Annual Meeting of the Japanese Society of Toxicology

Fipronil is a phenylpyrazole-class insecticide used for the protection of rice from Auchenorrhyncha and Oulema oryzae in Japan, and its pharmacological activity is from an interruption of GABA A receptor. Since Fipronil suppresses the action of GABAergic neurons, central nervous system (CNS) toxicity is well observed and characterized by toxicological studies. But Fipronil has no influences on pups during neurogenesis, interestingly. As well as neurons, thyroid gland and liver were identified as the target organ of Fipronil. Fipronil promoted hepatocyte vacuolization, and hypertrophy, hyperplasia, and oncogenesis in follicular cell of thyroid gland. However, Fipronil does not have any genotoxic activity and further studies revealed that thyroid gland-oncogenesis is caused by phenobarbital-like mechanism which is specific system for rodents. Therefore, the most important toxicity of Fipronil is CNS toxicity, and most of NOAEL was identified by CNS toxicity. Taken together, Fipronil has a great CNS toxicity which is directly linked to the pharmacological activity, but the safety and human risk assessment are well ensured by ADI.

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[Introduction] Polycyclic aromatic hydrocarbons (PAHs) distribute ubiquitously as complex mixtures in the environment. Pyrene is one of PAHs that is widely used as model of PAH contamination in environment. Pyrene is metabolized by cytochrome P450s in phase I reaction then conjugated in phase II metabolism, and excreted into urine and feces. Although their metabolites are available for use in human as indicator for PAH exposure, there are still less information in wildlife. In present study, we focus on the elucidation of pyrene metabolites in wild animals.
[Materials and Methods] Urine of 10 male sika deer (Cervus nippon), 1 to 5 year olds were collected from Hokkaido, Japan. All samples were extracted by Oasis WAX cartridge and they were analyzed by High performance liquid chromatography with fluorescence detector.
[Results and Discussions] We could detect pyrene-1-glucuronide largely in urine. Moreover, pyrene-1-sulfate, and 1-hydroxypyrene also detected. When we compared this results with other ruminant as cattle, pyrene-1-glucuronide was main metabolites same as sika deer. Pyrene conjugate compounds were easily detected in urine. Due to observe the amount of polluted chemical as PAHs in environment, we could suggest that not only elucidate PAH concentration, but also its metabolite as 1-hydroxypyrene, pyrene 1-glucuronide, and sulfate conjugates were important to establish the appropriate biomarker for the assessment for PAH exposures in various wildlife animal species in environment.

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