Special Report 19

Conclusions on Case Studies on Retinoic Acid

The above has shown that we now have extensive mechanistic knowledge on the central role of RA in vertebrate embryo development. Therefore, this theme provides a good starting point for deriving a DTO that will inform the construction of a developmental AOP network. KEs in the network can be defined which allow the collection of relevant assays in an IATA to detect a major part of developmental toxicants. Key ontological terms will have to be defined at the molecular, cellular, tissue, organ, and organism level in a hierarchical connectivity construct. Testing KE modulation in dedicated in vitro assays will allow the projection of compound effects upon the network, resulting in prediction of developmental toxicity hazard potential. The addition of kinetic models, especially those addressing the behaviour of KEs in a compound concentration-related way, should, in due course, allow quantitative inferences about potency and risk.

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