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Captan - Chemical Fact Sheet 3/86

                             CHEMICAL FACT SHEET FOR:

                                     Captan

FACT SHEET NUMBER:  75

DATE ISSUED:  MARCH 6, 1986

                   1. DESCRIPTION OF CHEMICAL

- Generic Name:  N-trichloromethylthio-4-cyclohexene-1, 2-dicarboximide
- Common Name:  Captan
- Trade Names:  Merpan, Orthocide, SR-406, and Vancide 89
- EPA Shaughnessy Code:  081301
- Chemical Abstract Service (CAS) Number:  133-06-2
- Year of Initial Registration:  1951
- Pesticide Type:  Fungicide
- U.S. Producer:  Chevron Chemical Company,
                  Stauffer Chemical Company,
                  Makteshim Beer Sheva Chemical Works, Ltd.,
                  Calhio Chemicals, Inc.

               2. USE PATTERNS AND FORMULATIONS

Application Sites:

     Captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) is a
fungicide federally registered for use on almonds, apples, apricots,
asparagus, avocados, beans, beets, blackberries, blueberries, broccoli,
brussels sprouts, cabbage, cantaloupes, carrots, cauliflower, celery,
cherries, corn (sweet), cotton, cranberries, cucumbers, dewberries,
eggplants, grapefruits, grapes, honeydew melons, kale, lemons, lettuce,
limes, mangoes, mustard, nectarines, onions, oranges, peaches, pears,
peas, peppers, pineapples, plums, potatoes, pumpkins, quinces,
raspberries, rhubarb, rutabagas, soybeans, spinach, squash,
strawberries, tangelos, tangerines, taro, tomatoes, turnips, and
watermelons. The following crops may be seed-treated: alfalfa,
asparagus, barley, beans, beans (lima), beets (table), bluegrass,
broccoli, brussels sprouts, cabbage, cantaloupes, carrots, cauliflower,
clover, collards, conifers (Douglas fir, Red pine, Scotch pine, Norway
spruce), corn (field and sweet), cotton, cowpeas, crucifers, cucumbers,
eggplants, flax, forage grasses, kale, lentils, lespedeza, millet, milo,
muskmelons, mustard, oats, okra, onions, peanuts, peas, peppers,
pineapples, pumpkins, radishes, rape, rice, rutabagas, rye, safflower,
sesame, small-seeded legumes, sorghum, soybeans, spinach, squash, sugar
beets, sunflowers, Swiss chard, tomatoes, trefoil, turnips, watermelons,
and wheat.  Ornamental crop uses include: foliar applications to
azaleas, begonias (tuberous), camellias, carnations, chrysanthemums,
dichondra, grasses (ornamental in nonpastured areas only), grasses (lawn
seedbeds), hollyhocks, lilacs, snapdragons, spireas, roses, and stocks;
for soil in plant beds and on green house benches used for the culture
of flowers, roses, shrubs and trees; and as a dip application to
gladiolus corms, to begonia tubers, and to azalea cuttings. Captan may
be applied to packing boxes for use in storage and shipping of fruits
and vegetables and to soil used in greenhouses for culture of
ornamentals and vegetables.

Household uses include:

     Application to fruit, vegetable and ornamental gardens, house
plants and lawns, in paints (oil based), on surfaces (awnings, blankets,
boats, closets, clothing, draperies, floors, leather goods, luggage,
mattresses, rugs, shoes, storage rooms, upholstery, walls, workshops),
and on other articles.  Industrial uses include incorporation into
lacquers, paints (oil based), paper, paste (wallpaper flour),
plasticizers, polyethylene, rubber stabilizer, textiles, vinyl, and
vinyl resins.

- Types of formulations:  dusts, wettable powders, aqueous suspensions
  and granules.
- Types and methods of application:  dusting, spraying, misting,
  dipping, mixing, and low pressure bomb aerosols.
- Application rates:  see use patterns in USDA Compilations of
  Registered Uses of Fungicides and Nematicides, Part I, pages
  C-10-0001 to C-10-00.21.
- Usual Carriers:  clay, talc, silica, and water.
- Efficacy review results:  Captan product registrations with EPA have
  been supported with efficacy data. Tolerant strains of target plant
  pathogens have not been reported.

