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EVALUATION OF POTENTIAL DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS.
Citation:
MOSER, GINGER AND K. EHMAN. EVALUATION OF POTENTIAL DEVELOPMENTAL NEUROTOXICITY OF ORGANOTINS. Presented at Society for Risk Analysis, Orlando, FL, December 04 - 07, 2005.
Description:
Organotins, including monomethyltin (MMT), dimethyltin (DMT), and dibutyltin (DBT), are widely used as heat stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for developmental neurotoxic effects were raised by published findings of a cognitive deficit in rat pups exposed to MMT, and as such, these compounds have been identified on the US EPA Candidate Contaminant List for needing further toxicity evaluation. We conducted developmental studies to evaluate and characterize potential neurotoxic effects of MMT, DMT, and DBT. In all studies, female Sprague-Dawley rats were exposed via drinking water through most of gestation and all of lactation; two studies included exposure prior to mating. Various neurobehavioral tests were used to assess neuromotor development and cognitive function from before weaning to adulthood. Two MMT studies, using concentrations up to 500 ppm, showed no effects on any measure of growth, development, or cognitive function. The neuropathological evaluation revealed mild cortical vacuolation. Two studies of DMT also revealed few developmental effects; however, both studies demonstrated a reproducible effect on spatial learning (mid-concentration, 15 ppm, only). Brain weight was decreased in DBT-exposed offspring (25 ppm) at weaning, but as yet, no neurobehavioral alterations have been observed which could be correlated with this effect (data analysis underway). Assays of apoptosis revealed changes in the DMT and DBT-treated rats at several ages, indicating an altered progression of naturally-occurring cell death processes. Overall, these studies showed that:1) MMT is the least biologically active organotin of the three tested; 2) both DMT and DBT produced some neurotoxicologically significant changes, but 3) the pattern of effects was quite different for these two compounds. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.