Prenatal exposure to tire-derived chemical mixtures and childhood neurodevelopment at 2 years: Integrating mixture and single-pollutant models

Tire-derived chemicals (TDCs) are emerging contaminants with potential neurotoxicity. Their detection in maternal biological matrices raises concerns about its effect on early neurodevelopment. In this prospective birth cohort of 226 mother-child pairs in Wuhan, China, we investigated associations between prenatal TDCs exposure and early neurodevelopment using an integrated framework combining mixture and single-chemical models. Repeated maternal urine samples across pregnancy enabled robust exposure assessment of TDCs, including substituted N, N′-p-phenylenediamines derived quinones (PPD-Qs), benzotriazoles and benzothiazoles. Prenatal TDCs mixture exposure was inversely associated with mental development index (MDI) scores in children, as estimated by both Bayesian kernel machine regression (−8.47, 95 % CI: −15.48 to −1.47 comparing the 90th to 50th percentile) and quantile g-computation (−7.98, 95 % CI: −15.24 to −0.71 per quartile increase in exposure). Single-chemical models suggested stronger associations with MDI during early to mid-pregnancy, indicating critical exposure windows. Tolyltriazole, 2-amino-benzothiazole, and 2-(isopropylamino)-5-(phenylamino)cyclohexa-2,5-diene1,4-dione were prioritized as key components for further investigation and regulation. Our study provides epidemiological evidence that prenatal TDCs exposure may adversely impact MDI. And the prioritized chemicals may inform future toxicologic and public health investigations focused on TDCs.