HEPTACHLOR—A REVIEW OF ITS USES, CHEMISTRI, ENVIRONMENTAL
HAZARDS, AND TOXICOLOGY
ENVIRONMENTAL PROTECTION AGENCJ
1972
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HEPTACHLOR--A REVIEW OF ITS USES, CHF:
HAZARDS, AND TOXICC...
:"„ ENVIRONMENTAL
Chapter I.
I.A. -
I.B.
Chapter II.
Chapter III.
Chapter IV.
Chapter V.
Appendix
Contents Page No.
Introduction . 1
Summary 2
Current Heptachlor Pestic i de "-vses With
Their Impact on the Env/raiwar:r and
Alternates. 4
Summary of Registered Ka/7f3_':r_br Uses
and Alternates. 5-22
Discussion of the Impact: o '. ::>7tachlor Uses 23
on the Environment and f A. e A Lfc-irnates.
Chemistry and Analytical AS".iv/^is 28
Fate and Implications c:: \\s.p tz\:hlor
in the Ecosystem. 40
Residue in Crops and Food Ittf^s. 52
The Toxicology and Epide/*/ o\ff
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Prepared for the Office of Pesticides Programs, Environmental
Protection Agency by:
Special Pesticide Review Group
Scientific Committee:
Homer E. Fairchild, Ph.D., Chairman
Lamar B. Dale, Jr., Ph.D., Executive Secretary
Ronald L. Baron, Ph.D.
Thomas Carver
Joseph G. Cummings
Allen J. Duvall
John C. Kolojeski
Calvin M. Menzie
0. E. Paynter, Ph.D.
Fred H. Tschirley, Ph.D.
Clara H. Williams, Ph.D.
Anne R. Yobs, M.D.
Special Working Group on Heptachlor
William V. Hartwell, Ph.D.
Samuel C. Billings
With Library Assistance Of:
Mr. Robert Ceder
Mrs. Claudia Lewis
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INTRODUCTION
Heptachlor, a chlorinated cyclodiene hydrocarbon, lias been registered
as a commercial pesticide since 1952. The early registered uses of
heptachlor included foliar and soil application fiar agriculture, home
garden and lawn use, termite control and insect control in homes and
public buildings.
The present soil uses of heptachlor account for ewer 98 percent of
the annual production. Twenty-eight percent is vs&d for termite
control and 70 percent for control of agricultural!, soil pests.
Tolerances for heptachlor have been established bj the U.S. Environmental
Protection Agency at 0.1 ppm for cabbages, snap baans, lettuce and
rutabagas. Zero or interim tolerances are in effect for barley, beans,
blackberries, blueberries, boysenberries, chestnuts, citrus, corn, cotton,
cranberries, dewberries, oats, peaches, pears, pegpers, pineapples , rasp-
berries, rice, rye, sorghum, soybeans, tomatoes aid wheat.
In 1969 the Secretary's Commission on Pesticides aid Their Relationship
to the Environmental Health recommended restricting the use of certain
persistent pesticides in the United States to specific essential uses
which create no hazard to the quality of the environment or to human
health. Heptachlor was included in this recommendation.
The Administrator of the Environmental Protection Agency issued a state-
ment on March 18, 1971, which said that "Active internal review is being
initiated as to the registration of products contzeining benzene hexachloride,
lindane, chlordane, endrin, heptachlor and toxaphzne, all products contain-
ing mercury, arsenic, or lead and all others deemed necessary to review. . . ,
In accordance with this charge, the Special Pesticides Review Group has
reviewed the hazards associated with the use of hzptachlor.
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SUMMARY
Heptachlor is a chlorinated hydrocarbon pesticide and is a member of
the group of cyclodiene insecticides which includzs: aldrin, dieldrin,
heptachlor, endrin, thiodan, chlordane, and telodrrfin. Technical
heptachlor is not a single entity but rather a miaiure of heptachlor
and related synthetic products. Technical heptachlior is manufactured
by a controlled process which yields a product wiafr a relatively
consistent composition. This consistency is said to have permitted
the chemical evaluation of its formulations and rvEsidues.
Heptachlor has been registered in the United Statasaj as an insecticide
for use in agriculture, home lawns, gardens, and ^structural pest control
since 1952. Of the total used in the United Stats; in 1971 over 98
percent was used for soil application in agriculture and termite control.
As with chlordane, heptachlor is used primarily as a soil insecticide.
Therefore, any consideration of possible environmaital effects must
place emphasis on the fate of heptachlor in the sml. In most of the
registered uses, the rates, methods of application,, and the environ-
mental conditions vary. However, while these factors may differ the
controlling factors are the characteristics of hepttachlor. These are
persistence and relative immobility in the soil. (Certain organisms in
the environment do bioconcentrate heptachlor, but it apparently does
not build up in the food chain.
Heptachlor has been reported to be less persistent in the soil than
chlordane, although it may be detected in the soil for as long as ten years
after application. Heptachlor may vaporize slowly from the soil; it may
be oxidized to form heptachlor epoxide, a substanes: more persistent and
toxic than the parent compound; or it may be converted to less toxic meta-
bolites by soil bacteria. Heptachlor is relatively immobile in the soil,
and various workers have demonstrated that the majority of the residues
are in the top few inches of the soil.
Several studies indicate that contamination of water by heptachlor is not
a widespread problem, however, residues of heptacbHor have been demon-
strated in fish from various bodies of water. In ^general, the values
found have been less than 5 parts per million (ppm*). Fish examined from
the Pacific Ocean have shown detectable levels and oysters taken from
the South Atlantic and Gulf of Mexico have demonstrated levels of
heptachlor up to 10 parts per billion (ppb).
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Earthwofius are able to concentrate heptachlor from the soil. Probably^
as a consequence of this, traces of heptachlor and heptachlor epoxide
have been detected in the fat of starlings. These birds are not at the
• top of the food chain but contribute heavily to the diets of raptorial
birds. Substantial levels of heptachlor epoxide have been found in the
eggs of coot, teal, and pheasant. However, no evidence of reproductive
problems have been associated with these residues.
On the basis of long-term feeding studies, FAO/WHO has established the
no-effect level for rats at 5 ppm in the diet, equivalent to 0.25 mg/kg
of body-weight/day and the no-effect level for dogs at 2.5 ppm in the
diet, equivalent to 0.06 mg/kg of body-weight/day. Accordingly, FAO/WHO
established the acceptable daily intake for man as 0.0005 mg/kg of body-
weight. A tolerance of 0.1 ppm has been established for cabbage, ruta-
bagas, lettuce, and snap beans. Zero or extended tolerances are in
effect for other food items.
Heptachlor acts on the central nervous system, but the exact mechanism
of this action is unknown. On repeated dosage, heptachlor produces
microscopic changes in the liver and kidneys of some experimental animals.
Multiple doses of heptachlor at relatively low levels have been shown to
increase liver microsomal enzyme activity in the rat.
In three generation reproduction studies carried out in both rats and
dogs, the administration of heptachlor or heptachlor epoxide was shown
to cause a reduction in the survival of pups. No teratogenic effects
were observed in these studies or in specific teratogenic studies in
rabbits. A mixture of heptachlor and heptachlor epoxide was not a mutagen
in the dominant lethal assay in mice.
There is some evidence for an increase in the incidence of benign
tumors of the livers in mice and rats after long-term administration of
heptachlor epoxide.
Human poisonings have been associated with occupational exposure to
heptachlor, however, the clinical pictures are confused due to the con-
current involvement of other pesticides.
-3-
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CHAPTER I
Current Heptachlor Pesticide Uses With Uheir Impact
on the Environment and Alternates
The patterns of use for heptachlor have changed since it was first
registered in 1952. Prior to 1960, the registered uses included
house and garden applications, termite control arafl soil and foliar
applications on sugar beet, vegetables, forage craps, cereal, oil
and seed crops. The use of heptachlor as a foliar agricultural
insecticide is now very limited. ->
The persistent qualities of heptachlor and heptadnlor-epoxide became
apparent with the development of more sensitive analytical methods.
: The residues of heptachlor in soil and translocatfon and absorption
by plants were recognized as means of food chain contamination. Certain
uses of heptachlor were eliminated in order to present the contamination
of milk, meat, and other food products. Heptachltnr is manufactured by
Velsicol Chemical Company, and 312 products are registered by 112 formu-
lators throughout the United States. ^ Heptachlor formulated as an emul-
sible concentrate may contain 2 and 3 pounds actrse toxicant; granules
may contain 2.5, 5, 10, 20, and 25 percent active toxicant; oil solutions
may contain 2, 3 and 3.3 pounds per gallon; and, dust concentrates and
wettable powders usually contain 25 percent active components .
Heptachlor is used primarily for control of soil pests. Other agri-
cultural uses include: seed treatment; transplanting water treatments;
certain treatments for fire ant control; foliar applications to pineapple
and certain limited usage on ditchbanks, field boirfers, roadsides, vacant
fields in forestry and as a household insecticide- Nonagricultural uses
include treatments of lawns, nursery soil and ornamental turf. It is
also used as a mosquito larvicide and as a termite soil poison.
Over 98 percent of the heptachlor sold in 1971 was used as a soil treat-
ment. Seventy percent was used as a soil insecticide to control agri-
cultural pests. Twenty-eight percent was used to (control termites. The
registered uses for heptachlor, tolerances, dosages, limitation of appli-
cation and possible substitutes for registered uses are presented in
Section IA of this chapter. The following general limitations are imposed
with these uses :
* •
1. Grazing is not allowed wherever heptachlar is applied.
2. Soil applications are limited to one treaament per year
unless specified otherwise.
3. While the use of heptachlor may be essential under certain
conditions (i.e., public health; protection of food, feed,
fiber; quarantine and forest pests), no general registration
for such uses has been granted. " '
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i.A. o Summary of Registered Heptachlor Uses and Alternates
—-2S. °r Use
AGRICULTURAL
Foliar
Ditch banks, Field
borders.Roadsides,
Vacant lands
Tolerance
(ppm)
6
Extended
NF
Dosage
(Ibs.a/A)
2.6
2-3 oz/A
Limitations
Pests
Substitutes
60 days
Ants
Grasshoppers
Chlordane
Carbaryl
Chlordane
foalathion
Toxaphene
Naled
Soil
Beans
(snap)
0
Extended
0.1
3.0
2.5
Preplanting soil Cutworms
application only. White grubs
Wireworms
Preplanting soil
application only. Cutworms
Work into soil
Chlordane
Chlordane
Chlordane
Chlordane
Diazinon
Parathion.
Tpxaphene
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Croo or Use
Tolerance
(ppm)
Dosage
(Ibs.a/A)
Limitations
Lettuce
0.1
3.0
Preplanting
cation only.
Work into
soil.
Pests
White-fringed
beetle larvae
white grubs
Wireworms
Cutworms
Japanese beetle
larvae
Substitute
Chlordane
Chlordane
Parathion
Chlordane
Diazinon'
Parathion
Chlordane
Oiazinoa
Lindane
Parathicn
Toxaphene
Chlordane
Lindane
Parathion
Root, maggots
White grubs
Wireworms
Chlordane
Diazinon
Lindane
Chlordane
Lindane
Parathion
Chlordane
Diazinon
EDB, Lindane
Parathion
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Crop or Use
Tolerance
Dosage
Limitations
Pests
Substitutes
Oats
Rice
Rutabagas
r.ye
Pineapples
0
Extended
Extended
0.1
3.0
3.0
5.0
3.0
3.0
Preplanting soil
application only
Preplanting soil
Preplanting soil
application to
furrow or broad-
cast. Work into
soil.
Preplanting soil
application only
Preplanting soil
application only.
Cutworms
White grubs
Wireworms
Rice water
Chlordane
Cutworms
Japanese beetle
White grubs
Wireworms
Cutworms
White grubs
Wireworms
Chlordane
Parathicn
Chlordane
-7-
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Croft or Use
Soybeans
Tolerance
Extended
Dosage
3.0
Cabbage
Wheat
0.1
0.
Extended
Extended
0.25
3.0
4.0
Boysenberries
T.ewberries
Raspberries
Limitations
Preplanting soil appli-
cation (or at time of
planting). Do not con-
taminate food or feed-
stuffs.
Pests
Substitutes
Soil application
to furrow at time
of planting or
transplanting.
Preplanting soil
application only.
Soil application
only. Do not apply
after edible parts
start to form.
Cutworms Chlordane
Grape colaspis Diazinon
larvae
Seed-corn
maggot
White-fringed
beetles
White grubs
Wireworms
Cutworms
Cabbage Maggot
Cutworms
Chlordane
Chlordane
Varathion
Chlordane
Chlordane
Chlordane
Chlordane
-8-
Cutworms
White grubs
Wireworms
Cutworm
Japanese beetle
larvae
Strawberry root
weevil larvae
White-fringed
beetle larvae
White grubs
Wireworms
Chlordane
Chlordane
Chlordane
Chlordane
Chlordane
Culordane
/'crdane
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Crop or Use
o
Blueberries
Tolerance
Extended
Dosage
4.0
Limitations
only. Do not
apply after
edible parts
start to form.
Pests
Soil application Cutworms
Japanese beetle
larvae
Strawberry root
weevil larvae
White-fringed
beetle larvae
White grubs
Wireworms
Root weevils
Substitutes
Chlordane
Citrus
Extended
3.0
Corn
0
Extended
3.0
5.0
Soil application
only. Apply
under trees without
pressure.
Soil application
only.
Soil application
to peat or muck
soils only.
Argentine ant
Citrus root
weevil
Fullers rose
beetle
Corn billbug
Cornfield ant
Corn rootworms
Chlordane
Chlordane
Chlordane
Buxten, Carbo-
furan, Chlordane,
Dasanit, Di-syston
phprate, Dyfonate
3.0
Preplanting or at
time of planting.
Cutworms
Carbofuran
Diazinon
Parathion
-9-
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Crop or Use
Q
Corn (cont.)
Tolerance
Dosage
Limitations
*Phorate
Pests
Grape colaspis
Green June
beetle larvae
Japanese beetle
larvae
Rough-headed
cornstalk
beetle (Sugar-
eane beetle),
Seed-corn
beetle
Seed-corn
maggot
White-fringed
beetle
larvae
White grubs
Wireworms
Asiatic garden
beetle larvae
Substitutes
Chlordane
Chlordanij
Parathion
Chlordane
Thimet*
Chlordane
Chlordane
Chlordane
Parathion
Chlordane
Diazihon
Parathion
-10-
I
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Crop or Use
ri
Corn (cont.)
Tolerance
Dosage
Peaches
Pears
0
Extended
Extended
3.0
3.0
Limitations Pests Substitutes
Flea beetle Chlordane
larvae
False wire- Chlordane
worms
Maize billbug Chlordane
Masked chafer Chlordane
larvae
Sod webworm Chlordane
Ground cover appli- Consperse
cation in spring stink bug
before petal fall.
Plum curculio Chlordane
Ground cover appli- Consperse stink
cation in spring bug
before petal fall.
Peppers
Extended
3.0
Soil application Cutworms
only. Do not apply
after edible parts
start to form.
Japanese beetle
larvae
Root maggots
Chlordane
Diazinon
Lindane, Parathion
Toxaphene
Chlordane
Lindane
Parathion
Chlordane
Diazinon
Lindane
-11-
White grubs
Chlo 'sne
Line .,4
Parathion
-------
Crop or Use
Tolerance
Dosage
• Limitations
Pests
Substitutes
Ratabagas
Tobacco
Wireworms
3.0 Soil application soon Japanese
after plants emerge beetle larvae
with a second appli- Root maggots
cation 3-4 weeks later.
Do not use tops as food White-frlnped
Of iJijiiU. iH:«.i. !. .' JUKviiJ
White grubs
Wireworms
3.0 Apply broadcast to soil White-fringed
and work into top few beetle larvae
inches.
Chlordane
Lindane
Parathion
Chlordanc
Parathion
Chlprdane
Chlnrdn-:--
Clilordnw
Parathion
Chlordane
Parathion
Chlordane
Apply broadcast
Apply as transplant
solution
White grubs
Wireworms
Wireworms
Chlordane
Chlordane
Diazinon
Dyfdnate
Parathion
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Crop or Use
'Tomatoes
Tolerance
0
Extended
Restricted Field
Application
Non-Food
Dosage
3.0
2.0
Limitations
Soil application.
Do not apply after
edible parts start
to form.
Pests
Cutworms
Japanese
beetle, larvae
White-fringed
beetle larvae
White grubs
Wireworms
Soil application Imported fire
ant
Substitutes
Toxaphene
Chlordane
Diazinon
Lindane •
Parathion
Chlordane
Lindana
Parathion
Chlordane
Chlordane
Lindane
Parathion
Chlordane
Diazinon
EDB
Lindane
Parathion
Mirex
-13-
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Crop or Use
Seed Treatment
Barley
Beans
Tolerance
(ppm)
Extended
Corn
Cotton
Extended
Oats
Dosage'
(Ibs.a/A)
2.0 oz./bu.
seed
2.0 oz./bu.
seed
2.0 oz./bu.
seed
2.0 oz./bu.
seed
Limitations
Pests
2.0 oz./bu.
seed
Seed treatment.
Do not use as
food or feed.
Seed treatment.
Do not use as
food or feed.
Corn rootworms
Seed-corn
beetle
Wireworms
Corn rootworms
Seed-corn
beetle
Wireworms
Seed treatment. Corn rootworra
Do not use as food Seed-corn
or feed. beetle
Wireworms
Seed treatment Corn root-
Do not use as food worms
or feed. Seed-corn
beetle
Wireworms
False
Wireworms
Seed treatment. Corn rootworms
Do not use as food Seed-corn
or feed beetle
Wireworms
Substitutes
Chlordane
Lindane
Chlordane
Diazinon
Lindane
Chlordane
Diazinon
Lindane
Chlordane
Lindane
Chlordane
Lindane
-14-
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Crop or Use
-------
Crop or Use
(Jabbage
(Cont.)
Tolerance
(ppm)
Tobacco
NF
Dosage
(lbs.a/A)
1.0
(dust)
2.5
(dust)
Limitations
Pasts
Substitutes
Apply to soil
around plants im-
mediately after
transplanting.
Apply to roots and
stems of plants prior
to transplanting.
Urfd 66
per 50 gals, water when tobacco
of water. plants are set in
field. Use a minimum
of 200 gallons per
acre.
beetle larvae
Wireworms
Qhiordane
Chlordane
Diazinon, Lindane
NON-AGRICULTURAL USE
Forestry plantation NF
4 oz.actual
per 50 Ibs.
of bran/acre,
Bait application.
Apply broadcast
before setting and
near plants after
setting.
Cutworms
Chlordane
Apply 1% or 2% spray in water
with sticker to upper half of
tree leaves during March or
early April.
White-pine weevil
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Crop or Use
Tolerance
(ppm)
•%
Subterranean termites in premises
Dosage
(Ibs.a/A)
Limitations
Pests
0.5% to 1%
in water using
standard founda-
tion trenching and
treatment methods.
Lawns, nursery..soJLl^._PxaainfijitaLtfi, turf.
NF 27,
Substitutes
Chlordane
Ants
Asiatic
garden beetle
larvae
Boxelder bug
Ticks
White-fringed
beetle larvae
White grubs
Wireworms
Armyworms
Cutworms
Carbaryl, Diazinon,
Mirex bait
Chlordane
Chlordane, Diazinon
Carbaryl, Chlordane,
Diazinon
Chlordane
Chlordane
Chlordane
Diazinon
-17-
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Crop or Use
Tolerance
(ppm)
Dosage
(Ibs.a/A)
Limitations
Pests
Lawns, nursery soil, ornamentals, turf (soil)
(Cont.)
NF 2%
Lawn chinch
bugs
Sod webworm
Black vine
weevil
Chiggers
Earwigs
European
chafer larvae
Fieas
Grasshoppers
Green June
beetle
Japanese
beetle larvae
Mole crickets
Mosquitoes
(adult)
Substitutes
Akton
Chlordane
Chlordane, Diazinon
Carbaryl, Chlordane,
Diazinon
Chlordane
Carbaryl
Chlordane
Chlordane
Diazinon
Carbaryl, Chlordane
-18-
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Crop or Use
Tolerance
(ppm)
Dosage
(Ibs.a/A)
Limitations
Pests
Substitutes
Lawns, nursery soil, ornamentals, turf (soil)
(Cont.)
NF 2%
Flower garden plants, ornamentals and shade trees
NF
3.0 lb/100 gal
(foliar)
soil
soil surface
foliar
Pillbugs
Snails
Sowbugs
Striped
grassworms
False wireworms
European crane
fly
Earthworms
Black vine Chlordane, Thiodan
weevil adults
Black vine Chlordane
weevil larvae
Imported fire Chlordane, Mirex bait
ant
Narcissus bulb Chlordane, Dylox
fly
White grubs Chlordane
Wireworms Chlordane (soil)
Japanese beetle Carbaryl,Malathion
adults
-19-
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Crop or Use
Tolerance
(ppm)
Dosage
(Ibs.a/A)
Limitations
Flower garden plants, o.rnamentals and shade trees
NF 3.0 Soil
Household and Commercial
(Spot residual applications)
NF 0.5% in
petroleum distil-
late or water.
Do not treat
animals.
Pests
Substitutes
Strawberry
root weevil
Brachyrhinus
rugosostriatus
Bulb fly
Earwigs
Root weevils
Ants
Boxelder bugs
Baygon, Chlordane,
Diazinon, Lindane,
Malathion, Pyrethrum,
Ronnel, synergized
pyrethrum
Chlordane, Lindane,
Malathion
Brown dog tick Baygon, Chlordrne,
Diazinon, Lindane,
Malathion, Ronnel
Carpet beetles Baygon, Chlordane,
Diazinon, Lindane,
Malathion, Ronnel
-20-
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Crop or Use
Tolerance
(ppm)
Dosage
(Ibs.a/A)
Limitations
Household or Commercial
(Cont.) NF
0.57» in
petroleum distil-
late or water.
