Free Motion for Discovery - District Court of Federal Claims - federal

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B-199618
1976 Bureau of Census data 'shows that'about 41.5 million of the nation's 79.3 ir-illion housing units <3o not have basements and 40.1 million had w&vni air furnaces. Therefore, there may be millions of honies constructed on slab with air ducts in or under the slab. .Also, while we could not determine the number of homes which have been treated with chlordane for. ~_f termite control, a wood protection expert at the Department of Agriculture told us that he believes most of the Nation's homes would have been or could be treated for termite control because termites are active throughout the country. -"'

In a May 1, 1980, letter to licensed termite control pesticide applicators, the Arkansas State Plant Board stated that until recently little thought has been given to termite control chemicals becoming involved in the air inside treated buildings, but that chlordane in treated housing is a probThe letter noted that the biggest problem is with .slab lem. houses with ducts in the slab, but that high chlordane readings in the air and on the interior surfaces of plenum houses are also common. The letter recommended that the^. licensees give serious consideration to the possibilities of air-contamination before treating any building, especially ':"' buildings with plenum construction.
CONCLUSIONS

.'

-.

-.

...'.

Assessing the health risk of a widely used pesticide is critical when a pesticide, such as chlordane, has been found to f.^use cancer in a laboratory animal and where there is' reason to believe that many people may be exposed to it. 8?=^ on the National Cancer Intitule's find ing that chlor-r dane causes cancer in laboratory mice, EPA should perform an RPAR on the pesticide to determine whether the potential As mentioned earlier, EPA risk outweighs its benefits. regulations require that EPA perform -an RPAR if_ a pesticide causes cancer in humans or experimental animals'.

_....

The n-s&d to perform an RPAR is further amplified because cf Air Force incidents showing that persons living in homes built on slab with air ducts in or under the slab Chlordane was found in the ho'^ been exposed to chlordane. air or nc'.'-ss treated for termites as much as 14 years prior to stmpling/ vhich may mean that residents are being exposed Collectively, the Air Force to chlordane for long'1 periods. studies r:3 other ot we obtained represent new information moLt of which was nor. available to EPA when it signed the l^B agreement with chlordane's manufacturer and others canceling most nontermite t:ses of chlordane.

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Aside from resolving questions on chlordane's continued use for hoir.e termite control, the question of the pesticide's possible harmful effects on persons living in homes already treated-with chlordane still remains. Because tfie RPAR program does not address this question, EPA needs to work with the Departments of Housing and Urban Development and ^/ Health and Human Services-to determine the potential for adverse effects in homes already treated with chlordane and practical methods for reducing unreasonable risk to occupants.
RECOV^ENPATIONS

We recommend that the Administrator, EPA, initiate a fon.-al risk/benefit review of chlordane to determine whether the pesticides registered for subsurface termite uses should be limited or canceled. The Administrator also should work with the Departments of Housing and Urban Development and Health and Human Services to determine the potential for adverse effects in homes already treated with chlordane and practical methods for reducing unreasonable risk to occupants.
AC^"CY COMMENTS

'.

We discussed these matters with the Deputy Assistant He agreed that of EPA's pesticide programs. EFA needs to look at chlordane's risk and benefit.
?.^r

--..-. is tra tor

We conducted our review at EFA headquarters in Washington, D.C. , where we interviewed numerous officials and examined pertinent legislation, regulations, and documents. We obtained information from officials of the Departments of Agriculture, Health and Human Services, Housing and Urban Development, and Defense and a pest control industry trade association. We also obtained and examined scientific reports and reviews from the above sources, as veil as technical data.

AR you know, section 236 of the Legislative Act of 1970 requires the head of a Federal ctoer.cy to submit a written statement on actions taken on our reco:r.77indations to the Senate Committee on Governmental Affairs and the House Committee on Government Operations not later than 60 days after the date of the report and to the House and Senate Committees on Appropriations with the agency^ first request for appropriations made more than
Reorcsrp.zation

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60 days after the .date of the report. We would appreciate being informed of any action you may take on matters discussed in this report.

