*Free* A new framework to assess health outcomes from endocrine-disrupting chemical mixtures

Researchers have presented a framework by which to more rigorously associate impacts of exposure to mixtures of endocrine-disrupting chemicals to health outcomes. Using their approach to study a large cohort of human mother-child pairs, they found exposure in pregnant women to mixed endocrine-disrupting chemicals (EDCs) may be associated with language delay in their children. The findings – so far, only correlative evidence for an EDC mixture associated with language delay – emphasize the need to take mixtures into account during chemical testing and risk assessment and also provide an integrative framework to guide risk assessment strategies. EDCs encompass a large class of chemical compounds, including perfluoroalkyl substances (PFAS), phthalates and phenols like BPA. They are common throughout the environment and found in a wide range of consumer products. Individually, many EDCs are known to interfere with hormone activity and the endocrine system and are suspected to be associated with adverse health impacts and disease in humans. They can also transfer from mother to child through the placenta and through breastfeeding, potentially leading to neurodevelopmental disorders in newborns. However, humans are rarely exposed to just one of these chemicals at a time; because they are so prevalent in the environment – contaminating our air, water and food – daily life regularly exposes us to mixtures of EDCs. Since risk assessments for these chemicals are often based on exposure to individual compounds only, little is known about the adverse health impacts of EDC mixtures – particularly the long-term developmental consequences of prenatal exposure – even at modest concentrations. Nicolò Caporale and colleagues evaluated chemical mixture exposure data in 1,874 mother-child pairs. They found that exposure to an EDC mixture during early pregnancy was associated with language delay in offspring. Moving to experimental human brain organoid and animal models, Caporale et al. then investigated several EDC mixtures identified during the cohort study. They studied how EDC mixtures interfere with hormonal pathways and dysregulate expression of genes. Using reference data this generated on exposure ranges of concern, they identified children in the cohort study who were sufficiently similarly exposed. This allowed the authors to determine the proportion of these children with exposure ranges of concern. The findings suggest that 54% of the children in the cohort had prenatal exposures above experimentally derived levels of concern, which translated to a 3.3 times higher risk of language delay. “Caporale et al. showed that the existing human epidemiolocal cohort data can be used to guide and determine typical human-relevant mixtures and subsequently test their biological and molecular effects in relevant in vitro and in vivo models,” write Zeyan Liew and Pengfei Guo in a related Perspective.