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EXTOXNET 1111'-METHIDAT1i10N p://ace.orst.edu/cgi-bin/mis/0I/pips/methidat.htm°-l; the rat [2]. Methidathion is only a mild skin irritant and is nonirritating to the eyes (in rabbits). Via the inhalation route, it may be slightly toxic, with a reported 4-hour inhalation LC50 of 3.6 mg/L in rats [131. Effects due to acute methidathion exposures are similar to those caused by other organophosphate pesticides, and may include nausea, vomiting, cramps, diarrhea, salivation, headache, dizziness, muscle twitching, difficulty breathing, blurred vision, and tightness in the chest [2]. High acute exposure may cause intense breathing problems, including paralysis of the respiratory muscles. • Chronic toxicity: Beagle dogs fed small doses of the compound for 2 years experienced no compound related effects at or below the dose of 0.10 mg/kg/day [2,8]. At doses of 0.4 mg/kg/dav I and above, the dogs experienced enzymatic changes and liver alterations. Inhibition of red blood cell cholinesterase, an enzyme, was observed only at the highest dose tested (1.6 mg/kg/day) [2]. Rats also have a low tolerance for the compound. Compound related effects were first noted in the rats at doses of 2 mg/kg and above and included cholinesterase inhibition in the blood and brain and some nerve related effects. At the highest dose of 5 mg/kg, the rats ate more food but had less body ` weight gain. They also developed skin lesions and foam in their lungs [2,8,81]. Rhesus monkeys fed small amounts of the compound developed changes in blood cholinesterase activity at doses of 1 mg/kg/day and above. Humans ingesting very small amounts of the compound at doses of 0.11 mg/kg/day for 6 weeks had no noticeable clinical effects [8]. A study of exposure levels of mixer/loaders of methidathion (Supracide applications) in California showed that the greatest exposure potential to the compound was through the skin (dermal) [821. Reproductive effects: Moderate amounts of methidathion caused a number of adverse reproductive effects. When male and female rats were fed moderate amounts of methidathion over two 1 ' successive litters, the parents experienced tremors, decreased food consumption and decreased { ovary weights at 1.25 mg/kg/day [2,8]. The low dose of 0.25 mg/kg/day disrupted mating behavior and also affected nursing offspring. At 2.5 mg/kg/day (the highest dose tested), stillbirths and ' decreased pup survival were observed [2]. Reproductive effects in humans as a result of methidathion exposure are unlikely under normal circumstances. • Teratogenic effects: Small to moderate amounts of methidathion administered to pregnant rats and rabbits produced no birth defects in the offspring. The pregnant females experienced several compound related effects, most of which were typical of cholinesterase inhibition [2]. The f compound is unlikely to pose a developmental risk to humans. ' • Mutagenic effects: Methidathion did not induce any genetic changes in a number of tests for gene mutation, chromosomal aberrations, and DNA damage. The various gene mutation studies were conducted on hamster bone marrow cells, in mammalian cells, and on several species of bacteria [2]. These data indicate that methidathion is not mutagenic. • Carcinogenic effects: Methidathion caused malignant and benign liver tumors (adenomas) in male ;I mice fed 2.5 mg/kg/day for 2 years. Additional tumors (carcinomas) were found in the male mice fed 5 mg/kg/day over the same period. This higher feeding level also produced numerous other signs of toxicity [2,8]. Since these results apply to only one sex in one species, the carcinogenic potential of methidathion is unclear. j • Organ toxicity: Target organs in animal studies include the nervous system, liver, gall bladder, and ' ovaries. i • Fate in humans and animals: Methidathion is rapidly absorbed, broken down, and eliminated in animals [8]. Following absorption of the compound, the majority is lost as a breakdown product through the lungs [2,61. Between 30 and 50% of the ingested amount is eliminated (as breakdown products) in urine [2,6]. Half of the initial amount of the compound is removed from mammals within 6 hours [2,6]. The breakdown products of the parent compound are not of toxicological Ij concern [8]. Only very small amounts of various metabolic products of methidathion have been detected in milk from cows [6] and in chicken eggs [21• 201'4 � 1l261ot1 5:16 AM