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Environ iTMrtttl Protection
Agmcy
Offin of PMtlefatai and Toxic Sutaunew
Office of Pwtidd* Program (T8-766C)
WMhington, DC 20460
xvEPA Pesticide
Fact Sheet
Name of Chemical:
Reason for Issuance:
Date Issued: *&• 30' 1985
Fact Sheet Number: 73
LINDANE
REGISTRATION STANDARD
Description of Chemical
Generic Name:
1,2,3,4,5,6-hexachloro-
Common Name
Trade Names
Gamma Isomer of
cyclohexane
Lindane •*"
Exagamma, Forlin, Gallogamma, Gammaphex,
Gammex, Gexane, Grammapoz, Grammexane,
Inexit, Kwell, Lindafor, Lindagrain,
Lindagram, Lindagranox, Lindalo, Lindamul,
Lindapoudre, Lindaterra, Lindex, Lindust,
Lintox, Novigram, and Silvanol
EPA Shaughnessy Code: 009001
Chemical Abstracts Service (CA) Number: 58-89-9
Year of Initial Registration: 1950
Pesticide Type: insecticide/acaracide
Chemical Family: chlorinated hydrocarbon
U.S. Producer: None
Foreign Producers: Celamerck GmbH KG
Ingelheim, Federal Republic of Germany
Rhone Poulenc Phytosanitaire
Lyon, France
Mitsui, Inc.
Fukuoka, Japan
Tianjin Interntl. Trust & Investment Corp.
Tianjin, China
USE PATTERNS AND FORMULATIONS
Application sites: field and vegetable crops (including seed
treatment) and non-food crops (ornamentals and tobacco),
greenhouse food crops (vegetables) and non-food crops (or-
namentals), forestry (including Christmas tree plantations),
domestic outdoor and indoor (pets and household), commercial
indoor (food/feed storage areas and containers), animal
premises (including manure), wood or wooden structures, and
human skin/clothing (military use only).
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Percent of lindane used on various crops/sites:
Hardwood Lumber 19%
Seed Treatment 48%
Forestry <1%
Livestock 20%
Pineapple 2%
Ornamentals 2%
Pecans 3%
Pets 3%
Structures <1%
Household 1%
Cucurbits 1%
Types and methods of applications: dip tank solution
(livestock, lumber, and pets), as a livestock spray, by
ground equipment delivering a ground or foliar spray
or dust, by soil incorporation, by soil injection in
combination with a fumigant (for the pineapple use only),
as a smoke (for greenhouse fumigation only), as a dust
for human skin/clothing (military use only).
Application rates: ranged from 0.25 to 2.25 oz/l00 lb of
seed for seed treatment; 0.1 to 2.0 .lb/A for foliar and
soil treatment; 0.8 to 1.5 oz/50,000 ft 3 of greenhouse;
0.006 to 0.11 lb/gal for bark; 0.023 to 3% sprays, dips,
and dusts for indoor and animal treatment; <0.01 lb/1,000
ft 2 for animal premises; <4 lb/1000 ft 2 (14.64% solutions
for wood and wooden structures; and 1% dust for human
skin/clothing treatment (military use only).
Types of formulations: 0.27%—ll.2% impregnated formulations,
0.5—75% Dusts, 3%—73% wettable powders, 0.5—25% liquids,
0.25—3% pressurized liquids, 1—4% flowable concentrates,
0.45—40% emulsifiable concentrates,
3. SCIENCE FINDINGS
Summary Science Statement: Lindane is a chlorinated hydro-
carbon of moderate mammalian acute toxicity. Lindane has
been shown to be oncogenic in mice but it is not genotoxic.
The Agency has concluded that lindane Is a possible human
carcinogen. The Agency is requiring that another rat
chronic/oncogenicity bioassay be performed. Lindane has
been associated with possible induction of blood dyscrasias
(aplastic anemia). The Agency is requiring a laboratory
animal study to permit assessment of lindane’s potential
to cause blood dyscrasias. Other toxicology studies
demonstrate systemic toxicity, targeting the liver and
kidney. Lindane’s behavior in the environment is not
well defined. The Agency is requiring a full complement
of environmental fate studies. Lindane is slightly to
moderately toxic to birds and highly toxic to some aquatic
organisms. Lindane is highly toxic to honeybees and
certain beneficial parasites and predacious insects.
