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' s a ,XTOXNET PIP - METHIDATHION Page 2 of 3 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) [82]. a 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 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 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 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. . Organ toxicity: Target organs in animal studies include the nervous system, liver, gall bladder, and ovaries. . 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 [2,6]. 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 concern [8]. Only very small amounts of various metabolic products of methidathion have been detected in milk from cows [6] and in chicken eggs [2]. Ecological Effects: . Effects on birds: Methidathion is highly toxic to birds following acute exposure. The reported oral LD50 values for the compound are 23 mg/kg to 33 mg/kg in mallards, 8.41 mg/kg in Canadian geese, 33.2 mg/kg in P g g g g pheasant, and 225 mg/kg in the chukar partridge 8 6 the ring-necked ph g g p g [ � ] . Effects on aquatic organisms: The compound is very highly acutely toxic to aquatic organisms (both vertebrate and invertebrate); the reported LC50 values of the compound are 10 to 14 ug/L in rainbow trout and 2 to 9 ug/L in bluegill sunfish [13,72]. Tests on lobsters indicated that the combination of methidathion and another organophosphate insecticide, phosphamidon, was more toxic than either compound separately or than would be expected if the toxicities were added together [13]. Studies with bluegill sunfish indicate that there is only a slight potential that the compound would accumulate in fish tissues [6]. Maximum levels of the residues of the pesticide after 1 month of exposure to very low concentrations in the water, 0.05 ug/L, were 1.0 ug/kg in the edible tissue, 3.9 ug/kg in nonedible tissue, and 2.4 ug/kg in whole fish. These concentrations indicate a low bioconcentration factor of 46 for whole fish. After 2 weeks in water without methidathion,the concentration in whole fish fell by nearly 80% [2]. . Effects on other organisms: Methidathion is slightly toxic to bees [13]. Envir6nmental Fate: . Breakdown.in soil-arid-groundwater:�Methidathion is of low persistence in the soil environment; reported field half-lives are 5 to 23 days, with a representative value of about 7 days [19]. Breakdown of the compound in soil occurs through the action of soil microorganisms [83]. Under alkaline conditions, methidathion is rapidly degraded by chemical action [8]. Methidathion and its breakdown products are poorly bound by soils, and so may be mobile [19,81]. However, they have not been detected in any groundwater sources. This is