Estrogen agonist/antagonist properties of dibenzyl phthalate (DBzP) based on in vitro and in vivo assays

The most commonly used phthalates have been banned or restricted for use as plasticizers in toys in some countries because of their endocrine-disrupting properties. Dibenzyl phthalate (DBzP) has been proposed as a possible alternative for the banned/restricted phthalates. In this study, the estrogen agonist/antagonist properties of DBzP were predicted by molecular docking and confirmed by yeast estrogen screen (YES) and immature mouse uterotrophic assays. The YES assay results showed a dose-dependent increase in DBzP estrogen agonist activity from 10−6 to 10−4 M, and at concentrations from 1.95 × 10−6 M to higher, DBzP significantly inhibited the agonist activity of 10−9 M 17β-estradiol (E2), inhibiting 10−9 M E2 by 74.5% at its maximum effectiveness. The in vivo estrogen agonist/antagonist activities of DBzP were demonstrated in immature mouse uterotrophic assays. The antagonist activity of DBzP inhibited E2-induced uterine growth promoted at 40 and 400 μg/kg bw (body weight) (P < 0.05). In addition, we also analyzed the estrogen agonist/antagonist potentials of benzyl butyl phthalate (BBP) by YES, and found both were weaker than those of DBzP, suggesting DBzP would be more toxic than BBP and should not be used as an alternative plasticizer.

► This study predicted estrogen agonist/antagonist properties of DBzP by in silico.
► In vitro and in vivo estrogen agonist property of DBzP was demonstrated.
► DBzP significantly inhibited the agonist activity of E2in vitro and in vivo.
► Estrogen agonist/antagonist potentials of DBzP were higher than those of BBP.
► DBzP should not be used as an alternative plasticizer for the banned phthalates.