Kepone:  Position  Document
         Kepone  Working Group
         -Environmental Protection Agency

Section IA.   Summary  Checklist
                                          CRPAR Checklist - Active Ingredient
decachloro - octahydro - 1,3,4 methano - 2H - cyclobuti (c. u) pentalen -2-one
" ACTIVE INGREDIENT: • ' COMMON NAME: PhlnrrWnno APPROX. 1974 PROD. VOL. : 840.000 lb.
TRADE NAME: Kepone •
USES: * .
Insecticide x' Fungicide 	 '
Herbicide • Disinfectant
Criteria ' •
Acute Toxicity - llumnns, Domestic Animals
1. Dermal LDjo £ 40 rag/kg (formulated) Dertnal LDen of 20X a
(Dust 1 label 5% active) 410. mg/kg
EC (cone. ) 5% = 1620 mq/kq
(raibblts) .. =
W? (cone. ) i
i •
G (cone. ) '
j ••'.-'
2. Dersul LD5Q < 6 g/kg, (diluted for spray,)
• Chlordecone products are not avail-able 1n these formulations
' EC (cone. ) - .
KP (cone. ) . : •
'* G '(cone. ) .
' i
3. Inhalntion LC 5Q < 0.01 mg/liter (formulated)
Test at 10S concentration, only chlordecdne dust label
EC (cone. ) at 5% active .
No significant difference
wp (cone. ) in weight gain or liver or
lung -pathology among •
c (cone. ) chlordeconfe dust & plaifl dust
exposed mice & controls
Applicable PERS data tl.ice exposed 19 hrs. over- 10
day period.
4.6 cases human. poisoning(primarily children) ' •
In only one case was the causitive agent confirmed. No
deaths were attributed to acute poisoning.
* ••'.*•• St
Plant Growth Reg 	 y
Other ' .' &&*&
Study Triggers
162.11 Criteria
Pest Pet
Doc *•'
'est Pet
)EO 919
Doc. #
* *
2nd Verfficastbn


Study Triggers Np_ • :
162.11 Criteria • Study 2nd Verification
Criteria ' •. . ' Yes
Chronic Toxicity
1. Oncogcnic effects - man or mammals
(species: rats & mice : exposure: or!al " )
- *
2.; Mutagenic effects
(tests: • ' . . )
3. Other chronic effects — man or mammals
a. teratogenic ' • ...

• ' *
b. ncurotoxic
effect: tremors '

c. reproduction testicular atr()phy 5Q & 8Q ppM '
- effect: reduced reproduction in rates & mice

dosage: 5 to 37.5 PPM •
d. ' other: . • '


• • .

a" . '

.' '

•'• ''.


( '



IB (1)
and' (2}
aiiu \ *• /



(4) and
(5) -
' •.

• *
• •

* •

• . ,
. •
• ' •'
. _ •
Needed? '
• i
• * m

* •
'..'•'"' i
.... • " r*
••'•".-• '
* • •

f *
' . '
* No trigger at this time.   Issue'unresolved.

 Chronic Toxicitjf  (continued)
            monitoring data                 '
 Mass we  amounts  destroyed beneficial bacteria1 (sewage  treatment)
            petition studies (residue, !*!&$$*«&&•$

   5.   Fatality to endangered species

 Lack of  Emergency Treatment

  1.  No antidote or first  aid  treatment         .    .  •'

Acute ToxicitY-Wilnlff.   (calculation on attached  sheet)
                  Not applicable See Discussion.           '
  1.  Mammal:  feed  residue > acute oral LD£Q           .  .

  2.1  Avian:  feed residue > subacute dietary LC5Q '

  3.  Aquatics:  6" concentration * 1/2 acute LC50

  Applicable PERS data:

  Applicable monitoring data:  None except  these resultino  in
  USB Of.Oeannt hnttov hafte fnr fiya an*c   Tk- «           V,
                        ting ?fiis  use?  :  There are c^fently
Study Trlf.r.orn No
162.11 Criteria


• x.'
„ ,

• .

