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captafol (Difolatan) Chemical Fact Sheet 10/84

                          CHEMICAL FACT SHEET FOR:




                      1. DESCRIPTION OF CHEMICAL

Generic Name:  cis-N-((1,1,2,2,-tetrachloroethyl)thio) 4-cyclohexene-
Common Name:  captafol
Trade Names:  Difolatan, Folcid, Haipen, Merpafol, Ortho 5865, Sanspor
              and Sulfemmide
EPA Shaughnessy Code: 081701
Chemical Abstracts Service (CAS) Number:  2425-06-1
Year of Initial Registration:  May 21, 1962
Pesticide Type:  Fungicide
Chemical Family:  Phthalimide
U.S. Producer:  Chevron Chemical Company


     Application sites:  Apples (Midwestern and Eastern states only), 
apricots, blueberries, cherries (unspecified use in California and 
Oregon only), cherries (sour), cranberries, grapefruit, lemons, limes 
(Florida only), macadamia nuts (Hawaii), nectarines, oranges (Florida 
only), peaches, pineapples, plums, prunes, tangerines, corn (sweet, 
Florida only), cucumbers, melons, onions, potatoes, taro (wetland) 
(Hawaii only), tomatoes (mechanically harvested only), watermelons 
peanuts, seed treatment uses (corn (field), cotton, peanuts, rice and 
sorghum (grain and forage)), and wood.

     Types of formulations:  Dusts. emulsifiable concentrates. flowable 
suspensions, wettable powders, and water dispersible granules.

     Types and methods of application:  Dusting. spraying, misting, and 
dipping under pressure for wood treatment.

     Application rates:  See use patterns in USDA Compilations of 
Registered Uses of Fungicides and Nematicides, Part I, Pages C-0995.01 
through C-09-95.11.

     Usual carriers:  Clay, talc, silica, water.

     Efficacy review results:  Captafol 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:  Crystalline solid
- Color:  White
- Odor:  Slight characteristic pungent odor
- Melting point:  Range 156-161 C (162 C, pure compound)
- Stability:  Stable under ordinary environmental conditions. Decomposes 
slowly at melting point. Very slight hydrolytic decomposition at acid or 
neutral pH at ambient temperature. Strong sodium and potassium hydroxide 
solutions may cause spontaneous ignition of concentrate forms. In 
neutral or weakly basic solution, captafol slowly decomposes at a rate 
depending upon pH and temperature, being very slow below 7.0 and rapid 
above 9.0.

Toxicological Characteristics:

- Acute oral LD50 - Rat - males, 6780 mg/kg, Category III - females,
  6330 mg/kg, Category III
- Acute inhalation LC50 - Data gap
- Dermal irritation - Rabbit - moderate dermal irritation at 72 hours,
  Category III. Severe dermal sensitization.
- Eye irritation - Rabbit - corneal opacity, iris and conjunctive
  irritation present through day 21, Category I.
- Teratology - Rat - no teratogenic effects seen. Highest dose tested:
  100 mg/kg/day. Rabbit - recently submitted tests currently under
  review. Hamster - no effect level (NOEL) for fetotoxicity and possible
  teratogenic effects = 300 mg/kg. New study must be submitted by the
- Oncogenicity - Mouse - Oncogenic lesions were observed at 1000 and
  3000 parts per million (ppm), but not at 300 ppm. Information
  concerning the control groups is being requested from the registrant
  in order for a final risk assessment to be performed. Rat Oncogenic
  lesions were seen at all dose levels. Additional histopathology
  examinations of liver and mammary tissues at low (56ppm) and mid (241
  ppm) dose levels have been requested from the registrant. This
  information is necessary for a complete risk assessment to be

Physiological and Biochemical Behavioral Characteristics:

- Foliar absorption:  Captafol and/or its metabolites and degradrates is
  (are) absorbed by roots and shoots of plants.
- Translocation:  Captafol and/or its metabolites and degradrates is
  (are) translocated in plant tissue. Captafol 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 captafol in plants are not understood. The metabolism
  of captafol is understood for ruminants but not for avian species.
- The following metabolites have been identified in animal tissues:
  - delta4-tetrahyrdrophthalimide
  - phthalimide
  - 4,5-epoxyhexahydrophthalimide
  - 4,5-dihydroxyhexahydrophthalimide
  - 3-hydroxy-delta4-tetrahydrophthalimide
  - 5-hydroxy-delta3-tetrahydrophthalimide
  - delta4-tetrahydrophthalamic acid
  - delta4-tetrahydrophthalic acid
- The above metabolites, with the exception of delta4-tetrahydrophthalic
  acid, were found in milk. No parent captafol per se was detected in
  ruminant tissues or in milk.