We are sending copies of this report to the Secretaries -/ of Agriculture, Housing and Urban Development, Health and Human Services, and t-he Air Force? the four committees men- ~i tioned above? the chairmen of environment- and agricult'u'rerelated committees? members of the Congress who have ex*-^"'pressed an interest in pesticide regulation? and other interested parties. .^2H
Sincerely yours/

Comptroller General of the United States

^

^

/

^

\^ "s^'-^-<3 b:
CU^

II

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C H L O R D A N, E

REVIEW OF THE LITERATURE
October 1974

WALTER U. MELVIN, JR.
Colonel, USAF, MC

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Introduction
General Information

C O N T E N T S

Page
1
5

Toxicology Experimental

,, 8
9
----------."-----.-.

Human Experience

22-

Experience in Industry and Human Habitations

33

Chtordane Contamination of Family Quarters and Personal Property
Environmental Residues
Conclusions
Literature Cited

40

81 ^9 9299

Bibliography

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INTRODUCTION

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possible to calculate the total weight of chlordane used in each housing

unit.

These parameters are not so easily or clearly defined for the

conditions which exist in the housing units at Wnght-Patterson AFB.

The

date of application of chlordane into the sub-slab layers can perhaps be

determined and the weight of chtordane injected could be estimated.

Whether the injection was made into the compacted sub-soil or into the

pea gravel layer appears open to question.

Whether there is an unusually

high true ground v/ater table in the area or whether there is an artifi-

cially created ."high ground water table" beneath the houses due to poor.

drainage is certainly not clear.

This could be of significant importance.

The contairii nation of the family quarters at Webb AFB was "acute" and the
concentrations of chlordane found on floors, waits, ceilings, and else-

where throughout the units

carpets., drapes, clothing, kitchen utensils,

etc.

were several orders of magnitude greater than those found in the

units at Wright-Patterson

AFB where the condition might be

described as
~\

"chronic and recurrent" with-low levels of contamination existing in a
few locations in a large number of quarters.
Decontamination was dearly

indicated and successfully conducted at Webb AFB.

In the case of Wright"

Patterson AFB this probt&m is not so easily defined and decontamination
even If successful might be followed by recontamination if, in fact, the

cause of contamination 1s

,a

rising and falling "water table" beneath the

houses, i.e., chlordane is carried by water into the heating-air condition-

ing ducts after a heavy rain or the thawing of snow.

Having been trans-

located into the ducts, chlordane is then distributed throughout ^the
flow of warm air from the furnace through the ducts.

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One area of primary interest in the search of the literature was data
on the effects of long term, low level exposures of man to chlordane.

Was such data available for higher animals especially primates or was the
data limited to rodent species.especially the rat?

It must be remembered

that for practical purposes, infants, young children and women occupy
these quarters for 24 hours a day and might occupy the same quarters- for

a three or four year tour of duty.

Of paramount importance are data on

very young infants, the "crawler" or "scooter", pregnant women or lactating
women.
The availability or absence of such data would be a fundamental

consideration as to the occupancy-of these quarters in the future.

will be made in the Conclusions in regard to the data available in this area
.of vital concern.

-

Comments

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(A

GENERAL

INFORMATION

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Under the rules on appellation.of the .Council on Nomenclature of the
International Union of Pure and Applied Chemistry and in United States

usage, chlordane is 1,2,4,5,6,7,88-octoch1oro-,2,3,3a,4,7,7a-hexahydro"4,
7-methanoindene.

The common name approved by the International Standards

Organization and the British Standards Institute is 12,4S,6,7,8,8-octo-

chl oro"3a,4,7,7a-tetrahydro-4,7-methyt eneindane.

Synonyms are CD68 and Chtordan.

Proprietary or trade names are "Octa

Ktor", "1068". "Velsicol 1,068", "Dowklor", "Ortho-Klor", "Toxichtor" and
others.

