Science Inventory

NEUROXOTOXICITY PRODUCED BY DIBROMOACETIC ACID IN DRINKING WATER OF RATS.

Citation:

Phillips, P. M., A. Levine, K. L. McDaniel, R. C. Sills, AND V C. Moser. NEUROXOTOXICITY PRODUCED BY DIBROMOACETIC ACID IN DRINKING WATER OF RATS. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.

Description:

The Safe Drinking Water Act requires that EPA consider noncancer endpoints for the assessment of adverse human health effects of disinfection byproducts (DBPs). Dibromoacetic acid (DBA) is one of many DBPs produced by the chlorination of drinking water. Its chlorinated analog, dichloroacetic acid, is a known human and animal neurotoxicant, but essentially no studies have evaluated the neurotoxic potential of DBA. This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats, using a neurobehavioral test battery to detect neurological and functional changes, followed by perfusion fixation at the end of dosing for neuropathological evaluation. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l, producing an average intake of about 0, 20, 72, and 161 mg/kg/day. In both sexes, weight gain was depressed in the high-dose group, but overall general health was not altered. Testing using a functional observational battery (FOB) and motor activity took place before dosing began and at 1, 2, 4, and 6 months. DBA produced dose-related neuromuscular toxicity characterized by limb weakness (both fore- and hindlimb), mild gait abnormalities, and hypotonia, as well as sensorimotor depression, with decreased responses to a tail pinch and click. Other signs of toxicity included decreased activity and chest clasping. The neurotoxicity did not appear progressive with continued exposure. The major neuropathological finding was degeneration of myelinated nerve fibers in spinal cord white matter (lateral and ventral areas) in the high-dose rats. In addition, small numbers of swollen, eosinophilic, and sometimes vacuolated neurites were observed in the spinal cord gray matter of mid- and high-dose rats. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. Based on the neurobehavioral data, the LOEL from this study was 20 mg/kg/day (lowest dose tested). These studies demonstrate that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.
This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/20/2002
Record Last Revised: 06/06/2005
Record ID: 62120