PESTICIDAL ASPECTS OF CHLORDANE IN RELATION TO MAN AND THE ENVIRONMENT
Prepared July 1972
Amended March 1975
Criteria and Evaluation Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
Washington, D.C.  20460
EPA-540/4-76-006
August 1976

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                                   Preface
Because of the Environmental Protection Agency's statutory mandate to protect
the public health and well being of its citizenry through control of economic
poisons, a comprehensive effort intended to insure intensive and regular
review of all economic poisons was initiated March 18, 1971, to identify
those pesticides which could represent potential unreasonable adverse effects
on man and his environment.  Since that date comprehensive "internal reviews"
have been conducted by staff of the Office of Pesticide Programs on a number
of pesticides.  The initial direction for this program came in a statement
outlined by the Administrator of the Environmental Protection Agency on March
18, 1971.

This report on chlordane was conducted from 1971 to 1972.  The chemistry and
methodology section was amended in 1975.  Other sections were updated in
a separate report entitled:  Pesticidal Aspects of Chlordane and Heptachlor in
Relation to Man and the Environment - A Further Review, 1972-1975.

This review evaluates scientific data in the areas of fish, wildlife, distri-
bution in the environment  (air, soil, water), residues in crops and food items,
and toxicology and epidemiology.

This review summarizes rather than interprets scientific data studied during
the process of reviewing chlordane.  It is not intended that this report
correlate data from different sources.  The review also does not present
opinions on contradictory findings.

The review of chlordane covers all uses of the pesticide in the United States
and should be applicable to future needs in the Agency.  The review was
researched and prepared by the Special Pesticides Review Group, Office of
Pesticide Programs, Environmental Protection Agency.
                                    iii

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                                 ACKNOWLEDGMENTS
Special Pesticide Review Group
Scientific Committee:

0. Garth Fitzhugh, Ph.D., Chairman (retired April 6,  1972)
Homer E. Fairchild, Ph.D., Chairman
Lamar B. Dale, Jr., Ph.D., Executive Secretary
Joseph G. Cummings
Thomas E. DeVaney
John C. Kolojeski
0. E. Paynter, Ph.D.
Fred H. Tschirley, Ph.D.
Clara H. Williams, Ph.D.
Anne R. Yobs, M.D.
Special Working Group on Chlordane:

Ronald J. Baron, Ph.D.
S. C. Billings
Roger L. Pierpont
Mary T. Quaife, Ph.D.
With Library Assistance of:

Robert Ceder
Claudia Lewis
Special Assistance with Amended Text:

George Beusch
Robert Caswell
Editorial Assistance:

Merle H. Markley
Kathy K. Smith
Rosemary Spencer
                                     IV

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                 Pesticidal Aspects of Chlordane in Relation
                         To Man and the Environment
                                  Contents
                                                                 Page No.
Summary
Chapter I.
            Summary of Current Pesticidal Uses
            of Chlordane with Alternative
            Pesticides Available 	
            Summary of Registered Chlordane
            Uses and Alternatives  	
            Discussion of Registered Uses
            of Chlordane and Its Alternatives  .  .  .
Chapter II.  Chemistry and Methodology 	
Chapter III.  Fate and Implications of Chlordane in
              the Ecosystem  	
Chapter IV.  Residues in Crops and Food Items  .  .  .
Chapter V.  Toxicology and Epidemiology of Chlordane
                                                                   45
                                                                   52

                                                                   65
                                                                   82
                                                                   90
                                      v

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                                     SUMMARY
Chlordane has been registered as an insecticide for use in agriculture, homes,
lawns and gardens, and structural pest control since its introduction about
25 years ago.  In addition, chlordane has been registered as a herbicide
primarily for the preemergence control of crabgrass.  These uses have
resulted in widespread application of chlordane in urban, suburban, and
rural areas.

Chlordane, a chlorinated hydrocarbon pesticide, is a member of the group of
cyclodiene insecticides which includes aldrin, dieldrin, heptachlor, endrin,
thiodan, chlordane and telodrin.  Chlordane is a term used to designate a
complex mixture of products.  Since 1950 technical chlordane has been manu-
factured by a process which is controlled so that the composition of the
product is relatively constant.  This consistency has permitted a more pre-
cise chemical evaluation of its formulations and residues.  Chemical and
instrumental analytical techniques are available and have been successful in
terms of sensitivity, precision and accuracy for certain components of the
chlordane mixture.

Chlordane is used primarily as a soil insecticide.  Therefore, any considera-
tion of possible environmental effects must place emphasis on the fate of
chlordane in the soil.  In most of the registered uses, the rates, methods of
application, and the environmental conditions differ.  However, while these
factors may differ, the controlling factors are the characteristics of chlor-
dane.  These are persistence, relative immobility in the soil, and a low
propensity for biological magnification.

The present agricultural use of chlordane accounts for approximately 25% of
the annual production.  Home use, including turf treatment and garden and
household applications, accounts for 25% of the annual production.  Profes-
sional use, primarily termite control, accounts for approximately 50% of the
production.

Chlordane was at one time registered for agricultural application to more
than 100 crops or uses.  This involved fruits, vegetables, field crops, and
noncropland applications.  A significant use was for soil insect control,
although foliar applications were also approved on fruits and vegetables.
Foliar use has become less important in recent years.

Chlordane persists in the soil.  Significant residues of chlordane can be
demonstrated in the soil 10 years after a single application.  Therefore,
the depletion of chlordane residues is a relatively slow process.  Chlordane
is relatively immobile in the soil.  Various workers have demonstrated that
chlordane does not move when applied to the soil and that the majority of
the residues are in the top few inches of soil.  Several studies indicate

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that contamination of water by chlordane is not a widespread problem.  Waters
examined in 1966 showed positive values of chlordane ranging from 5 to 75
parts per trillion.  However, abusive use of chlordane could result in
significant contamination of water.

Earthworms are able to concentrate chlordane from the soil.  Traces of hepta-
chlor and heptachlor epoxide have been determined in the fat of starlings.
These birds are not at the top of the food chain but are commonly found in
the diets of raptorial birds.  Substantial levels of heptachlor epoxide have
been found in the eggs of the coot, teal, and pheasant.  No evidence of
reproductive problems have been associated with these residues.

Residues of chlordane have been evaluated in fish from various bodies of
water.  In general, the values found have been less than 0.5 ppm.  Fish
examined from the Pacific Ocean failed to show detectable levels of chlordane.
Oysters taken from the South Atlantic and Gulf of Mexico had levels of
chlordane up to 10 ppb.

An examination for the presence of chlordane in water, suspended water plants,
algae, chubs, bass, and clams in water from an area of extensive agricultural
use indicated that the presence of chlordane was minute and no substantial
buildup was evident in any of the organisms or media examined.  The concen-
trating factor was 1.91 for algae, 1.20 for chubs, 0.9 for clams, and 0.45
for vascular plants, indicating no magnification of chlordane residues.

On the basis of results of two long-term feeding studies in rats, a no-effect
level for chlordane was established by the FAO/WHO Joint Expert Committee on
Pesticide Residues at 20 ppm; or 1 mg/kg/day.  On the basis of the results of
a 2-yr feeding study in the dog, a no-effect level for dogs was established
at 3 ppm or 0.07 mg/kg/day.  The acceptable daily intake for man was estimated
by FAO/WHO to be 0.001 mg/kg body weight.

A tolerance of 0.3 ppm was established for 65 fruits and vegetables in 1954.
This tolerance was reappraised and reconfirmed in 1965 by an advisory commit-
tee appointed by the Food and Drug Administration from a panel of experts
nominated by the National Academy of Sciences National Research Council.

Chlordane is absorbed from the gastrointestinal tract, the respiratory tract,
and through the skin.  It is stored in adipose tissue of rats, sheep, goats,
and cows and can be found in the milk.

Chlordane acts on the central nervous system, but the exact mechanism of this
action is unknown.   Large doses induce nausea and/or vomiting.  Low level
administration of chlordane produces histologic changes in the liver and
kidneys of some experimental animals as well as an increase in liver micro-
somal activity.

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Dietary levels (50-100 ppm) of chlordane in the diet produced a significant
effect on reproduction in mice.  However, 25 ppm chlordane had no effect on
reproduction in these long-term rat and mouse reproduction studies.  No
evidence of teratogenesis was apparent.  No specific mutagenic or teratogenic
studies have been carried out on chlordane.

No carcinogenicity studies, per se, have been carried out on chlordane.
However, chlordane was not shown to be tumorigenic in long-term studies in
rats.

Human poisonings and fatalities have been reported from both dermal and oral
exposure to chlordane.  In addition, chlordane, by direct circumstantial
evidence, has been implicated as a causative factor in several blood dyscra-
sias, including anemia, leukopenia, thrombocytopenia, and pancytopenia.

Since technical chlordane is a mixture of substances, including alpha-
chlordane, gamma-chlordane, chlordene, heptachlor, hexachlor, nonachlor, and
hexachlorcyclopentadiene, the pharmacological and toxicological properties
may vary from experiment to experiment because of possible variation in the
composition of chlordane.  However, the production of chlordane was standard-
ized in 1950 and the hexachlorocyclopentadiene content reduced to a maximum
of 1%.  Chlordane produced since that time is considered to be less toxic
than that produced prior to 1950.  In fact, the advisory committee appointed
by the FDA in 1965 concluded that the standards of production would allow the
constancy of the technical mixture.

In 1969 the Secretary's Commission on Pesticides and Their Relationship to
the Environmental Health recommended restriction of the usage of certain
persistent pesticides in the United States to specific essential uses which
create no known hazard to human health or to the quality of the environment.
Chlordane was included in their list of pesticides covered in this recom-
mendation.

In a statement issued on March 18, 1971, the Administrator of the Environ-
mental Protection Agency reported:  "Active internal review is being
initiated as to the registrations of products containing benzene hexachlo-
ride, lindane, chlordane, endrin, heptachlor and toxaphene, all products
containing mercury, arsenic, or lead, and all others deemed necessary to
review..."  In accordance with this charge, the Special Pesticide Review
Group has reviewed the hazards associated with the use of chlordane.

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                                  CHAPTER I

               Summary of Current Pesticide Uses of Chlordane
                    With Alternative Pesticides Available
Chlordane currently has  limited use as a foliar agricultural insecticide.  In
general, the  limitations  on the foliar use of chlordane on vegetable crops
include a caution not  to  apply after edible parts begin to form.  In all
instances the applications of chlordane by the foliar route include the limi-
tation not to graze treated fields with dairy animals or animals being pre-
pared for slaughter.   In  certain fruit registrations there are harvest limita-
tions of from 14 to 30 days following foliar applications.  In almost all
instances chlordane is not applied directly to an edible portion of the crop.
Alternatives  are available except for the use of foliar applications of chlor-
dane on pineapple to control ants.

Chlordane is  registered for foliar use in home gardens on ornamentals, shade
trees, and flower garden  plants for a multitude of pests.  The uses employ
concentrations of 1-2  lb/100 gal of water for foliar applications.  There are
alternatives  available for the home foliar uses which are less persistent
and/or less toxic materials.

The major use of chlordane in agriculture is as a soil insecticide.  In
general, soil treatment with chlordane controls soil insects such as ants,
wireworms, white grubs, Japanese beetle grubs, white-fringed beetle and cut-
worms.  Alternatives other than the chlorinated hydrocarbons are not effective
for certain of these pests.  The crops include certain bush and vine fruits,
citrus fruits, deciduous  fruits and nuts, field, fiber and forage crops,
grain crops,  bananas and  various vegetables.  The majority of the crops for
which chlordane.has a  registered use have a tolerance of 0.3 ppm.  The maxi-
mum allowable dosage to be applied to the soil is 10 Ib active ingredient
(AI)/acre.  However, the  usual rate of application is considerably lower.
The general limitation for the use of chlordane as a soil insecticide is as
a preplanting soil application or when no edible portion of the crop is
present above ground.

The use of chlordane as a soil treatment for the control of insects in lawns,
commercial turfs and nursery plant stock may be employed up to 10 Ib Al/acre.
The situation relative to alternatives is essentially the same as for the
agricultural  soil uses described above.  Use for nursery stock is extremely
valuable for  purposes  of  quarantine regulations in interstate shipment of
pest-free plants.

Seed treatment application utilizes 2 oz of actual chlordane per bushel of
seed.   This application is effective against the following pests:  seed-corn
beetles, seed-corn maggots, corn rootworms and wireworms.  Seed treatments
are registered with the limitation that the seed not be used as food or feed.
Diazinon is the only nonchlorinated hydrocarbon alternative available.  The
approved uses of Diazinonly are limited.

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Chlordane baits are limited to soil treatments for control of grasshoppers,
cutworms, crickets, and mole crickets.  This use is limited to those crops
for which soil treatment is allowed.  The concentration of chlordane used in a
bait is 1 Ib Al/acre with the limitation of not contaminating edible parts of
the crop.

Nonfood insecticide uses in agriculture include the treatment of agricultural
premises with a 3% oil or water spray or a 6% dust for the control of adult
houseflies, face flies, stable flies and mosquitoes.  The limitations on the
use of chlordane for agricultural premises exclude use in dairy barns and
poultry houses and caution that the materials not be applied to food or not to
contaminate feed or drinking water.  Adequate alternates are available.

Out-of-doors spray treatments of ditchbanks, field borders, roadsides and
vacant lands for the control of crickets, grasshoppers, mosquitoes, gnats,
flies, ticks, and chiggers employ chlordane at rates of up to 1.5 Ib Al/acre.
Suitable alternate pesticides are available.

Application of household uses of chlordane has been reported as one of the
significant uses.  The limitations preclude the use of chlordane in areas
where food is exposed in order to reduce the occurrence of residues on food.
Chlordane is used for household control of ants, ticks, mosquitoes, house
flies, roaches, spiders, scorpions and other general pests using either a 6%
dust or a 3% spray application, usually as a spot treatment.  Adequate alter-
nate insecticides are not available for all cockroach species.

Chlordane is used as a 5% dust or a 0.5% dip or spray on dogs for the control
of lice, fleas, ticks, and mange.  Limitations preclude use on young animals
or the excessive use of sprays and dips.  Alternatives for mange control are
limited to BHC and lindane.

Chlordane is registered as a herbicide for the preemergence control of crab-
grass on lawns.  The recommended dosage of chlordane for this treatment is
65-87 Ib Al/acre.  Several herbicides are very effective substitutes for this
use of chlordane.

The major use of chlordane in the United States is as a soil treatment around
and under buildings for the control of termites.  The usual rate of appli-
cation is 4 gal of a 1% chlordane solution per 10 linear feet along the in-
side and outside of foundation walls and partitions.  Aldrin, dieldrin and
heptachlor are the only alternatives available for termite control.

Chlordane is registered as a mosquito larvicide at a rate of 0.2-0.4 Ib AI/
acre in water.   It is registered as a mosquito adulticide at a rate of 1 Ib
Al/acre.  Paris green is an effective alternate for use as a mosquito larvi-
cide.  Chlordane is used in sewage treatment for the contol of Psychoda
larvae at a rate of 0.5 gal (90% concentrate)/3000 gal liquid sewage.

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Table 1 presents the currently registered chlordane uses by use pattern and
the registered alternative pesticides (substitutes) where available.  The
conclusions and effects of proposed actions are presented in subsection I.B.

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 I.A.
Crop or Site
of Application
Foliage Applications

Agricultural Crops

Blackberry
Blueberry

Grape



Strawberry
                                     Table 1.  Summary of Registered Chlordane Uses and Alternatives
Insect Pest
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
Strawberry root.
  weevil adults

Thrips
Strawberry crown
  borer

Strawberry root
  weevil adulrs

Spittelbug
Cotton
                         Boll weevil
                                                         1.5
 Registereu
Alternatives
Chlordane
Limitations
                                                  Apply before fruit starts to
                                                  form and after harvest.
                         Dibrom
                         Guthion
                         Parathion
                         Malathlon
                         Parathion

                         Carbaryl
                         Diazinon
                         Malathion
                         Methoxychlor
                         Parathion
                         Thiodan

                         Azodrin
                         Carbaryl
                         Endrin
                         EPN
                         Guthion
                         Methyl parathion
                         Methyl trithion
                                                                           Do not apply after bolls open.
                                                                           Do not graze dairy animals or
                                                                           animals being finished for
                                                                           slaughter  on treated fields.

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                                                                          Table 1. (continued)
                 Crop or Site
                 of Application
Insect Pest
                                     Cotton fleahopper
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

       1.5
CO
                                     Darkling beetle
                                     Fall armyworm
                                1.5
                                1.5
                                     Grasshoppers
                                1.5
 Registered
Alternatives
                         Bidrin
                         Carbaryl
                         DDT
                         Dibrom
                         Endrin
                         Guthion
                         Malathion
                         Methyl Parathion
                         Parathion
                         Phosphamidon
                         Trichlorofon

                         Carbaryl
                         DDT
                         Endrin

                         Carbaryl
                         DDT
                         Endrin
                         Methyl Parathion
                         Strobane
                         Toxaphene

                         Carbaryl
                         Malathion
                         Methyl Parathion
                         Strobane
                         Toxaphene
Chlordane
Limitations
                                     Tarnished  plant bugs
                                1.5
                         Bidrin

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                                                         Table 1.  (continued)
Crop or Site
of Application
Citrus
Apples
                    Insect Pest
                    Thrips
Grasshoppers
  (outer foliage to
  drip line)

Codling moth
                    Oriental fruit moth

                    Plum curculio

                    Bagworras
                    Thrips
                    Flea beetles
                         Maximum or Usual
                           Dosage Rate
                           (Ib actual
                         insecticide/acre)
                                                    1.5
 Registered
Alternatives
 Carbaryl
 DDT
 Endrin
 Guthion
 Malathion
 Methyl parathion
 Parathion
 Phosphamidon
 Strobane •
 Toxaphene

 Toxaphene
C- .lordane
Limitations
8
8
8

Carbaryl
Parathion
Malathion
Carbaryl
Carbaryl
Parathion
Malathion
14 days.  Apply to trunk and larger
branches and to outer foliage at
drip line.

30 davs
                                                                      Diazinon

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Table 1. (continued)
Crop or Site Insect Pest
of Application
•
Apricots Plum curculio
Nectarines
Peaches
Catfacing Insects
Pears Plum curculio .
Thrlps
Flea beetles
Pineapples Ants
Corn (field) Corn earworm
Maximum or Usual
Dosage Rate
(Ib actual
insecticide/acre)
8
8
8
8
8
2
' 1.5 .
Registered
Alternatives

Carbaryl
Dieldrin
Guthion
EPN
Malathion
Methoxychlor
Parathion
Carbaryl
Dieldrin
Guthion
Parathic.'.
Carbaryl
Parathion
Diazinon
Malathion
Diazinon
Aldrin
Dieldrin
Carbaryl
Diazinon
Parathion
Toxaphene
Chlordane
Limitations

30 days
30 days
30 ^ays

30 days


Do not feed bran or husks to
livestock.
Do not feed treated forage to
dairy animals or animals being
finished for slaughter.

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                                                         Table 1. (continued)
Crop or Site
of Application
Insect Pest
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
 Registered
Alternatives
Chlordane
Limitations
                    Corn silk fly
                                                                      Parathion
                                                                      No :estriction of grain.
Small Grains
(Barley, Oats,
Rye, Wheat)
Armyworms
                         Carbaryl
                         Malathion
                         Methyl parathion
                         Parathion (except
                           on rye)
                         Toxaphene
                     Do not apply after heads begin to form.
                     Do not graze treated fields.  No restric-
                     tion on use of grain.
Rice
                    Armyworms
                                                                      Do not apply after heads start to form.
                                                                      Do not graze treated forage.  No restric-
                                                                      tion on use of grain.
Flax
                    Crickets
                                                                      None
                                                                                          Do not apply after blossoms appear.
                                                                                          Do not feed treated forage to dairy
                                                                                          animals being finished for slaughter.
                                                                                          No restriction on the use of treated
                                                                                          grain.

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                                                         Table 1. (continued)
Crop or Site
of Application.
Asparagus
Beans
Beets
Insect Pest
Asparagus beetle
(post-cutting use)
                    Flea beetles
                    Green stink bugs
                    Cutworms (climbing
                      and surface)

                    Flea beetles
                    Annyworms
Maximum or Usual
Dosage Rate
(Ib actual
insecticide /acre)
1.0
Registered
Alternatives

BHC
Carbaryl
Malathion
Rotenone
Chlordane
Limitations

Post-cutting only
                                                  Carbaryl
                                                  Methyl parathion
                                                  Methoxychlpr

                                                  Carbaryl
                                                  Dibrom
                                                  Guthion
                                                  Methyl parathion

                                                  Dylox
                                                  Phosdrin

                                                  Carbaryl
                                                  Malathion
                                                  Methoxychlor
                                                  Methyl parathion
                                                  Parathion

                                                  Dylox
                                                  Malathion
                                                  Methyl parathion
Do not apply to green or snap bean
after pods begin to form.
Do not apply to green or snap beans
after pods begin to form.
Do not apply after seedling stage
if tops are to be u:-:d as food.

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                                                         Table 1. (continued)
Crop or Site
of Application
Blackeye peas
(Cowpeas)
Broccoli
Brussels sprout
Cabbage
Cauliflower
Collards
Kale
Kohlrabi
Insect Pest
Flea beetle
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
Cabbage worms
                    Flea beetle
 Registered
Alternatives
                         Carbaryl
                         Methoxychlor
                         Carbaryl
                         Guthion
                         Dylox
                         Parathion

                         Carbaryl
                         Dibrom
                         (except
                         kohlrabi)
                         Cuthion
                         (except collards,
                         kale and kohlrabi)

                         Lannate (cabbage,
                         broccoli, cauli-
                         flower only)
                         Parathion

                        • Phosdrin (except
                         kohlrabi)
                         Thiodan
                         Toxaphene
                         Carbaryl
                         Methoxychlor
                         Methyl parathion
                         Parathion
                         Rotenone
                         Thiodan
Chlordane
Limitations
                     Do not apply after pods start to form.
                     Do not apply after e
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                                                         Table 1,  (continued)
Crop'or Site
of Application
Celery
Cole Crops
Carrots

Corn, sweet
Insect Pest




Armyworms



Flea beetles

Green stink bugs




Harlequin bugs
Carrot rust fly

Corn earworms
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
       2

       1.5
                    Corn silk fly
                                1.5
 Registered
Alternatives
 Malathion
 Lindane
 Phosdrin

 Diazinon

 Dibrom
 Methyl parathion
 Parathion
 Thiodan

 Carbaryl
 Dibrom
 Parathion
 Thiodan

 Parathion

 Carbaryl
 Diazinon
 Lannate
 Parathion
 Thiodan
 Toxaphene

 Parathion
Chlordane  "
Limitations
                                             Do not apply after celery begins to bunch
                                             or after one-half grown.
                                                                                          Do not apply after edible parts  start  to
                                                                                          form.
No tine limitation

Apply primarily to silks.  Do not feed
treated forage to dairy animals or
animals being finished for slaughter.
                                             No restriction on the use of corn as humai
                                             food.

