Exposure assessment of aryl-organophosphate esters based on specific urinary biomarkers and their associations with reproductive hormone homeostasis disruption in women of childbearing age

The effects of aryl-organophosphate esters (aryl-OPEs) on female reproduction health are still unclear owing to the lack of specific exposure biomarkers. Here, we analyzed the hydroxylated metabolites of three aryl-OPEs (phenyl diphenyl phosphate [TPhP], 2-ethylhexyl diphenyl phosphate [EHDPP], and tricresyl phosphate [TCrP]) and diphenyl phosphate (DPhP) in urine samples from 913 women of childbearing age, and explored the association between exposure to the aryl-OPEs and reproductive hormone levels. The detection frequencies of 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), phenyl di-p-tolyl phosphate (4-OH-MDTP), and 4-hydroxyphenyl diphenyl phosphate (4-OH-TPhP) were 94.6 %, 93.3 %, and 84.2 %, respectively. Multivariate linear regression analyses revealed that the quartiles of 4-OH-TPhP were positively associated with the progesterone (P4) level (p-trend = 0.008), and the P level in the highest quartile of 5-OH-EHDPP was 7.2 % (95 % CI, 5.7 % to 8.7 %) higher than that in the lowest quartile. The 17β-estradiol levels in the highest quartiles of 4-OH-TPhP and 5-OH-EHDPP were 15.0 % (95 % CI, 13.7 % to16.1 %) and 5.9 % (95 % CI, 15.7 % to 16.1 %) lower than those in the lowest quartiles, respectively. The anti-Müllerian hormone level linearly increased across the quartiles of 4-OH-MDTP (p-trend = 0.036), and the follicle-stimulating hormone exhibited the opposite trend (p-trend = 0.0047). These results indicate that aryl-OPEs may disrupt hormone homeostasis using their specific biomarkers and may negatively affect female reproduction.