captafol (Difolatan) Chemical Fact Sheet 10/84
CHEMICAL FACT SHEET FOR:
FACT SHEET NUMBER: 35
DATE ISSUED: OCTOBER 1, 1984
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
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
2. USE PATTERNS AND FORMULATIONS
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
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
- 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
- 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-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.
- 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
- 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.
- 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
4. SUMMARY OF REGULATORY POSITION AND RATIONALE
- 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
- 1. Precautionary statements to be used on labeling of all end-use
- 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
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:
- 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
- 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
- Soil Metabolism - Aerobic soil (24), Anaerobic aquatic (24), Aerobic
- Degradation - Hydrolysis (6), Photodegradation in water, soil, and
- 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
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.