From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

Automated summary

This study found that exposure to EDC mixtures during early pregnancy is associated with language delay in offspring. The experimental results showed that at human-relevant concentrations, this mixture disrupts hormone-regulated and disease-relevant regulatory networks in the brain, as well as behavioral responses. Reanalyzing epidemiological data, it was found that up to 54% of children had prenatal exposures above experimentally derived levels of concern, resulting in a 3.3 times higher risk of language delay compared to the lowest decile of exposure.