OECD approaches and considerations for regulatory evaluation of endocrine disruptors

Abstract

Identifying the potential endocrine disruptor hazard of environmental chemicals is a regulatory mandate for many countries. However, due to the adaptive nature of the endocrine system, absence of a single method capable of identifying endocrine disruption, and the latency between exposure to endocrine disrupting chemical during sensitive life stages and the manifestation of adverse responses, satisfying the regulatory requirement needed to identify a chemical as an endocrine disruptor is a challenge. There are now a variety of validated regulatory tests that can be used in combination to provide evidence that a chemical affects the oestrogen, androgen, thyroid, and steroidogenic pathways of vertebrates, but most rely (at least to some extent) on animal testing and require considerable cost and time to produce the necessary data. Emerging research methods are able to evaluate other endocrine pathways, incorporate more sensitive endpoints, and combine multiple alternative methods to predict in vivo outcomes. Some research approaches may also bridge gaps that have been identified in current endocrine regulatory testing. For the near term, considering new endpoints in a regulatory context may require adding them to existing test methods in order to establish relationships between the traditional and the innovative. From the outset, endocrine testing has always required integration of multiple methods that provide data on different levels of biological organisation, thus, the area of endocrine disruption is particularly adaptable to adverse outcome pathway (AOP) frameworks and integrated test methods built around AOPs. Herein, we provide a review of the status of endocrine disruptors in the OECD context, examples where innovation from research is needed to improve or bridge gaps in endocrine testing, and suggestions for regulators and researchers to facilitate uptake of innovate methods for endocrine disruptor regulatory testing. The increase in several human complex human disorders that include an endocrine component and the alarming decrease in wildlife biodiversity are commanding directives to include the best, most informative, innovative approaches to accelerate the rate and throughput of chemical evaluation for endocrine disruption.

Keywords: AOP; Alternative methods; Chemical hazard identification; Ecotoxicology; Human health; IATA; Test guidelines.