Environmental Characteristics:

- Absorption and leaching in basic soil types:  Captafol per se does not
  leach from basic soils. The leachability and persistence of its
  metabolites and degradates are not understood.
- Microbial breakdown:  Inadequate data. Limited data indicate that
  captafol per se has a half-life of <3, 5, and 8 days in nonsterile
  organic, sandy, and clay loam soils, respectively. The soil degradates
  and metabolites have not been identified.
- Loss from photodecomposition and/or volatilization:  Inadequate
- Bioaccumulation:  No data.
- Resultant average persistence:  Inadequate data on metabolites and

Ecological Characteristics:

- Hazards to fish and wildlife
  - Rainbow trout:  96-hr LC50 = 0.027 - 0.190 ppm
  - Bluegill sunfish: 96-hr LC50 = 0.045 - 0.230 ppm
  - Characterized as very highly toxic to both coldwater and warmwater
    fish. Inadequate data for fish accumulation.
  - Avian toxicity:  LD50 = >2510 ppm, LC50 = >5620 ppm
  - Daphnia magna:  96-hr LC50 = 3.34 ppm. Moderately to very highly
    toxic to freshwater invertebrates.
  - Avian reproduction:  Strong potential for reproductive effect in
    birds (based on supplementary information).
  - Potential problems related to endangered species:  Additional data
    on exposure persistence, avian reproduction studies, and
    accumulation are required to complete the endangered species
    assessment for captafol.

Tolerance Assessments:

- 1. List of Crops and Tolerances:

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

                                Parts Per Million in Captafol Residues

Raw Agricultural Commodity      U.S.    Canada     Mexico     Codex

Apples                          0.25     0.1(N)      --         5.0
Apricots                       30.0      0.5         --        15.0
Blueberries                    35.0       --         --         --
Cherries, sour                 50.0     10.0         --        10.0
Cherries, sweet                 2.0      2.0         --         2.0
Citrus fruit                    0.5       --         --         --
Corn, fresh (sweet K+CWHR)      0.1(N)    --         --         --
Cranberries                     8.0       --         --         8.0
Cucumbers                       2.0      2.0         --         2.0
Macadamia nuts                  0.1(N)    --         --         0.1(N)
Melons                          5.0      2.0         --         2.0
Nectarines                      2.0       --         --         --
Peanuts, hulls                  2.0       --         --         --*
Peanuts, meats (hulls removed)  0.05      --         --         0.05
Onions                          0.1(N)   0.1(N)      --         0.05
Peaches                        30.0     15.0         --        15.0
Pineapples                      O.1(N)    --         --        10.0
Plums (fresh prunes)            2.0      0.2         --        10.0
Potatoes                        0.5      0.1(N)      --         0.5
Taro (corms)                    0.02     --          --         --
Tomatoes                       15.0      5.0         --         5.0
Carrots                         --       --          --         0.5

*Codex MRL for whole peanuts is 0.5 ppm.

- 2. Seed Applications:

     No tolerances have been established for captafol in or on any crop 
for which captafol is registered solely for seed treatment or plant 
propagule uses, because heretofore seed treatment and plant propagule 
uses have been considered to be nonfood uses. These crops include: corn 
(field), cotton, rice, sorghum (grain and forage), strawberries 
(propagating bed use), and sugarcane (seed piece use).

Results of Tolerance Assessment:

- Sufficient data are available to determine that the currently
  established tolerances for residue of captafol in or on the following
  commodities are adequate: apricots, blueberries, cranberries,
  macadamia nuts, nectarines, peaches. peanut hulls, and taro corms (40
  CFR 180.267). However, additional data concerning residues of
  metabolite THPI must be submitted for all commodities, since the
  residues of concern in or on plants have recently been modified to
  include THPI. In addition to THPI data, other residue data are
  required to support the tolerance for captafol in or on the following
  commodities: apples, citrus fruits, corn (sweet), cucumbers, melons,
  onions, peanuts, pineapples, plums (prunes), potatoes, and tomatoes.
  THPI data and tolerance changes must be submitted for sweet and sour
  cherries. Residue data and tolerance proposals must be submitted for
  the following commodities:  crops receiving only seed treatments
  (cotton, field corn. rice, and sorghum), pears (state label use only),
  strawberries (propagating bed use; Section 24(c)), sugarcane (seed
  piece use), and taro foliage. Tolerances for the following commodities
  are pending: carrots, coffee beans, pecans, soybeans, and soybean
  forage and hay. Plant metabolism of captafol is not adequately
  understood; therefore tolerance for residues other than captafol and
  THPI may need to be sought if those residues are deemed to be of
  concern. A poultry metabolism study will be needed. Also, feeding
  studies are required for ruminants and poultry. Additional storage
  stability data are necessary to validate the residue data. No crop
  group tolerance may be established based on the available data. 
- The Theoretical Maximum Residue Contribution (TMRC) is 1.4579 mg/day
  based on a 1.5-kg diet. The change in the residue definition (by
  including the metabolite THPI), the requested tolerance proposals, and
  the pending tolerances noted above will affect a change in the TMRC
- The maximum permissible intake (MPI) for a 60-kg person is 1.68 mg/day
  based on an acceptable daily intake (ADI) of 0.028 mg/kg. The present
  TMRC represents 86.8% of the MPI. 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 MPI utilized. 
- The ADI for captafol is based on a chronic toxicity study in rats. A
  NOEL was established at 56 ppm for non-oncogenic effects. In that
  study the next highest dose level caused cholangiectasis in liver,
  increase in hyperplasia of tubule epithelium, megalocytic cells and
  transitional cell hyperplasia in kidney, increased erosion/ulceration,
  hyperkeratosis/acanthosis, ground substance in glandular mucosa, and
  dilated pits in stomach. The reported dosage level was corrected from
  75 ppm to 56 ppm based on the instability of captafol in the diet. In
  the rat, 56 ppm is approximately equivalent to 2.8 mg/kg. Using a
  safety factor of 100 and a NOEL of 2.8 mg/kg/day, the ADI would be
  0.028 mg/kg for humans. The only registrant of technical captafol,
  Chevron Chemical Company, has been requested to complete the 
  histopathology examination of the low and mid-dose liver and mammary
  gland tissues; therefore, the NOEL for cholangiectasis in the liver
  may change. The NOEL of 56 ppm is for systemic effects excluding the
  issue of oncogenicity, for which a risk assessment will be performed.

Problems That are Known to Have Occurred with Use of the Chemical:

- Captafol is a skin sensitizer. Incidents of farmworkers being disabled
  from its effect have been reported. Restricting the use of captafol to
  mechanically harvested tomatoes, and labeling requiring use of gloves
  and protective clothing by citrus harvesters have reduced this


- Based on the oncogenic and fish toxicity potential risks of hazard,
  captafol is being placed under Special Review by the Environmental
  Protection Agency. The presumption of risk of hazards outweighing the
  derived benefits must be rebutted by the manufacturers of pesticide
  products that have captafol as an active ingredient. Based on the
  oncogenic potential and the fish toxicity potential, captafol is
  classified as a Restricted Use pesticide. All captafol products must
  be relabeled as Restricted Use pesticides.

      The following labeling restrictions will be required for continued
  registration of captafol products:

- All technical grade, manufacturing-use (MUP's) and end-use products
  (EUP's) must bear appropriate labeling as specified below and in 40
  CFR 162.10.

  - 1. Precautionary statements to be used on labeling of all end-use
       captafol products:

    - a. All end-use product labels must reflect the following 
statements:  RESTRICTED USE PESTICIDE. For retail sale to, direct 
supervision of a Certified Applicator, and only for those uses covered 
by the Certified Applicator's certification.

    This product is classified as a Restricted Use Pesticide because it 
contains captafol. which has been determined to cause tumors in 
laboratory animals.

    Exposure to captafol during mixing, loading, and application may be 
hazardous to your health. This product contains captafol which has been 
determined to cause tumors in laboratory animals.

    - b. All end-use products must have the labeling precaution under 
Direction for Use:  Wear impervious gloves and full body clothing during 
handling and application.

    - c. All end-use products intended for crop use, except seed, seed 
piece, and plant progagule treatments. must bear the following use 

      - i. Do not rotate treated crop with crops other than those with 
registered captafol uses.

      - ii. Do not allow persons to enter treated areas within 24 hours 
following application unless full body clothing is worn. Conspicuously 
post reentry information at sites of application.

      - iii. Do not use captafol-treated rice seed in fields 
subsequently to be used for agricultural crops other than those with 
registered captafol uses.

      - iiii. Water from cranberry bogs, wetland taro fields (foliarly 
treated with captafol), and rice fields planted with captafol-treated 
rice seed must not be used for irrigation of crops other than those with 
registered captafol uses.

  - 2. For products that bear label claims for use in greenhouses:

    - a. Only the applicator is permitted in the greenhouse during 
application of captafol to soil. Open vents to greenhouse during 
application and for at least one hour after application.

