Reversible photohydration in diene and triene steroids: A mechanism for unexpected persistence of unique, biologically active steroidal contaminants?

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CBET 1335711David CwiertnyUniversity of IowaTrenbolone acetate (TBA) is a high-value anabolic growth promoter used extensively in animal agriculture, yet its metabolites are potent endocrine disrupting compounds in aquatic organisms. Recently, the rapid phototransformation of TBA metabolites, long thought to mitigate their environmental risk, was found to be reversible in surface waters at ambient conditions. This unprecedented behavior results in unique diurnal cycling and substantial regeneration of TBA metabolites at rates that are temperature and pH dependent, implying unrecognized persistence for these emerging contaminants in surface waters. Notably, reversible photohydration also appears to occur for structurally analogous compounds, including some human pharmaceuticals, suggesting that dienone and trienone steroids may represent a new class of environmental contaminants whose behavior confounds nearly all current predictive fate models and regulatory ecosystem risk assessment paradigms. Motivated by these findings, this project represents a comprehensive mechanistic investigation of dienone and trienone steroid phototransformation. The PIs hypothesize that the occurrence, fate, transport and ecological risks of these steroids cannot be accurately assessed without evaluating photoproduct formation and long-term stability. Focusing efforts primarily on TBA metabolites due to their widespread use and capability for endocrine disruption, this study will (i) characterize TBA metabolite phototransformation products; (ii) determine environmental factors promoting the formation of metastable products capable of reversion to parent structures or related steroidal analogs; (iii) explore whether reversible photohydration is generalizable to other dienone and trienone steroids and pharmaceuticals; and (iv) assess quantitatively conservation of bioactivity for structurally similar steroidal transformation products. As a class, dienone and trienone steroids are among the most potent used therapeutically as pharmaceuticals or illicitly as performance enhancing agents. Included in this compound class are trenbolone acetate, an anabolic steroid used as a growth promoter for the overwhelming majority of beef cattle produced in the United States, and dienogest, a progestin used as an oral contraceptive that is 10 times as potent as levonorgestrel (i.e., Plan B). While these compounds readily degrade in sunlight, the products of this photoreaction are unstable and ultimately decompose or revert into the bioactive steroid from which they were generated. Thus, this project will establish dienone and trienone steroids as a new class of environmental contaminants whose transformations do not necessarily reduce threats to ecosystem health, thereby challenging fundamental paradigms by which we as a community assess and control the risk posed by contaminants. Collectively, outcomes of this project will facilitate the improved assessment of the occurrence, fate, transport, and modeling of dienone and trienone steroids in natural systems, and provide insights for optimization of engineered treatment systems designed to protect vulnerable aquatic ecosystems by sequestering or transforming this emerging contaminant class.