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thiodicarb (Larvin) Chemical Fact Sheet 8/84

                         CHEMICAL FACT SHEET FOR:
                               THIODICARB

FACT SHEET NUMBER: 18

DATE ISSUED: AUGUST 8, 1984


                     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
  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

Chemical Characteristics

   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.


Toxicological Characteristics

- 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
  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.
- 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.


Environmental Characteristics

   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.


Ecological Characteristics

   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.


Tolerance Assessment

   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 
pattern.


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)
Insecticide-Rodenticide Branch
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
(703) 557-2386


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.