A regulatory approach to assess the potency of substances toxic to the reproduction

Abstract

In order to develop a method for setting specific concentration limits (SCLs) for substances toxic to the reproduction within the European classification and labelling system, this study investigated possible parameters for reproductive toxicity potency and the quantitative distribution of those parameters. For that purpose, two databases were created comprising substances classified in the European Union for developmental toxicity or for effects on sexual function and fertility. For these substances six parameters including NOAEL, LOAEL and ED(10) were determined for effects on reproduction based on existing data summaries. The potency was defined independent of the type of reproductive effect as generally severe effects on reproduction warranting classification were already observed at the lowest dose showing reproductive effects. The reproductive toxicity potency range of substances in the databases was a factor of approximately one million. This shows that SCL setting is needed to adjust the classification of mixtures. The average potency distribution of substances classified according to the hazard classification as required by the European CLP regulation in category 1 versus category 2 was similar. The ED₁₀ for effects warranting classification is proposed as the best parameter for the potency based on its independence of administered dose levels.