Rex FitzGerald obtained an MA in zoology at Trinity College Dublin, Ireland, and a D.Phil in biological sciences at the University of Sussex, UK (1981). After post-doctoral research in Groningen, Netherlands and ETH Zürich on mammalian neuropharmacology, he joined Ciba-Geigy, where he was head of reproduction toxicology and medical advisor for gynecological endocrinology. He founded FitzGerald Toxicology & Clinical Services in 1996, providing safety documentation and regulatory advice to the chemical-pharmaceutical industry. He is a Diplomate of the American Board of Toxicology (DABT) and a European Registered Toxicologist (ERT). He joined SCAHT in February 2010. His research and professional interests include developmental neurotoxicity and human risk assessment.

OpenTox Euro 2019 workshop: What use are AOPs to regulators?

The OECD-initiated adverse outcome pathway (AOP) framework reflects a paradigm shift, from empirical animal toxicity endpoints to evidence-based toxicity pathways. AOPs are posted in an open access knowledgebase (https://aopwiki.org).

AOPs have many potential uses; for example, they can facilitate design, validation and regulatory use of in vitro bioassays (key event readouts which are plausibly related to defined human health adverse outcomes), and of biomarkers of exposure and effect in human epidemiology studies (usually late key events, close to the AO).

These applications, and many others may be very useful for regulators. However, it all depends on the question the regulator needs to answer; there is no one-size-fits-all.

For example, AOPs describe toxicodynamics (hazard), not toxicokinetics (exposure), and therefore not risk. Depending on the regulatory question, this may be sufficient. 

A 2016 OECD guidance document (GD260) describes how AOPs can contribute to IATA-based regulatory decisions. This will be illustrated with examples.