From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures.
Nicolò CaporaleMichelle LeemansLina BirgerssonPierre-Luc GermainCristina CheroniGábor BorbélyElin EngdahlChristian H LindhRaul Bardini BressanFrancesca CavalloNadav Even ChorevGiuseppe Alessandro D'AgostinoSteven M PollardMarco Tullio RigoliErika TenderiniAlejandro Lopez TobonSebastiano TrattaroFlavia TroglioMatteo ZanellaÅke BergmanPauliina DamdimopoulouMaria JönssonWieland KiessEfthymia KitrakiHannu KivirantaEewa NånbergMattias ÖbergPanu RantakokkoChristina RudénOlle SöderCarl-Gustaf BornehagBarbara A DemeneixJean-Baptiste FiniChris GenningsJoëlle RüeggJoachim SturveGiuseppe TestaPublished in: Science (New York, N.Y.) (2022)
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.