PMEP Home Page --> Pesticide Active Ingredient Information --> EXTOXNET: The Extension Toxicology Network --> 2,4-D to Captan --> Captafol

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Extension Toxicology Network

A Pesticide Information Project of Cooperative Extension Offices of Cornell University, Michigan State University, Oregon State University, and University of California at Davis. Major support and funding was provided by the USDA/Extension Service/National Agricultural Pesticide Impact Assessment Program.


Publication Date: 9/95


Trade names for products containing captafol include Crisfolatan, Difolatan, Difosan, Folcid, Haipen, Kenofol, Merpafol, Pillartan, Sanseal, Santar-SM and Sanspor (1, 2).


No longer sold in the United States (3, 4).


Captafol is a broad-spectrum protective contact fungicide belonging to the sulfanilamide group. It is effective for the control of almost all fungal diseases of plants except powdery mildews and is widely used outside the U. S. to control foliage and fruit disease on apples, citrus, tomato, cranberry, potato, coffee, pineapple, peanut, onion, stone fruit, cucumber, blueberry, prune, watermelon, sweet corn, wheat, barley, oilseed rape, leek and strawberry. It is also used as a seed protectant in cotton, peanuts and rice (1, 2, 9). Captafol is also used in the lumber and timber industries to reduce losses from wood rot fungi in logs and wood products (2, 4).

Captafol is a "general use" pesticide with a toxicity classification of IV (relatively non-toxic). Check with specific regulations for local restrictions which may apply. Products containing captafol must bear the Signal Word "Warning" (3).

Formulation types include dusts, flowables, wettables, water dispersibles, and aqueous suspensions. Mixed formulations include (captafol +) triadimefon; ethirimol; folpet; halacrinate; propiconazole; and pyrazophos (1). Captafol is compatible with most plant-protection products, with the exception of alkaline preparations and formulating materials (1, 3).



The acute oral LD50 for male rats, the amount that is lethal to one-half (50%) of experimental animals fed the material, is 6,780 mg/kg; and 6,330 mg/kg for female rats. A dermal irritation test on rabbits showed moderate dermal irritation at 72 hours with severe dermal sensitization. Another test for eye irritation of captafol in rabbits showed corneal opacity, iris and conjunctive irritation present through day 21 (8).

Other studies indicated an acute oral LD50 for rats of 6,200 mg/kg (maize oil suspension) and 4,200 mg/kg (aqueous suspension) (1, 4). An acute oral LD50 for rats of 5,000-6,200 mg active ingredient/kg; and 2,500 mg wettable powder formulation (administered as an aqueous suspension)/kg were also reported (2, 3).

A study of captafol in rabbits indicated an acute percutaneous LD50 of >15,400 mg/kg; and it was noted that some people may develop an allergy to captafol (2).


Rat feeding studies reported growth depression and some liver and kidney changes following exposure to 1,500 and 5,000 ppm and an increase in mortality at the 5,000 ppm level. Prolonged ingestion of 100 or 300 mg/kg/day in dogs caused vomiting, diarrhea, anemia, weight loss, growth deficiency, and depression. Effects on fertility have been reported from repeated ingestion during pregnancy in rabbits. Effects on the newborn have been reported from prolonged exposure in rats (5).

Other feeding studies indicated captafol when fed to rats at 250 and 500 mg/kg body weight for 2 months did not induce pathological changes, though growth was inhibited at 1,500 mg/kg. Feeding at 500 mg/kg body weight for 2 years had no effect, whereas feeding to dogs at 300 mg/kg for 2 years caused changes in urine and blood profiles and liver insufficiency. No accumulation in animals was noted (1).

Another source found no ill-effect was observed in rats receiving 500 mg/kg diet; and in dogs receiving 10 mg/kg daily for 2 years (2).

Groups of two male and two female dogs were given daily doses of 0, 10, 30, 100 or 300 mg/kg body of captafol over a two year period. Increased absolute liver and kidney weights and liver and kidney to body weight ratios were seen in all animals at the 30, 100 and 300 mg/kg levels. Histopathology, blood chemistry, urine analysis and liver function tests revealed no adverse effects that could be attributed to the administration of captafol (9, 10).