Pests
Centipedes
Crickets
Housefly
Mosquitoes
Roaches
Scorpions
Spiders
Silverfish
Substitutes
Baygon, Chlordane,
Lindane, Malathion
Baygon, Chlordane,
Lindane
Baygon, Chlordane,
Lindane, Ronnel
Baygor., Chlordane,
Diazinon, Lindane,
Malathion, Ronnel •
Baygon, Chlordane,
Diazinon, Lindane,
Malathion, Pyrethrum,
Ronnel, synefgized
pyrethrum
Baygon, Chlordane,
Diazinon, Lindane,
Malathion
Baygon, Chlordane,
Diazinon, Lindane,
Malathion, Ronnel
Baygon, Chlordane,
Diazinon, Lindane,
Malathion, Ronnel
-21-
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Crop or Use
Tolerance
(ppm)
Household and Commercial
(Cont.)
NF
Public Health
NF
Dosage
(Ibs.a/A)
0.57, in petrol-
eum distillate
or water.
Limitations
0.8 oz. to
1.6 oz. actual
in spray application
(ground). 1.6 oz.to
2.0 oz. spray applica-
tion (air).
5% granular—0.8 oz.
to 1.6 oz. per A.
Pests
Wasps
Waterbugs
FirebratB
Old-house
borer
Powder-post
beetles
Mosquito
larvae
Substitutes
Baygon, Chlordane,
Lindane, Malathion
Baygon, Chlordane,
Diazinon, Lindajic,
Malathion, Pyrethrum,
Ronnel, synergized
pyrethrum
Abate, EPN, Fenthion,
Lindane, Malathion,
Parathion, Paris
green
-22-
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7.-B. Zascussion of _the_ Impact, of Heptachior Us es £n_ the' Environment
' and _t \e_ Alternates - The Special Pesticide Review Group r.--s studied
the toxieological hazards to man and the environment associated with *
the use of heptachlor 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 Chlordane and Heytachlor (37FR6606).
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 heptachlor as a pesticide.
In an effort to evaluate the environmental and human health effects of
heptachlor, broad use patterns were established by the Special Pesticide -"•
Review Group. 'Basically, the uses grouped into four broad categories:
(1) foliar; (2) soil treatment; (3) seed treatment; and, (4) special uses.
The significant uses of heptachlor include application to agricultural
crops, home gardens, ornamental plants, lawns, and to houses or other
premises for termite control. These broad use patterns present distinctly
different degrees of hazard to human health, wildlife and the environment, i
The following is a. review of the broad use patterns as established for
the systematic consideration of the safety of this pesticide.
I.B.I. Foliar Applications - Foliar applications present the highest
degree of hazard involved in the various methods of applying heptachlor,
especially in terms of environmental contamination, direct human exposure
and hazards resulting from chemical residues in food' or feed crops. Dusts
or sprays for foliar applications have the following adverse 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 pesti-
cide may not reach the target area; and, (3) deposits of pesticide may be
left on the foliage of the treated crops and may contaminate the edible
portions either by direct application or by drift.
I.B.I.a. Agricultural Crops - All foliar applicatiuns of heptachlor on
agricultural crops except ant control on pineapples in Hawaii, have adequate
alternate pesticides. However, some of the alternates present a greater
acute toxicity hazard to man and the environment thai heptachlor when used
as a foliar spray on agricultural crops. Greater care will be needed in
using these products. Subject to those additional precautions in handling
more toxic products the loss of foliar use of heptachlor would create no
adverse economic impact.
I.B.l.b. Home Gardens and Ornamentals - Following t&e Federal Register
Notice for chlordane and heptachlor, there were no significant requests
to continue foliar applications of heptachlor for hone gardens, ornamentals,
-23-
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uhade trees, and flower garac-n plants. All foliar uses of heptachlor
on home gardens and ornamenta>.s have adequate alternate pesticides. o
Some of the alternates present a greater acute toxicity hazard but
most represent less long-term hazard to man and the environment than
heptachlor when used as foliar sprays. Loss of these foliar uses of
heptachlor would create no adverse economic impact.
I.E.I.e. Field and General Foliar Treatments - This use includes the
foliar application to ditchbanks, field borders, roadsides, and vacant
lands. Adequate alternate pesticides are available for this use. The
available alternates represent less long-term hazard to man and the
environment than heptachlor when used as a foliar treatment for these
purposes. Loss of these treatments would create no adverse economic
impact.
I.B.2. Soil Applications - There is a serious need for heptachlor to
control soil insect pests in agricultural crops, lawns, commercial turf,
nursery plant stock, and around homes and premises (termites). Insect
pests for which heptachlor is needed include ants, wireworms, white
grubs, Japanese beetle grubs, white-fringed beetle larvae, cutworms,
and termites. Alternates other than certain chlorinated hydrocarbon
pesticides are not registered for all uses nor are they likely to give
acceptable control of all the above pests. The loss of the currently
registered insecticidal uses of heptachlor as soil applications would
have significant economic effects.
Soil application of heptachlor presents more of a hazard to human health,
wildlife, and the environment than seed treatment use. The granules are
ordinarily applied to crops, including corn, as a band over the row for
control of pests such as corn root worms, wireworms, and white grubs.
The treated areas are at least 7-inches wide and the pesticides are often
applied from a device mounted on the planter. Granules are dropped just
ahead of the press wheel for proper insertion into the soil. Most agri-
cultural granules contain 5 to 20 percent active toxicant. The following
are the significant advantages for the use of the granules in minimizing
environmental contamination: (1) doses of pesticides in granular form
may be kept at a minimum because of reduced drift potential; and, (2)
minimized contamination of the edible portion of a crop because of the
more specific placement of the pesticide before the crop emerges or before
the edible parts are present.
I.E.2.a. Agricultural Crops - It has .been established that more than
53 million acres of corn were harvested in the North Central Region of
the United States in 1970. This area is still using large amounts of
aldrin, dieldrin, and heptachlor for soil insect control in corn. Presently,
at least one-half of the Kansas acreage of corn is probably still being
treated with aldrin or heptachlor, especially in conmunities not having
experienced organochlorine pesticide resistance.
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The Economic Research Service, U.S.).A. (Administrative Report.
May 26, 1972, appended) reports the total cost to ffnited States farmers,..
for discontinuing the use of heptachlor in 1971 woizld have been $2.0
million ($1.1 million for substitute insecticides and $0.9 million for
production losses). The added cost for substitute insecticides to con-
trol rootworms in corn was estimated to be $1.55 per acre. The total
added cost per acre for replacing heptachlor in soil insect control
programs,other than root worms, would be $3.89 per acre. The added
cost for replacing heptachlor seed treatments with alternative pesticides
would be about $28,000.
Increased use of heptachlor may result from the cancellation of the soil
insect control uses of other chlorinated hydrocarbon pesticides such as
chlordane, aldrin or dieldrin. Present evidence suggests that any added
soil use of heptachlor could increase its impact upon the environment.
I.B.Z.b. Seed Treatments and Transplant Water - Alternates other than
the chlorinated hydrocarbon insecticides are not registered for all seed
treatment uses nor are they likely to give the same acceptable degree of
control which is available with heptachlor on the various seeds to be
protected. Diazinon is the only nonchlorinated hydrocarbon insecticide
available. The registered uses for diazinon are Limited.
Seed treatment presents a low order of hazard to human health, the environ-
ment, and to wildlife, except for possible injury to buds. The treatment
procedure usually involves the application of the pssticide directly at a
relatively low dosage rate at a location remote frcnr the field. This treat-
ment is usually carried out by a commercial seed treatment company. However,
in some instances the pesticide is placed directly into the furrow along with
the seed. In either instance, the furrow is covered with soil thus keeping
the pesticide localized.
Transplant water treatments a-re relatively similar to seed treatment insofar
as environmental hazards are concerned and the availability of alternates.
Again, diazinon is the nonchlorinated hydrocarbon pesticide that is available
in some cases as an alternate. Small quantities of heptachlor are required
in transplant water and the chemical is covered with soil.
I.B.2.C. Lawns, Commercial Turf and Nursery Plant 5tock - Alternates other
than the chlorinated hydrocarbon pesticides are not registered for all uses
nor would they be likely to give acceptable control in all cases. The pests
involved are ants, sod webworms, chinch bugs, and other soil insects. In-
creased use of heptachlor could result from cancellation of soil insect
control uses of other chlorinated hydrocarbon pesticides such as aldrin and
dieldrin. Loss of the currently registered insecticidal uses of heptachlor
as a soil application to lawns, commercial turf and nursery plant stock will
have a significant economic effect.
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Ther >. have been numerous indications of the need to continue the usec
of heptachlor for control of soil insect pests far these purposes. It
has been estimated that the loss of chlordane and heptachlor for turf
use xrould 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 heptachlor for soil insect
control would be significantly damaging to the agricultural industry
of the state. South Carolina has reported that heptachlor is an
alternate for the quarantine and control of Japamse beetles and white-
fringed beetles.
I.B.2.d. Termite Control - Heptachlor is registered as a termite soil
poison to be used in and around domestic and comnercial premises.
Termite control is one of the major uses of heptaihlor. Alternates
other than the chlorinated hydrocarbon insecticides are not available.
Loss of this use of heptachlor would have a significant economic effect.
Subterranean termite control with heptachlor is a modified soil treat-
ment use. Less than 1 percent (330,000) of the total dwellings subjected
to termite attack currently receive treatments fear the prevention of
damage by these pests. The total cost of termite control is estimated
to be not less than $250 million per year. One-tMrd of this cost is
for damage repairs and the other two-thirds for chemical treatment. In
addition, termites do considerable damage to utility poles, fence posts,
and other wooden items, with an annual cost probaMy exceeding $500
million. In general, heptachlor is applied to the soil at critical
areas around and under the house. It is applied :to the soil before
pouring the cement for slab construction. Also, it is applied to the
soil and into the subsoil in trenches around the foundation of "base-
ment construction" homes. The chemical may also 3oe used along the
foundation of crawl-space homes.
I.B.Z.e. Baits - Heptachlor baits are not indicated to be essential
because other registered materials have the same spectrum of pest
activity and present less environmental hazard. loss of the currently
registered uses of heptachlor in bait formulations would not have a
significant economic impact.
I.E.3. Household and Commercial Uses - This use includes interior spot
treatment with residual sprays' for control of cockroaches, ants, ticks,
and a number of other household and commercial buiilding pests. The
insecticide treatments for pest control are usually app(lied inside the
buildings including kitchens and food service areas. Only limited spot
residual usage has been registered.
The household use of heptachlor is regulated by Interpretation Number 23
of The Regulations for the Enforcement of the Federal Insecticide,
Fungicide and Rodenticide Act. Liquid and pressurized products which
deliver a coarse spray are allowable. These products contain not over
0.5 percent heptachlor. Directions for use are £or spot treatment only
-26-
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"•c cracks, surfaces .ir other areas vhere the insects run, rest or
hide. L'usts cire not registered. Also, claims for space spraying
in the air or for use in fine mist sprayers are not acceptable.
There are no claims or directions which might lead to contamination
of foods.
I.E.4. Mosquito Larvaeide - Heptachlor has been registered as a
mosquito larvacide for many years and constitutes an unnecessary
direct contamination of water. Alternates include Paris green,
carbaryl, malathion, naled, pyrethrins, parathion, and Flit MLO.
Loss of the use of heptachlor as a mosquito larvacide would have no
significant impact on the public health.
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CHAPIEk II
Chenistry and Analytical Methods
The chemical "heptachlor" commonly refers to 1, 4 ,,5, 6,7,8, 8-heptachloro-
3a,4,7,7a, tetrahydro-4, 7-methanoindene which has an empirical formula
with an elemental analysis 0=32.17%, H-L.,35% and Cl=66.48%.
The molecular structure of the heptachlor which comprises the diene group
is complicated, and several isomeric forms are possible. Available
physical characteristics of technical heptachlor which are useful for
further processing have no value for assessing presence of isomers.
Melting point range and wide range in viscosity dearly indicate that
technical heptachlor is a mixture of substances wiith different molec-
ular weights. Although the elemental composition of components of .
technical heptachlor is carefully controlled during manufacture, no
evidence is available which describes spatial arnngement of elements
in the different molecular components of the mixture.
II. A. Chemical Synthesis and Reaction - Heptachlor is produced commercially
by selective chlorination of chlordene (C^Q^Clg , Hoi. Wt. 339) according to
U.S. Patent (1951, 1953, 1959). The general chemiical reaction is shown below:
Pi els-AIHer
Addition
cyclopentadiene
hexachlorocyclo-
pentadiene
Cl
Heptachlor
The mixture produced by this process is technical fteptachlor which contains
70*73 percent heptachlor, 20-23 percent gamma or tnans-chlordane (C^HgClg,
mol. wt. 410), 4.5-5.0 percent S-trichlorochlordeia (CiQE^Cl^, mol. wt. 444.5)
less than 1 percent of an initial reactant hexachlarocyclopentadiene and
traces of chlordene.
i •
Chemical reactions of heptachlor, including additions, substitutions, oxidation
and reductions were examined as means of preparing derivatives which could be
separated and quantitated in the presence of other chlorinated dienes.
Chlordane, pentachlorochlordene, acetoxychlordene, and hydroxychlordene have
been prepared under specific conditions (Cochrane .-Hid Chau 1968, 1970; Chau
and Cochrane, -1969, 1971; Chau, 1970).
-28-
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TT..B. Physical arH Chemical Properties - The technical heptachlcr is a
ligh!--*:an waxy solia with an odor of camphor. The 99% p-.:re chem.'oal
heptachlor is a whits crystalline solid with a did odor of camphor or
cedar. Both the technical and pure chemical are stable in daylight, air,
. moisture, and moderate heat, and are nonflammable. The pure compound is
stable upon heating to 160°C. The physicochemical data of heptachlor,
technical heptachlor and .heptachlor epoxide are shown in Table II.1. and
solubility data in Table II.2.
II.C. Analytical Methods - Several multiresidue analytical systems are
used for measurement of heptachlor and heptachlor epoxide as residues
or in formulations. As an example, hexane extracts are partitioned with
acetonitrile? fractionated on florisil, identified and quantitated by
gas chromatographic techniques, using electron capture or flame ionization
detection, and verified by thin layer or paper ciromatography (Corneliussen,
et al. , 1970). Various modifications of these techniques (Pesticides
Analytical Manual and AOAC method 29.001, llth Edition 1970) are sensitive
to 0.001-0.002 ppm heptachlor or heptachlor epoxide in milk and meat and
0.01-0.02 ppm in agricultural food crops. The group of industrial compounds
called polychlorinated biphenyls (PCS) interfere on commonly used GLC
columns with practically all organochlorine insecticides.
II.D. Chemical Derivatization Technique as a_ Confirmatory Test - The
artifacts having similar electron capture gas liquid chromatography
(ECGLC) responses or interfering responses which include previously
unknown derivatives or metabolites have been reported for heptachlor
and heptachlor epoxide. Chau and Cochrane (1969) reported that the dehydro-
chlorinated product trans-chlordane, namely, 2-chlorochlordene (shown-in
Figure II.1) from technical chlordane-treated caibbage have EC-GLC and thin-
layer chromatography (TLC) characteristic similar to heptachlor. To date
no suitable GLC column has been obtained that will successfully separate
these two compounds and, further, it is not known whether the 2-chloro-
chlordene originated as a minor constituent of technical chlordane or is,
in fact, a trans-chlordane metabolite.
A heptachlor epoxide artifact observed by Pollen, et al.. (1970) during a
cis and trans-chlordane feeding experiment in rats (Pollen, 1969), has been
subsequently identified by Schwemmer, et_ al^., (1970) as the closely related
compound, 1,2-dichloro-chlordane epoxide. This compound possesses one more
chlorine atom in the 2-endo-position than heptachlor epoxide itself as shown
in Figure II.1.
The four parameters from which the confirmation of identity of a chlorinated
hydrocarbon pesticide residue can be inferred with reasonable assurance are:
(1) Rt (EC-GLC retention time of the pesticide on a given stationary phase),
(2) Different retention time (Rt) of a derivative prepared from the pesticide,
(3) Rf values of either TLC or paper chroimtograpfay (PC), (4) "p" value of
solvent solubility.
-29-
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Table II.1-
Fhygjcu-chemical Properties of I-Teptacblor
NAME
Molecular Melting Boiling
Weight Point Point
Density
g/ml
Vapor Viscosity
Pressure Centistokes/
mm/Hg °C
Heptachlor
997, pure
Technical
heptachlor
Heptachlor
epoxide
99.5% pure
373,5
'-
389.3
93
(95-96)
46.74
160-
161.5
135-
145 at
L-1.5 mm
Hg
-
1.65-1.67
at 77°C
1.65-1.67
at 65°C
3xlO"4
at 25°C
3.75xlO"3
at 50°C
and .
1.5x10"
at 65°C
-
44-66
at 71°C
Table II.2
Solubility-g/100 ml at 27°C
NAME
Heptachlor
99% pure
Technical
heptachlor
Heptachlor
epoxide
99.5% pure
WATER
Insoluble
0.01
Insoluble
ALCOHOL
4.5
4.5
"•
KEROSENE
-
18.9
"*
XYLEEE
102
40
"
CC14
112
-
™
ACETONE
75
75
*•
BENZENE
106
106
.. "
-30-
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Chlordene
2-Chlorochlordene
A
H ---
Heptachlor
A
ci
3-Chlorochlordene
Heptachlor epoxide
1,2-Dichlorochlordene epoxide
Figure II.1.
Structure and Numbering for Some Chlordane Compounds and Isomers
-31-
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Vario.is confirmatory -ests of heptachlor have bees developed as s> source
of additional information in corroboration with residue identity. The^e
chemical methods are summarized in Table II.3.
Table II.3.
Various Chemical Methods for Confirmation of Heptachlor
and its Epoxide Residues
Pesticides
Heptachlor
Heptachlor
epoxide
Reaction
Utilized
a) Ally lie
acetylation
hydr oxy lat ion
dechlorination
b) Addition
c) Epoxidation
Epoxide
rearrangement
Limit of
Detectability
(ppm)
0.01
0.01
0.01
0.03
0.05
0.01
Pesticide
Interference
-
AMrin
Chlsrdene
*
Hepfeachlor
ip oxide
Reference
Cochrane and
Chau (1968)
Cochrane and
Chau (1970)
Chau and
Cochrane (1969)
San (1969)
Cochrane (1969)
As shown in Figure II.1. the presence of a reactira allylic chlorine atom
in the heptachlor molecule has been the basis of tnree confirmatory tests
based on its ease of replacement. Of the common crganochlorine pesticides,
heptachlor reacts quantitatively with a silver acetate-glacial acetic acid
mixture and yields 1-acetoxychlordene which, with the GLC conditions used,
had a retention time close to heptachlor epoxide. When the reaction of
heptachlor with silver salts was extended to silver carbonate in aqueous
alcohol, 1-hydroxychlordene was obtained which could easily be converted to
more volatile and GLC-responsive silyl ether. Thos silyl ether, unfortunately,
has an Rt identical to aldrin. It is noted, howeser, that heptachlor is the
only chlorinated pesticide to undergo modification with silver-carbonate and
to date (Cochrane and Chau (1968), this reaction ia the most specific confirm-
atory test observed for the organochlorine pesticides investigated . The
soluble silver salt of heptachlor is reacted with It C12 solution for the
allylic dechlorination of heptachlor to chlordenc. Cochrane and Chau (1970)
described the reaction pathways as shown in Figure II.2. The two secondary
products (dimer and 1-hydroxychlordene) present gi*e no observable GLC inter-
ference. Miles, et. al.,(1969) reported that chlorlene has been formed by
dechlorination of heptachlor by bacteria and subsocuent microbial epoxidation
to chlordene epoxide in soils; therefore, interf er.ince can'occur in such soil
sample specimens depending upon the degree of chloidene degradation.
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The o •.ner two confirmatory trusts for heptachior involve addition to "he
stericaily hindered double bond. Generally, chlorine doer not ada f.o ,.,
heptachior without the presence of an initiator s:Eh as antimony peircac
H l
Heptachior
H—i
Transition state
H—
Intermediate -1
Bi.Tolecular
-?» Dimer
Reduction
H
Chlordene
Figure II.-2
Reaction Pathways of Heptachior With Aqueous CrClT Solution..
I-Hydroxychlordene
-------
Heptachlor is also resistant to epoxidaticm by peracids but both addition
and epoxidation is readily done chemically with tert-BuOCl/HOAc and Cr03
oxidation respectively. The addition of tert-BuOCl to yield a single
derivative peak which has been identified as the corresponding chloro-
acetate, requires an excess of glacial acetic acid (Chau and Cochrane,
1969).
In the absence of the heptachlor epoxide the confirmatory identification
test most used for heptachlor is oxidation. This is carried out using
chromic acid to yield heptachlor epoxide (Singh, 1969). The simultaneous
identification of heptachlor and heptachlor epoxide mixture by this
oxidation procedure fails because of substantial degradation of the
epoxide compound to acidic products. This, however, can be achieved
during cleanup using a florosil column for their separation or
subsequently using TLC. In combination, heptachlor and its epoxide
can be simultaneously confirmed with strong basic reagents. Using
Potassium tertiary butylate in tertiary butyl alcohol, heptachlor produces
1-hydroxychlordene whereas heptachlor epoxide undergoes rearrangement
to secondary alcohol, l-hy.droxy-3 chlordene. Both derivatives can
be converted to more GLC-responsive compounds either by silylation or
acetylation of the allylic hydroxyl groups. This does not affect any
of the accompanying dehydrochlorinated products (Cochrane and Chau,
1968). The procedures described for acetylation, epoxidation, addition,
dehydrochlorination, etc., for the confirmation of identity of heptachlor
and its major metabolite, heptachlor epoxide, can also be applied to
minor metabolites as shown in Table II.3.
