Toxicants residue in food and cancer risk: Captan (C9H8Cl3NO2S) Environmental Toxicology Group 14 5/28/16 content Captan Residue in food Exposure D-R, exposure Acute toxicity Chronic toxicity Human health effects Distribution and excretion Cancer risk Characterization Toxicity on animal Toxicity to human Cancer risk Notes Captan introduction 1,2,3,6-tetrahydro-N- (trichloromethylthio) phthalimide C9H8Cl3NO2S A white solid agricultural fungicide Target pests: numerous fungi and microbial Residue in food Captan is highly recommended for preventing and controlling fungal diseases on: Fruits Apples, Grapes, Peaches and Strawberries Vegetables Seed Treatment Only Apple scab Bulbs Preplan Treatment - Gladioli and Tuberous Begonias Lawns and turf Ornamentals Azaleas, Carnations, Chrysanthemums, and Roses Oil farm Peach scab Exposure Pathways Food Air Water Routs Inhalation Ingestion Eyes contact Skin contact Distribution and Excretion Distribution Administered to rats orally, activity was recovered as follows:  51.8% urine  22.8% expired air  15.9% feces  0.6% tissues Excretion  first 24 hours, more than 90%  excreted in the urine and feces,  during the next two days  almost all the rest was excreted  Only 0.01-0.05% was deposited in the organs Dose and response, exposure Acute toxicity Chronic toxicity Human health effects Acute toxicity The mechanism of action may involve the degradation of captan into the short-lived thiophosgene, which is a highly reactive with thiols and other functional groups Test Results Oral LD50 - rat LD50 = g/kg (M) Dermal LD50 – rat LD50 > g/kg Inhalation LC50 – rat Eye Irritation – rabbit LC50 = 0.72 mg/L (M) LC50 = 0.87 mg/L (F) Irreversible corneal opacity at 21 days in unwashed eyes Dermal Irritation -rabbit Not an irritant at days Dermal Sensitization -guinea pig Moderate skin sensitizer Data extract from Captan technical fact sheet, US national pesticide information Chronic toxicity Reproduction In a three-generation rat reproduction study:  at 1000 mg/kg diet (50 (mg/kg)/day)  lowered lactation in rd generation (only effects)  at 500 mg/kg (5 (mg/kg)/day)  no effects Teratogenicity Rabbit: No malformed fetuses were observed from rabbits given up to 75 mg/kg of captan orally on days 6-18 of gestation Monkey: no fetal malformations from monkeys given up to 75 mg/kg on days 21-34 of gestation Human health effects Acceptable daily intake for man: - 0.1 mg/kg Signs of Toxicity – Humans: Individuals working with captan or in fields where captan was applied reported eye and skin irritation Investigators conducted patch tests with 0.1 to 1.0% captan which they placed on the upper backs of 279 to 442 individuals who were currently, one time, or never employed in agriculture:   Out of the 442 people tested, 13 individuals at the highest dose experienced irritant reactions 17 experienced allergic reactions Human health effects Case report acute 17 years old woman (suicide) 7.5 g of Captan after hours: headache, nausea, weakness, numbness of upper limbs, and substernal pain chronic A 73-yr old retired fruit grower Workers spraying operations using captan captan in air (5 mg/m3) (high concentration) persistent erythema, itching, & desquamation of the face & backs of hands eye irritation including burning, itching and tearing Cancer risk The U.S EPA has assigned captan a carcinogenicity classification of B2, probable human carcinogen (B2: Sufficient evidence of carcinogenicity from animal studies with inadequate or no data from epidemiologic studies in humans.) From PAN pesticide database cancer risk Test Charles River CD rats were fed 25 to 250 mg/kg/day captan for years  Males - exhibited hepatocellular hypertrophy and significant trends of adenomas and carcinomas in the kidney at 100 mg/kg/day - increased relative organ weight for heart, brain, liver, and thyroid/parathyroid Both sexes - showed an increased relative kidney weight and a decreased body weight - The lowest observable effects level (LOEL) was determined to be 100 mg/kg/day cancer risk Captan residues on apples, cantaloupe, cucumbers, grapefruit, lemons, lettuce, oranges, squash, strawberries, and spinach is substantially reduced by washing and almost non-detectable after peeling Captan residues in celery, cucumbers, squash, and spinach is almost non-detectable after cooking Residential