title: Simulation of acute reference dose (ARfD) settings for pesticides in Japan.
abstract: In order to develop guidelines for setting acute reference doses (ARfDs) for pesticides in Japan, we conducted simulations of ARfD settings based on evaluation reports for 201 pesticides assessed by the Food Safety Commission (FSC) in Japan over the last 8 years. Our conceptual principles were based on the concepts written by Solecki et al. (2005) and were adapted for toxicological data required in Japan. Through this process, we were able to set the ARfDs for over 90% of the 201 pesticides tested. The studies that provided the rationale for ARfD setting were primarily reproductive and developmental toxicity studies, acute neurotoxicity studies, and pharmacology studies. For approximately 30% of the pesticides simulated in the present study, it was not necessary to establish ARfDs. Some of the simulated ARfDs resulting from their endpoints may be conservative estimates, because the evaluation reports were written for acceptable daily intake settings. Thus, it was sometimes difficult to distinguish acute toxic alerts from repeated toxicities. We were unable to set an ARfD for 14 pesticides because of insufficient data on acute toxicities. This could be improved by more complete recordkeeping. Furthermore, we categorized the 201 pesticides by mechanism of action or chemical structure. Our simulation indicates that the conceptual framework presented here can be used as a basis for the development of guidelines on ARfD settings for pesticides in Japan.
authors.affiliation: Division of Pathology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan. midoriy@nihs.go.jp
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Daisetsu
authors.initials: D
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Mariko
authors.initials: M
authors.lastname: Shirota
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
mesh_terms: D000818:Animals; D005506:Food Contamination / Q000032:analysis*; D059022:Food Safety; D006077:Government Agencies; D017408:Guidelines as Topic / Q000592:standards*; D006801:Humans; D007564:Japan; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D012016:Reference Values
chemical_list: D010575:Pesticides