Additional studies on the ecological effects of lindane
are required.
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Chemical Characteristics
Technical lindane is a white crystalline solid.
Its melting point is 112° — 113°C.
It is soluble in most organic solvents and is Telatively
insoluble in water.
Lindane is stable to light, heat, air and strong acids,
but decomposes to trichlorobenzenes and HCL in alkali.
Toxicology Characteristics
Acute Oral: 88 mg/kg, Toxicity Category II
Acute Dermal: 300 mg/kg Toxicity Category II
Acute Inhalation: Data gap
Primary Eye Irritation: Data gap
Primary Skin Irritation: Irritant Toxicity Category I
Skin Sensitization: Data gap
Major Routes of Exposure: Human exposure from lindane
is greatest during mixing, loading, and application.
Derinal, ocular, and inhalation exposures to workers may
occur during application. Exposure can be reduced by
the use of approved respirators, protective clothing,
and goggles.
Oncogenicity: A two—year mouse oncogenicity study
demonstrated increased incidences of liver tumors
(male & female) when dosed at 400 ppm. An 80—week mouse
feeding study demonstrated increased irtcidences of
liver tumors at the 80 ppm level but not at the 160 ppm
level. Two subchronic studies provide supportive evidence
of oncogenicity. The mouse studies were referred to the
Agency’s Carcinogen Assessment Group (CAG) for evaluation.
Based on the weight of the evidence, CAG classifed lindane
in the range B2—C. OPP believes that the classification
C is appropriate at this time and, therefore, will regulate
lindane as a class C carcinogen, pending receipt of the
required rat oncogenicity study.
Metabolism: Lindane does not appear to bioaccumulate in
tissues.
Teratology: Teratology studies in the rat, rabbit, and
mouse were negative for teratogenic effects.
Reproduction: A 3 generation rat reproduction study was
negative at 100 ppm.
Mutagenicity: Available data show lindane to be negative
for gene mutation in bacterial Ames assays, host mediated,
and dominant lethal assays. Lindane has been reported as
negative in other in vitro assays for DNA damage/repair
in bacteria, rat and mouse hepatocytes, and mammalian cell
transformation assays.
Physiological and Biochemical Characteristics
Mechanism of pesticidal action: Lindane acts in the
nervous system through unknown mechanisms.
Metabolism and persistence in plants and animals: The
metabolism of lindane in plants and livestock animals
has not been adequately described. Additional data are
being required.
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Environmental Characteristics
Available data are insufficient to assess the environmental
fate of lindane. Data gaps exist for all required studies.
Preliminary adsorption data indicate that lindane has a low
mobility in mineral soils and is relatively immobile in
muck soils; however, the potential for lindane contarnina-
tion of surface and ground water exists based on the results
of a monitoring study conducted in certain southern states.
Ecological Characteristics
Avian acute oral toxicity: Data Gap
Avian dietary toxicity: 882 ppm for bobwhite quail,
561 ppm for ring—necked pheasant (moderately toxic),
and >5000 ppm for mallard duck (practically nontoxic).
Freshwater fish acute (LC 50 ) toxicity: cold water species
(rainbow trout) 27 ppb for technical lindarte (very
highly toxic), warm water species (bluegill) 68 ppb for
technical liridane (very highly toxic).
Aquatic freshwater invertebrate toxicity: Daphnia 460 ppb
(highly toxic). Additional data are required to fully
characterize the ecological effects of lindane.
Available data are insufficient to fully assess the environ-
mental fate of and the ecological effects from lindane.
Required Unique Labeling Summary
All manufacturing—use and end-use lindane products must
bear appropriate labeling as specified in 40 CFR 162.10.
In addition, the following information must appear on the
labeling:
All manufacturing—use products must state that they are
intended for formulation into other manufacturing—use
products or end—use products only for registered uses.
All manufacturing—use products shall contain the following
text in the Environmental Hazards section of the label:
“This pesticide is toxic to fish and aquatic invertebr3tes.
Do not discharge effluent containing this product into
lakes, streams, ponds, estuaries, oceans, or public waters
unless this product is specifically identified and addressed
in an NPDES permit. Do not discharge effluent containing
this product into sewer systems without previously notifying
the sewage treatment plant authority. For guidance, contact
your State Water Board or Regional Office of the EPA.”
