Abstract:

OBJECTIVE:In this study, the toxicokinetics and toxicodynamics of chlorpyifos were assessed in rats following one single subcutaneous exposure. METHODS:Adult female SD rats, randomly divided into three dose groups (69.75, 139.5, 279 mg/kg) and one control group (0 mg/kg), received one subcutaneous injection. Blood and cerebral cortex samples were collected on 3, 6, 12, 24, 48 and 72 hours in each group, and 0-24, 0-48, 0-72 h urine samples were collected continuously. The indicators included chlorpyrifos (CPF) in serum, 3, 5, 6-trichloro-2-pyridyol (TCP) in urine and serum, and acetylcholinesterase (AChE) in serum and cortex. RESULTS:With the increase in the exposure dose, the concentration of serum CPF, serum TCP, urine TCP and inhibition of serum and cortex AChE increased. The peak concentration of serum CPF and TCP were 6 and 12-24 h, respectively. Maximum inhibition of serum and cortex AChE occured at 24 and 24-48 h, respectively. Half-life(t_1/2) of serum CPF was 29-48 h, and 0-72 h area under the curve (AUC) was 31-110 h·μmol/L in each group. t_1/2 of serum TCP was 28-54 h, and 0-72 h AUC value was 897-3 450 h·μmol/L. Serum and cortex AChE activity demonstrated a positive correlation (P<0.01), and serum AChE activity had higher inhibition (P<0.01). There was a dose-response relationship between serum CPF and AChE, fitting by DoseResp curve. CONCLUSION:External exposure dose of CPF was correlated with CPF, TCP and AChE activity. There was a dose-effect relationship between CPF internal level and serum AChE activity. Excretion of TCP in urine can be used as a biomarker of exposure. Serum AChE activity was an effective biomarker of cortex AChE activity.

Key words: chlorpyrifos, 3,5,6-trichloro-2-pyridinal, acetylcholinesterase, toxicokinetics, toxicodynamics