Urinary phthalate metabolites associate with blood levels of estrogen quinone-derived hemoglobin adducts in Taiwanese pregnant women

In this study, we aimed to analyze the background levels of estrogen quinone-derived adducts in hemoglobin (Hb) obtained from pregnant women in Taiwan (n = 394) and to investigate the associations of these adducts with levels of urine metabolites of phthalates. Both 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen that are thought to be responsible for the estrogen-induced genotoxicity and carcinogenicity. Results confirmed that levels of estrogen quinone-derived adducts in pregnant women, including E2-3,4-Q-2-S-Hb and E2-2,3-Q-4-S-Hb, were detected at concentrations comparable with those of non-pregnant women with mean levels at 165 (range 108–428) and 97.2 (range 34.9–251) pmol/g, respectively. Levels of E2-3,4-Q-2-S-Hb correlated significantly with those of E2-2,3-Q-4-S-Hb (correlation coefficient r = 0.543, p < 0.001). The ratios of primary (mono-2-ethylhexyl-phthalate) to secondary (mono (2-ethyl-5-hydroxyhexyl phthalate), mono (2-ethyl-5-oxohexy) phthalate) metabolites of di-2-ethylhexyl phthalate (DEHP), positively correlated with levels of E2-2,3-Q-4-S-Hb and/or E2-2,3-Q-4-S-Hb plus E2-3,4-Q-2-S-Hb (p < 0.05). One of the urinary metabolites of phthalates, mono-isobutyl phthalate, a metabolite of diisobutyl phthalate (DiBP), positively correlated with those of E2-3,4-Q-2-S-Hb (r = 0.110, p = 0.034) and E2-2,3-Q-4-S-Hb plus E2-3,4-Q-2-S-Hb (r = 0.123, p = 0.018). Overall, this evidence suggests that levels of these estrogen quinone-derived Hb adducts associate with environmental exposure to phthalates, in particular DEHP and DiBP. We hypothesized that environmental exposure to phthalates may enhance bioactivation of estrogen to quinones leading to accumulation of reactive quinonoid metabolites in pregnant.