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From cohorts to molecules : Adverse impacts of endocrine disrupting mixtures

Caporale, Nicolò ; Leemans, Michelle ; Birgersson, Lina ; Germain, Pierre Luc ; Cheroni, Cristina ; Borbély, Gábor ; Engdahl, Elin ; Lindh, Christian LU orcid ; Bressan, Raul Bardini and Cavallo, Francesca , et al. (2022) In Science 375(6582).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science
volume
375
issue
6582
article number
eabe8244
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85124775819
  • pmid:35175820
ISSN
0036-8075
DOI
10.1126/science.abe8244
language
English
LU publication?
yes
id
4a613e1d-8624-4ad5-b071-23d14fb5c7da
date added to LUP
2022-04-12 15:12:02
date last changed
2024-06-18 02:41:50
@article{4a613e1d-8624-4ad5-b071-23d14fb5c7da,
  abstract     = {{<p>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.</p>}},
  author       = {{Caporale, Nicolò and Leemans, Michelle and Birgersson, Lina and Germain, Pierre Luc and Cheroni, Cristina and Borbély, Gábor and Engdahl, Elin and Lindh, Christian and Bressan, Raul Bardini and Cavallo, Francesca and Chorev, Nadav Even and D’Agostino, Giuseppe Alessandro and Pollard, Steven M. and Rigoli, Marco Tullio and Tenderini, Erika and Tobon, Alejandro Lopeg and Trattaro, Sebastiano and Troglio, Flavia and Zanella, Matteo and Bergman, Åke and Damdimopoulou, Pauliina and Jönsson, Maria and Kiess, Wieland and Kitraki, Efthymia and Kiviranta, Hannu and Nånberg, Eewa and Öberg, Mattias and Rantakokko, Panu and Rudén, Christina and Söder, Olle and Bornehag, Carl Gustaf and Demeneix, Barbara and Fini, Jean Baptiste and Gennings, Chris and Rüegg, Joëlle and Sturve, Joachim and Testa, Giuseppe}},
  issn         = {{0036-8075}},
  language     = {{eng}},
  number       = {{6582}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science}},
  title        = {{From cohorts to molecules : Adverse impacts of endocrine disrupting mixtures}},
  url          = {{http://dx.doi.org/10.1126/science.abe8244}},
  doi          = {{10.1126/science.abe8244}},
  volume       = {{375}},
  year         = {{2022}},
}