Co-exposure of PFASs, PAHs and metals, immune inflammation and triglyceride-glucose index: Exploring associations and mediation effects in children

The associations of co-exposure to per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), and metals with children's glycometabolism and the underlying mechanism of immune inflammation are largely unclear. We conducted a longitudinal panel study to explore the effects of individual and mixture of 27 contaminants on an emerging surrogate indicator of insulin resistance, triglyceride-glucose index (TyG), and the mediation of immunoglobulins and cytokines in children aged 4–6 years and 11–13 years. The results showed robust associations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and arsenic (As) with elevated TyG. The interaction of PFNA with PFOA was significant, showing a synergistic effect on TyG. And combined association of each pair of PFOA, PFNA, and As with TyG were enhanced. Meanwhile, the effect of contaminants mixture on TyG was significant for polyfluoroalkyl substances (PFAS) mixture, of which 6:2 Chlorinated polyfluorinated ether sulfonates (Cl-PFESA), PFNA, and PFUnDA weighted more than others. Notably, contaminants were related to immune globulins and cytokines, of which chemokine ligand (CCL) 4, interleukin (IL)-1β, IL-9, and tumor necrosis factor (TNF)-α significantly mediated associations of PFOA, PFNA, and PFUnDA with TyG. Accordingly, PFAS and metals were individually and jointly associated with TyG elevation, with 6:2 Cl-PFESA, PFNA, and PFUnDA contributing the most, and CCL4, IL-1β, IL-9, and TNF-α might be the underlying mediators in children.