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BEHAVIORAL AND NEUROCHEMICAL CONSEQUENCES OF DEVELOPMENTAL ORGANOTIN EXPOSURE IN RATS.
Citation:
Ehman, K., S. Jenkins, S Barone, AND V C. Moser. BEHAVIORAL AND NEUROCHEMICAL CONSEQUENCES OF DEVELOPMENTAL ORGANOTIN EXPOSURE IN RATS. Presented at Behavioral Toxicology Society, Philadelphia, PA, 6/21/03.
Description:
Behavioral and Neurochemical Consequences of Developmental Organotin Exposure in Rats.
Ehman, K.,1 Jenkins, S.,2 Barone Jr., S.2 and Moser, V.2 1Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, 2Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC
Organotins are widely used as stabilizers in PVC and CPVC piping, which results in their presence in drinking water supplies. Concern for neurotoxicity has been raised by published findings of a deficit on a cognitive runway task in rat pups developmentally exposed to both monomethyl tin (MMT) and trimethyl tin (TMT). The first objective of this study was to replicate and expand the dose-response characteristics of MMT, based on the earlier publication, and subsequently, to extend the findings to dimethyl tin (DMT). In separate studies, pregnant rats were exposed via drinking water to either MMT (0, 10, 50, 245 ppm) or DMT (0, 3 15, 74 ppm) before mating and throughout gestation and lactation (until weaning at postnatal day, or PND, 21). Behavioral assessments included a runway learning test (PND 11), in which the rat pups learned to negotiate a runway for dry suckling reward; motor activity habituation (PNDs 13, 17 and 21); and, as adults, the Morris water maze. Littermates were sacrificed on PNDs 1, 22, and as adults, and brain regions were analyzed for apoptosis (programmed cell death) as determined by oligonucleosomal DNA fragmentation. Overall, there were no effects on any endpoints of growth, development or cognitive function following MMT exposure. Although DMT-exposed individuals did not display deficits in the runway or motor activity tasks, the DMT middle dose group learned the water maze task significantly slower, but only in the first week. This difference may be due to the rats spending a longer time searching in the outer zone of the tank. During the memory probe (no platform) and the visual task (raised platform), there were no group differences. In agreement with the behavioral data, MMT did not significantly alter apoptosis at any of the time points. Conversely, DMT-exposed individuals showed no changes in apoptosis on PND1, but displayed decreased levels of apoptosis in the cortex (all doses) and cerebellum (middle and high doses) at PND 22, as well as in the adult brainstem (high dose only). The association between DMT-induced changes in apoptosis and behavior remains to be determined.
This abstract does not necessarily reflect EPA policy