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Carbaryl neurotoxicity across the life-span of the Brown-Norway rat
Citation:
MOSER, V. C., P. M. Phillips, AND K. MCDANIEL. Carbaryl neurotoxicity across the life-span of the Brown-Norway rat. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
We systematically compared the dose-response data across the age continuum for neurotoxicity produced by carbaryl, an N-methyl carbamate that produces acute toxicity via inhibition of acetylcholinesterase (ChE).
Description:
Demographics show that the proportion of older adults is increasing every year. While there has been considerable attention paid to potential sensitivity of the young to environmental chemicals, there is much less known about the relative vulnerability of the aged. Differences in response could be due to altered sensitivity as a result of toxicokinetic and/or toxicodynamic changes. We systematically compared the dose-response data across the age continuum for neurotoxicity produced by carbaryl, an N-methyl carbamate that produces acute toxicity via inhibition of acetylcholinesterase (ChE). Male Brown-Norway rats were tested on postnatal day 18 (PND 18), and at 1, 4, 12, and 24 months of age (n=9-1 O/dose/age), and were orally gavaged with vehicle (com oil), 3, 7.5, 15, or 22.5 mg/kg carbaryl. Horizontal (all ages) and vertical (rearing; adults only) motor activity was measured for 20 min beginning 15 min after dosing. Within 5 min after the activity session, rats were sacrificed and brain and RBC were collected for subsequent assay of ChE activity. The dose-response curves for brain ChE and horizontal activity were significantly different across ages. For brain ChE, the PND18 pups were more affected than the other ages. On the other hand, RBC ChE was similarly decreased across all ages. Older rats (12 and 24 mo) were more sensitive to decreases in horizontal activity, especially at the higher doses, whereas the 4 mo old rats were least sensitive. The same pattern was seen with vertical activity. In both control and treated rats, variability of the behavioral measures was greatest in the youngest and oldest rats, unlike ChE measures which showed similar variability across ages. Thus, the youngest rats were the most sensitive to the ChE-inhibiting effects of carbaryl, but older rats showed the most motor activity depression. The explanation for the dissociation between ChE inhibition and motor activity changes across ages is unclear. This is an abstract of a proposed presentation and does not reflect US EPA policy.