Categorization of nitrobenzenes for repeated dose toxicity based on adverse outcome pathways

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.