause., overereaced
cattle wading. into a pond, nnd an unspecified aerial applica—
ticu (77).. tn. addi ion, a 1976 report to EPA’s OffIce of
‘ater Plannin; and Standards noted. a kill of 230 trout after
sheep treated vith £ eixtu e of Lindane 3nd tezaphena adad
into a c:eek (78). FLab. kills reported to the gency often
do net specify the pesticIde or even the type of cheuL aL
responsible. These data, therefore, probably undsresc ace
the actuzLi. eUe.cts of Lindane use.
1/ heagcacy naintains a Pescic±de Episode B.apcrts Systen
(PEAS) vtLch coLlects reports of pesticIde ex osure affGctlng
hunaus, domestic an aLs, livestock, and wildlife.
-29—
-------
aoLcL (79) roportet that fish ioreaLLties due
to accidaaeal ot careLess discharge of sheep dippiag fl &id
Late atroa s occurred every year La Scotland. sigh residues
at bosh dteidvtn and Lid no were foui&t La 26 brova tro i:
killed La thta aaaer. Lt saculd be noted that Lindans’s
Vato soLtzbLLtty and vaLactJ.Lcy resuLt La a roLativol7
rapid.. disappoaraaca of most of: the LLndane appLied. to
va to t. ..
- Other water coatssinatian prabloes &y be associated.
with. .the use cit Lindane for aai=aL at ont. Tar exampL’
Land ’4isposa1,. of sheep dips caacaiaing persi tane pesticides
LncLnd i *cj Lindane. rendered. the- waters of Chew VaUe Lake in.
England teapararily cinpotabLo (80).. ha investigation e
pesticide use. on.. nearby faru and analyses of: aud sampLes-
L Ucated. tbe infU.taticiiz of iau .sed sheep dip spilLed. on
the ground. taco aa. ntderground. storage systee a tite cause
of death or p ene.Loa at repraduc.:ioa at erustaeean.r vhic h
I.pre, LousLy ontaU.ed. algae.
(2) L v tan s,ec _ ies
As noted previousLy- La seecton t.A.(2)(d) and. rLI:.D.(l),
re’aiduea at Liadaine. have been found. L a. certain Lrds ir this
COnntz7. t e use at Liadane an crops- a.nd se d.s. pra ptod . t!ie
Criteria. and. !ral.uatiacr Div Lsiorc to con eut. npaa the pat.auti iL
acute rtsl to birds. CED oicludcd. that bird - tC vaL ies
are generally- welL La excess of oxpacted foed residues of
Lindane for crops. (81).
tzr.. OTEZ! ELEVA 1D ?IDVERSZ cs
ThLs section addresses certain. eriterta for decerulita—
of unreasonable adverse off ec:s vhi.ch Lindane
produce, but for which. ia.snffic.ienc. evidence. exists to.
initiate a rebuttabLe.. presuaptian.
—10 - . .
-------
A. utaseaie Effoets
Seetion L62.LL(a)(Li)(A) provides thee a rsb ceab1e
preau ptLon shall arLse LI a. pesticide’s Legrudiects(s),
eocaboii:is(s), or do radaticn product(s) Laduco nutegenic
effects,, as tot i .ed by LgL—cost svLdonce. . Several.
LnvoseL ±oáscLia4atto’4 t ;eeL capaeLty appear Le. the
acieatLftc L ar tuve. test’s for PGLcC e tattoes performed. is
iicrobiaL systarsa end. vith DrcsoehiLa lasotastor are
negacive, indicating ch*c I adane doos not cause point
n raL of the custoesry anixaL and. pLant
t.s syscens far chrorsosorsai. ahorrattons, Lindaue acrr
sa a. sitoci’ inhibitor and. has boos shoun to produce changes
Ln pioidy. Eovev.r, a.ttaeic. LnkLbLtars are sac i&suaLiy
cLassUiet as nuagees,. and. the. evidence La sac suffLciest
to cLassify Liadane as. a. eh .:otaosonai. nu.tagen (82).. Thua
szLseing data do nat estabLish thac Liadan. is a
and.. chore La. so rebi. tcahl.. presuaç-cieu on this ground..
3. 1 e otaitie !ffscts L a 3u ans
40 CTS. 162.LL(a)(6) provides. chat the. Adrs inisirator-
ea decide to- cancel. a. pesticide or to hald. a. hearing if
pesticide pusey a. betantial. question of safety to hursaas
or the env iranaest “based. as. ricol.og.icaL data, epl4ursi.o. .Log —
c.aL studios, use history,. *ccident data, noiziroring data., or-
such ocher evi once. as La. available.” AccordLagly,. data. as
usa and. accLd.osc history vhich. su gesr- that
Lind .ane’ say pro4uce hanato c cffoc.:s La hursans uti .L be
incLuded. in. ehe narita of rebuttable praswspeioa against
rogiscrztioa -but not. as as a basis- for the rebutcabLe
prosuep tiou..
SeveraL repo:cs L a- the xod.ica.L. iLtora.curu iad.icacs that
Lindana nay - be a. pstaary- or c c:ibucLn; factor in the cievei.op—
sent. of severaL bunan bLood dyscrasias, partLcuLar1 aplastLc
aneeia and parsibly- Laukaoia. These reports, sumarized below,
are based. upon eedicaL ease histortes La. vhjch hwaae exposure
to L2.ndane, both fran- sornaL use and. Iron. accidental. over—
exposure, appeared Linked to subsequent devsLoprsest of bone.
ear-roy and blood. disorders. Ll.thaugh the- su.nber of cases is
reiaci -v-eiy snal.1. and the incLdeecs of disease appears to depend
nore- on ind.ividnaL susceptl.bLL.L:7 than oc exposure per- so, the
Wark .tag- Group beLieves- that the evidence is sufficient to var—
rant Agoscy- cansid .uratian. of lindana ’s pos LbLe henucoxia
effaces.. torscver, these reports of LLndaae—assoctaead Ptano—
toxto. effects La humarza are c oasi te e with retical reports
indicating that ocher- chioricated hyd:ocarbon pesticides such
as DDT and chiordane ay be hesotoxLa Ln husans, inducing bone
narrow and blood disorcors (83) , (99) , ( 100).
—31—
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Pos- these reasons, the orking Cr oup recuéiuends
that. the Agency soLicit cauenes on the availabLe evidence
sad request subuiesion of any additional eases or relevant
infatuation. In view of the infrequent but nonetheless
persistent reports of Lindaue—&ssouiated heaatozic ity Lu
only a snail portion of persons who bay a been. rs ui.ar1.y
eseased to Liudaae., the orkiug Group also reconnends chat
the Agency particularly solicit. coument on the- qu ations of
individual sensitivity to 1in iano ant the epideniology of
Liadsao—essocisted heaotuxic affects. The terking Group is
not aware- of definitive- aniasi studies Lu wbL Lindsao—
related henatozic affects have been obseevud, and the
ned±cal. L.Lteriiture indicates that there are no reliable
aniaai taste for confirming or denying the repasts of
kenatoxie effects in. kunans. 7e. thnrsfotn. ruconneud that
the. Agency aLso soLicit Lu.Cas2a:Lou. on aaiual test systens
Lu which. Liadaae—relatod.. henotax4.city has beau as co i.L4 he
ass ycd.
- j 3tood rserasiaf Assoeiated with x asure ca
Lindano Onl.w
(a) Aelast c Anenia and !v ,o ,lastie 3ooe Marrow
rest. (83) sunxa.aized.. the ced4.eaL ease histories of
five. Cal.ifomaia. residents. who dec eloped. aplastic anenia
foLlovtng exposure to Lindane.. Lu each ease the- patient was
ex- -ased. to Lindane that van izssd. for pest controL purposes
and bocaae ill. for nine- days to a year. Tvo e.f the patients
were o o3e& through Lindane. bane vaporizers
ouposed to Lindano whLcIr had been sprayed- Lu their hones,
and. the fifth patient was accidentally engulfed. Lu a ci.oud.
of rLud e halug- sprayed. L a- a; relative’s yard. ? diagnosis-
of aplaactc ana iLa. was cade L u. each. ease, and aplascic
aaenia. at hypopLasric. bans earrow was Listed, as a cause of
death L a. four of the five. cases..