' X


2nd Verification
. '


                                                                                              .   •

Monitoring Data



Data aval labile in Hopewell area
(atypical) .
Kepone generally not looked for is
monitoring programs
FDA Market Basket  Not examined for Kepone residues
USDA Aphis
Incident Reports
Tolerances  '.005 PPM bananas
            .01'PPM banana peels(Pet.  OE0919)
            Agency currently revising

                                               Section I.B  Data Supporting Kepone RPAR Triggers
Oncogenicity      (1) Report on Technical Grade Chlordecone.
                  Carcinogenesis Program, Division of Cancer
                  Cause & Prevention, National Center
                  Institute, January 1976
                  (2) lexicological Studies on Decachloro-
                  Octahydro - 1, 3, 4- metheno-2H-cyclobuta
                  (cd) pentalen-2-one.  Data submitted in
                  conjunction with Pesticide Tolerance
                  Petition OE0919.  Allied Chemical  Co.
                  July 1. 1961

                                                                                 Length of Test
  112 weeks
                                                                                    90 weeks
Periods between
one & two years
Dosages Resulting
in Observed Effects
Males     24 ppm
Females   26 ppm

          20 ppm
          23 ppm
          20 ppm
          40 ppn
25 ppm
25 ppro
10 ppm
25 ppm
Increase over
(P<.05) of
Incidence of

Differences of
opinion by four
examining clinical
existed as to the
nature of observed
carcinomas, the
most serious diagnosis
by an examining
pathologist, is
listed below:

                                                                  -5-  .

                                                                                   Length of Test     Dosages Resulting
Reproduction       (3)  Good, Ernest E., George W. Ware
                   and David F. Miller, Effects of
                   Insecticides on Reproduction in the
                   Laboratory House:  I. Kepone,
                   Journal of Economic Entomology,
                   Vol 58, p. 754 (1965)

                   (4)  Toxicological Studies on
                   Decachloro-Octahydro-1,3,4- metheno-
                   2H -cyclobuta (cd) pentalen-2-one.
                   Data submitted in conjunction with
                   Pesticide Tolerance Petition OE0919.
                   A11 i ed .Ghent i ca 1 Compa ny.

                   (5)  Huber. James J., Some
                   Physiological Effects of the
                   Insecticide Kepone in the
                   Laboratory Mouse, Toxicology
                  - and Applied Pharacology,  Vol. 7,
                   p. 516 (1965)
                                 (mixed lot
                                 used in
                                 initial test
                                 subsequent 3
                                 tests BALB/C)

120 days
3 months
130 days
in Observed Effects
5 ppm to 37.5 ppm
50 ppm
80 ppm
10 to 37.5 ppm
40 ppm
                Reduced reproduction rate
                in chlordecone-fed mice
                and in their progeny
                Reduced reproduction rate
                No reproduction

          Acute Toxicity to Humans and"Domestic Animals

Discussion:  Available data indicate chlordecone does not meet
the criteria for RPAR trigger.

         Does Chlordecone Meet or Exceed the Criteria
         for Oncogenic Effects on Man or other Mammals

Discussions:            .

    Part 162. ll(a)(3)(ii)(A) specifies that if the compound induces

oncogenic effects in experimental mammalian species or in man

as a result of oral, inhalation or dermal exposure; or induces

mutagenic effects, as determined by multitest evidence; a

rebuttable presumption shall arise. Available data indicate that

chlordecone induces oncogenic effects in both sexes of mice and

rats as a result of oral exposure.  "The Report on Carcinogensis

Program, Division of Cancer Cause and Prevention, National Cancer

Institute, released in January 1976, reports the results of a long-term

study on the oncogenic effects chlordecone on both sexes of Osborne-Mendel

rats and B6C3F1 mice. Chlordecone was administered orally

-for -a- -pa-riod-of -SO-weeks. -  Ttie miee-we-r-e-sa-cri-fi-ced-after -9-0

weeks and the rats after 112 weeks; moribund animals were sacrificed

and necropsied.  None of the control rats developed hepatocellular

carcinomas.  For the mice 16% of the male controls and none

of the  female controls developed heptacellular carcinomas. Pathological

diagnosis revealed a statistically significant increase (P< .05)

in the  incidence of hepatocellular carcinomas in rats fed an average

24 ppm (males) and 26 ppm (females) and in mice fed an average

of 20 and 23 ppm (males) and 20 and 40 ppm (females). Extensive

hyperplasia of the liver was  also reported in both species.

This report presents a clear indication of  chlordecone1 s oncogenicity.

