Thread by @gtesta72

#Mixtures matter! Check out our new study in @ScienceMagazine where we show the impact of real-life chemical exposure during pregnancy on language development, integrating epidemiology and experimental neurobiology (1/14) science.org/doi/10.1126/sc…

on the same issue, do not miss also the insightful perspective by @liew_zeyan and Pengfei Guo (2/10) science.org/doi/10.1126/sc… (2/14)

and here an animated summary of the story () by @secret_molecule (3/14)

Endocrine disrupting chemicals (EDCs) are compounds that interfere with hormones. Humans are pervasively exposed to #EDCs, and early life exposure has been associated to #neurodevelopmental disorders (4/14)

Chemical regulation is, however, based on #risk #assessment of individual compounds, leaving the impact of chemical mixtures unregulated (5/14)

while previous studies focused on single compounds, we identified an #EDC mixture associated with #neurodevelopmental outcomes in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) #pregnancy cohort, using weighted quantile sum regression (6/14)

We then tested this mixture (MIX N) in the lab, finding that real life relevant exposure disrupted hormone-regulated autism and intellectual disability genes in human fetal neural progenitors and 3D cortical #brain #organoids (7/14)

In vivo models validated by the #OECD confirmed #thyroid function as one of the key and unifying points of vulnerability to MIX N and linked #thyroid disruption to #neurodevelopmental effects measured as alterations in locomotor activity (8/14)

This enabled us to apply a similar mixture approach (SMACH) to identify individuals in SELMA who were sufficiently similarly exposed to the experimental mixtures and found that up to 54% of pregnant women had been exposed to experimentally defined levels of concern (9/14)

These results warrant the feasibility and the importance of novel #risk #assessment strategies that more faithfully recapitulate the ubiquitous real-life exposure to #chemicals of concern that act in combination even when individually below the currently accepted limits (10/14)

Stellar kudos to @NicoloCaporale Cheroni Germain for their relentless dedication and to the other members testalab.eu and special thanks to the amazing @JoelleRuegg @CGBornehag @BDemeneix for the immense team work and to all coauthors who enabled this journey (11/14)

None of this would have been possible without the @EU_Commission funded #EDCMixRisk project edcmixrisk.ki.se and the stamina of the great Ake Bergman who brought us all together (12/14)

Thanks to the vibrant ecosystems of the institutions that supported us throughout, @IEOufficiale #EDCMixRisk partner where this work started and unfolded, @LaStatale and @humantechnopole where this research line will further expand (13/14)

Finally, we dedicated this work to Bo A. G. Jönsson "Bosse" who left us far too early and was instrumental for this work. Our thoughts go to his daughter Hanna who defended her master thesis on #pesticide #leakage, hoping for a greener horizon for all of us (14/14)