Prediction and Assessment of the Effects of Mixtures of Four Xenoestrogens

Payne, Joachim; Rajapakse, Nissanka; Wilkins, Megan L.; Kortenkamp, Andreas

doi:10.2307/3435059

Cited by 53 publications

(67 citation statements)

References 16 publications

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“…For the quantification of responses, however, one should be extra cautious for the presence of partial and/or superagonistic estrogens. This study confirms the suitability of CA to describe the effects of mixtures of similar acting xeno-estrogens in reporter gene assays as reported earlier (3,12,17,18).…”

Section: Resultssupporting

confidence: 90%

“…Partial agonists only partially fulfill this requirement and thus cause the mixture curves to deviate from that of E2 at higher concentrations. The difficulty of predicting maximum effect levels of mixtures containing partial agonists with the CA model is also discussed by others (3,11). In our experiments, MILs of mixtures containing partial agonists could, however, roughly be estimated by calculation of the average MIL of the mixture components, weighted by their relative contributions to the total estrogenic activity of the mixture (last column in Table 2).…”

Section: Resultsmentioning

confidence: 67%

“…The contribution of each component to the total effect of the mixture is considered to be proportional to its estrogenic potency and its concentration in the mixture. The CA concept has previously been shown to be valid for the prediction of mixture effects of estrogenic compounds in the yeast estrogen screen (YES assay) (3,11,12). Like the YES assay, the ER-CALUX assay is based on a receptor gene construct, with activation of the endogenous estrogen receptors as the sole molecular mechanism leading to response.…”

Section: Introductionmentioning

confidence: 99%

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Monofluorinated Analogues of Polybrominated Diphenyl Ethers as Analytical Standards: Synthesis, NMR, and GC-MS Characterization and Molecular Orbital Studies

Luthe

Leonards

Reijerink

et al. 2006

Environ. Sci. Technol.

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Polybrominated diphenyl ethers (PBDEs), a group of 209 individual congeners distinguishable by the number and position of bromines, are produced for use as flame retardants in consumer goods. PBDEs have become ubiquitous environmental contaminants, present in increasing levels in the environment and humans. In the present study, 10 individual monofluorinated analogues of PBDEs (F-PBDEs) and one difluorinated PBDE (FF-PBDE) were synthesized and characterized, and their gas chromatographic (GC) and mass spectrometric (MS) characteristics determined. The synthesis method utilized a nucleophilic reaction of bromophenols with diphenyliodonium salts and the perbromination of fluorosubstituted diphenyl ethers. Reaction yields were between 10% and 59% with ≥98% purity. Apart from the aromatic ring carrying the fluorine atom, only minor chemical nuclear magnetic resonance (NMR) shift changes were observed in comparison to the corresponding parent PBDEs, with the exception that the J F,H coupling was stronger. Our preliminary data show that F-PBDEs and PBDEs have comparable retention times in gas chromatography with F-PBDEs demonstrating in general shorter or identical retention times, depending on the pattern of fluorine substitution. We also calculated the torsion angles and the dipole moments for both and report that there is a good correlation between GC retention times and the torsion angles but not with dipole moments. In MS, the difference of the ion peaks of the F-PBDE/PBDE pairs is m/z 19 (F), which allows a simultaneous MS detection without separation. On the basis of GC separation, simultaneous MS detection, and the stability of fluorine due to its generally resistance to nucleophilic displacement, we propose that F-PBDEs may function as valuable potential standards, markers, and tracers in environmental analysis.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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Monofluorinated Analogues of Polybrominated Diphenyl Ethers as Analytical Standards: Synthesis, NMR, and GC-MS Characterization and Molecular Orbital Studies

Luthe

Leonards

Reijerink

et al. 2006

Environ. Sci. Technol.

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“…When dealing with agents that exhibit sigmoidal concentration-response curves, as is the case with estrogenic chemicals, it is not possible to calculate expected additive effects by forming the arithmetic sum of individual responses (effect summation; ES). Although the pitfalls of this approach have been discussed extensively (Berenbaum 1985;Kortenkamp and Altenburger 1998;Payne et al 2000), its shortcomings are not widely acknowledged. For this reason, we have included ES here for purposes of comparison.…”

mentioning

confidence: 99%

“…To meet these requirements, we used the yeast estrogen screen (YES) (Routledge and Sumpter 1996), which has proven to yield highly reproducible results (Payne et al 2000;Rajapakse et al 2001). …”

mentioning

confidence: 99%

Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.

Rajapakse

Silva

Kortenkamp

2002

Environ Health Perspect

Self Cite

435

230

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The low potency of many man-made estrogenic chemicals, so-called xenoestrogens, has been used to suggest that risks arising from exposure to individual chemicals are negligible. Another argument used to dismiss concerns of health effects is that endogenous steroidal estrogens are too potent for xenoestrogens to contribute significantly to estrogenic effects. Using a yeast reporter gene assay with the human estrogen receptoralpha, we tested these ideas experimentally by assessing the ability of a combination of 11 xenoestrogens to affect the actions of 17ss-estradiol. Significantly, each xenoestrogen was present at a level well below its no-observed-effect concentration (NOEC). To derive accurate descriptions of low effects, we recorded concentration-response relationships for each xenoestrogen and for 17ss-estradiol. We used these data to predict entire concentration-response curves of mixtures of xenoestrogens with 17ss-estradiol, assuming additive combination effects. Over a large range of concentrations, the experimentally observed responses decisively confirmed the model predictions. The combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of the hormone's action, even when each single agent was present below its NOEC. Our results show that not even sub-NOEC levels of xenoestrogens can be considered to be without effect on potent steroidal estrogens when they act in concert with a large number of similarly acting chemicals. It remains to be seen to what degree these effects can be neutralized by environmental chemicals with antiestrogenic activity. Nevertheless, potential human and wildlife responses induced by additive combination effects of xenoestrogens deserve serious consideration.

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Effects of EDC Mixtures

Khetan¹

2014

Endocrine Disruptors in the Environment

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Prediction and Assessment of the Effects of Mixtures of Four Xenoestrogens

Cited by 53 publications

References 16 publications

Monofluorinated Analogues of Polybrominated Diphenyl Ethers as Analytical Standards: Synthesis, NMR, and GC-MS Characterization and Molecular Orbital Studies

Monofluorinated Analogues of Polybrominated Diphenyl Ethers as Analytical Standards: Synthesis, NMR, and GC-MS Characterization and Molecular Orbital Studies

Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.

Effects of EDC Mixtures

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