Something from "nothing" - Eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects
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.
Full-textDOI: · Available from: Elisabete Silva, May 15, 2015
SourceAvailable from: Stephen Lofts[Show abstract] [Hide abstract]
ABSTRACT: The overarching goal of the STAR Work Package 4 "Radiation Protection in a Mixed Contaminant Context" is to determine if radiation protection criteria for wildlife are robust, even within a mixed contaminant context. Within this framework, we have critically reviewed existing approaches, methods and tools developed in ecotoxicology for assessing exposures, effects and risks in a mixed contaminant context and evaluated their applicability for radioecological research and radiecological risk assessments.. The scope of the review is limited to multiple contaminant conditions (e.g. metals, organic contaminants as part of the mixture that includes radiation or radionuclides) and not to the wider context of multiple stressor conditions. A review of identified scenarios where such multiple contaminant conditions, may occur has been performed. We have reviewed approaches and tools for assessing the impact of cocontaminants on environmental availability and uptake of contaminants of interest and theoretically evaluated their usefulness for conditions that include radionuclides. Speciation models are well established tools for predicting the chemical speciation of metals and radionuclides. The application of selected chemical speciation models to two test scenarios suggested that cocontaminants would not significantly affect the speciation (and hence environmental availability) of uranium or thorium. Models were also tested for radium and polonium, but the lack of available thermodynamic data excluded speciation prediction for these elements. The modelling of contaminant bioavailability is most advanced for metals, where the Biotic Ligand Model (BLM) provides an established framework for understanding and predicting how the medium chemistry affects bioavailability. Examples of BLM models are presented. The structure of the BLM lends itself well to evaluate the influence of cocontaminants on the uptake and toxicity of the metal of interest, including radionuclides. Currently it has only been applied in a few cases as a tool to understand (nonradionuclide) metal mixture effects. Nevertheless, extension of the approach to understanding the effects of mixtures of radionuclides and metals is considered feasible. Approaches and tools to assess or predict the effect of contaminant mixtures have also been reviewed. Their advantages and disadvantages and applicability in the context of assessing effects in relevant mixed contaminant scenarios that include radionuclides have been evaluated. In particular component-based approaches are described: principles of Concentration Addition (CA) and Independent Action (IA) are presented for their application to descriptive data (dose-response curves) and to dynamic and integrated DEBtox (Dynamic Energy Budget Model) approaches to assess effects of mixtures. Further, a number of whole mixture approaches is described. A comparative overview of the different methods, data requirements and applicability of these different approaches and their capacity to identify and predict mixture effects is provided. All the concepts considered have advantages and limitations for effects assessment of situations where radionuclides are present in the mixture. Finally, an overview of the state of the art on Ecological Risk Assessment (ERA) of mixtures, including radionuclides, has been provided. ERA principles for chemicals and radionuclides are summarized. A general overview of different ERA approaches to deal with mixtures is presented, with their application in ERA assessments illustrated by some examples of application to mixtures. No comprehensive guidelines for the ecotoxicological assessment of chemical mixtures have yet been developed. Currently, regulation for mixtures is poorly developed and mainly concerns humans. There seems to be consensus that ERA approaches based on component based approaches (CA and IA) assuming no interactions between substances are valuable as a first tier approach to mixtures risk assessment, and CA appears a pragmatic and defendable default conservative approach. There remains, however, a need to consider uncertainty and variability within this modelling framework. For the generalization of this framework, there is still a clear need for a comprehensive classification scheme for contaminants (including exposure to ionising radiation or radionuclides) to support application of CA/IA models. Both from the exposure/effect analysis and the risk assessment perspective, the challenge with mixtures remains to identify the cases where interactions, especially synergistic interactions, occur. To achieve this there is a need for a mechanistic framework that accounts for mixture interactions at different process levels, e.g. absorption, metabolism, target site, physiological process. For nuclides, mechanistic models are an option if some cocontaminants are proven to affect bioavailability, toxicokinetics or detoxification of radionuclides. As for other toxicants, toxicokinetic rather than toxicodynamic mechanisms would seem to be more likely sources of toxicologically significant interactions. This is also a domain where experimental research and modelling development would be needed to explore the possibilities for interactions with various relevant chemicals. As mixture science and risk assessment develops, the identification of assessment factors and uncertainty and validation exercises with real mixture scenarios are also major challenges.
[Show abstract] [Hide abstract]
ABSTRACT: Microalgae has recently attracted much attention as a feedstock for biogas. Using wastewater as microalgae nutrition is a way how to produce algal biomass with low cost and minimum impact on environment. However, wastewater often is polluted with chemicals like pharmaceuticals which are among the commonly used chemicals in everyday life. The present study was aimed at the toxicity evaluation of a commonly used synthetic hormone, 17α-ethinylestradiol, using freshwater green algae Desmodesmus communis as a biotest organism. Parameters like healthy cell number and photosynthetic activity were determined and used to assess the toxicity. Lowest Observed Effect Concentration (LOEC) and 50% Effective Concentration (EC50) values were calculated for the parameters at different incubation times. It was found out that 17α-ethinylestradiol affects algal cell ability to grow, inhibits cell division and reduce photosynthetic processes in algal cells. Our research shows that inhibitory effect on growth of green algae D. communis start on concentration below 10 µg L-1 (4–8 µg L-1). Concentrations in the range of concentration 80–100 reduce growth by 50%, but concentrations 100–500 µg L-1 induce 100% reduction of growth rate and even calls initial algal cell destruction. Presence of EE2 in wastewater used for algal growth can affect productivity of a microalgae aquaculture.Biosystems Engineering 2015, Tartu, Estonia; 05/2015
[Show abstract] [Hide abstract]
ABSTRACT: Surface water contamination by chemical pollutants increasingly threatens water quality around the world. Among the many contaminants found in surface water, there is growing concern regarding endocrine disrupting chemicals, based on their ability to interfere with some aspect of hormone action in exposed organisms, including humans. This study assessed water quality at several sites across Missouri (near wastewater treatment plants and airborne release sites of bisphenol A) based on hormone receptor activation potencies and chemical concentrations present in the surface water. We hypothesized that bisphenol A and ethinylestradiol would be greater in water near permitted airborne release sites and wastewater treatment plant inputs, respectively, and that these two compounds would be responsible for the majority of activities in receptor-based assays conducted with water collected near these sites. Concentrations of bisphenol A and ethinylestradiol were compared to observed receptor activities using authentic standards to assess contribution to total activities, and quantitation of a comprehensive set of wastewater compounds was performed to better characterize each site. Bisphenol A concentrations were found to be elevated in surface water near permitted airborne release sites, raising questions that airborne releases of BPA may influence nearby surface water contamination and may represent a previously underestimated source to the environment and potential for human exposure. Estrogen and androgen receptor activities of surface water samples were predictive of wastewater input, although the lower sensitivity of the ethinylestradiol ELISA relative to the very high sensitivity of the bioassay approaches did not allow a direct comparison. Wastewater-influenced sites also had elevated anti-estrogenic and anti-androgenic equivalence, while sites without wastewater discharges exhibited no antagonist activities. Published by Elsevier B.V.Science of The Total Environment 04/2015; 524-525C:384-393. DOI:10.1016/j.scitotenv.2015.04.013 · 3.16 Impact Factor