Exposure Assessment of Aryl-Organophosphate Flame Retardants Based on Specific Urinary Biomarkers and Their Associations with Reproductive Hormone Homeostasis Disruption in Women of Childbearing Age

Abstract

The effects of aryl organophosphate flame retardants (aryl-OPFRs) on female reproduction health are still unclear owing to the lack of specific exposure biomarkers. Here, we analyzed the hydroxylated metabolites of three aryl-OPFRs (phenyl diphenyl phosphate [TPhP], 2-ethylhexyl diphenyl phosphate [EHDPP], and tricresyl phosphate [TCrP]) in urine samples from 913 women of childbearing age, and explored the association between exposure to the aryl-OPFRs 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 (P) 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 (AMH) 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-OPFRs can disrupt reproductive hormone homeostasis using their specific biomarkers and may negatively affect female reproduction.

Keywords: aryl-OPFRs, progesterone, 17β-estradiol, female reproduction health