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II. 3
Chemicil Derivation C nfirniatorv Ma-iun
for Minor Metabolites of HentachLo:
Parent
Pesticide
Metabolite
•Broup Utilized Derivative
Heptachlor
a) chlordene
b) 1-hydroxychlordene
c) l-hydroxy-2,3-epoxy-
chlordene
hyikogen
2. Doiftle bond
1. AH&lic
hytimxy
2. DoiifcLe bond
1. Hytoxyl
2. EposdLde
1-Bromo-chlordene
chlordene epoxide
silyl ether
chloroacetate
epoxide
silyl ether
Trihydroxychlordan
II.E. Spectroscopic identification methods — TheG.L.C. detection system
(electron capture or flame ionization) are ultra sensitive but none cf the
detectors are completely specific and cannot provide an unequivocal identi-
fication based only on retention times (Rt). Verification by various
independent methods is required for positive identification.
II.E.I. Infrared spectrophotometry -- The usefulness of infrared micro-
techniques in helping establish and confirm, the ideitity of organic
chemical pesticides, and/or their metabolite(s) or degradation products as
residues at microgram level has been well established. Functional group-
absorption band correlation charts are well known aid routinely used by
analysts for characterizing chemicals of unknown idaitity. The positive
identification and confirmation of identity of the unknown is done by
exact comparison of the various absorption bands of the unknown with
those of a compound prepared synthetically by an equivocal procedure.
Where a synthetically prepared compound is not avaiJOable for spectral
comparison with the unknown, infrared data in conjunction with mass,
ultraviolet and nuclear magnetic resonance can allow the deduction of
the unknown compound's structure with reasonable asaairance.
II.E.2. P-value as «i confirmatory test — The P-valkies of pesticides
and related compounds are determined by single or multiple distributions
between immiscible solvents at 25.5°+0.5°C and are arranged according to
ascending gas chromatographic retention times (Rt) Bowman and Beroza,
1965; and Beroza, ejt al., 1969). This method has bear employed as an
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analytical tool in clann-up, for confirmatory identification of a
pesticide, and Jor selecting solvents for partition clean-up procedures.
The P-values in- certain solvent system? for heptachiioi: are shown in
Table II.4. "
II.E.3. Nuclear Magnetic Resonance—The NMR spectra, of most of the
organo-chlorine pesticides (standard 99% + pure chemical compounds)
have been published. Singh (1969) reported that the NMR spectrum of
heptachlor epoxide gave one proton doublet at T 6.7Ewith J-values of
3 and 8 CPS, three proton triplets at T 6.3 with J-ralue of 3.5 CPS, and
multiplet at T 5.70. The low sensitivity and the high cost of instrumen-
tation at ultra micro-levels has precluded the wide acceptance of NMR
except as a useful technique in conjunction with other independent measure-
ment methods for positive identification of an unkncnm compound.
II.E.4. GLC-Mass Spectrometry—Chlorinated hydrocatfion pesticide residues
in human adipose tissue and liver tissue samples hara been identified by
mass spectrometry coupled with gas chromatography. 3iros and Walker (1970)
positively identified that the GLC peak for heptachJmr epoxide in human
adipose tissue was actually heptachlor epoxide and met a derivative of
chlordane. The characteristic Mass Spectral Peaks aad Intensities for
heptachlor epoxide are found to be m/e 81(100%), 353 (84%), 355 (76%),
351 (48%), 357 (35%), 237 (33%), 386 (molecular ion, 8%). Several individual
and multiresidue analytical methods are available fair GLC-Mass spectrometric
confirmation and identification of pesticide residues. Evaluation of mass
spectral fragmentation pathways provide definitive aid conclusive confirmation
of residue identity as well as characterization of residues and their meta-
bolites of unknown structure. This combined technique in residue analysis
is one of the most significant advancements for uneqiivocal identification for
pesticides, their metabolite(s), or degradation products.
Table II.4
P-value of heptachlor in different solvent systems
Sblven
it System
Name of
Pesticide
Heptachlor
Rt
(relative
to Rt of
Aldrin)
0.77
Hexane
Aceton-
itrite
0.55
Iso-
octane
DMT
0.21
Iso-
octane
85%
DMF
0.73
ibexane
90%
•mso
tt.77
Heptane
90%
Ethanol
•
0.71
Iso-
octane
80%
Acetone
0.96
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II.F. Phr.'ioisomor.q — Photodecompositicn hai been investigated since
the volatility of hcptachlor affords possible additional contamination
of the environment. Substances derived from heptachlor are described
by formula in the Figure II.3. A product, believed to be identical to
a caged isomer which is formed when heptachlor is exposed in sunlight,
.has been formed by ultraviolet irridation (Rosen, 1969; Benson^ et al.,
1971; Vollner, et al., 1971).
Rotenone and pyrethrin have been reported to enhance photoisomerization
(Rosen, 1969). Dechlorination occurs when low concentrations of hepta-
chlor in hexane or cyclohexane are irridated for short periods of time
(McGuire, 1971). Hydrogen migration and ring closure, and rearrangement
from the epoxide to the keto form without loss of chlorine occurs when
heptachlor epoxide is irridated. The caged form of heptachlor is more
toxic to insects and fresh water animals, but information on mammalian
toxicity is limited (Georgackis and Kuhn, 1971).
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Substances derived fron hent,,v.chior
Chlordene epoxide
Heptachlor epoxide
Hsilf-caged products
Hydroxychlordene
Cl
H
Pentachlorochlordene
hydroxy-2,3-epoxychior:
-37a-
1-Ketochlordene
-------
CHAPTER II
Bibliography
: (Chemistry and Analytical Methods)
Benson, W. R., Lombardo, P., Egry, I.G., Ross, Jr.t R.D., Barren, R. P.,
Mastbrook, D. W. , and Hansen, E. A. ChLcardane photoalteration
products: Their preparation and identification. £. Agr. Fd.
Chem. 19: 857-62 (1971).
Beroza, M., Inscoe, M.N., and Bowman, M.C. Distribution of pesticides in
immiscible binary solvent systems for cleanup and identification
and its application in the extraction of giesticides in milk.
Res. Rev. 30:1-61 (1969).
Biros, F. J., and Walker, A.C. Pesticide residue analysis in human tissue by
combined gas chromatography-mass spectronetry. J_. Agr. Fd. Chea.
18:425-9 (1970).
Biros, F.J. Enhancement of mass spectral data by means of a time averaging
computer. Anal. Chem. 42:527-40 (1970).
Bowman, M.C., and Beroza. M.J. Extraction of P-values of pesticides and related
compounds in six binary solvent systems. J^. Assoc. Of fie. Anal.
Chem. 48:943-52 (1965).
Chau, A.S.Y. Chromous chloride reductions. III. Identification of products
obtained from prolonged contact of chlordene and heptachlor with
chromous chloride. Bull. Environ. Contain Toxicol. 5:429-34 (1970).
Chau, A.S.Y., and Cochrane, W.P. Cyclodiene chemistry. I. Derivative
formation for the identification of heptachlor epoxide, cis-chlordane,
trans-chlordane and aldrin pesticide residues by gas chromatography.
£. Assoc. Of fie. Anal. Chea. 52:1092-1100 (1969a).
Chau, A.S.Y. and Cochrane, W. P. Chromous chlorida reductions. IV.
Derivative formation for the simultaneous identification of heptachlor
and endrin pesticide residues by gas chronatography. J_. Assoc. Of fie.
Anal. Chem. 54:1124-31 (1971).
Cochrane, U. P. and Chau, A.S.Y. Note on gas chronatographic identification
of heptachlor pesticide residue by derivative formation. J. Assoc.
Offic. Anal. Chera. 51:1267-70 (1968). ~
Cochrane, W. P., and Chau, A.S.Y. Ring-opening isroierisation of heptachlor
epoxide with base. Chem. Ind. London 169f-7 (1968).
Cochrane, W. P. and Cuau, A.S.Y. Use of chromous uiloride for the confirmation
of heptachlor residues by derivatization. Bull. Environ. Contain. Toxic
5:251-54 (1970).
-38-
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Cornelius sen., P.E.. Biros, F., Burke, J.A., and Caul, J.A. Pesticide
Analytical Manual. V. I. f1970).
A>
Georgackis, E. and Kahn, M.A.Q. Toxicity of the photoisomers of cyclodiene
insecticides to freshwater animals. Nature 233:120-121. (1971).
Julius Hyman and Co. U.S. patent 2, 576, 666 (1951).
McQuire, R.R., Zabik, M.J., Schuetz, R.D., and Flotard, R.D. Photochemistry
of bioactive compounds - photolysis of 1,4,5,6,7,8,8-heptachloro-
3a,4,7,7a-tetrahydro-4, 7-methanoindene (cage formation vs. photo-
dechlorination).. _J. Agr. Fd. Chem. 18:319-21,(1971).
Miles, J.R.W., Tu, C.M., and Harris, C.R. Metabolism of heptachlor and its
degradation products by soil microorganisns. J_. Econ. Entomol. 62:
1334-8 (1969).
Polen, P.B., Hester, M., and Benziger, J. Characterization of oxychlordane,
animal metabolite of chlordane. Bull. Environ. Contain. Toxicol. 5:
521-28 (197ffl).
Polen, P.B. Terminal chlordane residue: evaluation. ^J. Assoc. Offie. Anal.
Chem. 53:300 (1969).
Rosen, J. D., Sutherland, D.J., and Kahn, M.A.Q. Properties of photoisomers
of heptachlor and isodrin. £. Agr. Fd. Chem. 17:404-5 (1S69).
Rosen, J. D., and Siewierski, M. Sensitized photolysis of heptachlor. J^_ Agr.
Fd. Chem. 18:943 (1970).
Sans, W. W. Multiple insecticide residue determination using column chroma-
tography, chemical conversion and gas liquid chromatography. _J. Agr.
Fd. Chem. 15.: 192-8 (1967).
Schwemmer, B., Cochrane, W.P., and Pollen, P.B. Oxychlordane animal metabolite
of chlordane isolation and synthesis. Science 169:1087 (1970).
Shell Development Co., U.S. patent 2, 661, 377-8 (1953).
Singh, J. Conversion of heptachlor to its epoxide. Bull. Environ. Contam.
Toxicol. 4:77-9 (1969).
Velsicol Chemical Corp., U.S. patent 2, 904, 599 (1959).
k
Vollner, L., Polar, H., Klein, W., and Korte, F. Beitraege zur Oekalogischen
Chemie XXXI. Photoreaktionen der Komponenten des Technischen
Chlordans. Tetrahedrox 27: 501-09 (1971).
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CHAPTER III
Fate and Implications of Hepta-hlor
in the Ecosystem
The fate and implications for heptachlor in the ecosystem must include
a review of the pesticide's distribution in soil, sater, air, and related
effects upon the flora and fauna of the environment. The distribution
and loss of heptachlor from the environment is influenced by various
processes such as volatilization, movement with water and absorption and
metabolism by plants and microorganisms of the soil.
III. A. The Fate of Heptachlor in the Soil - Retention of heptachlor by
soil is influenced by climate, soil type, and management and cropping.
practices (Harris and Lichtenstein, 1961; Harris, _£t_ ^1., 1966; Lichtenstein
and Schultz, 1960, 1965; Wilkinson, et_ al_., 1964). Retention is longest when
the soil remains undisturbed. Following heptachlor applications for uses
such as termite control, the penetration of heptachlor into any soil type
is influenced by moisture content, and the greatest penetration (25-30 cm)
will occur in damp or wet soils (Carter and Stringer, 1970). The greatest
amounts of heptachlor are found in the upper 5 cm of soil. The best
retention of heptachlor occurs in clay soils or in sandy soil with a high
content of organic matter (Carter and Stringer, 1971). Heptachlor and
heptachlor epoxide were detected 12 years after a single application of
heptachlor for wireworm control in grasslands of Nora Scotia. The greatest
residues were observed from fall applications. The ieptachlor penetrated the
soil 8-10 inches but 80 percent remained in the upper 0.4 inches (Stewart
and Fox, 1971).
V.
In general, the persistence of heptachlor in soils msed for diversified
agriculture is less than for dieldrin but greater tihan for lindane or
endrin. Studies have also shown that for some time after soil application
there will be residues of heptachlor and heptachlor epoxide for plant uptake.
Five percent of the total 5-year application remained as heptachlor epoxide
after the fifth annual application of heptachlor at 5 pounds per acre to
sandy loam soil. Potatoes and carrots were grown inc. the soils for 5 successive
years without further pesticide treatment. These crops contained residues
greater than one-third that amount found in the soil. The residues found
were: 0.5 ppm in the soil; 0.35 ppm in carrots; arafl 0.28 ppm in potatoes.
The residues of heptachlor epoxide found in beets, radishes and cucumbers
grown in these soils were 8.1, 19.8, and 12.0 percent, respectively, of the
measured soil residue (Lichtenstein, et_ £l_., 1970).
•
Soil samples were collected from 51 locations in the United States in 1965-
1967. The locations included seventeen at which pesticides were used
regularly, sixteen locations with a record of at least one application and
eighteen locations with no history of pesticide use (Stevens, et_ ^1_., 1970).
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Residue? of heptarhlor we:v. defected oi.ly from the areas of regular use.
Htpcachlor epoxlde ras found in 24 percent of the soil samples from £.'<;ids
used i.or vegetables, cotton, small grain, and root crops. Recovery of
residues could be correlated with history of use, but the amount detuc'tzd
could not be related to rates of application (Mullins, £t_ ^1^., 1971).
III.A.I. Degradation of Heptachlor by Soil Organisms - Results from
laboratory studies suggest there are two possible pathways for microbial
degradation in soil. By one route, heptachlor is converted to chlordene
and subsequently epoxidized to chlordene epoxide. Via the other pathway,
heptachlor may be oxidized to 1-exohydroxychlordene and epoxidized to
l-exohydroxy-2, 3-epoxychlordene (Miles, _et_ al_., 1971). Heptachlor epoxide,
chlordene, and 1-exohydro-oxychlordene have been recovered from field soils.
III.A.2. Translocation to Plants - Grasses and legumes have been found to
absorb heptachlor and heptachlor epoxide from the soil residues of the
pesticide. Bromegrass, especially the second cutting, was found to contain
heptachlor and heptachlor epoxide at amounts equivalent to one-third of the
soil residue when grown on heptachlor-treated plots (Beall and Nash, 1969).
These toxicants were also absorbed by alfalfa with the greater amounts found
in the root crown. Residues found in the stem and leafy portions of the
alfalfa were equally distributed.
Soybeans were grown in soil for 4 consecutive years after a single application
of heptachlor and were found to contain approximately 10 percent
of the soil residue. After the 4th year, 15 to 25 percent of the pesticide
applied to the clay loam soil was detected as heptachlor and heptachlor
epoxide in plants or soil (Bruce and Decker, 1966).
III.B. Heptachlor in Water - Heptachlor and heptachlor epoxide have not
been found in amounts greater than 0.04 ppb in waters of rivers west of the
Mississippi River since 1965. Water samples were taken monthly from twenty
sampling sites representing major drainage areas during a recent 5-year
survey and the samples analyzed for pesticide chemicals. Heptachlor or
heptachlor epoxide were found to occur with the least frequency. Heptachlor
or heptachlor epoxide were not detected in any water samples obtained from
western water sheds after October 1967 (Mangold and Schulze, 1969). Surveys
of surface water in the United States after October 1967 (Mangold and Schulze,
1969) did not indicate residues of heptachlor were major contaminants of
surface water. Heptachlor and heptachlor epoxide were not detected in the
river waters of the United States after 1968 (Lichtenberg, et al., 1970).
However, in some localized areas there have been found detectable amounts
(0.09 - 0.5 ppm) of heptachlor and heptachlor epoxide in storage ponds
(Guerrant, ^ al., 1970).
•
Translocation of heptachlor from the site of application by water has been
investigated in laboratory and field trials; and, by monitoring open and
closed drains from fields where the pesticide had been applied. The vertical
movement of heptachlor or heptachlor epoxide through the soil profile was
minimal. After 4 months, 97-99 percent of the applied insecticide was
recovered in the top 15 cm of the soil from treated sites. Organic matter
and clay content were factors which limited vertical movement. Slight but
detectable leaching occurred in sand (Harris and Sans, 1972).
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Heptachlor residues were measured in soil, wells, rud run-off wata's
during 4 consecutive years of annual application a£ 0.5 pound per acre •••
to soil in a new irrigation district of Kansas (Kmtson, _et_ _al. , 1971).
During this period, no buildup of heptachlor residues were noted in soil
and no heptachlor or heptachlor epoxide were detected in the wells.
Residues no greater than 1 ppm were detected in silt. Heptachlor epoxide
was found only once at 5 ppt in surface water. A raservoir and an adjoin-
ing river were sampled 18 times during 3 years of itiie study period. Hepta-
chlor was found at 6-10 ppin and heptachlor epoxide was found at 6 ppt in
one sample from the reservoir. Heptachlor was found 3 times at 1-2 ppt
in the river.
Plots were treated in Ohio with 2 pounds of heptac&lor per acre, and only
trace amounts of heptachlor and heptachlor epoxide were found in water
of two tile drains and two open surface drains frait the plots (Schwab,
et al., 1970).
In water samples taken from treated soils, the insecticide content of the
sediment fraction was much greater than that of the water fraction. The
heptachlor and heptachlor epoxide content of sedimmts were found to decrease
as the clay content of the soil increased (Sievers,, et_ ai_. , 1970).
III. C. Heptachlor in Air - Volatilization of heptachlor begins immediately
after application and it will continue at a slower !3ut consistent rate after
fixation to soil pesticides. The volatilization process occurs fast enough
to contaminate foliage growing above the application site and to kill insects
which are exposed to the vapors. Using Drosophila melanogaster and the
house fly as test organism, it has been estimated .that 16 to 38 percent of
the applied toxicant is lost through volatilization. The rates of volatili-
zation of heptachlor are relatively rapid immediately after application to
the soil. As the insecticide becomes "bound" to the soil, the volatili-
zation decreases to a constant rate which is influenced by the relative
humidity of the air and the soil type (Harris and lichtenstein, 1961).
Corn leaves from fields treated with 4.6 Ibs heptadilor/acre were found to
contain 180 ppm heptachlor and heptachlor epoxide. The concentration of
heptachlor residues decreased with the height of the plant and with lateral
distance from the sites of application. The corn leaves taken 180 cm
above ground were found to contain only 20-30 percmt of those residues
found at 60 cm above ground. The heptachlor residtes on corn leaves taken
30 meters from the site of application had only 5—]Q percent the residues
of similar leaves from the treated area (Caro, 197Q) . Similar results
were observed for soybeans grown in pots under gremhouse .conditions with
regulated airflow and protection for individual plaits (Nash and Beall, 1970).
Pesticides are transported long distances on dust particles by air currents.
Dust from fields treated with chlorinated insecticides was carried by winds
from east of Dallas, Texas and deposited by rain ov>r Cincinnati, Ohio. The
dust deposits recovered from a specially prepared surface in Cincinnati
contained 1.34 ppra organic chlorine materials of wlu.cn 0.5 pj>m was chlordane
and 0.04 ppm heptachlor epoxide (Cohen and Pinkertoi, 1966).
-42-
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III. D. Toxicity and Effects of Hep.tichlor on Lirds -
III. D.I. Acute Toxicity of Heptachlor - The LDgg and LC^Q values of
heptachlor in selected species of birds are presented in Table II. D.I.
These data emphasize the variability of toxicity between species.
Table II. D.I. — Toxicity p_f_ Heptachlor to Wild Birds -
Tucker and Crabtree (1970)
Heath, e± al. (1970)
DeWitt and George (I960)
Heath, ^t al. (1970)
DeWitt and George (I960)
Heath, et_ al . (1970)
Heath, &t al. (1970)
Species LDsn (rag/kg)
Mallard (male) =2000 ----
Bobwhite (quail) 125 450-700
Pheasant 150-400 250-275
Coturnix ------ 80-95
III. D.2. Heptachlor Effects and Residues for Birds in the Fields -
Forty-six sharp-tailed grouse were collected from 6 counties and 48 pheasants
were collected from 4 counties of South Dakota during 1965-1967. Seventy-
four percent of the grouse contained less than 0.01 parts per million
heptachlor epoxide and the balance of the birds contained 0.01-1.0 parts
per million heptachlor epoxide. Seventy-one percent of the pheasants
contained 0.01-1.0 parts per million heptachlor epoxide and the balance
of the pheasants contained less than 0.01 parts per million (Greichus ;
and Greichus, 1968).
Bald and golden eagles found in 13 states and Canada were analyzed for
pesticide residues. Dieldrin and metabolites of DDT were found in all
specimens whereas heptachlor epoxide «^ 0.05-0. 8 ppm) was found in
37 of the 67 birds.
Numerous accounts of population reduction have been reported for birds
following the use of heptachlor. A significant decrease in quail popu-
lation persisted in Georgia for 3 years after the treatment of land with
2 pounds of heptachlor per acre (Rosene, 1965). Applications of one-half
pound of heptachlor per acre caused a decline of numbers of cocks and
coveys. Bobwhite quail were introduced into areas immediately after
application of heptachlor at rates of 2, 1-1/2, and 1/4 pound per acre.
The mortalities observed within 15 days were: 61 percent , at 2 pounds; 50
percent at 1-1/2 pound; and 17 percent at one-fourth pound (Kreitzer
and Spann, 1968).
An aerial application of heptachlor granules was made over a forest
preserve consisting of a 25-square mile area. The granules were applied
at the rate of 2 pounds active per acre for Japanese, beetle control.