- Vodapick (84) described aplastie anexia in a tvo—y ar—
aid, child who was exposed. to L.indiae 4u:ing a ebree—nanch
period La- which a preparation containing. Lindane was used to
treat the faeily dog far nauge. The patient had no kuowa
exposure to any ocher kaov he ccosie agent. hes the sange
reatmeat was discontinued. foUgviug decerniuacion of- the
Lindane source, the child recevered. Uoodli.ff at al.. (85)
described a sluilar case La- AescraLia. A wànan who had
washed her dog each veek far :vo- years in a z: Lindar.e-
sointion was diagnosed as having. bane sarrow hypopLasia,
Nprobably consequent. upon exposure to Lindane..” She died.
three nooths later.
1/ As observed in Section , several. ‘one—shot” iLadane
vaporizers are still.. being. produced and. se d..
1,
d
-------
?flS Report 71-1 73 4e eribed a case La ultich a
79’ytar ’ 1d voeaa de’itel.opod aplazcic ae ia after she “ ad
sa error whij.,n sLng a spray coizcaiaing Lindana agaiast a
nest La her hono and. sprayed hersel,f ta the. eye.
She. first sou hr edtcaL tracisenc fivo days acer. !vo
noaths after the spraying Lac .4cnc her condition was diag-
noa as pancytcpea ia. vith s ’ero- anemia and savers throubccy -’
topenia. She died three ontbs after empasure. The
La edLa:s cau a of death was a cerebra va ciaLar accident
with tha boaytnpenia. and toxic apiastic bone narrow ListerL
as secondary factors. The medicaL roporca 4escrtbod hemocozic
effâcts only and. did not indicate any d.anago to the eye or
-skin (86).-
Samuels and.. Mitby (87) studied th. effects af Lindane
exposere on 79 Cal..iforn.ia ras dents. who- bad been reg &i.ariy
xposed to Lindane La chair hamsa or b isLnaases, and. a
companion study (LiZ) compared. a smalL aapL. (4 O parsons)
which. had. been ocrnpa:ionaii.y exposed.. to Liadaae - with a.
sampLe v ick bad nor. The. first. scudr reported Lindane—
a&eaetacad changes. in. five blood. parameters (LLod.ane csnt,
blo-at:ereaciae 1.ev-eL,. rectctzlacyee- count, white bLood csi.L
count, aud poiymorphonuclear Leukocyte count), but there was-
no- widence of pancyropenia with rarirulopenia . ., a Icey
indicator of hypcpLascic or apl.zac-ic anemia. Speeific .atLy .
name of- the chatagen exceeded. the.. normal gangs,. and. there was
ne iLloe s . attributable. to- hanar.aloçical.. disorder.. Those-
invosti atar* did. note-,. howe#ar,. char some. abser,acions . vero
aa Ztcio!LtLy “bl.zarr&’ to re-q&ire a- conclusion that the
hemaeo Letic syscea. was aoc “entirely- normal” in a: fow
(b) Ocher- BLood- OvscrasLaa
_________ edicaL roport , swe Linked tindane. to other bloat
dyscras ias in parsons who bive had. no known exposure. to any
other itnavu henatoxic agent. tm the report described. above,
Teaç (83 ) Uscod rhu ease- of a. child exposed to a.- Liadana
hams vaporizer far- over a year. Liter in. initial. “teacacLva
diagnosis of. atypical. Loukania” her condition. was Later
described as a. “serious blood dysc raaia..” She rec.âverad.
if cot the ‘vapori:sr- was tomoved. L Isa,. as reported above,
SamuaL _and Lil.by- noted. unusuaL and. unclassifiable bema - .-
_____ LI
coLogic findings in a- few- of the subj errs Ln their- study-b
LI La a study of Lind.anaPs possibLe. facotoxic effoets,
Pac escu at al.. (73) reported that d ec-ary L ndana ( , 10,
or- U fl/kg) did not affect the blood or bone arraw in
experLaencal rats.
-33-.
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(2) Cest oL E, t,osure o Lindano in Combinatton
Uich Other Cbe icaLs
(a) cic i aenia nd v o Lastje 8o 1arro
some reports. of aptascic: ana .ia actribuced to
exposure cc Lindsue. and/or another ;os iblci hemocozie a euc.
LJ 1 .baharaT at. nJ. (88) ds.ecribed. ebii case of. a sanitation
department a apLayee vho dweicped “p yeLopc.hisis”k’ 9 days
after ei tp ure to DDt and undone. Sinilarly, a
boy 4 za.Lop a Lat i1. c@sa of aplascic ans ia after being
e pa e4. to Lindane and.. DDt fer eva eanths hila woc cing ow
a CeJ.Lfcrnia. fare C89). The c.1.i .icaL diagnosis in
part,. apLa e .c anemia d.1u3- to- L3secticidas.” - Liz tiscussig
thia case ac Ua uas acsp’i. .caL CLinica.L PatbalogicaL Canf1s .
renca, Cr.. Sha&z. stated. kis beLief, based upa his re,iew of tt
medical.. racure. and. ease reports, that. Lndaae rather than..
ODrvas earn’ prababl the responsi L hoeoccxic agent (89)..
?EZS a porr TL —L83 (90) described a ease of fatal.. apLa.ac
anemic La an Orcgoi faruer vho exposed to Lindane and-
toxaphene v Lit the iakalation arid ternal. rautszr whiLe sprayiig-
c:atc3.e in. ApriL 1969.. H a was treated. far a3pirat0rT ayepeo s
for uetu Ly year faLioving eh, onset at illness.. La pc b-er
1970 h!.s. cinditian.. yes. diagnosed as aplascie a,eeia eeeandar7-
to lindane. and. to:a hoae expastzra. The autapay report
identified. the cause of: dt ath as CL) acquirod aplasrie anscLa
tuci to LLndznci ard cozap?zea a exposure and (2) scum eyeiaeonoc
Lei keeia. sec:o c.ery en- i dic.i ti. CL)..
(b) Other 91eod Dvse?asLa
The- medical. Lit ature includes reports of other
bone- ar ou- aed blood- di.sordar - foli.c ving sinuicaceous
exposure cn LLndane and acachor heeotoxLc agent. Je41.ick.a
ec: al... (9!) daseribad t.aa 20 .year—oLd cousins ha Lived and
worked. cogechi arid. who,. a ftet siiultanacue exposure cc
Lindane -and DD , back developed p ariyeJ.oblasttc 1euke ta.
The aurkcrs coricind ad kat exposure Ca Liadarie cauzad the
1/ Dotj.azid’ flndL aL ø ceiQnar7 describes this condition
as. “general. aplasia. of. the- bone arrov.
—34—.
-------
leak.eeta Lit iiase cases. )Ioah :akL at al. (92) also reported
o. case of Leukuaia La a aaicatioa dopart ea saployus who
wee raga aeLy axpased co DOt aed.
