Behavioral evaluation of the neurotoxicity produced by dichloroacetic acidin rats

Dichloroacetic acid (DCA) is commonly found in drinking water as a by-produ ct of chlorination disinfection. It is a known neurotoxicant in rats, dogs, and humans. We have characterized DCA neurotoxicity in rats using a neurob ehavioral screening battery under varying exposure durations (acute, subchr onic, and chronic) and routes of administration (oral gavage and drinking w ater). Studies were conducted in both weanling and adult rats, and comparis ons were made between Long-Evans and Fischer-344 rats. DCA produced neuromu scular toxicity comprised of limb weakness and deficits in gait and rightin g reflex; altered gait and decreased hindlimb grip strength were the earlie st indicators of toxicity. Other effects included mild tremors, ocular abno rmalities, and a unique chest-clasping response (seen in Fischer-344 rats o nly). Neurotoxicity was permanent (i.e., through 2 years) following a 6-mon th exposure to high dose levels, whereas the effects of intermediate dose l evels with exposures of 3 months or less were slowly reversible. The severi ty, specificity, and recovery of neurological changes were route, duration, and strain dependent. Fischer-344 rats were more sensitive than Long-Evans rats, and weanling rats may be somewhat more sensitive than adults. Oral g avage produced significantly less toxicity compared to the same intake leve l received in drinking water. Neurotoxicity was progressive with continued exposure, and was observed at exposure levels as low as 16 mg/kg/day (lowes t dose level tested) when administered via drinking water in subchronic stu dies. The data from these studies characterize the neurotoxicity produced b y DCA, and show it to be more pronounced, persistent, and occurring at lowe r exposures than has been previously reported. Further research should take into account these marked route, age, and strain differences. Published by Elsevier Science Inc.