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                                                         Table 1. (continued)
Crop or Site
of Application
Cucumbers
Melons
Squash
Insect Pest
Cucumber beetle
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

       1.5
                    Squash bug
                                1.5
 Registered
Alternatives
 Carbaryl
 Lindane
 Malathion
 Methoxychlor
 Parathion
 Rotenone
 Thiodan

 Carbaryl
 Lindane
 Parathion
 Thiodan
Chlordane
Limitations
Do not apply af-
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                                                         Table 1. (continued)
Crop or Site
of Application
Lettuce
Insect Pest
                    Armywonns
                    Lygus bugs
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
 Registered
Alternatives
                         Dlbrom
                         Dylox
                         Lannate
                         Methyl parathion
                         Parathion
                         Phosdrin

                         Carbaryl
                         Parathion
                         Phosdrin
Chlordane
Limitations
                                                                      Do not apply af • ir edible parts .start to
                                                                      form.
                    Serpentine leafniner
                                                  Dizalnon
                                                  Dime cheat-:
                                                  Dibrora
                                                  Parathion
Okra
Onion
Spotted cucumber
  beetle

Serpentine leafminer
                    Stink bugs
                    Thrips
                         Parathion
                         Phosdrin

                         Parathion
                         Toxaphene

                         Carbaryl
                         Parathion
                         Phosdrin

                         BHC  '
                         Diazinon
                         Dibroin
                         Guthion
                         Malathion
                         Parathion
                         Phosdrin
                     Do not apply after edible parts start to
                     form.
                                                                      Do not apply to green or spring onions.

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                                                         Table 1. (continued)
Crop or Site
of Application
Peas


Peppers
Potato
Insect Pest




Pea Leafminer


Climbing cutworms


Flea beetles


Serpentine leafminers



Potato flea beetle
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

       1.5
                    Colorado potato beetle
                                                    1.5
                                1.5
 Registered
Alternatives
 Parathion
 Toxaphene

 Carbaryl
                         Carbaryl
                         Parathion

                         Malathion
                         Lindane
                         Diazinon

                         Carbaryl
                         Diazinon
                         Dibrom
                         Dieldrin
                         Parathion
                         Phospnamidon
                         Rotenone
                         Thiodan

                        'Carbaryl
                         Dibrom
                         Diazinon
                         Guth'ion
                         Phosphamidon
                         Thiodan
Chlordane
Limitations
                                             Do not apply after edible parts are
                                             starting to form.
                     No time limitation.

-------
                                                               Table  1.  (continued)
     Crop or  Site
     of Application
     Tomato
                          Insect Pest
                          Serpentine  leafminer
                          Flea beetles
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

       1.5
oo
                          Leafminer
                          Leafminer
 Registered
Alternatives
 Diazinon
 Dibrom
 Dimethoate
 Guthion
 Parathion

 BHC
 Carbaryl
 Dibrom
 IDE
 Thiodan
 Toxaphere

 Carbaryl
 Dibrom
 IDE
 Thiodan
 Toxaphene

 BHC
 Diazinon
 Dibrom
 Diaethoate
 Guthion
 Parachion
 Phosphamidon
Chlordane
Limitations
                                             Do not apply after fruit begins to form.

-------
                                                         Table 1. (continued)
Crop or Site
of Application
Home Gardens

Flower Garden
Plants
Ornamentals and
  Shade Trees
  (foliar)
Insect Pest
Ants
                    Bagworms
                    Black vine Weevil
                      adults
                    Crickets
                    Earwigs

                    Elm leaf beetles
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
1 Ib actual/
50 g^l water
                         1 Ib actual/
                         100 gal water
                         1 Ib actual/
                         100 gal water
                          1  Ib  actual/
                          100 gal water

                          1  Ib  actual/
                          100 gal water
*Soil application
 Registered
Alternatives
                                                  Dlazinon
                         Bidrin
                         Carbaryl
                         Diazinon
                         Dinethoate
                         Dylox
                         Malathion
                         Toxaphene
                         Trithion

                         Dieldrin
                         Hepca' '-.lor
                         Thiodan

                         Dieldrin*
                         Dieldrin*

                         Carbaryl
                         Dieldrin
                         Di-Syston*
                         Lead arsenate
                         Metasystox-R(R)
                         IDE
                         Thiodan
                         Toxaphene
Ohlordane
Limitations

-------
                                                                      Table 1.  (continued)
             Crop or Site
             of Application
Insect Pest
                                 Fullers rose
                                 beetle

                                 Grasshoppers
                                 Imported fire ant
                                 (mound treatment)

                                 Lacebugs
NJ
O
                                 Leafminers
                                 Leafrollers
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

1 Ib actual/
100 gal water

100 ^al water
1 Ib actual/
50 gal water

1 Ib actual
100 gal water
                         1 Ib actual/
                         100 gal water
                         1 Ib actual/
                         100 gal water
 Registered
Alternatives
                                                                                   Lindane
 Dieldrin
 Heptachlor*
 Mirex bait*

 Carbaryl
 Demeton
 Dimethoate
 Di-Syston*
 Malathicn
 Methoxyclilor
 IDE
 Pyrethrins

 Bidrin
 Dimethoate
 Dylox
 Lindane
 Malathion
 Phosphamidon

 BHC
 Carbaryl
 Diazinon
 Diir.ethorte
 Pyrethrins
 IDE
Chlordane
Limitations
             *Soll application

-------
                                                         Table 1.  (continued)
Crop or Site
of Application .
Soil Application

Agricultural Crops

Blackberry
Insect Pest
Blueberry
Grape
Boysenberry
Dewberry
Huckleberry
Loganberry
Raspberry
Youngberry
Strawberry
Cutworms

Root weevil larvae
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
     2.5-4

     10

     2.5-4
 Registered
Alternatives
Chlordane
Limitations
                    Japanese beetle bugs
                    White grubs-
                    Wireworms
                    White fringed beetle grubs
Cutworms                      2.5-4
Japanese beetle grubs
White grubs
Wireworms
White fringed beetle grubs

Cutworms                 •     2.5-4
Japanese beetle grubs
White grubs
Wireworras
White fringed beetle

Cutworms                      2.5-4
Japanese beetle grubs
White grubs
White fringed beetle grubs
Wireworms

Brachyrhir.us weevil           10.
 Heptachlor

 Heptachlor

 Heptachlor
                                                                      Dieldrin
                                                                      Heptachlor
                         Dieldrin
                         Heptachlor
                         Heptachlor
                          (registered on
                         Boyscr.berry,
                         dewberry and
                         raspberry only)

                         Aldrin
                         Dieldrin
Preplanting soil application or when no
fruit is present.
                                             Preplanting soil application or when no
                                             fruit is present.
                     Preplanting soil application or when no
                     fruit is present.

-------
                                                                  Table 1. (continued)
CO
ISJ
Crop or Site
of Application.
,



Pineapple
Cotton
Citrus


Peaches
Apple, Pear, Plum
Quince, Apricot,
Insect Pest
Cutworms
Earwigs
Mole crickets
Strawberry root weevil
White grubs
Wireworms
Ants
White fringed beetle
Argentine ant
Little fire ant
Termites
Plum curculio
General soil parts
Maximum or Usual
Dosage Rate
(Ib actual
insecticide/acre)
2.5-4
2.5
2.5
10
2.5-4
2
' .5
2
2
2
•>
2
Registered Chlordane
Alternatives Limitations

Aldrin
Dieldrln
Lindane
Toxaphene
Diazinon
Dieldrin ' .
Aldrin
Parathion
Aldrin
Dieldrin
Aldrin Do not feed bran or busk to livestock.
DDT Preplanting soil application.
Heptachlor Soil treatment . Apply when no food is
present.

Dieldrln
Aldrin Soil application when no fruit is
present.
Heptachlor
        Cherry,  Nectarine,
        Prune

-------
                                                                Table 1. (continued)
       Crop or Site
       of Application
       Corn(field)
Insect Pest
Asiatic garden beetle
  larvae
Cornfield ants
Corn root aphid
Corn rootwrons
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre),

     2.5-4  .

     2-4
     2-4
     2-4
ix:
u>
 Registered
Alternatives
 Heptachlor
 Heptachlor
 Bux
 Carbofuran
 Dasanit
 Di-Syston
 Dyfonate
 Heptachlor
 Phorate
 Parathion
Chlordane
Limitations
                     Preplanting soil application.
                           Cutworms
                              2.5-4
                           Green June beetle
                             larvae
                           Japanese beetle larvae
                           White grubs
                              2.5-4
                         Aldrin
                         Carbaryl
                         Diaziaon
                         Heptachlor
                         Parathion
                         Toxaphena

                         Heptachlor

                         Aldrin
                         Heptachlor
                         Parathion
                           Seed corn beetles
                              2.5-4
                         Aldrin
                         Heptachlor
                         Thimet  (Iowa and
                         Illinois Only)

-------
                                                        Table 1. (continued)
Crop or Site
of Application
Small Grains
(Barley, oats,
rye, wheat)
Soybeans
Flax

Peanuts

Sugar beets
Insect Pest
                    Seed corn maggot
                    White fringed beetle

                    Wireworms
Red harvester ants and
Cutworms
Wireworms
White grubs

Cutworms
                    Japanese beetle grubs
                    White grubs
                    Wireworms
                    White fringed beetle grubs
Sugar beet root maggot
Maximum or Usual
Dosage Rate
(Ib actual
insecticide /acre)
2.5-4
2.5-4
. 5/colony
2.5-4
2.5-4
2.5-4
33 2.5-4
2.5-4
2.5-4
4
Registered
Alternatives

Aldrin
Heptachlor
Aldrin
Diazinon
Heptachlor
Parathioix
CS- (mound
treatment)
Heptachlor
Diazinon
Heptachlor
Heptachlor
Parathion
Heptachlor
Heptachlor


Diazinon
Di-syston
(limited to
2 states)
Phorate
Chlordane
Limitations



Preplanting soil application
Preplanting soil application

Preplanting soil application
Preplanting soil application
Preplanting soil application

-------
           Crop or Site
           of Application
           Tobacco
ro
Ln
           Hops

           Sorghum
Insect Pest
                               Wirewonns
Wirewonns (transplant
  solution)
                               Wirewonns  (broadcast)
                                White grubs (broadcast
                                White fringed beetle
                                  grubs (broadcast)
                                                                    Table 1.  (continued)

                                                        Maximum or Usual
                           Dosage Rate
                           (Ib actual
                         insecticide/acre)

                              2.5-4
                                                              1.5
                              2.5-4
                              2.5-4



                              2.5-4



                              2.5-4

                              2.5-4
 Registered
Alternatives
 Diazinon
 Dyfonate
 Parathlon

 Aldrin
 Diazinon
 Dieldrin
 Heptachior
 Lindane

 Aldrin
 Diazinon
 Dieldrin
 Dyfonate
 Heptachior
 Lindane

 Aldrin
 Dieldrin
 Parathion

 Aldrin
 Dieldrin
 Keotachlor
Chlordane
Limitations
Transplanting
treatment
Preplanting soil application.
                     Preplanting soil application.

-------
                                                         Table 1.  (continued)
Crop or Site
of Application
Asparagus
Beans
Insect Pest
Cutworms
                    Japanese beetle grubs
                    White grubs
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

     2.5-4
                                                  2.5-4
                                                  2.5-4
 Registered
Alternatives
Chlordane
Limitations
White fringed beetle grubs    2.5-4

Cutworms                      2.5-4
                    Japanese beetle grubs         2.5-4

                    White grubs                   2.5-4


                    Wireworms                     2.5-4
 BHC
 Lindane
 Calcium
   arsenate
   bait

 BHC
 Lindane

 BHC
 Aldrin
 Lindane
 EDB (virewonas only)
 Parathicn
Preplanting soil application or at time
of planting or transplanting.
                                                  Dlazinon
                                                  Heptachlor
                                                  Parathion
                                                  Toxaphene

                                                  Parathion

                                                  Heptachlor
                                                  Parathion

                                                  Diazinon
                                                  Heptachlor
                                                  Parathion
                                                                                          Preplanting soil  application  or  at  time
                                                                                          of planting or  transplanting.
                    White fringed beetle grubs    2.5-4
                                                  Heptachlor

-------
Table 1. (continued)
Crop or Site
of Application

Insect Pest Maximum or Usual

Dosage Rate
(Ib actual
Registered Ohlordane
Alternatives Limitations

insecticide/acre)
Beets


Blackeyed peas
(cowpeas)


Cucurbits
Eggplant






Cutworms
Japanese beetle grubs
White grubs
Whiteworms
White fringed beetle grubs-
Cutworms
Japanese beetle grubs
White grubs'
Wireworms

White fringed beetle grubs
White fringed beetle grubs
Cutworms




Japanese beetle grubs
White grubs

2.5-4
2.5-4
2.5-4
2.5-4
2.5-4
2.5-4
2.5-4
2.5-4 .
2.5-4

2.5-4
2.5-4
2.5-4




2.5-4

Preplanting soil application or at time
of planting or transplanting.
Parathion

Diazinon
Preplanting soil application or at time
of planting or transplanting.
Diazinon
Parathion

Aldrin
Dieldrin
Aldrin
BKC
Dieldrin
Lindane
Toxaphene
Aldrin
BHC
Dieldrin
Lindane . '

-------
                                                              Table 1.  (continued)
     Crop or Site
     of Application
                    Insect Pest
                         Wireworms
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

     2.5-4
NJ
00
Broccoli*
Brussels sprout
Cabbage
Cauliflower
Collards
Kale
Kahlrabi
     Cucurbits
                         White fringed beetle
                           grubs

                         Cabbage maggots
     2.5-4


     2.5-4
                         Cutworms
                                                       2.5-4
 Registered
Alternatives
 Aldrin
 BHC
 Dieldrin
 EDB
 Lindane
 Parathion

 Aldrin
 Dieldrin

 Aldrin
 Diazinon
 Dieldrin
 Dyfonate**
 Heptachlor
   (furrow,
   transplant,
  •water, and
   drench.  Cab-
   bage only.)

 BHC
 Aldrin
 Diazinon
 Dieldrin
 Lindane
Chlordane
Limitations
                                                                                               Preplanting soil application or at  time
                                                                                               of planting or transplanting.
Preplanting soil app.1.-1 cation or at time
of planting or transplanting.
                                                                                               Preplanting soil application at time of
                                                                                               planting or transplanting.
     * Aldrin and dieldrin are not registered for use on collards, kale, and kohlrabi.
     * Diazinon is not registered on kohlrabi.
     EDB registered for use on broccoli and cauliflower only.
     **Seed crop only.

-------
                                                                 Table 1.  (continued)
        Crop or Site
        of Application
                            Insect Pest
                            Japanese beetle grubs
                            White grubs
                            Wirewonns
NJ
VO
        Lettuce
                            Cutworms
Maximum or Usual
Dosage Rate
(Ib actual
Insecticide/acre)
2.5-4



2.5-4



2.5-4





2.5-4








Registered Chlordane
Alternatives Limitations


Aldrin
BHC
Dieldrin .
Lindane
Aldrin
BHC
Dieldrin
Lindane
Aldrin
BHC
Dieldrin
Diazinon
Lindane
Parachion
Aldrin Preplanting soil application or at time
BHC of planting or transplanting.
Diazinon
Dieldrin
Heptachlor
'(lettuce only)
Lindane
Parathion
Toxaphene

-------
                                                            Table 1.  (continued)
    Crop  cr  Site'
    of  Application
Insacc Pest
                        Japanese  beetle  grubs
                        White  grubs
                        Wireworr.s
Maximum or Usual
  Dosage Race
  (Ib actual
insecticide/acre)

     2.5-4
 Registered
Alternatives
                                                  Aldrin
                                                  BHC
                                                  Dieldrin   '
                                                  Heptachlor
                                                    (lettuce only)
                                                  Lindane
                                                  Parathion
Chlordane
Limitations
UJ
O
    Celery,
                        Mole  crickets
                        Root maggots
Carrot rust fly
Cutworms
                        Japanese beetle grubs
                        White grubs
                              2  •


                              1.5
     2
     2.5-4
                              2.5-4
 Aldrin
 Diazinon

 Aldrin
 Diazinon
 Dieldrin
 Hepbachlor.
    (lettuce only)
 Lindane

 Diazinon
 Aldrin
 BHC
 Diazinon
 Lindane    :
 Parathion  '
 Toxaphene

 Aldrin
 BHC
 Lindane
 Parathion
Preplanting soil application or at tine
of planting or transplanting.

-------
Crop or Site
of Application
Corn (sweet
  and pop)
Garlic
Onions
Leeks
Insect Pest
                    Mole crickets
                    Wlreworms
White fringed beetle grubs

See field corn

Onion maggots
                                     Table 1. (continued)

                         Maximum or Usual
                           Dosage Rate
                           (Ib actual
                         insecticide/acre)
Okra
Peas
                    Wireworms
                    Wirewonns
                              2.5-4
                                                  2.5-4
                              2.5-4
                              2.5-4
 Registered
Alternatives
 Aldrin
 Diazinon

 Aldrin
 BHC
 Diazinon
 Lindane
 Parathion
 Diazinon
 Dieldrin
 Ethlon
 Dyfonate
 Parathion
 Trithion
 Diazinon
 Parathion

 BHC
 EDB
 Lindane
 Parathion

 Diazinon
 Parathion
Chlordane
Limitations
Preplanting soil application or at
time of planting or transplanting.
Preplanting soil application or at
time of planting or transplanting.

-------
                                                             Table 1.  (continued)
     Crop  or  Site
     of Application
    Parsnips



    Mustard greens
U)
N3
     Pepper
Insect Pest
Cutworms
Japanese beetle grubs
White grubs

Cutworms
Japanese beetle grubs
White grubs
Wireworms
White fringed beetle grubs-

Cutworms
Maximum or Usual
                           Dosage Rate
                           (Ib actual
                         insecticide/acre)
                         Japanese beetle grubs
                        White grubs
     2.5-4
     2.5-4
     2.5-4
     2.5-4

     2.5-4
                              2.5-4
                              2.5-4
 Registered
Alternatives
 Dieldrin
 Dieldrin
                         BHC
                         Diazinon
                         Lindane
                         BHC
                         Lindane
                         Diazinon
                         Aldrin
                         BHC
                         Dieldrin
                         Diazinon
                         Heptachlor
                         Lindane
                         Toxaphene

                         Aldrin
                         BHC
                         Dieldrin
                        1 Lindane
                         Parathion

                         Aldrin
                         BHC
                         Dieldrin
                         Heptachlor
                         Lindane
                         Parathion
Chlordane
Limitations
Preplanting sc-.l application or at time
of planting or transplanting.
                     Preplanting soil application or at time
                     of planting or transplanting.
                                                                      Preplanting soil application or at time
                                                                      of planting or transplanting.

-------
                                                              Table 1. (continued)
      Crop or Site
      of Application
      Pepper
      Potatoes
U)
      Radish
      /
Insect Pest
                         Wireworms
Wlreworms



White fringed beetle.

Colorado Potato Beetle


Potato flea beetle




Serpentine leafminer


Cutworms
                          Japanese beetle grubs
                          White grubs

                          Wireworms
Maximum or Usual
Dosage Rate
(Ib actual
insecticide/acre)
2. 5- A
2.5-4
2.5-4
1.5
1.5
1.5
2.5-4
2.5-4
2.5-4
Registered Chlordane
Alternatives Limitations

Aldrin
BHC
Diazinon
Dieldrin
EDB
Heptachlor Preplanting soil application or at
Lindane time of planting or transplanting.
Parathion
Aldrin
Diazinon No limitation.
Carbaryl
Malathion No limitation.
Carbaryl
Diazinon
Malathion No limitation.
Diazinon
Diazinon Preplanting soil application or at
Dieldrin time of planting or transplanting.
Dieldrin
Parathion
Dieldrin
Diazinon
Parathion

-------
                                                        Table 1. (continued)
Crop or Site
of Application
Rutabaga
Spinach
Insect Pest
White fringed beetle grubs

Cutworms


Japanese beetle grubs
White grubs
Wire worms

White fringed beetle grubs

Cutworms
                    Japanese beetle grubs
                    White grubs
                    Wireworms
Turnips
Cutworms
Maximum or Usual
Dosage Rate
(Ib actual
insecticide/acre)
is 2.5-4
'2.5-4


2.5-4



as 2.5-4
2.5-4



2.5-4






bs 2.4-5
1.4-5

Registered Chlordane
Alternatives Limitations


Dieldrin
Heptachlor
Parathion Preplanting soil application or at time
of planting or transplanting.
Heptachlor
Parathion
Heptachlor
Parathion
Heptachlor
BHC Preplanting soil application or at -.ime
Diazinon of planting or transplanting.
Lindane
Parathion
BHC
Parathion
Lindar.e
BHC
Diazinon
' Lindane
Parathion

Diazinon Preplanting soil application or at time
Parathion of planting or transplanting.
                    Japanese beetle grubs
                              2.5-4
Parathion

-------
Table 1. (continued)
Crop or Site
of Application

.



Sweet potato



Tomato













Insect Pest



White grubs
Wireworms
White fringed beetle
Flee beetle larvae


White grubs'
Cutworms







Japanese beetle grubs
White grubs




Maximum or Usual
Dosage Rate
(Ib actual
insecticide/acre)
2.5-4 .

grubs 2.5-4
2.5-5


2.5-5
2.5-4







2.5-4





Registered
Alternatives


Parathion
Diazinon

Diazinon
Dyfonate
Parathion •
Parathion
Aldrin
BHC
Diazinon
Dieldrin
Heptachlor
Lindane
Parathion
Toxaphene
Aldrin
BHC
Dieldrin
Heptachlor
Lindane
Parathion
Chlordane
Limitations


Preplanting soil application or at time
of planting or transplanting.

Preplanting soil application or
at time of planting or transplanting.


Preplanting soil application or at
time of planting or transplanting.













-------
                                                         Table 1.  (continued)
Crop or Site
of Application
Insect Pest
                    Wireworms
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

     2.5-4
 Registered
Alternatives
                                                  Aldrin
                                                  BHC
                                                  Diazinon
                                                  Dieldrin
                                                  Heptachlor
                                                  EDB
                                                  Lindane
                                                  Parathion
Chlordane
Limitations
Watermelons
Pumpkins
Melons
Squash
                    Wireworms (transplant
                      treatment)

                    White fringed beetle
                      grubs
Cucumber beetle
Squash bug
Squash vine borer
                               .75
                              2.5-4
     2.5
 Aldrin
 Dieldrin
 Heptachlor

 Thiodan
 Carbaryl
                                                             Soil Insects
                                             Transplant treatment.
                                             Preplanting soil application or at time
                                             of planting or transplanting.
Do not apply after edible parts start
to form.
General claims for Wireworms, white grubs, Japanese beetle grubs, white fringed beetle and cutworms are acceptable
for soil treatment of all crops listed in the "EPA Compendium of Registered Pesticides."