(3) LdeaiaLo LcalCo Lder*ctoos
The L portaaca of the. r aLag oba.r &tLoas of
Liadaaeaaeocisccd h atazieS.ty is so svhat Li3itad by the
relatively a.L1.aaaber of cases this pr eatz aLuatiou
of these reports La acco a ca with cu.stoaary statisticaL
eat epidea ioLa;i:sl. critarLa eat thas precladms dor aias-
tiea of ether there is or ear a ca isa aed effect
relaeioa S tweea liedauc ozpos ra sad bloat dyscrasias. A
secout factor pr eeriu def .ttiv. stadis& L the Lack of a
suitable aaL ’a1 sodeL foe ezp eizeatatioe
After r ta; se,era.. of c e reports. cited. shave,
Dr . Jack. Crt.ffith EPA. v?ata that zoce port the
coues .t.Lo that exposura ta... ...iin4aee resu. :s La huaae. blood
dyseruLas. t ’ Re qeaiif Lad. this. coecLt.tsio b7 s tressiaS that.
tb data base was teadequace aa that. the hcdoLo y foi
____ ches 4ecor Laatiaus Lr 1. i:et (97)32
The aeticai case histories’ aue ari ed hers aud eLse—
where do ar s .cLsfy• api aetoLogic. c.ritarLa. far esta.blishiar
i’ ce se and- efface :eiatioaahip- hstveoa Undane aed. blood
tyacrasia.. aepo rs toseribieg- sLtiLrae.o &z exposure- of
meaerai peopLe to. Liadaae foLLowed. by the tevaLopeauc. of
ini.caL. iyapcaii La. aeLy- an of. the perscu so. expos d
that. adverse. :eac.e.teu. to U dae. ix hi tz1y indLritus.—
tixed. For eu pLa, La. cb report. of. the chiLd. who developod.
apiscic. aeuia. after the i&se- of. a. Liadaae produce to couc oL
the fantif do ’& aau e,. aoithar th chiLd 5z 9-yoar—oLd brother
ace his father exhibited sy pcaas evee though they too were
exposed to the ereae aec ej. curs (84). t U@ t’g fLrac
case, :h:aa faa .Ly ueb.rs. wore e posod. to. the pssc .cide L
their hoee, but. oaLy oee persaa deveLoped apLastic aneeia.
Further, the child. in. Vast’s third. case was exposed while
pLayiu La a aeiZhbarin3 child”s hous, but. there is ao
indicatice that this child.,. who presunably via exposed. :o a
Other .toilar- cases- is which LLsdane ay be a factor
are- eat. iziciudod here bocausa :he publ shad reports refer
only to “bea:ou- ho:acniortde” (!EC) and do cot speci r
vbac’er the cern refer3 to LL3daue, the gac a. Lsoaer of 3 C,
or o :ttcheicaL rzde 3ffC which is - a. iLx: re of 3RC .scners.
Sea, far eraeplee. Cavis. (93) and Danapoulcus (94).
1/ See also vart (9 ), who co tests reports of Licdaee’5
he ocoxi .L: snd an. - (96), h’i dLsputad t. Zavons svai a—
‘.4
-------
greacar e cant thza her visitor, da o1opod say a ptou,. tu
other caz £Lagricssd as “atypicaL Lou na” other seubers
of tho far ti.y did pruosut “abaaraaL” bLood c nnts and “nLLd
snsuii” (83).
Ocet. patiuaiaL ozpaaura to Liadano has been LLakmd to
bone .sarruu dyscrastas La peopLe v ita worked with LL:idaae
shortly before doeoi.opta3 iy ptaes (83), (39). (91), (92),
(98), CL13). Rawe et, Sauu.i.s and XLiby (87) La £ aysteaa:ic
Lu eatigacLaa of 79 persons eaposed reguLarLy to Liadana did
Oet uuco e: any aL3aLiLc&Dt kenato1o icaL dtsarders. Those
Lnwosti ators did oota, however, that if Liadanc.ossacia.cad
haeaeo1.c tcai. disturbaee is dopcadeet an individuaL citarac—
tartetics such as rat. so ttiv ity or 3soeci .c predLopasittea,
study vould. not. have do ac:od this - off ec becausu. of
cit. snail. eanpia population. Other physicians and ienti:t:
hew. ai.so conen:od thac LLndanas adverse offa ru. na ’-
depend an i divLcLuaL sessLtLvtcy.
.. Aenee- Iasards to l!ueaas atd Douesete La1 a1s
Section L62.LL(a.7)(3)(L)(A) provides :itac a robuttibL t
preauspt.Len shai.L a tsu. Lf the. pesticide as fornulaced
hs as sc are dernaL L 50 of 40 e /k or Less, if thu
pesticido- has sn- acute darn s - I of 6 Ik; at lass
as. diluted fat use La. the. frarn of a niec or °P °T . a-
the. peettaido has s o Lois-cLan of 0.0’ e /LLtor
or Lass- as fermolatat.. Th. IaritLag- Group Ls cotly-
riwjovjn score darns). and. i zLa:iou. data far the 641
dane. produces oither federaLLy istsret or far which
federaL. to aeration has- Soon sau he.. Dots- ops ozLse.. L-
anchor of those products- eoneaLn athar pestietdos as aettva
in redLeucs L u addition to Liodane. ho hasard posed by
products rtth several. active i:g:ndiau:s eay differ narkedly
frau. products labelod for- thu sane use hLck contain auly
Lindanc as an activa ingredient. Thu orki:g Group mean—
that sack re Lserane ha d reerad to certify to the.
the gLserants detar . atton as to whether or not
the- farnc,.iaeian as volt. as each d .uttau. re -tseared for- use
coa t or ozcead. thu. acute- easieiry enter-ta above. The
cestifiea:iau aunt Specify the acute t.D or LC of t!tc.
formu .LatLoa and. the eaitolaeioos or- data reLied upon L a
asking :nat decerniascion. In a4dt:Lou. t a 3 LR aotLcs
sha,al.d salLot: relay ant data.. an :he s effects fran- aU
sou .-cus. ShouLd any of the-abcv e c: .:erta be- exceeded by a
lindane product, the rebuttable pre uoptioa. should be
exteedod to taciuda issuance as :be basis of acute deraL
and/or i aLation effects of soy produ : eneeedL:g these
criteria.
—36—-
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£ abservod provio*aaly tho A oa y aaLaC F -I .
ctdo Z’Ln. dn opcvt Sy ten CP RS) vhich colisets and
biil.ates ropo ts of p.attcidc expoonre isveLvin tuina s aod
don.sti a a1.s.
A rov.i.ov of ?EU data far all opts..doti reportod
b.tveen 1966 sad Juno 15, 1976, which ipllcatod products
contaiais liadan. has discLosed 84 tacLdsntx inVolvLn3
sad. 15 tacldeata involving doees:tc asinats. “tact—
dents” iuclo4o sU association with a given pesticLdo and d’
ao alvays inply ingestion.
So —ieuea of 84 human incidents were ruportod to
bgv . o&currnd in the hone. Of tho S hui ae episodes, 49
roporti Lfsced Liadane alone and 35 Listed lind.an, L.a
caisation with snottier active ingredient. The. eajarity of
the Lindsao—snly cases involved. eh Area, and in. eeaty—fonr
of theSe. easee. rho child ingested. the penrtci4 . E pasure t a
Li.adau lad to cli icaL synpcoe.s La. baU of the Liidaae’-au1
reports. hospttalization. foLLowed, by death. occ &rret La five
at the ‘reported. episodes. Many- reported. tngosriaa.s of.
LLad aae by children wars of liadan. pe.i.L.ts far . se L x the now
cancelLed continuous weparL:eis..
ta coetrast. to Lind.ane alone, the aaority - sf the
Lnciden:s resv..Lting fra... pasurc . to Liadaas in. cou biaa . Laa.
with snottier pesticide Lnvolve@. siLts. Ienty—one of these
incidents occurred. La the! hone. Clin ral- syaptoas were
isted. for Less than. half of chose cases, and cits cases
rQLLtad.. ira. death.
Pit teen- Livestock, or so osta.c pe t iacLSents vote-
parted. t nina at these casos Liadano alone was
was ipLic. :od; Ltadans was preneac Ira. coobi.nattoa with
another acttvs ingredient in- ha - remaining six asso (77).
Th P &S. data dose not, however.. cessarily- include
aLl. incidents which hays- occurred duriag t s giv-ea time-
span.
