| Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects Amy L. Filby,1 Teresa Neuparth,2 Karen L. Thorpe,1 Richard Owen,2,3 Tamara S. Galloway,1 and Charles R. Tyler1 1School of Biosciences, University of Exeter, Exeter, United Kingdom; 2Ecotoxicology and Stress Biology Research Centre, University of Plymouth, Plymouth, United Kingdom; 3Environment Agency, Westbury-on-Trym, Bristol, United Kingdom Abstract
Background: Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. Objectives: We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent) . Methods: Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17α-ethinylestradiol (EE2) ], and to EE2 alone. Results: In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism ; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent) , suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. Conclusion: These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures. Key words: 17α-ethinylestradiol, environmental estrogen, fish, genotoxicity, health, immunotoxicity, metabolism, mixture effect, wastewater treatment works effluent. Environ Health Perspect 115:1704–1710 (2007) . doi:10.1289/ehp.10443 available via http://dx.doi.org/ [Online 30 August 2007]
Address correspondence to A.L. Filby, Environmental and Molecular Fish Biology, School of Biosciences, Hatherly Laboratories, Prince of Wales Rd., Exeter, Devon, EX4 4PS UK. Telephone: 44 (0) 1392 263752. Fax: 44 (0) 1392 263700. E-mail: a.l.filby@exeter.ac.uk Supplemental Material is available online at http://www.ehponline.org/members/2007/10443/suppl.pdf We thank G. Maack (University of Exeter) and T. Worsey (University of Plymouth) for technical assistance ; and R. Benstead (Environment Agency) for her comments on this work. This work was funded by the Environment Agency to C.R.T. (project no. SC040078) . T.N. was supported by a Fundação para a Ciência ea Tecnologia (FCT) fellowship (BPD/18192/04) . The authors declare they have no competing financial interests. Received 8 May 2007 ; accepted 30 August 2007.
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