More than 300 birds, including mallards, robins, tackles, s.tarlings,
cardinals, cowbirds, meadowlarks, brown thrashnrs, and house sparrows
were found dead in the area over a 2-month period following treatment ..
-43- ;
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I-el; yc.-r' in-the area inhabited Vy these species, a uota] -,.' throe or
four dead birds are found. Hundreds of oLher birdr. Jrora tit'- thrush,
sparrow, and w.^valer families visiLed ft-3 area during the period of
observed rrr-rtalif.y without demonstraci:^ my ill effects. Due banded
roL/in had 11,1 ppm heptachlor epoxide in tissues. Some mortality among '"'
the mammals was also observed (Bartel, 1960).
A program to eradicate the introduced sugarcane root weevil from an
urban area in Florida in the spring of 1969 was studied to assess
effects on fish and wildlife. Two basic techniques were utilized:
analyses of residue accumulations in selected species, and search for
dead animals. Results are summarized in Table III, D2. Residues increased
substantially-in birds but not in earthworms, fishes, or aquatic
invertebrates. Considerable bird mortality followed treatment with
granules containing 10 percent heptachlor applied at 30 Ib. per acre.
Residues in specimens analyzed indicated death from heptachlor poisoning.
(Oberheu, 1971).
TABLE III, 02»
INSECTICIDE RESIDUES IN PRE- AND POSTTREATVENT SAI.PLES OF ANIMALS COLLECTED FROM
THE TREATMENT AR£A
Species
Campled
Pool of 10
Sparrow brains
Pool of 10
Sparrow carcasses
Pool of forage
fish
Pool of predator
fish
Pool of earthworm
5ool of aquatic
invertebrates
Collected
Prctreatment
Posttreatment
Pre treatment
Posttreal.-rent
Pretreatment
Post treatment
Pretreatment
Post treatment
Pretreatment
Post treatment
Pretreatment
Posttreatment
PPM IU2LC7IC1DE
">OT-ODE-DOD
.S3
.29
1.65
.94
1.97
1.32
_
1.64
.09
.08
.22
.02
Oielci'ln
.02
.01
.04
.09
.13
.OS
_
.00
.01
Trice
.05
Trace
lieptochlcr Epoxirie
.05
.53
.04
1.69
.04
.04
—
.02
.01
.04
.03
.00
* {Oberheu, 1971)
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III.r>,3. ..'necific Sff.-.'cts of tleptachlor on jj^jh and Wild' ife Following
Use to Cs \tjro_l Fire Ants -- Four farms were surveyed for £:Lsh and
wildlife effects after treatment with heptachior at 2 pounds active
per acre for fire ant control. The following crustacean, fish and
wildlife deaths were observed within 3 weeks after application: 53
mammals consisting of 12 species; 222 birds consisting of 28 species;
22 reptiles consisting of at least 8 species; many species of frogs;
several kinds of cray fish; and, many fish including 8 species (Smith
and Glasgow, 1963).
In a 2-year study carried put to determine the effects of heptachior
on a bird population during fire ant control, the pesticide was applied
at 0.25, 0.5, and 2-pounds per acre. After application, there appeared
to be no arthropod population and alterations in the behavioral patterns
of birds and bird mortality were observed. The nesting and ground-
dwelling insectivorous birds were most severely affected. Fairly
complete recovery of both bird and insect populations occurred 1 year
after the last application of heptachior (Ferguson, 1964).
In 1957, the U. S. Department of" Agriculture in cooperation with several
states treated approximately 27 million acres with 2 pounds active
heptachior per acre for fire ant control. The bird nesting success
for a treated study area (May 1958) was only 11.4 percent, and the
nesting success increased to 45.4 percent in 1959 (Pimentel, 1971).
III.E. Toxicity of Heptachior to Fish and Other Aquatic AnimaL Life —
Table III.E. summarizes the toxicity of heptachior to fish and other
species of animals which are commonly found in water. In general, these
data would indicate that certain species are readily affected by small
amounts of heptachior.
Trout withstood exposures to larger amounts of heptachior at lower
temperatures (Macek, et al., 1969). Bluegill growth was reduced in
heptachlor-treated (0.05 parts per million) ponds, averaging only
7,85 grams after 84 days compared with the controls which grew to
13.5 grams in the same time (Cope, 1966). It was (Andrews, et al.,
1966) found in an investigation of the persistence of heptachior in
fish that 50 percent of the chemical was lost in about 1 month.
Samples of fish were collected from 50 sampling stations locat_i in the
Great Lakes and in the major river basins throughout the United States
for a study of pesticide residues. Heptachior and heptachior epoxide
were found with greater frequency among samples taken from the lower
Mississippi. Greatest amounts were found in specimens from the Great
-44a-
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TABLE III. E.
Tlu 1^50 of heptachlor for arthropods and various fishes
Species
Fish
Rainbow Trout
Harlequin fish
Bluegill
Goldfish
Mosquito fish
.Exposure
(hours)
24
24
24
48
96
96
48
LC5Q
(ppm)
0.250
0.015
0.090
0.026
0.019
0.230
0.070
Reference
Mayhew
Cope
Alabaster
Cope
Henderson, Pickering
and Tarzwell
Henderson, Pickering
and Tarzwell
Boyd and Ferguson
Year
1955
1965
1969
1966
1959
1959
1964
-45-
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TABLE III. E.
The LC5Q of heptachlor for arthropods and various fishes
Exposure
LC'50
Species
Stone fly (Pteronarcella badia)
(hours)
24
(Pteronarcys californicus) 24
nymph (P. californicus)
(Claassenia sabulosa)
',.'a';er flea (Daphnia . pulex)
Amphipod (Ganunarus lacustris)
Sand Shrimp
Grass Shrimp
Permit Crab
48
48
24
48
24
24
24
24
Xppm) Reference
0.006
0.008
0.006
6.000
0.009
0.042
0.150
0.110
76.500
0.460
Sanders
Sanders
Sanders
Cope
Sanders
Sanders
Sanders
liisler
Eisler
Eisler
& Cope
& Cope
& Cope
& Cope
and Cope
Year
1968
1968
1968
1966
1968
1966
1969
1969
1969
1969
-46-
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Lakes -and Atlantic .-ireas (0.01-;';,46 rpm), Hepta-iilor c-'_ heptaciilor
epoxide were not detected in s^ci^as from the interior basins, bui
were fon?iu in less than 10 percant of the specimens from the California
streams, Columbia River, Pacific Coast streams and Alaska (Henderson, '-
et_al., 19C9).
Heptachlor and heptachlor epoxide were not detected in 807 composites
representing 30 species of fish from the Pacific Ocean (Duke and
Wilson, 1971).
III.F. Studies of Heptachlor Which Indicate Biomagnification of the
Pesticide May Be A Significant Environmental Factor — Oysters exposed
10 days in flowing sea water that contained 0.01 parts per million
heptachlor concentrated the pesticide in their bodies 17,600 times
(Wilson, 1965).
In pond water containing .05 parts per million heptachlor, bluegill
fish concentrated heptachlor to a level of 15.70 parts per million
(Cope, 1966).
-47-
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CHAPTER III
t>
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* •
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t
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Biol. Prob. Water Poll., Trans. 159 Seminar, Robert A. Taft
Sanit. Eng. Ctr. Tech. Rep. W60-3:76-92 (1959).
-49-
-------
Knutsox, H. , Kadoum, A. M. , ar.d Hopkins, T. L. Insecticide usage ar'i
residues in a newly developed Great Plai~-s Irrigation District.
Pesticides Monit. £. 5(l):17-27 (1971).
. Kreitzer, J. F., and Spann, J. W. Mortality among bobwhites confined to
'"••• a heptachlor contaminated environment. £. Wildlife Manag. 32:874-
878 (1968).
Lichtenberg, J. J., Eichelberger, J. W., Dressman, R. C., and Longbottom,
J. E. Pesticides in surface waters of the United States -
a five-year summary, 1964-1968. Pesticides Monit. J_. 4(2):
71-86 (1970).
Lichtenstein, E. P., and Schulz, K. R. Epoxidation of aldrin and heptachlor
in soils as influenced by autoclaving moisture and soil types.
£. Econ. Entomol. 53:192-197 (1960).
Lichtenstein, E. P., and Schultz, K. R. Residues of aldrin and heptachlor
in soils and their translocation to various crops. _J. Agr.
Fd. Chem. 13:57-62 (1965).
Lichtenstein, E. P., Schulz, K. R., Fuhremann, T. W., Liang, T. T. Degradation
of aldrin and heptachlor in field soils daring a 10-year period—
translocation into crops. J_. Agr. Fd. Chem. 18(1) :100-106 (1970).
Macek, K. J., Hutchinson, C. , and Cope, 0. B. The effects of temperature on
susceptibility of bluegills and rainbow trout to selected pesticides.
' 'Bull. Environ. Contain. Toxicol. 3:174-183 (1969).
Manigold, D. B., and Schulze, J. Pesticides in selected western streams: a
progress report. Pesticides Monit. J. 3(2):124-135 (1969).
Mayhew, J. Toxicity of seven different insecticides to rainbow trout,
Salmo gairdnerii Richardson. Proc. Iowa Acad. Sci. 62:599-606
(1955).
Miles, J. R., Tu, C. M., and Harris, C. R. Degradation of heptachlor epoxide
and heptachlor by a mixed culture of soil microorganisms. ;J. Econ.
Entomol. 64(4):839-841 (1971).
Mullins, D. E., Johnsen, R. E., and Starr, R. J. Persistence of organochlorine
insecticide residues in agricultural soils of Colorado. Pesticides
Monit. J. 5(3):263-271 (1971). .
Nash, R. G., and Beall, M. L. Jr., Vapors - another route of plant contamination.
Agr. Res. 18(9):3 (1970).
Oberheu, J. C. Effects on'fish and wildlife of heptachlor applied to eradicate
the sugarcane root weevil in'Apopka, Florida. Proc. of the 24th
_Ann. Conf., Southeastern Assn. jxf Fish ^and Game Commissioners.
Sept. 27-30, 1970. ' '
-50-
-------
Piment^l, T1. nco.lu.t, Leal effects ot pesticides on u'>ntarget species.
Executive Office of the President, Office of Science and Technology.
220 pp. (June 1971).
Rosene, W. The effects of field application of he>tachlor on bobwhite quail
and other animals. _J. Wildlife Manag. 20i.f 554-580 (1955).
Sanders, H. 0., and Cope, 0. B. Toxicities of several pesticides to two
species of Cladocerans. Trans. Am. Fish.. Soc. 95:165-169 (1966).
Sanders, H. 0., and Cope, 0. B. The relative toxiiities of several pesticides
to naiads of three species of stoneflies.. Limnol. Oceanogr. 13:
112-117 (1968). ~~'
Sanders, H. 0. Toxicity of pesticides to the crustacean, Gammarus lacustris.
Tech. Paper 25. Bur. Sport Fish. Wildlife, U.S. DeptT Interior,
18 pp. (1969).
Schwab, G. 0., Taylor, G. S. , and Waldron, A. C. Feasure pollutants in
agricultural drainage. Ohio Rept. Res. aid Develop. 55(4):
87-89 (1970).
Sievers, D. M. , Lentz, G. L. , and Beasley, R. P. Ihvement of agricultural
fertilizers and organic insecticides in .-airface runoff. Trans.
Am. Soc. _Agr. Eng. 13(3):325 (1970).
Smith, R. D. , and Glasgow, L. L. Effects of heptadilor on wildlife in
Louisiana. Ann. Conf. Southeastern Assoc.. Game & Fish Comm.
17:140-154 (1963).
Stevens, L. J., Collier, C. W., and Woodham, D. W. Monitoring Pesticides
in soils from areas of regular, limited, and no pesticide use.
Pesticides Monit. J. 4(3):145-164 (1970)..
Stewart, K. D. R. , and Fox, C. J. S. Persistence d: organochlorine insecticides
and their metabolites in Nova Scotian soaLs. _J. ECon. Entomol.
64(2):367-371 (1971).
Tucker, R. K. , and Crabtree, D. G. Handbook of To>icity of Pesticides to
Wildlife. U. S. Dept. of Interior. Resource Pub. No. 84, 131 pp.
(Rev., June 1970).
Wilkinson, T. A. S. , Finlayson, D. G. , and Morley.II. V. t Toxic residues in
soil 9 years after treatment with aldrin and heptachlor. Science
143: 681-682 (1964).
Wilson, A. J. Chemical assays p. 6-7. In Annual Ibport of the Bureau of
Commercial Fisheries Biological Laboratory, Gulf Breeze, Florida,
Fiscal Y-o-ai- ending June 3C, i'965. U.S. Jlir. Comm. Fish. Circ.
247 (1965),
-51-
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CHAPTER IV
RESIDUE IN CROPS AND FOOD ITESB
The use pattern for heptachlor has changed since its introduction
as an insecticide. Prior to 1960, heptachlor was widely used on
forage crops, oil crops (seed), vegetable crops, careal crops, sugar
beets and crops such as peanuts. The present uses of heptachlor have
been primarily as soil applications and seed treatments.
•IV.A. Tolerances - Tolerances for heptachlor have fteen established by
the Environmental Protection Agency in the United States at 0.1 ppm
for cabbage, snap beans, lettuce and rutabagas. Zaro or extended
tolerances are in effect for barley, beans, blackberries, blueberries,
boysenberries, chestnuts, citrus, corn, cotton, cranberries, dewberries,
oats, peaches, pears, peppers, pineapples, raspbecri.es, rice, rye,
sorghum, soybeans, tomatoes and wheat. Exhibit I fives the details of
approved tolerances for heptachlor.
Action levels have been established for residues of heptachlor in some
foods or crops for which formal tolerances have no± been established.
These action levels are the Food and Drug Administration's criteria
for legal action. The following action levels ha\rt been recognized
for heptachlor and heptachlor epoxide, individually or in combination:
0.3 ppm for (edible portion only) fish (smoked, frozen, canned or raw):
shellfish (smoked, frozen, canned or raw); 0.05 pprc for apricots, black-
berries, blueberries, boysenberries, citrus fruit, cranberries, currants,
dewberries, elderberries, figs, gooseberries, huckfleberries, loganberries,
melons, nectarines, pears, plums, quinces, raspberries, strawberries, arti-
chokes, asparagus, beans (except snap beans), broccoli, celery, collards,
cucumbers, eggplant, endive, kale, mustard greens, okra, parsley, peppers,
pimentos, pumpkins, squash, spinach, summer squash^ swiss chard, winter
squash; 0.03 ppm for eggs, rice, hay (all not covered by tolerances); and
0.3 ppm in fat of cattle, sheep, goats, swine, and poultry (Pippen,
H. N., 1972).
IV. 3. Acceptable Daily Intake - The estimate of acceptable daily intake
for man has been established at 0-0.0005 rag/kg body-weight. Lavels of
heptachlor causing no significant toxicological effect in experimental
animals were: in rats the level was 5 ppm in the diet, equivalent to
0.25 mg/kg body-weight/day; and, in dogs the level was 2.,5 ppm in the
diet, equivalent to 0.06 mg/kg body-weight/day (FAlD/WHO, 1971).
-52-
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bs::!-, ... .••ro'.s. -.LJl/.^v-cr. coli.v..;.. •..?•!:-
toiijt;... : -uo. :-i'i:7,ar. ruU'-.b.-Tas Cvooto), .r,y-
beoris (iiry unu juceulcni). sweet com
(kernels plus cob with hi;:!: removed),
turnip crceaa, turnips (roots).
Also, the following tolerances for resi-
dues of captan arc established on an
Interim basis pending evaluation of new
data to be presented to the Food and
Drug Administration before January 1,
1970, on the transmission of such residues
to meat, milk, and eggs from feeding
.cattle or poultry with raw agricultural
'commodities or their byproducts when
such commodities have been treated with
captan:
100 parts per million In or on almond
• hulls.
25 parts per million In'or on beans (dry
and succulent), grapefruit, lemons, limes,
; oranges, pineapples, potatoes, tangerines.
2 parts per million in or on almonds.
/ § 180.104 Heptachlor and licptechlor
epoxide; tolerances for residues.
Tolerances for total residues of the
Insecticide heptachlor (1,4,5.8,7,8.8-hep-
tachloro-3a,4,7,7a-tetrahydro-4,7-meth-
anolndena) and Its oxidation product
heptachlor epoxlde (1.4,5.G.7.0,8-heptr.-
. chloro - 2,3 - epoxy - 2.3.3a,4.7,7a - hcxa«
hydro-4,7-methanolndene) from appli-
cation of heptachlor In or on raw agri-
cultural commodities are established as
follows:
C.I part-per million in cr oil cabbase,
lettuce, rutabagas, snap beans.
Zero in or on alfalfa, apples, barley,
beets (including sugar beets), black-eyed
peas, brusseis sprouts, carrots, cauli-
flower, cherries, clover, com. cottonseed,
cowpeas, grain sorghum tmllo), grapes.
gross (pasture and range), kohlrabi,
lima beans, meat, mil:-;, cats, onions,
peaches, peanuts, peas, pineapple, pota-
toes, radishes, rye, sugarcane, sweet
clover, swestpotatoes, tomatoes, turnips
(Including tops), wheat.
§ 180.105 Dcmelon; tolerances for resi-
dues.
Tolerances for residues of the insecti-
cide demeton (a mixture of O.O-tilethyl
O(and S)-2-(ethyllhio) ethyl phospho-
rothloates) in or on raw agricultural
commodities are established as follows:
12 parts per million in or on alfalfa
hay, clover hay.
5 parts per million in or on almond
hulls, barley (green fodder and straw),
fresh alfalfa, fresh clover, oats (green
fodder and straw), surrar beet tops, and
wheat (green fodder and straw).
1.25 parts per million in or on grapes,
hops.
0.75 part per million In or on almonds,
apples,' apricots, barley rrrain, broccoli,
brussels sprouts, cabbane. cauliflower,
celery, cottonseed, filberts, grapefruit,
lemons, lettuce, muskmclons. nectarines,
oat grain, oranges, peaches, pears, psas,
pecans, peppers, plums (fresh prunes),
potatoes, strawberries, tomatoes, wauiuts,
wheat grain.
^cn in ^. on i.or:jhum
0.2 pr.rt v.:r r.-.
Knur., :;orr;'.u."ii forase.
§ ISO.IOfi Uitiron; lolcr:mrt s for resi-
dues.
Tolerances for residues of the herbi-
cide dluron CS-'S/.-rilcnlorophc".:;; ''-!,!-
dlmethylurea) in or on rav,- p.r.:r!rul!;u-al
commodities are established as follows:
7 parts TKT million in or on asparagus,
Bermudairrass. and Ecrmudafirnss hay.
2 parts per niillion In. or on p.lfilfa;
corn fodder or fcra?e (Including sweet
corn, field corn, und popcorn) ; jrass
crops (other than Bermudagrass) ; ^rsss
hay (other thr.n Bermuciagmss hr.y) ;
hay, forane, and straw of barley, cats,
rye, and wheat; hay and forage of
birdsfoot trefoil, clover, peas, and vetch;
peppermint hay, sorghum fodder and
forage.
1 part per million In or on r.pplss, arti-
chokes, barley grain, blackberries, blue-
berries. boysenberrles, citrus fruits, com
in grain or ecr form (Including sreet
com, field com, popcorn), cottor.rsed,
currents, dory-berries, gooseberries.
Erairps, huckleberries. loganberries, cat
.3 rain, olives, pears, peas, pineapple, po-
tatoes, raspberries, rye grain, sorrhum
sraln, sugarcane, vetch (seed), v.-i.eat
grain.
1 part per million In or on meat, fat,
and meat byproducts of cattle, scats,
hogs, horses, and sheep.
0.1 part p^r million (nejfltoibls r?ol-
due) in or on bananas, nuts.
§ 130.107 Aramilo; lolcruncrs for resi-
dues.
A tolerance of zero Is establlshsd for
residues of the Insecticide Aramite f2-
(p-fert-butylphenoxy)-iscpropyi-2-ch!o-
roethyl sulflte) in or on each of the fol-
lowing raw agricultural commoditisa:
Alfalfa, apples, blueberries, cantalctps,
celery, cucumbers, grapefruit, grains,
green beans, lemons, rauslsnoirns,
oranges, peaches, paars, plums, raspi-sr-
ries, soybeans (whole plant), strawi:r-
ries, swent com (kernels) and forise
thereof, tomatoes, watermelons.
§ 180.103 Momiron; tolerances fur rwi-
dues,
Tolerances for residues of the herbi-
cide monuron (3-(p-ch!orophsnyl)-!,l-
dimethylurea) ars established la or on
raw agricultural commodities as jolloTs:
7 parts par million in or on esparaois.
1 part per million in or on avocr-cja,
citrus citron, cottonseed, irrtpefriit.
grapes, kumquats. lemons, limes, on:;xia
(dry bulbs only* , oranges, pineapple.
spinach, sugarcane, tangerines.
§ 180.109 Klliyl •t.4'.itifli|.>rol..-nzil£!c;
tolrranccf lOr rcviilucs.
Tolerances for residues of t!;s JnssKt-
clde ethyl 4.lm-:,.~d
hulls.
0.2 port, per rci.'.'on in 01 en a.:::
\vnlnui!>.
g 1HO.HO Mnnrb; lolcrnncf* fo.-
duos.
Tolsrances for rc.':)i5nrs of tJ-.s .. -
elds moncb (mc;>.TD.r.oii5 othylc-n: .
in or on raw agricultural commoalt..
43 pai-ts per million In or on r
beat tops.
15 parts per million in or on br>n.x-.
of which not mprr> than 2 carts per :_
lion shall be in :he pulp after p=.:
removed and discarded. The toi2ra.
applies to uccumujatlva reslduss r:
both prcharvest mid poslhrjvest ur-:.
