thiodicarb (Larvin) Chemical Fact Sheet 8/84
CHEMICAL FACT SHEET FOR:
FACT SHEET NUMBER: 18
DATE ISSUED: AUGUST 8, 1984
1. DESCRIPTION OF CHEMICAL
- Generic Name: dimethyl n, n'-thiobis(methylimino) carbonyloxy bis
- 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
application rates range from 0.5 lbs. active ingredient per acre to
0.75 lbs. active ingredient per acre, not to exceed 7.5 lbs. active
ingredient per acre per use season.
- 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
Thiodicarb is a white crystalline powder with a slight sulfurous
odor. It has a melting point of 173-174 C. Thiodicarb is stable in
light and ambient conditions and unstable in alkaline conditions. Its
main degradation product is methomyl.
- Thiodicarb technical is moderately toxic (Toxicity Category II) via
the oral and inhalation routes of exposure, with LD50 values of 325
milligrams (mg)/kilogram (kg) and >0.32 mg/liter (L), respectively.
The acute dermal LD50 for thiodicarb in rabbits is >2000 mg/kg
(Toxicity Category III). Corneal opacity and conjunctival redness,
chemosis, and discharge were observed in the eyes of rabbits admin-
istered 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 repro-
duction 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 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 acetamide 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 two 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 off the acetamide diet and placed on a control diet for the
remainder of the testing period. Hepatomas were noted in 4 of 48
animals in Group I. 1 of 18 animals, 6 of 22 animals, and 4 of 24
animals tested in Group II, subgroups 1-3 respectively, and 22 of 81
animals tested in Group III. In a study conducted by U. H. Weisburger,
R. S. Yamamoto, R. M. Glass, and H. H. Frankel in 1959, 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
12 months. Test animals in Group II were removed from the acetamide
diet after 12 months and continued on a controlled diet for an
additional 3 months. Animals in both test groups were administered 75
milligrams/liter of oxytetracycline (Terramycin) for one week every
sixth week of the study. Hepatomas were noted in 2 of 8 animals
tested in Group I and 7 of 16 animals tested in Group II. No effect
was noted in the 15 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.
- The Agency has evaluated the four acetamide studies and has found the
studies inappropriate for addressing the tumorigenicity 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 determination 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 cast 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 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 10-4 mg/day for a 60-kg person, and with an exposure risk of
3.07 x 10-3, the resulting lifetime carcinogenic risk estimate is 7 x
10-9. This lifetime carcinogenic risk assessment is based on the
- 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.
- This mathematical relationship between dose and response that holds in
the low dose region is based on the application of the one-hit model
of carcinogenesis 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 animals, and the highest value of
risk obtainable from the animal data is appl.cable 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 Behavioral Characteristics
- The metabolic pathway of thiodicarb in livestock has been
demonstrated to be thiolysis to methomyl, followed by hydrolysis 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.
Thiodicarb is very stable at pH 6 and unstable in alkaline
conditions. It is subject to decomposition by eight. The major
byproduct of photolysis is methomyl. Light textured soils cause more
rapid degradation than heavy texture soils. Thiodicarb exhibits low
mobility in all soils. Degradation is also influenced by increasing
temperatures, degree of aeration, and microbial activity. The half-
life on soil and plant surfaces is less than one week. Thiodicarb is
non-persistent in the environment.
Thiodicarb is moderately toxic to fish, with an LC50 value of 2.55
ppm for the rainbow trout and 1.21 ppm for the bluegill sunfish. The
avian acute LD50 for the bobwhite quail is 2023 ppm. The subacute
dietary LC50 for the bobwhite quail and the mallard duck is 5620 ppm.
The 48-hour acute LC50 for aquatic organisms is 0.0053 ppm.
A tolerance of 2.0 parts per million (ppm) has been established to
cover residues of thiodicarb and its metabolite 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
ppm tolerance level is adequate to cover anticipated residues in or on
sweet corn as a result of application under the currently registered use
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 byproducts of thiodicarb in animals is acetamide, a
potential carcinogen. Thiodicarb is not expected to leach or reach
groundwater or to bioaccumulate in the environment.
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 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 do 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 unconditionally registered.
6. CONTACT PERSON AT EPA
Jay S. Ellenberger
Product Manager (12)
Registration Division (TS-767C)
Office of Pesticide Programs
Environmental Protection Agency
401 M St., S.W.,
Washington, DC 20460
Office location and telephone number:
RM. 202, CM #2
1921 Jefferson Davis Highway
Arlington, VA 22202
DISCLAIMER: THE INFORMATION PRESENTED IN THIS CHEMICAL INFORMATION FACT
SHEET IS FOR INFORMATIONAL PURPOSES ONLY AND NOT TO BE USED TD FULFILL
DATA REQUIREMENTS FOR PESTICIDE REGISTRATION AND REREGISTRATION.