    Data submitted by Allied Chemical Company in conjunction

with Pesticide Tolerance Petition OE0919, entitled "Toxicological

Studies on Decachloro-Otahydro- 1, 3, 4-metheno-2H-cyclobuta(cd)

pentalen-2-one" (Document No. 108253.  July 1, 19&1) also indicates

that chlordecone is oncogenic in rats. Six groups of male and female

albino rats were fed  0,  5, 10, 25,  50, and 80 ppm chlordecone

respectively for periods of up to two years.   Only seven male rats

were examined at the 25 ppm dose  level.  Four clinical pathological

examined the slides made from the liver tissue of these  treated rats.

Liver lesions in one rat were diagnosed as hepatocellular carcinoma

by 2 pathologists and "evolving  carcinoma" by one pathologist who also

found "evolving carcinoma" in a second  male rat at this  feeding

level.   Of the sixteen female rats surviving at the 10 ppm feeding

level,  liver lesions in three were diagnosed as hepatocellular carcinoma

by one pathologist.  Of the nine female rats  surviving at the 25 ppm level,

liver lesions in one was diagnosed  as "evolving carcinoma" by one

pathologist.  None of'the 23 control rats developed heptocellular


    The primary  supportive data for  this trigger is from NCI.  The

Allied Chemical Company test,  which also indicates oncogenic effects,

may not of itself be definitive enough to  trigger for  oncogenicity.  The

method of conducting the latter  test,  however, may have minimized

the possibility of discovering heptocellular lesions.   In  the Allied

test mice were numbered and survivors of a given numerical

sequence were  sacrificed and examined  on selected dates. Examinations

were made only of rats surviving to these selected dates. Rats

which died in the interim were not examined.  It is probable

that rats not surviving to a given examining date may have exhibited

a higher incidence of hepatocellular lesions.

    It must be observed that liver biopsies of humans suffering from

chlordecone poisoning have shown this organ to have the highest

content of chlordecone of any tissue in the body.  Some  samples

have shown a mild toxic hepatitis on light microscopy.

              Other Chronic or Delayed Toxic Effects


    40 C.F.R. 162. ll(a)(3)(ii)(B) provides that "(a) rebuttable

presumption shall arise if a pesticide's ingredients . . .  produces

any other dosa'ge up to a level, as determined by the Administrator,

which is substantially higher than that to which humans can

reasonably be anticipated to be exposed taking into account ample

margins of safety	"

    There may be difficulty  in relating many pesticide uses to human

exposure.  The use of chlordecone baits is a  case in point.  The

major use of kepone in the continental United States is as  a roach

and ant bait in houses and on lawns and gardens.  Several registrations

for kepone bait formulation  enclosed or not enclosed in traps provide

for general applications along baseboards,  shelves,  sills, or wherever

ants may-appear.  Label directions do not always limit the amount of kepone

bait that can be applied to a single room.  Although these  labels also

provide a warning not to apply in areas accessible to children or domestic

animals,  the direction to apply where ants appear could result in

application in areas clearly accessible. This is contradictory to the

warning and could be followed before a warning is read.
    Another use in which a certain amount of  human exposure is entailed

is the use of 5% chlordecone dust on banana plants in Puerto Rico.  As

noted on the CRPAR checklist (Section IA), there is only one registered

product having this use. Directions call for  surface application of 8 Ibs.

of active ingredient per acre and allow for application at six month intervals.

   The direct hazard to humans would be a chronic dermal or inhalation .   '"•

effect.  The acute toxic effects of chlordecone for these routes of

exposure are, as noted, insufficient to trigger a RPAR.

    The registered product label specifying this use prescribes a

respirator for workers.  The hazard of this use depends upon the

degree of compliance with label directions.  Label revisions might

reduce neurological and reproductive hazards of chlordecone use.

The words "might reduce the hazards" are used in connection with

label revision because we obviously cannot insure that directions will

be followed by all users nor do we currently know if they are being

followed.   Should we assume that label directions, if clear and precise

and accompanied by adequate restrictions and warnings which if followed

would mitigate or eliminate the human or wildlife exposure, are adequate

to achieve  those ends regardless of the nature of the given pesticide?