-------
                                                                   Table 1. (continued)
LO
          Crop or Site
          of Application
          Home Gardens

          Flower garden
            plants

          Ornamentals and
            Shade trees
            (soil)
                              Insect Pest
Mole crickets
Narcissus bulbflies
                              Seed corn maggots
                              Black vine weevil
                                larvae
                         Maximum or Usual
                           Dosage Rate
                           (Ib actual
                         insecticide/acre)
1 Ib actual/
100 gal water

1 Ib of 6% dust/
75 ft of row

1 level tsp
40% wp per Ib

5 Ib actual/
acre (soil
treatment
                    Registered
                   Alternatives
                                                  Diazinon
Dieldrin
Dylow
Heptachlor
Dieldrin*
                                                  Aldrin*
                                                  Dieldrin*
                                                  Heptachlor*
                                                  Ihiodan*
                    Chlordane  .
                    Limitations
          *Soil applications

-------
                                                              Table 1.  (continued)
     Lawns and Ornamental Turf
     Soil and Surface Applications
                                                                                Registev-d Alternatives
Aldrin
fr
•0
o
9
Carbaryl
Diazinon
Dieldrin
Ethion
Dursban
X
n>
•o
rr
0)
O
0
Toxaphene
Trithion
oo
Insect ?est

Ants
Asiatic garden
  beetle larvae
Boxelder bugs
Chiggers
Chinch bugs
Cicada killers
Wild bees
Cutworms
Earthworms
Earwigs
European chafer larvae
Green June beetle
  larvae
Japanese beetle larvae
Lawn moths (sod
  webworm)
Mosquito adults
Ticks
White fringed
  beetle larvae
White grubs
Wireworas
Imported fire  ants
1.5

2.5-5
1
1.5
2
5
5
5
10
1
2.5-5
2.5-5

2.5-5

3
.2-.4
1.5

2.5-5
5-10
5-10
1.5
X



X


X
X
X

X
X
X
X
X
X
X
X
X

X
X


X
X
                                                                           X
                                                                           X
                                                                                     X
                                                                                     X
                                                                                     X
      X - Registered

      Note:   Chlordane is registered for control of moles  in lawns.
X

X
X
X

X

X
                                                                                               X
                                                                                               X
                                                                                               X
                                                                                                             X
                                                                                                             X
                                                                                                             X
                                                                                                             X
X
X

X
X

X
X
X
                         X

                         X

-------
                                                       Table 1. (continued)
Seed Treatments
Crop Treatment

Beans
Blackeyed peas
Corn
Co.tton
Cowpeas
Oats
Peas
Rice
Rye
Sorghum
Soybeans
Wheat
                            Insect Pest .
                         Seed corn beetle
                         Seed corn maggot
                         Corn rbotuonn
                         Wireworms
                           (Temporary
                           protection against)
2 oz. actual
insecticide
per bushel
                              Registered
                              Alternatives
                                                                                o
                                                                                H*
                                                                                re
                                                                      K-    H-    o.
                                                                      3    g    H
                                                                           3    3
                                        ff
                                       •a
                                        it
                                        u
                                        n
                                        31
                                        O
                                        n
                                                                                          s    s
                                                                                          3    O
                                                                                          a.
                                                                                          3
                                                                                          (5
X
X
X
X
X
X
X
X
X
X
X
X

X



X



X
X
X
X
X
X
X
X
X
X
X
X
X

X
X

X

X
X
X
X
X

X
X
X
X
X
X
X
X
X
X
X
X

X

X
X
X
X
X
 Chlordane
Limitations

 Do not use for
 food, feed, or
 oil purposes
X - Registered

Baits - Chlordane baits limited to soil  treatment? are acceptable  for use against grasshoppers, cutworms, crickets, and mole
crickets.  This type application nay be  used only in accordance with approximate "Summary" clearance and limitations on crops
so specified.  In general, toxapher.e baits are registered  for nar.y of the same uses as chlordane baits.  Use of 1 Ib  of actual
insecticide per acre.  Do not contaminate edible r-'.rts.

-------
                                                         Table 1. (continued)
Crop or Site
of Application
Insect Pest
Maximum or Usual
  Dosage Rate
  (Ib actual
 Registered
Alternatives
Chlordane
Limitations
                                             insecticide/acre)
Agricultural Premises

(excluding dairy
barns and poultry
houses)
                    Housefiles
Outdoor Treatments

Ditch Banks,
Field Borders,
Roadsides,
Vacant Lands
Chiggers
                    Ticks
                    Flies
                    Gnats
                    Mosquitoes
     1.5
                                                  1.5
                              .2-.4
                                                  Clodrin
                                                  Dibroin
                                                  Diazinon
                                                  DDVP
                                                  Dimethoate
                                                  Lindane
                                                  Malathiop.

                                                  Methoxychlor
                                                  Synergized
                                                    pyrethrins
                                                  Ronnel
 Lindane
 Toxaphene
                         Gardona
                         Lindane
                         Toxaphene

                         Lindane
                         Ronnel
                         Carbaryl
                            (Mosquito only)
                                             3% spray (in oil or water).   Use as a
                                             residual surface spray.  Do not apply
                                             to feed stuffs.  Do not contaminate
                                             feed or drinking water.
                                                                                          6% dust.  Thorough application to  .
                                                                                          interior and exterior surfaces.  Do
                                                                                          not apply to feed stuffs.  Do not con-
                                                                                          taminate feed or drinking water.
Do nou feed or graze dairy animals or
animals being finished.

-------
                                                         Table 1.  (continued)
Crop or Site        Insect Pest
of Application
                    Grasshoppers
                    Crickets
Maximum or Usual
  Dosage Rate
  (Ib actual
insecticide/acre)
 Registered
Alternatives
                         Carbaryl
                         Dieldrin
                         Lindane
                         Toxaphene

                         Dibrom
                         Heptachlor
                         Malathio-.i
Chlordane
Limitations

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Crop or Site        Insect Pest
of Application
Household and Commercial Uses

Sprays and Dusts

                    Ants v
                    Boxelder bugs
                    Brown dog ticks
                    Carpet beetles
                  •  Centipedes
                    Crickets
                    Houseflies
                    Mosquitoes
                    Roaches
                    Waterbugs
                    Scorpions
                    Spiders
                    Silverfish
                    Wasps
X - Registered

Dogs
                                             6% Dust
                                             3% spray
Lice
Fleas

Ticks
                                         to
                                        •5
                                              5%  Dust
                                              .25 or  .5%  dip
                                              or  spray.
                                              Shampoos
Table 1. (continued)

   Registered Alternates

                   §   3
                   H- -o >i
                   to O n>
                                                                       ro
                                                                  H-    D.
                                                                  3    1
                                                                  O    H.
                                                                  3    3
                                                                            TO
                                                                           13
                                                                                 3
                                                                                 D.
                                                                                 0)
                                                                                 3
                                                                                 re
                                                                  0* CL 3*
                                                                  H- (0  1
                                                                           BHC
                                                                           Carbaryl
                                                                           DDV?  (Jet
                                                                           use only)
                                                                           Lindane
                                                                           Malathion
                                                                           Pyrethrins
                                                                              (synergized)
                                                                           Rotenone
X

X

X
X
X
X
X
X
X
X
X
X
X
X
X
X


X
X
X
X
X
X
X

X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

X
X
X
X
X
X
X

X







X
X

X


X

X
X


X
X
X
X

X
X

                                                                                                               Chlordane
                                                                                                              Limitations
                                                                                     Do not use in serving areas
                                                                                     while food is exposed.  Do.
                                                                                     not use in the edible pro-
                                                                                     duct areas of food proces-
                                                                                     sing p._ants, res laurants,
                                                                                     or other areas where food
                                                                                     is processed or  served.
                                                                                                          Spot  treatment.
                                      Do not use on young ani-
                                      mals.  Do not apply  .25% .
                                      solution more than once
                                      per we1*.  Do not r.pply
                                      .5% solution more than
                                      once everv 2 weeks.

-------
                                                         Table 1.  (continued)
Crop or Site
of Application
Insect Pest
                    Sarcoptic Mange
Herbicide

Preemergence
Crabgraas Control
Termite Control

Buildings           Termites
Household and
Industrial
Oil-Treatment

Special Uses

Mosquito Adulticlde
and Larvicide
Maximum or Usual
  Dosage Rate
  (Ib actual
Insecticide/acre)

     5% Dust, .5%
     or .25% dip
     or spray
                              65-87 Ib/acre
 Registered
Alternatives
Chlordane
Limitations
                              1-3% Solution
                         Adulticlde: 1 Ib
                         Al/acre

                         Larvicide: 0.2-0.4 Ib
                         Al/acre
                         Benefin
                         Betesan
                         Dacthal
                         Siduron
                         Zytron
                         Aldrln
                         Dieldrin
                         Heptachlor
                         Carbaryl
                         'Malathlon
                         Naled
                         Pyrethrins .
                         Para'thion
                         Paris green
                         Flit MLO

-------
                                                         Table 1. (continued)
Crop or Site
of Application
Sewage Treatment
for Psychoda flies
                    Insect Pest
Maximum or. Usual
  Dosage Rate
  (Ib actual
insecticide/acre)

One treatment con-
sists of 1/2 gal of
product containing
1 11 chlordane/gal
Two treatments one
tfeek apart, then
1-2 : reatments per
month during summer
months.
 Registered
Alternatives
 Mevinphos
  plus DDVP
Chlordane
Limitations

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 I.E.  Discussion of  Registered  Uses  of  Chlordane  and  its Alternatives - The
 Special  Pesticide Review Group has  studied  the toxicological hazard to man
 and  the  environment associated with the  use of chlordane as a pesticide in
 the  United  States.   In  making  this  study, the Group  has consulted pesticide
 experts  in  EPA and  other Federal  agencies and has  evaluated the  information
 received in response to the Federal Register notice  on October 6, 1971 on
 chlordane and  heptachlor (36FR19453).  The  Group considered, but was not able
 to fully evaluate,  the  social  and economic  effects which would result from
 the  cancellation of specific uses of chlordane as  a  pesticide.

 In an effort to evaluate the environmental  and human health effects of chlor-
 dane, broad use patterns were  established within the Special Pesticide Review
 Group.   Basically,  the  outdoor uses may  be  grouped into four broad categories
 1) foliar;  2)  soil  treatment;  3)  seed  treatment; and 4) special  uses.  The
 significant uses of chlordane  include  application  to agricultural crops,
 home gardens,  ornamental plants,  lawns,  and for  termite control.  Other broad
 categories  include  indoor applications for  household pests and for use on dogs.
 These broad use patterns present  distinctly different degrees of hazard to
 human health,  wildlife, and the environment.

 Seed  treatments present the lowest  order of hazard to human health, wildlife,
 and  the  environment of  the four outdoor  categories.   The treatment procedure
 usually  involves the application  of the  pesticide  directly at a relatively low
 dosage rate at  a location remote  from  the field.   This seed treatment is usu-
 ally  carried out by a commercial  seed  treatment  firm.  However, in some in-
 stances  the pesticide is placed directly into the  furrow along with the seed.
 In either instance,  the furrow is covered with soil,  keeping the pesticide
 localized.

 Soil  applications of chlordane present the  next  lowest order of hazard.
 Granulated  formulations of chlordane are generally used in this procedure.
 These granules  are  usually applied  to  agricultural crops as a band over the
 row  for  soil insect control, especially  in  cornfields.  The treated bands
 are at least 7  in wide.   The applicator  is  usually mounted on a planter, and
 the band  of granules is dropped just ahead  of it and  the press wheel of the
 planter.  The press wheel may  make  a slightly concave hand over the row.  Most
 agricultural granules contain  10  to 20%  AI.  Following are the significant
 advantages  for  use  of granules of a pesticide as far  as minimizing environ-
 mental contamination:   (1)  dosages  of  pesticides in  granular form may be kept
 at a  minimum because drift is  minimized, and; (2)  minimizes contamination of
 the edible  portion  of the crop because of the more specific placement or ap-
 plication before the crop emerges.

 Foliar applications  present  the highest  degree of  hazard of the three methods
 of application  of chlordane, both in terms  of environmental contamination, and
 also  in terms of  human  hazard  resulting  from residues in food or feed crops.
 Pesticides  may  be applied  to plant  foliage  in the  form of either dusts or
 sprays.   In  the  latter, wettable  powders or emulsifiable concentrates are
mixed with water  and  are  applied  by ground  or aerial equipment.


                                       45

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Dusts or sprays for foliar applications have the following characteristics:
(1) They are subject to drift, thus contaminating food crops or water outside
of the desired area of application; (2) much of the applied pesticide does not
reach the target area; and, (3) deposits of pesticide are left on the foliage
of treated crops, thus contaminating edible portions.

Of the methods described for the application of chlordane, seed treatment and
soil applications offer the least possibility for environmental contamination
or for the production of residues in food or feed.  Foliar applications, on
the other hand, have a great propensity for contamination of food, feed, or
the environment.

The following broad use patterns were established for the systemic review of
chlordane:

I.B.I.  Foliar Application -

I.B.I.a.  Agricultural Crops - All foliar applications of chlordane on agri-
cultural crops except ant control on pineapple in Hawaii have adequate alter-
nate pesticides.  Although some of the alternatives present a greater acute
toxicity hazard, most represent less long-term hazard to man and the environ-
ment than chlordane when used as a foliar spray on agricultural crops.  At
the present time, there are no Federal or State recommendations for agri-
cultural use of chlordane as a foliar treatment in the continental United
States.  Loss of most agricultural foliar uses would create no adverse econo-
mic impact.

I.B.l.b.  Home Gardens and Ornamentals - There were no significant requests
to continue foliar applications of chlordane for home gardens, ornamentals,
shade trees, and flower garden plants.  All foliar uses of chlordane to home
gardens and ornamentals have adequate alternate pesticides.  At the present
time, there are no Federal or State recommendations for use of chlordane as a
foliar treatment on home gardens or ornamentals.  Loss of all home garden
and ornamental foliar uses of chlordane would create no adverse economic
impact.

I.B.l.c.  Herbicide for Crabgrass Control - Chlordane is registered as a pre-
emergence herbicide for 'the control of crabgrass on lawns.  The rates of
chlordane recommended for this use are 65 to 87 Ib/acre.  There are a number
of more widely recommended alternates including benefin, siduron, dacthal,
betasan, and zytron and elimination of this high quantity use of chlordane
would minimize the human and environmental hazard of this pesticide.  The ap-
plication rate is in effect a biological sterilizing dose and will probably
restrict most animal life in the soil for considerable periods of time after
application.  Loss of this use will present no adverse economic impact.

I.B.2.  Soil Applications - The effective alternatives for several of the
significant soil uses of chlordane include the chlorinated hydrocarbons,
aldrin, dieldrin, and heptachlor.  Alternatives other than the chlorinated
pesticides are not registered for all uses nor are they likely to give

                                        46

-------
equivalent control of insects such as ants, seed corn maggots, wireworms,
grubs, cutworms, and termites.  This is especially true for certain soil ap-
plications for agricultural crops, lawns, and termite control.  These uses
are reported to account for almost all of the poundage of the total chlordane
used in the United States at the present time.

Another consideration in the review of chlordane is the current status of the
registrations of aldrin and dieldrin.  Actions against the registered uses of
aldrin and dieldrin could result in an increased use of chlordane.  This may
increase the impact upon man and his environment.

I.E.2.a.  Agricultural Crops - Under present conditions, 8-10,000 acres of
citrus in California require soil treatment for ant control each year.  The
Argentine ant and the gray ant in California do not cause any direct damage
or injury to the citrus tree but their presence in large numbers in the aerial
parts of the tree significantly decrease the effectiveness of natural enemies
against certain primary citrus pests.  The Argentine and gray ants destroy
adult parasites and the larvae of predators.  The primary problem of the
endemic fire ant in California is direct injury to young citrus trees.

The University of Idaho reports chlordane as an effective soil treatment for
control of the sugar beet wireworm in potato fields.  Chlordane was also reported
to have a lesser acute toxicity hazard than two other insecticides on
sugar beet wireworms.

An administrative report of the Economic Research Service, U.S. Department of
Agriculture  (May 26, 1972, appended) explains that the total cost to United
States farmers for discontinuing the use of chlordane in 1971 would have been
$1.84 million ($1.56 million for substitute insecticides and $0.28 million
for production losses).  The added cost for the substitute insecticides ranged
from a low of $0.18 per acre for cotton to a high of $6.77 per acre for corn.
The added cost for substitute insecticides in potato, tomato, vegetable and
strawberry production is estimated at $2.50 per acre.  The per-acre value of
production losses are $23.00 for vegetables, $31.00 for citrus, and $75.00
for strawberries.

Production of cabbage has decreased substantially in the chlordane-realstant
maggot areas of Maine, primarily because of the high cost of Diazinon^in
relation to the value of cabbage and to the poor control obtained with this
pesticide.  In many instances a single application of chlordane is sufficient
for wireworm control for several years while other more toxic materials
require several annual treatments.

Increased use of chlordane may result from the cancellation of the soil
insect control uses of other chlorinated hydrocarbon pesticides such as
aldrin and dieldrin.  Present evidence suggests that any added soil use
of chlordane could increase its impact upon the environment.
                                       47

-------
I.B.2.b.  Home Gardens - Alternatives other than chlorinated hydrocarbon pesti-
cides are not registered for all uses nor are they likely to give equal control
of insects such as ants, wireworms, grubs, cutworms and various other soil
pests.  Increased use of chlordane could result from the cancellation of soil
insect control uses for other chlorinated hydrocarbon insecticides such as
aldrin and dieldrin.

I.B.Z.c.  Lawns, Commercial Turf and Nursery Plant Stock - Alternatives other
than the chlorinated hydrocarbon pesticides are neither registered for all
uses nor likely to give equal control of pests such as ants, wireworms, grubs,
cutworms and other soil insects.  Increased use of chlordane could result from
the cancellation of soil insect control uses for other chlorinated hydrocarbon
insecticides sucy as aldrin and dieldrin.  Loss of the currently registered
insecticidal uses of chlordane as a soil application to lawns, commercial turf
and nursery plant stock will have a significant impact.

There have been numerous indications of the need to continue the uses of
chlordane for control of soil insect pests on lawns, commercial turf and
nursery plant stock.  For example, the State of New York recommends the use of
chlordane at a rate of A Ib Al/acre for the control of scarabaeid grubs which
will be sufficient for four seasons of protection.  The best available sub-
stitute as recommended by the State of New York is DiazinonR which must be
applied at the rate of 6-8 Ib Al/acre on an annual basis.

It has been estimated that the loss of chlordane and heptachlor for turf use would
result in damage estimated at approximately $0.50 per square foot in Pennsylvania.
One acre of lost turf would cost approximately $20,000 to replace or renew.
Turf grass is a primary agricultural industry in Pennsylvania and the loss of
chlordane for soil insect control would be significantly damaging to the agri-
cultural industry of that State.

The State of Mississippi has indicated that the cancellation of chlordane
would leave no pesticide available for certification for movement of nursery
stock under the provisions of the imported fire ant, white-fringed beetle and
Japanese beetle quarantine progran involving interstate commerce of live plants.
New York State also recommends the use of chlordane to control white grubs and
strawberry root weevils in the New York State Tree Nursery.  Chlordane is
used to protect against damage from soil insects on crops that are valued in
excess of $15,000 per acre with experimental trees being valued at upward of
$5 - $10 apiece.

The States of Virginia, West Virginia, North Carolina and South Carolina
recommend chlordane to control insects in nursery beds of tree seedlings needed
to replant cut over timber areas.  Total cost of the replanting procedures
in North Carolina is approximately $50-$70 per acre.  This forestry based
industry has been reported to provide an estimated 227,000 jobs in North
Carolina.  The South Carolina State Commision of Forestry recommends chlordane
for control of white grubs of May and June beetles and grubs of Japanese
beetle in their forest tree nurseries.  Without chlordane they would expect
to lose practically all of the tree seedlings.  The State of Vermont has
estimated that damage to lawns due to the Japanese beetle larvae and mole
tunneling would be approximately 50% of the turf in that state.
                                     48

-------
In addition to  the above statements  found  to give specific information of
value in considering use of chlordane on lawns,  there have been numerous indi-
cations of the  need to continue use  of chlordane for control of lawn pests.

I.E.3  Seed Treatments - Alternatives other than the chlorinated hydrocarbons
are not registered for all uses nor  are they likely to give control equal to
that available  with chlordane.  Diazinon is the  only nonchlorina.ted hydro-
carbon alternate pesticide available.  The registered uses for diazinon are
limited.  Loss  of the seed treatment uses of chlordane would have\a signifi-
cant impact.                                                       'j
                                                                   \
                                                                   VK
I.E.4  Baits -  Chlordane baits are indicated to  be essential because ho other
materials in baits have the registered spectrum  of pest activity.  Toxaphene
is one pesticide which might be used as an alternate to retain the specVrum of
activity established for chlordane.  Loss of the currently registered usi\s of
chlordane in bait formulations would have a significant impact.

I.E.5.  Agricultural Premises (excluding dairy barns and poultry houses).  \
Chlordane is registered for control  of a number  of pests in agricultural prev,
mises, excluding dairy barns and poultry houses, and may be applied in areas M\
where animal feed is stored.  There  are no suitable alternate pesticides for  {'>
control of certain pests infesting agricultural  premises.               \
                                                                          V
The uses of chlordane on agricultural premises are similar to the household^.
uses of chlordane in that they are for the control of insects in and around
farm buildings, excluding dairy barns and poultry houses.  When used as
intended, these uses should not contaminate food or feed or present an undue
health hazard.

I.E.6.  Outdoor Treatments - This use includes ditchbanks, field borders,
roadsides, and  vacant land^s.  It is  recognized that this use is actually a
"foliar use" and general comments of I.B.I are applicable.

I.E.7     Household and Commercial Uses - This use covers the use of sprays
and dusts for control of cockroaches, ants, ticks, and a number of other
household and commercial buildings pests.  The insecticide treatments for
pest control are usually applied inside the buildings as well as those areas
near food processing or serving.

The concentrations and use directions for chlordane are regulated by inter-
pretation number 19 of the Regulations for the Enforcement of the Federal
Insecticide, Fungicide, and Rodenticide Act.  Petroleum distillate solutions,
diluted or concentrated, water emulsions, dusts, and pressurized dispensers
which deliver   a coarse spray are allowed.  Pressurized dispensers may not
contain over 37° chlordane while the  concentrates may contain up to 12%.
Dusts may not contain more than 6%, chlordane.  The directions for liquid formu-
lations and pressurized sprays under all circumstances provide for applica-
tions as a coarse, wet spray or by the use of a paintbrush or similar means.


                                        49

-------
The use of chlordane to control Psychoda larvae in sewage plants constitutes
a direct, although minimal, contamination of water.  Psychoda fly larvae con-
gregate on and clog the filter beds of sewage treatment plants.  Chlordane is
currently used at a rate of one-half Ib AI poured over the bed for a period
of one minute during which time approximately 3,000 gal of water will pass the
filter.  This gives an immediate dilution to 20 ppm of chlordane in the water.
If the effluent enters a stream flowing at a rate of 500,000 gal of water per
minute, it is diluted to 0.125 ppm in the first minute and to 0.04 ppm by the
third minute.
                                        51

-------
                                      CHAPTER  II
                              Chemistry  and Methodology
II.A.  Chemistry - Chlordane  is  a member  of  a  group  of  polycyclic chlorinated
hydrocarbons called "cyclodiene  insecticides"  which  include  heptachlor,
aldrin, Thiodan^ (endosulfan), and  TelodrinR (isobenzan).  The first insecti-
cide of the cyclodiene group  to  be  developed was  chlordane (M-410,  German
designation) which has been industrially  manufactured  in  the United States
since approximately 1947.

