Towards EU regulatory hazard assessment of metabolic endocrine disrupters: Integrating new biomarkers into OECD test guidelines

Exposure to ‘metabolic disrupting chemicals’ (MDCs) are increasingly implicated in obesity, diabetes and/or fatty liver disease; indeed, these metabolic changes may play a role in the global metabolic disorders’ epidemic. To better assess and manage the health risks of MDCs, improved hazard identification is needed. This review describes how current in vivo OECD Test Guidelines (TGs) can better capture MDC effects. The biological and clinical evidence to support the inclusion of promising human relevant biomarkers, blood parameters, endpoints and relevant tissues for MDCs for potential inclusion in OECD TGs is documented. Current clinical chemistry routine requirements could be utilised further, and the additional assessment of relevant hormones such as a decrease in adiponectin, increase in resistin and leptin, which impact satiety, could be additionally included. Additionally, assessment of fatty tissue distribution in alert animals and insulin resistance, is recommended, and histological parameters in relation to the different types of adipose tissue. How specific biomarkers and endpoints could be incorporated into OECD mammalian in vivo assays, and how they can be included in the EU strategy for Endocrine Disrupting Chemicals identification and the forthcoming update to the OECD Guidance Document on the Testing and Assessment of Endocrine Disruption chemicals, are discussed. • Metabolic disrupting chemicals (MDCs) hazard assessment could be greatly improved with the evaluation of existing and additional metabolic disruption specific clinical chemistry and biomarkers • As a short-term implementable action to enrich TGs, adding the measurement of the three hormones insulin, adiponectin and leptin would be helpful for the identification of MDCs. • To better characterize MDC properties of chemicals, it is also proposed to weigh peri-gonadal adipose tissue • Fatty tissue distribution and metabolites and proteins measured in the serum, insulin, adiponectin and leptin should be measured in overnight fasted animals