Correlation between neurotoxicity and chlordecone (Kepone) levels in brain and plasma in the mouse

The brain and plasma levels of chlordecone were monitored after daily oral administration of chlordecone at 10 to 50 mg/kg/day. At a low dose, the plasma level of chlordecone increased steadily and the brain level showed a steady increase and then a plateau. However, at the higher dose the brain and plasma concentrations of chlordecone decayed biphasically. The data also revealed that chlordecone-induced neurotoxicity correlated closely with both brain and plasma concentration of chlordecone. Brain and plasma concentrations required for low and high dose for induction of the loss of motor coordination were estimated to be 10 to 65 ug/g and 10 to 25 microgram/ml, respectively. In addition, the chlordecone levels in the brain at time of death were 0.10 and 0.41 mg/g in groups receiving 10 and 50 mg/kg/day, respectively. However, the cumulative lethal dose of chlordecone in animals treated with different doses was about the same. This study established the threshold levels of chlordecone in plasma and brain for motor incoordination and mortality in the mouse.