PNNL

Abstract

Age-dependent, enzymatic chlorpyrifos (CPF) metabolism was quantified by in vitro product formation in human hepatic microsomes (ages 13 d-75 y) and plasma (ages 3 d-43 y) with gas chromatography/mass spectrometry (GC/MS). Hepatic CPF desulfation (CPF to chlorpyrifos-oxon [CPF-oxon]) and dearylation (CPF to 3,5,6-trichloro-2-pyridinol [TCPy]) Vmax values were 0.35 ± 0.21 and 0.73 ± 0.38 nmol/min/mg microsomal protein (mean ± standard deviation[SD]), respectively. The mean (± SD) hepatic CPF-oxon hydrolysis Vmax was 78 ± 44 nmol/min/mg microsomal protein. None of these hepatic measures demonstrated age-dependent relationships on a per microsomal protein basis using linear regression models (p = 0.90, 0.60, and 0.17, respectively). Ratios of CPF bioactivation to detoxification (CPF desulfation to dearylation) Vmax values were consistent across ages (p = 0.87). CPF-oxon hydrolysis in plasma demonstrated age-dependent increases on a volume of plasma basis (p = 0.01), as did total plasma protein levels (p = 0.005). Mean (± SD) CPF-oxon hydrolysis Vmax values for children