Endocrine Disruption

Background

Endocrine disruptors are natural or synthetic chemicals that interfere with the body’s endocrine system, triggering a wide array of responses in biological pathways responsible for regulating fundamental biological functions, such as growth, development, reproduction, energy balance, metabolism, or body weight regulation. The most investigated endocrine pathways from a chemical safety perspective are the oestrogen, androgen, thyroid, and steroidogenesis (EATS) systems and, to a lesser degree, the retinoid pathway.

New Approach Methodologies

Much is understood about the mechanisms through which chemicals can interfere with endocrine pathways in humans and wildlife. Numerous adverse outcome pathways (AOPs) related to endocrine disruption are included in the AOP-Wiki, and the Organisation for Economic Co-operation and Development (OECD) has published several case studies on integrated approaches to testing and assessment.

Recent decades have seen advances in the implementation of in silico and in vitro approaches to assessing endocrine disruption, and additional approaches are under development.

Regulatory Landscape

The Environmental Protection Agency (EPA) is the US agency charged with screening chemicals for their ability to cause endocrine effects. The EPA Office of Research and Development (ORD) is developing in silico and in vitro assays as well as AOPs to support the robust assessment of chemicals for effects on the endocrine system.

In the European Union (EU), the European Chemicals Agency (ECHA) and the European Food Safety Authority (EFSA) are responsible for providing scientific opinions on the potential of chemicals to cause endocrine disruption (ECHA for industrial chemicals and biocides, and EFSA for active ingredients of plant protection products). Member states and the European Commission are responsible for regulating endocrine disruptors, taking the scientific opinions of ECHA and EFSA into account. ECHA hosts the Endocrine Disruptor Expert Group to support regulators by analysing scientific evidence on particular substances of concern.

Projects

Listed below are a selection of ongoing efforts to advance non-animal testing approaches for endocrine disruptors.

• EURION, the European Cluster to Improve Identification of Endocrine Disruptors, includes eight projects, funded by the European Commission’s Horizon 2020 research and innovation programme, which aim to reduce and replace animal tests for endocrine effects. The SCREENED project aims to develop three-dimensional in vitro methods to screen for the influence of endocrine disruptors on the male and female thyroid gland.
• The Science Consortium participates in the OECD Advisory Group on Endocrine Disrupters Testing and Assessment to advance in silico and in vitro testing approaches. This group helped coordinate updates to OECD Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption.
• The Science Consortium participates in the European Commission’s expert committee—the Competent Authorities for REACH and CLP (CARACAL) subgroup for endocrine disruptors (CASG-ED)—to discuss the identification and assessment of endocrine disruptors under the EU’s Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and Classification, Labelling and Packaging (CLP) regulations.

Select publications on endocrine disruption testing can be found here.