Exposure to phthalate and phenol mixtures and obesity in children and adolescents: the dominant role of bisphenol A

Little research has explored the association of exposure to phthalates and phenols with obesity in Chinese children and adolescents, especially with regard to co-exposure. The mechanisms by which exposure to phthalates or phenols contributes to obesity in children and adolescents remain unclear. Therefore, this case-control study was aimed at examining the effects of multiple phthalate and phenol exposures on obesity and further exploring the potential key role of insulin. The cross-sectional study involved 293 pairs of children and teenagers with obesity and normal weight matched on age (± 1 year) and sex. In addition, 21 urinary endocrine-disrupting chemicals (EDCs), including 11 phthalate metabolites and 10 phenols, were measured. The associations of individual EDCs and EDC mixtures with obesity were investigated using conditional logistic regression models, weighted quantile sum (WQS) analyses, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to evaluate the mediated effects of insulin on the relationships between EDCs and obesity. In the single-EDC model, the highest quartiles of mono-iso-butyl phthalate (MiBP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-carboxymethylhexyl phthalate (MCMHP), and bisphenol A (BPA) were positively associated with obesity compared to their lowest quartiles. In mixed-exposure analyses, the WQS and BKMR model results consistently suggested that exposure to phthalate and phenol mixtures showed a positive association with obesity. BPA was identified as an essential exposure in the mixture with dominant effects on obesity in children and adolescents. Further mediation analysis revealed that insulin partly mediated the relationship between BPA and obesity, with the proportion of mediation at 50.13%. These findings suggested that exposure to phthalates and phenols, either alone or in mixtures, was significantly linked to childhood obesity. The obesogenic effect of exposure to BPA in children and adolescents deserves further attention, which may be mediated by insulin in part.