Neurotoxicity Produced by Dibromoacetic Acid in Drinking Water of Rats
| Autor: | Katherine L. McDaniel, Mark T. Butt, Virginia C. Moser, Pamela M. Phillips, B. S. Jortner, A. B. Levine, Robert C. Sills |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Time Factors Dose Drug Evaluation Preclinical Administration Oral Physiology Acetates Motor Activity Weight Gain Toxicology Drug Administration Schedule Body Temperature White matter Sex Factors Water Supply Water Pollution Chemical medicine Animals Behavior Animal Dose-Response Relationship Drug Chemistry Neurotoxicity Alopecia Spinal cord medicine.disease Rats Inbred F344 Hypotonia Rats Spinal Nerves medicine.anatomical_structure Hair loss Anesthesia Nerve Degeneration Toxicity Female Neurotoxicity Syndromes medicine.symptom Weight gain Disinfectants |
| Zdroj: | Toxicological Sciences. 79:112-122 |
| ISSN: | 1096-0929 |
| DOI: | 10.1093/toxsci/kfh081 |
| Popis: | An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids. |
| Databáze: | OpenAIRE |
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