Carcinogenesis, Teratogenesis & Mutagenesis ›› 2015, Vol. 27 ›› Issue (5): 386-393.doi: 10.3969/j.issn.1004-616x.2015.05.013

Previous Articles     Next Articles

Toxicokinetics and toxicodynamics in juvenile rats following repeated oral exposure to chlorpyifos by using PBTK/TD model

YAO Xinya, ZHAO Minxian, CAO Zhengying, WANG Cannan   

  1. The Key Laboratory of Medical Engineering Environment, Nutrition and Food Hygiene Department, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China
  • Received:2015-04-16 Revised:2015-06-26 Online:2015-09-30 Published:2015-09-30

Abstract:

OBJECTIVE: To describe the characteristics of toxicokinetics and toxicodynamics of chlorpyifos (CPF) in juvenile rats after repeated oral gavage of chlorpyrifos by using PBTK/TD model. METHODS:21 days-old female SD rats were given daily gavage doses of CPF at doses of 0, 1.0, 2.5, 5.0, 10.0 and 15.0 mg/kg/d for 10 days. Serum and cerebral cortex were collected on days 3, 6, 10 and 11, to determine the concentration of CPF and 3, 5, 6- trichloropyridinol (TCP) in serum and the activity of acetylcholinesterase (AChE) in cerebral cortex. Urine samples were collected on days 3, 6 and 11, to determine the cumulative amount of TCP in urine. PBTK/TD model was used to predict the time-concentration curve of the indexes. RESULTS:The concentrations of serum CPF and TCP first increased and then decreased with time every 24 h during the period of administration, significantly different with the control group (P<0.05). The activities of AChE in serum and cerebral cortex also showed cyclical changes over time. The activities of AChE in cortex and serum both decreased as the CPF dose increased (P<0.05). The first day after exposure stopped, the activity of AChE in serum had a remarkable recovery (P<0.05). CONCLUSION:In repeated exposure, toxicokinetic and toxicodynamic indexes showed periodic variation. Continuous exposure to chlorpyrifos resulted in AChE in cortex and serum to be maintained at a certain level of inhibition, which only recovered when until significantly exposure stopped.

Key words: chlorpyrifos, PBTK/TD model, repeated oral exposure, toxicokinetics, toxicodynamics

CLC Number: