United States Office of Pesticides end Toxic Sutaanc*
Environmental Protection Office of Pectiode Programs (TS-766C)
Agency Washington, DC 20460
xvEPA Pesticide
Fact Sheet
Name of Chemical: Thiodicarb
Reason for Issuance:
Date Issued: Feb. 27/ 1984
Fact Sheet Number:
18
1. Description of Chemical
Generic Name: dimethyl N, N'-thiobis(methylimino) carbonyloxy
bis ethanimidothioate
Common Name: thiodicarb
Trade Name: Larvin®
EPA Shaughnessy Code: 114501
Chemical Abstracts Service (CAS) Number: 900
Year of Initial Registration: 1984
Pesticide Type: insecticide
Chemical Family: carbamate
U.S. and Foreign Producers: Union Carbide Corporation
2. USE PATTERNS AND FORMULATIONS
Application Sites and Rates;
Thiodicarb is currently registered for use on sweet corn
(fresh market only in the state of Florida). The applica-
tion rates range from 0.5 Ibs. active ingredient per acre to
0.75 Ibs. active ingredient per acre per acre, not to exceed
7.5 Ibs. active ingredient per acre per use season.
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Types of Formulations :
Thiodicarb is commercially formulated into five (5) flowable
products and one (1) wettable powder. There is also a 95%
technical product federally registered.
Types and Methods of Application :
Application to sweet corn is made with both ground and air
equipment.
3. Science Findings
Summary Science Statement
Thiodicarb is a cholinesterase inhibiting pesticide. Studies
on the formulated products demonstrate a moderate toxicity to
man (Toxicity Category II). The metabolism of thiodicarb is
adequately understood. One of the metabolic by—products of
thiodicarb in animals is acetamide, a potential carcinogen.
Thiodicarb is not expected to leach and reach ground water
or to bioaccumulate in the environment.
Chemical Characteristics :
Thiodicarb is a white crystalline powder with a slight sul-
furous odor. It has a melting point of 173—174°C. Thiodicarb
is stable in light and ambient conditions and unstable in alka-
line conditions. Its main degradation product is methomyl.
Toxicology Characteristics :
Thiodicarb technical is moderately toxic (Toxicity Category II)
via the oral and inhalation routes of exposure with LD 50 values
of 325 milligrams (mg)/kilogram (kg) and >0.32 mg/liter (L), re-
spectively. The acute dermal LD 50 for thiodicarb in rabbits is
>2000 mg/kg (Toxicity Category III). Corneal opacity and con-
junctival redness, chemosis and discharge were observed in the
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eyes of rabbits administered 44 mg of thiodicarb; however, all
lesions cleared by day 7.
The toxicological data submitted in support of the established
tolerance for residues in or on sweet corn includes a 2—year
rat feeding/oncogenicity study which was negative for oncogenic
effects at the levels tested (1.0, 3.0 and 10.0 mg/kg/day) and
had a cholinesterase (ChE) and chronic toxicity no—observed-
effect level(NOEL)of 10.0 and 3.0 mg/kg/day, respectively; a
mouse oncogenicity study which was negative at the levels
tested (1.0, 3.0 and 10.0 mg/kg/day); a 6—month dog feeding
study with a ChE and subchronic NOEL of 15.0 mg/kg/day; a rat
teratology study which was negative at 30.0 mg/kg/day and had
a fetotoxic NOEL of 3.0 mg/kg/day; a mouse teratology study
which was negative at 200 mg/kg/day and also had a NOEL of
200 mg/kg/day for fetotoxicity; a 3—generation rat reproduc-
tion study with a NOEL of 10.0 mg/kg/day (HDT); and an acute
delayed neurotoxicity study which was negative at 660 mg/kg.
Studies on mutagenicity showed negative potential. Based on
the 2—year rat feeding study with a chronic toxicity NOEL of
3.0 mg/kg/day and using a safety factor of 100, the acceptable
daily intake (ADI) for humans is 0.03 mg/kg of body weight
(bw)/day. The theoretical maximum residue contribution (TMRC)
from the established tolerance on sweet corn utilizes 2.38
percent of the ADI.
The oncogenic potential of acetamide has been demonstrated
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in four different studies, the first being a study conducted
by F. I. Dessau and B. Jackson in 1955, where two groups of
Rockland albino rats were treated with a 40% solution of acet—
amide at a rate of 4000 mg/kg (equivalent to 40,000 ppm for
younger rats or 80,000 ppm for older rats) by intubation 5
days/week for a period of 117 days for Group I and 205 days
for Group II. Histopathological examination showed cytologic
irregularities consisting of a greater variability of cellular
and nuclear size, giant nuclei, and the presence of numerous
mitoses, some of unusual appearance. Benign hepatocellular
adenomas were also found in 2 treated animals in Group II.
Doctors Dessau and Jackson conducted a second study in 1961,
with 3 groups of Wister albino rats. The test duration was 12
months. Group I animals were administered via diet a 5% (50,000
ppm) solution of acetamide continuously. Group II animals
were divided into three subgroups receiving 5%, 2.5% (25,000
ppm) and 1.25% (15,000 ppm) acetamide. Test material was
administered in a diet of ground Wayne Laboratory Blox. Each
week, two rats from treatment Group III were taken of f the
acetamide diet and placed on a control diet for the remainder
of the testing period. Hepatomas were noted in four of forty
eight animals in Group I, one of eighteen animals, six of
twenty—two animals and four of twenty four animals tested in
Group II, subgroups 1—3 respectively, and twenty-two of eighty
one animals tested in Group III. In a study conducted by J.
H. Weisburger, R. S. Yamamoto, R. M. Glass and H. H. Frankel
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in 1969, 2 groups of male Wister rats were administered 2.5%
(25,000 ppm) acetamide in a diet of Wayne Laboratory Blox.
Group I animals were sacrificed after twelve months. Test
animals in Group II were removed from the acetamide diet after
twelve months and continued on a controlled diet for an addi-
tional three months. Animals in both test groups were adminis-
tered 75 milligrams/liter of oxytetracycline (Terramycin) for
one week every sixth week of the study. Hepatomas were noted
in 2 of eight animals tested in Group I and 7 of sixteen animals
tested in Group II. No effect was noted in the fifteen control
animals.
The fourth study, a carcinogenesis bioassay of acetamide in
rats and mice was conducted by R. W. Fleischman, et. al. in
1980. This study included 8 compound—dosage groups per sex
for rats and 10 such groups for mice. Rats received 2.36%
(23,600 ppm) of acetamide via diet. The mice were divided
into two groups with Group I receiving 1.18% (11,800 ppm) of
acetamide and Group II receiving 2.36% of acetamide. Test
material was administered to animals in a diet of ground Wayne
Lab Blox for a 12 month period and was then replaced with a
controlled diet of Wayne Blox pellets for an additional 4
months. There were no apparent compound related effects noted
in male and female mice. However, 41 liver carcinomas and 1
neoplastic nodule were noted in male rat test animals and 33
liver carcinomas and 3 neoplastic nodules were noted in female
rat test animals.
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The Agency has evaluated the four acetamide studies and have
found the studies inappropriate for addressing the tumorigeni—
city potential of acetamide in accordance with today’s standards
for oncogenicity testing. Only a small number of male rats
were used in 3 of the 4 studies in either the test groups or
the controls or both. A single dietary level was administered
to rats in 3 of the 4 studies which does not allow the determi-
nation of a dose related effect. In all studies, the exposure
rates were extremely high which may have been responsible for
the excessive weight loss and mortality noted in several of
the studies. The administration of oxytetracycline (Terramycin)
to test animals in the study conducted by Weisburger et. al.
(1969) raises questions on the quality of the animals used and
the possibility of adversely influencing the results of the
experiment. A time related dose response which may or may not
be real from a biological point of view was noted in the Dessau
and Jackson study of 1961. Also the results of this study
which indicated that there were no tumor effects in similar
rats receiving a diet of acetamide in Purina Laboratory Chow
versus effects in test animals receiving a diet of acetamide
in ground Wayne Laboratory Blox casts doubts on the certainty
of acetamide’s oncogenic potential, as well as its potential
hazard to humans. In the study conducted by R. W. Fleischman,
et. al. in 1980, test animals (mice) used came from different
lots and suppliers. Data describing weight gain, survival and
intercurrent disease were not provided. Also, in this study
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the number of tissues examined varied between study groups.
Based on the conduct of the available studies on acetamide and
in consideration of the available oncogenicity testing in the
rat and mouse for thiodicarb which demonstrated a negative
oncogenic potential, the Agency has not determined that
thiodicarb is oncogenic under normal agricultural practices.