‘. Posolatica d lons in Mn tarret OrranLs
Section 162.lL(3)(L .i)(C) praitdee that a reburtablo
presumption shall. arise if a pssticLde.s iagradiee:(s),
narabolics(s), or degradation product(s) can reasonably be
anticipated to resuLt in significant Local., tog anAl,
or national populatton reductions La nancargec araUlsnr, or
fataLities to aerabors of endangered pocies. This provision
reflects concern that- ;esticLde toncauLnants La air, water,
soil, and food supplics nay- adv crseiy affect the reproductLve
efficiency of natural pop . LaeLo s. cter ’ this ction., the
Agency nay- consider a pescLci-des patentLai for accunulation
—37—
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the e Lronent, sod its capaeLty for prod cLog chronic
effects which can reaoousbty be anetctpsted to Lead to
popnlattoo reductions. o reconi snd that the Agency not
presune agsLu t lindane on this baeia at this tine, b sc
seek. L a the iocLca of aebuttable ?res iapciou ir fornacLon
vbich viii. pernL coeplete a assuent of Lindaoes poencial
foi producing population reductions, porti.cu.Lariy anong
avian q,tl4LLg .
bLs rebuttable p au ptLon e ’itorLou La based on
scientific studies which euggost that another orgaisochlorLao
pesticide, DD, adversely affected natural. avLa.a papuLaticu .
through tbc actLa of its aboiite, DDE, au avian eggs.
I. en study, P.atcLiife (101) reported that & decraas in
eggsheLl ekaesa in. nat rsL raptor popuLat. .ons in. 3rica..in.
“coi cLdsd closely” vLth the pcat—11orL4 ar L tatro4ucttcn
of D ? into ;eoeaL usage. R.isebrougb. and Andersen (102)
sotablishet tba fecting 60 ppe O0E to exp .oentaL naiLar .
pauuLa:iou . reduced. eggsheLL thiclaeas by 17, and. T.cn;core
and.. Sanson (103) reported that 10 pptt DDE Ln the feed. of
b 1.acIt. ducts led. to. a. Z2 raductLan in. eg sa.LL thickness
at the .qnatorJi
CL) Lindarte itt !ixds
aesid e studies. hay e indicated that Lindane Ls -
reaenc in. avian specice ezposcd. to Undasa in 3atu:al..
and oxperlaeutal settings (see SectLon. t.A.(.)(d)) and is.
present in poui.try’ for huan to snnpticn. (seeSeerian. r..
A.(Z)(e)).. This deoeserat.ä that. L.Ln ann can. ant doen.
accuulaoe itt aviao. tissues. and. eggs,. thereby presenciag. the
potential. for causing population. reductions In. avian. wi1d1i ce.
1e recconend that the Agency soLicit additional
Lnfarnatiae. an LLndane ’s passLbia Long—cer n . chronic effects
on avIan. vt l .d .1 .if a based on several separate stadLes which
report that lindane residues are present in. tissues and.
.g s of wild, birds, indicating that such populatIons nay
be exposed. to and nay accunulare LLnd.ano and. that exposure
to L.iadac. nay Lr.c:eas enbryonic norraiity in. birds.
These- observations suggest chat pestic±de uses vhich nay-
sLilLcan. .Ly contribute to Liadano residues- L a ovine
eggs say- inereasa. embryonic mortality, an effeer which
would uitinateiy Load, to popuLation. reductions.
1/ 0t er studLes suggest that the nechaolsn involves
pesticide- Interference with haruocal re ziatloc of. eel—
cLun netaboilsu end. naose uea: abnormaL zobi I atIon of
celeL un for eggshelL formation (104), ( .35-).
-38—
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(2) £ffee os arod ceL:ac t
Saster a z4 SteeL. (106) assayed LLadan.s effects oa
the r . toduetive capacity of WhLt L .gbOr c ick .us (rable
2). Folla L:; an LaLtLaL. L0—see p —.xp sri enca1. obe. ,a—
tLo peetod, hens wore fed diets toataLoin5 0.1. 1.0.
10.0 ppe Liadan . far 10 weeks. T.in4ane—femdtn g had ao
aaaet. rabLs effect oa e g fartt.Lity. £c each t*ateent
leve l, hoveve:, Ltnta.ne—feeding vedt&cod batchabllity and
pdnctivo ef LeLQscy, which w as defined as the ratio of
the aeber of ChiCk.n hatchod p.: ten, etch controls set at
100. T irther, hens La escing 1.0 and 10.0 ppn. lindan.
prodneed. eggs whIch had. sa early no::ality rate (enbryonic
death b.tveen days 1 and. 7 of Lacnbatlon) si;f.Icanc1.y
oa.eeg than. the e &cla (pc0.0 ). s add Lo u., the data.
stiggest that Li an.e—Ceeting- aLso £.ne.r.asod the incidence. oL
enbryor..tc nartaLity late La inenba ioa (after’ day 7), bnt
since the control. data fat- the dIfferent createn.t groups
w arI .t . this reported. Increase Vn.3 ne conclusive.
TL8LZ 2. !TTZCT ’ OF L I —E ’EE3t 0 1 CRIC !f !CGS £10 t3& 0S
Cantro’L
0.1. ppn.
1.0 pp i.
LO . O_pp..
-rrere.
!arc i.
Reorod.
7 8_
94 . .
1.00.0
97.9
!].3
‘3.
.T.9
83.
73.1
9T.L
81.9
66.1
£ar ly
4.
2.1
1.1.
L.O
L.0 -
o :tal ity
(0—7 days of
3 -
‘.9
8.3
10.9
tneub n to i
-
Lace
s .
ã.a
.6
Z.1.
L.L.9
— 1ara1ity
(8—21. days of.
3
11.6
8..3
7 . 2.
- incubatton)
.
Eggshnt 1 .
4.
0.37
0.37
0.38
0.36 -
ThicknesS
3
0.31
0.31
0.33
A. 10—week pre—e per’t:ectaL abser atiou petod.
3. 10—week enp .rincnta .1. pertod.
Source: Saucer’ and. Steele ( 1.35).
—.39—.
-------
LO5 erc g (107) cbeer e4 sLaL1 r Lin4 ae—
relats4 effecta La four S c ost 1 .tve araetoas of the
Jspaaes. quaIl. ta this 5et ’ a s were sprayed wtt
1.5, -3.0, aed 6.0 LL daae. The ‘abryo .ic eortaLity
La rtated.. og s yes 6.06Z. After Liudaao
t sat eac far L4 days, the eoreali.:y rates were
L6.8 for L.5 Liadaae eat 2O.8Z for 3.O liadaae.
V arthsr, Lladane treat ea: delayed eg preductica La
the affaprlag of birds froe tr.ac@4 s s by 8 to 15
days reLat e to untreated graup3. L.tndaae treatasac
reduced eaziau e vaL hts f aa L5.6 far coacrels
to 14 ta U L a oçs of offeprLn of LLada —created.
htrds.
-40—
-------
Liedsus: ?osit .oa ocu cat 1..
T 1 ist of R z css
1.. U.S. Dep : aeat of Uo ith, diicatioa, sad 1fars.
1.969. - aepo t of ttte Se y s coamissLoft oa po3ei Lds
41 t sLr rs.stioa:hip •to e Lroua etai. beaLt . ‘ ra1c.
rsport. 1 iagtaa, DC. xwit + 677 pp.
2. eL ik v, SJ. 1971.. Chc stry of ps ticLdes. (TrsasL.
frost a%8 5L60.} VoLast. 36 La T.L. Gitat. or, od., Restd.&.
rev Love: reoiduos of psticides sad. oc or foroiga
cksiaieala La foods sad feece.. Spr .r.Vcrlag, New
ta rk .
3. :aa . - I.O’C.. sad. Z.E.A.. au.ztcka. - 1.967. 0r auocb.Lartne.
pesticides is. rctics. Uattzro 2.L3:3a6—348.
4.. CIzuaoa, 1.,. t.. Va.serap, sad 0.. 3er . 19Th.. The
cutout of paLych-Lariusted bydrocarbas is Arctic
ez &Lz.. Es.LL. EavLroa . Caataa. & oa.-LZ(5):52 —534.
3. eeo: BEC (Li idaiàe) Lu vater, dsted. Iul.y’ 1.9, 1.976..
Fraa D. Steve DeuuLs,. Natioaai .L Veter Noaits:iug. Progras,.
to Coarga BsgLey,. Of!Lcw of Special.. Psi cicido Rs, Lovs.
6.. S.. EsrioaasataL Tratoc os Ag.acy,. V eee SuppLy
Pra -se.. 1.976.. Laborstory .aatLoo. of d.rLsIiing. veter
pesticide auaLyaia. 6 pji. (bLL e4).
