Comparison of in vitro hormone activities of selected phthalates using reporter gene assays

Phthalates are widely used in the plastic industry and food packaging, imparting softness and flexibility to normally rigid plastic medical devices and children's toys. Even though phthalates display low general toxicity, there is increasing concern on the effects of endocrine system induced by some of phthalate compounds. The hormone activity of dibutyl phthalate (DBP), mono-n-butyl phthalate (MBP) and di-2-ethylhexyl phthalate (DEHP) were assessed using the luciferase reporter gene assays. The results showed that DBP, MBP and DEHP, not only exhibited potent antiandrogenic activity, with IC50 value of 1.05 × 10−6, 1.22 × 10−7 M and exceeding 1 × 10−4 M respectively, but also showed the androgenic activity with EC50 value of 6.17 × 10−6, 1.13 × 10−5 M and exceeding 1 × 10−4 M. We also found that all the three related chemicals possessed thyroid receptor (TR) antagonist activity with IC50 of 1.31 × 10−5, 2.77 × 10−6 M and exceeding 1 × 10−4 M respectively, and none showed TR agonist activity. These results indicate that TR might be the targets of industrial chemicals. In the ER mediate reporter gene assay, three chemicals showed no agonistic activity except for DBP, which appeared weakly estrogenic at the concentration of 1.0 × 10−4 M. Together, the findings demonstrate that the three phthalates could simultaneously disrupt the function of two or more hormonal receptors. Therefore, these phthalates should be considered in risk assessments for human health.