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DEVELOPMENTAL NEUOTOXICITY EVALUATION OF MIXTURES OF MONO- AND DIMETHYL TIN IN DRINKING WATER OF RATS.
Citation:
MOSER, V. C., K. MCDANIEL, AND P. PHILLIPS. DEVELOPMENTAL NEUOTOXICITY EVALUATION OF MIXTURES OF MONO- AND DIMETHYL TIN IN DRINKING WATER OF RATS. Presented at International Neurotoxicology Association, Pacific Grove, CA, June 10 - 15, 2007.
Description:
Developmental Neurotoxicity Evaluation of Mixtures of Mono- and Dimethyl Tin in Drinking Water of Rats
V.C. Moser, K.L. McDaniel, P.M. Phillips
Neurotoxicology Division, NHEERL, ORD, US EPA, RTP, NC, USA
Organotins, especially monomethyl (MMT) and dimethyl (DMT) tin, are widely used as plastic stabilizers and have been detected in environmental samples such as domestic water and house dust. A few limited studies have suggested cognitive deficits in offspring developmentally exposed to MMT, and neurotoxicity in adults exposed to a MMT:DMT mixture. Since these important outcomes could not be replicated in our laboratory using the individual chemicals, we wondered if mixtures may be more biologically effective. We therefore exposed pregnant Sprague-Dawley rats from day 6 of gestation through weaning to 1) control water, 2) MMT:DMT 1:9 75 ppm, 3) MMT:DMT 4:1 68 ppm, 4) MMT:DMT 4:1 338 ppm; 5) DMT 68 ppm, or 6) MMT 270 ppm. These doses and ratios were selected to replicate previous studies and/or represent environmental exposures. Male and female offspring were tested in numerous behavioral procedures: ontogeny of motor activity, spontaneous alternation, functional observational battery, and Morris water maze. In addition, brains were weighed at multiple times and neuropathological evaluations were conducted in adult offspring. Maternal fluid consumption and weight gain was depressed in dams receiving DMT alone, the 1:9 mixture, or the high-dose 4:1 mixture; these three treatments had equivalent levels of DMT. No other signs of toxicity were observed in the dams. Likewise, pup weight gain was depressed in the same groups through weaning. Despite the obvious maternal toxicity and pup weight effects, there were almost no treatment-related changes in any of the neurobehavioral assays. The DMT groups showed longer latencies in the water maze test in adults; this was most evident during the reversal procedure. Brain weights were not altered; neuropathological examination is underway. These data appear to indicate general toxic effects of the high dose of DMT, but no additional or potentiated effects in MMT:DMT mixtures.
(This abstract does not necessarily reflect USEPA policy)