For its manufacture, hexachlorocydopentadiene, made by the chtorination of pentanes

(USP 2,509,160) or by the

action of sodium hypochtorite

on cydopentadiene (USP 2,606,910) is condensed with cyclopentadiene to
produce chtordene,

CloHeCle? chlordene

is further chlorinated to

ch1ordane.

CloHeCle.

The trade name "Octachlor" is protected by B.?. 618432.

(Pesticide Manual) The compound contains about 68% chlorine.
it is a pate yellow liquid with a low vapor pressure,of
The molecular weight is 408.75.

When purified

1X10-5 mmHG at 25C.

The technical products is a viscous amber--

colored liquid of d25 1.59 to 1.63, viscosity of 75 to 120 centistokes at

130F.

It is insoluble in water but is soluble in most organic solvents

including petroleum solvents or fuels such as kerosene.

It decomposes in

the presence of alkali.
The commercial product consists, of

ct-CioHeCIs (melting point of 106.5

to

108C)

cind

Y-CioHGCIs (melting point of 104.5 to 106C) and a large

number of other chlorinated compounds some of which are insecticidally

inert (Fairhati,

1969).

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TOXICOLOGY

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TOXICOLOGY

EXPERIMENTAL

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Ingle (1965) stated that there have been two distinct periods in the

history of chlordane:

"Period .1.
a.
b.

Early Chlordane: 1945 through 1950

*1068 chlordane', produced by the Velsicot Chemical Corporation.
*Octa-K1or chlordane', produced by a different manufacturer.

Period 2.

Later Chlordane:

1951 to present

Chlordane produced exclusively by Vetsicol Chemical Corporation.'11

"Early Ch1ordane"was more toxic to warm blooded animals than was "Later

Chlordane." This was chiefly due to the presence of a toxic and irritating,
unreacted intermediate, hexachtorocyclopentadiene ("hex") which was reduced
to a negligible quantity in Later Chlordane; ...."Octa-Ktor" chlordane was

more toxic than was Velsicol chlordane of either period."

." Fou.ts (1970)

states, as quoted from Biological Abstracts, "Chlorinated

hydrocarbon insecticides such as chlordane and DOT are capable of affecting

hepatic microsomat mixed-function oxidases (Drug-Metabolizing Enzymes) in a
variety of animal species.

The effects produced in most species studied are The stimulation is probably caused by

stimulations of these liver enzymes.

an increased synthesis of these microsomal systems (enzyme induction) similar

to that produced by-treatment of animals (or man) with any of a variety of
barbiturates, e.g., phenobarbitat.

Not a11 such effects produced in animals

are extrapolated to man.

Preliminary evidence suggests that man wilt respond
in

to insecticides like DOT

the same way as the rat.

This response in man
Of great impor-

can occur at relatively tow levels of insecticide exposure.

tance are current studies to determine whether these insecticides can significantly upset steroid hormone homeostasis in animals or man, e.g., by stimulating steroid metobotism by liver nncrosomes.
Studies .of drug,

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(

chemical or steroid actions in animals and man exposed to insecticides are

also of interest.

Insecticides, by stimulating hepatic microsomal enzymes,

can cause increased or decreased drug or chemical toxicity or-actions.

The

effects of such enzyme stimulation depend on whether hepatic metabolism of
the drug or chemical increases or decreases their actions."

Ortega, et. a1. (1957) selected the chlorinated hydrocarbons, including
chlordane, for study because they represented a group of economically useful
poisons.

They stated, "Although human fatalities have resulted from massive

exposure, most interest has centered on the possible cumulative effects of
repeated low dosages which the general population may potentially obtain from
residues of foods or, in the case of "lindane, from thermal vaporizers."

The

chtordane was administered with the rations at dose levels of 2.5 ppm and 25

(A

ppm for a duration of up to nin'e months.
:rats necropsied.

No gross disease was observed on

At these tow levels of exposure only the liver demonstrated

cellular lesions which could be definitely related to exposure to chlorinated
.hydrocarbons.
Alterations such as pigment storage and hyaline droplet accumu-

lation were noted in the renal tubules'but proved indistinguishable from

changes seen in the controls.

