Is there any added value of the second generation in the Extended One-Generation Reproductive Toxicity Study (EOGRTS)? A retrospective analysis of 24 EOGRTS

Abstract

The Extended One-Generation Reproductive Toxicity Study (EOGRTS) is a standard information requirement under Registration, Evaluation, Authorization and restriction of Chemicals (REACH) in Europe. Inclusion of an F2 generation is considered useful if this impacts hazard identification or when it provides additional information altering the reproductive or developmental No Observed Adverse Effect Level (NOAEL) and subsequent risk assessment. In this retrospective analysis the added value of the F2 generation in 24 EOGRTS was evaluated. Our retrospective analysis showed a added value of the second generation in 1/24 EOGRTS only, where extending with the F2 generation lowered both the reproductive and developmental NOAEL. For this substance, extension with the F2 generation lead to classification for effects on fertility. Hazard identification for developmental effects was not impacted based on clear developmental toxic effects already observed in the F1 generation and in previous studies with this substance. Risk assessment may be impacted if the developmental toxic effects are the most critical effects observed for this substance. For 23/24 studies included in this retrospective analysis, hazard and risk assessment were unaffected by inclusion of the F2 generation. Moreover, for 13/13 studies with external triggers for inclusion of the F2 generation hazard and risk assessment were unaffected. By decreasing the number of EOGRTS that are extended with an F2 generation, the number of animals used in regulatory developmental and reproductive toxicity studies may be significantly reduced in the future without negatively affecting the ability to identify potentially harmful chemicals.

Keywords: 3R’s; Extended One-Generation Reproductive Toxicity Study; chemical safety assessment; classification and labelling; developmental and reproductive toxicity; second generation.