    It is difficult to obtain information  on the degree of label compliance

for the multitude of users.  The degree of compliance  will obviously

depend upon education and a "host" of s'ocio-economicfactors." Label

directions  of pesticides are one method the Agency possesses for

controlling end use of pesticides.  Many hazards to man, wildlife,  and

non-target species are possible through noncompliance with label

directions  of most pesticides.

    To set a precedent of triggering an RPAR on this basis may be

to insert an unnecessary stumbling block to an effective and necessarily

expeditious review of the many possibly hazardous pesticides on the market

and scheduled for Agency review.   On  the other hand,  a RPAR is a mechanism

through which information may be elicited.  Because a presumption may be

rebutted through the submission of exposure data or data showing  that the Agency


presumption was erroneous, it does not constitute the Agency's

final determination.

    In addition, the effects of chlordecone exposure on many plant

workers as well as the oncogenic and reproductive effects in laboratory

mammals indicate that this compound is capable of extreme harm to

man.  Another pesticide compound may not trigger an oncogenic or

mutagenic  effect, yet may have other chronic effects which also

indicate its potential harm to man.  The triggering of RPAR by these

other chronic  effects is dependent upon human exposure. Can

we always  assume that adequate  label precautions attempting

to minimize human or wildlife exposure will always eliminate
the hazard?                  .'•  •" •.  ,    '

                      • Reproduction


     Several available studies on the effects of chlordecone on

mammalian species indicate that chlordecone produces chronic

effects on reproduction at levels ranging from 5-80 ppm.  A
                                '•   i •
1965 experiment performed at Ohio State University on the effects

of chlordecone on mouse reproduction revealed significant reductions

in reproduction in mice  fed chlordecone at dosages ranging
from 5 ppm to 37. 5 ppm.      The progeny of the chlordecone-fed

mice also suffered reductions in reproduction at the 5 ppm feeding


     Another  study performed at Ohio State University in 1965 revealed

reduced numbers of progeny in mice fed chlordecone at 10-37. 5 ppm
dosages.       At 40 ppm reproduction was entirely eliminated.

      In addition, a 3 month rat study reported in Allied Chemical

Company's Pesticide Tolerance Petition revealed testicular atrophy

in male rats at dosage levels of 25, 50 and 80 ppm.  Document

No.  108285 pp.  16-17 (April 11, I960).

      Sperm analysis of  chlordecone production workers exposed

to extremely high levels showed absent  or decreased sperm count

with markedly decreased motility.
±/  Good, Ernest E., George W. Ware, and David F. Miller,  Effects
    of Insecticides on Reproduction in the Laboratory Mouse:  I.
    Kepone,  8 Journal of Economic Entomology 754 (1965).

 7J  Huber, James J., Some Physiological Effects of the Insecticide
    Kepone in the  Laboratory Mouse,  7 Toxicology and Applied
    Pharmacology 516 (1965).

                    Neurological Effects


    Available studies on the effects of chlordecone on mammalian

species indicates that chlordecone produces neurological effects

at levels of 
              Fatality to Endangered. Species


    There appears to be no labeled use which would permit large

scale use against fire ants.  Except for the use against banana
                     .  . • •'   .-'.'•.'•...'.   v
root borers, all other uses appear to be for homeowner use

inside or outside the home.  There is little or no possibility of

hazard to endangered species from chlordecone in this regard.

    The hazard to an endangered species or  any species from the

banana use, which is a  surface application to the base of the

banana stem,  would appear to  be primarily from runoff.  We

have no data on the extent of this runoff nor  on residue levels

in streams or in aquatic organisms.  The extent of feeding by

any wildlife at the base of banana plants is an unknown. There

is no information presently available to the Agency that suggests

that a species' survival is endangered by this use.

                Acute Toxicity to Wildlife


    There are currently no registered label  directions  permitting

large scale use of chlordecone against  fire ants.  This would be the only

possible use which might result in application to areas frequented

by wildlife. As noted,  the banana use is an  unknown in this regard.

This  criteria  for RPAR is specifically  triggered only by  application

of pesticides to the feed crop of birds and mammals or by an

aquatic use.

 4. TJH» Md SubtttU
                 KEPONE:    Position Document  1
                S. Report Date
                   January  1976
                ft. Performing Organization Rept. No:
 ». Pa«loiii»lin Organization Name and Address
    WASHINGTON, D.C.   20460
                10. Prof*ct/TMk/Work Unit No.
                11. Contract