Fipronil is a phenylpyrazole-class insecticide used for rice protection, and its pharmacological activity is an interruption of the GABA A receptor. Since fipronil suppresses GABAergic neurons, central nervous system (CNS) toxicity is well observed. However, fipronil has no influence on neurogenesis. Fipronil promoted hepatocyte vacuolization and thyroid oncogenesis only in rats. It had no genotoxic activity, and thyroid oncogenesis was promoted by accelerated thyroxin clearance under the genetic lack of thyroxine-binding globulin (TBG), suggesting an apparent rat-specific mechanism. Therefore, in relation to human health concerns, the most important toxicity of fipronil would be CNS toxicity, which was commonly observed in most of the toxicological studies with various species. Most of the NOAELs were established by CNS toxicity, and a minimum value was contributed for the ADI setting. Thus, the safety and human risk assessments are well ensured by the ADI.
