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NEUROTOXICITY STUDIES
Impact/Purpose:
he purpose of these studies is to develop hazard identification and dose response data on the neurotoxicity of selected DBPs. A neurotoxicological screening program involving a collaboration between the EPA and the National Toxicology Program (NTP) was initiated in FY99. Previous research at EPA was focused on dichloroacetic acid (DCA), and neuropathological assessments of DCA-treated rats are being finalized. Additional studies examined potential neurotoxicity of other DBPs -- dibromoacetic acid (DBA), dibromoacetonitrile, and bromodichloromethane. These studies involved neurobehavioral testing of the rats at specified time intervals during 6-month exposure studies, followed by neuropathological evaluations. All compounds were delivered in drinking water. The Stage 1 DBP rule proposed an MCLG for DCA and an MCL for haloacetic acids (five) (HAA5). The results of these studies could increase our understanding of the toxicity of several DBPs and lead to a more accurate estimation of the risk, if any, to humans exposed toDBPs in finished drinking water for the Stage 2 DBP rule.
Description:
The neurotoxicity of DBPs in general has not been well characterized. The literature provides reports of neurotoxicity of DCA following exposures to relatively high doses. Studies completed at EPA, however, have shown that relatively low doses of DCA (as low as 16 mg/kg/day; similar to the lowest doses at which other noncancer effects have been observed experimentally) can cause neurotoxicity after several months of exposure. The effects are reversible at low-dose, short-term exposures, but are irreversible following high-dose exposures. The DCA neurobehavioral studies have been published in a peer-reviewed journal. The neuropathological changes that accompany the behavioral changes observed are currently being evaluated. These findings suggested that additional research to characterize the potential neurotoxicity of DCA as well as related haloacids is warranted and will provide additional information for the estimation of risk in humans. A neurotoxicity screening battery was used to evaluate the neurotoxic effects of candidate compounds. The screening battery included functional assessments (some of which are equivalent to a neurological exam for humans), along with neuropathological assessments on perfused tissues from the nervous system of treated and control rats. Functional assessments were carried out before, during and after exposures, to determine the time-course of effects.