Toxicological categories - A necessary extension of the chemical category approach

Category approaches are an important tool to reduce, refine and replace (3R principle) animal testing under REACH. Two strategies for developing categories may be distinguished: chemical categories are based on structural properties of the substances such as structural alerts, similarity and molecular properties. These are refined and evaluated by analysing toxicological properties. Numerous chemical categories have already been analysed by this strategy e.g. in the OECD HPV programme. They can be used to estimate endpoints like mutagenicity, irritation, sensitization, but may not suffice for complex endpoints such as repeated dose toxicity or reproductive toxicity. Toxicological categories may be useful for complex endpoints: they can be developed based on the toxicological fingerprint where critical target organs and effects observed in animal studies are taken into account. Another possibility is to derive toxicological categories for specific effects. An example is already established for urinary nephropathy which is associated with branched hydrocarbons. Finally rare target organs e.g. adrenals may be investigated. Common structural properties are then identified to characterize the category further. Repeated dose toxicity data for 587 chemicals and 1739 studies within the database RepDose© developed by Fraunhofer ITEM (http://www.fraunhofer-repdose.de) will be used to develop new categories. Both strategies are demonstrated using examples such as glycol ethers.