Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. Export

@article{citeulike:4890181, abstract = {We tested whether multicomponent mixtures of xenoestrogens would produce significant effects when each component was combined at concentrations below its individual NOEC or EC01 level. The estrogenic effects of eight chemicals of environmental relevance, including hydroxylated PCBs, benzophenones, parabenes, bisphenol A, and genistein, were recorded using a recombinant yeast estrogen screen (YES). To ensure that no chemical contributed disproportionately to the overall combination effect, a mixture was prepared at a mixture ratio proportional to the potency of each individual component. The performance of four approaches for the calculation of additive combination effects (concentration addition, toxicity equivalency factors, effect summation, and independent action) was compared. Experimental testing of the predictions revealed that concentration addition and its application, the toxicity equivalency factor approach, were valid methods for the calculation of additive mixture effects. There was excellent agreement between prediction and observation. In contrast, independent action and effect summation led to clear underestimations of the experimentally observed responses. Crucially, there were substantial mixture effects even though each chemical was present at levels well below its NOEC and EC01. We conclude that estrogenic agents are able to act together to produce significant effects when combined at concentrations below their NOECs. Our results highlight the limitations of the traditional focus on the effects of single agents. Hazard assessments that ignore the possibility of joint action of estrogenic chemicals will almost certainly lead to significant underestimations of risk.}, author = {Silva, E. and Rajapakse, N. and Kortenkamp, A.}, citeulike-article-id = {4890181}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11993873}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11993873}, day = {15}, issn = {0013-936X}, journal = {Environmental science \& technology}, keywords = {additivity, superlist, thelist, xenoestrogen}, month = {April}, number = {8}, pages = {1751--1756}, posted-at = {2009-06-18 10:21:53}, priority = {2}, title = {Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11993873}, volume = {36}, year = {2002} }

TY - JOUR ID - citeulike:4890181 L3 - citeulike-article-id:4890181 N2 - We tested whether multicomponent mixtures of xenoestrogens would produce significant effects when each component was combined at concentrations below its individual NOEC or EC01 level. The estrogenic effects of eight chemicals of environmental relevance, including hydroxylated PCBs, benzophenones, parabenes, bisphenol A, and genistein, were recorded using a recombinant yeast estrogen screen (YES). To ensure that no chemical contributed disproportionately to the overall combination effect, a mixture was prepared at a mixture ratio proportional to the potency of each individual component. The performance of four approaches for the calculation of additive combination effects (concentration addition, toxicity equivalency factors, effect summation, and independent action) was compared. Experimental testing of the predictions revealed that concentration addition and its application, the toxicity equivalency factor approach, were valid methods for the calculation of additive mixture effects. There was excellent agreement between prediction and observation. In contrast, independent action and effect summation led to clear underestimations of the experimentally observed responses. Crucially, there were substantial mixture effects even though each chemical was present at levels well below its NOEC and EC01. We conclude that estrogenic agents are able to act together to produce significant effects when combined at concentrations below their NOECs. Our results highlight the limitations of the traditional focus on the effects of single agents. Hazard assessments that ignore the possibility of joint action of estrogenic chemicals will almost certainly lead to significant underestimations of risk. IS - 8 JF - Environmental science & technology SN - 0013-936X EP - 1756 TI - Something from "nothing"--eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. VL - 36 SP - 1751 KW - additivity KW - superlist KW - thelist KW - xenoestrogen AU - Silva, E AU - Rajapakse, N AU - Kortenkamp, A PY - 2002/04/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/11993873 ER -