10 pcrts per mllilcn in or on npric;
beans (succulent i'onn), broccoli, bi
sels sprouts, cabbage, cauliflower, eel.-
Chinese cabbage, uollArcis. endive 'c:-
role), kale, kohlrabi, lettuce, inus::-
greens, nectarines,- papayas, peac::
rhubarb, spinach, turnip tops.
7 pr.rt-s per million !n cr en r.v.;-'
beans (dry form), crrro;;. era:-.;);':--
cucumbers, er:rp«-r.t:, -~c. '.".
melons, onions, pep:--nj. pumpliias, T-.
mer squash, sweet corn (iicmels piur. •
with busies removed), tomatoes, tu:
root:, winter squrvi.0.
0.1 PJJ^; per siiiiisn ia or on alrssn.
potato::.
§ 120.111 T'laiuUiiuii; tolerances <
rceiducs.
Tolerances arc establiihya for rcsirJ-
of the insecfclcids r.na.'.'-.'.U;on (O,O-
methyl dtthiophoaph.ata r.i clethyl ::..
captojuccinate) in or e:i rr\w a,-;--.1
turr.l coiruT.oditles as ;:oilov/s:
From preharveatf.pr'Ucaiion: 125 TV
per million in or on aUalia. ciz:
cowpnn, forage and ;;r.r, jrr-ss, grass '••
lespsdssa hay and .-.tratr. lupine hav E
straw, v:eonut forr.?e ".:id hay, soyr:-
forage and hay, and vetch hay r.:
straw.
Prom prehorvest application: 50 pro-
per million hi or on almond hulls.
Prom prcharvest r.pniicatlon: 3 pi:-
per million In or on apples, carl".;'
asparagus, avocados, bi;s.;is, beets u.
cludin? tops), blucirierrles, hlucberr.
boyson berries, brccco:i, brussels sprc-..
cabbage, cinrots, cauilllower, cvr.c
chernes, collards, corn i'orage, cranL-.
rles, cucumbers, currants, danuu'::
dates, dev.'beiTics. e^-plonra. nndivo '•:
caro'.c). figs, ffarlic, cosseberries. rr.v:
fnsit, ftrr.pes, guavas. horseradish, r:.
kohlrabi, kumquats, Icr.:^;, ;cmon;. :_
tils, luspndeza seed, l?tti:c?. '.'iaos, .-.-• ' .
berries, lupine ieed. incncros, rnr;--
mushrooms, mustard GT^'.W, •,-.CCIT.::
o!-a, ov.lons (Inc.'tnl'.nT -yroen on: .•:•.•
oranir.is. parclcy, par-nir-", pasolon ;.;
peaches, peam, peas, pr-avines. pc-?.v..
hay, ptcans, peppermint, ijepoers, ;:;•
applos. plums, pot,"tO'.T-:. ;jrun.:3. pu.:.
tins, ciuincos, i-atli.',h->s, r:-:pl)c-rr:::-.:. r: ..
bagaa, salsify (Inciuainr; tops), .-.::;•.;:,
FEDERAL BEGiSTER, VOL. 36, NO. 228—fHUKSCAV, MO-.JMBCR 25,-
-------
TABLE 2:—Dietary ir.takc of pesticide chemicals
COMPOUND
AUIrin x-i
Oiclilrin
Total
Carbaryl
DDT
DDE
TIM;
Total
Dichlorvos
Diplu-nyl
Gamma BHC (Lindanc)
Bromide
IIcr>i:ich!or
Hc.-v.achlor cpoxidc
Total
Malachion
D:a/inpn
Paratliion
nuc
Dicofol (Kclihanc)
Erulrin
Total Chlorinated Pesticides
Tot:il Orpanopho.spiiatcs
Total Herbicides
Mc/Ko or BODY WI-ICIM/DAY
V.'HO-FAO
Accrr-T.
DAILY
INTAKE
0.0001
0.02
0.005
0.004
0.125
0.0125
1.0
0.0005 ,
0.02
0.002
0.005
TOTAL Dnrr STUDIES
1965
I):!""!!!!
0.00008
0.00009
0.002
0.0004
. 0.0003
0.0002
0.0009
IVf.6
n,<:i"Mii
0.0(1009
0.( KIOI
0.0005
0.0. 105
O.O.iO.l
0.(KII)2
(l.lilll
1967
n-t'l'!!'"
0.00005
0.00006
0.0001
0.0004
0.0002
0.0002
O.OOO.S
0.00007
1 0.39
0.000003
O.OCOM
0.00003
0.00003
0.00004
0.000009
0.0012
0.00012
O.OfK06
• o.;:
0.00005
o.tiooos
0.01)01
0.0;I002
o.oiiooi
0.00004
O.noni
0.000004
0.0016
0.00014
0.00022
0.00007
1 0.29
o.oooooi
o.diiooz
O.OOC.02
0.0002
o.oooooi
0.00001
0.00003
0.0002
0.000004
0.0012
0.00025
0.00005
1968
luiiitiOl
0.00(105
0.00006
—
0.0003
0.0002
0.0002
0.0007
DIITCKMIN
DETIIRMIN
0.00004
1 0.41
O.OOOOOI
0.00003
0.00003
0.00004
O.OOOOOI
O.OOOOOI
0.00004
0.0(101
o.ooooi
0.0010
0.00007
0.00006
I0f,9
tl.llllilcthlll
0.00007
0.00007
0.00004
11.01102
0.01)02
0.0001
. 0.0005
1970
i|.iiuiifiHi|(i
0.00007
0.00007
—
0.0002
0.0001
0.0001
0.0004
6-yr.m
AVCRAGC
O.i'ilHH!
0.00007
0.00008
0.0005
0.0003
0.0002
0.0002
0.0007
0.00002
' 0.24
O.OOOOOI
0.00003
0.00(103
0.0002
0.000004
0.00001
0.00002
0.0001
0.000004
o.ooos
0.0002.1
0.00005
0.00002
1 0.24
0.000000 1
0.000,12
0.00002
0.0002
0.00001
0.000003
0.00002
0.00005
0.0000005
0.0006
0.00026
0.000008
. 0.00005
1 0.30
O.OOOOOI
0.001)03
0.00003
0.0001
0.00001
o.ooooi
0.00003
0.0001
O.OOOO05
0.001 1
0.00019
0.00008
1 Total bromides present—includes naturally occurring bromides.
-54-
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V,C. Residues in Food - Foods arc monitored for pesticide itsiducs
through market-basket surveys. Market basket saToles for the toial
diet studies are purchased i.'rom retaJ 1 stores, bimonthly, in five
regions of the United States. A shopping guide totalling 117 foods
for all regions is used, but not all foods are represented in all
regions because of differences in regional dietaiv patterns. The food
items are separated into 12 classes of similar fcads and prepared for
consumption by dieticians. After preparation, tin food items are
composited into 12 classes of similar foods (e.g.,. dairy products;
meat, fish and poultry; legume vegetables; and garden fruits)for more
reliable analysis and to minimize the dilution faitor. Each class in
each sample is a composite. The proportion of f:cod items used represents
the high consumption level of a 16-to-19-year-ol'd male. Each sample
represents a two-week supply of food (Duggan, R. 3., et_ al_. , 1971).
Another method of sampling residues is via surveillance samples which
are generally collected at major harvesting and distribution centers
throughout the United States and examination in 36; FDA district labora-
tories. Surveillance samples are not obtained in retail markets.
Samples of imported food are collected when offeisrd for entry into the
United States.
V.C.I. Recent Market Basket Surveys - Table 1 gi?es the dietary intake
of heptachlor and heptachlor epoxide for 1964-1963 (Duggan,_et al.. 1971).
These results obtained during a five-year period, June 1964-April 1969,
are compared with the acceptable daily intake (AJE) established by the
FAO-WEO Expert Committee. The amounts of these pesticide chemicals
calculated from this high consumption diet (FAO-U10), approximately twice
that consumed by a normal individual, are well below the daily intake
regarded as safe by the FAO-WEO Expert Committee oxcept for the combined
residues of aldrin and dieldrin which have approaihed the ADI during the
period of this study.
Heptachlor epoxide was reported as present in a mjority of food groups
for samples of domestic food examined during the qeriod of July 1, 1963-
June 30, 1969. A total of 111,296 samples of donHStic food were examined
(Duggan, et_ al. , 1971).
V.C.2. United States Department of Agriculture I-feat and Poultry Sampling—
Meat and poultry samples are obtained from animal* and poultry slaughtered
in all federally inspected establishments and froa shipments offered for
entry into the United States. The samples are examined in seven laboratories
of the Consumer and Marketing Service, USDA (Duggin, .et al. , 1971).
-55-
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HciOtachlor and heptiT.Iiior e.uorid£ were nmunjj Che aight pesticide
chemict is commonly found in the fat of poulr.ry duaing the fwc-year
period reported (FY1968-1969). The incidence of HDT, dield"in, and
heptachlor-heptachlor epcxide exceeded those fount! in any other class
of foods.
Data from a total of eight studies on the relationship between the
levels of heptachlor and heptachlor epoxide in fesd to the levels
in meat and milk show that the maximum residue lexel in animal feed
that can be permitted without exceeding the practical residue limits
for these animal products is 0.04 ppm of combined residues (FAO/WEO,
1971). Further, FAO/WHO indicated that residues of: heptachlor and its
epoxide should each be determined and the sum expressed as heptachlor.
.The tolerances of FAO/WHO apply to residues from Explication to seed
and soil only.
-56-
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CHAPTER IV
BIBLIOGRAPHY
/:>
(Residues in Crops and Food Items)
.Duggan, R. E., and Lipscomb, G. Q. Dietary Intake, of Pesticide Chemicals
in the United States (II), June 1966-April 1968. Pesticides
;. Monit. J. 2(4): 153-162. (1969).
Duggan, R. E0, Lipscomb, G. Q., Cox, E. L., Heatwcle, R.E., and Kling,RoC0,
Residues in Food and Feed--Pesticide Residue Levels in Foods
in the United States from July 1, 1963 to June 30, 1969,
Pesticides Monit. J^ 5(2): 73-212. (19.71).
Food and Agricultural Organization of the United Rations World Health
Organization. 1970 Evaluations of Some Pesticide Residues
in Food. 571 pp. FAO/WHO. Rome. (1971)..
Pippen, H. N., Current FDA Action Levels for Pesticide Residues
(Personal Correspondence). (July 26, 1912).
-57-
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CHAPTER V
The Toxicology and Epidemiology of Beptachlir
Technical heptachlor is a mixture of compounds consisting of heptachlor,
gamma-chlordane, nonachlor, hexachlorocyclopentadicne and traces of
octachlor. Since heptachlor is a complex mixture , its toxicity consists
of the sum of the intrinsic toxicities of the varicis components.
Accordingly, the toxicity of technical heptachlor xiil vary as the
ratios of its components vary.
V.A. Toxicity to Laboratory Animals - The toxicities: of heptachlor, its
oxidation product, heptachlor epoxide, and several Heptachlor metabolites
and analogues have been investigated in certain speaies of laboratory
animals. These studies include, but not for all ccnpounds, the effects
of both short-and-long-term administration, the effects on reproduction
and the viability of the young produced, mutagenic and teratogenic effects,
and the ability of the compound to increase the incidence of tumor formation.
V.A.I. Acute Toxicity - When absorbed in sufficient concentrations into
the tissues of experimental animals, heptachlor or ±its epoxide produce signs
and symptoms of toxicity which are related to centrrl nervous system stimu-
lation. These signs and symptoms are characterized by hypersensitivity to
auditory or tactile stimuli, ataxia, tremors, lac.viration, salivation, severe
clonic and tonic convulsions, respiratory difficul'ifes, weakness, and terminal
coma. In some species, depression of body temperature occurs during convul-
sive seizures. These responses to toxic doses arc-not influenced appreciably
by the route of absorption of the compounds. The tiine of death may vary from
2 hours to 11 days after administration of the test compound.
V.A.I.a. Acute Oral Toxicity - Numerous studies ha*e been carried out on
the toxicity of heptachlor, heptachlor epoxide, and related compounds in
experimental animals. The acute oral LD^Qtg of hepjachlor and related
compounds appear in Table V.I.
V.A.l.b. Acute Dermal Toxicity - Only a limited nuiber of studies have
been reported for the dermal toxicity of heptachlor.. Gaines (1969) reports
heptachlor (in xylene) to have an LD5Q of 195 mg/'-g in male rats and 80
mg/kg in female rats. Lehman (1952) reports an acitie dermal LD^Q of
heptachlor (dry powder) in rabbits to be greater t'hm 2000 mg/kg. There
was no apparent skin irritation.. The animals di..pjayed severe anorexia,
hyperexcitability, and convulsions. _A dermal exposire of 5 hours duration
to 940 mg/kg of heptachlor epoxide, 10 percent in paanut oil, caused re-
duction in rates of growth of male and female rats. In rabbits, four
consecutive daily exposures of 5 hours each to 300 -ig heptachlor epoxide,
dermally, produced a decrease in weight gain (Witheiup, et al. , 1959a).
-58-
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Acute Oral
's of Heptachlor and Related Compounds
Compound
Hfe.pt ichlor
Heptachlor-
epoxide in
peanut oil
'ieptachlor-
epoxide in
Methocel
Heptachlor-
epoxide
Heptachlor+
Hp.ptachlor-
'ipoxide-l:3
u-chlcrdane
y-chlordane
a-y-chlordane
.1 -hydroxychlordene
^onachlor
Chlordene
3-chlorochlordene
i-chlordene epoxide
Animal
Rat (M)
Rat (F)
Mice (M)
Mice (F)
Miee (M)
Rats (M)
Rats (F)
Dogs (M)
Dogs (F)
Rat (M)
Rat (F)
Rabbit (F)
Mice (M)
Mice (F)
Mice (M)
Mice (F)
Rat (M)
Rat (M)
Rat (M)
Rat
Rat**
Rat
Rat**
Rat**
Rat**
LDrn(mg/kg)
60(38-95)
142(119-169)
93.9(59.3-148.2)
104.8(71.5-153.6)
-jfcMOa.i-fcg.bj
61.3(42.1-88.0)
46.5(34.5-62.9)
8-55*
16-80
107(64-178)
142(110-184)
110(52-232)
41.3(35.4-48.2)
43.6(30.6-62.1)
56.2(49.9-63.4)
. 68.5(55.6-34.3)
392(345-446)
327(261-408)
371(287-480)
2402
^4600
326
t>4600
>4600
Reference
Witherup
Witherup
Wazeter
Wazeter
Wifehetup
Witherup
Witherup
Witherup
Witherup
, e_t al.
, et al.
(1971)
(1971)
, e£ ai.
, et al.
, et_ al.
, et al.
, et al.
(1959a)
(1959a)
(1959a)
(1959a)
(1959a)
(1959a)
(1959a)
Wazeter, et^ al . (1968)
Wazeter, et al. (1968)'
Wazeter, ££3^. (1968)
Wazeter (1971)
Wazeter (1971)
Wazeter (1971)
Wazeter (1971)
Wazeter, £t aJ. (1971)
Wazeter, et^ al^. (1971)
Wazeter, e_t aj^. (1971)
Ingle (1962)
Mastri, C., Keplinger, M.L., and
Fancher, 0 E. (1969)
Ingle (1962)
Mastric, Keplinger, M.L.,
and Fancher, O.E. (1969)
it it
'"'Lethal range -59-
*• -Groups containing equal numbers of male and female animals.
-------
V.A.l.c. Acute Intravenous Toxicity - When heptacMor epoxide was
administered intravenously to female rabbits as a I percent solution
in peanut oil, deaths occurred 20 minutes to 2 days after the injection
of 5 mg/kg and within 10 to 20 minutes after the injection of 7 mg/kg.
In male rabbits, 10 mg/kg killed half of the animals within 8 hours
(Witherup, et al. , 1959a).
V.A.2. Subacute Toxicity - For the sake of organization studies of less
than 2 years duration have been considered under "subacute" toxicity, •
regardless of the species of animal involved.
The effects of the administration of heptachlor or its epoxide to experi-
mental animals for periods of up to 1 year are qualitatively similar to
the administration of the compounds for longer periods of time ; the one
exception was the incidence of neoplasms. The liver appears to be the
target organ, with the extent of alteration increasing with the concentration
of the pesticide in the diet and the duration of administration. The
alterations include increased liver weight with hepatocellular changes
consisting of enlargement of the hepatic cells in the central zone of the
lobule. These enlarged cells present aggregation of the acidophilic cyto-
plasmic granules in the cell periphery. There also appears to be a decrease
in the number of these granules. After longer expcsure there is an accumu-
lation of lipid matter in the cytoplasm of the hepatic cells. Changes have
also been reported in the adrenal medulla and the Sidneys of some animals.
V.A.2.3. Subacute Oral Toxicity - In the studies reported below, hepta-
chlor, heptachlor epoxide, or a mixture of the two compounds were fed to
rats or dogs for periods of time up to 1 year.
The effects of feeding subacute levels of 1 to 32 jipm heptachlor epoxide
were studied in 4 and 6 week old female albino CNF rats. The purity of
the heptachlor epoxide was not stated. Each group was composed initially
of 4 rats that were 4 weeks of age and 3 that were 16 weeks of age. A
control group of similar composition was utilized. The test animals were
fed on diets containing 1, 2, 4, 8, 16, and 32 ppm heptachlor epoxide. The
younger rats were fed the pesticide for 49 weeks sad. the older rats for
68 weeks. Four of the seven rats fed 32 ppm died within 48 weeks. Three
of these were younger rats. One death occurred in each group receiving
0, 2, or 8 ppm heptachlor epoxide at week 63, 57, snd 48, respectively. No
signs of toxicity were observed in the surviving animals. Increases in
weights of livers could be detected in the animals fed at the'4 ppmflevel
and were proportionately greater in association with the feeding of higher
concentrations of heptachlor epoxide in the diets. The weights of the
brains, hearts, lungs, and kidneys were normal. Tbe weights of the adrenal
and thyroid glands were unusually high' in the younger rats at the 2 ppm
level; average weights of these glands from the animals at other feeding
levels were within normal limits (Witherup, et al.., 1959a) .
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Groups 01: weanling Sprague--Dr."lsy rats, cousistim-. or 25 males an1
25 females were fed diets containing 0 to 2000 ppn: l-hydroxychlordene /:.
for 224 days. At 1.1.0 days three females and three males were separated
from each group and mated. The pups were weaned it. 21 days and examined
for birth defects. The test compound did not increase the mortality
rate among rats of any group during the 224 days dl feeding. One female
at 2000 ppm showed a hepatoma, one male at 500 ppm and one female at
100 ppm showed tumors involving the parotid glands. One control female
showed a mammary gland tumor. No other gross pattelogy was noted. Histo-
pathological changes were noted in the liver sections from rats at 1000
or 2000 ppm. The changes consisted of moderate cyl'.oplasmic margination
in some of the liver cells (Ingle, 1965).
A total of 269 rats of unspecified sex were fed 40.. 45, or 60 ppm hepta-
chlor or 35, 40, or 45 ppm of heptachlor epoxide a?: 40, 45, or 60 ppm of
a 75:25 percent mixture of the two compounds. The purity of the compound
was not stated. After feeding for 140 days, some .rmimals were returned
to a basic uncontaminated diet and others were continued on the test diet.
The animals were then sacrificed after 10, 20, 30, 60, 80, or 120 days
from the 140 day feeding period. Hepatocellular alterations observed after
exposure to the insecticides for 140 days consisted of enlargement of the
hepatic cells in the central zone, of the lobule. Dhese enlarged cells
showed aggregation of the acidophilic cytoplasmic granules in the cell
periphery (margination). At the same time there was a decrease in the
number of these granules. After longer exposure, ohere was accumulation
of lipid material in the cytoplasm of the hepatic aells. Typical liver
lesions were shown to regress after discontinuing Ceding, as evidenced
by the observations of the rats which were returned to a normal diet.
After 120 days, a significant number had normal lixers. The largest
number of recoveries occurred in the group fed heptachlor; next with the
mixture; and least with the group fed heptachlor epxide. Some of the
rats fed a treated diet for 260 days displayed a second type of lesion in
the periphery of the liver lobule, consisting of an enlargement of the cells.
The boundaries of the cells became prominent and the cytoplasm had an empty
appearance. In most instances both were present in the same liver lobule
separated by'a mid-zone of almost normal cells. It was not reported if these
lesions regressed after returning the animals to a normal diet. The examin-
ation of the adrenal medulla revealed a normal morpiologic picture in those
rats that were discontinued and had complete regression of their hepatic
damage. In animals that had not recovered, and in those that were maintained
on the contaminated diet, the medulla exhibited sigis of depletion of
catecholamines. The cytoplasmic granules in these aells were diminished.
Some of the cells showed vacuolation within the cytoplasm.^ These vacuolated
cells were located primarily in the center of the mudulla (Stemmer and Jolly,
1964).
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Thirty female rats of the Wistar strain were ixposal co DDT and hepta-
chlor, respectively. The purity of.the pesticides was not stated. TI;e
insecticides were mixed into the diet in concentraiTLons of 10 ppm DDT 1J
or 10 and 5 ppm of heptachlor. Ten rats were exposed at each level
and, additionally, 10 rats were used for controls. The animals were
sacrificed after 8 months and the livers taken for examination by light
and electron microscopy. Under light microscopy, tile cells in the central
zone of the hepatic lobule appeared swollen. In seme of these enlarged
cells there was margination of the acidophilic granules. The cytoplasm
showed a net-like pattern. Occasionally, a hepatic cell contained fat
droplets. These alterations were seen in both DDT and heptachlor-treated
animals. Under electron microscopy, there was hypertrophy of the rough
and smooth endoplasmic reticulum. The mitochrondria were of normal
structure. The authors suggest these findings indicate an increase in
protein metabolism. Apparently, a true hypertrophy and not.degeneration
of the liver cells is present at this stage (Stemmer, and Hamdi, 1964).