Reproductive Effects

Groups of 8 male and 16 female rats were fed captafol at 0, 50 (raised to 100 after first generation), 250 (raised to 500 after first generation), and 1,000 ppm in the diet in a three-generation reproduction study. There were no adverse effects on body-weight gain, mortality, or organ-weight of parental animals or on reproductive performance, fertility and lactation indices, litter size or number of stillbirths in any test groups. Pup survival in the test groups at various intervals in the lactation period was not significantly different from the control group. Gross examinations and histopathology carried out on parental animals and on F3b weanlings in the 0 and 1,000 ppm groups revealed no changes that could be attributed to captafol (9, 11).

There is a strong potential for reproductive effects in birds (7, 8).

Teratogenic Effects

In one study, no teratogenic effects were seen in rats at the highest dose tested of 100 mg/kg/day (8). In other studies, effects on the embryo or fetus and fetal developmental abnormalities have been reported from the ingestion of a single dose during gestation in hamsters. Effects on the embryo or fetus have been reported from the administration of a single dose on the fifth day prior to mating in male rats (5).

Teratogenicity studies in rabbits indicated a teratogenic NOEL > 50 mg/kg/day; and a fetotoxic NOEL = 16.5 mg/kg/day; fetotoxic LEL = 50 mg/kg/day (increased minor skeletal abnormalities and resorptions); maternal NOEL = 16.5 mg/kg/day; maternal LEL = 50 mg/kg/day (deaths, decreased weight gain and food intake); levels tested 0, 5, 16.5 and 50 mg/kg/day (6).

In another study, when captafol was administered to two strains of rabbits at dosages ranging from 37.5 to 150 mg/kg/day from 6 through 16 weeks of gestation or to rats at different dosages of 100 and 500 mg/kg/day from 6 through 15 weeks, no evidence of teratogenicity was found (9, 12). Furthermore, captafol was not teratogenic when administered to rhesus monkeys at dosages of 6.25, 12.5 and 25 mg/kg/day during day 22 through 32 of gestation (9, 13).

Teratogenicity studies in hamsters indicated a fetotoxic NOEL = 300 mg/kg on days 7 or 8; and a teratogenic NOEL = 300 mg/kg on days 7 or 8 (6, 7, 8); the levels tested were 100, 200, 300, 400, 500, 600, 800, 1,000, 1,500 mg/kg/day (treated days 6-8, 6-10, 7 or 8) (6).

Mutagenic Effects

Captafol is found not to be mutagenic in both dominant lethal test in mice and host mediated assay in rats, although Seiler (1973) observed it to be a weak mutagen on certain strains of Salmonella. However, on other strains it was non-mutagenic.

Captafol was given to male rats intraperitoneally at rates of 2.5, 5.0 and 10 mg/kg/day or orally at 50, 100 and 200 mg/kg/day for 5 days, then the animals were bred for the following 10 weeks in a dominant lethal test. Neither fertility nor mean total implants were affected. An oral dosage of 50 mg/kg/day was considered a no effect level (9, 15).

Male mice were given a single intraperitoneal injection of captafol (1.5 and 3.0 mg/kg) and a dominant lethal test was carried out. There was no increase in early embryonic death among conceptuses of females mated to treated males. A similar result was obtained in rats after the males were dosed orally for 14 days at rates of 125 or 250 mg/kg/day. Indicator microorganisms isolated from the peritoneal cavity of treated male rats showed no increase in reversion rate. Thus, captafol was not mutagenic at the dosages tested in any of these systems (9, 16).

Captafol was studied for mutagenic activities in a microbial system. The effect on the mutagenic activity of captafol of adding S-9 mix or L-cysteine to the system was investigated. The mutagenicity of captafol observed in Escherichia coli WP2 her and Ta 1535 disappeared after addition of S-9 or L-cysteine (9, 17).

