Alternative methods for mechanistic studies in toxicology. Screening of hepatotoxicity of pesticides using freshly isolated and primary cultured hepatocytes and non-liver-derived cells, SIRC cells.
We constructed a screening battery for the evaluation of hepatotoxicity using freshly isolated and primary cultured rat hepatocytes (abbreviated to FIH and PCH, respectively) and rabbit eye derived cell line, SIRC cells. Effects on cell viability and drug metabolizing enzyme activities were examined by several pesticides and compared to those of in vivo. Among the pesticides studied, prometryn and ametryn showed cytotoxicity on PCH at lower concentration than on SIRC cells. Cytotoxicities of these chemicals on FIH were inhibited by metyrapone. They also increased rat serum AST in vivo. On the other hand, cytotoxicities of IBP, erusan, alanicarb, benfuracarb, and swep in PCH were observed at similar concentration to those in SIRC cells. Linuron, nitrofen, and chlomethoxifen increased ethoxycoumarin O-deethylation activities by almost similar concentration to those of benzo[a]pyrene. Linuron also induced ethoxycoumarin O-deethylation activity in vivo. These findings indicated that a battery of in vitro tests consisting of FIH, PCH and SIRC cells was useful to screen the hepatotoxicity of pesticides.