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European chemicals legislation (registration, evaluation, authorisation and restriction of chemical substances (REACH)) requires a broad assessment of chemicals with respect to, inter alia, their health-relevant properties. Due to the extreme number of substances to be assessed and the limited current toxicological knowledge on their respective properties, REACH implicitly requires a paradigm change: away from knowledge generated mainly from costly animal experiments towards the use of mechanistic findings. Moreover, effect mechanisms at the biochemical or cellular level are essential when conclusions shall be drawn about "new" endpoints and mixtures of xenobiotics. This study (funded by the German Federal Environment Agency) describes examples of biochemical processes in the mammalian organism and how xenobiotics interfere with them. Interference with physiological processes expected to lead to adverse health effects is characterised as "toxicity pathway". The study describes toxicological endpoints not usually covered in routine animal testing and the respective toxicity pathways.

environmental sciences europe

Project summary: a critical synopsis of mechanisms of action of low-dose xenobiotics in mammalian organisms as a basis for assessing aggregated effects of chemical mixtures and identifying "new" toxicological end points