                     3. SCIENTIFIC FINDINGS

Chemical Characteristics

- Physical state:  pure is white crystals, technical is white to
  buff colored amorphous powder.
- Color:  white to buff
- Odor:  pure is odorless, the technical is pungent.
- Melting point:  158-164 degrees C
- Vapor pressure:  less than 10 to the minus (-6) mm Hg at 25 C.
- Solubility:  practically insoluble in water, soluble in acetone,
  ethanol, kerosene, xylene, chloroform, and benzene.
- Stability:  regarded as stable. Decomposes slowly at the melting
point. In solution captan decomposes rapidly depending on the pH and
temperature, being slower at pH 4 and rapid at pH above 10.

Toxicology Characteristics

- Acute oral LD50 - rat: 9 gm/kg, Category IV.
- Acute inhalation LD50 - rat:  males  5.8 mg/l, Category III
                                females > 8.9 mg/l, Category III
- Eye irritation - rabbit: corneal opacity, iris and conjunctive
  irrigation present through day 21, Category I.
- Dermal sensitization:  moderate sensitizer.
- Subchronic rodent:  filled by the 2 year chronic feeding study in
  rats.

Teratogenicity:

- Rabbit - not teratogenic at 6, 12, 25, or 60 mg/kg/day. Maternal
  toxicity observed as weight loss at high dosage.
- Hamster - dosed, at 50, 200, and 400 mg/kg/day. Severe maternal weight
  loss at 400 mg/kg/day. Incidence of skeletal abnormalities;
  i.e., fused ribs, was increased at high dosage. These lesions were
  considered to be within normal background incidence.

Reproduction and fertility effects (feeding):

- a. Three generation reproduction study - rats:
  Rats were fed 25, 100, 250, and 500 mg/kg/day for three generations.
  Body weight reductions occurred at 100, 250, and 500 mg/kg/day and a
  reduction of food consumption occurred at 100, 250, and 500 mg/kg - in
  F1 males and F2 females.  Pup litter weights were decreased in all
  dosage groups.

- b. One generation reproduction study - rats:
  Rats were fed a diet of 6, 12.5, and 25 mg/kg/day. No treatment
  related effects due to captan were seen. (The NOEL for these studies
  (a and b) when combined, is 12.5 mg/kg/day.)

Mutagenicity:

Gene mutation:

- In vivo somatic mutation assay with mice - no mutations were observed.
- Captan was mutagenic to various strains of S. typhimurium in saline.
  Decreased mutagenicity was observed when captan was incubated with
  blood or urine. Captan was not mutagenic in the host mediated assay in
  mice or rats with S. typhimurium hisG46 or TA1950. Negative findings
  were also obtained in vitro with blood or urine of captan-treated mice
  or rats.
- Captan was mutagenic for point mutations in E. coli and S typhimurium.
  However, it did not produce heritable chromosome aberrations in vivo
  (this was the conclusion of a working group chaired by W. M.
  Generoso.)
- Captan was not mutagenic for the dominant lethal test using C3H male
  and SLR-ICR female mice. No significant increases in chromosomal
  aberrations were observed in human fibroblasts in vitro or in bone
  marrow cells of Wistar rats in vivo.

Chromosomal aberrations:

- Chinese hamster V79 cells were treated with captan technical at
  concentrations up to 6.0 x 10 to the minus (-5) M. Chromosomal
  aberrations were observed at 4.5 x 10 to the minus (-5). Increased
  frequency of sister chromatid exchanges were observed at 1.5 x 10
  to the minus (-5) M and above.

Unscheduled DNA synthesis (UDS):

- W1-38 cells were incubated with captan technical and tritiated
  thymidine for 3 hr without or 1 hr with S-9 activation. The DNA was
  extracted and the incorporated labeled thymidine counted. Captan did
  not induce UDS in W1-38 cells.

Chronic toxicity (feeding):

- a. Rat:  In a rat feeding study at 0, 25, 100 and 250 mg/Kg/day
treatment-related neoplasms (renal bubular adenomas and carcinomas) in
males were observed at 100 and 250 mg/Kg/day. The LEL was 100 mg/kg/day
based on hepatocellular hypertrophy, increased kidney weight (male and
female) and decreased body weight (male and female). The NOEL was 25
mg/Kg/day. This study partially satisfies the chronic testing
requirement for registration.

Oncogenicity (feeding):

- a. Rat:  see a above, chronic toxicity in the rat.

- b. Mouse (high dose study):  In a CD-1 mouse study technical captan at
dietary concentrations of 6,000, 10,000, and 16,000 ppm induced both
benign and malignant duodenal tumors in both males and females.

