title: Products of aqueous chlorination of 4-nonylphenol and their estrogenic activity.
abstract: Seven reaction products (2-chloro-4-nonylphenol [NP], 2,6-dichloro-4-NP, trichlorophenol, 4-propyl-2'-hydroxyphenol, 4-isobutyl-2'-hydroxyphenol, 4-isoamyl-2'-hydroxyphenol, and 4-isopentyl-2'-hydroxyphenol) were identified by gas chromatography/mass spectrometry (GC/MS) in order to assess the estrogenic activity originated from 4-nonylphenol (4-NP) in drinking water. The estrogenic activities of the aqueous chlorinated 4-NP solution at 10, 60, and 120 min chlorination time were assessed by a yeast two-hybrid system based on the ligand-dependent interaction of two proteins, a human estrogen receptor (ER), and a coactivator. It was found that all three solutions inhibited transcriptional activation induction by 4-NP. Further experiments showed that these solutions also inhibited beta-galactosidase induction by 17beta-estradiol. For the solution at 10 min, the inhibition was found to be due to its toxicity, with an inhibition concentration (IC50) of about 10-fold of concentration of chlorinated 4-NP solution, suggesting the existence of some products with higher yeast toxicity than that of the parent 4-NP. Similar inhibition trends were also found in the dose response of the two solutions at 60 and 120 min, with an IC50 of 10-fold concentration. In these cases, the effects were considered to result from their antagonist action because the two solutions show lower yeast toxicity of which IC50 is 45-fold concentration. This suggests that some products in the chlorinated 4-NP solution elicit the antiestrogenic activities.
authors.affiliation: Department of Urban and Environmental Science, Peking University, Beijing, China. hujy@urban.pku.edu.cn
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Hu
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Xie
authors.forename: Takako
authors.initials: T
authors.lastname: Aizawa
mesh_terms: D002733:Chlorophenols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D018508:Water Purification; D014881:Water Supply; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors
chemical_list: D002733:Chlorophenols; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011960:Receptors, Estrogen; D014874:Water Pollutants, Chemical; D001616:beta-Galactosidase; C041594:4-nonylphenol