Four groups, each comprising 10 male and 20 female irats, were given daily
oral doses of 0, 5, 50 or 100 mg/kg body-weight of pure heptachlor starting
at about 4 months of age. Administration was continued for 200 days or
until the animals died. By the tenth day all the ac-imals in the groups
fed 50 or 100 mg/kg had died. At day 200, the surviving animals in the
5 mg/kg group and the. controls were sacrificed for autopsy. Prior to death
the 50 and 100 mg/kg groups became irritable and haA accelerated respiration
by the second day. Convulsions preceded death. In the group given 5 mg/kg
no clinical abnormalities were seen until the fiftieth day, when hyper-
reflexia, rapid respirations and chronic convulsions were observed. Two
males and two females in this group died before completion of the experiment,
compared to only one female in the controls. Weighe gain was not affected
by 5 mg/kg. Gross pathology revealed changes in liver, kidney and spleen.
Histopathologic examination showed fatty degeneration of the liver cells
and moderate fatty infiltration of the cells of the urinary tubules, as
well as hyperplasia of the smooth endoplasmic reticalum of the liver and
spleen in the group fed 5 mg/kg(Pelikan, et^ _al., 1938).
Five groups, each consisting of 10 male and 10 female Charles River CD-I
mice, were maintained for 30 days on diets containing 1-50 ppm of a mixture
of heptachlor and heptachlor epoxide. No deaths occurred with 1-10 ppm.
With 25 ppm, one female died at 3 weeks. With 50 pjm, nine males died
between week 2 and week 4 and nine females died between weeks 1 and 3.
Significant pathologic findings were limited to Irrar and consisted of
hepatomegaly and accentuated lobulation in mice fed 10-50 ppm of the
mixture. Livers were enlarged and contained hepatoxytes 'with finely
granular homogeneous cytoplasm. Severity of the lei-ions was dose-related
(Wazeter, 1971).
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Dosts of u.25-2 mg/kj; oi: hepLachlor epox.idc in peanut oil were administered
to beag.'e dogs daily by intubation for 5 to 6 days per week for 54 weeks.
The control animals received peanut oil without the pesticicV.. At 'week. 20,
there was 100 percent mortality in the 2 mg/kg group; at week 43, one animal
receiving 1 mg/kg died. Prior to death, animal receiving 2 mg/kg displayed
"glassy" and slightly protruded eyes. There were periods when auditory and
visual senses were impaired and mild tactile stimuli invoked biting or
snapping. These periods terminated abruptly and animals returned to normal.
Body weight of animals varied inversely with the dosage. At termination,
the liver/body-weight ratios varied directly with the dose of heptachlor
epoxide. Histopathological evidence of degenerative changes in the liver
was characterized by swelling and vacuolation of cytoplasm of hepatic cells
in central zones of lobules. As the dosages increased, lesions were found
in central and- middle zones of hepatic lobules with increased diffuse
degeneration and multiple foci of necrosis. Renal tubule degeneration
was observed in fatal intoxications (Witherup, _et_ ad., 1959a).
Five groups of beagle dogs, each group being composed initially of two males
and three females, were fed diets containing heptachlor epoxide in concen-
trations of from 0.5 to 7.5 ppm for a period of 60 weeks. The mortality was
limited to three deaths, all of which were attributed to incidental infectious
disease. The weight gains in the males was depressed in proportion to the
logarithmic concentration of heptachlor epoxide in the diet. There was no
effect of feeding the test compound on weight gains of the females. Food
consumption was not influenced by the presence of heptachlor epoxide in the
diets of either sex. Liver weights of both male and female dogs increased
with the concentration of the chemical in the diet. Pathological changes
were detected in the liver of one dog fed 7.5 ppm heptachlor epoxide. These
changes were characterized by cloudy swelling of the cells and slight hyaline
clumping of the cytoplasm, with loss of fine glycogen vacuolation and compression
of the sinusoids (Witherup, _et_ al_., 1958).
Ninety-five Wistar rats were given five administrations of 10 mg/kg pure
heptachlor in corn oil each by stomach tube, every second day starting at
10 days of age. Seven animals died before weaning. No early deaths were
recorded among 36 controls given corn oil only. Twenty-nine experimental
animals were killed at 60 weeks of age to detect early changes which were
nevertheless absent. Growth and survival rates were similar in experimental
and control animals. The incidence of tumors at different sites in males
and that of adrenal, thyroid, and pituitary tumors in females were comparable
in both groups; 9 of 28 treated females developed a total of 12 tumors in
various organs (including 5 mammary tumors and 2 renal liipomatous tumors)
whereas 4 of 27 control females developed a total of 4 tumors (2 of which
were located in the breast). In view of the different locations of the
tumors: and the lack of the reproducibility of the finding among males the
results are not considered as evidence of carcinogenicity of heptachlor
under the present experimental conditions (Cabral, et al., 1972).
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V.A.2.L). Subacutc 1/^rnal Toxicity - In the Investigation nf the dermal
toxicities of a number of pesticides, Lehman (1955) studied the effects
of daily applications of sublethal amounts of heptachlor to the skin of
albino rabbits. Lehman reported that there were ro survivors after 14
days of applications of 20 rag/kg heptachlor.
V.A.3. Chronic Toxicity - Two-year or life-span studies in mice and rats
have been considered in this section. The studies have been carried out
using pure heptachlor, pure heptachlor epoxide, or mixtures of the two
compounds. In the studies using heptachlor without specifying purity, it
is assumed that the technical material was utilizel.
The effects of the long-term administration of hepfiachlor or heptachlor
epoxide in the diets of experimental animals is qualitatively similar to
the effects produced by the administration of othea chlorinated hydro-
carbon pesticides. The liver appears to be the orjan most affected by
these compounds in the diet and the effects of hepfeachlor on this organ
are more pronounced than those reported in the subrrcute studies. There
are also alterations in the structure of the hepatic cells. These changes
are characterized by swelling, homogeneity of the cytoplasm, and peripheral
arrangement of the cytoplasmic granules of the hepatic cells in the central
zones of the lobules. Under electron microscopy, ithere is an increase in
the rough and smooth endoplasmic reticulum and the mitochrondria. Hepatic
changes are produced in rats fed 7 ppm or greater Heptachlor in their diets.
At higher levels (40 ppm) degenerative effects on Ohe renal tubules are
noted. In two studies presented there is an indication of an increase in
the incidence of hepatomas in heptachlor epoxide fad animals.
The level causing no significant toxicological effect is 5 ppm in the diets
of rats, equivalent to 0.25 ing/kg body weight; for dogs (from 60-week study)
it is 2.5 ppm in the diet, equivalent to 0.06 mg/kj. body weight.
Six groups of rats, each group being composed inittially of 10 males and
10 females of the CFW strain were fed diets containing levels of hepta-
chlor epoxide from 10 to 300 ppm. Each diet was fed to the animals to
which it had been assigned until all of the animals in the group died, or,
until they had survived over the period of 2 years. One hundred percent
mortality was observed within 2 weeks at the two hughest dosage levels.
The mortality of the males was unaffected by diets containing heptachlor
epoxide in concentrations of 40 ppm or less. The-rortality among the females
was increased at 40 ppm, but was unaffected by diels containing 20 ppm or
less. Food consumption could not be related to the heptachlor epoxide
content of the diets. The growth rates of males £ed 40 ppm heptachlor
epoxide were retarded, levels of 20 ppm or less had no effect on growth
rates of either sex. Liver weights increased directly with the heptachlor
epoxide content of the diets for both sexes. Pathological lesions which
could be attributed to heptachlor epoxide in the diets were observed in the
livers and kidneys of both sexes and were directly related to the level of
the contaminant in ..-the diets. :-Unifcjr-m- Atypical" degeneration of slight to
-64-
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raoderai. • degree wis nutred at 10 ppm. Marked to severe hepatic degeneration
and sliguL to moderate renal tubular degeneration were press nt at It -els of
40 ppm. Consistent pathological changes were not associated with levels of
less than 10 ppm heptachlor epoxide. The incidence and types of tumors found
in the test and control groups were essentially the same (Witherup, et al. ,
' 1959a).
Witherup, et al., (1955) fed CF strain albino rats levels of heptachlor in the
diet for 2 years. Six groups of rats, each composed of 20 males and 20
females, were fed levels of 1.5 to 10.0 ppm heptadalor in their diets for
2 years. The mortality was of the same order in all of the groups and was
not increased significantly by the presence of heptachlor in any of the
concentrations- investigated. While the food consumption varied significantly
with time and between groups it could not be related to the heptachlor content
of the diet. Growth was directly related to food .consumption and was not
related to the heptachlor content of the food. There was a relatively high
mortality among pups whose progenitors had been fed! diets containing 7 ppm
or greater heptachlor. The liver weights of the males fed 10 ppm heptachlor
were relatively high, but not sufficiently high as to be significant. There
was no correlation . between liver weight and heptadilor levels fed in the
females. Several male and female rats fed levels -of 7 ppm or higher hepta-
chlor had slight alterations of the liver cells of the type characteristic
of chlorinated hydrocarbons. These were characterized by swelling, homo-
geneity of the cytoplasm, and peripheral arrangement of the cytoplasmic
granules in the hepatic cells in the central zone .trf the lobules. No
hepatomas were noted and the incidence of tumors w.ss independent of the
heptachlor content of the diet.
Witherup, _et_ a^. t, (1959b) studied the effects of deeding heptacblor epoxide
in the diets of rats for 2,years. Six groups of CM strain albino rats, each
group being composed of 25 males and 25 females weare fed diets containing
levels of heptachlor epoxide of from 0.5 to 10.0 pjm for 2 years. The
mortality of the animals, either male or female, was not significantly
affected by the level of heptachlor epoxide in the diets. The presence of
heptachlor epoxide in the diets at any dosage level did not affect food
consumption.- Variation in the growth of the animals was within normal limits
and was associated with the variation in the amounts of food eaten, irrespective
of the content of heptachlor epoxide in the diet. The hemoglobin content and
the distribution of the cellular elements in the peripheral blood ofthe rats
were essentially normal. The average weights of tie livers of the females
showed an increase in the weight of this organ which was proportionately
related to the concentration of heptachlor epoxide in the diets. The average
weights of the livers of the males showed a slight increase which was not
statistically significant. Microscopically the lesions in the liver were
characterized by the accumulation of lipid materiaO. within the cytoplasm of
the hepatic cells, either as large droplets having a positive reaction for
neutral fat by special staining technique or as very fine droplets reacting
histochemically as a phospholipid. Vacuolar changes were present in the cells
£>f.,..the liver and were .pr,esen.t in .the--ceater £>,£ the hepatic lobule in the low
dose animals and having patchy or irregular distribution in the high dose
animals. Degeneration of the hepatic cells was manifested by clumping of
the cytoplasm, enlargement of the nuclei, and the presence of multiple nuclei.
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There.were 11 benign and 1 malignant hepatcmac i:. die treated females and
(- benign and 1 malignant hepatornas in the treated males. No hepatomas
were reported in the controls of either sex, other-rise, the incidence w.as
not dose-related. The authors conclude that the data is insufficient to
implicate heptachlor epoxide as the agent responsible for the development
of the hepatomas.
Jolley, ^t_ al., (1966) fed female albino rats for 2 years on diets containing
a mixture of pure heptachlor and pure heptachlor ejoxide in the ratio of
3 parts to 1 part by x^eight. The animals were di.vnded into 5 groups, 4 of
which contained 25 animals each, while the 5th groap of 54 was used as control.
A mixture containing 75:25 percent (by weight) of Heptachlor and heptachlor
epoxide in corn oil was fed in the diets of rats at levels of 5, 7, 5, 10,
and 12.5 ppm. The test animals demonstrated no o\rt-rt signs of toxicity. A
statistically significant increase in mortality was found for rats at the
12.5 ppm diet level during the final quarter of ths test period. The animals
in the three highest dosage levels tended to gain 'Jin weight more rapidly than
did the control rats and those fed the diet containing the lowest concentration
of the test compounds. The average weights of the brain, heart, lung, spleen,
kidneys, and adrenal did not differ between control], and test animals. The
liver/body-weight ratios in the female rats increased proportionally with the
concentration of the test compound in the diet with an effect being noted at
5 ppm. The liver/body-weight ratios in the males 'diowed a slight increase
which was not significant. Pathologic changes whldi were attributed to the
experimental compound consisted primarily of enlarged cells in the central
zone of the hepatic lobules which. contained fewer '.th'an normal cytoplasmic
granules. These cells were quantitatively differeit from but qualitatively
similar to lesions in the control rats. Necrosis cf hepatic cells was not
observed in the livers of any of the test animals. Electron microscopic
studies indicated that degenerative changes of the subcellular structures
were present in the hepatic cells of the rats whose diets contained 10 or 12.5
ppm of the insecticide mixture, as evidenced by vestculation and breakdown of
the rough endoplasmic reticulum, swollen mitochrondcia, and changes of the
nuclear membrane.
As a portion of a larger study, 100 male and 100 Eanale CoIIeb/Fe/J mice
were fed diets containing 10 ppm heptachlor or heptachlor epoxide for 2 years.
A similar number of animals served as control. As the mice died during the
experiment or were sacrificed at termination they wjre autopsied and their
viscera were fixed in formalin. The significant findings may be summarized
as follows:
Control Heptadtlor Heptachlor
. Epoxide
Surviving 78 weeks 150 135 109
Surviving 2 years 62 60 19
Hepatic hyperplasia 38 108 65
Benign hepatoma 27 47 85
Hepatic carcinoma 4 ' 4 9
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Davis noted that while there were .150 survivors ii. the control goup
at 78 weeks with an incidence of 27 L^nign hcpatonus and 4 hepatic carcinomas.
there were only 109 survivors in the heptachlor e;»xide group with an incidence
of 85 benign hepatomas and 9 hepatic carcinomas (Divis, 1965).
V.A.4. Effects on Reproduction - Studies of the effects of heptachlor and
heptachlor epoxide on reproduction have been carried out in rats, dogs, and
chickens. Pure heptachlor or heptachlor epoxide were used in the majority
of these studies, however, technical heptachlor was utilized in one rat study.
The test compounds apparently do not have an effedt on the ability of the
experimental animals to reproduce. There is also TO significant effect on
the number of litters born, the birth weights of tie offspring, the number
of offspring, and the body weights of the weanling rats. However, levels
of the pesticide of 7 ppm and higher caused relatively high mortality in
the offspring. There is some evidence that heptachlor epoxide passes the
placental barrier and is excreted in the milk of dogs.
As a part of a larger study (Witherup, et_ al_. , 1955), five female rats
from each dosage level of heptachlor (1.5, 3.0, 5.0,. 7.0, and 10.0 ppm) were
mated x^ith five males of corresponding dosage levels after the animals had
been on their diets for 7 weeks. Following the sanB procedure, but
selecting other animals from each group, matings were attempted after 22
weeks of feeding. The offspring were kept with their mothers until weaned
at 3 weeks of age, when they were placed on an uncoitaminated diet and
observed for an additional 8 weeks. Seventy and sight-tenths percent of
the matings of Che animals t^ere fruitful. Failure to reproduce could not
be ascribed to the heptachlor content of the diet. There was a relatively
high mortality among the pups whose progenitors had subsisted on diets
containing 7.0 and 10.0 ppm heptachlor. There was Tittle, if any, evidence
that the mortality of the offspring was influenced jy the presence of a
toxic agent in the milk of the mothers. It did appear that the presence
of heptachlor in excess of 5.0 ppm in the diets of idie parents may have
lowered the resistance of the offspring to the normrl hazards of life.
There was no evidence that the heptachlor content ol the diets of the
parents affected either the birth weight or the wearing weights of the
pups, either male or female.
Male and female rats of the CD strain were fed exclusively on diets
containing a mixture of heptachlor and heptachlor epoxide (3:1) in amounts
of 0, 0.3, 3, or 7 ppm were mated through three succeeding generations.
The number of pregnancies in the FQ and F£ generation was slightly
reduced in the 0.3 ppm group, but not at higher levels. There was a
slight increase in the mortality of the pups in the second and third
week after birth in the 3 ppm group. This was not consistent with other
data obtained in these experiments. The number of pregnancies in the FQ
and F2 generations was slightly reduced in the 0.3 ppm group, but not at
higher levels. During three successive generations, the compound exerted no
apparent effect upon the fertility of the progenitors or the ability of the
progenitors or the ability of the progeny to survive (Witherup, et al. , 1967b).
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Four groups, each consisting of 10 male and 10 female CNF rats were fed on
diets containing heptachlor apoxide at levels of concentration of 0.0, 5.0,
10.0, or 20.0 ppm, respectively. After the animals had been maintained on
their respective diets for 12 or 13 weeks, the females of each group were
paired with the males of the same group and each pair was housed in a
separate breeding cage. When the pregnancy of the female became evident,
or otherwise, after a maximum period of 7 weeks, the male was removed.
After the offspring were weaned at 21 days of age, they were separated from
their mothers and placed upon the same diet as their dams and sires. After
weaning of the offspring, the mother was rested for 3 weeks and then remated
with the same male. In a similar manner, the females among the offspring
were mated with the males of their generation (from other litters) which
were being fed on the same diet. Portions of the litters resulting from
the first mating of the rats on the diet which contained no heptachlor-
epoxide were assigned to diets containing 0.5 or 2.5 ppm of .the compound.
Otherwise, the rats of each generation were maintained on the same diets
as their progenitors. Mortality was high among the offspring of the first
mating of rats fed at the 10.0 and 20.0 ppm levels. With respect to the
numbers of litters born, the numbers of offspring aed their distribution
according to their sex, the birth weights of the offspring, and the body
weight of the weanlings, the various groups were generally similar.
In general, the data indicate that diets containing the heptachlor epoxide
in concentrations of 10.0 ppm or less, when fed excltasively to three successive
generations of rats, exerted no adverse effects on tSie reproductive capacity
the probability of survival, or the bodily growth of the animals (Witherup,
et al., 1959b).
Six groups of weanling male and female rats of the CD strain, each consisting
of 20 females and 10 males, were fed diets containing 10, 6, 3, 0.3, or
0 ppm heptachlor (99.9 percent pure). The animals were mated through three
succeeding generations. The content of heptachlor in the diet had no effect
on the fertility and gestation of the animals as measured by the number and
size of the litters they produced. The diets did noil reduce the viability of
the offspring at birth and during the first week thereafter. No anomaly in
anatomical structure was found in any of more than 4sOO pups whose progenitors
had been sustained exclusively on the heptachlor dietts; there was no indication
that the compound was teratogenic. The body growth md development of the
progeny through the period of suckling 'was not retarded by'the content of
heptachlor in the diets fed to lactating dams. There were no pathological
changes in the viscera of the F3 pups (Witherup, et^ jil. , 1957a).
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Twenty-four male and 2>\ female beagle dogs were separated ir.Uo one control
and five treated groups of four male and four female dogs each. Tht treated
groups of dogs were fed 1, 3, 5, 7, or 10 ppm, respectively, heptachlor
epoxide in the diet. When the female dogs attained an age of approximately
14 months they were bred, one female to one male. During estrus, each female
was bred twice with a male from the same dietary level, and four female and
'two male pups from each level were saved for the next generation. All pups
from one F^ female fed 10 ppm died between 1 and 10 weeks of age. In the
?1 generation, one female fed 1 ppm failed to conceive and one female fed
5 ppm showed no estrus period. In the P£ generation, two matings from the
control groups, two from the 5 ppm, and one from the 7 ppm failed to produce
pups; two males from the 3 ppm and 7 ppm levels were disinterested in
breeding. • The number of deaths among the pups of the P£ generation at
10 weeks were nine in the control, one in the 1 ppm, three in the 3 ppm,
five in the 5 ppm, seven in the 7 ppm, and seventeen in the 10 ppm group.
No changes were noted in the eyes of the ?„ generation by opthalmoscopic
(indirect technique)examination. Congested livers or livers grey or greasy
to the touch were noted in some of the dead pups in the 7 to 10 ppm groups.
The weak pups had concave sternums. Two pups from the ?2 generation at
10 ppm heptachlor epoxide had elevated serum alkaline phosphatase and SCOT .
values.
In the 2-year withdrawal period the alkaline phosphatase values in serum
from the 3 to 10 ppm heptachlor epoxide treated dogs remannad elevated
but elevated SCOT values returned to normal. At the beginning of the with-
drawal period, microscopic lesions in the livers of the 3 to 10 ppm animals
consisted of enlargement and vacuolation of groups of centrolobular hepato-
cytes or scattered hepatocytes, occurrence of eosinophilic hyaline bodies
in scattered hepatocytes, increased presence of finely granular brown pigment
in hepatocytic cytoplasm, and a finely granular "ground glass" appearance of
the cytoplasm of a large number of hepatocytes in contrast to the usual coarse
granularity of parenchymal cells of the control livers. Six months after
withdrawal similar conditions were observed in these animals, but to a lesser
degree. No teratogenic effects were noted during this study (Wazeter, 1971).
In studying'the reproductive effects of heptachlor epoxide on white leghorn
chickens, Wolvin, et_ a^-, (1969) utilized one control and three test groups,
each consisting of four male and twenty female fifteen-week old white leghorn
chickens. Heptachlor epoxide was added to the diets at the levels of 0.02,
0.1, and 0.2 ppm. As each group began laying, the daily egg production and
egg weights were recorded. When the eggs were consistently between 50 and
60 grams in weight, the daily egg production was collected and placed in
preincubation storage for the reproduction phase. A minimum of 100 eggs
from each group was collected for incubation and hatching. No adverse
findings were noted with respect to body-weight patterns, behavioral reactions,
food consumption, mortality and egg production. The percent of eggs hatched
in the two highest dosage levels was lower than the low dosage level or the
control group, however, hatchability in all groups fell within the normal
range of the chickens studied.
