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 IC(50) value of 1.05x10(-6), 1.22x10(-7)M and exceeding 1x10(-4)M respectively, but also showed the androgenic activity with EC(50) value of 6.17x10(-6), 1.13x10(-5)M and exceeding 1x10(-4)M. We also found that all the three related chemicals possessed thyroid receptor (TR) antagonist activity with IC(50) of 1.31x10(-5), 2.77x10(-6)M and exceeding 1x10(-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 1.0x10(-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.
Shen
Ouxi
O
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, China.
Du
Guizhen
G
Sun
Hong
H
Wu
Wei
W
Jiang
Yi
Y
Song
Ling
L
Wang
Xinru
X
D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004396:Coloring Agents; D003993:Dibutyl Phthalate / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D010795:Phthalic Acids / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors; D011988:Receptors, Thyroid Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014284:Triiodothyronine / Q000494:pharmacology
D059002:Androgen Receptor Antagonists; D000728:Androgens; D004396:Coloring Agents; D052244:Endocrine Disruptors; D006728:Hormones; D008024:Ligands; D010795:Phthalic Acids; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D013778:Tetrazolium Salts; D013844:Thiazoles; D014284:Triiodothyronine; D003993:Dibutyl Phthalate; D004958:Estradiol; D004051:Diethylhexyl Phthalate; C022616:thiazolyl blue