| Mixtures of Estrogenic Chemicals Enhance Vitellogenic Response in Sea Bass Ana D. Correia,1,2 Sandro
Freitas,1 Martin Scholze,3 José F.Gonçalves,1,4 Petra
Booij,5 Marja H. Lamoree,5 Evaristo Mañanós,6 and
Maria A. Reis-Henriques1,4 1CIIMAR-Centre
of Marine and Environmental Research, Environmental Toxicology
Laboratory, Porto, Portugal; 2Instituto de Bioquímica,
Facuidade de Medicina de Lisboa, Unidade de Biopatologia Vascular,
Institute
de Medicina Molecular, Lisboa, Portugal; 3Centre for
Toxicology, The School of Pharmacy, University of London,
London, United Kingdom; 4ICBAS-Instituto de Ciências
Biomédicas de Abel Salazar, Porto, Portugal; 5Institute
for Environmental Studies, Vrije Universiteit, Faculty of Earth
and Life Sciences, Amsterdam, the Netherlands; 6Instituto
de Acuicultura de Torre la Sal (CSIC), Torre la Sal,
España Abstract
Background: The potential impact of natural and synthetic estrogens on aquatic ecosystems has attracted considerable attention because it is currently accepted that their joint effects are more severe when they are present in mixtures. Although it is well-known that they occur as mixtures in the marine environment, there is little information about the combined effects of estrogenic chemicals on marine biota. Objective: In 14-day tests with juvenile sea bass, we analyzed singly and in combination the estrogenic activity of estradiol (E2) , ethynylestradiol (EE2) , and bisphenol A (BPA) using vitellogenin induction as an end point. Methods: Fish were exposed to each compound, and on the basis of these concentration–response data, we predicted mixture effects by applying the model of concentration addition. The mixtures were tested using a fixed-ratio design, and the resulting mixture effects were compared to the predictions. Results: EE2 was the most potent steroid, with an EC50 (median effective concentration) of 0.029 µg/L, 3.6 times more potent than E2 (EC50 = 0.104 µg/L) ; BPA was the least potent chemical, with an EC50 of 77.94 µg/L. The comparative assessment yielded a good agreement between observed and predicted mixture effects. Conclusions: This study demonstrates the potential hazard of these compounds to seawater life by their ability to act together in an additive manner. It provides evidence that concentration addition can be used as a predictive tool for assessing the combined effects of estrogenic chemicals in marine ecosystems. Key words: bisphenol A, concentration addition, estradiol, ethynylestradiol, mixture effects, sea bass, vitellogenin. Environ Health Perspect 115(suppl 1) :115–121 (2007) . doi:10.1289/ehp.9359 available via http://dx.doi.org/ [Online 8 June 2007]
Address correspondence to A.D. Correia, CIIMAR- Centre of Marine and Environmental Research, Environmental Toxicology Laboratory, Rua dos Bragas, 289, 4050-123 Porto, Portugal. Telephone: (351) 223401833. Fax: (351) 223390608. E-mail: anacorreia@ciimar.up.pt This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects." We thank A. Kortenkamp (School of Pharmacy, London) for the English revision of the manuscript. This research was part of the ACE project, which was sponsored by the European Commission under the 5th Framework Programme (contract no. EVK1-2001-00091) . The author declares he has no competing financial interests. Received 22 May 2006 ; accepted 5 September 2006.
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