Carcinogenic Effects

Oral administration in mice produced a high incidence of adenocarcinomas of the small intestine, vascular tumors of the heart and spleen, and heptocellular carcinomas. Oral administration in rats caused a dose-related increase in the incidence of renal carcinomas in males, benign renal tumors in females, and liver tumors in both sexes (5).

A two-year mouse study (Chevron Chemical Company, 1981) showed both compound and dose-related oncogenic lesions at the middle and high dose groups. These lesions included lymphosarcomas, myeloproliferative disease, harderian gland hyperplasia, benign harderian gland adenomas, and hemangiosarcomas. This compound also produced dose-related non- oncogenic lesions at all dose levels. There was a significant increase in mortality in the middle and high dose mice, frequently accompanied by neoplastic lesions (7). Oncogenic lesions were observed at 1,000 ppm and 3,000 ppm but not at 300 ppm (8).

In another 2-year rat feeding study (Hazelton Laboratories, 1983) a dose- related increased incidence of fibroadenomas of the mammary gland and an increased incidence of neoplastic nodules in the liver on females occurred. Not all the animals at the middle and low doses were subjected to histopathological examination so that the numbers may not be representative (7).

US EPA has determined that captafol has oncogenic potential (potential to cause cancer) (7).

Organ Toxicity

In a two-year feeding/oncogenic study in mice, the oncogenic NOEL was found to be 300 ppm; the oncogenic LEL = 1,000 ppm (lymphosarcomas); the systemic NOEL = 300 ppm; the systemic LEL = 1,000 ppm (decreased body weight, increased mortality, decreased in hematological parameters, atrophy of pancreas, testicles, spleen, bone marrow and kidney tissue); levels tested were 300, 1,000, 3,000 ppm (6).

Fate in Humans and Animals

Degradation and metabolism in animals is through hydrolytic cleavage to tetrahydrophthalimide (THPI) and dichloroacetic acid. THPI is degraded to tetrahydrophthalimidic acid and further to phthalic acid and ammonia (1).

No parent captafol was detected in ruminant tissues or in milk. Several metabolites were identified in animal tissue (8).


Effects on Birds

The LD50 for avian toxicity to captafol was > 2,510 ppm; and the LC50, that concentration of a chemical in air or water that kills half of the experimental animals exposed to it for a set period of time, was > 5,620 ppm (7, 8). Another study found a 10 day LC50 to be > 23,070 mg/kg diet for pheasants (2).

In a 21-day study it was found that the lethal dose of captafol for leghorn chicks was >10,000 mg/kg body weight and was > 10,500 mg/kg body weight for pigeons (9).

Effects on Aquatic Organisms

Captafol is considered toxic to fish (1, 3). Rainbow trout had a 96-hr LC50 = 0.027-0.190 ppm; and 0.045-0.230 ppm for bluegill sunfish. Captafol is characterized as being very highly toxic to both cold water and warm water fish (7, 8).

Another study found the LC50 (96 hour) for rainbow trout to be 0.5 mg/l; 3.0 mg/l for goldfish; and 0.15 mg/l for bluegill (1, 2, 3).

The aquatic crustacean Daphnia magna has a 96-hr LC50 = 3.34 ppm. Captafol is considered moderately to very highly toxic to freshwater invertebrates (7, 8).

Effects on Other Animals (Nontarget species)

Field exposure studies with eight volunteers exposed to the spray drifts of captafol for three consecutive days at the rate of six hours per day did not show any abnormalities which could be attributed to the effects of this fungicide (9).

Captafol is considered non-toxic to bees (1).


Breakdown of Chemical in Soil and Groundwater

Stable under ordinary environmental conditions. Captafol has a half-life of < 3, 5, and 8 days in nonsterile organic, sandy and clay loam soils, respectively (7, 8). Captafol does not leach from basic soils (8).

Breakdown of Chemical in Surface Water

No information was available.

Breakdown of Chemical in Vegetation

The half-life periods of captafol sprayed on most crops have been less than 5 days. Residues were below the tolerance limits at the time of harvest (9, 18).

Degradation and metabolism in plants and animals is through hydrolytic cleavage to tetrahydrophthalimide (THPI) and dichloroacetic acid. THPI is degraded to tetrahydrophthalimidic acid and further to phthalic acid and ammonia (1).