Minor fluctuations of the splenic lymph.oid

stroma were present.

Ortega, et. al. state, "The type of hepatic change observed with these
compounds (chlordane, dietdrin, lindane, and toxaphene) was identical to that

seen at low levels of DDT feeding.

As exposure was increased in both dosage

and duration, three stigmata of cellular disease were-observed:

(1) centra"

lobular-ce'n hypertrophy, (2) peripheral migration of basophilic cytoplasmic
granulations, and (3) the presence of distinctive cytoplasmic inclusion
bodies.

The latter were called tipospheres for convenience in order to dis-

tinguish them from nonspecific hyaline or retractile cytoplasmic inclusions,

H

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(

which lacked the characteristic structure and staining reactions of lipo-

spheres." ,Severa1 other 'liver-cell lesions were seen though they were
difficult to evaluate.

Two types of parenchyma! bleeding were noted. 'The

first consisted only of unencapsulated masses of red blood cells apparently'

actively dissecting the cyloptasmic substance of the liver cells.

It was

seen in animals exposed to the tindane and toxaphene,series only.

In the

second type, there was more passive nondisruptive appearance which consisted
of small groups of red blood cells within a cytoplasmic hydropic vacuole

which had a distinct capsule or border.

The vacuoles stained fat negative

and contained a finely granular material which took the same stain as the

surrounding intrasinusoidal plasma.

The picture was one of plasma inhibition

by liver cells.

If.

was observed in those animals exposed to the chlordane

(jft

series.

It tended to be most prominent in the male animals at higher dosage
The authors state, "We are in agreement that careful microscopic

"levels.

examination of the liver cell wiTI reveal cytoplasmic alterations at levels

where biochemical and clinical examinations have so far failed to reveal any

^change, and the over-all consistency of these studies would tend to refute
the suggestion by Cameron

(1951) that laboratory

artefact is involved."

The

previously reported minimal dietary level (to produce histologic change) for

chlordane was confirmed and was 2.5 ppm in the diet.

Stohlman, Thorp and Smith (1950) found degenerative changes in the intestinal submucosa and convoluted

tubules

of the kidneys as we1'l as focal necro-

sis of the liver and edema and congestion of the lungs in chronic poisoning.

Ingle (1952) reported the significant chronic toxic effects of chtordane in

rats consist of retardation of growth rates, enlargement of the liver and

<-^

kidneys, "liver injury" myocardial damage and splenic alterations.
12

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Most investigators agree that, when used with care and ss directed,
chtordane would be considered a "safe" insecticide if, -in fact, any chlorinated hydrocarbon insecticide can be considered to be "safe."

These same

investigators, would also agree that until recently there have been only
minimal

frequently inadequately controlled

studies of the effect of low

concentration, long term exposure of animals and very minimal data on man.

In 1974, Barnett and Dorough stated, "Although chlordane is one of the older
and most commonly used chlorinated hydrocarbon insecticides, its metabolism
in animals has received little attention until recently.

This stems, in

part, from the fact that technical chlordane

is

composed of a complex mix*

ture of components including the cis- and trans- isomers of the insecticide.

'C'-labeled pure cis- and/or trans- chlordane has not been generally available."

One metabolite -whos-e significance appears to increase with each new

investigation on the fate.of chlordane is Oxychlordane

(1-exo,2,3,3a,4,7,7a

hexchydro-4>7-methanoindene).

This metabolite is formed from both cis- and

trans- isomers in animals and there are clear indications that it is a
sistent storage product.

per-'

(Schwemmer, et. a1. 1970; Poten, et. at. 1971;

Street and Blau, 1972; Dorough and Hemken, 1973.)

In the study by Barnett and Dorough (1974) a highly purified (98.1+% of a
3:1 mixture of the cis- and trans- isomers) chlordane designated HCS-3260 by
the Vest cot Chemical Corporation, the manufacturer, was used.

In addition to

^ne cis- and trans- isomers, other isomers or analogs were oxychlordane,

dichlorochlordane and seven other compounds were not fully identified and

were designated by tetters A through G.