7. Eavtraaaaatai. Protoccios Ageacy. 1.976. Aebisat
air uouitarLa act.ivj.tios. Poet. No:. Quart. apt. No.
4.: 5.
8. heat1ey, C.A., sad l.A. rdssu.- 1.965.. Thdicacioas
of tbo preseace of a aaoebLorLoe Lusetfaidas La.
raiavacsr La - coatral. £ag Laad . . tu 207:486—487.
9. Lahuans, E., sad. P.. Nersel..- 1911..- P.sci: 4— ascicmung
is. Loft: aud NiedmrschLaages. (Pestietds doterinstioas
L a. air aud precipitatieu.I Gesoudii—Eag. 92(L2):366—368..
10. Cabea, J. ., and . Ficker:oa. 1966. Vide pread
crans1cea ioc. of pestictdes b air :rasspàr sad rais—Guic.
Pagu 153 —L76 La Oraaic pascLeides Lu e enuLronneat:
sdvancea L a. che zist: -y-, r .e z 50. Aór caa ChanicaL
Sociec , ashiugtos, D.C.
U. L cbteasteiu, s..?., tJ . - F zn recaan, SchuLz.
1971... ?ers -Lstaoee and verticaL dLs:rL ucLaa of DD,
LLuda:e-, sad a1de± -esiduaa , 10 sad 15 years a :or a
siagle soil. appl.Lca Laa. .1. Ag:. ca4. Cieir. 19(4);
7L8—T2 ..
-------
1.2. Vos S ., aud &.T.E. I se e . 1.970. esLdu. of
di€aL4 in, LL 4a a, DOT, a d ps achLoii to a Liakt 8an47
soil. after :sp at:d app1L tioa chrou hou a pe:Lod
of 13 yaaro. .1. A r. TaodCbs. L8(4):T17. .’719.
1.3. M550: 3 C and LLndan es14uo to. aoi,L, da od J 1y
22. 1.916. Ttro Lnn E. Carey, Tattotuil Soils Ztoaitortng
Pro r t a, to &kLLa Par on&i, 0ffi e of Spoetal.. ?ostieid
aav L4tV3I.
1.6. Va soo., A., sod .C flan. 1.964 . asLduss of or aL%ac Lo—
riae Lasecttcj4es La . golden aG1e. Srtttsh BLr4s 31(9):
34 1 —344.
1.5. Li 4er, LL., and. LS. DabLgrsu . 1970. C c c rence of
organochLorine L ecrici4ea Lo pb asaat s uL Sonth.
DT*kota.. Pes: . son. I. 3C4 U7—Z32.
1.6. Groichiis,. Y.A., Raonow, at d A.C. Fox.. 1969.. S &iwe’
pe ic de- si4 La t e Lake Poinsec: .co7 ru.
Proc.. I.fl.. Acad. Sd . .. 48:L51-L6Z.
1.7. Qathr t.C. 1.969 . atiaovtds residwas of ar anochJ.orioci
pesticides to. tngs of oaLLi zds ant bl .ac1c. ducks.. Pes:.
co. . 1. IC2):L1 .5—LZ3 1 .
1.8. Ke&:h, a.a.., and S.A. rtt . . L974 . . Uationvide org a ioc1iLa—
c Lne and. oercury residue, Lu vines af u .Lr ai,lards- and
bLack ducks dtng the 1.969—TO .une’ing sansoo... ?es: .
Moo,. 1, T(3/4 .):L53 - .L5 .
19. 7zLee, 0.!.., and S.C. !e&tlz. 1.976. 1atLouvtds residues
of or anachLorines in. vtng s of adult ulJ.a:ds. and.
bLeclc ducka, 1.972—73. Pen:. 1oo.. 1. 9(4):1.76 —L83 .
20. tLo. . 1969. 0r a brine tosecticido residues
La. stirLi. s . . Pest.. on . 1.. 3(Z) :1.02—114.
21.. otchun, TIA., A.. Gretcliua, and .C . . Reider. 1968..
vosLdues L&t ;rouse and ph ssoc of South
0akøca. Peac. non. . .1 .. Z(Z):90-9Z...
22. oeaan, 1.8., and 8. vao. Conderen. 1966. Sc e pLi inar
no tes on residues of chlorinated hyd carbon insacrtc.ides
in birds and. anoaLs to the So erL, nds. J. Ape. EcoL. 3
(Supp.):99- .L06.
23. T.iska, I.,G.CI 4os :ert , 3 .E.. Lauglais, and n.J. Stadalzan.
1964. Prabisos rssub:±ng fran the nisuse- of. 1..tndane
for chigger ouc?oL on turkey ra gos as elated to
residue in edibLe ttssu.. .1. Econ. E tanoL. 57:662—683.
-------
24. S deL àn, W.J., 3.3. LL’,’ a, 8. . T.aá3LoL , G.C. oe er:,
cnd 1.965 . ?o sLs:anc a f c ii.crLnatod bydraca’li”
bo t o Uiid.e rosi & s La c Lc cu L sues and eggs.
Poultry Sct. 44:435-437,
5. Stadelman, Z.J. 1973. Record of sans c emLcaL residues
L a pau.ltr7 products. BiaSeS... 23(7):6Z4 —428.
26. Lsb, 1.3., sod. L TayLor. 1 64. 3.osearek r porr:
fther eria1 on the effocts of gan a 3liC ieod dressL:tg
on brsedLng poassats. Cams Res. ASsoc., 4th Len.
Rep. Pp. 1.6.20.
27. 3urrago, R.U., ant I.C. Saba, 1.912. IanecrLcid r.sidttes
La ph santa alter being fed on. vhsat seod treatet vith
heptachlar and 1.4 C - LLntania. .1. Lean... onaL . 65(4):
LO 13-101.7..
22.. French, I.C.,. and.. 0 .t.. Jeff ertes .. 1968. Disappearance-
of 4 c fran ar-ian. Li’rer after death.. cn.re. 2.1.9:
. 1 .64— 1 .66.
2.9.. WaLsh,. D.F.., 3.1... 3.cgsr, and D.1. . . StaL1.ings. .a:ed ...
0r anoch.Loria t resi4uos in. fish 1.972—73: ationa1..
pesticide monitoring program. t .ooeo—LsaE. 1.8 pp..
Cunpublialted) . .
30.. Cakatarrer, 3.L,. and. C . . Veiss. L96T.. The eLia .inacicn.
of: D O T —C 33 , tieLdrLa - C 1.1 and. Lindaiie —C 1 from. fisb
falLci iug a. singLe aiubla;haL s pasure in.. aqv.aria.. Tgan .
Air . . Fish.. Sac.. 96(3);30L—307.
31.. Taskroubach., .T.,G. ttahmood, and 1.. SuLL ian. 197!.
Chlorinated hydrocarbon residues to sbeL .Lftah (Pelecypoda)
from. s usrios of. Long Island, ew TorL Pest. on. .1.
3(3) :242 —24.7
32. Grenwooi , a. .i.., t.A. Creichus, and. E.3.. 3ug hLes.
L9G7. teseceicido residues in,bi; gane mannsi.s of
South. Dakota. .1.. UL]4L.. Manage. 31(.) :Z33—Z92.
33. eme: 1973 and 1.974 .- lindana’ residues La food, dated
ovcmber 24, 1976.. Tram. FraderLck !agamai, Offlee
of Special. Pesticides Re’ iews, to files..
34. izt:, F.U., 4.3.. Tabs, and. SC. Strassnan. 1976. Or;ano—
chlorine pssetctde residues in human adl;oso tissue.
BuLL. Sac. ?hara. nvLron. Path. (1j:L7—L9.
-------
35. Connci on P arnacy ar d C nnt ry. Maclean sdica1.
£aooeia ion. 1951. anpor: en ha Ca nciL: eázie
offoces of baussna bssae Lcrtdo n4 Its prt cipaI
Lao ors. J.L. 1.A.. L47(6):57L—57 ’.
36. anzio, C.V. 1969. eeaboLLsn of pascicidos.
pacLa1 sciontif It r pact — vLidLiZa no. 127.
