Hazardous Substances Data Bank,
National Library of Medicine, Bethesda, MD.
http://toxnet.nlm.nih.gov/
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THIOPHANATE METHYL
CASRN: 23564-05-8
For other data, click on the Table of Contents
Human Health Effects:
Human Toxicity Excerpts:
Among men who treated citrus with thiophanate-methyl as well as emulsified sulfur and calcium polysulfide in Kumamoto Prefecture, the incidence of dermatitis was 30.3, 48.2, and 52.8% in 1972, 1973, and 1974, respectively. The corresponding values for women were 32.3, 56.3, and 64.8%. The areas affected were the abdomen, back, and waist. Symptoms included itching, redness, swelling, dryness, and sometimes sensitized dermatitis. Symptoms frequently appeared 1 wk after exposure. The ocular mucosa was congested. The incidence of positive patch tests was only about 5%. Medical exam revealed some abnormalities of hemoglobin.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1458]**PEER REVIEWED**
Skin, Eye and Respiratory Irritations:
Mild skin & eye irritant.
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
Probable Routes of Human Exposure:
Occupational exposure to thiophanate-methyl may occur through inhalation and dermal contact with this compound at workplaces where thiophanate-methyl is produced or used(SRC). Worker re-entry exposure to pesticides residues in greenhouses is a probable exposure route based upon a study in which thiophanate-methyl was applied to carnations via high-volume spraying at application rates of 150 and 325 g ai/1000 sq m, showing half-lives of 22 and 41 days, respectively(1). Dermal exposure of greenhouse workers to thiophanate-methyl (applied by spraying) on carnations cultured in greenhouses was found to be 64 mg/day (during cutting operations) and 23 mg/day (during sorting and bundling)(2).
[(1) Brouwer DH et al; Bull Environ Contam Toxicol 58: 976-84 (1997) (2) Van Hemmen JJ et al; Med Fac Landbouww Univ Gent 57/3b: 1271-1283 (1992)]**PEER REVIEWED**
Emergency Medical Treatment:
Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
Flow cytometric technique was used to study the effects of the fungicide Thiophanate-methyl on cell proliferation, micronucleus induction, and apoptosis in human peripheral blood lymphocytes treated in vitro. Most micronuclei induced by Thiophanate-methyl did not reveal any centromeric signal, thus demonstrating clastogenic action of this fungicide. Moreover, it was found that as a function of the concentration of Thiophanate-methyl, cellular proliferation was delayed and the frequency of apoptotic cells was increased.
[Fimognari C et al; Environ Mol Mutagen 33 (2): 173-6 (1999)]**PEER REVIEWED**
No observable effect level (2 yr) for rats & mice 160 mg/kg diet.
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
Single exposures of mice for 30, 60, or 120 min to an aerosol of 70% wettable powder under dynamic conditions at a nominal concn of 100,000 mg/cu m caused lacrimation, salivation, & nasal exudation within 5-6 min after exposure began. For a few days after exposure the mice wheezed, & a crust was present around their eyes. However, they recovered completely & showed no change in growth compared to controls.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
Large oral doses caused tremor beginning 1-2 hr later; the animals became sensitive to touch & had tonic or clonic convulsions. Rabbits & dogs showed a slight decr in respiratory rate, lethargy, loss of tone of the abdominal muscles, discharge from the eyes, & mydriasis prior to death.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
When mice were fed thiophanate-methyl for 6 months, there was a slight retardation of growth in those receiving 8000 ppm, and, when killed, these rats had slight enlargement of the liver with enlargement of some liver cells. The no-effect level was 1600 ppm (about 250 mg/kg/day). Similar results were obtained in rats; the no-effect level of 1600 ppm in this species corresponds to about 78 mg/kg/day.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
A 2 yr study in rats showed that a dietary level of 640 ppm caused a slight reduction in growth in both male & female rats & a slight incr in the relative weight of the kidneys in males. There was no indication of incr thyroid or liver weight such as had been seen in an earlier, briefer study; however, at the end of 2 yr there was some enlargement of thyroid epithelial cells, especially in the males. Food consumption, survival, behavior, laboratory findings, and, with the exception of the thyroid, gross & microscopic morphology did not differ from those of the controls. A dietary level of 160 ppm (about 8 mg/kg/day) was a no-effect level.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
When dogs were fed capsules of thiophanate-methyl 7 days a week for 2 yr, those receiving 250 mg/kg/day showed a marginal effect on thyroid weight; those that received 10 mg/kg/day or less showed no effect. Even the highest dosage did not affect survival or the gross or microscopic morphology of any tissue other than the thyroid.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
Repeated dermal application of a 10% concn to rabbits caused slight erythema, but this disappeared a few days after the last treatment. A 1% suspension was not irritating. Even the 10% suspension produced no clinical effect and no change in histology of the tissues. Studies in guinea pigs with repeated sensitizing injections and a delayed challenge dose indicated that thiophanate-methyl produced no primary irritation and only slight sensitization. The compound showed no phototoxic property.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
This study was conducted to evaluate the relationship between Benomyl, Carbendazim, Topsin-M, Dimethoate, and TPTA administrated by gavage, and the external and skeletal changes of fetuses in rats. Results showed that Benomyl and Carbendazim could cause external malformations and skeletal malformations, anomalies, and variations, but similar changes were not found in Topsin-M, Dimethoate, and TPTA. The Carbendazim-inducing skeletal changes in rats had a dose-response relationship. The external malformations observed in Benomyl-treated fetuses induced exencephaly and gastroschisis. Exencephaly, rhinocephaly, anury, kinky or bent tail, edema, astomia, and fetal death occurred in Carbendazim-treated fetuses. The skeletal anomalies revealed in Benomyl and Carbendazim-treated rats were absence (< 7) of arch, bifurcated arches, extra ossification on an arch, fused arches/centers, hypoplastic arches/centers, variation in shapes/size, reduction in the number (< 13) of ribs, small 13th rib, fused ribs, dumbbell- shaped center, wavy and variations in shape.
