Associations between urinary phthalate metabolite concentrations and rheumatoid arthritis in the U.S. adult population

Phthalates are ubiquitous environmental contaminants. Nevertheless, limited data is available about the impacts of phthalates on rheumatoid arthritis (RA). The purpose of this study was to use National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2018 to assess the individual and combined effects of exposure to phthalate mixtures on RA in adults. A total of 8240 participants with complete data participated in the study, of whom 645 had RA. The levels of ten phthalate metabolites were detected in urine samples. In the single-pollutant models, independent associations were identified between urinary mono-(carboxyoctyl) phthalate (MCOP), mono-(3-carboxylpropyl) phthalate (MCPP), mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP) with the incidence of RA. The results of multi-pollutant models, including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) approaches consistently revealed that co-exposure to phthalates was positively associated with RA incidence. Such association was more pronounced in adults over 60 years of age, where MCOP was identified as the dominant positive driver. Overall, our findings add novel evidence that co-exposures to phthalates might be positively associated with RA incidence. Given the limitations of the NHANES study, well-designed longitudinal studies are required to verify or disprove these results.