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Caporale, Nicolò; Leemans, Michelle; Birgersson, Lina; Germain, Pierre-Luc; Cheroni, Cristina; Borbély, Gábor; Engdahl, Elin; Lindh, Christian; Bressan, Raul Bardini; Cavallo, Francesca; Chorev, Nadav Even; D'Agostino, Giuseppe Alessandro; Pollard, Steven M; Rigoli, Marco Tullio; Tenderini, Erika; Tobon, Alejandro Lopez; Trattaro, Sebastiano; Troglio, Flavia; Zanella, Matteo; Bergman, Åke; Damdimopoulou, Pauliina; Jönsson, Maria; Kiess, Wieland; Kitraki, Efthymia; Kiviranta, Hannu; Nånberg, Eewa; Öberg, Mattias; Rantakokko, Panu; Rudén, Christina; Söder, Olle; Bornehag, Carl-Gustaf; Demeneix, Barbara; Fini, Jean-Baptiste; Gennings, Chris; Rüegg, Joëlle; Sturve, Joachim; Testa, Giuseppe
Science (American Association for the Advancement of Science), 2022, Volume: 375, Issue: 6582Journal Article
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 and , 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.
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