    - b. Workers planting in captafol-treated soil in greenhouses must 
wear impervious gloves and full body clothing.

  - 3. All products, manufacturing-use and end-use, must bear the 
labeling precautionary statements:

    - DANGER
    - Causes irreversible eye damage. Harmful if swallowed or inhaled. 
May cause allergic skin reactions. Do not get in eyes. Wear goggles or 
face shield when handling. Avoid contact with skin and clothing. Remove 
and separately launder clothing before reuse. This product contains 
captafol, which has been determined to cause tumors in laboratory 

    - In addition, the following specific environmental hazard labeling 
requirements apply to either technical, manufacturing-use, or end-use 
products as indicated.

    - a. All technical and MUP's must bear the following precautionary 
statements: This pesticide is extremely toxic to fish. Do not discharge 
into lakes, streams, ponds, or public waters unless in accordance with 
an NPDES permit. For guidance, contact your Regional Office of the 
Environmental Protection Agency. Do not discharge effluent containing 
captafol into sewage systems without obtaining permission from the 
sewage treatment authority.

    - b. All EUP's that allow for foliar applications, except foliar 
application to cranberries, must bear the hazard precaution:  This 
pesticide is extremely toxic to fish. Do not apply directly to water. 
Drift and runoff from treated areas may be hazardous to aquatic 
organisms in neighboring areas. Do not contaminate water by cleaning of 
equipment or disposal of wastes.

    - c. All EUP's that allow foliar application to cranberries must 
bear the following environmental hazard precautions: This pesticide is 
extremely toxic to fish. Fish may be killed at recommended application 
rates. Drift and runoff from treated areas may be hazardous to aquatic 
organisms in neighboring areas. Do not contaminate water by cleaning of 
equipment or disposal of wastes.

    - d. All EUP's that allow seed treatment must bear the following 
environmental hazard precaution: This pesticide is extremely toxic to 
fish. Do not contaminate water by cleaning of equipment or disposal of 

  - 4. Both MUP's and EUP's may need special labeling to protect 
endangered species. This will be determined after required environmental 
chemistry data are reviewed, and in conjunction with EPA's evaluation of 
the potential risk of hazards to endangered species.

    Based on historical use experience (human health effects reports) 
and the benefits from the pesticide uses, the Agency will allow the 
registration of captafol products to continue for existing use patterns 
until the risk of hazards is better defined by the data submitted in 
response to the Captafol Registration Standard and the completion of a 
Special Review by the Agency, and provided that the required labeling 
under the Standard is submitted within the time specified.

                    5. SUMMARY OF MAJOR DATA GAPS

Product Chemistry Data (6)a

- Description of beginning materials and manufacturing process
- Discussion of Formation of Impurities
- Preliminary Analysis of Product Samples
- Density, Bulk Density, or Specific Gravity
- Vapor Pressure
- Dissociation Constant
- Octanol/Water Partition Coefficient
- pH
- Solubility


- Inhalation LC50 - Rat (6) 
- 90-day feeding - Rodent, Non-rodent (18) 
- 90-day Inhalation - Rat (18) 
- Chronic Toxicity - 2 species:  Rodent and Non-rodent (36) 
- Oncogenicity study - 2 species:  Rat and Mouse preferred (6) 
- Teratogenicity 2 species - needs hamsters study using two test groups,
  one dose on day 7, and the other dose on day 8 of gestation (12) 
- Gene Mutation (12) 
- Dermal Absorption (6) 

Residue Chemistry (24) 

- Analytical Method 
- Plant Metabolism 
- Animal Metabolism (poultry) 
- Storage Stability 
- Magnitude of Residues on all food-use crops 

Environmental Fate 

- Soil Metabolism - Aerobic soil (24), Anaerobic aquatic (24), Aerobic
  aquatic (24) 
- Degradation - Hydrolysis (6), Photodegradation in water, soil, and
  air (6) 
- Dissipation - Soil (24), Aquatic (sediment) (24) 
- Reentry (24)
- Mobility Studies (6)a - Leaching and Absorption/Desorption 
- Accumulation Studies (24) - Rotational Crops

Wildlife and Aquatic Organisms 

- Acute LC50 Estuarine and Marine Organisms (6)

NOTE:  a. Data to be submitted in number of months after receipt of the 
Guidance for the Reregistration of Pesticide Products Containing 
Captafol, EPA Case Number 116.

                         6. CONTACT PERSON

Eugene M. Wilson
Office of Pesticide Programs
Registration Division (TS-767C)
Crystal Mall #2
1921 Jefferson Davis Hwy.
Arlington, VA  22202
Telephone (703) 557-1900