Non-Linear Model Analysis of the Relationship between Cholinesterase Activities in Rats Exposed to 2, 2-Dichlorovinyl Dimethylphosphate and its Metabolite Concentrations in Urine

摘要

Background and aim 2, 2-dichlorovinyl dimethylphosphate (DDVP) is an organophosphate (OP) widely used for the insect pest control operation and to maintain the household environment. However, there are few reports about the relationship between dimethylphosphate (DMP) excreted into urine as a metabolite and health effect. In the present study, the non-linear model analysis was performed to estimate the threshold of DMP corresponding to the cholinesterase inhibition. Methods A total of 40 male Wistar rats (11-week-old) was divided into four groups and orally administered DDVP (control, 0.2, 1.0 and 5.0 mg/kg/day) for two weeks (five-day treatment per week). The blood, brain and urine were collected after the final administration. The cholinesterase (ChE) activities of the brain, red blood cell (RBC) and plasma were analyzed by Ellman method (Voss G et al, 1970). DMP was examined by using gas chromatography-mass spectrometry. Statistical analyses and model estimation were conducted with drc package (version 3.0-1; Ritz C et al, 2015) for R (version 3.4.1). Results Each of the ChE activities in the 5.0 mg/kg/day group was significantly inhibited when compared with the control group (Steel-Dwass method, p<0.05). The relationships between ChE activity and total urinary DMP excretion were represented as dose-response curves by three non-linear models for brain and RBC ChE and one model for plasma ChE. The estimated DMP corresponding to 20% inhibition of ChE was 0.34 mg/24h for brain and 0.11 mg/24h for RBC, which were calculated by averaging the results of three models, and 0.23 mg/24h for plasma. Their lower limits of 95% confidence intervals were 0.04, 0.06 and 0.09 mg/24h, respectively. Discussion and conclusion In this study, the non-linear model analysis, i.e. Benchmark Dose (BMD) analysis (Crump et al, 1984), was used to estimate the reference value of DMP derived from DDVP. The estimated concentration could be used to assess the human health risk of DDVP exposure.