| An Assessment of the Model of Concentration Addition for Predicting the Estrogenic Activity of Chemical Mixtures in Wastewater Treatment Works Effluents Karen L. Thorpe,1 Melanie Gross-Sorokin,2 Ian Johnson,3 Geoff
Brighty,2 and Charles R. Tyler1 1School of BioSciences, The Hatherly Laboratory, Exeter University,
Exeter, Devon, United Kingdom; 2The Environment Agency, National
Center for Ecotoxicology and Hazardous Substances, Howbery Park, Wallingford,
Oxon, United Kingdom; 3WRc plc, Blagrove, Swindon, Wiltshire, United
Kingdom Abstract
The effects of simple mixtures of chemicals, with similar mechanisms of action, can be predicted using the concentration addition model (CA) . The ability of this model to predict the estrogenic effects of more complex mixtures such as effluent discharges, however, has yet to be established. Effluents from 43 U.K. wastewater treatment works were analyzed for the presence of the principal estrogenic chemical contaminants, estradiol, estrone, ethinylestradiol, and nonylphenol. The measured concentrations were used to predict the estrogenic activity of each effluent, employing the model of CA, based on the relative potencies of the individual chemicals in an in vitro recombinant yeast estrogen screen (rYES) and a short-term (14-day) in vivo rainbow trout vitellogenin induction assay. Based on the measured concentrations of the four chemicals in the effluents and their relative potencies in each assay, the calculated in vitro and in vivo responses compared well and ranged between 3.5 and 87 ng/L of estradiol equivalents (E2 EQ) for the different effluents. In the rYES, however, the measured E2 EQ concentrations in the effluents ranged between 0.65 and 43 ng E2 EQ/L, and they varied against those predicted by the CA model. Deviations in the estimation of the estrogenic potency of the effluents by the CA model, compared with the measured responses in the rYES, are likely to have resulted from inaccuracies associated with the measurement of the chemicals in the extracts derived from the complex effluents. Such deviations could also result as a consequence of interactions between chemicals present in the extracts that disrupted the activation of the estrogen response elements in the rYES. E2 EQ concentrations derived from the vitellogenic response in fathead minnows exposed to a series of effluent dilutions were highly comparable with the E2 EQ concentrations derived from assessments of the estrogenic potency of these dilutions in the rYES. Together these data support the use of bioassays for determining the estrogenic potency of WwTW effluents, and they highlight the associated problems for modeling approaches that are reliant on measured concentrations of estrogenic chemicals. Key words: concentration addition, effluents, estradiol, estrogen, estrone, ethinylestradiol, mixtures, nonylphenol. Environ Health Perspect 114(suppl 1) :90-97 (2006) . doi:10.1289/ehp.8059 available via http://dx.doi.org/ [Online 21 October 2005]
This article is part of the monograph “The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife.” Address correspondence to K.L. Thorpe, School of Biosciences, University of Exeter, Prince of Wales Rd., Exeter, EX4 4PS, UK. Telephone: 44 1392 263 752. Fax: 44 1392 263 700. E-mail: k.l.thorpe@exeter.ac.uk This work was sponsored by the U.K. Environment Agency and the University of Exeter. The work was also sponsored by AstraZeneca, a pharmaceutical company. I.J. and M.G-S. are employed by WRc plc, a research and consulting company. The remaining authors declare they have no competing financial interests. Received 31 January 2005 ; accepted 21 October 2005.
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