The rat was the experimental animal.

Excretion was predominately by way of the feces in both male and female rats.

A total of 6% was voided in the urine of females and 2% in the urine of

males,

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Residues in the fat of rats fed 1, 5, and 25 ppm of HCS-3260 in the diet for
56 days was three times the level (in ppm) found,in the food.

In the liver

kidney, brain and muscle the levels were 1/8, 1/10, 1/25, and 1/50 that of

the level present in the food.
tissues.

Oxychtordane was the major residue i.n the

Its concentration ranged from 50% of the radiocarbon in the kidney
Oxychl.ordane was the most persistent residue in

to about 90% in the fat.

the tissues after chlordane was removed from the diet.

A number of investigators including Cram, et. at. (1965), Fouts (1965)

Burns (1966), Bernstein (1968), Dixon (1968). Fouts "(1968) studied the effects
on the hepatic metabolic pathways when chlordane was administered prior to or concurrent with administration of a drug.
animals were included in some studies.

Fetal and newborn (weanling)

It was demonstrated that several

hepatic microsomat, drug-metabolizing.enzymes are present-at very low levels

or absent in the livers of the fetus and newborn animals.

Phenobarbitone

and chlordane, inducers of hepatic drug metabolizing enzymes when given to
weanling or adult animals, are capable of causing increases in drug metabolism

in the new born and in 1 ate fetal life.

These enzyme inducers do no function

in early or middle fetal life.- These results were compared with those of drug
metabolism by hepatomas..

The multiple, rapidly growing hepatomas resemble the

liver in early or middle fetal life both in the patterns of detectable micro-

somat drug metabolism and in the absence of response to enzyme inducers.

In

the squirrel monkey it was shown that the intraperitoneat injection of.y-chlpr*
dane

(10 mg/kg) once daily for seven days resulted in a two to

six fold increase

in the activity of hepatic microsomat enzymes which metabolize 3,4-benzpyrene,

p-nitrobenzoic acid, aminopyrene and several other drugs.
binding power was increased.

Carbon monoxide

It was concluded that the effects of y-chlordane

treated squirrel monkeys and their hepatic microsomal enzyme systems are

14

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c

qualitatively similar to those previously observed in phy1ogenetica11y lower
species namely mice, rats, and rabbits.

In one study it was shown that

-y-chtordane treatment increased cytochrome P-450 and increased the rates of

drug metabolism in vivo and.in vitro, while decreasing the toxicity of each
of the drugs studied.

In young rats, prior treatment

with chlordane resulted

in an increased cyclophosphoamide toxicity.

Cydophosphoamide is converted

to a cytostatic agent by enzymes present in the hepatic microsomal systems.

Pretreatment

of rats with chlordane stimulated the liver enzyme which meta/

bolizes warfarin, thus markedly reducing the toxicity of the acute dose of
warfarin.

Phenobarbitat and chlordane, administered in dosage schedules

known to induce drug-detoxifying enzymes increased the concentration ratio of ^^"thyroxine between the liver and plasma in rats,.
Since no effects of

(J^

plasma binding of thyroxine were observed, these drugs stimulate the hepatocellular factors responsible for-the reversible accumulation of thyroxine in
'the liver.

Catlahan (1970) investigated the percutaneous absorption of dry chlordane
residues.

Female Albino ^ew Zealand rabbits, nine to ten months old were the
Results indicated that approximately 50% of the chlordane was

test species.

transferred from the glass slide to the rabbit after 10

12 minutes of con-

tact.

Other investigators have also reported on this rapid dermal absorption

of chlordane.

Boyd and Taytor (1969) writing in the Journal of Industrial Medicine and
Surgery report on a comparative study to determine the acute oral .toxicity of

chlordane in weanling rats fed a normal or a tow protein diet.

Wistar strain

weanling rats weiqhing 50 to 60 grams were divided into three groups.

Group

A ~-^-

one consisted of 133 rats fed a tow protein diet.
rats kept on a normal protein diet.

