Identification and Environmental Implications of Photo-Transformation Products of Trenbolone Acetate Metabolites

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• 作者：Edward P. Kolodziej ; Shen Qu ; Kristy L. Forsgren ; Sarah A. Long ; James B. Gloer ; Gerrad D. Jones ; Daniel Schlenk ; Jonas Baltrusaitis ; David M. Cwiertny
• 刊名：Environmental Science & Technology (ES&T)
• 出版年：2013
• 出版时间：May 21, 2013
• 年：2013
• 卷：47
• 期：10
• 页码：5031-5041
• 全文大小：527K
• 年卷期：v.47,no.10(May 21, 2013)
• ISSN：1520-5851

文摘

Despite the widespread use of the anabolic androgen trenbolone acetate (TBA) in animal agriculture, evidence demonstrating the occurrence of TBA metabolites such as 17尾-trenbolone (17尾-TBOH), 17伪-trenbolone (17伪-TBOH), and trendione (TBO) is relatively scarce, potentially due to rapid transformation processes such as direct photolysis. Therefore, we investigated the phototransformation of TBA metabolites and associated ecological implications by characterizing the photoproducts arising from the direct photolysis of 17尾-TBOH, 17伪-TBOH, and TBO and their associated ecotoxicity. LC-HRMS/MS analysis identified a range of hydroxylated products that were no longer photoactive, with primary photoproducts consisting of monohydroxy species and presumptive diastereomers. Also observed were higher-order hydroxylated products probably formed via subsequent reaction of primary photoproducts. NMR analysis confirmed the formation of 12,17-dihydroxy-estra-5(10),9(11),dien-3-one (12-hydroxy-TBOH; 2.2 mg), 10,12,17-trihydroxy-estra-4,9(11),dien-3-one (10,12-dihydroxy-TBOH; 0.7 mg), and a ring-opened 11,12-dialdehyde oxidation product (TBOH-11,12-dialdehyde; 1.0 mg) after irradiation of 14 mg of 17尾-trenbolone. Though unconfirmed by NMR, our data suggest that the formation of additional isomeric products may occur, likely due to the reactivity of the unique 4,9,11 conjugated triene structure of trenbolone. In vivo exposure studies employing Japanese medaka (Oryzias latipes) indicate that low concentrations of 17伪-TBOH photoproduct mixtures can alter ovarian follicular development, and photoproducts alter whole-body 17尾-estradiol levels. Therefore, direct photolysis yields photoproducts with strong structural similarity to parent steroids, and these photoproducts still retain enough biological activity to elicit observable changes to endocrine function at trace concentrations. These data indicate that environmental transformation processes do not necessarily reduce steroid hormone ecotoxicity.