II.A.I.   Synthesis -  The  carbon  structure of the  cyclodienes is obtained by
Diels-Alder addition  of an olefin  to a chlorinated diene.  For the manufacture
of chlordane, hexachlorocyclopentadiene is reacted with cyclopentadiene  to
form chlordene  (CiQHfcCl^) and this  adduct is chlorinated  to  approximately 65%
as is described in Table  1.   The registered  mixture  of  chlorinated products
is called technical chlordane.   The synthesis  of  chlordane is illustrated as
follows:
                                      Mels-Alder
                                      Reaction
          hexachlorocyclo-
          pentadiene
cyclopentadiene
                          chlordene
                                       Cl,
II.A.2.  Composition - The  term  chlordane  has  been  used  to designate a complex
mixture of chlorinated hydrocarbons,  a  single  chemical substance,  and a mix-
ture of isomeric forms (Food  and Drug Administration  Advisory Committee,
1965).  Technical chlordane consists  of the  alpha and gamma isomers  of 1,2,4,
5,6,7,8-octachlor-4, 7-methano-3a,4,7,7a tetrahydroindane  (chlordane), hepta-
chlor, nonachlor, isomers of  chlordene,  and  other related  compounds.   The
alpha isomer and the gamma  isomer of  chlordane (Velsicol notation) are known
as cis-chlordane and trans-chlordane, respectively.   According to  Ingle (1965)
technical chlordane is manufactured by  a rigidly controlled process.   Composi-
tion of preparations obtained by this process  are consistent,  but  technical
chlordane contains a number of compounds.
                                        52

-------
                         Table 1.  Approximate Composition ciC Technical CUord.ine*


                   (A)  Dlele-Alder Adduet (|>AA) of Pentuchlorocyclopentudlene and 	
                       cyclopentadiene  C.Qil.rCl,-                             2 + Ijf
                   (B) Ghlorilene learners in order of GLC retention time  c-in^(f-^f.

                          (l)  Teomei — 1,  chlordene-AA: hexachlorocyclopentadlene
                              (Hex) nnd "Cyclo"                            I ±_ 1%

                          (2)  Ieomer-2                                  7-5 i 2^

                          (3)  IsomerB-3 and U (combined)                    13 + 2^

                   (C) Heptachlor  C^lljCly                               10 + yf,

                   (D) Chlordane. iBomeru  CjQH^Cl,-
                          (l)  Alpha-chlordane if c IB -chlordane)                19 + 3$

                          (2)  Garama-chlordane (trano-chlordane)        .       21' +_ ?/<

                   (E) Nonachlor   ci0H5C1                                  7 - ^

                   (F) Other ConBtltuents

                          Hexachlorocyclopentadlene (CrClg)  (Hex)     Maximum     1^

                          Octachlorocyclopentene  (C^Clo)                     1 ^ 1.%

                                                                      8.5 ± P%
                          Constitutentc of lover GLC retention
                          time than C^ClQ, including Hex

                          Constituents of higher GLC retention
                          time than nonachlor
                   *The foregoing approximationn are based uj)on untid.luPted vnlnps derived  from
                   gas-liquid chromato^rnphy.  Apparent value:; obtained are typically in["]ueticed
                   by conditions of analysis and the chroma\.or,i r>ph!c Dystems emplDyed, and vhe
                   relative response nensltlvity of the compnnonts.

                   Source: Volsicol Chemical Corporation.
The  composition  of technical  chlordane has been essentially,  but  not complete-
ly,  determined.   Reports in  the literature based on  early work state that
technical  chlordane contains  60-75% alpha- and  gamma- isomers of  chlordane and
25-40% subsidiary products.   (Riemschneider,  1963; Melinkov,  1971;  Metcalf,
1971;  Buchel, 1970).   According to  data  from  Velsicol Chemical Corporation, as
presented  in Table 1,  technical material  contains a  total of  38-48% of  alpha
and  gamma  chlordane.

Chromotographic  techniques were used to  detect  seven components  in technical
Chlordane  (Thruston,  1965; U.S. Department of Health Education and Welfare,
1970).   Saha and Lee  (1969)  and Bevenue  and Yeo  (1969) described  14 distinct
chromatographic  components from technical and formulated chlordane.  Saha and
Lee  (1969)  and Polen  (1966)  using various analytical techniques confirmed the
identity of the  major components of technical chlordane, but  the  assignment
of structures to some of the  major  components appeared to differ  from
structures  assigned by others (Hill, 1970).

                                             53

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'Brooks  (1974) has written an extensive review of  the  chemistry  of  chlorinated
 insecticides  including  technical  chlordane  and its  components.

 Riemschneider (1963)  reported technical chlordane contained  four isomers  of
 octachlor-adducts,  2-heptachloro-derivatives,  1-nonachloro and  1-decachloro
 derivative  in addition  to hexachlorodicyclopentadiene.   Evidence has  been
 presented by  Reimschneider (1963)  confirming  the  structure of  the  intermediate
 hexachlorodicyclopentadiene and the special assignment  of isomers  of  the  chlor-
 dane  synthesis.  The  major isomers of  chlordane have  the endo-configuration  in
 the carbon  skeleton.  The alpha isomer is an  endo-isomer in  which  the two
 chlorine atoms  are  in a cis-configuration and the gamma isomer  is  an  endo-
 configuration in which  the chlorine atoms are assigned  in the  trans-configura-
 tion.   Different nomenclature systems  have  been used  in the  past,  leading to
 confusion.

 Technical chlordane.  with a viscosity  of 75-120 cetitistokes  at  130°F.,  is a
 light yellow  oil; d20 1.59-1.63;  Nd20  1.57-1.58.  The product  is practically
 insoluble in  water  (Gunther e_t_al^,  1968) but highly  soluble in organic sol-
 vents.  The aromatic  hydrocarbons, ketones, esters  and  chlorinated solvents
 are completely  miscible with chlordane.  The  chlorine content  is 64-67%.   The
 melting points  of the cis- and trans-  isomers are very  close (Benson,  1971).

                    cis-chlordane            107.0  -  108.0°
                    trans-chlordane          103.0  -  105.0°

 Chlordane is  relatively volatile  with  a vapor pressure  of approximately 1x10
 (25°C).  The  FDA Advisory Committee (1965)  considered these  aspects of  the
 manufacture,  production and identification  of synthesis products of chlordane
 and noted that  the  standards of production  were such  as to allow the  constancy
 of the  technical mixture.   This constancy has allowed adequate  analyses to be
 made  of the formulation and residues present.   In the case of  technical chlor-
 dane, despite difficulties inherent with a  mixture  of components,  the current
 analytical  means for  residue determination  are apparently successful,  in  terms
 of sensitivity, precisibn,  and accuracy.

 II.A.3  Chemical Reactions - Chemical  reactions of  chlordane are many and
 varied  and  a  complete analysis of  them is beyond  the  scope of  this review.
 Some  of these reactions have been described in the  extensive reviews  by
 Melnikov (1971) and Buchel (1970)  in Wegler (1970)  and  Reimschneider  (1963).
 Benson  (1969) indicated that the  chlorine atoms are relatively  unreactive
 toward  base.  The hydrogen and chlorine atoms  are not in the proper trans-
 planar  positions for  low energy elimination reactions.   The  four chlorine
 atoms attached  to the aliphatic positions are protected from displacement reac-
 tion by the bicyclic  bridge system.  Benson indicated that the  two chlorines on
 the olefin  are  also generally unreactive towards  base.   These chemical  condi-
 tions generally coincide with the  reactions that  have been obtained both  in
 vivo and in vitro with  chlordane  isomers.  However, other data  obtained photo-
 lytically (Crosby,  1969),  and chemically (Chau, 1970) indicate  the relative
 stability of  chlorine atoms on the bicyclic ring.
                                       54

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Chau  (1970) has demonstrated that prolonged contact with chromous chloride
solution causes dechlorination of the methylene bridge of heptachlor and
chlordene.  Thus,  the photolysis results of Crosby  (1969) and Chau (1970)
suggest the chlorinated bicyclic ring is not a completely stable entity
and may undergo partial degradation,

II.A.4.  Photodecomposition - Light is an important environmental force that
may induce chemical  transformation.  With some noticeable exceptions, includ-
ing plant photosynthesis, photoperiodism and color photography, most photo-
chemical reactions to sunlight are energized by the ultraviolet (UV) compo-
nents at wave lengths shorter than 400 nm.

Light intensity, including UV, is strongly affected by season, climate, lati-
tude  and other factors.  The atmosphere effectively absorbs UV light, with
287 nm being the minimum wavelength ever recorded on the earth's surface; 300
nm probably represents the practical UV limit at most locations.  The total
intensity at wavelengths below 313 nm increases sixfold from a December mini-
mum of 30 uW/cm2 to  a June maximum of 180 yW/cm^ and doubles for each kilo-
meter rise in elevation.

Korte examined the photodecomposition of some components of chlordane in
acetone solution, and observed a high conversion of heptachlor, heptachlor
epoxide, beta-dihydro-heptachlor and chlordane to cage-type compounds.  Trans-
chlordane did not yield a product even after 100 hr (Hill, 1970).

Benson et al. (1971) found that chlordane, cis-chlordane, heptachlor and
heptachlor epoxide were converted on photolysis to cage-type compounds, and
isolated them.  The materials were irradiated in acetone solution using fil-
ters and as thin films by sunlight or by UV lamps.  Although both cis and
trans-isomers were degraded at similar rates, under the conditions employed
only the cis-isomer formed a photo-product which was apparently a half-cage
compound formed through hydrogen migration and carbon-to-carbon bond formation.
The photoisomerization of cis-chlordane was apparently similar to that
produced by photoisomerization of dieldrin.  Photolysis of technical chlor-
dane for 70 hr resulted in a complex mixture of products.

Trans-chlordane does not photolyze to a half-cage compound but does disappear
very slowly on irradiation; trans-nonachlor behaves similarly.  Also beta-
dihydroheptachlor failed to yield an isolatable compound.  Crosby (1969)
studied the photolytic decomposition of aldrin and dieldrin and described
a dechlorinated product resulting from the loss of chlorine from the
olefinic portion of the presumably stable bicyclic ring.   Although the .photolytic
alteration of technical chlordane under actual field conditions, in sunlight
from various areas, has yet to be reported, it seems reasonable to assume x
that similar products would be obtained following ultraviolet degradation
of chlordane.
                                       55

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'1I.B.   Methods of Analysis - A number of  methods have been used  for  the
 determination of residues of organochlorine compounds and most of  these can be
 used for determining residues of technical chlordane.  A gas  chromatographic
 procedure given in the Pesticide Analytical Manual,  Volume I  (U.S. Department
 of Health, Education and Welfare, 1971).   The history of the  multiple residue
 technique was discussed in a review article by Burke (1971).  The  section on
 gas liquid chromatography discusses this  further.

 II.B.I.a.  Colorimetric and Total Chlorine Methods,  and Color Reactions -
 These methods were commonly used about 1950-1965 but have largely  been super-
 seded by gas chromatographic methods.

 Following extraction of material from biological samples, various  methods have
 been used for quantitative determinations of total residues of chlorine-
 containing compounds.   Chlordane forms several colored derivatives.   When an
 alcoholic solution of chlordane is heated with KCH and p-aminophenol, a red-
 brown color is obtained; with pyridine and ethylcellosolve, a red  color; with
 pyridine and ethylene glycol, a red violet color;  with diethanolamine, a
 violet color.  These color reactions were demonstrated by Ard (1948), Davidow
 (1950), Ordas _et al^ (1956), Malina (1965), and Faucheux (1965).  In general,
 plant and wax components, which qualitatively interfere with  colorimetric
 measurements of several of the more commonly used cyclodiene  insecticides,
 reduce the sensitivity of colorimetric methods for chlordane. Measurement of
 total chlorine by sodium biphenyl reduction was considered to be the most
 reliable quantitative method for chlordane, but it is not specific.   Excellent
 agreement has been obtained with this method in several laboratories using
 chlordane formulations (Meyer, 1962).   A  field test  developed by Chisholm et^
 al- (1962) to examine termite treatments  uses a color produced with  2-
 phenoxyethanol.

 II.B.l.b.  Bioassay - Chlordane residues  may be determined semi-quantitatively
 by bioassay.  Several insect species have been used, including housefly
 (Stansbury and Dahm, 1951), mosquito (Hartzell et al., 1954), and  a  parasite
 of the oriental fruit moth, Marcrocentrus spp.  (Fleming et al.,  1951).
 Recently, Sadar and Guilbault (1971) suggested the use of the enzyme system,
 hexokinase, as a substrate for the determination of  several chlorinated pesti-
 cides.  This enzyme system has a rather unique sensitivity to certain chlorin-
 ated insecticides, including chlordane, heptachlor,  aldrin and DDT,  but not
 dieldrin, kelthane or DDT analogues.  At  best,  bioassays have been shown to
 be non-specific and relatively insensitive.

 II.B.I.e.  Thin-Layer Chromatography - Thin-layer chromatography,  featuring
 various solvent systems and adsorbents, has been used to separate  chlordane
 isomers from extraneous biological materials.   Systems for organochlorine com-
 pounds are discussed in the Pesticide  Analytical Manual,  Volume  1, (U.S. De-
 partment  of Health,  Education and Welfare,  1971).   In general, this  procedure
 has been  used as a qualitative tool in combination with gas liquid chromato-
 graphic techniques.  Means for detection  of material on thin-layer chromato-
 grams  are as varied  as  the solvent systems  employed  and generally  require the
 same reagents and methods used in the  colorimetric methods.

                                        56

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Faucheux  (1965) suggested the use of diphenylamine-zinc chloride as a
chromogenic reagent with a sensitivity of 5 mg.  He reviewed the use of
several reagents including N,N-dimethyl-phenylenediamine HCG; methanolamine-
AgNOy, 2-phenoxyethanol-AgN03; bromphenol blue-AgN03; Iodine; H2S03; bromo-
f luorescein-AgNC>3.

II.B.l.d.  Gas Liquid Chromatography - Gas liquid chromatography is the method
of choice for the qualitative and quantitative estimation of chlordane residues
in foods  (U.S. Department of Health, Education and Welfare, 1971); Noren and
Westdb, 1968; Duggan and Cook, 1971), air (Yobs, 1971a), water  (Lamar et al.,
1966; Feltz ejt al^_, 1971; Carver, 1971), human tissue (Weirsma and Sands, 1971;
Yobs, 1971b), fish (Inglis et al., 1971); and wildlife (Dustman et al., 1971).
With GLC techniques contamination in small samples may be measured rapidly with
high levels of sensitivity.  In  general, this method of detection is at least
10 times more sensitive than the colorimetric methods previously employed.  This
is emphasized by the analysis of 1 mg of fish tissue with a precision of 20% and
25 mg samples analyzed with a precision of +5% (Seba and Land, 1969).

The Pesticide Analytical Manual, Volume I Section 302.44c (U.S. Department of
Health, Education and Welfare, 1971) gives the procedure used by the Food and
Drug Administration for determination of residues of chlordane.  Technical
chlordane contains several significant components, and the residue of chlor-
dane usually contains these components in proportions different from those in
technical chlordane.  The procedure considers all peaks representing the resi-
due.  Calculation may be based on the total area of the peaks or by "peak
height addition".  Procedures are also given for extraction and cleanup for
the preparation of samples (Chapter 2); for the cleanup on Florisil, technical
chlordane elutes with the first  fraction (Eluant A, using 20% methylene
chloride in hexane).

Thompson (1970), examining the in vitro weathering of technical chlordane,
showed that not all peaks in the1 GLC tracing disappear at the same rate.  Be-
cause of various rates of volatilization of components in the technical chlor-
dane, the use of signal peaks versus the whole spectrum might well account for
the lower values obtained with GLC than with total chlorine analysis.

Other systems of solvent partitioning have been used.  Solvent partitioning
with mixtures of hexane and methanol or ethanol are effective (Saha, 1971).
Noren and Westoo (1968) described a method of analysis using a combination of
dimethylformamide (containing 8% water) — hexane partitioning extraction with
a recovery for fortified samples ranging from 83% to 92%.  The sensitivity of
the extraction when using approximately 10 g samples of fat appeared to be 10
ppb.

The advent of GLC techniques with the use of sensitive detectors has enabled
the chemist to extend the range  of analyses to the submicrogram levels.  How-
ever, this technique has introduced some of the following problems 1) coordina-
tion of recent data with those obtained with older methods, primarily colori-
metric analyses; 2) in the case  of chlordane GLC assays usually result
in lower numerical values than the total chlorine assays; 3) establishment of
a uniform GLC system for residue determination.
                                     57

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Alpha-Chlordane, gamma-chlordane, and particularly oxychlordane and heptachlor
epoxide are difficult to separate on most GLC columns.  Conder et al. (1972),
report that a column containing 1.5% 0V 17 plus 1.95% 0V 210 will separate
all four materials.

Su (1973) determined heptachlor epoxide, oxychlordane and certain other pesti-
cides in the presence of PCB's using the Coulson electrolytic conductivity de-
tector in the non-catalytic reductive mode at 660°C, and the column used by
Conder et al. (1972).  PCB's are not detected under these conditions.

II.B.2.  Interference - Naturally occurring chlorinated materials usually pose
no problem in the determination of chlorinated pesticides by the total chlorine
method (Hylin et al., 1969).  Although some chlorine-containing materials have
been found in certain fungi, the possible occurrence of fungal contamination
in samples for chlorinated organic assays is small.  The possible interferences
with polychlorinated biphenyl contaminants appear to be significant.

II.B.3.  Confirmatory Methods - Because GLC detection systems (electron capture
or flame ionization) are sensitive but cannot provide an unequivocal identifi-
cation based on retention times, various confirmatory methods have been employ-
ed (some in combination with the GLC).

II.B.3.a.  GLC - Mass Spectrometry - The use of GLC - mass spectrometry for
the qualitative and quantitative estimation of pesticide residues is one of
the most significant advancements in residue analysis in recent years.
Francis Biros discusses applications of this technique in a chapter entitled
"Applications of Combined Gas Chromatography - Mass Spectrometry to Pesticide
Residue Identifications in Advances in Chemistry Series 104:  Pesticides
Identification at the Residue Level (American Chemical Society,   L971).

Using the combination of GLC-mass spectrometry, Biros and Walker (1970)  showed
that the peak with the retention time of heptachlor epoxide was in fact hepta-
chlor epoxide.  An unidentified peak was later found to be the metabolite des-
ignated as oxychlordane.

Without highly specific confirmatory techniques such as mass spectrometry
these residues would not be readily identified.  Possible errors have been
made in the past on the identification of some GLC peaks.

II.B.S.b.  Neutron Activation - Bogner (1966) reported on the potential use
of neutron activation analysis for the qualitative determination of chlorin-
ated pesticides; primarily the high cost of instrumentation has precluded the
wide acceptance of neutron activation analysis.

II.B.3.C.  P-values - Another confirmatory method employs the extraction of
solute between two immiscible solvents.  Using this technique Beroza et al.
(1969), developed p-values which they have defined as the fraction of a pes-
ticide which is distributed in the non-polar phase (usually upper) of equal
volumes of a solvent pair.   This method has been used as a tool in cleanup
and for confirmatory identification of a pesticide and for selecting solvents
                                        58

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 for partition cleanup procedures.   The p-values for gamma-chlordane have been
 reported with 6-solvent pairs (Beroza et al.,  1969).

 II.B.3.d.   Carbon-Skeleton Chromatography - When chlordane is pyrolytically
 dechlorinated (hydrogenated,  and chromatographed),  the method is called
 "carbon-skeleton chromatography" (Asai et al.,  1967) .   The confirmatory tech-
 nique of carbon-skeleton chromatography lacks  sensitivity (10 ug of sample)
 and materials having the same carbon-skeleton,  e^g.,  heptachlor, heptachlor
 epoxide, etc.,  cannot be differentiated.   Carbon-skeleton chromatography has
 been used successfully to confirm the identity  of  peaks of GLC which have re-
 sulted from interferences by  polychlorinated biphenyls (Asai et al., 1971)  and
 in certain instances will serve as a confirmatory  method.

 II.B.3.e.   Derivatization - A sensitive means  for  the confirmative determin-
 ation of chlordane has been shown to be derivatization.  (Chau and Cochrane,
 1969a, 1969b;  Cochrane, 1969; Cochrane and Chau, 1970).  The reaction of chlor-
 dane with Potassium tert-butoxide/tert-butanol  with subsequent silylation
 achieves routine confirmation of chlordane at  a level of 10 ppb when 10 gram
 samples are used.   It was found that cis-chlordane was converted rapidly to
 3-chlorochlordene and trans-chlordane was converted slowly to 2-chlorochlordane.
'in combination with GLC simple derivatization  is useful in the qualitative  con-
 firmation of residues.

 II.B.4.  Formulation Analysis - The Association of Official Analytical Chemists
 (AOAC) methods for technical  chlordane formulations are the total chlorine  method
 and the colorimetric methods  (Association of Official Analytical Chemists,  1970).

 A method for determining the  impurity hexachlorocyclopentadiene (Hex) in tech-
 nical chlordane is also given.   (AOAC, 1975, par 6.229 - 6.232).

 A product AG Chlordane consisting of at least 95%  of  the alpha and gamma
 isomers of chlordane has been developed,  but it is  not registered.   Malina
 (1972, 1973) has developed an AOAC infrared method  for alpha-chlordane and
 gamma-chlordane, and a GLC method for heptachlor in AG Chlordane (Associa-
 tion of Official Analytical Chemists,  1973).
                                         59

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                                   CHAPTER  II

                                  Bibliography


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Brooks, G. T.  Chlorinated insecticides, Volume I:  Technology and application;
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Crosby, D. C.  The nonmetabolic decomposition of  pesticides.   Ann. N.Y. Acad.
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Davidow,  B.   A spectrometric method for the quantitative estimation of
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Feltz, H. R.,  Sayers,  W.  T.,  Nicholson, H.  P.  National monitoring program
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Fleming,  W.  E.,  Coles,  L.  W.  and  Maines,  W. W.  Biological assay of residues
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Gunther,  F.  A.,  Westlake,  W.  E. and Jaglan, P. S.   Reported solubilities
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Ingle, L.  A monograph  on  chlordane, toxicological  and pharmacological
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Inglis, A.,  Henderson,  C.  and  Johnson,  W.  L.   Expanded program for pesticide
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Lamar, W. L., Goerlitz,  D.  F.  and  Law,  L.  M.   Determination of  organic
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Malina, M. A., Rozek, A. and  Schwemmer,  B.   AG  Chlordane:   development of
     methods for  its analysis and  control.   J^  Ass.  Offic.  Anal.  Chem. 55:942
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     Anal. Chem.  45:513-17  (1962).

Metcalf, R. L.  The chemistry and biology of pesticides.  p.  1-144.   In
     Pesticides in the Environment.  Vol. 1:4970.  White-Stevens,  R.,  Ed.,
     Marcel Dekker, Inc.,.N.Y.  (1971).

Noren, K. and WestHB, G.  Determination  of  some chlorinated pesticides in
     vegetable oils, butter,  milk,  eggs, meat and  fish by gas  chromatography
     and thin-layer chromatography.  Acta.  Chem. Scand. _22(_7_) : 3389-93  (1968).

