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':XTOXNET PIP - ENDOSULFAN ttp:Hace.orst.edu/cgi-bin/ml's/01 /pips/endosuit'.htin Acute toxicity: Endosulfan is highly toxic via the oral route, with reported oral LD50 values ranging from 18 to 160 mg/kg in rats, 7.36 mg/kg in mice, and 77 mg/kg in dogs [2.9]. It is also highly toxic via the dermal route, with reported dermal LD50 values in rats ranging from 78 to 359 mg/kg [2,9]. Endosulfan may be only slightly toxic via inhalation, with a reported inhalation LC50 of 21 mg/L for 1 hour, and 8.0 mg/L for 4 hours [2]. It is reported not to cause skin or eye irritation in animals [2]. The alpha -isomer is considered to be more toxic than the beta -isomer [2]. Animal data indicate that toxicity may also be influenced by species and by level of protein in the diet; rats which have been been deprived of protein are nearly twice as susceptible to the toxic effects of endosulfan [2]. Solvents and/or emulsifiers used with endosulfan in formulated products may influence its absorption into the system via all routes; technical endosulfan is slowly and incompletely absorbed into the body whereas absorption is more rapid in the presence of alcohols, oils, and emulsifiers [2]. Stimulation of the central nervous system is the major characteristic of endosulfan poisoning [51 ]. Symptoms noted in acutely exposed humans include those common to the other cyclodienes, e.g., incoordination, imbalance, difficulty breathing, gagging, vomiting, diarrhea, agitation, convulsions, and loss of consciousness [2]. Reversible blindness has been documented for cows that grazed in a field sprayed with the compound. The animals completely recovered after a month following the exposure [2]. In an accidental exposure, sheep and pigs grazing on a sprayed field suffered a lack of muscle coordination and blindness [2]. Chronic toxicity: In rats, oral doses of 10 mg/kg/day caused high rates of mortality within 15 days, but doses of 5 mg/kg/day caused liver enlargement and some other effects over the same period [2]. This dose level also caused seizures commencing 25 to 30 minutes following dose adiministration that persisted for approximately 60 minutes [2]. There is evidence that administration of this dose over 2 years in rats also caused reduced growth and survival, changes in kidney structure, and changes in blood chemistry [2,51]. Reproductive effects: Rats fed doses of endosulfan of 2.5 mg/kg/day for three generations showed no observable reproductive effects, but 5.0 mg/kg/day caused increased dam mortality and resorption [2,51]. Female mice fed the compound for 78 weeks at 0.1 mg/kg/day had damage to their reproductive organs [52]. Oral dosage for 15 days at 10 mg/kg/day in male rats caused damage to the semeniferous tubules and lowered testes weights [2,5]. It is unlikely that endosulfan will cause reproductive effects in humans at expected exposure levels. Teratogenic effects: An oral dose of 2.5 mg/kg/day resulted in normal reproduction in rats in a three -generational study, but 5 and 10 mg/kg/day resulted in abnormalities in bone development in the offspring [2,51]. Teratogenic effects in humans are unlikely at expected exposure levels. Mutagenic effects: Endosulfan is mutagenic to bacterial and yeast cells [51]. The metabolites of endosulfan have also shown the ability to cause cellular changes [2,51]. This compound has also caused mutagenic effects in two different mammalian species [51]. Thus, evidence suggests that exposure to endosulfan may cause mutagenic effects in humans if exposure is great enough. Carcinogenic effects: In a long-term study done with both mice and rats, the males of both groups experienced such a high mortality rate that no conclusions could be drawn [52]. However, the females of both species failed to develop any carcinogenic conditions 78 weeks after being fed diets containing up to about 23 mg/kg/day. The highest tolerated dose of endosulfan did not cause increased incidence of tumors in mice over 18 months, and a later study also showed no evidence of carcinogenic activity in mice or rats [2,52]. It appears that endosulfan is not carcinogenic. Organ toxicity: Data from animal studies reveal the organs most likely to be affected include kidneys, liver, blood, and the parathyroid gland [51 ]. • Fate in humans and animals: Endosulfan is rapidly degraded into mainly water-soluble compounds and eliminated in mammals with very little absorption in the gastrointestinal tract [2]. 2 ol'4 5/12/00 2:01 PM