Associations of urinary organophosphate metabolites with oxidative stress levels in physical examination population in two hospitals of Nanjing

Background Organophosphate esters (OPEs) are widely used as flame retardants and additives, and have become a ubiquitous pollutant in various environmental media. Phosphodiesters in urine have been identified as a biomarker for assessing human OPEs exposure.

Objective This study is conducted to detect the levels of seven human urinary OPEs diester metabolites and oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and assess their relationships.

Methods The cross-sectional study included a total of 304 adults, 135 women and 169 men, aged 18-65 years, who participated in health checkups in two hospitals in Nanjing. The levels of urinary diethyl phosphate (DEP), di-n-butyl phosphate (DnBP), diphenyl phosphate (DPhP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(2-butoxyethyl) phosphate (BBEP), bis(1, 3-dichloro-2-propyl) phosphate (BDCPP), and 8-OHdG were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. Pearson correlation test and multiple linear regression analysis were used to test the correlation between urinary OPEs metabolites and 8-OHdG.

Results BCPP geometric mean (GM): 4.88 μg·g^-1 and DnBP (GM: 4.61 μg·g^-1) were the most abundant urinary OPEs metabolites. There were gender differences in urine DEP, DnBP, BCPP, BBEP, and BDCPP levels (P < 0.05): The DnBP, BCPP, and BDCPP levels in urine were higher in males (GM: 5.83, 6.44, 0.86 μg·g^-1 vs 5.47, 3.42, 0.69 μg·g^-1), while the DEP and BBEP levels in urine were higher in females (GM: 7.44, 5.25 μg·g^-1 vs 0.67, 0.80 μg·g^-1). The pearson correlation test results showed that urinary 8-OHdG was positively associated with DEP (r=0.4170.219), DnBP (r=0.4170.417), DPhP (r=0.4170.308), BCEP (r=0.4170.420), BDCPP (r=0.4170.287), and Σ7OPEMs (r=0.4170.276) (all P < 0.01). After gender stratification, male urinary 8-OHdG was positively correlated with DEP (r=0.4170.240), DnBP (r=0.4170.436), DPhP (r=0.4170.367), BCEP (r=0.4170.448), BDCPP (r=0.4170.348), and Σ7OPEMs (r=0.4170.327) (all P < 0.05), while female urinary 8-OHdG and BBEP were positively correlated (r=0.4170.233, P < 0.05). After further adjusting for gender and age, the results of multiple linear regression analysis showed that urinary 8-OHdG was positively correlated with DEP (b=0.182), DnBP (b=0.418), DPhP (b=0.303), BCEP (b=0.418), BDCPP (b=0.284), and Σ7OPEMs (b=0.281) (all P < 0.05).

Conclusion The study findings show that DEP, DnBP, DPhP, BCEP, and BDCPP are associated with increased levels of 8-OHdG, indicating that being exposed to OPEs may cause oxidative stress during their metabolism in adults.