Ordas, E. P., Smith, V. C. and Meyer,  C. F.  Spectrophotometric determination
     of heptachlor and technical chlordane  on food and forage  crops.   J_.  Agr.
     Food Chem. 4_:444-51 (1956).

Polen, P.  Chlordane:  composition,  analytical  considerations  and  terminal
     residues.  Presented to  IUPAC  Commission on Terminal Residues,  Geneva,
     Switzerland  (1966).

Riemschneider, R.  The chemistry of  the  insecticides of the diene  group.
     World Rev. Pestic. Contr.  ,2:29-61 (1963).

Sadar, M. H. and  Guilbault, G.  G.   A specific method for the assay of  select
     chlorinated  pesticides.   £. Agr.  Food  Chem. l£:357-59  (1971).

Saha, J. G.  Comparison of several methods  for  extracting chlordane  residues
     from soil.   J_. Ass. Offic. Anal.  Chem.  54_:170-4 (1971).

Saha, J. G., Lee, Y. W.  Isolation  and identification  of the components of a
     commercial chlordane formulation.   Bull. Environ.  Contam.  Toxicol.
     4. (5) : 285-96  (1969).

Seba, D. B., Lane, C. E.  Rapid microdetection  of  organochlorine pesticides
     in submilligram fish tissue samples.   Bull. Environ. Contam.  Toxicol.
     4_(5): 297-305 (1969).

Stansbury, R. E.  and Dahm,  P.  A.  Alfalfa dehydration  upon  residues  of aldrin,
     chlordane, parathion and  toxaphene.  J. Econ. Entomol.  44:45-51  (1951).
                                        63

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Su, G. C. C. and Price,  H.  A.   Element  specific gas chromatographic analyses
     of organochlorine pesticides  in  the  presence of PCB's by selective
     cancellation of  interferring  peaks,   j;.  Agr.  Food Chem.  ^L:1099 (1973).

Thompson, D. W.  Volatility of  technical  chlordane:  An alternative approach
     for quantitative measurement  of  residues.   _J.  Ass.  Offie.  Anal. Chem.
     _53_(_5):1015-7 (1970).

Thruston, A. D., Jr.  Preliminary  studies of  weathering of chlordane residues.
     J_. Ass. Offic. Anal.  Chem.  4J3:952-54 (1965).

U.S. Department of Health,  Education  and  Welfare,  Food and Drug Administration.
     Pesticide Analytical  Manual,  (1970,  1971).

Wegler, R.  Chemie der pflanzenschutz und Schadlings-bekampfungsmittel Band 1,
     671 pps. Springer-Verlag,  Berlin (1970).

Wiersma, G. B. and Sand, P.  F.   A  sample  design to  determine  pesticide levels
     in soils of the  conterminous  United  States.   Pestic.  Monit.  J_.  5^63-66
     (1971).

Yobs, A. R.  National monitoring program  for  air.   Pestic.  Monit.  J_. _5_:67
     (1971a).                                                         ~

Yobs, A. R.  The national  human monitoring program for pesticides.   Pestic.
     Monit. J. 5:44-46 (1971b).
                                        64

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                                   CHAPTER III

                       Fate and Implications of Chlordane
                                in the Ecosystem
III.A.  The Fate of Chlordane in the Soil - Chlordane persists in the soil.
Under experimental conditions and actual field application of pesticides
chlordane has been shown to persist for extended periods of time, will not
migrate, and is apparently bound to soil particles.  Dependent upon the soil
and climatic conditions, chlordane will dissipate.  However, complete removal
of the residue is a slow process.  Control of some insect species in the soil
is obtained for considerable lengths of time under most conditions.
Analyses of agricultural lands extensively treated with chlorinated pesticides
do not show the residues as might be expected from results obtained with ex-
perimental plots.  For example, there is no indication of why only 10% of the
agricultural soils in Canada show only minute residues of chlordane after
extensive treatments with heptachlor which contains considerable quantities
of Y-chlordane.  The possibilities exist that 1) the material is in the
soil and bound so tightly that it cannot be extracted and analyzed or 2)
under field conditions, after agricultural application, dissipation is more
rapid than is anticipated from experimental conditions, or 3) the material
is metabolized to products which are not recognized with the available
methods of analysis.

III.A.I.   Build-up and Persistence in the Soil - Chlordane is recommended for
use and is used extensively for soil insect control.  Studies have been car-
ried out to determine the duration and extent of soil contamination, either
under experimental or field conditions.  In a series of experiments,
Lichtenstein and Polivka (1959) reported the persistence of chlordane in the
soil in Wisconsin.   Using bioassay techniques they demonstrated that approxi-
mately 15% of active insecticide materials persisted 12 yr  after application
to turf soils.   They further demonstrated that chlordane was more persistent
than heptachlor in the soil.  This could be due to the differences in the
vapor pressure of the two compounds:  chlordane, 1X10-5 mm/Hg; heptachlor,
3X10-4 mm/Hg  (Edwards, 1966).  (Tables 1, 2, 3 and Figure 1).

Chlordane, when applied at dosages of 8 to 10 Ib/acre for the control of
European chafer, provides complete control for at least seven to eight growing
seasons (Gambrell et al., 1968; Shorey et al., 1958).  When chlordane was
applied to Hawaiian soils for the control of subterranean termites it was found
that the material begins to degrade slowly within 4 yr although after 6 yr it
was active as a termite insecticide.  In the last three experiments, bioassay
was used as a means of evaluating chemical effectiveness and no indication was
given to the concentration of chlordane in the soil.

In a more recent study, Lichtenstein et al.  (1970)  determined that approxi-
mately 18% to 20% of an applied dose of chlordane was present in the soil 10
yr after application.   Following the application of approximately 7.5 Ib/acre,
a residue of 0.925 ppm was observed after 10 yr.


                                        65

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       TABLE 1.  Insecticide Vapor Pressures vs. Disappearance from Soils
Insecticide
Average ^ insecticide
in soil after JL_ yr
     Vapor pressure
     at_ 20°C  (mm Hg)
DDT


Dieldrin

Lindane


Aldrin


Chlordane

Heptachlor
          80


          75

          60


          26


          55

          45
l.OxlO"7
     Slightly Volatile

l.OxlO-7

9.4xlO-6
     Moderately volatile

6.0xlO~6
     Volatile

1.0xlO~5

3.0xlO-4
Reprinted from Persistent pesticides in the environment, 2nd ed., by C. A.
Edwards by permission of CRC Press, Cleveland, Ohio  (1973).
                                        66

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   TABLE 2.  Persistence of Some Chlorinated Hydrocarbon Insecticides in Soil
Chemical
Aldrin
Chlordane
DDT
Dieldrin
Heptachlor
Lindane
Telodrin
Average dose in Ib Al/acre
1-3
1-2
1-2% (10)
1-3
1-3
1-2% (5)
k-1
Time for 95%
disappearance (years)
1-6 (3)
3-5 (4)
4-20 (10)
5-25 (8)
3-5 (3*5)
3-10 (6%)
. 2-7 (4)
a.   Figures in parenthesis are doses which may be used for particular pests
    in unusual circumstances.

Reprinted from Persistent pesticides in the environment, 2nd ed., by C. A.
Edwards by permission of CRC Press, Cleveland, Ohio (1973).
                                        67

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            TABLE  3.   Persistence  (ppm)  In  soil  after  1  and  2 yr.
Insecticide
Aldrin
Heptachlor
Chlordane
Lindane
Dieldrin
DDT
1 yr
25
45
55
60
75
80
2 yr
5
10
15
—
40
50
Reprinted from Persistent pesticides in the environment, 2nd ed., by C. A.
Edwards by permission of CRC Press, Cleveland, Ohio (1973).
                                      68

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             100
                                                       DbT
                                              Undone
                       i
                       2
 i
J
  Iteptcclihr	
_   .    r—p
 4   H   6   7
i
8
9  10   II
                                 Time [yean)—>
    Figure 1.   Breakdown of chlorinated hydrocarbon insecticides  in soil
Note:  Regression  based on all available data.


Reprinted from Persistent pesticides in the environment,  2nd  ed.,  by C.  A.
Edwards by permission of CRC Press, Cleveland, Ohio  (1973).
                                        69

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Chlordane was more persistent  than heptachlor whether  the soil was cultivated
or planted in alfalfa.  Cultivation  reduced  the residue level of heptachlor
but not chlordane.

Degradation of a chemical  in the soil is a function of many conditions.
Generalizations on the persistence of chlordane in the soil on the basis
of experimental work  in another area with different soil types is not valid
(Bess et al., 1966).  The  penetration of chlordane into the soil is primarily
dependent upon the soil type and the organic matter content.  Other factors
such as moisture, pH, silt, and clay content play a lesser role in the pene-
tration and stability (Carter  and Stringer,  1970).

The reduction of residues  of chlordane is a  relatively slow process.  Only
45% of the initial dose of chlordane was removed from the soil 1 yr after
application; approximately 3 to 5 yr are required to remove 95% of the
residue of chlordane  (Edwards, 1966).
                                                     **
Lichtenstein et_ al. (1971) found that, under the conditions of their study,
chlordane does not move when applied to the  soil.  Ninety-five percent of the
residue was found in  the top 6 in  of soil, with 52% of the residue being in
the top 2 to 4 in layer,

Chlordane was applied to soil  at a rate of 145.7kg/hectare  (Nash and Woolson,
1968).  Thirteen years after the initial application, approximately 11% of
the total material applied to  the soil was present as a residue.  Out of 9
chlorinated pesticides examined, chlordane was the least mobile and tended
to remain in the upper soil layers.  Except  for dieldrin and endrin, cyclodiene
insecticides were present  in quantities of less than 11% of the administered
dosage.

Onsager et al. (1970), demonstrated  that the loss of chlordane from a loam
soil was proportional to the amount applied.  When application rates varied
from 1.25 to 20 Ib /acre,  residues after 30 months in the soil were observed
ranging from 0 to 48% of the initial concentration.

Chlordane was applied at 8 and 10 Ib/acre and approximately 18 to 30% of the
applied dose was found as a residue after 12 yr (Steward and Fox, 1971).
Penetration of the pesticide was generally into the top 0 to 4-in layer of
the loam soil although some penetration of 6 to 8 inches was observed.

Studies have been carried out  in Canada on residues of chlordane in soils
from various sections (Saha et al., 1968).   In agricultural soils in
Northeast Saskatchewan,  only one of 20 soil samples examined contained a
measurable level of chlordane  (0.02 ppm).  Sixteen of the 20 soil samples
had residues of other cyclodiene pesticides.

In the Atlantic provinces of Canada, Duffy and Wong (1967) were able to
detect chlordane in less than 10% of the agricultural lands and only at
concentrations below 1 ppm.  For many years the land had been exposed to
heptachlor which was contaminated with high concentrations of Y-chlordane.
                                        70

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A more recent survey of  the build-up of  chlordane  soLls  in  Saskatchewan
indicated  that chlordane was present in  17%  of  the  soils  sampled  (Saha and
Sumner,  1971).  Seven of 41 samples were  positive-  lor  Hi lord.mr with  3 ol
the samples showing residue levels of 0.01 to 0.1  ppm; 3  samples  showing
residue  levels of 0.11 to 0.5 ppm; and one sample  showing a residue level of
3.91 ppm.  These soils were sampled from  farms  having  an  extensive history
of cyclodiene insecticide applications.

Samples  of soil from six states  in 1967  showed  the  most  commonly  occurring
pesticides to be members of the  DDT group, dieldriri, or  chlordane (Wiersma
et^ aJ.,  1971).  Only 5.4% of all samples  had chlordane residues.   Soils from
four of  the six states showed levels of  chlordane  less than 0.01  - 0.02 ppm.

Gish (1970), in an examination of residues in soils  from  eight states, showed
that only one area had small residues of  ychlordane which  presumably came
from contamination resulting from heptachlor application.

Attempts have been made  to reduce residue levels in  soil  with cultivation
(Lichtenstein et al., 1971) or by treatment with activated  charcoal
(Lichtenstein ej^ JL^. , 1968; Ahrens and Kring, 1968).   This  technique  does
not appear to be practical on a  commercial scale and,  on  the basis of sur-
veys of  agricultural croplands in the U.S. and  Canada, is probably not
necessary.

III.A.2.   Translocation  into Plants - Chlordane, when  applied to  soil for
control  of soil insects, will translocate to certain plants, primarily root
crops.

Onsager  et al. (1970) , reported  that 2 yr after application of chlordane  to
a loam soil small residues were  found in  sugar  beets.  The  concentrations
were proportional to those applied to the soil.

Winnett  and Reed (1968) applied  chlordane to a  loam  soil  at a Level of 4  to
6 Ib/acre.  Residues of  75 to 100 ppb were detected  in potatoes during the
first year of planting.  No residues were found after  1 yr.  No indication
was given as to the concentration of chlordane  in  the  soil.

.^..,, v.^  ».t. vo-j/uuy d|>pj.j.ea cnxordane at  10 Ib/acre  and also,if blind residues
the first year in carrots, sweet potatoes anil rutabagas.  Several other crops
were, found to contain no residues.  In general, it  has been/found that root
crops will absorb small quantities of. chlordane.  Carrots,  radishes,  turnips
and onions have been observed to absorb  low  levels  of  pesticides  from the
soil.  Boyd (1971) demonstrated  that chlordane  was  easily translocated from
soil to  alfalfa, but only in the first year after application.

Harris and Sans (1967) found that although residues of insecticides were
present  in high levels in soil,  the quantities  translocated to crops were
not above tolerance levels set for Canadian! agriculture.  Although translo-
cation did occur, it appeared to be rather snail.  Lichtenstein et al. (1970)
observed that in carrots, the crop which generally absorbs  the greatest quantity
of pesticide from the soil, approximately 10 to 15% of the  soil residue levels


                                        7.1

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were  found  in  the  edible  portion.   Boyd  (1971)  reported  that  the  relationship
of  the  soil residue  to  the  crop  residue  was  not consistent  or  precl i c: t;ihl e.
Soil  containing  an average  of  0.38  ppm in  the  top  one  quarter-inch,  and  soil
containing  1.32  ppm  in  the  top one  quarter-.inch, both  gave  approximately  the
same  residue in  the  alfalfa.   Caro  (1969)  was  not  able to establish  a  rela-
tionship  between the concentration  of pesticide in the soil and  that  taken  up
by  plants.

III.B.  Build-up of  Chlordane  in the Water - Several studies have indicated
that  contamination of water by chlordane is  not a  widespread problem.  Waters
examined  in 1966 showed positive values  of chlordane ranging from 5  to 75 ppt.
The sensitivity  of the method  was reported to  be 1 to  5  ppt.  (Green  et al.,
1966).  Water  from Galveston Bay was essentially free  of chlordane  residue  in
1964  following a mosquito control program  in which chlordane was  used  (Casper,
1967).  Large  amounts of  chlorinated pesticides applied  to  crops  in  the
Mississippi River  Delta showed as residues of  cyclodiene insecticides  in only
two areas close  to manufacturing and formulating plants  (Barthel  e_t_ al^. , 1969).

Schafer e_t  ji^L. (1969), examined  drinking water,  originating I rom  the
Mississippi and  Missouri  rivers,  for chlordane  and other pesticides.   They
observed  that  chlordane did not  appear to  be a  si  nificant  contaminant of.
drinking water.  Levels above  0.25  ppb were  found  in 14  of  63  samples  of
drinking water examined.  Twelve of the  14 samples were  from one  location
(Kansas City).   Twelve of 28 samples taken from the Kansas  City area were
positive  for chlordane.   Examination of  raw  water  showed that  11  of  46 samples
had traces  of  chlordane.  Again  the majority of the samples were  from  the
Kansas City area and all were  not uniformly  contaminated.   Although  the  study
showed a  large proportion of samples containing chlordane (>0.25  ppb)  most  of
the samples  were from one area which apparently had a  local contamination.
The chlordane  concentration of the Kansas  City  water samples was  in  excess  of
0.25  ppb.   Abusive use of pesticides will  result in residue levels  in  water
as  evidenced by  Shea (1970) who  described  the high chlordane content of  a
stream into  which  a  commercial applicator  had  dumped a pesticide.

Measurements of  chlordane content in rainwater  in  the  United Kingdom at  a
sensitivity  of 1-2 ppt showed  that no detectable levels  of  chlordane were
evident (Tarrant and Tatton, 1968).  Significant quantities of BHC, DDT  and
its analogues, arid dieldrin were observed  in rainwater at all  t Lines of the
year  and  in  all  locations in the United  Kingdom.

in  vitro studies indicate that chlordane residues  in water  will not be a sig-
nificant problem.  Bowman et al.  (1964) , examining the fate of several chlor-
inated pesticides  in a static, nonmoving water  system  concluded that the non-
polar materials  will co-distill  with water and  thus be removed more quickly
than  the more polar  pesticides.  They demonstrated chlordane was  removed more
readily than other chlorinated pesticides  including lindane, DDT, dieldrin
and heptachlor epoxide.  Although these  studies  do not correlate  all of the
factors occurring  in nature, it  is conceivable  that co-distillation phenomena
in  the aquatic environment will  result in  a  reduction  of the residues  of
chlorinated  insecticides which might otherwise occur.   Further in vitro stu-
dies by Bevenue  and  Yeo (1969a,  1969b)  show  that when  chlordane is exposed  to
                                        72

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water or water vapor, various changes occur, and some of the components are re-
moved with  a  short period of  time.  This study indicates that heptachlor, a
natural component of  technical  chlordane, disappears when exposed  to water for
14 days.  This study  confirms the observations by  Bowman ej__ ;i I .  (1964)  that
heptachlor  in aqueous solutions  is more volatile and is removed  faster  than
y-chlordane.  The relationship  of chlordane  to heptachlor in water is similar
to that observed in soil, where  because of differences in the vapor pressure,
heptachlor  is less persistent.

It has been demonstrated that chlordane residues probably will not occur  in
drinking water or water supplies within the  United States except under  condi-
tions of misuse.  However,  if contamination  does occur the removal of contam-
inants can  be accomplished  with  charcoal (Weber and Gould, 1966).  It has been
found that  levels of  pesticides  in the range of 1  to 100 ppb can be effectively
removed from  water by activated  charcoal filtration.

III.C.  Air - The atmospheric contamination  by chlordane does not  appear  to be
a major environmental problem.   Tabor  (1966) reported the presence of chlor-
dane in air over agriculture and nonurban areas at levels approximating 30
ngm/m .  Chlordane was not  found in air over urban areas where it  had been
used for mosquito abatement programs.  In the fall season, when agricultural
use of chlordane ended, atmospheric contamination was not observed in agri-
cultural areas.  Jeigier (1969)  observed that detectable levels of chlordane
were found  in the atmosphere of  apartments,  stores and cafeterias  which had
been treated  by professional pest control operators for insect control.  Levels
of 0.8-0.92 mg/m^ were frequently observed during  the spray operations.  Cal-
culations indicated that the high level exposures were significanlty low so as
to not represent a toxicological hazard to the operator.

Examination of chlordane in air  of homes treated for termite control showed
essentially that no traces  of chlordane from newly treated houses  was evident
(Malina et_  al., 1959).  Of  12 houses studied, two showed positive  levels of
chlordane with a maximum level of 0.04 ug at 126 days after treatment.  Con-
centrations of chlordane in the  air of houses treated for insect control ap-
pear to be  extremely low.

III.D.  Effects on Flora and Fauna - As chlordane is primarily a soil insecti-
cide, one of  the most significant features of its effect on the environment
should be considered to be  its effect on the soil fauna.

Edwards (1969, 1970) evaluated the ecological role played by invertebrates in
the soil and  the effects of pesticides on these organisms.  A primary role of
the soil fauna is the disintegration and digestion of plant residues to their
organic and inorganic constituents, and working of the products into the soil
structure.

The most important of the animals involved in soil conditioning are the earth-
worms followed closely by related worms and  other arthropods.  In places where
only a few  of these animals are present the  soil is usually of poor structure
and contains  distinct layers of undecomposed organic matter near the surface.
If there were no invertebrate populations in soils the process of soil


                                        73

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formation would be  slow or would stop altogether with drastic effects on the
soil's fertility.   Although not all soil animals are beneficial, the vast
majority are vital  to  the continued well-being of  the environment.

The general relationship between the amount of insecticide applied to the soil
and the number of soil animals killed is not directly proportional but is more
nearly logarithmic:  a dose 10 times greater may kill only twice as many
animals.  It is, however, the more persistent pesticide, rather than the more
toxic ones, that have had the most dramatic affect on the numbers of soil
animals.

The most valuable of all soil invertebrates to man is probably the earthworm;
these animals break down much of the plant debris  reaching the soil and turn
over the soil and aerate it.  Although earthworms are not susceptible to many
insecticides, chlordane, heptachlor and certain selected organophosphate and
carbamate insecticides seriously decrease populations of earthworms.  This
aspect of chlordane toxicity to earthworms is valuable only in its use as a
turf insecticide, whereas on golf course greens the presence of earthworms is
undersirable and control is effected by chlordane.  Another aspect is that
chlorinated hydrocarbons can concentrate in the fatty tissues of earthworms,
and although these are not toxic in themselves they may serve as a lower link
in a food chain and as a source of residues in higher animals.

Gish (1970), examining the chlordane residues in soils from agricultural
lands, observed that only one of eight states examined had levels of chlordane
present.  On the other hand, there were levels of approximately 25 ppb in
earthworms indicating that earthworms tended to concentrate chlordane in their
bodies when y-chlordane was present below the sensitivity of the methods used
to detect it in the soil.

II.D.2.   Microflora - Data on the effects of chlordane on various other non-
target organisms within the environment are scant.  Chlordane at 1 ppm was
found to affect phytoplankton by inhibiting carbon fixation (Ware and Roan,
1970).  All cyclodiene insecticides, except endrin, were effective in inhib-
iting phytoplankton carbon fixation.

Winely and San Clemente (1970) observed that chlordane inhibited the growth
and nitrite oxidation of Nitrobacter agiles.  This organism is vital for the
oxidation of the ammonium ion to the nitrate ion in the soil.   The physiologi-
cal effect of the interaction of chlordane with other organisms affecting
nitrate production is extremely important and has not been determined.   These
authors also indicated that chlordane inhibited cytochrome-C-oxidase activity
in Nitrobacter.

An examination for the presence of chlordane in water,  suspended water plants,
algae, chubs,  bass,  and clams in water from an area of  extensive agricultural
use indicated that the presence of chlordane was minute and no substantial
build-up was evident in any of the organisms or media examined (Godsil and
                                  74

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Johnson,  1968).  The  concentration  factor was  1.91  for algae,  1.20  for  chubs,
0.9  for clams, and 0.45  for vascular  plants, indicating no magnification of
chlordane residues.

III.D.3.   Shellfish -  Examination of  132 samples of oysters  from  the South
Atlantic  and Gulf of Mexico areas showed that  20 samples were  positive  for
chlordane with 19 of  the 20 indicating  levels  of less than 10  ppb and one
sample showing a level of  10 ppb  (Bugg  et al., 1967).  Almost  no  chlordane was
found to  be concentrated in the oyster  samples although positive higher values
were obtained for most other chlorinated pesticides.  Casper (1967) observed
that oyster samples taken  from Galveston Bay in 1964 were free of chlordane
residues  which was at  that time being used in  extensive mosquito  control
programs.

