title: Categorization of nitrobenzenes for repeated dose toxicity based on adverse outcome pathways.
abstract: Adoption of the data-gap filling method for complex endpoints such as repeated dose toxicity (RDT) and reproductive/developmental toxicity is one of the most important issues affecting international chemical management at present. A categorization method based on adverse outcome pathways (AOPs) has recently been investigated for such complex endpoints. In this paper, we report results of the categorization of nitrobenzenes for RDT based on the AOPs obtained by analysing the detailed RDT test reports for 24 different nitrobenzenes already evaluated. In most RDT testing of nitrobenzenes without hydroxyl groups or acid groups, findings related to haemolytic anaemia and liver effects were observed at low dosages. It was, therefore, possible to assume common AOPs for haemolytic anaemia and liver effects induced by these nitrobenzenes. As a result, a group of nitrobenzenes was defined as a single category for both haemolytic anaemia and liver effects, respectively, based on these AOPs.
authors.affiliation: Chemical Management Center, National Institute of Technology and Evaluation, Tokyo, Japan. sakuratani-yuki@nite.go.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuratani
authors.forename: H Q
authors.initials: HQ
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Nishikawa
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: J
authors.initials: J
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry* / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009578:Nitrobenzenes / Q000737:chemistry* / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment; D013737:Testis / Q000187:drug effects / Q000473:pathology
chemical_list: D004785:Environmental Pollutants; D009578:Nitrobenzenes