U.S. Cepact iont at tba Interior, Tisti and Wildlife
Sswiee, 3croan of Sport Fisheries and Wildlife,
Vaatiin tou, D.C.
37.. (ensio, C.?. 1974.. MetabalLs of poseieLdos: an
•apdato. Special. seisntUic report — vL14Lt o no.
184.. U. !.. Dape:tnenc at e t, Interior, FLSt and.
i.Ld1iie Sari Le n,.. Washigron, D.C.
38.. Grover,. P.1., and. P.. Sins. ,. 1965. Th netabaliss of
‘Y’—2.,1,4,5 ,6—p etLoroeyc 1 .ohox—L—an. and. 1’—bQxa—
ch.Lacacyeloh.xan. in. rots.. 8iac.hen. .1.. 9fr:5ZL—5Z3.
39.. Treai, .J.. and.. Z..U .. Chadvicic. 1973. ntaboLisn
at bazacbLaeoc eLahsxane to c LarapheaoLs and. off set
.at Laoner pcataat as Lindano neeabolisn in rae . .
.T.. A r.. Food. Chen... ZLC3 ) :6.2.4—6.27..
40.. evLand. T.. ., C.. rters,. and. C.!.. Lair. 1969.
De rodanion. of 1’— W in. ninulacat ia .ka inocundaents
as- affaetad b aeratLa .. .1.. Wa.ear ?aZ.l... Coacr.. Fed...
4 .L .:al74. aL88 . -
41. Esuazat,. R.J., and F. atsuura. 1973. rsanarizaes.en
to o —31LC. is. tha environnen:.. atnre 26.3:
480—481..
42.. atscnura, F.. U.J. !onezec, and .C. Path. 1976..
Factors- aft ocring nic:abiaL aecabo3. an of T—31IC. J.
Pesticide Sci. 1:3—8.
43. annda, T. 1971.. UygLarthc. acndies of pesticide
residues: report no. 1. Aceonulation af the 8EC
iSOners ;Y’znd ) in. ti a- body of the rat and.-
nrinary snerecion fcLi.owtng- oral. adnLnLst:aclon.
(! ans1... fran Japanese.) Zap. J.. 1yg. 26(6):358—
364..
44. memo: Lsoneri .aatien of Liadane La the- eavZ.roninenr,
dated August. 23, 1976. F;on l.W. C aduick., tabolic
Pathways Section. en Ron Rausnann, (u.S. avironnántal
?raeac: on Agencyj.
-44.—
-------
45. In atiatt L Agency for ea rch on Cancer, Uorld
!.aje 0r anLzacton. 19Th. IARC nonographi d ‘he
a .org of the carcinogenic rick of chenicals
to man. some o anocbl.orine pescicidei, vol. 5.
Lyon, (fracee3..
66. Taderaj. LLogLstc r. ‘Javsmber 6, 1969. 34 Efl 17962.
47. U.S. Depsrt enc of aai.tIr, Education, and Welfare.
Toad and Aduini3craciciu. 1972. C &c action
levels fat pesticide? rusidues.. I.oosc—Leaf.
(unpublished).
48. U.S. D.partnsn of AgricuLture.. 1968.. ra Natice
68—6: notice to ma ac.turers, formulators, 41s—
tribztors, and. regiacraa.ts of economic. pctscas.
Laosa—Leaf pub. 1.6. pp.
49.. 0..!.. !nvira uncal. P:oeeccLoe.Agauny. 1.971.. Fa
&e:ice 71—3: notice to naufacturers,. formulators,
tiztributors,. and. regLstra.ncs oL economic. poisons..
Looa.—Leaf pub.- 8 pp.
50.. U.S. Department of A rtcuLtura 1970.. P S. otic e
70—2.: nacLc cc nafacturers-, formulators, tie—
ttib t0tS, and..- registrants- of economic- poisons..
Loose—leaf pub.. 1.. p..
St.. flemo: su geec -ad actions on the posc1.cidaL uses- of
beuxtene hezachlori4a (35C) and Li.ndaoe, dated
ovsubor 27, 1974. To Director, Cr-i eria and
Evaluation Division.
Draft: not .ee of intent to cancel registrations of
a ll. pesticide products coucai Lng benzeae hoxachl.orida
and- o cancel. registrations of : ose lindane products
intended for use in feed. bins, dated Fahruary 15, 1975.
52. aeaL 3.eseareh. Group.. 1.97!.. Petition c c suspend all
household. aerosol p etJ.c.ide praduc.ts coacainiog Lindana.
Lease—Loaf pub.. 6 pp . . ( mpubLiebed.).
53.- emo: Lindane production, Januar7 1 . , 1977. TrederLck
tagenan, Project !anager, ospa, to Sdvia I. Johnson,
Deputy Assistant Adniniseracor, Offiée of PestIcide
Programs. C0tE fTLtL . -
54. 1.S.. nvtraunenca1.. oteerløn Agency, Sunan Effects
MonitorIng 3ranch-. 19Th .. ! aeional study of agri—
cul .turai, governmental, and. industrial. uses of
pesticides. (In press.)
53. U.!. Deparc enc. of Agriculture, Acul:ural
Stabil.izcion and Conserratiou Se r7ice. 1.973.
The pesticIde :r’rLev: 1974. ‘Zashlgtoc ,. D.C..
—45—
-------
56. U.S. Dop4art 1out of grie ro, A ic eur J. SrabLl.iza—
tio Lod Cot23ecvacLaa Sorv Ice. 1976. Tha psoticide
review: 1975. WaebLn too, D.C.
57 Chrj to sme. s.!., eed T.T. L gLbyh1, ads. 1975.
Sti pa :o4 cainogana: a. s abfL1o of tha 1IOSI1
tozic subotaucas ti . U.S. Dep rt eat of eaL ,
E4ucati,n, sod J.L aro, UaLoosl. ti &te far
OccupatLoaaL Safety sad eaith, aockvilLe, taryLsud.
58. Thorpe, S., and A. .T. a1ker. 1973. The. eo ieoLog7
of dialdrin (HEOD). ri. apaacive long-terio oral.
cazicitT studies .a aice vLth dioLdrta, DOT, pLieco—
barbitane, , —aaa d. T—aac. Yd.. cower. rozicol.
1 1:433—442.
59. 1., t.. isse an . oel.1ser. 1975. 4
corbution to the q astian of tbe possLhle hapatocar
ei ogen.ic off ac. at Lindano. ro icaLogy 4:91—96.
60 .. Coe,o-, 11.,. f. . aerorL,. and T. 1972.. Coa .- .
t ibu .tious to ecologicaL cheuLscr7. rr. Sepatowa
d cLopce.nr in iiee aftor adai seratian. of HC LSCnQ5
La. high. doeagu. . (t:ansl ... froa. C mu..) Checiesphero
I C 6) : 279—28 2.
6L. Nagasaki,. IL ., S.. TontL,. t.. iega,. .. ariigani, and. N.. tea.
1971.- CareLnogeu eLtT of bcnzene hersahioride (BaC).
Pages 343—333 . kahara, S. takayaua.,. t. $u ura,
and. S. Odasizina, ads., Topics- L cbe LcaJ. car aogeiicois -.
P SSS,. aa.LtL cre, 1aryLand.
62. eeo: carc4.nogcoteity of ilodane, dated arch 15, 1976.
Traa Chief, IetaboLLc ffacts 3raoch, to Cao e . Sagley,
(Office.. of Special Pesticido Z ’ievs1.
63.. feno: Carcinogen Ass snent Group pr.iiaiuar7 rerLe’,
of oncogenie data. on. LLndane, iia:ad Auguse 6, 1976.
Troe. E2.iaabsth. Andorsoc, tateri . Carcinogan Laze
Group, to Edvin. .1ohnson , Dop&CT Assiscanc Adninistracor
for- ?esticldas.
64. Sanada, t., C. Tutani, and T. 1iyaji. t duccian of
bepseona in nice• by- bennene ha ach1orida. Cane. 64(i):
5L 1—5L3..
65. Sher, S.?. 1974. znat In controL nice: Literature
tabulation.. Ton. App.. ?har . 30:337—359.