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V.A.5. Tr.ratojpenlcj l'y - Ti.: one L^aLo^en.ic study carried out in rabbit?
indica^.-s that hcotachior epoxide docs not produce visceral or structural
malforau'.rions.
' O
Forty-two adult female rabbits of the Dutch strain were separated into
one control group of 22 rabbits and one treated group of 20 rabbits.
.;• The act of mating was directly controlled and verified by vaginal smears.
• The day of mating was considered to be day 0 of gestation. Heptachlor
epoxide (98.9 percent pure) was administered in a 1 percent methylcellulose
suspension by gastric intubation at a dosage level of 5 mg/day from the
6th day through the llth day of gestation. All rabbits were taken for
Caesarian section on the 28th day of gestation. No unusual alterations
in behavior and appearance were observed during tha study. All rabbits
survived the study. No compound related effects ware observed with respect
to numbers of viable and nonviable term fetuses, resorptions, empty
implantation sites, corporalutea or nongravid females. The treated group
had an average of 5.3 pups per litter and in the control group, the average
litter size was 5.7 pups. There was a significant increase in fetal weight
in the treated group. No difference was observed in survival of incubated
pups between the two groups. No gross abnormalities were observed at
dissection of any of the pups from the treated gro.jp. The results of ali-
zarin staining were also negative with regard to any compound-related
effects. The only variation seen in the pups from the treated group was
varying presence and length of the 13th rib and incomplete ossification
of the central portions of the parietal bones. Pups from the control group
also had absent 13th ribs and incomplete parietal bone ossification. No
instances of short 13th ribs were seen in control pups from this study.
However, the authors report that this condition is commonly seen in pups
from control groups of other studies in their laboratories and do not
consider the effect significant (Wazeter, et al., 1969).
V.A.6. Carcinogenicity - In the studies carried out with heptachlor epoxide
in the rat by Witherup, et_ a^., (1959b) and in the nouse by Davis (1965)
there was an increase in the occurrence of hepatomas in the treated animals
above that found in the untreated controls. There was also a suggestion of
an increase in the incidence of heptachlor carcinomas in the Davis study.
Based on the. Davis study, the Secretary's Commission on Pesticides and Their
Relationship to Environmental Health concluded that heptachlor epoxide is
positive for tumor induction in the mouse (Mrak, 1%9). In their 1970 "Evalu-
ations of Some Pesticide Residues in Food," FAO/UHfl concluded that an adequate
carcinogenicity study in a second species of animal other than the rat is needed.
V.A.7. Mutagenicity - Various methods are available for mutagenicity testing.
From the criterion of presumptive human relevance, they have been categorized
as ancillary submamtnalian systems and definitive msmmaliati systems. The
human relevance of data obtained from ancillary test systems is uncertain,
in view of factors such as cell uptake, metabolism, detoxification, dosage, and
method of administration. Mammalian systems entail fewer of these limitations.
The mammalian systems include cytogenetics, the host mediated assay, the
specific locus test, and the dominant lethal tes.t. A positive result in any
mammalian system represents evidence of a potential mutagenic hazard
(Epstein and Legator-. 1971). - ,
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Orisi domirc'.nt lethal .:onu for •autasenesj.s he,., been reported. Groups of
eighu C-urles Rivsr strain male mice 60-70 diys old re re £:-~'cl' single
oral or mtraperitoneal doses of 7.5 - 15 nig/kg of a mixtu?:e containing,.-;-
1/4 heptachlor and 3/4 heptachlor-epoxide in corn oil. Erch male was
maintained with three virgin females for 3 weeks aftei- whic.li females
were replaced with new females. Breeding was conducted for 6 consecutive
weeks. One week after separation from the male each female was sacrificed.
The number of implantation sites, resorption sites aid embryoes were
recorded. All males survived treatment. Hating indices and number of
pregnant females per number of females mated were sinilar for all groups.
Average number of implantation sites, resorption sites, and embryoes were
similar, suggesting no mutagenic effects on treated miles (Keplinger, 1971).
V.A.8. Metabolism - The information on the metabolisr. of heptachlor is
incomplete. The formation of heptachlor epoxide in Tavo in several species
of mammals and in vitro using rat and rabbit liver mocrosomes in the presence
of NADPH has been described (Wong and Terriere, 1965;; Nakatsugawa, 1965;
FAO/WHO, 1967). It was suggested early that heptachOar epoxide might be
further metabolized to a diol (Davidow and Radomski, 1953), but the occurrence
of such a compound has not yet been demonstrated. Rovever. when 25 jig of
14^-labelled heptachlor was administered to male and female rats, the radio-
activity was largely encountered in the feces as heptachlor epoxide, along
with a second metabolite; this second metabolite was also encountered in
the urine, but heptachlor epoxide was not. In both -rats and rabbits treated
with heptachlor, heptachlor epoxide was the main metabolite found in tissues.
The urinary metabolite was found to be l-hydroxy-2,3-ipcxychlor-1ene (Korte,
1968; Klern, et^ al_. , 1968). It is not known if this (Compound aiises via
heptachlor epoxide or via a direct hydrolysis of heptachlor first to form
1-hydroxychlordene. The information available on the mammalian metabolism
of heptachlor has been reviewed (Brooks, 1969). In experiments with rabbits
and pig liver microsomes, the hydration of heptachlor epoxide to a diol has
been demonstrated (Brooks and Harrison, 1969) (Figure V.I.).
V.A.9. Enzyme Induction - The metabolism of various cchemical substances
is stimulated, both in vivo and in vitro, by many different types of drugs
and chemicals and in the environment over 200 drugs aid other chemicals,
including heptachlor, are known to stimulate drug metibolism in laboratory
animals. Several extensive reviews have been published since the mid-1960's
on the inductive effects of chemicals on drug metaboliizing enzymes in the
liver (Kuntzman, 1969; Conney, 1969; Street, 1969; Comey, et_ a_. , 1969;
and Kupfer, 1967).
The drug metabolizing enzymes are located primarily in the smoo<_h endo-
plasmic reticulum (SER) of the liver cells. These emymes,catalyze the
metabolism of drugs by pathvrays such as hydroxylation., dealkylation,
deamination, sulfur-oxidation, azo-link reduction, and glucuronide
formation. Studies conducted in the last decade have demonstrated that
treatment of animals with drugs, polycyclic hydmcarbotE, and chlorinated
insecticides increase the activity of liver microsomal oxidative drug-
metabolizing ei^ymes. "The most'-potent ihducers of 'these enzymes are some of
the chlorinated insecticides. Single or multiple doses at relatively low
levels significantly increase the microsomal enzyme activity in rats.
-71-
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U
Cl
•
X.
N
Cl
Heptachlor
\\ . r- .-• !
yi. ' ( --11 smmnals, "J.\: " I
'""' ----------------- ....... - ....... > I \ ., ':N
in vitro -liver I V
raicrosomes, NADPH ) L
\ (hyi.'rolysi sr
» soil bacteria)
C1
'Cl
Heptachjor epoxide
(excreted in'reces \
or stored, in «i.-.fu?:\
excreted in rjlk 01
dniry animals)
Mam-ial?
Kamnals
(Soil
bacteria)
>i
ci-j
C1
1-hydroxychlordene
(soil bacteri.n)
1-hydroxy-2,3-epoxychiordene
{urinary metabolite)
Cl
Cl
.
\ jci
chlordene
l-l
-------
Repczichl r. r and' hep tact'lor epoxide'were ad;:!ir. ic.f:crec to male rats at
dietary I'-'-vcls of 0,1.0 or 5.0 ppm for 2 x-;ec-ks (Alcrin or d.\eldrin
were also fed at the same levels to other groups). After completion
of the feeding, the animals were sacrificed and rcicrosomal preparations
made from their livers. Microsomal epoxidation, as measured by the
epoxidation of aldrin to dieldrin, was unaffected by 1.0 ppm, but was
significantly affected by 5.0 ppm of heptachlor or its epoxide. The
increase in the rate of epoxidation was correlated to the dietary level
and to the concentration of the cyclodiene compounds in the microsomes.
Both heptachlor and aldrin appeared to be substrates for the same enzyme,
which is inhibited by the epoxide. Microsomal metaiolism of the epoxides
was not found to proceed further (Gillett and Chan, 1968).
Female rats were fed with heptachlor in the diet at a dose level.corres-
ponding to 5 mg/kg body weight/day for 3 months. After this period -^P
fenitrothion at a dose of 24 mg/kg body weight was administered in oil per
os, and radioactive measurements were made (five tines during 24 hours) of
the total activities of the liver and of the degradation products in blood
and liver. The results were compared with those of the control group not
pretreated with heptachlor. Total activity in the liver of the group pre-
treated with heptachlor was 50 percent higher than in the control group,
with a maximum after 4 hours. In the control group, the values diminished
gradually after the exposure to fenitrothion. The ratio of the oxygen
analogue to fenitrothion in the blood and liver suggests that the conversion
of fenitrothion to its oxygen analogue is enhanced and accelerated. Results
of this experiment demonstrate that pretreatment of rats with heptachlor
increases the metabolism of fenitrothion (Mestitzova, ^t ai_. , 1970).
V.B. Human Toxicity and Epidemiology - The toxicity of heptachlor to
humans is similar to that of the other cyclodiene insecticides. Based
on data derived from experimental animals, heptachlor is 3 to 9 times
as toxic as chlordane. The fatal oral dose of chlordane is estimated
to be between 6 and 60 grams (Rays, 1963). The fatal oral dose of
heptachlor should be much lower than this. The estimated minimal single
dermal dose which is required to produce symptoms is 1.2 gms/day. The
threshold limit for heptachlor in air is 0.5 mg/M3 (Rays, 1963).
V.B.I. Signs and Symptoms of Poisoning - The signs and symptoms of acute
heptachlor poisoning may be expected to be similar to those produced by
the other cyclodiene insecticides. Irritability, salivation, labored
respiration, muscle tremors, convulsions, and death,- with or without an
immediately preceding period of deep depression, have been reported to
follow the ingestion of toxic amounts of chlordane and should be expected
to occur in cases of heptachlor poisoning. '
V.B.2. Laboratory Findings - Clinical laboratory tests are usually
normal, however, liver function may be impaired as revealed by appropriate
tests. A fat biopsy may reveal the presence of a cyclodiene derivative
(Dreisbach, .1963).
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V.I'. 3. T re client - TJ'^-.ciK-\.!g u.i t'n-~ cc'iciifion of tin pntient, attention
sh.H'ld cirst be f;ive-i to sedation or to the .removal of the heptachlor
which .nay have been ingested. Syrup of ipecac, gastric lax age, anc .saline
laxatives may be used. Oil laxatives should be avoided since they may "
increase the absorption of heptachlor. Convulsions may be controlled by
the use of barbiturates alone or in conjunction with calcium gluconate
: (Hayes, 1963).
V.B.4. Human Poisonings - The clinical picture of himan poisonings
reported for heptachlor has been complicated by the presence of other
toxic pesticides in the ingested formulations.
V.B.5. Epidemiological Studies - Studies have been conducted in the
attempt to rela,te organochlorine pesticide concentrations in human fat
with the geographic location. Samples of human fat oollected from Arizona,
Kentucky, and Washington were shown to contain low levels of BHC and easily
detectable amounts of dieldrin, in any of the samplee with methods which
were sensitive to amounts of these substances comparable to those of BHC
and dieldrin. Heptachlor epoxide was detected in 25 specimens from New
Orleans, but none was found in samples from other cities which were cited
for comparison (Dale and Quinby, 1963).
Heptachlor epoxide was found in all specimens of adipose tissues taken
from 123 persons from the Union of South Africa and -.trace amounts were
found in 12 different types of human tissues obtained at autopsy in
Hawaii. The highest total residues of organochlorimr insecticide were
from those subjects with evidence of emaciation, resisting from carcinoma
or extensive focal or generalized pathologic conditions of the liver
(Wasserman, _e_t al. , 1970). Five hundred and five sarnies of human tissue
were analyzed in an attempt to correlate pathological tissue changes with
pesticide concentration in fat. No heptachlor epoxicfe was detected in
35 specimens, 93 contained trace amounts, 12 contained 0.10-0.29 ppm,
and 7 contained 0.50-0.74 ppm (Hoffman, at al. , 1967').
The distribution of chlorinated pesticides in the plasma of pregnant
women and in the milk of lactating women was compared with the amounts
found in the plasma and tissues of stillborn or new-barn infants. The
concentration of heptachlor epoxide in the plasma anil milk of pregnant
or lactating women was found to be 0.003 + 0.0001 and 0.0007 + 0.0003 ppm,
respectively (Curley and Kimbrough, 1969). In an earlier study, milk from
lactating women was found to contain 0.0027 ppm heptaihlor epoxide.
The organs of stillborn infants contained 0.80 + 0.3D ppm heptachlor epoxide
and the blood of newborn infants contained 0.001 +_ 0.0002 ppm (Curley, •>
et al., 1966).
•
In 53 human milk fat samples the average total DDT content was 2.40 ppm.
The values for lindane and heptachlor epoxide were 0...08 and 0.16 ppm,
respectively. The level of total DDT was higher in samples from mothers
nursing for the first time, but no information was available on the initial
pesticide burden of the mothers. The relationship~diil not hold for lindane
or heptachlor epoxide. Only eight of the samples analyzed had total DDT
concentrations below the 1.25 ppm tolerance estMblislud in tlie U.S. Code of
Federal Regulations for milk fat of dairy cattle. Hejtachlor epoxide and
lindane have zero tolerances in cow's milk. The possible health hazards of
tnese levels cannot be predicted at this time (Kroger, 1972).
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Cbc.pter V
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-------
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its epoxide into their daily diets. Unpublished report
by the Kettering Laboratory, dated February 27, 1967,
reported by Velsicol Chemical Corp. (1967)}.
Wolvin, A., Jenkins, D0 H0> and Fancher, 0. E. Toxicity, residue and
reproduction study on heptachlor epoxide,, Unpublished
study by Industrial Bio-Test Laboratories, Inc., dated
April 10, 1969, submitted by Velsicol Chenaical Corp,, (1969).
Wong, D. T., and Terriere, L. C. Epoxidation of aldrri, isodrin and
heptachlor by rat liver microsomes. Biocham. Pharmacol. 14:
375-377 (1965).
-79-
-------
APPENDIX
Economic Impact of Discontinuing Farm
Uses of Heptachlor.
-------
ECONOMIC Ii/PACT OF JTfSCOIITINuIHO-
USES OF HEPTAC/ILOR
Herman W. Bilvo
Austin S. Fox
Robert P. Jenl':In:-;
Ft!.nn Pc-sticiclcT. Group
Production PrsourccK Rrc'.nch ~ •
Ta.rm ?:i.-odu.c:!.io:'! L'co;io::;:i.rr; Division
]yjojio;::'!.c R£:Si'.-.'.xr'j]'i Ccrvico . • • • •
U. D .• Dopnrr.•;.;:•)•;t of ;\r.r:i. culture V,1o.r;!ii:jf;ton, T>,
-------
C>"i'i''v»,'~\
AiVj.V.J
Farm uses' of heptachlor
Fconorr.ic ijr.py.ct of dis continuing; frccm user; of
heptacblor --------------------------------- ' ------ ----- 7
Additional costs and lesser:1, on corn ------------- 8
Additional costs on tobacco ----------------------- 11
Additional costs for other uses ----------------- 11
Total additional costs; and losses ---------------- 13
Appendix tables --------------- =•• ----------------------- l'i
-------
The total added cost to U.MJted Gtatos farrors for discontim::n.(j;
the use of heptachlor would have been !;'2.0 j.-dl/J.on in 1971—$1.1
Hdllion for alternative insecticides and $0.9 million for production
losses. Most of these added costs would be fee controlling coil
insects in coin.
Corn yields could have been maintained w';t:re alternative
nonorganochlorine insecticides were used to control corn rootworns.
• But where other soil insects vere a problem, alternative insecticides
are not as effective as heptachlor and yield "would have been reduced
about 2 bushels per acre. Corn farmers' prochntion costs would have
increased $2.0 million annually on 669,000 -ac3>:es. The added cost '•
per acre ranges from $1.55' to $1.73 per acre ti.vu.ted' depending on
vhether corn rootworm or other soil insects Wvtce the problem. A loss
in the value of .production of $2.97 an acre woild have occurred on
)f07,000 acres of corn treated fcr other soil iisect control.
Tobacco producers would have an added cos-, of $21,600 for
alternative insecticides—$9,000 for 3,000 acres of field treatment
and $.12,600 for seedbed treatment.
Seed treatment costs, primarily for corn,.would increase $15,^00
if hoptachlor use were cancelled.
•
Eliminating the use of heptachlor in fan,-: production would have
little effect on the total quantity of insecbi-;ices used. Heptnchlcr
use would decrease an estimated 6.9^000 pounds.. The total increased
ur.o of alternative insecticides would ranr.o vrsn: 562,000 .pouruis to
ii
-------
69>>OGO p o >.:•;; ci.s . /jfiditiGnal qu;:.ntitief; or ivlt-..-rn::tivc ins
used in corn production would rwgv i'ro-n 53'> >f-00 pouinlu to 669,000
pounds d^poiidlng on vh.lch or^anophopphate or carbajnatc insecticide
farir.ors use on corn. Orgsnyphouphate insecticide use in tobacco
production and for seed treatment > priinari.ly corn, voiUd increase
26.000 pounds if hcptadilor registration u'crc cancelled.
-------
\y'''1'' ,';".' ;: :.'v^:'- ',(••;;! i".':>
by
llernon U. Delvo., Austin 3. Fox., and KoLert P. Jenkins I/
Fa.r~.err, ur.e heptc.chlor primarily to control in sects in cr.op
production. The major farm use is on. corn to control soil •
insects. . Heptachlor is also used to control termites in residential
and commercial structures. Information on the total quantity of
nonfarn use of heptachlor in the United States is not available.
Ho-v.-cver 5 1971 pesticide use data for California r-how more than
98 percent of the heptachlor used' in the State vas for nonagricu'J.tural
•purposes. 2j ' ' •
.Tiiis analysis of the effect of discontinuing farm uses of
heptachlor is presented in 2 parts. First » far!'.; uses of heptachlor
are identified. Second, the economic 'impact of discontinuing farm
uses, of heptachlor is estimated.
The study vas developed under the following general assumptions:
(l) nonagricultural uses were not considered, (2) damages to vegeta-
tion on land not cropped or pasture v?ere not considered, and
(3) nonorgariochlorinec vere the only alterntitive insecticides
»
considered.
I/ Agricultural Eco'.io;;iists, Farm Pesticides Group, Production
Resources Branch, Farm Production Lkionomics Divirjicn, Economic
Research Serv.lcc, U.S. D-pt. A^r.
?J Peryc:ic:i
-------
The l:.'.st ar.-sumption vns because the best alLejnativc 5 aluriri *"
an or^uiiochlor.ine, is chemically roll ated to hqytaohJor ;;nd its
uses are currently bein^ reviewed by the Environmental Protection
/i»,er!cy. The Aldriii-Dieldrln Advisory Coraaittcs has reco::v.:!ondcd
that aldrin be retained for treatment of soil insects; ho*-: ever, a
ruling has not been made. If.the farm use of "ieptachlor is
cancelled and aldrin can still be used to tro;xf, soil insects, there
probably vould be no additional cost. The per acre application
rate and costs are about the same for heptacbloT and aldrin in the
• control of coil insects on corn and tobacco.
It is recognised that many of the nonorgaiochlorine insecticides
are nore toxic than heptachlor. Thus;, there is: a greater hn?,ard to
farm operators arid workers handling these matc;2ic.ls. Organophos-
phorns and carbaiate insecticides are also less persistent than the
organochlorines. In serne cases, they need'to 1x5 applied irrore fre-
quently resulting in adverse effects to beneficial insects. But for
this study, it was assumed that one application of a nonorganochlorine
insecticide replaces one application of heptachlor on crops.
Far;n Us c:.; of 1 lept achlor
Corn producers are the major farm users of hejjtachlor. About
1.0 million pounds of heptachlor vtis used on ccssn in 19nH (table l) .
In 1966, about 1.5 udl.'lion pounds of heptachlor vas applied to 2.0
million acres of corn. The Corn Belt, Lake Stales and Northern
Plains accounted for about 99 percent of the hcrptachlor used on corn.
-------
m . ,
Crops :
Other
AlftuLf
Other
Citrus
Other
Ml
Livestoc
bui.ldin
Other us
To
P'C' Of USC1
-
i ."i. e j. c. c .re i ; ?j
ha.;; and pasture —
.fruits and nuts--
k and. livestock
•*•"'! ' •-
' ' • >;>
Qua-.ily u.eo I/ ; Aer, ;;e [ Percentage of
------- _ - - - - i. .[.-;:• i. •.:»!. u.i..-.:.)., !.-(.: d t-CJ. v':>
19o'i ' 19^6 1 in ly'OC [ treated in 1966
1,000 _poundf.: 1..00J: acres Percent
1,009 '2/1,539 2,^6 3.1
2''i 7 3 • '-.3
3/175 V ^ 5/
6./ 3 12 s/
6/ 10 Ji8 "'3/
7/ 1 6 .2
• k/ p . ? •
V 2 .1
1,298 1/1,570 2 .,10 3
• 3 •
lj ' 20
1,302 ' 1/1,593
I/ Active innredient,- • .
2/ Revised est:i::.ite r.ince data Arere publirvlic.-d.
3/ Includes heptachlor used on alfalfa, other hay •;!:£ pasture.
V LSKE than oOO pound:; used.
5/ Le:-;; than 0.05 jvercent.
6/ Included in other field crops.
"jj V.r:icn J.esn than 10,000 acree vere treated the m:.-nt:Lty uyed var, not
reported.