- c. Mouse (low dose study): In a second CD-1 mouse study there was an
increased incidence of focal hyperplasia, adenoma/polyp(s) and primary
carcinomas in the gastrointestinal tract of both male and female mice at
the highest level tested (6,000 ppm) and a possible increase at the
highest dosage levels.

Physiological and Biochemical Behavioral Characteristics

- Foliar absorption:  Captan and/or its metabolites and degradates is
(are) absorbed by roots and shoot of plants.
- Translocation:  Captan and/or its metabolites and degradates is (are)
  translocated in plant tissue. Captan and/or its metabolites and
  degradates is (are) absorbed and translocated within plants as a
  result of seed treatment, soil treatment and foliar application.
- Mechanism of pesticidal action:  unknown.
- Metabolism and persistence in plants and animals:  The metabolism and
  accumulation of captan in plants are not understood. The metabolism of
  captan is understood for ruminants but not for avian species.

Environmental Characteristics

- Data gap.

Ecological Characteristics

- Hazards to fish and wildlife:
  - Bluegill sunfish     96 hr LC50 = 0.047 - 0.111 ppm
  - Rainbow trout        96 hr LC50 = 0.066 - 0.808 ppm
- Characterized as "very highly toxic" to both cold water and warm
  water fish.
- Daphnia magna: 48 hr LC50 = 7.06 - 9.96 ppm
- Moderately toxic to aquatic invertebrates.
- Avian toxicity:  LC50 = quail > 2400 ppm
- Avian reproduction:  Available data indicate that captan does not
  impair avian reproduction.
- Potential problems related to endangered species. The Agency has
  made a preliminary finding that the use of captan as a fungicide
  in rice, cranberries, and citrus may affect the status of
  endangered birds, fish, and insect species. An endangered bat may
  be affected by the use of captan on taro in Hawaii. The Agency
  will seek the opinion of the U.S. Fish and Wildlife Service in
  these matters, to better determine what, if any, actions are
  necessary to protect these species.

Tolerance Assessments

- List of crops and tolerances:

- The following table lists the present status for tolerances in parts
per million (ppm) for residues of captan:

                               Part per Million in Captan Residues
Raw Ag. Commodity            U.S.     Canada     Mexico     Codex

Almond, hulls              100.0I*      --         --         --
Almonds                      2.0I       --         --         --
Apples                      25.0*      5.0       25.0       25.0
Apricots                    50.0       5.0         --         --
Avocados                    25.0        --         --         --
Beans, dry                  25.0I       --       25.0         --
Beans, succulent            25.0I       --       25.0       10.0
Beets, greens              100.0        --         --         --
Beets, roots                 2.0        --         --         --
Blackberries                25.0        --         --         --
Blueberries (Huckleberries) 25.0       5.0         --       20.0
Broccoli                     2.0        --        2.0         --
Brussels sprouts             2.0        --         --         --
Cabbage                      2.0        --        2.0         --
Cantaloups                  25.0        --       25.0         --
Carrots                      2.0        --        2.0         --
Cattle, fat                  0.05       --         --         --
Cattle, MBYP                 0.05       --         --         --
Cattle, meat                 0.05       --         --         --
Cauliflower                  2.0        --        2.0         --
Celery                      50 0        --       50 0         --
Cherries                   100.0       5.0         --       50.0
Collards                     2.0        --         --         --
Corn, sweet (K+CWHR)         2.0        --        2.0         --
Cotton, seed                 2.0        --        2.0         --
Crabapples                  25.0       5.0       25.0       25.0
Cranberries                 25.0       5.0         --       10.0
Cucumbers                   25.0        --       25.0       10.0
Dewberries                  25.0        --         --         --
Eggplant                    25.0        --         --         --
Garlic                      25.0        --       25.0         --
Grapefruit                  25.0I       --         --       15.0
Grapes                      50.0       5.0         --         --
Hogs, fat                    0.05       --         --         --
Hogs, MBYP                   0.05       --         --         --
Hogs, meat                   0.05       --         --         --
Honeydew melons             25.0        --       25.0         --
Kale                         2.0        --         --         --
Leeks                       50.0        --         --         --
Lemons                      25.0I       --         --       15.0
Lettuce                    100.0        --      100.0       10.0
Limes                       25.0I       --         --       15.0
Mangoes                     50.0        --       50.0         --
Muskmelons                  25.0        --       25.0         --
Mustard greens               2.0        --         --         --
Nectarines                  50.0        --         --         --
Onions, dry bulb            25.0        --       50.0         --
Onions, green               50.0        --       25.0         --
Oranges                     25.0I       --         --       15.0
Peaches                     50.0       5 0       40 0       15 0
Pears                       25.0       5.0       25.0       25.0
Peas, dry                    2.0        --        2.0         --
Peas, succulent              2.0        --        2.0         --
Peppers                     25.0        --         --       10.0
Pimentos                    25.0        --         --       10.0
Pineapples                  25.0I       --       25.0         --
Plums (fresh prunes)       100         5.0         --       10.0
Potatoes                    25.0I      2.0       15.0         --
Pumpkins                    25.0        --         --         --
Quinces                     25.0        --         --         --
Raspberries                 25.0       5.0         --       10.0
Rhubarb                     25.0        --         --       15.0
Rutabagas, roots             2.0        --         --         --
Shallots                    50.0        --         --         --
Soybeans, dry                2.0        --        2.0         --
Soybeans, succulent          2.0        --        2.0         --
Spinach                    100.0        --      100.0       20.0
Squash, summer              25.0        --         --         --
Squash, winter              25.0        --         --         --
Strawberries                25.0       5.0       25.0       20.0
Tangerines                  25.0I       --         --       15.0
Taro (corn)                  0.25       --         --         --
Tomatoes                    25.0       5.0         --       15.0
Turnips, greens              2.0        --         --         --
Turnips, roots               2.0        --         --         --
Watermelons                 25.0        --       25.0         --

