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Pesticide Information Profiles
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TRADE OR OTHER NAMES: Trade names for products containing captafol include
Crisfolatan, Difolatan, Difosan, Folcid, Haipen, Kenofol, Merpafol, Pillartan, Sanseal,
Santar-SM and Sanspor (1, 242).
REGULATORY STATUS: No longer sold in the United States (223, 243).
CHEMICAL CLASS: Carboximide
INTRODUCTION: 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, 242, 248).
Captafol is also used in the lumber and timber industries to reduce losses from wood rot fungi
in logs and wood products (242, 243). 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" (223).
FORMULATION: 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, 223).
- Acute Toxicity: 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 (247). 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, 243). 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 (242,223). 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 (242).
- Chronic Toxicity: 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 (244). 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 (242). 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 (248, 249).
- 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 (248, 250). There is a strong potential for reproductive effects in
birds (246, 247).
- Teratogenic Effects: In one study, no teratogenic effects were seen in rats at the highest dose tested of 100 mg/kg/day
(247). 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 (244). 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 (245). 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 (248, 251). 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 (248, 252). 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 (245, 246, 247); 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) (245).
- 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 (248, 254). 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 (248, 255). 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 (248, 256).
- 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
(244). 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 (246). Oncogenic lesions were observed at 1,000 ppm
and 3,000 ppm but not at 300 ppm (247). 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 (246). US EPA has determined that captafol has oncogenic
potential (potential to cause cancer) (246).
- 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 (245).
- 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 (247).
- 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
(246, 247). Another study found a 10 day LC50 to be > 23,070 mg/kg diet for pheasants (242). 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 (248).
- Effects on Aquatic Organisms: Captafol is considered toxic to fish (1, 223). 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 (246, 247). 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, 242, 223). The aquatic crustacean Daphnia magna has a 96-hr LC50
= 3.34 ppm. Captafol is considered moderately to very highly toxic to freshwater invertebrates (246, 247).
- 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 (248). 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 (246, 247). Captafol does not
leach from basic soils (247).
- 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 (248, 257). 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 (246, 247). Grapes, apples and citrus have been injured from phytotoxicity under certain
weather conditions. Roses have shown injury at high rates of application (243).
PHYSICAL PROPERTIES AND GUIDELINES:
- Appearance: Colorless to pale yellow crystals, the tech. grade is a light tan powder, with a characteristic odor(1).
- Chemical Name: cis-N-(I, 1,2,2,-Tetrachloroethylthio)-4-cyclohexene-I,2-dicarboximide
- CAS Number: 2425-06-1 (1)
- Molecular Weight: 349.1
- Water Solubility: 1.4 mg/L at 20 degrees C (1, 242)
- Solubility in Other Solvents: 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 (244, 246)
- Vapor Pressure: less than 1.3 x 10 to the minus 9 mbar at 20 degrees C (1)
- Partition Coefficient: 3.8
- Adsorption Coefficient: Not Available
- ADI: Temporary ADI withdrawn 1985 (1).
- MC: Not Available
- RfD: Not Available
- PEL: Not Available
- HA: Not Available
- TLV: 0.1 mg/m3 OSHA (244)
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
References for the information in this PIP can be found in Reference List Number 10
DISCLAIMER: The information in this profile does not in any way replace or supersede the information on the pesticide
product label/ing or other regulatory requirements. Please refer to the pesticide product label/ing.