Chemical exposome and children health: Identification of dose-response relationships from meta-analyses and epidemiological studies.

ABSTRACT

BACKGROUND: Health impact assessment studies quantifying the impact of the chemical exposome on children's health generally consider a small fraction of the exposome. Synthetizing available dose-response relationships is an essential step to fill this gap. We reviewed the literature for dose-response relationships relating the chemical exposome with children health. METHOD: We focused on 78 substance-outcome pairs for which the level of evidence had previously been classified as 'likely' or 'very likely'. We searched for dose-response relationships for these pairs from meta-analyses and, if none was available, from single epidemiological studies, from which we conducted meta-analyses whenever possible. RESULTS: We identified dose-response relationships for 50 of the 78 prioritized substance-outcome pairs (64%). Dose-response relationships stemmed from meta-analyses for 21 pairs, from de novo meta-analyses for 1 pair and single studies for 28 pairs. Dose-response relationships were available for tobacco (fetal and infant death, congenital heart defects, birth outcomes, orofacial clefts, respiratory health), lead (asthma, cognition, delayed puberty onset and iron deficiency anaemia), polychlorobiphenyls (PCBs) (cognition, respiratory infections and birth outcomes), bisphenol A (cognition), hexachlorobenzene (HCB) (respiratory health), Polybrominated diphenyl ethers (neurodevelopment), DDT (hypospadias, cryptorchidism, miscarriage), pesticides (neurodevelopment), methylmercury (cognition), PFAS (immune system, birth weight, behavior, miscarriage), arsenic (cognition, birth weight, death, respiratory health), cadmium (cognition, birth weight), manganese (behavior), sodium (blood pressure) and thallium (birth weight). For 28 of the 78 substance-outcome pairs (36%), no dose-response relationship was available from epidemiological studies in children. CONCLUSIONS: We identified dose-response relationships for 50 substance-outcome pairs, corresponding to 20 chemicals and 17 health outcomes. These can be used to perform more comprehensive quantitative health impact assessment of the exposome on child health. We also identified 28 substance-outcome pairs corresponding to 'likely' or 'very likely' effects for which research generating dose-response functions in children would be relevant.