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All end—use products containing lindane that were classsi—
fied as restricted by the Final Notice of Determination
concluding the RPAR shall continue to be classified for
restricted use and the restricted use label must include
the cancer hazard warning statement.
All end—use products shall continue to carry the applicator
protection statements previously required by the Final
Notice of Determination concluding the RPAR. Products
with directions for foliar applicatiofl to crops whose
culture involves hand labor must bear the statements
required under PR Notices 83—2 and 84—1 for farinworker
safety, including a 24 hour re—entry interval.
End—use products with directions for spraying uninhabited
buildings or empty storage bins must include protective
clothing requirements including the use of a respirator.
All end—use products for indoor use shall indicate that
lindane is not to be applied to edible product areas
of food processing plants or to serving areas while
food is exposed.
All end—use products with uses on livestock or livestock
premises must indicate not to contaminate food, feed,
or water with the pesticide. Also, there must be a
statement that indicates lindane Is not to be applied
to poultry houses, dairy barns, and milk rooms. All
feed or water troughs must be covered and all livestock
should be removed from animal shelters (barns, sheds,
etc.) prior to treatment of the structure.
All end—use products for structural pest control must
indicate that lindane is not to be applied In currently
occupied areas (i.e. regular living or working areas,
including finished basements or finished attics) of
homes or other buildings. The characterization of a
use site depends upon its intended function and not
upon whether there are occupants in the area at the
time of treatment.
Tolerance Assessment
The Agency is unable to complete a full tolerance assess-
ment because the metabolism of lindane in plants and
livestock animals has not been adequately described.
Also, seed treatment is now considered to be a food
use requiring a tolerance unless results of a radio-
labeled study indicate that there is no translocatiOn
to edible parts of the plant following seed treatment.
No new tolerances, except those required to support
the existing seed treatment uses of lindane, will be
considered until the toxicology and residue chemistry
data gaps identified in the Standard have been filled.
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Established tolerances are published in 40 CFR 180. 133.
A listing of U.S. tolerances includes the following:
Tolerance expressed
Commodity as parts per million
Apples 1.0
Apricots 1.0
Asparagus 1.0
Avocados 1.0
Broccoli 1.0
Brussels Sprouts 1.0
Cabbage 1.0
Cattle, fat 7.0
Cauliflower 1.0
Celery 1.0
Cherries 1.0
Collards 1.0
Cucumbers 3.0
Eggplant 1.0
Goats, fat 7.0
Grapes 1.0
Guavas 1.0
Hogs, fat 4.0
Horses, fat 7.0
Kale 1.0
Kohlrabi 1.0
Lettuce 3.0
Mangoes 1.0
Melons 3.0
Mushrooms 3.0
Mustard Greens 1.0
NectarineS 1.0
Okra 1.0
Onions, dry bulb only 1.0
Peaches 1.0
Pears 1.0
Pecans 0.01
Peppers 1.0
Pineapples 1.0
Plums, md. Prunes 1.0
Pumpkins 3.0
Quinces 1.0
Sheep, fat 7.0
Spinach 1.0
Squash 3.0
Summer Squash 3. 0
Strawberries 1.0
Swiss Chard 1.0
Tomatoes 3.0
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The best available data for determining an interim accept-
able daily intake level of lindane is a subchronic feed-
ing study in rats (1983) which demonstrated a No Observed
Effect Level (NOEL) of 4 ppm. Based on dietary analysis,
food intake, and body weight data from this particular
study, the NOEL of 4 ppm is equivalent to 0.3 mg/kg/day.
Using this latter value and a safety factor of 1000, the
Provisional Acceptable Daily Intake (PADI) is 0.0003
mg/kg/day and the Maximum Permissible Intake (MPI) for
a 60 kg person Is 0.018 mg/day. The Theoretical Maximum
Residue Contribution (TMRC) for lindane, based on all
established tolerances, is 1.4189 mg/day/l.5 kg of diet
The percent of the MPI used by the TMRC is 7883%.
Although the theoretical concentration from existing
tolerances greatly exceeds the MPI, FDA market basket
surveys indicate that actual residues of lindane are
much lower. The Agency believes that the actual risk
to consumers from the daily consumption of lindane,
based on FDA market basket data for 1978—1982, is only
0.000002 mg/kg/day. Under this scenario, only 0.7% of
the Maximum Permissible Intake is actually used.
