Variation between three strains of rat: inhibition of neurotoxic esterase and acetylcholinesterase by tri-o-cresyl phosphate.
J Toxicol Environ Health 1988 Jan; 25(3):259-268
The effect of the strain of rodent on the results of a test for neurotoxicity was studied in rats exposed to the organophosphorus compound tri-o-cresyl-phosphate (78308) (TOCP). Sprague-Dawley-rats (SD), Long-Evans-rats (LE), and Fischer-344-rats (F344) were administered TOCP by oral gavage at doses on the basis of their established delayed neurotoxicity in LE (290, 580, or 1160mg/kg); animals were sacrificed 48 hours after dosing and the brain homogenized for measurement of inhibition of neurotoxic-esterase (NTE) and acetylcholinesterase (AChE) as end points for organophosphorus compound induced delayed neurotoxicity and acute toxicity, respectively. Differences in basal levels among the strains were found for NTE (LE greater than F344 greater than SD) but not AChE. Strain differences in inhibition by TOCP were found with both assays, with SD rats much less sensitive to esterase inhibition than LE or F344-rats; the median effective dose values for NTE inhibition were estimated to be 458, 209, and 288mg/kg for SD, F344, and LE rats, respectively. Liver microsomes from the F344 rats had less cytochrome-P-450 than those from the other two strains. The authors conclude that differences in the ability of the strains to form or inactivate the active metabolite of TOCP may account for the observed variations in this study; the results may be important in selecting a strain for the study of the toxic effects of organophosphorus compounds in rats.
NIOSH-Publication; NIOSH-Grant; Laboratory-animals; Neurotoxicology; Toxic-effects; Toxic-dose; Comparative-toxicology; Enzyme-activity; Organo-phosphorus-compounds
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Journal of Toxicology and Environmental Health
Duke University, Durham, North Carolina