ABSTRACT
OBJECTIVE To develop and validate a physiologically based toxicokinetics and toxico?dynamics(PBTK/TD)model for chlorpyrifos(CPF)in rats following both oral and subcutaneous expo?sures to CPF. METHODS ①A PBTK/TD model was established with toxicokinetics and toxicodynam?ics data in literature,which was used for predicting contents of CPF and 3,5,6-trichloro-2-pyridinol (TCP)in blood and activities of acetylcholine esterase(AChE)in the plasma and brain of rats exposed to CPF.②Rats were given 50 mg · kg-1 CPF oral and 50 mg · kg-1 CPF sc simultaneously. Blood and brain samples were collected at 0,1,2,4,6,8,12,24 and 48 h,respectively,after CPF administration (n=5). CPF And TCP contents in plasma,activities of AChE in the plasma and brain were deter?mined,and compared with the simulation values by PBTK/TD model in order to validate the accuracy of the model. RESULTS It was predicted by the PBTK/TD model that after the administration (oral+sc) of CPF 20+20,10+30 and (30+10)mg · kg-1,the concentrations of CPF and TCP in plasma increased and then decreased with time in each group. The inhibitory level of AChE activity in the plasma was orally dose-dependent,while AChE activity of the brain was more sensitive to CPF subcutaneous exposure. The simulation values obtained by the PBTK/TD model were not significantly different from the experimental values obtained by co-administered CPF at(50+50)mg · kg-1. CONCLUSION This CPF PBTK/TD model can quantitatively estimate target tissue dosimetry and AChE inhibition.
ABSTRACT
OBJECTIVE Calculate the dietary exposure and exposure risk of Chinese consumers to acephate,using the margin of exposure method.METHODS Determine the bench mark dose of acephate by 21 -day gavage experiment of rats.According to the data from the 2002 National Diet and Nutrition Survey,the 2000 -2006 national food conta mination monitoring program,the 2005 -2006 export monitoring data of customs,calculate the dietary exposure of Chinese consumers to acephate by probabilistic assessment.Estimate the exposure risk by co mparing the margin of exposure with 100. RESULTS The bench mark dose of acephate was 0.75 mg·kg -1 ,the BMDL was 0.51 mg·kg -1 .The exposure of children was higher than that of adults.The proportion at risk of group 1 -6 y,7 -17 y and 18 y or higher was 5%,1 % and 0.1 %,respectively.CONCLUSION So me consumers was of dietary exposure risk to acephate.The high exposure of children should be of great concern.