III.D.4.   Fish - Extensive surveys  have been made for chlordane residues in
fish during the past several years.  Henderson, et_ _al. (1969), examined 590
fish samples from 50 stations in the Great Lakes and major river basins.  One
hundred and twenty-eight samples had residues  of chlordane.  However, only
two areas  (one in New  York's Hudson River and  one in Alabama's Tombigbee
River) had residues greater than 1  ppm.  Of the 128 positive fish samples
obtained,  61 had residues of both chlordane and heptachlor epoxide.  In
general,  the values were well below 0.5 ppm in most positive samples, and
apparently the residues  of chlordane existing  in fish are extremely low and
scattered.

Henderson  e^ al. (1971), in a continuation of  this study reported that  resi-
dues of chlordane were found in fish at 6 of the 50 stations examined in 1969.
Positive values were found in 16 of the 147 samples examined ranging from 0.09
to 13.5 ppm.  Duke and Wilson (1971) examined  the livers of fish from the
Pacific Ocean and found no chlordane present in the 34 species of fish
examined.  Other chlorinated pesticides and PCB's were evident.  It appears
reasonable to assume at  the present time that  there is no substantial build-
up of chlordane in fresh water fish, salt-water fish and lower forms of
marine life including  the oyster which is well known for its tendency to con-
centrate organochlorine pesticides.

Fish sensitivity to chlordane varies with the species, with fathead minnow
more sensitive than goldfish, guppy, channel catfish,  and rainbow trout
(Jones,  1964).   Chlordane was found to be less toxic than aldrin, dieldrin
and endrin to the minnow, goldfish  and guppy but more toxic than heptachlor.
Chlordane is the least toxic of the cyclodiene compounds to the rainbow trout.
Chlordane was found to be less toxic than DDT,  y-BHC and toxaphene to finger-
ling bluegill and large mouth bass.  Macek ejt al.  (1969), confirmed that
chlordane was less toxic than other chlorinated pesticides to  the bluegill.
The following compounds were observed in order of decreasing toxicity:
endrin,  toxaphene, aldrin, dieldrin, methoxychlor,  lindane and chlordane.
Temperature was shown to have a marked effect on the susceptibility of blue-
gills to chlordane.   This may be explained by the increased rate of absorption
or the increased metabolic conversion of chlordane to a more toxic metabolite
at higher temperatures.
                                  75

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III.D.5.  Birds - There is little available data on the toxicological hazard
of chlordane to various species of wildlife.  Tucker and Crabtree  (1970)
reported that the female mallard duck  (4-5 months old) was relatively
insensitive to the acute effects of chlordane with an acute LI>5o of 1.2 g/kg.
Wazeter  (1968) studied the subacute toxicity of chlordane to the Cotunix
quail  (2 weeks old).  Quail were fed diets containing chlordane at levels
of 25-200 ppm for 28 days.  Death occurred at 200 ppm dietary levels, preceded
by signs of hypoacticity, ataxia and prostration.  The same signs were seen
at 100 ppm although no deaths occurred and the animals appeared to recover
rapidly, appearing normal at 28 days.  No toxic effects were noted at 25 ppm
in this study.

Although chlordane has been found as a residue in soil and as a contaminant
in water, the build-up in wildlife from environmental exposure does not appear
to be significant.  Benson and Gabica  (1970) found no chlordane residue in
starlings, although traces of heptachlor and heptachlor epoxide were found in
their fat.  These birds are not at the top of the food chain but contribute
to the diets of raptorial birds.

No chlordane was found in eggs of several birds (pheasant, bluewinged teal,
and coots) by Johnson et £LL. (1970).  Substantial levels of heptachlor epoxide
were found in all eggs at levels varying from 0-10 ppm in the coot, 7-79 ppm
in the teal and 16-220 ppm in the pheasant.  In addition to the high concen-
trations of heptachlor epoxide there was evidence of high concentrations of
other pesticides in the eggs.  However, there was no evidence of reproduction
problems.

An examination was made of birds and insects found in association with cotton
fields heavily treated with insecticides including chlordane.  No chlordane
was found in any of the bird samples and only a trace of chlordane was found
in an adult mayfly (El Sayed et al., 1967).
                                  76

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                               CHAPTER  III

                               Biblography
Ahrens , J. F. , and Kring, J. B.  Reduction  of  residues  of  heptachlor  and
     chlordane in carrots with soil  applications  of  activated  charcoal.
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Barthel, W. F. , Hawthorne, J. C. , Ford, J.  H. , Bolton,  G.  C. ,  McDowell, L. L.,
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     of the lower Mississippi River  and its tributaries.   Pestic.  Monit.
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Benson, W. W. , and Cabica, J.  Insecticide  residues  in  starlings in Idaho.
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Bess, H. A., Ota, A. K. , Kawanishi,  C.  Persistence  of  soil  insecticides  for
     control of subterranean termites.  J^.  Econ .  Entomol.  59 (4_) :   911-915
     (1966).                            ~

Bevenue, A., and Yeo,  C. Y.  Gas chromatographic  characteristics of chlordane.
     I.  Effect of an  aqueous environment on  the  heptachlor  component.  Bull.
     Environ. Contam.  Toxicol. 4(2):68-76 (1969a) .

Bevenue, A., and Yeo,  C. Y.  Gas chromatographic  characteristics of chlordane.
     II.  Observed compositional changes of the pesticide  in aqueous  and
     nonaqueous environments.  J^. Chromatogr . j4_2_CO :45-52  (1969b).
Bowman, M. C. , Acree, F. Jr., Lofgren, C. S. , and Beroza, M.   Chlorinated
     insecticides:  Fate in aqueous suspensions containing mosquito  larvae.
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Boyd, J. C.  Field study of a chlordane residue problem:  soil and plant
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Bugg, J. C. , Jr., J. E. Higgins, and E. A. Robertson, Jr.  Chlorinated
     pesticide levels in the eastern oyster  (Crassostrea virginica)  from
     selected areas of the South Atlantic and Gulf of Mexico.  Pesti. Monitor.
     J^ 1(3):9-12 (1967).

Caro, J. H.  Accumulation by plants of organochlorine insecticides from the
     soil.  Phytopathology, 59_:1191-97 (1969).

Carter, F. L., and Stringer, C. A.  Soil moisture and soil type influence
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     Contam. Toxicol.  5:422-28.   (1970).
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Carter, F. L. , Stringer, C. A., and Beal, R. H. Penetration and persistence
     of soil  insecticides used for termite control.  Pest Contr.  38:18-20,
     22, 24,  & 62  (1970).

Casper, V. L. Galveston Bay pesticide study — water and oyster samples
     analyzed for  pesticide residues following mosquito control program.
     Pestic. Monit. J. 1:13-15 (1967).

Chiba, M.  Factors affecting the extraction of organo chlorine insecticides
     from soil.  Residue Rev. 30:63-113  (1969).

Cohen, J. M. , and  Pinkerton, C.  Organic pesticides in the environment.
     Widespread translocation of pesticides by air transport and rainout .
     Amer. Chem. Soc. Adv. in Chem. Series 60:163-76 (1969)

Duffy, J. R. , and Wong, N.  Residues of organochlorine insecticides and  their
     metabolites in soils in the Atlantic Provinces of Canada.  J^. Agr .  Food
     Chem.  15(3):457-64 (1967).

Duke, T. W. ,  and Wilson, A. J., Jr.  Chlorinated hydrocarbons on livers  of
     fishes from the Northeastern Pacific Ocean.  Pestic. Monit . J_.
     50(2):228-32  (1971).

Edwards, C. A.  Critical reviews in environmental control, 1, CRC Press,
     Cleveland.

Edwards, C. A.  Insecticide residues in soils.  Residue Rev.  13:83-132  (1966).

Edwards, C. A.  Persistent pesticides in the environment, 2nd ed., by C. A.
     Edwards by permission of CRC Press, Cleveland, Ohio (1973).

Edwards, C. A.  Soil pollutants and soil animals.  Scientific Amer.
     228(14) :88-89 (1969).

El Sayed, E.  I.  Graves, E. I., and Bonner, F. L.  Chlorinated hydrocarbon
     insecticide residues in selected insects and birds found in association
     with cotton fields.  Jf. Agr. Food Chem.  15:1014-17 (1967).

Gambrell, F. L., Tashiro, H. , and Mack, G. L.  Residual activity of
     chlorinated hydrocarbon insecticide in permanent turf for European
     chafer control.  J. Econ. Entomol.  jrl (6_) : 1508-11 (1968).

Gish, C. D.  Organochlorine insecticide residues in soils and soil inverte-
     brates from agricultural lands.  Pestic. Monit. J^. ^(4_): 241-52 (1970).
Godsil, P. J., and Johnson, W. C.  Residues in fish, wildlife and estuaries —
     pesticide monitoring of the aquatic biota at the Tule Lake National
     Wildlife Refuge.  Pestic. Monit .  £. _l:_21-26 (1968).

Green, R. S., Gunnerson, C. G. , and Lichtenberg, J. J.  Pesticides in our
     national waters.  AAAS Symposium - "Agriculture and the Quality of our
     Environment."  Dec. 27, 1966.

                                    78

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Harris,  C.  R.,  and  Sans,  W.  W.   Absorption of organochlorine insecticide
     residues  from  agricultural  soils by root crops.   J_.  Agr.  Food Chem.
     15/.861-3  (1967).

Henderson,  C.,  Johnson, W. L., Inglis,  A.   Organochlorine insecticide
     residues  in  fish.  Pestic.  Monit.  .J.  3(3):145-70 (1969).

Henderson,  C.,  Inglis, A., and Johnson, W.  L.  Organochlorine insecticide
     residues  in  fish  —  Fall, 1969,  National Pesticide Monitoring Program.
     Pestic. Monit.  J_. , !5Q.)1-11 (1971).

Jeigier, Z., Pesticide residues  in the atmosphere.   Ann.  .N.  Y.  Acad.  S_ci_.
     160:143-154  (1969).

Johnson, L. G., Morris, R. L., and Harrison,  H.   Preliminary study of
     pesticide  levels  on  the eggs  of  Iowa  pheasants,  blue wing  teal and
     coots.  Bull.  Environ.  Contain. Toxicol.  _5:474-478 (1970).

Jones, J. R. Erickson.  Fish and river  pollution.   Butterworth  & Co.  Ltd.,
     London, pp.  128-141  (1964).

Lichtenstein, E.  P., Schultz, K. R. ,  Fuhremann,  T.  W., Liang, T.  T.
     Degradation  of  aldrin and heptachlor  in  field  soils  during a 10-year
     period.  Translocation  into crops.  J_. Agr.  Food Chem.  18(1) :100-6
     (1970).

Lichtenstein, E.  P., Schultz, K. R.,  and Fuhremann,  T. W.   Pesticides in
     soil.  Effects  of a  cover crop versus  soil  cultivation  on  the fate and
     vertical distribution of insecticide  residues  in soil 7 to 11 years
     after  soil treatment.   Pestic. Monit.  J_. 5(2) :218-23 (1971).

Lichtenstein, E.  P., Fuhremann,  T. W.,  and  Schultz,  K. R.   Use  of carbon to
     reduce the uptake of insecticidal  soil residues  by plant crops.   J_. Agr.
     Food Chem. 16:348-55 (1968).

Lichtenstein, E.  P., and  Polivka,  J.  B.  Persistence  of some chlorinated
     hydrocarbon  insecticides in turf  soils.   J_.  Econ. Entomol.  52:289-93
     (1959).

Macek, K. J., Hutchinson, C., and  Cope,  0.  B. The  effects of temperature on
     the susceptibility of blue  gills  and  rainbow trout to selected pesti-
     cides.  Bull. Environ.  Con tarn. Toxicol.  4^(3):174-83  (1969).

Malina, M.  A., Kearny, J. M., and  Polen, P. B.   Determination of chlordane in
     air of habitations treated  for insect  control.   J_. Agr.  Food Chem.
     7:30-33 (1959).

Muns, R. P., Stone, M. W., and Foley, F.  Residues  in vegetable crops follow-
     ing soil applications of insecticides.   J_.  Econ.  Entomol.  53:832-4
     (1960).
                                  79

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Nash, R. G., and Woolson,  E.  A.   Distribution of  chlorinated insecticides in
     cultivated soil.   Soil  Sci.  Soc.  Amer.  Proc.  3^:525-7  (1963).

Onsager, J. A., Rusk, H. W.,  and  Butler,  L.  I.  Residues  of aldrin,  dieldrin,
     chlordane and DDT  in  soil  and  sugarbeets.  J_.  Econ.  Entomol.  63(4):
     (1970).

Saha, J. G., and Sumner, A.  K.  Organochlorine insecticide  residues  in soil
     from vegetable  farms  in Saskatchewan.   Pestic.  Monit.  J_.  Ml):28-31
     (1971).

Schafer, M. L., Peeler, J. T.,  Gardner, W. S.  and  Campbell, J.  E.  Pesticides
     in drinking water:  Water  from the Mississippi and Missouri rivers.
     Environ. Sci. Technol.  3_(12) : 1261-9  (1969).

Shea, K. P., Dead Stream.  Environment 12:12-15 (1970).

Shorey, H. H., Evans, W. G.,  Burrage,  R.  H.  and Gyrisco,  G. G.   The  residual
     effect of insecticides  applied to meadow and  pasture sod  for control
     of the European chafer.  J_.  Econ. Entomol. _5.1: 765-67 (1958).

Stewart, D. K. R. and Fox, C. J.  S.  Persistence  of  organochlorine insecti-
     cides and their metabolites  in Nova  Scotian  soils.   ^J. Econ.  Entomol.
     64U):367-71 (1971).

Tabor,  E. C.  Contamination  of  urban air  through  the use  of insecticides.
     Trans. N.Y. Acad.  Sci. ^8(_5) : 569-578 (1966).

Tarrant, K. R. and Tatton, J. C.  G.  Organochlorine  pesticides  in rainwater
     in the British  Isles.   Nature,  219 (5155):725-7 (1968).

Tucker, R. K. and Crabtree,  D.  G.   Handbook  of  toxicity of  pesticides  to
     wildlife.  U.S.D.I.   Bureau  of  Sprot Fisheries  and Wildlife.  Resource
     Publication.  <84_:34-35  (1970).

Ware, G. W. and Roan, C. C.   Interaction  of  pesticides with aquatic  micro-
     organisms and plankton.  Residue  Rev. _3.3:15-45  (1970).

Wazeter, F. X.  One  month  oral  subacute toxicity study  in Coturnix quail.
     Unpublished study by  International Res.  &  Dev.  Corp.,  submitted by
     Velsicol Corp.  (1968).

Weber,  W. J., Jr., and J.  P.  Gould.  Sorption of organic  pesticides  from
     aqueous solution.  Advan.  Chem. Ser.  No.  60:280-304.   (.1966); See also
     Advances in water polution control,  Intern. Conf., 1966,  3(1):253-281
     (1967).
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Wiersma, G. B., Sand, P. P. and Schutzmann, R. L.  National soils monitoring
     program - six states, 1967, Pestic. Monit. j;. _5(2J : 223-227  (1971).

Winely, C. L. and San Clemente, C. I.  Effects of pesticides on  nitrite
     oxidation by Nitrobacter agiles.  Appl. Microbiol.  19(2):204-19
     (1970).

Winnett, G. and Reed, J. P.  Aldrin, dieldrin, endrin,  and chlordane
     persistence — a 3-year study.  Pestic. Monit. J[. ^(3): 133-6 (1968).
                                  81

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                               CHAPTER IV

                    Residues in Crops and Food Items


 IV.A.   Tolerances - During the year 1950, public hearings were held on
 tolerances for certain pesticides on raw agricultural commodities.   At
 that time toxicity and residue data for chlordane were presented.   Taking
 all the evidence into consideration, and on the basis of  criteria  for
 safety at that time,  the Food and Drug Administration (FDA)  deemed  that the
 margin of safety was  sufficient to justify a tolerance of 0.2 ppm  for resi-
 dues of chlordane in  or on 46 raw agricultural commodities (Federal Register.
 March  11, 1955;^20 FR 1473).

 In  1963,  FDA reevaluated the  toxicological data on chlordane and found the
 available data inadequate to  support a conclusion regarding  the safety of
 the  tolerances for chlordane  and proposed that these tolerances be  repealed
 and  a  tolerance  of zero be established for all listed crops  (Federal Regis-
 lejL, December 5,  1963,  28 FR  12938).   The Velsicol Chemical  Corporation
 challenged  the decision by  the  FDA,  and  the  National  Academy  of Sciences,
 National  Research Council appointed an FDA Advisory Committee to review the
 situation.   The  Advisory Committee recommended that the tolerance level of
 chlordane remain at 0.3 ppm.   The FDA,  after consideration of the findings
 and  with  the recommendations  of the Advisory Committee and other available
 data,  concluded  that  a  tolerance of 0.3  ppm chlordane containing not more
 than 1% of  the intermediate compound hexachlorocyclopentadiene  be estab-
 lished on various raw agricultural commodities (Federal Register, April 5,
 1965,  65  FR 3563).

 Tolerances  for chlordane were reviewed by the Food and Agricultural
 Organization/World Health Organization  (FAO/WHO)  (1968), and  the following
 levels  were presented:  United States,  0.3 ppm (on wide variety  of foods,
 approximately  50  individual crops);  Canada,  0.3  ppm (on a  wide  variety  of
 foods); European  Economic Community,  0.2  ppm (combined total  of all
 cyclodiene  residues on  fruits and vegetables); Netherlands, Belgium,
 Luxembourg,  0.1 ppm.

 IV.B.   Acceptable Daily  Intake  -  On the basis  of  results of two long-term
 feeding studies in the  rat, a no-effect level  was  established at 20  ppm;
 or 1 mg/kg/day (FAO/WHO,  1968).   On the basis  of  the  results  of a 2-yr.
 feeding study  in  the  dog, a no-effect level  for  dog was established  at  3  ppm
or 0.07 mg/kg/day.  The  acceptable  daily  intake  for man was estimated to
be 0.001 mg/kg body weight  (Food  and Agricultural Organization/World Health
Organization,  1968).

 IV.B.I.  Acceptable Daily Intake  -  Chlordane  residues  in crops and food items
were evaluated by the 1967  FAO/WHO  Joint  meeting  (FAO/WHO, 1968).   In general, the
 data suggest that the highest residues consistent with  good agricultural practice
                                  82

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will result in residues in root crops and, under certain conditions, in the
leafy and stalk vegetables.  General information concerning residues resulting
from uses constituting good agricultural practice are summarized in Table 1.


               TABLE 1.  Residues of Chlordane in Crops


Crop	Residue (ppm)
Alfalfa                                                     0.01-0.16
Barley, grain                                               0-0.06
Barley, straw                                               0.98-2.65
Beans                                                      <0.01
Beets                                                       0.17
Beet tops                                                   0.01-0.1
Bell Peppers
Broccoli
Cabbage
Cantaloupe                                                  0.01-0.1
Carrots                                                     0.01-1.5
Collards
Cucumbers                                                   0.08
Eggplant
Lettuce                                                     0.04
Peaches                                                     0.08
Peanuts                                                     1.74
Pineapple                                                   0.15
Potatoes                                                   <0.01-0.23
Radishes                                                    0.03
Rutabaga                                                    0.08-0.5
Snap beans                                                 <0.01
Strawberries                                               <0.01
Sweet potatoes                                              0.01-0.4
Sugar beets                                                 0.04-0.37
Tomatoes            .                                       <0.01
Turnips                                                     0.01-0.16
Turnip tops                                                 0.01-0.1


IV.B.2.  Residues in Meat, Milk, and Eggs - Chlordane is absorbed from the
gastrointestinal tract and through the skin.  It is stored in the meat and
adipose tissue, accumulates in the milk, and will pass into eggs.  Administra-
tion of chlordane either by a single dermal application (Kawar, e^ al., 1968),
in the feed (Carter _et £l_. , 1953; Herrick £t _a_l. , 1969), or from being fed
in pastures containing chlordane residues (Westlake et^ al. , 1963; Knipling and
Westlake, 1966) has been shown to result in significant residues in milk, meat
and eggs.
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Westlake  et  al.  (1963) observed  that  cows grazing on pastures  to which levels
of 0.5 Ib/acre had been applied  showed an average of 0.03 ppm  chlordane in
their milk.  Lower treatment  levels of chlordane produced no milk  residues.
Heptachlor epoxide was observed  in the milk samples and may have risen frrom
the presence of  heptachlor  (6.4%) in  the chlordane formulation or  might be
an artifact  related  to the  presence of oxychlordane.

Tuinstra  (1971)  examined human milk and reported the presence  of 0.06 ppm
heptachlor epoxide although no chlordane was observed.  Saha (1969a) reviewed
some early data  showing residues in milk and fat from chlordane-treated crops
and from  chlordane-treated  animals.   He concluded that chlordane occurring as
a residue in food crops will  pass into milk.

Chlordane as a soil  contaminant  will  migrate to certain crops.  However, the
probability  is small that contamination of meat and milk will  result from
such residues.

Herrick et al. (1969) fed chickens levels of 0.08 ppm chlordane in feed for
one week  and detected no residues in  the egg.  They reported that  a subsequent
study at  higher  dosages resulted in residues in eggs which were reduced very
slowly upon  cessation of the  feeding.  The administration of 10 to 15 ppm
chlordane to hens for five  days  resulted in residues of chlordane  in fat (11
ppm) light meat  (2.1 ppm) and dark meat (2.3 ppm).  Hens, fed  chlordane-
containing diets for 5-1/2  months, were found to have residues of  chlordane-
containing materials in the fat  and egg yolks.  The residues in fat consisted
primarily of 0-chlordane, nonachlor,  oxychlordane and compound E (probably a
chlordene isomer).  The total residues in fat were not substantially removed
upon cessation (for periods of up to  30 days) of feeding.

Chlordane in commercial animal feed,  as a source of residues in meat and milk,
has been  shown to be generally in the range of less than 0.05  ppm.

IV.C.  Pesticide Monitoring

IV.C.I.   Market-Basket Surveys - Surveys of foodstuff for the  presence of
chlordane have demonstrated that chlordane is infrequently present and only
in low levels.   Fifty percent of over 50,000 total samples taken during the
period of 1964 to 1966 by the FDA contained pesticide residues.  Approximately
0.1% of the  samples contained residues of chlordane.  Kraybill (1969), Duggan
(1969) and Duggan et^ al. (1971), examining the market-basket surveys of the
FDA, reported that chlordane was present above tolerance levels in only 17
of 25,000 samples examined.   Chlordane is not among the top 10 chlorinated
pesticides usually found as residues  in food.