However, the Agency has conducted a risk assessment of the
proposed tolerance request based on the four acetamide studies.
The estimated maximum daily human exposure to acetamide from
conversion of consumed thiodicarb residues is 1.4 x iO
mg/day for a 60 kg person and with an exposure risk of 3.07 x
i03 the resulting life—time carcinogenic risk estimate is 7
x lOs. This life—time carcinogenic risk assessment is
based on the following assumptions:
— Acetamide is presumed definitely to be carcinogenic.
— Carcinogenic effects noted in experimental animals
at acetamide dietary levels of 10,000—80,000 ppm
are applicable to humans exposed at a maximum level
of 9.3 ppb.
— The mathematical relationship between dose and
response that holds in the low dose region is based
on the application of the one—hit model of carcino-
genesis which yields the highest risk of any of the
plausible models of dose response relations.
— The metabolic pathway of thiodicarb in humans is
presumed to be the same as that found in test
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animals and the highest value of risk obtainable
from the animal data is applicable to humans.
— The conversion ratio of thiodicarb to acetamide in
test animals is 306, based on metabolism studies,
and this is the same in humans.
— Total production of sweet corn components in the
United States will contain thiodicarb residues at
the tolerance level.
Physiological and Biochemical Behavior Characteristics :
The metabolic pathway of thiodicarb in livestock has been
demonstrated to be thiolysis to methomyl, followed by hydro-
lysis to the methomyl oxime and subsequent metabolization to
acetonitrile. Acetonitrile is then metabolized to acetamide,
a potential carcinogen, and further hydrolyzed to acetic acid
which enters the intermediary metabolism cycle of the animal
and is ultimately expired as carbon dioxide.
Plant metabolism studies show that thiodicarb is likewise
metabolized to the methomyl oxime followed by acetonitrile
and carbon dioxide, both of which are then volatilized.
Environmental Characteristics :
Thiodicarb is very stable at pH 6 and unstable in alkaline
conditions. It is subject to decomposition by eight. The
major by—product of photolysis is methomyl. Light textured
soils causes more rapid degradation than heavy textured soils.
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Thiodicarb exhibits low mobility in all soils. Degradation
is also influenced by increasing temperatures, degree of aera-
tion and microbial activity. The half—life on soil and plant
surfaces is less than one week. Thiodicarb is non—persistent
in the environment.
Ecological Characteristics :
Thiodicarb is moderately toxic to fish with a LC 50 value of
2.55 ppm for the rainbow trout and 1.21 ppm for the bluegill
sunfish. The avian acute LD 50 for the bobwhite quail is
2023 ppm. The subacute dietary LC 50 for the bobwhite quail and
the mallard duck is 5620 ppm. The 48—hour acute LC 50 for
aquatic organisms is 0.0053 ppm.
Tolerance Assessment :
A tolerance of 2.0 parts per million (ppm) has been established
to cover residues of thiodicarb and its rnetabolite methomyl in
or on sweet corn grain (kernels plus cob with husk removed
(K+WHR)) under the provisions of the Federal Food, Drug and
Cosmetic Act (FFDCA). The 2.0 pm tolerance level is adequate
to cover anticipated residues in or on sweet corn as a result
of application under the currently registered use pattern.
4. Summary of Regulatory Position and Rationale:
Geographical Restrictions :
Thiodicarb is currently registered for use on sweet corn only.
Products containing thiodicarb are also limited to application
to sweet corn only in the State of Florida. Grazing and feeding
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of treated corn fodder and forage is prohibited.
Summary of Risk Assessment
On the basis of the available studies on acetamide and the
chronic oncogenicity studies for thiodicarb, the Agency has
concluded that the human risks posed by the use of thiodicarb
on sweet corn does not raise prudent concerns of unreasonable
adverse effects.
5. Summary of Major Data Gaps
All data requirements have been addressed for thiodicarb.
Therefore, all products containing thiodicarb have been uncondi-
tionally registered.
6. Contact Person at EPA
Jay S. Ellenberger
Product Manager (12)
Insecticide—Rodenticide Branch
Registration Division (TS—767C)
Office of Pesticide Programs,
Environmental Protection Agency,
401 M St., SW.,
Washington, D.C. 20460.
Office location and telephone number:
RM. 202, CM #2,
1921 Jefferson Davis Highway,
Arlington, VA 22202,
(703—557—2386).
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