Halogenated 17ß-estradiol surrogates: synthesis, estrogenic activity, and initial investigations of fate in soil/water systems

Authors: CASEY, FRANCEIS - North Dakota State University; Shappell, Nancy; Hakk, Heldur

Submitted to: Journal of Environmental Quality
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/20/2017
Publication Date: 5/18/2017
Publication URL: https://handle.nal.usda.gov/10113/5801874
Citation: Casey, F.X., Shappell, N.W., Hakk, H. 2017. Halogenated 17ß-estradiol surrogates: synthesis, estrogenic activity, and initial investigations of fate in soil/water systems. Journal of Environmental Quality. 46(4):802-810. doi: 10.2134/jeq2017.02.0053.

Interpretive Summary: 17ß-Estradiol (E2) is a natural, endocrine-disrupting, steroid hormone eliminated by animals in urine and feces. Several field studies have measured significant background concentrations of E2 of unknown origin in water and soil. The background E2 could have originated from wildlife or even from historical sources. We hypothesized that synthesis of an E2 analog, placed in manure, and applied to soil would be easy to track in the environment since it would not be naturally found. If true, the analog would provide a powerful tool to distinguish between new and historical inputs of endocrine disrupting estrogens into the environment. In this study, three brominated E2 surrogates were synthesized and compared to native E2 in laboratory soil/water studies and in assays for biological activity. Consistent with our hypothesis the brominated analogs were easy to identify in soil/water systems, had generally lower biological activities. However, one analog had fate and transport properties that closely matched native E2. Our findings suggest that this synthetic brominated E2 analog could be useful in a field-scale tracer studies designed to distinguish between historical and recent E2 inputs.

Technical Abstract: 17ß-Estradiol (E2) is a natural, endocrine-disrupting, steroid hormone excreted by all vertebrates that can enter the environment from domestic animal and wildlife wastes. Multiple field studies using food animal manures as E2 sources suggest significant background concentrations of E2 (e.g., wildlife sources, hydrolysis of E2 conjugates, redistribution of previous inputs). To accurately understand field fate and transport processes of E2, it is necessary to address the issue of background detections. In this study, two fluorinated and three brominated surrogate compounds of E2 were synthesized and evaluated against native E2 using soil/water batch experiments, as well as for biological activity. Analytical difficulties presented by the two fluorinated congeners deemed these compounds to be unsuitable surrogates of E2, and further assessment was abandoned. However, the brominated congeners proved promising, with Log Koc values that fell within the range previously reported for E2. Equilibrium batch studies yielded similar relative aqueous concentrations and linear sorption isotherms across time for E2 and 2-bromo-17ß-estradiol; however, the relative aqueous concentrations and linear sorption isotherms of 4-bromo-17ß-estradiol and 2,4-dibromo-17ß-estradiol were different from E2, but similar to one another. All three brominated congeners possessed estrogenic activity by E-Screen assay, albeit three orders of magnitude less than native E2, putatively due to steric interference introduced by the large bromine atom on the phenolic ring, the group that mediates interaction with the estrogen receptor. The data suggests that 2-bromo-17ß-estradiol will serve as a suitable surrogate for E2 in planned field-scale tracer studies designed to distinguish between antecedent and de novo inputs.