From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures

Science. 2022 Feb 18;375(6582):eabe8244. doi: 10.1126/science.abe8244. Epub 2022 Feb 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / epidemiology
  • Autism Spectrum Disorder / genetics
  • Brain / drug effects
  • Brain / embryology
  • Child, Preschool
  • Endocrine Disruptors / toxicity*
  • Estrogens / metabolism
  • Female
  • Fluorocarbons / analysis
  • Fluorocarbons / toxicity
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Humans
  • Language Development Disorders / epidemiology*
  • Locomotion / drug effects
  • Neural Stem Cells / drug effects
  • Neurodevelopmental Disorders / epidemiology*
  • Neurodevelopmental Disorders / genetics
  • Organoids
  • Phenols / analysis
  • Phenols / toxicity
  • Phthalic Acids / analysis
  • Phthalic Acids / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Assessment
  • Thyroid Hormones / metabolism
  • Transcriptome / drug effects*
  • Xenopus laevis
  • Zebrafish


  • Endocrine Disruptors
  • Estrogens
  • Fluorocarbons
  • Phenols
  • Phthalic Acids
  • Thyroid Hormones