4. SUMMARY OF REGULATORY POSITION AND RATIONALE
The Agency has determined that it should continue the
registration of all currently registered uses of lindane.
The Agency concluded in the RPAR that most uses of lindane
would be continued because a risk/benefit assessment
demonstrated that the benefits from the uses outweighed
the risks provided certain labeling restrictions, such as
restricting some uses to certified pesticide applicators,
requirements for protective clothing, and label statements
describing necessary precautions were added to all lindane
labels. The Agency has reevaluated that decision and
concludes that, except as described below, the risks and
benefits are substantially the same as those described in
the RPAR process.
Based on FDA market basket residue levels, which the
Agency believes In this case is more generally representa-
tive of actual residues than theoretical calculations,
the estimate of the upper 95% confidence level for excess
cancer risk is 2x10 6 . The estimate of the upper 95%
confidence level for excess cancer risk to applicators for
various uses is estimated to be from l0 to l0 , depend-
ing upon the site and method of application. The Agency
has recalculated the exposures and margins of safety for
applicators for 24 use patterns and has developed initial
calculations for mixer/loaders or combination mixer/loader!
applicator for 3 use patterns (forestry, cucurbits, and
pecans). This reassessment is based on current Agency
methods and models and consideration of a lower NOEL from
the subchronic rat study for uses involving subchronic
type exposure.
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Based on these calculations, the Agency will initiate
Special Review for the forestry and uninhabited buildings
and empty storage bins spray uses on the basis of risks
to applicators. Use of protective clothing, including an
MSHA/NIOSH approved respirator, is now being required for
spraying uninhabited buildings and empty storage bins
while the Special Review is underway. Protective clothing
requirements stipulated in the Final Notice of Determination
of the lindane RPAR will continue for all other uses. No
significant changes from the exposure values presented in
PD—4 occurred for twelve of the uses. The calculated
exposures for cucurbits, crawl spaces, dog dusts, dog
dips, shelf paper, and commercial moth sprays increased
by approximately an order of magnitude, but are still
acceptable. Applicator exposure data is being required
for seed treatment, structural treatment, livestock
spraying, dog washes, dog shampoos, and dog dusts. Air
monitoring data are required for the structural treatment
and dog treatment uses. Exposure studies are required,
in addition to toxicity studies, to support the registra-
tions for application of lindane to human skin/clothing
by the military.
Lindane seed treatments were registered many years
ago as non—food uses not requiring tolerances. The Agency
now considers seed treatment to be a food use and requires
data to support a tolerance unless results of a radiolabeled
study indicate that there Is no translocation to edible
parts of the plant following seed treatment. Data from
one of these two alternatives must be submitted to support
the seed treatment uses. No new tolerances, except those
required to support the existing seed treatment uses, will
be considered until the chronic feeding and residue chem-
istry data gaps Identified in the Standard have been
filled.
Available data are insufficient to fully assess the
environmental fate of lindane and its ecological effects.
A full complement. of such studies is being required. Pre-
cautionary label statements will continue to be required.
5. Summary of Major Data Gaps Due Date
— An acute inhalation study 9 months
— A 90—day inhalation study 15 months
— A dermal sensitization study 9 months
— A 21—day derma]. toxicity study 12 months
— A rat chronic/oncogenicity study 50 months
— Laboratory animal blood dyscrasias study pending
— Full complement of environmental fate studies 39 months
— Plant metabolism studies 24 months
— Livestock animal metabolism studies 18 months
— Residue chemistry studies on all crops, 48 months
including seed treatment uses
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Contact Person at EPA
George T. LaRocca
Product Manager (15)
Insecticide—Rodenticide Branch
Registration Division (TS—767C)
Office of Pesticide Programs
Environmental Protection Agency
401 M Street, SW.
Washington, D.C. 20460
Office location and telephone number:
Room 204, Crystal Mall Building #2
1921 Jefferson Davis Highway
Arlington, VA 22202
703—557—2400
DISCLAIMER: THE INFORMATION PRESENTED IN THIS PESTICIDE
FACT SHEET IS FOR INFORMATIONAL PURPOSES ONLY AND IS NOT
TO BE USED TO FULFILL DATA REQUIREMENTS FOR PESTICIDE
REGISTRATION AND REREGISTRATION.
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