66. Ito, 1., H. Tagasa L, M. AraJ.. S. Sugthara, and S. tura
1.973. isto1ogLc and. tlazcruc:uraL dLes on bu
patocarclocgenitity eL beuzane he ac or . de in nice.
.1. latl.. Cancer .nsc.. 51(3):81.7—a26.
6—
-------
67. Titzhu h, 0.C.. L.A. tiolson aud J.P. T avLey.
1950. the chrouic toxietties of ceehuiezl ieuzeue
hsz ehLo Lde aed Its &].pha, b st aud ga sia iso ors.
1. Phar . Exp. therap. 1.00:59—66.
68.ot haut, a. 1954. Couuicatiaa au ey posiu iu:srn.
4. l.a preveucioft du eascer, SaO P&t.%LOe Citod Lu Food
aad Agricu uro Orgauiaatiou/’Jorld Uealth Orgaaizaclou.
1967. al .uatieu of sass pesticIde rostdt&es La food.
69. Ito, L, L. r1aga aki, !. Loe, S. Sugihara, I. iyaea,
4. LtaL. and T. ShiraL. L915. Briàf con unciaciou:
deuoLop euzc of paeaceL1 i1ar carciao as L.a. rata treated
vith. bensane ach1ortdc. .1. Natl.. Caacsr East.
34(3) :301—805.
70.. Ortega. P., W.J. Rayes, Jr.., and V.?. Durha -. 1.957.
?atheLo ie changes Lu. the- Liver of rats after feeding
La. Levels, of. r none Lsectictdes. A. .L. Lrch. Path.
64.: 614—6Z2.
Ti . ,. NaIshnoin, S.Ta., and U. !.. T.eibovicb. 1971.. Effect of
aaa .LL. doses of DOE and Liadane and their izturo an
sozuaL functIon and eubryogenosis Lu rats. Ilyg.. Sanir.
36(4—6) :190—1.94.. -
12 . . Caurtusy, E.D.. (1976.1 EvaLuation of three Liziclane
atjcLes.. t.eos,—Laaf. 1 pp. (unpubLished).
73.. Peerescu, St., V. Dabre, H.. L.Lbcuiei, Z. Pserescu,
and S.A. Cholbeng. L974 Stu4ie of the-effects of
lang—cern adninistration of argauachlora:e pesticides
(Lindane, DDT) on ch. uhito Laboratory rat.. Rev.
- !ed . Chirur-g, Ia. i. (4).
74.- EarL. F. ! .., I. XLLLer, and F.J. Van Loon. 1.973..
Reproductive, eseatogenic, and neonatal .f!ecás of
sone pesticides and related conpo uds is beagle
dogs and niniaturo- .eviao.. Pages 253—Z66 v.3.
Osichuana, ed. , Pesticides and. the onvironnene:
a. continuing controversy-. LstercontLuon:aJ. 2tedical
3ook Corporation, Xev lark.-
75. Saird 5 1cCgire, Inc. product Label: zo: Llndans
aenLailtable. concentrate. EPA Rag. 1o. 351.—Z21.
Octagon Process, Inc. product Label.: 12 Lindane
e ui tfLabLu concentrate. PL Rag. Xe. 6330—2.
—47-
-------
76. Hone: Liodaize &PL&, dated Septenber 29, 196. Fro
Chief, BcoLo ica1. Effects Branch, to frodoricic Ha onan,
Office of Special Peeticides C j Rrviqes.
Hone: aoizne of Lindace appLied to vc:or, dated
October 13, 1976. Fran Fred Bagenan, Office at SpecLa ..
Pesticide ftw,io , to iiLe .
Scbinsi, S.C., J.H. Patrick, Zr., and. . . Foreseer.
Undated. Toricicy and biocoaconcracion of BRC and.
L.thdaee La sei,.eted Q3t’zartn&e aninais. GuLf Breeze.
Concrib zeLog Uo. 288. U.S. £ac’Lonnontai . ?rotoctioa
A eaey, Environmental ko eartb T.aboratory, G if Breeze,
FLorida (unpub L shed).
Home: OPP—C&Z review of BBC—lindane, d emd March ZT,
L975.. o Thomaa 1. Duke, Laboratory ireccar, GRE3.L
to Dr. Donna B... Buroda, Of fLcs. of ?ro ran Integration..
Mac ok, B.J., and. i SA.. McAL lister.. 1970.. Iaseetic.ide
susceptibility- of ueo common dish fa i1y representatives.
Trans. A. YLsh. Soc.. 99(1) :20—27.
77. U.S .. T.avironsncal !.ratsctiaa. Agency, Pesticide Epi odc
Response 3raoch.. 1.976.. Episode summary- for reports
involving L &zdanc. Pesticide episode reviev system.
report Uo. 73. L .i aee—LeaE. 39 pp. (unpubLished).
78.. EPA Fort 7500—8: Eeport of palixation—caused. fish kiLl,
dated. July 7, L9T6..
79. Rolden A.?. 1.966.. Organrchlaeine insecticide resiiues
in. salnauid fish. r. App. E o1. 3(Sizpp . .):15—53.
80. Bays, T..&. 1971. - Vsaticide pollution. and. the effects on
the bioca of Chow 7aiLey Environ. ?ollut. L;Z05—
2.34..
81.. Memo: 3S;:,’j.tndan 1PjLI, dared !ebruar7 LL, 1.976. ro
WiJ.Lian. G. PhiLlips, Criteria and Evaluation Division, to
George agley, Office of SpeciaL Pesticide Key L ows.
82.. Memo: sueagen cL:y- of BMC—Liudane, undated. pram Ruth
Pertel, 0SP3.. to Fred. aa man, Project Manager.
Shirasu, r., M. Horlyn., B. !Ca.ta, .‘i. Furubashl., and. .
Fade. 1976. Mutagcniciry ser.ent g of pesticLdes in
microbial system. Mut. aes. O: .9—3O.
Bonus, V., and B.. Scam. L969. utagenic aelvity of some
pesticides in r sooht1a 1a a. ter . i3dust. sad.
38( 12 ) 50—3 2.
—48—
-------
3 &an1zajoL , Vo ., C. Kobrborn, and P. Prapptng.
191 1. MuCa;onitats — n or c i ngon nLt P s 1,zt4o L
Eo—nadiatad assay znd tr d. øominan:ea .ocaL aae an
dor aue. 51.oL. ZbL. 91:31,1—323.
tLscar . C., and La Piccolo. fL9l(?)]. Survop of
• p.arlcidoa for n a anicity by cbo bzctaria.L—p]aee
usay oc od. !nv. ant. Soc. !ovelc:. C?! pp. 6—8.
Scylaa, J.L. l916(?)). Cycatonic affects of vartoua
peocicidsa invivo and ‘Ltro (Abstract). Enrop.
zu . Soc. pp. so—n.
!xonora — anc,a .T. 197 1. The- tnflnonea of d azinon
and lindano an tko nitotic sLty and raryarype of
Lynpbocyrns ci Ltivatet t . . 31h1. 5aenoiol.-
38(L):344—34T.
Shar3a,. A. . ., and 3. Con i. 1969. £ cnaparat vs study
at tbn effsct.n of certain. cbaical agents. en chronosenas.
Acta. ioL. S d. Enng. 0(L):LL—Z1.
V’ .Ison, C.3.,. .. Eavthorna, and ... Tsou. 1951.
Spontansa ss and Lo4 &cad variations in nitosis. J.
asrod.. .;1.33—LS9.
V brig, L. . 1974... opagacL r. nucagsnLcL:y sc4Les
vttb poccicidso. L&&C. 3d. Pubi. LO;L L—L8L.
Ior’as, I.? . , and C. Cise :— ar:in. 1976. ents
of nnLripo1a anapbasos praduc:Lon by -T b.sac 2orocyc1o-
bsrane in onLon. root. tip coils. Cyrobiolog.te 9(2):
Z33—L 9. .
Epstein, s.s., E. Arnold, .7. An4:aa, . Sass, and
t. Sisbop. L 72. Dotonclon of cbaical nucagens by t e
Loniaanc. LethaL assay La : e• noun. oz. App.. ?barn.
