METABOLIC VARIABLES AFFECTING THE EFFICACY, SAFETY, AND FATE OF AGRICULTURAL CHEMICALS
Location: Animal Metabolism-Agricultural Chemicals Research
Title: Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows
Submitted to: Aquatic Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 3, 2010
Publication Date: October 1, 2010
Citation: Shappell, N.W., Hyndman, K., Bartell, S.E., Schoenfuss, H. 2010. Comparative biological effects and potency of 17a- and 17ß-estradiol in fathead minnows. Aquatic Toxicology. 100:1-8. DOI:10.1016/j.aquatox.2010.07.005.
Interpretive Summary: A natural female hormone can exist in two structural forms, 17 a-estradiol (a-E2) and 17ß-estradiol (ß-E2). The latter form has been found in environmental water samples, and its biological effects on fish have been studied. Recently a-E2 has been found in wastewater associated with dairy and swine concentrated animal operations. Because the biological effects on aquatic species have not been documented, it is impossible to assess the environmental risk associated with a-E2. This study compared the effect of a-E2 to ß-E2 on sexually mature male and female fathead minnows, an organism that has a long history of use in evaluation of endocrine disruptors. Three concentrations of each form were tested. Fish were exposed for 21 days to the compound, after which one half of the fish were killed and body, liver and sex organ weights were assessed and organs were preserved for microscopic examination. Secondary sex characteristics were also measured as well as blood concentrations of an egg protein (vitellogenin) not normally produced by male fish. The remaining fish were transferred to tanks, housing one male and female per tank in the absences of E2. Male fish were tested for their capacity to defend the nest against a male fish mimic 3 and 12 days after removal of E2. Fish were killed after 13 days, and the same measurements described above were taken. Aggressiveness in nest defending tended to decrease with increasing concentrations of both estradiols. While recommendations for the lowest concentration of ß-E2 causing effects in fish is 10 ng/L, for a-E2 the lowest concentration will likely be greater than 25, but less than 75ng/L. Based on vitellogenin concentrations, ß-E2 appears to be 8 to 9 time more potent than a-E2.
17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the literature even though it has been found in the aquatic environment, sometimes at higher concentrations than 17ß-estradiol. The central objective of this study was to determine how the anatomical, physiological, and behavioral effects of exposure to 17a-estradiol compare to the well-documented effects of 17ß-estradiol exposures in aquatic vertebrates. A 21-day flow-through exposure of mature male and female fathead minnows to three concentrations each of 17a and 17ß-estradiol (averaged measured concentrations 27, 72, and 150 ng/L for 17a-estradiol, and 9, 20, and 44 ng/L for ß-estradiol, respectively) yielded significant, concentration-dependent differences in plasma vitellogenin concentrations among estradiol-exposed males when compared to fish from an ethanol carrier control. Interstitional cell prominence in the testis of fish was elevated in all estradiol treatments. Aggressiveness of male fish to defend nest sites appeared depressed in many of the higher concentration estradiol treatments (albeit not significantly). No clear effects were observed in female fish. Based on plasma vitellogenin data, it appears that 17ß-estradiol is 8 to 9 times more potent than 17a-estradiol and that the lowest observable effect concentration (LOEC) for 17a-estradiol in fathead minnow is greater than 25 ng/L and may be less than 75 ng/L.