[Lu SY et al; J of the Chinese Society of Veterinary Science 22 (6): 402-12 (1996)]**PEER REVIEWED**
Non-Human Toxicity Values:
LD50 Rat oral 6640 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Rat ip 1140 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Mouse oral 3400 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Mouse ip 790 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Rabbit oral 2270 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Guinea pig oral 3640 mg/kg
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996. 2653]**PEER REVIEWED**
LD50 Rat (male) oral 7500 mg/kg
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LD50 Rat (female) oral 6640 mg/kg
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LD50 Mouse (male) oral 3510 mg/kg
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LD50 Rabbit (male) oral 2270 mg/kg
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LD50 Rat percutaneous > 10,000 mg/kg
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LC50 Rat inhalation 1.7 mg/l air/4 hr
[Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994. 988]**PEER REVIEWED**
LD50 Rat (male) ip 1640 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Rat (female) ip 1140 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Mouse (female) oral 3400 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Mouse (male) ip 790 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Mouse (female) ip 1110 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Guinea pig (male) oral 3640 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Guinea pig (female) oral 6700 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
LD50 Rabbit (female) oral 2250 mg/kg /from table/
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
Studies in mice with four radioactive forms of the molecule (14C in the ring or as the thiourea carbon of the methyl carbon and 35S) showed that the C=S bond was cleaved to a great extent prior to absorption from the gastrointestinal tract. Some of the methyl carbon apparently is metabolized to carbon dioxide. The major urinary metabolites are carbendazim and its 6-hydroxy derivative; these are excreted as O- or N-glucuronides. A compound in which the two =S's of thiophanate-methyl are replaced by =O's is a minor metabolite. Some other metabolites detectable by thin-layer chromatography of radioactive material remain unidentified.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
Absorption, Distribution & Excretion:
Nearly all thiophanate-methyl is eliminated from the body in 24 hr; that left in tissues after 24 hr is largely eliminated within 96 hr.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 3. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 1457]**PEER REVIEWED**
Pharmacology:
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Thiophanate-methyl's production and use as a fungicide is expected to result in its direct release to the environment. If released to air, a vapor pressure of 7.13X10-8 mm Hg at 25 deg C indicates thiophanate-methyl will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase thiophanate-methyl will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 5 hours. Particulate-phase thiophanate-methyl will be removed from the atmosphere by wet and dry deposition. If released to soil, thiophanate-methyl is expected to have high mobility based upon an estimated Koc of 137. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 1.2X10-9 atm-cu m/mole. Thiophanate-methyl degrades rapidly in soils of various textures to methyl 2-benzimidazolecarbamate and the rate of degradation is four times faster in soil at pH 7.4 than in soil at pH 5.6. Thiophanate-methyl degraded by 90% during a 6-18 week period in soils of various textures (humus 2-4%; pH 5.5-6.5). A half-life of 28 days was estimated for thiophanate-methyl applied to leaves of green house crops. If released into water, thiophanate-methyl is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. Thiophanate-methyl degrades in aqueous solution (25 deg C; 48 hr) by 60% to methyl benzimidazole-2-yl carbamate (MBC). An estimated BCF of 2.4 suggests the potential for bioconcentration in aquatic organisms is low. Occupational exposure to thiophanate-methyl may occur through inhalation and dermal contact with this compound at workplaces where thiophanate-methyl is produced or used. (SRC)
**PEER REVIEWED**
Probable Routes of Human Exposure:
Occupational exposure to thiophanate-methyl may occur through inhalation and dermal contact with this compound at workplaces where thiophanate-methyl is produced or used(SRC). Worker re-entry exposure to pesticides residues in greenhouses is a probable exposure route based upon a study in which thiophanate-methyl was applied to carnations via high-volume spraying at application rates of 150 and 325 g ai/1000 sq m, showing half-lives of 22 and 41 days, respectively(1). Dermal exposure of greenhouse workers to thiophanate-methyl (applied by spraying) on carnations cultured in greenhouses was found to be 64 mg/day (during cutting operations) and 23 mg/day (during sorting and bundling)(2).