Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

Abstract

a b s t r a c tConsiderable progress has been made in assessing the combined effects of chemicals, but the effect of mixtures remains one of the most daunting challenges in environmental toxicology. In this study, the effects of binary mixtures of estrogenic chemicals were investigated using plasma vitellogenin (VTG) induction in male adult Japanese medaka (Oryzias latipes) as the endpoint. We focused on whether or not the factorial design using rigorous statistical methods was appropriate for the identification of possible interactions. The estrogenic activities of 17b-estradiol (E2), 4-tert-nonylphenol (NP) and bisphenol A (BPA) were investigated in medaka following 14 d of exposure. Although all chemicals induced concentration-dependent increases in plasma VTG, a complete concentration-response curve was obtained only for E2, while partial curves were obtained for NP and BPA. Therefore, a 3Â3 factorial design was employed to identify both the individual and interactive effects. A significant difference in mean plasma VTG induction was found when any chemical was considered alone. However, no significant interactions between E2 and NP, E2 and BPA, and NP and BPA were demonstrated. These results suggest that these three model estrogenic chemicals share a common mechanism for inducing VTG synthesis, and that no interactions occur when they act in combination. We also demonstrated the ability of this experimental design to detect interactions between binary mixtures, which will allow the assessment of biological effects of more complex mixtures in future research.

Combined effects of estrogenic chemicals with the same mode of action using an estrogen receptor binding bioassay

“…Although the paper was retracted the following year because the result was lack of reproducibility in other laboratories (McLachlan, 1997), it led to academic concern and intense follow-up research. There have been lots of researches to study the effects of estrogenic mixtures on organisms ranging from recombinant yeasts and estrogen-sensitive cells (Arnold et al, 1997;Payne et al, 2001;Rajapakse et al, 2004;Silva et al, 2011Silva et al, , 2002Suzuki et al, 2001) to vertebrates such as fish and mice (Brian et al, 2007;Ramamoorthy et al, 1997;Ribeiro et al, 2012;Sun et al, 2009;Thorpe et al, 2005;Tinwell and Ashby, 2004). Among these test organisms, the recombinant human ER gene yeast obtained wide application because it provided not only fast and sensitive detection but also single MoA and ToA.…”

Effects of estrone on the early life stages and expression of vitellogenin and estrogen receptor genes of Japanese medaka (Oryzias latipes)

“…Numerous studies have reported adverse effects when fish were exposed to low concentrations of steroidal estrogens. These effects include increased plasma vitellogenin concentrations in males, increased rates of intersex, altered behavioral responses and decreased reproductive success (Panter et al, 1998;Imai et al, 2007;Zha et al, 2008;Sun et al, 2009;Hyndman et al, 2010). In particular, feminization of male fish due to long term exposure to low concentrations of steroids in aquatic environments has caused great concern throughout the world (Vethaak et al, 2005;Randak et al, 2009;Lu et al, 2011).…”

Combined action of estrogen receptor agonists and antagonists in two-hybrid recombinant yeast in vitro

“…All of them are released to the environment via different sources and are presented simultaneously instead of separately. Thus, these chemicals not only have adverse effects on organisms at very low-level exposure (Myers et al, 2009), but also have the potential of additive or even synergistic effects when acting in combination (Kunz and Fent, 2006;Sun et al, 2009).…”