Z3: 238—3Z5 .
83. . 5t, I.. 1967. kLndane and. nateLogL react .ous.
Arek.. Environ. RaaLtb 13:97—101.
84.. Vodopick,. .. 1973. C is:cba .a ch anuo: erytbropotettc
hypoplasia after- exposure to i’—ban:sne hexacbiorLde.
.I .A . . .A.. Z3 3) $3a—a5L.
85. ocd1ff, ?. 1. Cannor, and J. Seopa. 1966.
Aplastic an snia as3oc at d wLt sac:Lcidcs. ted.
1. AustralIa 1:628—629.
36. 7.5. !nvironencaL ? otoc Lon A;oncy. .971.. ?EaS
taper: TL—L3. L oe.—Leaf. (unpubli.shad).
—49—
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87. 5a sLs, A..J., a 4 L’lt. LcIL. ilum. • posare
to LL 4s s: eLL iictiL, bo atoLo Lcsj. s 4 bLoct s LcaL
•ffscts. S. Occup. 1.d. L3(3):L47—L32..
83. A1b ry, C. .1., Dubrtz y, od Guertft. L937. Obstinate
aplasti: aito ta causod by oxpoo ar. to Li da o, cr sL.
from I aeb.) Ar . taL. ?ref. 1 .8:687—691,,
8 . ae4sLo f, A.J., and D.E. Snitb, o4a.. 1,955, CLiatco—patho—
Lo Lc co &fo snca: ezpooure to tasacticidse, bono
nar:au hiituo, gascraincesti.naL blsoding, and uncontroil—
abL3 L .footiono. £a . S. sad. 1.9:274—286.
u. S. E vtrnnmos. .aL Procoetioc £g ncy. L971 . PEIS report
no. 71,—iSi. L. osa—Lcaf. ( inibLL ha4).
‘91.. Ssdieka,. V.!...., . . 8o ,iunska, E. SnLda, and. A. Kouba.
1.95$.. P o.!.ob1.astic Lenk.nia appearing sLutana au3L7
eva bLood. consins afee einu.Ltancoua contac vtth
axana Cha a LorocycLahezaa.). Acta S aad.
1 .61.: 447 .45 1 ,•
fl. !aahL:ak..L., ., . !iki, 8.. tajina. T. tarada., and.
A. £aoa a:a . . 1.969.. 4 . nasa of Len ania Loilovin; e peeure
ta .asactLc.iLn.. Lcta. ataL.. Iap... 2(4) :‘ 72—6 iT.
91.. Cavt , 8. . L959.. Latter: b sean hydrochLoride and
apLasC2 .c anaa .i.. 1.71:1.624—1625.
96. Qanopculoa, E., L. eLisatnoo, and C. zesas. 1953.
Sarioua poLsonL by chic eye hezane: ciiaics].
and Laborator ”- ob va:iaua on five casea. Aznh.
In4nn . Lyg . Oceop.. to4. 3:582—587.
95. aveo., 1.976. Letter: aasociat .an vs. causation.
S. i.&. 235:1841..
96. lIens, !..J’. 1976. Loe:er: apL .scLc anenia associated
with q—bsiixene hsxaehlorids. J.A.1.4. 236(9):1009— IQLO.
9T. ona: seud.ien daaLi ; with cases of bLood dySerasia,
nadaced frc Jae Crtlfich, Unnan Effects aaitarisg
Praneh, to Trans. Parsons, OSP!.
98. Vriber , I .., end. .7. I r:onssca. 1.953. Case of paonyeicph—
thists after ex osure to c orophesoehane and Sensene
hezach.Larid .e. £r:h. tndusc. E . Occup. 1ed. 8:L56—L6 .
99. Schua::maniz, . C1i ica1- obse a i us on t e
chronic :oz ci:’ of nhLor aated Sydrocarbon. (:aasl.
fran Cernan.) . Cesanca ;. L7;L —t!.
—50—
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100. satr a: oa, !. L9 4. a acoLo;Lc ’L LLserdors foiLovtng
exposer. o Laa.c cLd a. Cicad. Lied. Assoc. .1. 90:1166—
1 . 1 .68.
101... fti cctLIfo. ).&. 1967. D.coase La e ahetL vaLg t La
cogtaiz birds of prey. er . ZL3:208 Z1.O.
1.02. Ltscbroe;h, ft. ., and D. Z. £dsrson. 1.975. Sane effects
at D0 . sad PCS an xnl.Lards tad chair o;gs. .1. UL141.
liansa s. 39(3):30.3—il3.
103. Lou cote, J. .., sad T.3. Sanson. 1973. gsbeL1
br.ak.588 b7 Lac:Sattng b14cb decka fad DD 1. WL1 .dl.
sna e. 37(3: 9’3.394.
104. Jofferioo, D..I LJ 7. e dolay L aviz.La iaa prodw ted
by pp—GOT sad its poseIhIe si ificanc. La the firai4.
EbL.t L09:166—27Z.
105. ?ssk.aL1 ., .3_ 1.967. 3Lach.eLsery? pestf Lde—tadeca
eny e b s 4esen of steroids La birds. Sates. 21.6:
305 306.
106. Starer, 5.4.., and ES. Steels. 1.972. The effeer of
Lo i s lsveL-pes:ic .t&c..feedLag an -the fnr:1.LLry sad
hacctisbii.icy of .ckan eg s. Eanlery Sd. 51:71—76.
1.07. taO ertaa, T.. 1.974. The affects of Lisdine over
sesersi. a rac iooa an tiL .:y and eabrycaic nor:aL—
Lty-Lov&.s, tabi.LL y, eag p:adi&cc ion, and c sad
chick veighe.. (traniL. fran Trench.) Lrch. Last.
aiscal. Eabtyo . .. £xp. 57(2):269—232.
108. Spaul4iag, I.E.. 1.972. Pasticido and tRae.y natal.
resides. Proc. sac taduac. ae3. Caif., Aner. ieat
tas . Found., ChLcago, 1L., pp. L1—Z3. Cited tt u. !.
StadeLsaa. 1.973. Lecard of sonu cheaical.. resL ues La
poeLtry products. SLoSci. 23(1):62’—423 [ Sac relereaco
251.
1.09. Clirisrausan, . , and T.. Leaiabyhl. ads. 1.974. The
toxic. substances L Ist, 1.974 edition. u.S. Oepart oat
of Kesith, Education, and o1far., !!acLonai tastitete
for OccupationaL Safety and ea1ch, Rcc ULe, aryLand
1.1.0. t.S.. virocnentai. ?ratnc:ios A ane7, Office of
oxit Substances. 197 .’ ?raiLziaary assessaeac of
suspactad car so eas in drnt .in vater report to
Congress. ashiagton, 3.C. -
- —51.-
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UI.. u.S. £nvLo entzL Practe Lon A;ency, ‘ats S &ppLy
DL,Lston. L97 e. 1974 d Ln vate:: standards and
oLLnes. (Va ta , D.C.1.
112. T.R., and £.. Sa e1s. 1971. u an expos zre
to Li daue: eanpa:L ’e i of ao exposed a 4 nxpoae4
peptitatton. 1. Ocetip. !ed. L3(5):2 .56—238.
11.3. friber , I.., and 1. a san. 1953. Cases of
paa yc1opbthLata after exposure to chiorophenothan.
and bc n:eas hnxacblortde. Arch. suat. ayg. Occup.
ned .. 8:i.66
I .. . D aLt : C/LL:d .aize in reiacLon a nan and the environ—
a posn .nt4o r v ew — 1.973. Cri.:erLa and EvaLua—
CLan tvi Lcn, Ogflc. of ?escLc .d.e ?ra ra s, .$.
!nvironzentaI. ? acec iae Aency. F;. 157—175.
113. CnLf 3o &ch a.s4areh 9. 1976. xc:
csrcinaenssi- btaaaea7 ex rinutal dcsL n scac’ s
report: Lnconpl.eco — n t v,rL ted. Spp. (unpublLshed)
o a —
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