8/ Tncluaer; u::,e on .c:yi-:iber!..~ , sl'.ara.^e L^uildin^s , t.iavi::pla.nt.r:. , se-ed treat;;.ents
and o';l:or farn ur.'-s. Does not include use around ho^i-o, garden;;, ].avms, shrubbery
and shade trees.
Couree: Quantities of Pesticides U::sd by Fc'.r.'.-ierr, in l^u'l , U.S. Dept. A^r. , Eccu.
Res. fjerv., A;;r. Econ. i'\pt. "o. 131, January 1968.
Qu;i:itit:i.es of Pesticides Used by ]''ar::;er;; .in 15)66, U.8. Pvpt. A^r., hVon.
Res. Serv. , Af.r. EGO:), h'pt. J,:o. 179, April .'l.f'f'O.
-------
i'.v "197'1> use of };?. pl-aehlor on corn luvJ u<-ereaGcd to about
6'3'ijOOO r.0'.i;:t'in on 669,000 acres (table ?-} . T:.:;- perccnta/rc of planted
corn acrct.^e treated. vith hept rich lor decre;..:.;e<] from 3.0 percent in
1966 to 1,0 percent in 1971. Changes in the use of heptachlor on
corn in Illinois in recent years sh ov.vs this cicsarKard trend — the
percentage of pi anted acres treated vas 11.3 percent i)i 19(->9 > 6.3
percent in 1970 and If Ji percent in 1971. I/
The rather extent;! ve use of heptachlor on corn in the middle
I960 's vac in response to the spread of corn raotworrcs throughout
the Corn Belt. Large infestations of corn roo'-nvorins developed in the
•western Corn Belt around 19uO and spread eastvsrd. A severe corn ;:..
t
rootvoris outbrealc occu3.'red in Illinois in 19^5 and 19-56. l.'ov^vei1,
rocrlv.vGrjr-n soon developed resistavice to tiie or-jfiiochlorinc inaccticidcs
in the vent em part of the Corn Belt arid northern Illinois. Thus »
the decreased use of heptachlor betveen 1966 oi;d 1971 inft-y he partially
explained by the spread of resistance to it. In addition, some
farmers ir.ay have stopped usih^ heptachlor beca'cse of possible residues
Currently i'arjsora are using heptachlor to control nonrcsistant
corn rootvornis and other soil insects- — pri!;:ari:ly virevoriris^ cutvrorino ,
»
vhitc-j pruos n.r;d sod vetavrorj;;S in southern Illincas and the eastern Corn
3/ Daka for '.\[l6f-) and 1970 vcre obtained frcr "Pesticide Use by
.Illiincds ]''ar!:V.-;rs._ -19.70"} Il?.:; ::ci.r . CcG.perati.vo Crop Reporting Service,
Illinois Pepart.-i-jnt of Agriculture o.nd U.S. Pert. Ar,r., Myy .197-1.
]\J B'j.'.;ed en dJsvusKiens vritli entOJiKOog:! s Is ;.:. Illincxls-j F:;ebr;,;.s];a
and Chio.
-------
Table 2.—Uoptachlor: Corn ' acrea',e tr.;ato?d and qv.ci-ii:itic:3 used, by selected
State::-;, . Uni ted States, 1971
States
.Cnc3 J.UMQ —
1'jinnosota : —
14 ether States 3/
All other .States 4/
United States
Ticres
pi anted 2/
1,000 acres
5,679
10,470
6,572
3,332
719
40,695
6,630 '
74,097
: /icres
: treated
1,000 acres
63
461
33
43
42
27
669
: Quantity
• used
l,,00b pound
63
424
20
86
27
14
634
Percentage
| of planted
acrc-'S trr--.a-ted
'.; Percent
1.1
4.4
.5
1.3
5.9
.4
.9
_]./ Br.ccd on UMpuV.ilinhed data fro-.n "Pesticide Use — 11T/X Objoctivi Corn Yield
Survey". 'I'c'nn Production Economics Division, KR?, UGDA. HinetcKn States crrov.-ivig
91 pprcont of the corn in the United States in 1971 were included in the survey.
2/ Crop Production, 1371 Annual Suiru-nary, Ktet._ Rpt;v. Gerv., Cr'j.'r 2-1(72), Jar:ua
V Other St.ut.es included in the survey wore Delaware, Georgia, Iowa, Kansas,
Kentucky, Maryland, j;.i chic.an, Nebraska, Kori-.ii Carolina, .uhio, Pennsylvania, Couth
D;J-ota, Yiroinia, and ifisconain.
o,-7 J^;, Stat°S W':5"° n0l; ^^"^d in the "Pasticid,, lBo-1971 C»b-jective Co,-n Yrr
Pe"t^-id'. -,M° r^^'^ ,trC2^Ci ^d.^^tity us:ed are bared on information fro:, the
it-ot^cid'.; ana Laneral rarra Survey in 1966.
-------
Bolt.' In .'1.971 •''•''• v;;:;-v re corner; c'icd for control of coil inL-;-cl-:.; other
than corn rootvor;::3 in the ;.":v..j or corn proaucii.^ fJttvl.es or-icc-pt
Illinois. 2./
Heptachlor is a] so used to control soil issects., priinarily
virev.'Oj-fiG, in tobacco, About 2-';..GOO pounds of heptachlor vas used
on tobacco in 19c-i. Tts use on-tobacco decreased in 1966 to about
7,000 poundo ana vc-.s applied to 3,000 acres (table l).
In 196'-!, about 1715,000 pounds of heptachl'ir vat; ur.ed on other1 field
crops -which included alfalfa, other hay and. f crags, and pasture.
By 1966, use on these crops had decreased -to aiout 23V000 pounds.
It v:as used primarily in the Southeast, Delta. States and Mountain
P.egicns. Heptach.loi* vc.s ' used on l\:?:y crops ' to'.control alfalfa,
veevil and frr5/3fihoppera. The registration for use on alfalfa., other
hay and forage and pasture vas cancelled in tlsi mid 1960's. 6_/
About 6,OQO acres of ve gat able;; vere -I rested VD th 1V000 pounds
of heptad'.'lor in 1966. Tnir; use occurred in Ih'e Northeast and
Delta States. Small amounts vc-re used on citius in the Southern
Plains ar.'d or; other fruits and nuts in the Pact.fie Region in .1906.
These treatments are generally to control soil insects wid antr.,
•frequo.'itl'j-1 as spot tree.L;r.onta . Jfeptachlor is no longer recomiiiontjed
for use on vegetable:.; in tho.:;e arc ay vljere it •.Tar. reported used in
'2/ Based oil 3971 insect control rec.O!irnc-r;dat'r.'oi;:; for Illinois,.
Indiana, Ic-.:a, Minncrota, i-:i:;:;onri.., Kebra;;}ia aid Ohio.
6_/ Based on discissions vitli Lv. William Piirllip::. v Pesticide
^e^ulaticn J)ivisir.n, Environ-.enL.al r'rottoction ..'•'cy.iiicv', Vaoliin^ton, D.C.
-------
.'UX'd. TL 'in rcco;::"::.-:':;lc:(i for- r ;.•»'.. '.;-,;:.:A;,.--I; I- of >•;!;; f;i citm::. in To :•:.•;
'.>
It vac no!, registered for u.?-e in i'ho prod'-.'!-:/'', i <"'"• of ir/!f;i fruits ^'oa
nuts in 1971. I/
In addition to the use of h-r-pt rich lor on crops > 3:.OOG pou.no:".
vac; uned on livestock and livef.t,oc:k 'bivildii.i'.f;!; iu 1966. Currently it
is not registered, for use on livestock and livestock 'biri.ldin^s. B/
Other l'ar;n v" registered, for use on liny crops, p.sir,tare 5 and. Kioat fruits
and nuts. It is registered for ur:c on. vegetables- ;nid citrus as a
preplant soil application. It is also registered for vegetables as
a root dip. IIovevcr5 the effect of cancelling keptachlor is not
ojjo.lyx.ed for vegetfr.bles or citrus because 1966 TICSticicle use data
indicate that it was p.robab2.y ur-:ed on these crojG only for spot
tre'.itrnen'ts of soil insects. Thus., a f.w indj.vicual producers i-d.gVit
be affected but the total economic ii&pact vould "be S7r:all.
77 "Bi;;--aiy of Registered Agricultural Pe;;tic:ide Ciic-inical Ur.r::>",
Vol\y;.o III, Pesticide ]\egulatio."! Division, AKC, ^.JJ'JA (3rd .Kd.iti.on
ns ,a)'-i!.:?jZ;ed.)
O/ On. cit.
-------
A'.U-'!it JO.' .'-: '|__f:f"£^;'|_-"-':'-'l '"'''_"' ;-'-"S_Cn L^"
Ca>icr-ll:;.nr; the use o:i' heptachlor vcul c' a:\Tect fu.vjvi-L-rii in tvo
vayE . Producer," GJ" corn vould have: (l) ].'if^:->r costs with
substitute insect controls, and. (2) losses in Talus of production
v.'here substitute insecticides are lees effective 'than hcptacblor.
It vas assumed tliiit the nonor^anochlorinc insecticide
substitutes for heptiiclilor for corn rootvor,-n. control would be just
as effective and there vrould be no yield losses. But Giibntitute
insecticidec would cost more.
The nonor^anochlorine insecticides substitilcd for other soil
insect control in corn are only partial substitutes for heptach.lor. ;
sx3. yield losses vould occur. Thus for other roil insect -control
in corn., costs are higher becc.use of wore expensive substitute
insecticides and losses from sales of less corn. • •
Of the 669,000 acres of corn treated vita heptachlor in 1971. it
is estimated that 262>000 acres vas for rootv.'onn control only and
)407}000 acres for other insect control (table 3l;.
The total added, cost to corn proc'iucern for replacing heptachlor
vith nonor^ano"hlorinc insecticides in 1971 vould have been about $2.0
million (table '<) . The cost of alternative in:;:;octicides for corn
rootvorm control only vould have been $0.'l ir.illilon. ''Die per acre
coot of the alternative insecticides is $2.95 compared to •v'.l.hQ pel-
acre \.'hen heptachlor is used. The additional -cost for controlling
rootuor/ris in corn vould.be $1.55 per acre treated.
-------
-•-iHli.ii;;:c:!,j ••:!.•: Corn <-;c.r <•.••;.' treat'.cl :hr ••'OCi v.):.'.-i c;nd oth
soil inject contrn] , by fjelccu-t'i Stai:c:;,
United SUit-:.:r-;, 1971 .!./
State
.
Colorado . —
.14 other States 4/
All other .States 5/
U n i t e d S t ate s
Acre;, ere treat
Rootworm
control
only
44
184
21
.
13
262
ed with icptac-;
Other R-f.il
ins eat.
• control 2/
] ,000 <:C.-".-.K
19
277
00
A o.
21
. 14
407
: lor .Cor 2/
All :'joil
insect
control
63
461
o, 1
A O
42
27
669
I/ B£;^;.:d on unpublished data from ."Pestic.-i'b Use —1971 Objective:
Corn Yield Survey,-" I-'arn Production Economics Division, EKS, USD7-..
Kincv.eon S1:fjt.e.s grov.'ing 91 percent of the con. in the United States
in 1971 v:fcre inc.l.udsd in the survey.
2/ The distribution of lieptr-chlor v.'as between rootv.'orm. control.
on.ly and other soil inject control is based 01. on Adiuinictrative
report prei.-ar-.va by Jo'nn 1-i. Rcrii/, I'iobert P. aQihins, Theodore R.
Jilidierc, and Austin S. Fox, "Economic Ir.oact-rf Discontinuing Far;n
Use.s of Aldrin and Dieldrin", Farm Production Economics Division,
KJ-S, US HA.
_3/ I'nc.luderj v/irev.'or;;is, white grxibs, cutv/ons,' seed corn beetles,
seed corn !\\;--.qgot.s 'and v.'obv.-orr-.:;.
_4_/ Other States included in the survey we;:? Delaware, Georgia,
lo'.va, K;:ni?ii?-., iientuoiy, i-'arylc-nd, Michicjan, K(braska, llor'di Carolina,
Ohio, Pcnnsylvf.iiia, Sor.t'ii D;,'-.oto, Virginia, cud VJir-consin.
L>/ 'ihasij .states we:re not included in the "lest.icidc Use—1971
Objective Corn Yield Survey."
-------
Co^t ccr acre I/
.'!.CaCU CCS" Cl
:' treatment:''
•creac-cnr
1.40
.13
1:55
1.73
] ,00^ ac"'""? 1 r".:'"• .'.-i'!.--
GG9
;f -rrocurrtion losse:
•" ':h;.:r soil insects
Tc":.:.l cost and value of losses
5/2.15
1.35
3.63
2.97
407
669
1,533
omativs insectic.xco—: 2.SO
!.l corn end t.cbacco •—:'
5.70
2.90
3
672
T -^ c :ri vaticr. of these eGtir.v3.tes are shewn ir. e.pper.aix fccbls 3.
'?../ Co'.-' '• c-2 ?.3 tc motive insecticide minus the cost of heptachlor. Costs of application clicl not cnr.nce.
;-,.' Corn acreacei- arc from tr^ols 3 and tobacco acreages are from table 1.
" _•",::•:; '.c^t o: o.lfccrnac.iv2 insecticide or value of production losses per acre ti~es the estimated acres
.
": ' :':J::.:-\-.cGd" loss of 2 bushels an acre tines the 1971 corn price of $1.CG a bur-hel. The loss of 2 bu-hels .?.
... : v:,;.-'-r ?n alternative insecticide treatment for heptachior to control soil in.ve::Ls otlior ti": :;r. re -r.t" ;:•:."• 3 is
: s u: ;<• c1. the scino as losses estiraate.d earlier for aldrin. It is based on infomtvtio-.i frorr, er.ton-.o legists at TurcV
v.-.-t :f .'•.-. The price of corn is frorr. "Field and Ssed Crops: Production, Farr.i Use and Value " Stat . ~.pt" i"::.:v
-------
. - 11 - .
For other soil insect control, the tol;':l cost to replace
heplachlor would have bcc.-n $1.6 raj lion~-$0 . Y J:i.lllon for a 1 tern at i vfi
insecticides and $0.9 irdU.icn in production ."ii.-.rr.eu . The cost per
, p.cre for filt.tr native iiiOocticidGs vrould inoro ti.-.:ui double; — increasing
i'roia ^iJiO for lieptaohl.or to $3.13 foi^ altfor^yaiive insecticides. Tlis
total additional per acre cost i'o?- replacing hcptuclilor on 'lO'fiOOO
acres tretited in 197-1 'for soil insects other than rootvorms voxild be
$3.89 per acre treated.
/idditiori"! Co".ts_ on jv^acco
It wr.s asfjujned that the nonorganochlorJ no. .snsecticide used to
substitute for heptcxhlo" to control' soil In^ecH?- on tubfcco would
be equally effective v:i.t . no yield losses. It.'ils estimated
that ft'r.oufc 3,000, acre;: of tobacco vrcre treated ^.ith licptuchlor in
1ST:. (Table 4).
j.lv.1 :j.05ea cost 'to tobacco producers for rc-Tlacin^ heptachlor
vith a ncnorgGJiochlci-'.Vi-:: insecticide ' in 1971 vcrild.be $2.90 per
Dore treated for a tot:O. of about $9,000.
Addition a!! Josts ffr Ct>"-' rU:s
Tne adu.ed cor, 1. for replacing heptac:hloi-' v.-i-il) alternatiA'-e
insecticides for other uses would be $20,000— •$!£ ,600, for tobacco
seed}.)e6'o and $15,^00 for seed treat.-v.ents by fanr-.'rs (table !j).
Additional co~t& for cor.-.-.ercially treated seed ~ere nc'l estimated.
-------
sorghum
] Hcptachior
T«.,,. ." Quantity of _" Cost per °
~ L^"' ] active \ pound
' ingredient ' of -active
] used \ ingredient \
: Founds Dollars
•--c-'---"-)od^ 11 • 9.00^ 1.40
':-'::.-. eats 2/ : 11,000 1.40
:
: v:;:- .?•-. sunsd that diar^iii.on v;ould substitute fcr'h
'• '-"sec oil discussions with Mr. Muilctt, Oxtcnsion
and sr;.a.ll grains, United States.. 1971
' Dia-inen ;
\ Quantity of \ Cost -;-zr ' .erst for
Total ] active ; pound «| Tote I altcvr.' tive ;
cost ] ingredient ] of active '_ cost iMsoetieido
| used | ingredient ' '
Collars . Pounds Cellars Dollars "cl!".r.7
12,600 5,000 2.80 2S.200 1 7. :'-"•:"•
i.?,4oo 11,000 . .2. so 50, sco ' :;-.4:o |
•
i
eptachlor in a 1:1 ratio' -for soil insect control in seedbeds. ;
J;.it.o::'.oio?. ist , University of Tennessee,
u::iod that 1 oz. of hcptachlor or diar.inon can be used for seed treatments of corn, ,<~rain sc.rjhu;-
his estimate is based on insect control rocorjnendations for selected States.
-------
The total auJcd co:;t to United f/tateD .f:.;.-;. .::,•;: tor j-epVieinjj
h(-'pt.":':ilo:r '.:ith nonor^.nochlorine in:;;--eticid:.; in 197-1- voul.u have
been. :;:•£. 0 ;r..i.'i la 0:1 (tubik: M—.^l.J. jnilD.ion I'oi- ;:,ltcrnat:i.vc
iijsecticidi;:.' used on ccrn juicl tobacco> $0.9 :r.-:.Vl:i".on :i n prodxict.ion
IOSF.-.OG on cor.Oj ?-Jid v?o.,000 for • alternative iu;ect:i. cidor. used on
tobacco r,eed".jed:-. and for :>ced treatment by l'ar:^rs—pr:i:.i:i.rily corn.
Eliminating the use of heptachlor in fa:-.;-: production would have
little effect on the total quantity of inf3ecj,.lr:id-2s used. The
ou-uitity of hcptachlo;- used vould be reducec V; an outinntcd C9i>>000
•jjounds—669 >000 pound:-, or; corn» 6,000 poundo 07 tobacco, and 20V000
]K>undc for tobacco P.t-cnb'jds and seed. trof±;:;;;:ri. Tac total u.:,;; of
alternative insecticides would ranrn fron; ^62.200 poundn to 695jOOO
pound;;.. Alternative insecticide::-, u^ed in co;;-n production vould i'an~e
from ^:)6,000 pounds to 669,000 pounds dcpendi;^ on whether furriers
used BUJC, co-rbofur^n, dyfonate or phorato to control root\,'orr:is nnd
other coil insects. Diar.inon use in tobacco po duct ion and for seed
treatip.snts v.'ould increase 26..000 pouiidc if fai^ use of I'M-ptacliJor
vero cancelled.
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.'.'•-pcn'dix table 1.--lieptachlcr: Quantity used, on selected crops, by rec-ions , Unite:! S-c'inr, ~i •"••'••
?our.6>. of active ingredients
:\-ortn-
east
Corn " Northern
43
3/
-1,000 pounds-
=•/
7
14 3/
4
1
2/7
48 1,412 , 2/65
./ Includes Southern Plains, Mountain and Pacific Kcgions.
/ ". :>vir:s-3 estimate sines data was pxjblishca.
Loos tl'ic.r. 300 uouncl.".
•".-r-.:.-: :/•'~ 73~cicide and General Farnx Sur\-eyf 195G.
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,'prendi;-: table 2.—Heptachlor: Acreage of selected crops treated, "by regions. United
Croi
' Stater, " Belt
r-.crcr.ern. .-vpp1:
Plains ' laehi
150 1,71?
131
1.7:
TO
lur:;s Southern Pls.ins, Mo'jsritain and Pacific Pv
s than. 500 acres.
-i?3 Pesticide and General Farn Survey, 1965
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'?&
o insect control
Quantity of
active
.
*^>^c'j^'^c:i'r*vi'C
"""" " ~ .' ".'
aoDiicsa
rer acre ]./
Cost per
pour.d of
active
ingredient
Co.-:t
I n s e c 'c i c .1. tl e
' .rc':'..~crrr. control only -----
1.0
1.40
1.40
3.T-0
-':\C:.T' ^c ;.l insect control-:
1.0
1.40
-'. L inject control :
' 0
• • -J
1.40
2.80
Carbcfuran
Fhcrate
Average cost
Carbofuran
Dyfonate
Pherats
Diar; ir.cn
1.0
1.0
2-0
Ir.-•T':;T.i.stion for corn based on unpublished data .
ticids Usc--1971 Objective Corn yield Survey," T
tiop. oc:cnorr.ics Division, EPS, US DA. The rr.ts per acre is for a banded application. Freli-
ir.'.ii•.•'•.'r?. that 35 ;:orcent of the fa.rr.ors using n?:pt:;c./ilo:: acplied it in a band over the rev.
'O \" ~ ->?r 2. /? ^""r-^dcc-*.*~ •!--!-o?i"'*7*-p^'i~ r^^o^r^er'd'0^ ~'*v rj0"' oc^~'^d '"• ^"<"~-vr>5v
recei—
.7 f '-hcpbachlor use in corn production is car.celled there are several insecticides that riicht be used by f-
1 corn rootv:erjrs and other soil insects. The list cf alternative insecticides is based on insect centred
.-..••v'-.t ions for selected States and preliminary results from the "Pesticide Use—1971 Objective Corn Yield
-i:-"t frequently used insecticides in those States where hcptachlor was reported used in 1S71. If h-?.pt-.:
acco is cancelled enterr.cloc'ists in selected States indica^te dia~.inon wex?.ld r>ro!eably be r:-est froouently u"
:ihe rate per acre is for a b~";ccd application on corn and broadcast application or. tobacco based cn.ir.3o:
variations for selected States.
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