Carbaryl and 1-Naphthol Tissue Levels and Related Cholinesterase Inhibition in Male Brown Norway Rats from Preweaning to Senescence
Studies incorporating both toxicokinetic and dynamic factors provide insight into chemical sensitivity differences across the life span. Tissue (brain, plasma, liver) levels of the N-methyl carbamate carbaryl, and its metabolite 1-naphthol, were determined and related to brain and RBC cholinesterase...
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Published in | Journal of Toxicology and Environmental Health, Part A Vol. 76; no. 20; pp. 1151 - 1167 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Taylor & Francis
18.10.2013
Taylor & Francis Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Studies incorporating both toxicokinetic and dynamic factors provide insight into chemical sensitivity differences across the life span. Tissue (brain, plasma, liver) levels of the N-methyl carbamate carbaryl, and its metabolite 1-naphthol, were determined and related to brain and RBC cholinesterase (ChE) inhibition in the same animals. Dose-response (3, 7.5, 15, or 22.5 mg/kg, 40-45 min postdosing) and time course (3 or 15 mg/kg at 30, 60, 120, or 240 min postdosing) of acute effects of carbaryl (oral gavage) in preweanling (postnatal day [PND] 18) and adult male Brown Norway rats from adolescence to senescence (1, 4, 12, 24 mo) were compared. At all ages there were dose-related increases in carbaryl and 1-naphthol in the dose-response study, and the time-course study showed highest carbaryl levels at 30 min postdosing. There were, however, age-related differences in that the 1- and 4-mo rats showed the lowest levels of carbaryl and 1-naphthol, and PND18 and 24-mo rats had similar, higher levels. The fastest clearance (shortest half-lives) was observed in 1- and 4-mo rats. Carbaryl levels were generally higher than 1-naphthol in brain and plasma, but in liver, 1-naphthol levels were similar to or greater than carbaryl. Brain ChE inhibition closely tracked brain carbaryl concentrations regardless of the time after dosing, but there was more variability in the relationship between RBC ChE and plasma carbaryl levels. Within-subject analyses suggested somewhat more brain ChE inhibition at lower carbaryl levels only in the PND18 rats. These findings may reflect maturation followed by decline in kinetic factors over the life span. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1528-7394 1087-2620 2381-3504 |
DOI: | 10.1080/15287394.2013.844751 |