Captafol and/or its metabolites and degradates are absorbed by roots and shoots of plants. Captafol is also translocated in plant tissue as a result of seed treatment, soil treatment and foliar application (7, 8).

Grapes, apples and citrus have been injured from phytotoxicity under certain weather conditions. Roses have shown injury at high rates of application (4).


Exposure Guidelines:

TLV-TWA: 0.1 mg/m3 OSHA (5)

Physical Properties:

CAS No.: 2425-06-1 (1)
Chemical name: cis-N-(I, 1,2,2,-Tetrachloroethylthio)-4-cyclohexene-I,2-dicarboximide
Chemical Class/Use: Carboximide/Foliar protectant fungicide (4)
Solubility in water: 1.4 mg/L at 20 degrees C (1, 2)
Solubility in other solvents (all in g/100 ml): isopropanol 1.3, benzene 2.5, toluene 1.7, xylene 10.0, acetone 4.3, methyl ethyl ketone 4.4, dimethyl sulphoxide 17.0 (1)
Melting point: 160-162 degrees C; 320-323 degrees F (5, 7)
Decomposition temperature: slowly decomposes at its melting point (2)
Vapor pressure: less than 1.3 x 10 to the minus 9 mbar at 20 degrees C (1)


Rallis India Ltd.
Agrochemical Research Station
P.O. Box 5813
Peenya Industrial Area, Phase II
Bangalore, India 560 058
Fax: 91-80-835994015
Telephone: 91-8394959

Review by Basic Manufacturer:

Comments solicited: October, 1994
Comments received: December, 1994


  1. The Agrochemicals Handbook. 1983. The Royal Society of Chemistry, The University, Nottingham, England.
  2. C. R. Worthing (ed.). 1983. The Pesticide Manual: A World Compendium. Seventh edition. Published by The British Crop Protection Council.
  3. Farm Chemicals Handbook. 1994. Meister Publishing Co. Willoughby, OH.
  4. W.T. Thomson. 1992. Agricultural Chemicals. Book IV: Fungicides. Thomson Publications, Fresno, CA.
  5. OHS Database. 1993 (December). Occupational Health Services, Inc. MSDS for Captafol. OHS Inc., Secaucus, NJ.
  6. U.S. Environmental Protection Agency. February, 1985. Office of Pesticides. TOX Oneliners - Captafol.
  7. U.S. Environmental Protection Agency. September, 1984. Guidance for the Reregistration of Pesticide Products Containing Captafol as the Active Ingredient. US EPA, Office of Pesticide Programs, Registration Div., Washington, DC.
  8. U.S. Environmental Protection Agency. October, 1984. Pesticide Fact Sheet Number 35: Captafol. US EPA, Office of Pesticide Programs, Registration Div., Washington, DC.
  9. Review by Rallis India Ltd. December 1994.
  10. FAO/WHO. 1970. 1969 Evaluation of some pesticide residues in food. FAO, Rome.
  11. Kennedy, G., O. E. Fancher and J. C. Calandra. 1967. Report, Chevron Chemical Co., USA.
  12. Kennedy, G., O. E. Fancher and J. C. Calandra. 1968. Toxicol. Appl. Pharmacol. 13:421-430.
  13. Vondruska, J.F., O. E. Fancher and J. C. Calandra. 1971. Toxicol. Appl. Pharmacol., 18:619-624.
  14. Seiler, J. P. 1973. Experientia. 29:622.
  15. Collins, T. F. X. 1972. Food Cosmet. Toxicol. 10:363-371.
  16. Kennedy, G. L., Jr., D. W. Arnold and M. L. Keplinger. 1975. Food Cosmet. Toxicol. 13:55-61.
  17. Moriya, M., K. Kato, Y. Shirasu and T. Kada. 1975. Mutat. Res. 38:333-354.
  18. Agnihothrudu, V. and M. S. Mithyantha. 1978. Pesticide Residues - a review of Indian Work. Rallis India Ltd., Bangalore.