Group two consisted of 122

In Group three there were 141 rats
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receiving.a 25% protein ration as mixed animal and plant proteins.
The average lethal dosages were .137 rng/kg, 267 mg/kg, and 311 ing/kg for

Groups one, two, and three respectively.

Death occurred ens to four days

following chtordane dosing with the time interval to death decreasing as

.chlordane dosage increased.

Autopsies which were performed within one hour
,.l

after death reflected the same findings prevalent among the rats regardless
of dietary group. There was wide spread damage to the gastrointestinal

system, stress reaction in the adrenals, thymus and spleen, hepatitis, nephr-

itis, congestion of the blood vessels, associated dehyderation and organ
weight loss.
',

'-

The rats that survived chlordane exposure experienced irritation of-the

central nervous system, muscle spasms, increased urination, loss of appetite

(A.

and reduced body temperature. month after .chlordane exposure.

Organ weight Toss was in evidence even one

Sazonova, et. a1. (1959) reported that the LD^pp of a single dose of
chlordane given in an oily solution was 50 mg/kg for cats,, 700 mg/kg for

rats and 1000 mg/kg for mice.

The toxicity of chlordane applied to the skin
"Chlordane

of rabbits was essentially the same as in oral administration.

is a nerve poison, affects the central nervous system, is cumulative and

causes chronic poisoning.
chlordane in a dose of 1

Prolonged feeding of animals with food containing
5 mg/kg inhibited growth, induced changes in the

liver and caused poisoning of offspring.
and altered the blood morphology.

Chlordane stimulated respiration

Extensive affections of the respiratory

organs were observed in animals following a daily spraying for 20 days with
a aqueous suspension of chlordane

(Z gm/m3) or dusting

with a 10% powder for

9

10 days." 16

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c

'.
Table I shows the distribution of
a

chtordane in exposed rabbits and

.

rats.

Table II lists some of the chronic effects of chlordane.

(see pages 19

through 21.)
Deichmann and MacDonatd

(1971)-wrote in Biological Abstracts regarding
..,^_

the lexicological effects of DDT, aldrin and dieldrin on residents'of Dadei.,.,

County FL, and on rodents and dogs.

The autopsy results of non-occupation-

a11y exposed humans revealed a mean concentration of DDT of 9.7 ppm in 42

cases of accidental death, 9.4 ppm in 31 cases where DDT had been used
sparingly in home and garden applications, 19.4 ppm in 65 cases of moderate

use and 27 ppm in 22 cases where little safety precautions were taken, in the use of-DDT.
Studies involving human volunteers who were fed DDT and dieldrin singly

(j9

or in combination reflected different results between

males^and

females.

When DDT and dieldrin levels in the blood were towered and body fat concen-

trations.were increased, a decrease of body weight occurred in males.

In

females, this change was more marked but differed due to the fact that DDT

levels in the blood increased rather than decreased.
Feeding of aldrin and dieldrin (20-50 ppm) and endrin (2-12 ppm) to.

Osborne Mendel rats caused neither tumors nor cancer.
,rsts were fed atdrin and dieldrin but

In the case where the

not endrin occurrences of tumors were

low.

When combinations of aldrin

(3-25 ppm), dieldrin (3-25 ppm), chlordane
Swiss mice, "....viability and

(50-100 ppm), or DDT (100-250 ppm) were fed to

lactation indices were the most sensitive indicators of subtle adverse effects.*
When dogs were fed DDT and atdrin, either singu1ar1y or in'combination, the

development of the mammary glands, ability to conceive, and the survival

rate of the newborn were adverse side effects.

Higher concentrations of DDT

and dieldrin in the blood and fat tissues of dogs occurred when these compounds
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were fed in combination rather than singuTarly.
absorbed DDT

It was-concluded that

fs. influenced

considerably by.the presence o'f

.at drin or

dieldn'n and vice versa.

