Associations of phenols, parabens, and phthalate compounds related to personal care products with osteoarthritis: evidence from population-based and network toxicology studies

Osteoarthritis (OA) is a prevalent chronic musculoskeletal disease leading to significant disability worldwide, exacerbated by environmental factors and exposure to personal care products (PCPs). This study investigated the associations between phenols, parabens, and phthalates related to PCPs and OA. The relationship between 14 PCPs-related chemicals in urine and the prevalence of OA in 6,972 participants from the National Health and Nutrition Examination Survey was assessed using generalized linear models. MCiOP, BP-3, BPA, MeP, and PrP were identified as having a significant positive correlation with OA. Furthermore, non-linear associations with OA for BP-3 and BPA was found by restricted cubic splines. Additionally, the mixed exposure models such as Weighted Quantile Sum, Quantile G-computation, and Bayesian Kernel Machine Regression indicated an overall positive association between PCPs-related chemicals and OA. Network toxicology analysis identified 37 potential target genes influenced by PCPs on OA. Among these, MFAP5, PRELP, and CLEC3B were selected as key targets by the optimal machine learning model (LASSO + GBM). Finally, molecular docking technology validated the interactions between MFAP5 and PRELP with PCPs-related chemicals. In summary, we herein reveal that phenols, parabens, and phthalates related to PCPs are significantly associated with the prevalence of OA, and MFAP5 and PRELP may be potential targets through which PCPs affect OA.