An examination of the chlordane  residues in food in the United States from
1963 through 1969 indicated that there were traces of chlordane found on
several domestic food crop  items.  The average value of these  residues was
between 1 and 5 ppb and was less than 1% of the samples tested.  Occasional
higher values were obtained which were always lower than 0.5 ppm.   In the
following products no residues of chlordane were observed:  milk,   dairy


                                  84

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products, fruit, vegetables  (leaf and stem), beans, meat  (fat), eggs, fish,
animal grains,  infant  and junior foods, nuts, and milk.   Traces (0.001-0.005
ppm) were found on  the following items:  grains and cereals, vine and ear
vegetables,  root vegetables, poultry, shellfish, soybean  products, corn,
grain and oleomargarine.  Finite residues were found on several cotton seed
products:  seed, 3  ppb; crude  cotton seed oil, 14 ppb; cotton seed meal, 8
ppb; refined oil, 6 ppb; corn  oil, 77 ppb.

IV.B.2.  Other  Residue Surveys - Field, wholesale and retail market sampling
of agricultural commodities  in Georgia indicate that levels of chlordane
(some slightly  higher  than tolerance) were not widespread  (Brown, 1969).  In
two of the three years during which the samples were taken, levels of chlor-
dane above tolerance were reported.

Of 66 samples of a  total diet  in England and Wales taken  in 1966-67, no
chlordane (with a limit of sensitivity of 1 ppb) was observed (Abbott et al.,
1969).  Small quantities of  Heptachlor epoxide were reported in meat, fat
and cereals. .

IV.C.3.  Residues on Prepared Foods - Chlordane may become a contaminant of
foods by several means in the household.  The most obvious means of contamina-
tion is by direct treatment  of cupboards (Wright and Jackson, 1971) by
absorption from chlordane-treated shelf paper (Yeo and Bevenue, 1969a).  Un-
packaged wheat  flour,  polished rice and sugar were reasonbly effective in
absorbing volatile  components of chlordane.  Chlordane will penetrate packag-
ing materials and contaminate foods.

IV.D.  Effect on Food  Flavor - Although chlordane may be present in foods as
a result of  soil application, several studies have shown  that its probable
presence in  food will  result in no off-flavor or reduction of quality of the
agricultural product.  Studies have been reported for potatoes (Kirkpatrick,
1955; Greenwood and Tice, 1949), strawberries (Sweeney e_t_ aJU , 1968) and
peanut butter (Gilpin  et^ al., 1954).  Although these studies did not measure
the residue  levels  in  the food it was assumed that a concentration of chlor-
dane was present.   However, Morgan et al. (1967) found residue levels greater
than 1 ppm in peanuts  following treatment at 2 Ib/acre.

IV.E.  Removal  of Residues - When excessive pesticide residues occur in food
and other media there  are several common procedures for the removal of these
contaminants.   Street  (1969) reviewed the common procedures for the removal
of residues  from food  and from the environment including removal of residues
from animals which might be  contaminated.  The problem of removing residues
from soil and water takes on a significant dimension and removal is not only
generally ineffectual  but costly and prohibitive.

General methods including cultivation, planting absorbable crops, carbon
absorption and  leeching, all of which generally transfer the residue from one
environmental factor to another.  Many food processing operations, including
washing, cooking, heating, etc., reduce the residues of most materials on
                                  85

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food, depending primarily on the individual compounds.  Cooking procedures
which remove fat are generally helpful in removing chlordane residues from
meat (Liska and Stadelman, 1969).

The International Union of Pure and Applied Chemistry Commission on Terminal
Residues  (Egan, 1969) considered the influence of cooking or processing
operations on the nature and extent of residues of chlordane.  Simple cooking
had no significant effect on the level or composition of residues although
processing operations for milk drastically reduced residues in certain products
A reduction of almost 90% of the residue found directly after spraying alfalfa
was obtained by standard handling and drying procedures normally used (Dahm,
1962).  In the normal commercial production of vegetable oils, processes,
including hydrogenation and carbon clarification, removed all traces of
chlordane residues (Gooding, 1966).

Several recent studies have indicated that processing of milk into various
products is effective in reducing chlordane residues (McCaskey and Liska,
1967; Li ejt al. 1970).

Approximately 90 to 100% of chlordane residue in potatoes was observed to be
present in the peel and removal of the peel effectively reduced chlordane
levels to zero (Saha et al., 1968).  Boiling whole potatoes for 25 min re-
moved only minute quantities of the residue while baking at 400°F for 1 hr.
was effective in removing 80% of the residue.  Washing and boiling rice con-
taminated with clordane was effective in removing 60 to 80% of the residue
(Bevenue and Yeo, 1969).  Cooking wheat flour was somewhat less effective but
did remove an average of 53% of the residue.  During the processing of chicken
containing residues of chlordane, the pesticide content was dramatically re-
duced (Me Caskey et^ al^. , 1968).  Cooking chicken which contained from 2.1 to
2.3 ppm in meat, for 3 hr reduced the pesticide level to 0.8 ppm.  When chick-
en was processed most pesticides associated with the fat were removed when the
fat content was reduced by cooking.  Apparently, with chlordane, washing and
cooking are effective means of reducing residues in certain instances.
                                  86

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                              CHAPTER  IV

                             Bibliography


Abbott, D. C. , Holmes, D.  C., Tatton,  J. 0.  G.   Pesticide residues in the
     total diet in England  and Wales,  1966-1967.   II.   Organochlorine pesti-
     cide residues in  the  total  diet.   J_.  Sci.  Food  Agr.  2!0(4)  245-9 (1969).

Revenue, A., Yeo, C. Y.  Effects  of  the cooking process on the  removal of
     chlordane residues from wheat,  flour  and  rice.   Bull.  Environ.  Contain.
     Toxicol. 4.(6): 370-4 (1969).

Brown, J. D.  Pesticides residue  levels among  fresh  fruits and  vegetables in
     Georgia.  10 p.   IJ. of Ga.  College of Agriculture  Experiment Stations
     Res. Report 42, March  (1969).

Carter, R. J., Hubands, P.  E., Poos, F. W. ,  Moore, L. A., and Ely, R. E.
     J_. Dairy Sci. 36.:1972  (1953).

Carter, R. H. , Hubanks, P.  E., Poos, F. W.,  Moore, L. A., and Ely, R. E.   The
     toxaphene and chlordane content of milk from cows  receiving these
     materials in their feed.  J_. Dairy Sci.,  36:  1172-77 (1953).

Dahm, P. A.  Effects of weathering and commercial dehydration upon residues
     of aldrin, chlordane  and toxaphene applied to alfalfa.   J_. Econ. Entomol.
     45_: 763-66 (1952).

Duggan, R. E. , Pesticide residues in food.   Ann.  N_.  Y_.  Acad-  Sci. 160:173-82
     (1969).

Duggan, R. E., Lipscomb, G. 0.,  Cox, E. L.,  Heatwole, R.  E.,  and Kling, R. C.
     Pestic. Monit. J_. 5.(2) :73-212 (1971).

Egan, H.  IUPAC Commission  on Terminal Residues.   ^J.  Ass. Offie. Anal. Chem.
     52^(_2): 299-304  (1969).

Food and Agriculture Organization of the United Nations/World Health Organization.
     1967 Evaluations  of some pesticide residues  in  food (1968).

Gilpin, G. L., Redstrom, R. A.,  Reynolds,  H. and  Poos,  F. W.   Flavor of peanut
     butter as affected by  aldrin, chlordane,  dieldrin, heptachlor and toxa-
     phene used as insecticides  in growing peanuts.   ,J. Agr.  Food Chem.
     (21): 778-80 (1954).

Gooding, C. M. B.  Fate of  chlorinated organo  pesticide residues in  the
     production of edible vegetable oils.  Chem..Ind. 344 (1966).

Greenwood, M. L., and  Tice, J. M.  Palatability tests of  potatoes grown in
     soil heated with  the insecticides  benzene, hexachloride, chlordane,  and
     chlorinated camphene.   £. Agr. Res. _78_:477-82 (1949).

                                  87

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Herrick, G. M., Fry, J. L., Fong, W. G.,  and Golden,  D.  C.   Pesticide
     residues  in eggs resulting  from the  dusting  and  short-time  feeding  of
     low levels of chlorinated hydrocarbon  insecticides  in hens.  J. Agr.
     Food Chem. 17(2):291-5 (1969).

Kawar, N. S.,  Bostanian, N. J.,  and Badawi, S. M.   Insecticide residues  in
     milk of dairy cows treated  for control of ectoparasites.  J. Dairy  Sci.
     51(7):1023-5  (1968).

Kirkpatrick, M. E.  Flavor of sebago potatoes grown in soil  treated with
     chlordane, heptachlor, dieldrin, aldrin and  endrin.  J. Agr. Food Chem.
     3^:409-12  (1955).

Knipling, E. F., and Westlake, W. E.  Insecticide use in livestock produc-
     tion.  Residue Rev. 13:1-32  (1966).

Kraybill, H. F.  Significance of pesticide  residues in foods in  relation to
     total encironmental stress.  Can. Med. Ass.  J. 100:204-215  (1969).

Li, C. F., Bradley, Jr., R. L.,  Schultz,  L. G.  Fate  of  organochlorine
     pesticides during processing of milk into dairy  products.   J. Ass.
     Offie. Anal. Chem. 53:127-39 (1970).

Liska, B. J.,  and Stadelman, W.  J.  Effects on processing of pesticides  in
     foods.  Residue Rev.  29:61-72 (1969).

McCaskey, T. A., and Liska, B. J.  Effect of milk processing methods on
     endosulfan and endosulfan sulfate and  chlordane  residues in milk.
     J. Dairy  Sci. 50:1991-93 (1967).

McCaskey, T. A., Stemp, A. R., Liska, E.  J., and  Stadelman, W. J.  Residues
     in egg yolks and raw  and cooked tissues from laying hens administered
     selected  chlorinated hydrocarbon insecticides.   Poultry jScj^ ^]_(2) :564-9
     (1968).

Morgan, L. W., Leuck, D. B., Beck, E. W., and Woodham.   Residues of aldrin,
     chlordane, endrin and heptachlor in  peanuts  grown in treated soil.
     J. Econ.  Entomol. 60:1289-91 (1967).

Polen, P. B., Hester, M. and Berziger, J.   Characterization of oxychlordane,
     an animal metabolite of chlordane.   Bull. Environ.  Contain.  Toxicol.
     5.:521 (1970).

Saha, J.  G.  Significance of organochlorine insecticide  residues in fresh
     plants as possible contaminants of milk and  beef products.  Residue
     Rev. 26:89-126 (1969a).

Saha, J. G., Burrage, R. H., Nielson, M.  A. and Simpson,  E.  C. R. Chlordane:
     composition of commercial formulation  residues in potatoes  grown in
     treated soil and their reduction by  home processing. Pesticide Progress
     (16): 117-21  (1968), as cited in Yeo,  W. and Bevenue,  A.  The absorption
     of chlordane by wheat flour from chlordane-tested shelf paper.  Prod.
     Res. 5:325-36 (1969).
                                     88   '

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Street, J. C.  Methods of removal of pesticides  residues.   Can.  Med.  Ass.
     J_._ 100:154-60  (1969).

Sweeney, J. P., Chapman, V. J. and Hepner, P. A.   Effect  of selected
     pesticides on  quality of  strawberries.   J.  Agr.  Food Chem.  16:632-4
     (1968).

Tuinstra, L. G. M.  Organochlorine insecticide residues  in human milk in
     the leiden region.  Med.  Melk-Zuweltijdschs 25(l):24-32 Abstract in
     HAPAB 4(10):561  (1971) (#71-2118).

Westlake, W. E., Corley, C., Murphy, R. T., Barthel,  W.  A., Bryant, H.  and
     Schutzmann, R. L.  J. Agr. Food Chem. 11:244-47  (1963).

Wright, C. G., and  Jackson, M. D.  Propoxur chlordane and diazinon on
     porcelain china  saucers after kitchen cabinet spraying.   J.  Econ.
     Entomol.  (640:457-9 (1971).

Yeo, C. Y., Revenue,  A.  Uptake of chlordane  vapors by foodstuffs of  low
     moisture  content.  J_^ Ass. Offic. Anal.  Chem.  52.(6) : 1206-13 (1969a).

Yeo, C. Y., and Bevenue, A.  The absorption of chlordane  by wheat flour
     from chlordane-treated shelf paper.  Prod.  Res_.  5:325-36 (1969b).
                                     89

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                                   CHAPTER V

                  Toxicology  and  Epidemiology  of  Chlordane


V.A.  Toxicity  to Laboratory  Animals  - No exact standards of  identity  exist
for  technical chlordane except  the percent of  chlordane  (68-69%)  in  the pro-
duct.  Thus, the pharmacological  and  toxicological properties may vary from
experiment  to experiment bacause  of possible variation in the composition
of chlordane.   However, Ingle (1952)  contends  that chlordane  is not  as toxic
"as  reported several years  ago,"  due  to elimination of the highly toxic
intermediate, hexachlorocyclopentadiene which  is  now present  in amounts of
less than 1% in technical chlordane.  The U.S. specifications of  chlordane
call for not more than 1% hexachlorocyclopentadiene.

Technical chlordane, on which the  majority of  the toxicity studies have
been carried out, is a mixture  of  substances,  including alpha-chlordane,
beta-chlordane, chlordene,  hexachlor, heptachlor, nonachlor, and several
minor components including  hexachlorocyclopentadiene.  The technical grade
is a mixture containing 36-46%  chlordane isomers  and closely related
chlorinated bicyclic analogs.

Chlordane is absorbed from  the  gastrointestinal tract, the respiratory
tract, and  through the skin (Ambrose  et al., 1953).  It is stored in the
adipose tissue  of, rats, sheep,  goats, and cows and is transmitted to the
milk.

Chlordane acts  on the central nervous system,  but the exact mechanism  of
this action has not been elucidated.  Large doses induce nausea and/or
vomiting.  On repeated dosage,  chlordane produces microscopic changes  in the
liver and kidneys of some experimental animals.   Somewhat different  lesions
may be produced by a single fatal  dose.

Chlordane stimulates liver  microsomal activity.   Single doses or multiple
doses at relatively low levels  have been shown to increase microsomal
activity in the rat.  It has  been  demonstrated that the acute administration
of chlordane affects steroid  action in mammals.

V.A.I.  Acute and Subacute  Toxicity Studies — Chlordane is a central
nervous system  stimulant and  toxic doses produce hyperexcitability,  lack of
coordination, tremors, and  convulsions.  Barbiturates are effective  against
convulsions induced experimentally from all central locations.  It,  there-
fore, appears that the symptoms of chlordane poisoning have their origin in
the central nervous system  (Stohlman and Smith, 1950).

V.A.I.a.   Acute and Subacute  Oral Toxicity - Radeleff(1948), Choudhury and
Robinson (1950), and Choudhury  (1953) described the typical chlorinated
hydrocarbon insecticide signs and symptoms which include motor ataxia,
convulsions and cyanosis followed by death.   The pathological signs include
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hemorrhage  of  the  gastrointestinal  tract, kidneys, lung, and heart.
Pulmonary congestion  and  edema,  and degeneration  of the central nervous
system are  also  observed.

When a  diet  containing 1000 ppm  of  chlordane was  fed to 12 male rats, all
of them died within 10 days.  When  12 rats were fed 500 ppm, all died within
70 days; Nine  of 12 rats  fed 300 ppm were alive after 100 days (Stohlman
e^al^, 1950).

Daily oral doses of 6.25  to 25 mg/kg of chlordane given to 5 rats for 15 days
produced no  tremors or convulsions, but daily doses of 50 mg/kg produced
toxic symptoms and two of the animals died.  When chlordane was fed at levels
of 100 mg/kg,  all of  the  animals died.  Intracytoplasmic bodies in the liver
cells were found at all levels and  their number as in proportion to the dose
used (Ambrose  et al., 1953).

Groups of 6  females and 6 males were fed 2.5 ppm or 25 ppm of a sample of
technical chlordane containing 60 to 75% chlordane and 25 to 40% unrelated
products for up to nine months.  Centrolobular cell hypertrophy, peripheral
migration of cytoplasmic  granules and the presence of cytoplasmic bodies were
observed in  1 male at 2.5 ppm and in 5 males at 12.5 ppm (Ortega et al.,
1957).

Chlordane was  given in varying oral doses to dogs for 7 days; convulsions
were seen in one dog  at 200 mg/kg (lowest dose) but 700 mg/kg (highest dose)
did not produce any effect (Batte and Turk, 1948).

Four groups  of 2 to 4 dogs were given chlordane orally in doses of 5 to
200 mg/kg body-weight.  All of the  dogs died within periods of 25 days to
93 weeks (Lehman, 1952).

V.A.l.b.  Dermal Toxicity - Ingle (1965) observed that hexachlorocyclopentadiene
in small amounts was  rapidly absorbed through the skin producing severe liver
damage.  He  attributes much of the  toxicity of early technical chlordane to
its content  of this intermediate.   Ingle states that the dermal toxicity of
the current  technical chlordane  is  reduced due to its lower content of hexachloro-
cyclopentadiene .

V.A.l.c.  Inhalation  Toxicity -  Ingle (1965) described deaths of pigeons at
FDA and mice at Carworth  Farms,  Inc. which were placed in an animal room
after it had been cleaned with solutions containing chlordane.  Nickerson
and Radeleff (1951a,  1951b) exposed pigeons (60 days) and young chicks (30
days) to high  levels  of chlordane (Ig/sq ft) with no apparent adverse effects
on either.   Moore and Carter (1954) observed that spraying turkey cages with
a mixture of 2% chlordane and 0.4 lindane caused subsequent high mortality of
the turkeys.   Findings by Ingle  (1965) and others on a wide variety of animals
indicate in  early preparations that hexachlorocyclopentadiene, not chlordane,
was probably the primary cause of the irritant and toxic properties of the prep-
aration.  Ingle (1965) observed that small amounts of the intermediate were
rapidly absorbed through the skin to produce severe liver damage.


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                               Table 1.  Acute Toxicity of Chlordane in Animals
ANIMAL
Rat

Mouse
Rabbit

Goat
Sheep
Chicken
ROUTE
Oral
Oral
Oral
Oral

Oral
Oral
Oral
LD5Q
200-590*
335-430
430
100-300*
20-40
180
500-1000
220-230
REFERENCES
Ambrose et al.
Ingle, (1955)
Stohlman et al.
Gaines (i960)
FDA (1947)
Stohlman et al.
Ingle (1955)
Welch (1948)
Welch (1948)
Turner and Eden

(1953)
(1950)


(1950)



(1952)
*The differences are explained by the use of different solvents and by the fact that the chlordane produced
prior to 1950 contained a considerable amount of hexachlorocylopentadiene (Ingle, 1965; Lehman, 1952).

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V.A.2.  Chronic Toxicity Studies - All rats on 1,000 ppm dietary chlordane
died within  10 days; all rats on 500 ppm died within 70 days; and, 3 of 12
rats on 300  ppm died within  100 days (Stohlman e£ al., 1950).

Daily oral administration of chlordane at levels up to 25 mg/kg to rats for 15
days produced no tremors or  convulsions, but caused toxic symptoms and death of
2 of 5 rats  (Ambrose et al., 1953).  Rats fed dietary chlordane for up to nine
months showed cellular alteration of the liver in 1 of 3 males and none of 3
females on 2.5 ppm and 2 of  3 males and none of 3 females on 25 ppm.  "Lipospheres"
were observed in the liver cells of one animal at 2.5 ppm chlordane.  Hepatic
cell margination and/or hypertrophy were observed in the males at 25 ppm chlordane
(Ortega et al., 1957).

In experiments conducted by  FDA, rats were given from 25 to  75 ppm chlordane in
the diet for 2 yr.  The two  higher levels caused moderate to severe signs of
intoxication.  The lowest level caused histologically evident liver damage.
Lehman (1965) reported that  all rats fed chlordane at dosage levels of from
2.5 to 400 ppm in the diet for 2 yr showed specific, though minimal hepatic cell
changes characteristic of chlorinated hydrocarbon insecticides.  These changes
were apparent at the lowest  dose, though minimal, and progressively increased
in severity  with increasing  feeding levels.  Liver/body-weight ratios increased
in males at  25 ppm and in females at 75 ppm and were proportionately greater
at higher levels.

Rats were fed 5 to 300 ppm technical chlordane for 2 yr.  The lowest level at
which tremors and convulsions appeared (or could be induced) was 30 ppm; growth
was affected at 150 ppm; and liver damage was detected histologically at 10 ppm
(Ingle, 1952).  Rats showed  no symptoms of toxicity on a diet of 150 ppm
chlordane for 80 weeks, followed by 4 weeks on a chlordane-free diet, and
then starved in an attempt to induce rapid release of residual chlordane from
body fat.

In reinvestigation of the above study, levels ranging from 2.5 to 300 ppm chlor-
dane in the  diet were fed (Ingle, 1965).  Lowest levels to affect growth and
mortality and to cause microscopically evident liver damage were 300 and 50 ppm,
respectively.  Ambrose et al. (1953) fed rats levels ranging from 10 to 1280 ppm
chlordane in the diet for 407 days.  Liver weight was increased at 320 ppm and
above.  Cytoplasmic vacuoles containing fat and clusters of granules at the
periphery of the cytoplasm were seen in males at 40 ppm and above and in
females at 80 ppm and above.

In dogs fed  chlordane at levels ranging from 80 to 320 ppm for up to 90 weeks
(Lehman, 1965) growth was adversely affected at all levels, and all animals
died.  In a  histopathological examination of the dogs, fatty degeneration of
the liver was found to be the principal lesion at the 200 ppm level.

V.A.3.  Reproduction Studies - Rats in a 3-generation reproduction study
received dietary chlordane at levels ranging from 0.3 to 60 ppm.  Levels up
to and including 30 ppm chlordane had no affect on fertility, numbers of
young, numbers of litters, or weight, growth, or mortality of the young
animals to weaning.   Autopsies of animals,  after weaning,  showed no gross or
microscopic  differences between the goups.   At 60 ppm there was a high mortality
in the second ?3 generation during the latter part of the nursing period.

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Those animals that died showed gross and microscopic pathology changes charac-
teristic of chlordane intoxication.

Survivors of this generation, however, showed no tissue changes.  A third set
of F3 litters at 60 ppm again showed high mortality during the nursing period
with gross and microscopic tissue changes characteristic of chlordane intoxi-
cation.  A third ?3 generation litter from females removed from the 60 ppm
group and placed on a chlordane-free diet for 30 days prior to remating showed
no differences in any respect from control litters.  There was no evidence
of teratogenicity or tumorigenicity observed during the study (Food and Agri-
culture Organization/World Health Organization, 1968).

In a review of the perinatal toxicity of chlordane, Khera and Clegg (1969)
reported that control rat pups suckled by parents fed 150 ppm chlordane
exhibited toxicity due to chlordane residues in the milk.

The normally low levels of drug-metabolizing enzymes in the new-born rabbit
were enhanced by treating the rabbit pups or the mothers with chlordane
(Fouts and Hart, 1965).  Chlordane apparently was excreted in the milk and
stimulated the rabbit's drug metabolizing enzymes.

Tuinstra (1971) observed that human mother's milk did not contain chlordane
as such but did contain 0.6 ppm heptachlor epoxide.  As mentioned in other
sections this observation might well be a combination of materials including
oxychlordane.  It was indicated that there appeared to be no physiological
effect on infants to the presence of the chlorinated pesticides in the milk.
Keplinger et al. (1968) reported that 25 ppm chlordane in the diet of mice for
three generations had no effect on reproduction, but 50 and 100 ppm caused
significant effects.

