Novel Estrogenic Microsomal Metabolites from Phthalate Esters

抄録

Many researchers have found evidence of the estrogenic effects of phthalate esters (PEs), but the disruption mechanism is not fully elucidated. Once PEs are hydroxylated at the ring 4-position, the resulting compounds exhibit unequivocal binding affinity for human estrogen receptors. In this study, we first succeeded to demonstrate the generation of potent estrogenic metabolite from PEs. We used rat liver microsomes and dimethyl phthalate (DMP) as a representative for the metabolism of PEs. Among the metabolites detected by HPLC, one of them was consistent with an authentic compound, 4-hydroxylated DMP (DMP-4OH) on their HPLC profiles. Together with the UV (λmax = 257 nm) and MS (m/z 210) data, the metabolite was concluded to be DMP-4OH. We propose that this ring-hydroxylated metabolite could be a key active species in the endocrine disrupting processes of PEs.