Exposure Activity Primary handler - Mixing/loading/applying wettable powders to fruit trees Residential Food Aggregate DWLOC cancer Cancer Cancer Food and ppb Risk Risk Residential 6.5x10 Secondary handler - Painting with a brush 8.5x10 Post application - Ornamentals 4.2x10 -7 -8 -8 1.3x10 1.3x10 1.3x10 -7 -7 -7 7.8x10 2.2x10 1.7x10 -7 -7 -7 3.2 11 12 Aggregate Cancer Risks for Captan, EPA DWLOC: drinking water levels of comparison Characterization Toxicity on animal Toxicity to human        low in toxicity if eaten by low in toxicity if breathed in skin irritation allergic reactions low in toxicity if contacted with skin highly toxic to the eyes Decrease immune function with large amount used Cancer risk   Rats and mice developed various types of cancers B2 category to human by US EPA Notes within captan residues in food Many fruits and vegetables may contain captan residues but it can be easily washed Cooking eliminates captan residues Do the following if you experience any: Route of Exposure Symptoms Inhalation First Aid Fresh air rest Refer for medical attention Skin MAY BE ABSORBED! Redness Eye Redness Pain Blurred vision Ingestion Diarrhea Vomiting Remove contaminated clothes Rinse and then wash skin with water and soap Refer for edictal attention First rinse with plenty of water for several minutes (remove contact lenses if easily possible) then take to a doctor Rinse mouth Refer for medical attention Thank you We welcome any question or comment [...]... washing and almost non-detectable after peeling Captan residues in celery, cucumbers, squash, and spinach is almost non-detectable after cooking Residential Exposure Activity Primary handler - Mixing/loading/applying wettable powders to fruit trees Residential Food Aggregate DWLOC cancer Cancer Cancer Food and ppb Risk Risk Residential 6.5x10 Secondary handler - Painting with a brush 8.5x10 Post application... Captan after 3 hours: headache, nausea, weakness, numbness of upper limbs, and substernal pain chronic A 73-yr old retired fruit grower Workers spraying operations using captan captan in air (5 mg/m3) (high concentration) persistent erythema, itching, & desquamation of the face & backs of hands eye irritation including burning, itching and tearing Cancer risk The U.S EPA has assigned captan a carcinogenicity... types of cancers B2 category to human by US EPA Notes within captan residues in food Many fruits and vegetables may contain captan residues but it can be easily washed Cooking eliminates captan residues Do the following if you experience any: Route of Exposure Symptoms Inhalation First Aid Fresh air rest Refer for medical attention Skin MAY BE ABSORBED! Redness Eye Redness Pain Blurred vision Ingestion... 3.2 11 12 Aggregate Cancer Risks for Captan, EPA DWLOC: drinking water levels of comparison Characterization Toxicity on animal Toxicity to human        low in toxicity if eaten by low in toxicity if breathed in skin irritation allergic reactions low in toxicity if contacted with skin highly toxic to the eyes Decrease immune function with large amount used Cancer risk   Rats and mice developed... weight for heart, brain, liver, and thyroid/parathyroid Both sexes - showed an increased relative kidney weight and a decreased body weight - The lowest observable effects level (LOEL) was determined to be 100 mg/kg/day cancer risk Captan residues on apples, cantaloupe, cucumbers, grapefruit, lemons, lettuce, oranges, squash, strawberries, and spinach is substantially reduced by washing and almost non-detectable... human carcinogen (B2: Sufficient evidence of carcinogenicity from animal studies with inadequate or no data from epidemiologic studies in humans.) From PAN pesticide database cancer risk Test Charles River CD rats were fed 25 to 250 mg/kg/day captan for 2 years  Males - exhibited hepatocellular hypertrophy and significant trends of adenomas and carcinomas in the kidney at 100 mg/kg/day - increased... attention Skin MAY BE ABSORBED! Redness Eye Redness Pain Blurred vision Ingestion Diarrhea Vomiting Remove contaminated clothes Rinse and then wash skin with water and soap Refer for edictal attention First rinse with plenty of water for several minutes (remove contact lenses if easily possible) then take to a doctor Rinse mouth Refer for medical attention Thank you We welcome any question or comment