Chlordane is a possible contaminant of milk in the form of heptachlor epoxide
or oxychlordane.  Traces of chlordane or its metabolites in milk have been
shown to have an effect on offspring.  Apparently this affect appears to be
limited to increased metabolic rates in the liver.

Chlordane fed at 25 ppm in the diet for eight weeks produced levels of 18
and 12 ppm chlordane in the fat of calves and sheep, respectively.  After
feeding was halted, the former level declined to zero within 20 weeks and the
latter level was reduced in four weeks (Claborn et al., 1953).

V.A.4.  Carcinogenic Studies - No carcinogenicity studies, per se, have been
carried out on chlordane.  However, chlordane was not shown to be tumorigenic
in long-term studies in rats (Ingle, 1965) or dogs (Wazeter, 1967).

V.A.5.  Mutagenic and Teratogenic Studies - No mutagenic or teratogenic studies
have been carried out on chlordane.  However, in long-term rat (Food and
Agricultural Organization, 1968) and mouse (Keplinger et al., 1968) reproduction
studies no evidence of teratogenesis was apparent.

V.A.6.  Metabolic Studies - The metabolic fate of chlordane in biological
systems is complicated due to the complex of components in the technical
product.  A complete picture of it would have to account for biological fate o
each component, modified by any interaction of those that might occur in vivo.

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Recently,  the  synthesis  of both  14^ radioactive  isomers of chlordane was
reported  (Korte,  1966).  Following administration of  these to rodents, chiefly
hydrophilic metabolites  and unchanged  parent  compound were excreted.  Follow-
ing an  intravenous dose  of Q-chlordane to  rats the principal excretion was
via the feces  with only  minute amounts occurring in the urine (Poonawalla and
Korte,  1964).

Oral administration of these radioactive compounds to rabbits caused excretion
of hydrophilic metabolites primarily in the urine and to a lesser extent in
the feces.  (Ludwig, 1966).  The most  polar urinary metabolite was assigned
the structure  l-hydroxy-2 chloro-dehydrochlordene, with the stereochemical
configuration  of  the 1-  and 2-substituents unspecified.

However, Brooks  (1969) assumes that the 2-chlorine atom will be  in the endo-
position and the  1-hydroxy group would be  exo, which  would imply simple hy-
drolytic replacement of  one chlorine atom without inversion.  Its molecular
weight  was estimated to  be 391 and its empirical formula, C^QHyCly.  Its acute
toxicity to mice  was approximately three times less than that of the a-chlordane
(>1800  mg/kg).

Male rats given an acute dose of a-chlordane  intravenously and killed 60 hr
later showed approximately 75% of radioactivity  excreted in the  feces in the
form of hydrophilic metabolites.  There were  high concentrations of radio-
activity in both  the fat and the GI tract  (Poonawalla and Korte, 1964).  Male
rabbits orally administered transchlordane for 10 weeks, eliminated 47% of the
dose in urine  and 23% in feces.  The major hydrophilic metabolite was again
assigned the structure l-hydroxy-2-chloro-dihydrochlordene.  However, in this
metabolite derived from  ychlordane, the 2-chlorine atom would probably be in
the endoposition, and the hydroxy group would probably be in the endoposition,
again indicating  hydrolytic replacement of the chlorine atom or  simple oxida-
tive dechlorination (Poonawalla and Korte, 1971).

Recently, a previously unreported metabolite  of  chlordane was isolated from
mammalian fat  milk and cheese (Polen et^ jil_. ,  1970, Schwemmer ejt^  al. , 1970;
Lawrence et al.,  1970).  This metabolite, which  often migrates on a GLC column
concurrently with heptachlor epoxide,  may have been mistaken for it in residue
analyses of certain foods.  The metabolite, oxychlordane, an epoxide derivative
of chlordane is postulated to be l-exo-2-endo-4,5,6,7,8,8-octachloro-2,3-epoxy-
2,3,3a,4,7,7a,-hexahydro-4,7-metahnoindene.   The compound is formed from both
a- and y~chlordanes although to a greater extent from the former.  When cows
were fed 0.3 ppm  cis, trans, or a cis- trans- mixture of chlordane for 30 days,
no oxychlordane was found in milk.  Cows on 1 ppm excreted low levels of oxy-
chlordane in milk.  Oxychlordane was also found  in adipose tissue.

Street and Blau (1971) recently identified a  metabolite, l-exo-2-endo-dichloro-
chlordene-2, as an intermediate in the formation of oxychlordane.  They found
oxychlordane is produced by oxidative  metabolism in rat liver homogenates
fortified with NADP.   It is formed very slowly by normal rat liver homogenates
but was readily induced  by DDT, dieldrin, heptabarbital and y-chlordane.
Rabbit preparations apparently convert  dichlorochlordene readily to oxychlor-
dane but do not readily  convert chlordane to  dichlorochlordene unless induced
by exogenous substrates  in vivo.

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V.A.7.  Effect of Chlordane on Enzymes

V.A.7.a.  Enzyme Induction - Studies during the past decade have shown that
the duration and intensity of action of many drugs depends upon the activities
of drug metabolizing enzymes located primarily in the smooth endoplasmic
reticulum (SER) of the liver cells.  These enzymes catalyze the metabolism
of drugs by many pathways such as:  hydroxylation, dealkylation, deamination,
sulfur-oxidation, azo-link reduction, and glucuronide formation.

The acute or chronic administration of a chemical may alter the pharmacologic
activity of another by increasing the amount of drug metabolizing enzymes in
the liver.  This may facilitate the inactivation of the drug on the one hand;
on the other it may activate the drug if the compound is metabolized to com-
pounds which possess enhanced physiological activity.

Drug metabolism has been shown to be stimulated in animals by many different
types of drugs and chemicals in the environment, including chlordane.  Over
200 drugs and other chemicals are now known that stimulate drug metabolism in
laboratory animals.  Several extensive reviews have been published since the
mid-1960's on the inductive effects of chlordane and other chemicals on drug
metabolizing enzymes in the liver (Kuntzman, 1969; Conney, 1969; Street, 1969;
Conney e± ^1., 1969; Kupfer, 1967).

Studies conducted in the last decade demonstrated that treatment of animals
with drugs, polycyclic hydrocarbons, and chlorinated insecticides increase the
activity of liver microsomal oxidative drug-metabolizing enzymes.  In turn,
such an increase in microsomal enzyme activity was found to lead to an acceler-
ated transformation of drugs in vivo and cause an altered duration of drug
activity.  The most potent inducers of these enzymes are some of the chlorin-
ated insecticides, including chlordane.  Single or multiple doses are relative-
ly low levels that significantly increase the microsomal enzyme activity in
rats.

Chlordane has been compared with phenobarbital in its stimulatory action on
hepatic microsomal drug metabolism in mammals.  Both agents cause increases in
liver weight, microsomal protein, microsomal NADPH-oxidase, and microsomal
cytochrome CO-binding pigments.  Both agents can affect stimulation on drug
metabolism in adrenalectomized or hypophysectomized rats.  Ethionine can block
the enzyme stimulation by both agents in normal rats  (Hart and Fouts, 1965).
The stimulatory actions of chlordane on microsomal drug metabolism do not add
to those of phenobarbital.   The actions of both chlordane and phenobarbital
seem to be associated with a proliferation of SER in the liver cell.

Whether this biochemical and morphological response to chlordane can be con-
sidered to be a hepatoxic effect of chlordane or is rather an adaptive response
to the toxic actions of these chemicals has been under deliberation for a con-
siderable time.   Several workers consider this inductive effect on animals and
the associated cellular changes in the liver to be physiological adaptive re-
sponses rather than toxic effects.
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It has been well demonstrated  that acute administration of chlordane and other
nonspecific inducers of  liver  metabolizing systems affect steroid actions  in
mammals.  Chlordane pretreattnent  increases metabolism of estradiol-17-B to
polar metabolites  (Conney ££_§!_•> 1965); decreases the growth promoting action
of testosterone on the seminal vesicles of young  rats (Levin et al., 1969);
inhibits the increase of uterine  weight caused by estrone (reduces uterotropic
action of estrone); and  decreases the concentration of estrone in the uterus
(Welch et_ _al. , 1971).

The metabolism of Cj^-steroids (progesterone and  deoxycorticesterone) and  a
subsequent decrease in their pharmacological action was stimulated in male rats
by pretreatment with chlordane (Kupfer, 1969).  In adult ovariectomized mice,
treatment with chlordane (but  not DDT) increases  estradiol-17-B metabolism,
reduces estradiol-17-B-or estrone-increases in uterine weight, and decreases
the concentration of estrogen  in  the uterus (Welch et_ al_. , 1971).

Lage et al. (1967) administered chlordane to adult male squirrel monkeys and
found that the metabolism of digoxin was stimulated  (DDT was not active under
the conditions employed).

Pretreatment of rats with chlordane also decreased the toxicity of warfarin
in vivo and increased its metabolism in vitro (Ikeda et al., 1968).  Dogs  pre-
treated with chlordane followed by dicumarol had  a reduced plasma level of
dicumarol and the anticoagulant effect was reduced through the increased meta-
bolism of the drug (Welch and  Harrison, 1966).

Rats administered chlordane followed by phenylbutazone did not develop gastric
ulcers as did similar animals  treated with phenylbutazone alone (Welch and
Harrison, 1966).  The stimulatory effects of chlordane on drug metabolism  in
dogs was observed to be prolonged for as long as  21 weeks after discontinuing
chlordane treatment (Burns et  al., 1965).  Oral treatment three times per  week
(5 mg/kg) for 7 weeks resulted in this prolonged  accelerated metabolism of
phenylbutazone.

Hydroxylase activity was stimulated in vivo by chlordane while in vitro
chlordane (10-^M) inhibited this  enzyme reaction  (Welch et al., 1967).

There are apparently substantial  differences in the selectivity of drug
metabolizing enzymes and in the stimulation as observed with different inducers
and in various animal strains.  Cram and Fouts (1967) observed differences in
two mouse strains when examining  the affect of chlordane and DDT on the meta-
bolism of various substrates.  In these two mouse strains there are significant
differences in the inductive effects of y-chlordane and DDT.  The two mouse
strains not only show similar  stimulatory effects of DDT and y-chlordane but
also show differences in their inductive capabilities.  The inductive effect
of DDT and chlordane in the squirrel monkey are qualitatively similar (Juchau
et al.,  1966;  Cram £t al.,  1965).

Chlordane is more active than  DDT in stimulating drug metabolizing enzymes in
primates although the spectrum of activity in the primates is similar with the
two inducers.


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The newborn infant is more sensitive than the adult to many drugs and ocassion-
ally drugs produce neonatal effects after administration to the mother.  An
explanation for the sensitivity of infants to drugs came from the observation
that newborn animals generally lack microsomal enzyme systems for the metabo-
lism of many compounds.  The normally low levels of drug metabolism enzyme
activity in newborn rabbits was enhanced by treating the pups or the mothers
they nursed with chlordane (Fouts and Hart, 1965).

The inductive effect evident in animal studies will presumably be observed in
man.  Kolmodin et al.  (1969) observed that the plasma half-life of antipyrine
in men occupationally exposed to chlordane is shorter, indicating that the
microsomal enzyme system in man is induced.

The enhanced metabolism of chlordane by these inductive mechanisms may lead
to the further formation of oxychlordane, a potent metabolite formed and stored
in mammals.  The toxicological significance of this effect has been evaluated
in the chronic studies done with chlordane where induction of oxidative enzymes
through the normal feeding of chlordane in the diet would result in the occur-
ence and storage of oxychlordane.

The inductive interaction involving chlordane and the metabolism of toxicants,
drugs and other substrates in mammals has been demonstrated to be an increase
in enzyme synthesis rather than a stimulation of activity.  This increased
enzyme synthesis has apparently manifested itself in production of enzymes
which are not necessarily specific for oxidative mechanisms.  For example,
Crevier et_ _al. (1954); Ball jet al. (1954); Kay (1966); Triolo and Coon (1966);
Triolo et al. (1970); Williams and Casterline (1970) ; Casterline and Williams
(1969a, 1969b), reported on the increased activity of esterases following
chlordane treatment.  It was postulated that this increased activity was
responsible for the protective effect of chlorinated hydrocarbons when admin-
istered prior to organophosphate and carbamate esters.  Williams jet_ _al_. (1967),
assumed that the chlordane-induced increase in liver and serum aliesterase
activity was not primarily responsible for the protective effect of chlordane
against two carbamate insecticides.  More recently, Chapman and Liebman (1971)
have assumed that the protective effect of chlordane and other inducing com-
pounds against the toxicity of parathion is primarily due to the oxidative
production of diethylhydrogen phosphate.  On the basis of their data it seems
reasonable to assume that the nonspecific oxidative induction mechanism of
chlordane rather than esterase interaction may be responsible for the protec-
tive effect of chlordane against the toxicity of certain organophosphate esters.

The interactions of chlordane with other pesticides has been examined (Williams
and Casterline, 1970; Street et al_., 1969).  It was observed that chlordane was
less active than DDT in stimulating EPN detoxication and in the removal of
stored dieldrin from fat.  Chlordane decreased the mortality of a carbamate,
Banol(R), but the protective effect was reduced by pretreatment with piperonyl
butoxide.

Several studies have been reported on the interactions of diet and/or essen-
tial dietary factors with chlordane (Casterline and Williams,  1969a, 1969b;
Boyd,  1969; Boyd and Taylor,  1969;  Wagstaff and Street, 1971). Animals


                                     98

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 maintained on a protein-deficient  diet  showed  a  significant  increase  in  suscep-
 tibility to acute chlordane  toxicity.   In general,  it may  be concluded that
 malnutrition plays a significant role in increasing the  toxic effects of
 chlordane.  Apparently,  ascorbic acid is necessary  for induction.   Reduced levels
 of  ascorbic acid resulted  in lower induction levels of chlorinated  hydrocarbons.
 Although the report of Wagstaff and Street (1971) did not  primarily deal with
 chlordane induction the  interaction of  ascorbic  acid in  the  inductive effects
 of  chlorinated hydrocarbons  was reported.   Presumably this would be the  same
 for chlordane.

 V.A.7.a.   Miscellaneous  Effects -  Studies  on the mode of action of  chlordane
 in  insects and mammals have  been limited to studies of adenosinetriphophos-
 phate  (ATPase)  activity  (Koch, 1969; Koch  et al., 1969;  Chu  and Cutkomp, 1971;
 Akera  et al.,  1971).  This relationship has not  been conclusively defined as
 the etiological cause of the central nervous system stimulation seen  in
 acute  toxic response.

 Chlordane has  been shown to  affect oxidative metabolism  in a yeast  system
 (Nelson  and Williams, 1971);  nitrite oxidation by Nitrobacter agiles  (Winely
 and San  Clemente,  1970); and carbon fixation in  aquatic  plankton (Ware and
 Roan,  1970).   Gabliks and  Friedman (1969)  reported  chlordane to be  more  toxic
 than DDT to mouse  and human  cells  in cell  culture and indicated that  chlordane-
 exposed  cells were more  susceptible to  infection by polio  virus.

 Chlordane  had no effect  in vitro or in  vivo on an enzyme which hydrolyzes 3,
 4-dichloropropionanilide (Williams  and  Jacobson, 1966).  Williams (1969) found
 that a single dose of chlordane to  rats reduced  serum (23%)  and liver (28%)
 glucuronidase activity eight  days  after administration.

V.B.  Human Toxicity  and Epidemiology - Fatality in humans has followed  ex-
 posure to  chlordane by both  the oral and dermal  routes.  Acute poisoning may
 also follow inhalation exposure to  chlordane.  Low  concentrations,  estimated
 by  Lensky  and Evans (1952)  to be about  10  mg/kg, result  in classic  signs of
 poisoning,  including  ataxia  and convulsions.   The fatal  oral dose of  chlordane
 for man  is  estimated  to be between  6 and 600 g,  although death of a patient
with chronic liver disease has followed the exposure to  an oral dose  estimated
 to be between  2  and 4 g.  The dermal exposure  to 30 g of a 25% solution  of
 chlordane  has resulted in death (Hayes,  1963).

V.B.I.   Signs and  Symptoms of Poisoning -  The  signs  and  symptoms of acute
 chlordane  intoxication in humans are similar to  those observed in poisoning
by other chlorinated hydrocarbons.   Irritability, salivation,  labored respir-
ation, muscle tremors, convulsions, and  death, with  or without an immediately
preceding period of deep depression, is  a  classical  pattern  of poisoning in
experimental animals.  These symptoms,  which are referrable  to the central
nervous system, have all been observed  in humans.   In addition, nausea,  vomi-
ting, diarrhea, and abdominal pain have been reported to follow the ingestion
of toxic doses of  chlordane.   Blurred vision,   cough, ataxia,   confusion,  de-
lirium, and mania  are further symptoms  noted after inhalation and skin absorp-
tion of toxic amounts of chlordane.  Acute  signs of poisoning usually appear
                                    99

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within 45 minutes  after  ingestion.  Death may  occur within 24 hr, but  it may
be delayed many  days  following a  toxic dose  (Hayes, 1963; Stormont and Conley,
1955).

V.B.2.  Laboratory Findings - Laboratory findings are usually negative and
always nonspecific except  that chlordane or  related compounds may be demon-
strated in stomach contents, urine, or tissues, especially fat  (Hayes,  1963).

V.B.3.  Treatment  - Depending upon  the condition of the patient, chlordane
should be removed  from the stomach  either by an emetic or gastric lavage, fol-
lowed by a saline  laxative.  Convulsions may be controlled by the use  of bar-
biturates alone  or in conjunction with calcium gluconate  (Hayes, 1953;  Stormont
and Conley, 1955).

V.B.4.  Human Poisonings - Several  deaths have occurred after exposure to
relatively high  concentrations of chlordane.   In some instances, the poisoning
resulted from the  exposure to chlordane in combination with other agricultural
chemicals (Dinman, 1964; DePalma  ei_t^ a.l_. , 1970); in other instances the exposure
was to chlordane alone (Derbes et^ aJ^. , 1955; Stormont and Conley, 1955; Lensky
and Evans, 1952; Barnes, 1967; Aldrich and Holmes, 1969; and Curley and
Garrettson, 1969).  The high susceptibility  of children to chlordane has been
pointed out by several of  the above authors.

Convulsions followed  by recovery  occurred in an infant following a dosage of
about 10 mg/kg and in an adult following 32  mg/kg (Lensky and Evans, 1952).

One person receiving  an accidental  skin application of a 25% solution  amount-
ing to something over 30 g of technical chlordane developed symptoms within
40 min and died before medical attention was obtained (Dadley and Kammer, 1953).

In one patient, known to be an alcoholic, death followed exposure to a low
oral dosage of chlordane (2-4 gin).  Microscopic examination of  the tissues
revealed severe chronic fatty degeneration of  the liver, characteristic of
chronic alcoholism.   Although this  fatality  cannot be attributed exclusively
to chlordane, it is consistent with previous observations that  the toxicity
of some chlorinated hydrocarbons  is much more  enhanced in the presence of
chronic liver damage  (Hayes, 1963).

A woman with suicidal intent who  ingested 6  g  (104 mg/kg) of chlordane in
talc suffered chemical burns of the mouth, severe gastritis, enteritis, dif-
fuse pneumonia, lower nephron syndrom, and central nervous system excitation
with terminal mania and convulsions.  Death  occurred after 9.5  days.   The most
important autopsy  findings were those of severe necrotizing bronchopneumonia,
and desquamation and  degeneration of the renal tubular epithelium (Derbes
et al., 1955).

An 18-yr old female showed convulsions but recovered after a dose of approx-
imately 30 mg/kg.  The amount retained after vomiting was estimated to be 10
mg/kg.  Two infants,  15 months and  3 years of  age, who ingested chlordane at
10 and 40 mg/kg, respectively, showed signs of severe poisoning (Stormont and
Conley,  1955).
                                   100

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 Chlordane ingestion by a 4-yr-old girl weighing 11 kg.,  resulted  in inter-
 mittent clonic convulsions,  coordination loss,  and increased  excitability.
 The use of gastric  lavage and parenteral  phenobarbital was followed by dis-
 appearance of  these  neurological  signs  and restoration of health.   Initially,
 urine concentrations of  chlordane were  high, but fell rapidly  to 0.05 ppm on
 the third day, although .a sample  of urine obtained  on the 40th postingestion
 day revealed a rise  to 0.13 ppm.  Serum half-life  of chlordane in  this patient
 was found to be approximately 88  days  (Aldrich  and  Holmes, 1969).

 V.B.5.  Epidemiological  Studies - Workers engaged  in the manufacture and for-
 mulation of chlordane  for periods up to 15 yr have  exhibited no evidence of
 harmful effects attributable to this insecticide.   Air concentrations of 1.7
 to 5 mg/m-' have been reported for industrial manufacturing operations with
 exposure of personnel  to .this level producing no known adverse effects
 (Alvarez and Hyman,  1953; Fishbein et al., 1964).   In a survey of  more
 than 1105 persons who had been engaged  in pest  control operations  for 1
 to 30 yr  (318  for 5  to 19 yr), three cases of toxicity due to  chlordane
 were reported, the  only  symtoms specified being dizziness and  headache
 (Stein and Hayes, 1964).  An examination  of persons occupationally  exposed
 to chlordane showed  that there were no  apparent effects on renal function
 (Morgan and Roan, 1969).

 Based on direct or circumstantial evidence, chlordane has been associated with
 several blood dyscrasias, including anemia, leukopenia, thrombocytopenia, and
 pancytopenia (American Medical Association Council  on Drugs, 1962).

 The role played by exogenous agents suspected of having an etiologic relation-
 ship to bone marrow  failure is difficult  to assess.  The number of  affected
 individuals usually  is small in proportion to the  population exposed.  In
 addition, many of the suspected agents  fail to  reproduce marrow depression in
 the experimental animal.  Since demonstration of a  cause-and-effect relation-
 ship between a given agent and bone marrow failure  can be established only by
 re-exposure of the affected individual, following  recovery, such proof can
 rarely be established in human beings.  Although the evidence  implicating many
 chemicals, therefore, is entirely circumstantial,  observations have been made
with reference to certain agents and sufficient frequency to make  a reasonable
 supposition as to the etiolgic relationship.  That  some persons are frequently
 exposed to prolonged contact with these agents  and  suffer no obvious effects
 cannot be denied, but the occurrence of bone marrow failure under  such condi-
 tions is great enough to demand caution in occupational exposure to these agents
 (Loeb,  1967).

Hoffman et^ _al.  (1964; 1967) and Hayes et^  a^. (1965) state that there is no
 evidence of the build-up of chlordane in  adipose tissues of humans.  However,
 in a recent unpublished  study,  Biros and  Enos (1972) report finding a mean of
0.14 + 0.09 (range from  0.03-0.40 ppm)  random samples of human adipose tissue
analyzed.   Presumably this residue of oxychlordane  in human fat has occurred
as a result of exposure  to chlordane.   The source of exposure  to yield these
levels  is a point of extreme interest and while it  does not appear  to result
in any  way defined toxicological response, the source of this contamination
should  be identified.
                                    101

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                                     CHAPTER V

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