(Deichman and MacDonald, 1971)

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TABLE I
The Distribution of a Chlordane in Exposed Rabbits and Rats

Rabbit^.
Dose
C-14 aChlordane
20 mg orally 5 times per week for 10 weeks (100 mg/wk)

I.V. 27

Rat^
ug

% C-14 excreted in urine
% C-14 excreted in feces % C-14 stomach + duodenum less contents % C-14 gut less contents % C-14 abdominal fat

47.2% (in 12-wks)
22.72 (in 12 0.43 (13.62

1% (60 hrs)

wks)

29% (60 hrs)
0.6 (0.163

ppm) ppm) ppm) ppm)

ppm)

0.27 (20.43 2.59 (240..9 I.53 (231.82 0.05 (35.22 0.52 (44.32 0.09 (90.90

5.7 (0.245 ppm)
11.9 (0.489 ppm)

% C-14 subcutaneous fat % C-14 kidneys % C-14 "liver

.7.0 (0.167 ppm)
1.2 (0.159
1.6 <0.1

ppm)

ppm)

ppm5
ppm)

(0.038 ppm)

% C-14 heart
% C-14 spleen % C-14 brain % C-14 carcass
% C-14 blood

0.03 (75.00 ppm).
0.04 (25.0 II.25

<0'.l
0.1 (0.030 ppm) 26.2 (0.124 ppm)

ppm)

.(86.37 ppm)

0.34 (40.91 ppm)

<0.1

a.
b.

Animals were treated for 10 wks and sacrificed at 12 wks

Animals were treated once and sacrificed at 60 hours.Modified after Poonawalla,

NOTE:

K.R..

et.al. (1964) and Koch (1969)

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TABLE II
Soir;e Chrome Effects of

Chlordane

Dose

Duration

Species

Sex

Organ System

Effect

Reference

8 rng/kg '8 mg/kg

"

"

$ &o

Liver Kidney

Enlargement
Thromboses & fibroses Edema & necrosis'" of myofibri'is

Ingle (1952) Ingle (1952)
Ingle (1952)

Lung
Heart

B ing/kg
'8 mg/kg

Duodenum Necrosis of rnucosa ingle (1S52) & submucosa

.1 ppra

In 1

Rabbit

Brain

.-treatment
25 mg/kg -10 days

Inhibition of Mg,

Koch

(1969)

Cortex

Na, K-ATPase
Increased polar
metabotites of
Kupfer (1969)

Rat'

-$

Liver

;.

testosterone X 2.5
Kupfer (1969) Increased polar rnetabolites of Progresterone X.2.2
n
I)

Kupfer (1969) Increased polar metabolites of Desoxycorti costerone X 1.8

0.1 ug/fnl

84 days Human Ce^s

Ds rived
from cervi cat carcinoma

Cytopathic effects & growth inhibition

Gabliks & ^riedaan

(1969)
Gabliks &

10 ug/ml

>107 days

"

Large abnormal rounded cells

rriedraan

(1969)

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(
TABLE II (contd)
Organ

Dose
0.1 ug/m1

Duration

Soecies

Sex

System

Effect

Reference
Gabliks & Friedman

77 days Human Celts

10 fold" increase Derived into poliovirus from cervical susceptibility carcinoma

(1969)

5.0 us/mi

11 days

'15SS reduction in
vaccinia virus

Gabliks & Friedinan

replication
25 nig/kg 3 days
ti

(1969)
Fouts &, Rogers

Liver

Proliferation of smooth Endoplasmic re ti cut urn

(1964)
Hart &
Fouts

25 mg/kg

3 days

" "
"
Brain

31% increase In nncrosomal protein
Shortens CNS

(*65)

'<5 ppm

C . '-

.

14 days

'';'''."-.
14 daysLiver

-depression by

Kuntzman, et. al. (*65); Cormey,

steriod hormones et.al. (T66)
Stimulates the
Street

<5 ppm

metabolisniof drugs (1969) (amino pyrine,
warfarin, phenylbutazone, digi toxin, zorazolaniine,

chlorpromazine, hexabarbitot

KOTE:

Modified

references cited.

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