Chimeric mice with humanized liver as a model for testing organophosphate and carbamate pesticide exposure

BACKGROUND: Diagnosis of acute intoxication with organophosphate (OP) or carbamate (CM) pesticides in humans is achieved by measuring plasma butyrylcholinesterase (BuChE) activity. However, BuChE activity is not an ideal biomarker in experimental animal models. The aim of this study was to establish an experimental mouse model for evaluating exposure to OP and CM pesticides by monitoring BuChE activity using chimeric mice in which the liver was reconstituted with human hepatocytes. RESULTS: A single oral administration of acephate (300 mg/kg), chlorpyrifos (10 mg/kg), fenobucarb (300 mg/kg) or molinate (250 mg/kg) in chimeric mice led to inhibition of >95%, > 95%, 28% and 60% of plasma BuChE activity after 7, 0.5, 0.5 and 7 h, respectively. Dose-dependent decreases in plasma BuChE activity were also observed for acephate and chlorpyrifos. A 5-day repeated-dose study with 10 or 30 mg/kg acephate found a constitutive reduction in plasma BuChE activity to 80% and 70% of pre-dose levels, respectively. CONCLUSION: Changes in plasma BuChE activity in chimeric mice with humanized liver clearly reflected the exposure levels of OP and CM pesticides. These results suggest that the humanized-liver mouse model may be suitable for estimating levels of exposure to these pesticides in humans. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.