Special Report 19

The need for a developmental toxicity ontology

Developmental biology is characterised by a complex interplay between a multitude of processes at the molecular, cellular, tissue and organism level, which change continuously with time in development and location in the conceptus. These processes need to be mapped, at least to the extent that is necessary for understanding developmental toxicity. In the OECD AOP terminology, this implies that a network of mutually interacting AOPs needs to be defined that would lead to the identification of a limited number of KEs in the network. These KEs, in turn, can be used as biomarkers of developmental toxicity and can be represented in a limited number of test systems in an integrated testing strategy, which aims to cover developmental toxicity in its entirety. The genesis of this approach begins with, and is critically dependent on, an integral description of the developmental toxicity ontology. The ontology will provide an overview of the essential physiological/toxicological routes (and their interrelationships) leading to developmental toxicity, providing a blueprint for a comprehensive integrated approach for testing and assessment (IATA) for developmental toxicity. A successful IATA of the complete ontology would, by definition, detect all developmental toxicants, providing confidence for scientists and regulators that application of the IATA will be sufficient for hazard and risk assessment. The ontology will also be useful as an organising principle for expanding understanding in the field, such as defining novel KEs for in vitro testing and a refinement/reduction or replacement for in vivo testing. The ontology should be formatted such that it is available for computational approaches for risk assessment. Whereas the integral approach provided by the developmental toxicity ontology would provide significant merit over individual IATA and AOP approaches, it will be, by definition, limited by the state of knowledge of the mechanisms of embryofoetal development, and will require continuous update as scientific knowledge progresses.

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