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662075 
Journal Article 
Abstract 
Efficacy Of In Vitro Carboxylesterase Detoxication Of Organophosphates In Adult And Juvenile Rat Liver And Serum 
Pittman, JT; Moore, CA; Shows, EB; Chambers, HH; Wagner, JL; Chambers, JE 
2004 
1 
Toxicologist
ISSN: 0731-9193 
TOX/4002103 
78 
1-S 
378 
English 
Juvenile animals are more vulnerable than adults to the acute toxicity of organophosphorus (OP) insecticides. Acute toxicity levels are strongly related to the presence and the efficiency of specific detoxication mechanisms, primarily several protective esterases such as carboxylesterases (CbxE). The in vitro sensitivities of liver [adult, postnatal day (PND) 12, and PND1] and serum [adult and PND 12] CbxE were determined for the active metabolites (oxons) of a group of OP insecticides (e.g. paraoxon, chlorpyrifos-oxon), to investigate age-related differences in toxicity. In addition, the effect of tissue concentration on the in vitro potency of the CbxE inhibitors was investigated. CbxE activity was assessed spectrophotometrically using 4-nitrophenyl valerate as the substrate. The assessment of the protective capabilities of CbxE for each oxon, in each age group, was based on IC50 values, calculated by linear regression. All oxons showed higher IC50 values for high tissue concentration compared to low concentration, reflecting the higher number of CbxE molecules present. The oxons tested showed a variable range of IC50 values for both liver and serum for each age group. Of the compounds tested, chlorpyrifos- oxon (Cpxn) had the lowest IC50 for both liver and serum in all ages, reflecting the high sensitivity of CbxE for Cpxn. IC50s were higher in serum than liver in most cases. Generally, for all of the OP compounds tested in both liver and serum, the IC50 for each age group increased with increasing age which may reflect the higher CbxE levels in adult tissue. These data indicate that the stoichiometric detoxication efficiency of CbxE is compound-specific as well as age-dependent, and it is of paramount importance to consider comparable tissue or enzyme concentrations when making comparisons of potency among compounds. 
Rats; Animals; In Vitro; Liver/*DRUG EFFECTS/ENZYMOLOGY/GROWTH & DEVELOPMENT; Aging/*METABOLISM/BLOOD; Carboxylesterase/*METABOLISM/BLOOD; Paraoxon/*BLOOD; Chlorpyrifos/*analogs & derivatives/*BLOOD; Phosphoric Acid Esters/*BLOOD; Metabolic Detoxication, Drug; Research Support, U.S. Gov't, P.H.S.; 311-45-5; 2921-88-2; 5598-15-2; NO CAS RN