543 © 2008, Japanese Society for Alternatives to Animal Experiments Evaluation of health risk due to the exposure to endosulfan in the environment

Endosulfan, an organochlorine (OC) insecticide belonging to the cyclodiene group, is one of the most commonly used pesticides to control pests in vegetables, cotton and fruits. To evaluate the health risk due to the exposure to Endosulfan in the environment, a framework was developed by combining three sub – models: (1) the fugacity model which evaluates the dynamic performance of Endosulfan in the environment, (2) the dietary exposure evaluation model and (3) the physiologically based pharmacokinetic (PBPK) model which evaluates the Endosulfan performance in the human body. The developed framework was applied on the Japanese environment, to calibrate each sub – model with the observed data and to fix the default parameter values. The PBPK model was constructed based on the pharmacokinetic data of our experiment following single oral administration of 14C-Endosulfan to male Sprague – Dawley rats and extrapolated to humans. The model was verified by simulating the disposition of 14C-Endosulfan in vivo after single and multiple oral dosages and comparing simulated results with experimental results. Cytotoxic experiments on the glial and neuronal cell cultures from rat and human were used to estimate the neurotoxic risk. Based on these experiments, there was no specific scientific evident to prove/estimate the quantitative neurotoxic risks. However, we deduced that humans may likely develop some neurological diseases induced by endosulfan. It was known that nerve cells could not be regenerated when these cells were damaged. It is also hoped that the newly-developed framework could be applied in the human health risk assessment in the near future