*I Interim tolerance pending evaluation (under Special Review) of
transfer of captan residues to meat, milk and eggs from feeding the raw
agricultural commodity or their byproducts.
** Established tolerance under regulation, Section 180.103, 40 CFR.

****************************************************************************
NOTE: On March 14, 1990, EPA proposed to revoke the tolerances for crab-
      apples, cranberries, grapefruit, lemons, limes, oranges, pineapples,
      quinces, rhubarb, and tangerines (Federal Register, 3/14/90).  EPA
      initiated this action because all uses of captan on these commodities
      have been cancelled.
***************************************************************************
------------------------------------------------------------------------

- A feed additive regulation (561.65, Title 21, Code of Federal
  Regulations; Parts 500 to 599) permits residues of captan at 100.0 ppm
  remaining on corn seed from its intended use as a seed protectant
  after detreatment. Detreated corn seed can be used only as a feed for
  cattle and hogs up to 14 days prior to slaughter.
- A food additive regulation (193.40, Title 21, Code of Federal
  Regulations Parts 170 to 199) permits 50.0 ppm residues of captan in
  or on washed raisins when present as a result of fungicidal treatment
  by preharvest application to grapes and postharvest application during
  the drying process.
- No tolerances have been established for captan residues in or on any
  crop commodity for which captan is registered solely for seed or plant
  propagule application, because heretofore seed or plant propagule
  applications were considered as nonfood uses. Seed use sites are
  listed under Use Patterns and Formulations.

Data GAPS in Residue Chemistry:

- Available plant metabolism data are not completely adequate for
  identifying the metabolites that may result from the maximum uses and
  necessary to support the established tolerances.
- Available animal metabolism data are not adequate to support the
  tolerances in meat; and to establish tolerances in milk, and poultry
  and eggs.
- For enforcement purposes, FDA's Pesticide Analytical Manual, Method I,
  Vol. II, Pesticide Regulation Section 180.103 is acceptable for plant
  commodities. No validated method is available for enforcement of
  tolerances for residues of captan in animal commodities.
- Inadequate data are available on the storage stability of residues of
  captan in animal commodities or in or on plant commodities.
- The following uses need tolerances to allow continued registrations:
  - California, Special Local Needs registration CA780027 - use of
    captan as a seed treatment or as a root dip in the culture of
    asparagus.
  - Washington, Special Local Needs registration WA800035 - use of
    captan as a seed treatment or as a soil treatment in the culture of
    kohlrabi.
  - Use-patterns for treatment of soil and greenhouse benches in which
    vegetables (without tolerances) are grown.
- The data are insufficient to assess the established tolerance for
  residues in or on detreated seed corn because no data were submitted
  depicting residues resulting from detreated seed that originally had
  been treated at the maximum allowable rate. A mechanism must be
  implemented to prevent the feeding of detreated seed corn which
  contains residues of pesticides in addition to those of captan.
- Heretofore, seed treatments and plant propagule treatments have
  been considered nonfood uses. Available plant metabolism data indicate
  that residues of captan may be taken up into mature plants from
  treated seed. Therefore, seed treatments are uses for which residue
  data and requests for EPA Pesticide Petitions for proposed tolerances
  must be submitted.
- Processing studies are required for the following commodities:
  potatoes, beans, soybeans, tomatoes, oranges, plums, sweet corn, and
  cottonseed. Captan may be used as a component of paper and paper board
  that may come in contact with aqueous and fatty foods {21 CFR
  176.170(c)}. Residue data to support this regulation are required to
  support the EPA registered use-pattern. Alternatively, label
  amendments are required to restrict the use of captan-treated packing
  boxes for fruits and vegetables having tolerances for residues of
  captan.
- The theoretical maximum residue contribution (TMRC) from established
  tolerances is 12 mg/day based on a 1.5 kg diet. The changes in the
  residue definition, the requested tolerance proposals, and the pending
  tolerances noted above will all affect a change in the TMRC level. The
  data requirements to support established tolerances as listed in 40
  CFR 180.103 are identified.
- The Provisional Maximum Permissible Intake (PMPI) for a 60 kg person
  is O.75 mg/day based on a Provisional Acceptable Daily Intake (PADI)
  of 0.0125 mg/kg. The present TMRC represents 1600 percent of the PMPI.
  The inclusion of the major metabolite (THPI) in the tolerance
  expression may result in an increase in the TMRC and a greater
  percentage of the PMPI utilized.
- The PADI for captan is based on a reproductive toxicity study in rats.
  A no-observed-effect level (NOEL) was established at 12.5 mg/kg/day
  for decreased pup weights. A safety factor of 1000 is used to derive
  the PADI because there was only chronic data on one species. The PADI
  will be changed to an ADI when chronic data on a second species
  (nonrodent) are submitted and found adequate. The data from the most
  sensitive species and a safety factor of 100 will be used. The NOEL of
  12.5 mg/kg/day was based on reproductive toxicity excluding the issue
  of oncogenicity for Which a risk assessment has been made.

           4. SUMMARY OF REGULATORY POSITIONS AND RATIONALE

     The Agency has concluded that studies conducted with mice and rats
have shown statistically significant increases in incidences of certain
tumors. Use of captan results in dietary and environmental exposure that
may pose unreasonable risks to human health unless certain steps are
taken. Accordingly, the Agency proposed in the Federal Register of June
21, 1985 (50 FR 25884) to cancel or deny federal registrations of
products containing captan for use on food crops with the proviso that
in the final decision EPA would continue any use on food where data
submitted demonstrate that captan residues on food are sufficiently
lower than EPA's estimates or that alternative application methods will
sufficiently reduce dietary exposure to captan. EPA also proposed in its
preliminary determination that protective clothing and/or equipment be
worn or used for specific non-food agricultural and non-agricultural
uses of captan and that revised labeling be required on products
intended for non-food uses. Extensive dietary data are due from
registrants in May, 1987. A decision document, Position Document Number
4, is expected to be issued in August, 1988.

     Required labeling reflects use restrictions needed to reduce human
exposure to captan. The following areas of labeling will be required
within 90 days from the receipt of the Standard:

- 1. Ingredient Statements
- 2. Precautionary Statements
- 3. Environmental Hazards Statements
- 4. Use Precaution Statements

- Summary of risk/benefit review:
  - An EPA document entitled "Intent to Cancel Registration of Pesticide
    Products Containing Captan: Availability of Position Document 2/3
    (50 FR 25884-25899, June 21, 1985) discusses the risks and benefits
    of captan.

                 5. SUMMARY OF MAJOR DATA GAPS

Product chemistry

Toxicology:

- Acute testing
- Subchronic testing
- Chronic testing
- Special testing

Environmental fate:

- Photodegration
- Metabolism studies - laboratory
- Mobility studies
- Dissipation studies field
- Accumulation studies
- Subdivision K, reentry studies

Wildlife and aquatic organisms:
- Aquatic organism testing
- Nontarget insect testing - aquatic insects

Residue Chemistry

                    6. CONTACT PERSON AT EPA

Eugene M. Wilson
Assistant Product Manager (21)
Fungicide/Herbicide Branch
Registration Division (TS-767C)
Office of Pesticide Programs
Washington, C. C. 20460

DISCLAIMER:  THE INFORMATION PRESENTED IN THIS CHEMICAL INFORMATION FACT
SHEET IS FOR INFORMATIONAL PURPOSES ONLY AND NOT TO BE USED TO FULFILL
DATA REQUIREMENTS FOR PESTICIDE REGISTRATION AND REREGISTRATION.