Urinary phthalates and phthalate alternatives, and their associations with oxidative stress biomarkers in Chinese...

As phthalates face increasing restrictions, the use of alternative plasticizers has grown substantially. However, the spatial patterns of exposure to these compounds and their associations with oxidative stress remain understudied, particularly in developing countries. We conducted a multi-city biomonitoring study to assess geographic and seasonal variations in exposure to phthalates and their alternatives among Chinese adults, and to evaluate their associations with oxidative stress biomarkers. A total of 850 paired urine samples were collected from 425 individuals across six geographically diverse Chinese cities (Shanghai, Dalian, Wuhan, Taiyuan, Chengdu, and Lanzhou) during warm (September-October 2018) and cold (December-January 2019) seasons. Spatial analysis revealed higher specific gravity-adjusted concentrations in urban than in rural areas (p < 0.05). Wuhan and Lanzhou showed relatively higher exposure levels for most analytes, except for phthalic acid and monobenzyl phthalate (MBzP), which were highest in Chengdu and Taiyuan. Seasonal comparisons indicated that only mono-butyl phthalate (MBP) and MBzP were higher in the warm season, whereas other analytes showed no seasonal differences. Both linear mixed models and mixture approaches (weighted quantile sum and quantile g-computation) revealed that individual metabolites and mixture were positively associated with higher oxidative stress biomarkers. In the mixture, monomethyl phthalate (MMP) and MBP were identified as primary contributors to lipid damage (4-hydroxy nonenal mercapturic acid, HNE-MA) and nucleic acid damage [8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG)], respectively. These findings demonstrate higher exposure levels to phthalates and their alternatives in urban than in rural areas, and suggest that these compounds may contribute to oxidative stress. Our results highlight the need to evaluate the cumulative health impacts of both traditional phthalates and their alternatives in risk management.