Accurate Prediction of the Response of Freshwater Fish to a Mixture of Estrogenic Chemicals (original) (raw)
Related papers
Evidence of Estrogenic Mixture Effects on the Reproductive Performance of Fish
Environmental Science & Technology, 2007
Recent research into the effects of mixtures of estrogenic chemicals has revealed the capacity for similarly acting chemicals to act in combination, according to the principles of concentration addition. This means that, collectively, they may pose a significant environmental risk, even when each component is present at a low and individually ineffective concentration. The aim of this study was to investigate the ecological significance of mixture effects at low-effect concentrations by assessing the combined effect of estrogenic chemicals on the reproductive performance of fish. Pairs of fathead minnows were exposed to five estrogenic chemicals.
Water research, 2018
Decades of studies on endocrine disruption have suggested the need to manage the release of key estrogens from municipal wastewater treatment plants (WWTP). However, the proposed thresholds are below the detection limits of most routine chemical analysis, thereby restricting the ability of watershed managers to assess the environmental exposure appropriately. In this study, we demonstrated the utility of a mechanistic model to address the data gaps on estrogen exposure. Concentrations of the prominent estrogenic contaminants in wastewaters (estrone, estradiol, and ethinylestradiol) were simulated in the Grand River in southern Ontario (Canada) for nine years, including a period when major WWTP upgrades occurred. The predicted concentrations expressed as total estrogenicity (E2 equivalent concentrations) were contrasted to a key estrogenic response (i.e., intersex) in rainbow darter (Etheostoma caeruleum), a wild sentinel fish species. A predicted total estrogenicity in the river of ...
Mixtures of Estrogenic Chemicals Enhance Vitellogenic Response in Sea Bass
Environmental Health Perspectives, 2007
The potential impact of natural and synthetic estrogens on aquatic ecosystems has attracted considerable attention because it is currently accepted that their joint effects are more severe when they are present in mixtures. Although it is well-known that they occur as mixtures in the marine environment, there is little information about the combined effects of estrogenic chemicals on marine biota. OBJECTIVE: In 14-day tests with juvenile sea bass, we analyzed singly and in combination the estrogenic activity of estradiol (E 2 ), ethynylestradiol (EE 2 ), and bisphenol A (BPA) using vitellogenin induction as an end point. METHODS: Fish were exposed to each compound, and on the basis of these concentrationresponse data, we predicted mixture effects by applying the model of concentration addition. The mixtures were tested using a fixed-ratio design, and the resulting mixture effects were compared to the predictions. RESULTS: EE 2 was the most potent steroid, with an EC 50 (median effective concentration) of 0.029 µg/L, 3.6 times more potent than E 2 (EC 50 = 0.104 µg/L); BPA was the least potent chemical, with an EC 50 of 77.94 µg/L. The comparative assessment yielded a good agreement between observed and predicted mixture effects. CONCLUSIONS: This study demonstrates the potential hazard of these compounds to seawater life by their ability to act together in an additive manner. It provides evidence that concentration addition can be used as a predictive tool for assessing the combined effects of estrogenic chemicals in marine ecosystems. KEY WORDS: bisphenol A, concentration addition, estradiol, ethynylestradiol, mixture effects, sea bass, vitellogenin. Environ Health Perspect 115(suppl 1):115-121 (2007). doi:10.1289/ehp.9359 available via http://dx.doi.org/ [Online 8 June 2007]
Aquatic Toxicology, 2009
Knowledge of possible toxic mechanisms (or modes) of action (MOA) of chemicals can provide valuable insights as to appropriate methods for assessing exposure and effects, thereby reducing uncertainties related to extrapolation across species, endpoints and chemical structure. However, MOA-based testing seldom has been used for assessing the ecological risk of chemicals. This is in part because past regulatory mandates have focused more on adverse effects of chemicals (reductions in survival, growth or reproduction) than the pathways through which these effects are elicited. A recent departure from this involves endocrine-disrupting chemicals (EDCs), where there is a need to understand both MOA and adverse outcomes. To achieve this understanding, advances in predictive approaches are required whereby mechanistic changes caused by chemicals at the molecular level can be translated into apical responses meaningful to ecological risk assessment. In this paper we provide an overview and illustrative results from a large, integrated project that assesses the effects of EDCs on two small fish models, the fathead minnow (Pimephales promelas) and zebrafish (Danio rerio). For this work a systems-based approach is being used to delineate toxicity pathways for 12 model EDCs with different known or hypothesized toxic MOA. The studies employ a combination of state-of-the-art genomic (transcriptomic, proteomic, metabolomic), bioinformatic and modeling approaches, in conjunction with whole animal testing, to develop response linkages across biological levels of organization. This understanding forms the basis for predictive approaches for species, endpoint and chemical extrapolation. Although our project is focused specifically on EDCs in fish, we believe that the basic conceptual approach has utility for systematically assessing exposure and effects of chemicals with other MOA across a variety of biological systems.
Health Impacts of Estrogens in the Environment, Considering Complex Mixture Effects
Environmental Health Perspectives, 2007
BACKGROUND: Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established. OBJECTIVES: We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent). METHODS: Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17α-ethinylestradiol (EE 2 )], and to EE 2 alone. RESULTS: In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE 2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes. CONCLUSION: These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures. KEY WORDS: 17α-ethinylestradiol, environmental estrogen, fish, genotoxicity, health, immunotoxicity, metabolism, mixture effect, wastewater treatment works effluent.
Toxicological Sciences, 2005
Estrogenic potencies of four herbicides (triclopyr, 2,4-dichlorophenoxyacetic acid (2,4-D), diquat dibromide, glyphosate), two alkylphenol ethoxylate-containing surfactants (R-11 and Target Prospreader Activator (TPA)), and the binary mixture of surfactants with the herbicides were evaluated using an in vivo rainbow trout vitellogenin assay. Juvenile rainbow trout exposed to 2,4-D (1.64 mg/l) for 7 days had a 93-fold increase in plasma vitellogenin (Vtg) levels compared with untreated fish, while rainbow trout exposed to other pesticides alone did not show elevated vitellogenin levels compared to the control fish. When combined with surfactants, trends indicated enhanced estrogenicity for all combinations, but only 2,4-D and triclopyr caused significant induction of Vtg. Concentration-response studies demonstrated that the lowest observed effect concentrations (LOECs) for 2,4-D and triclopyr were 0.164 mg/l and 1 mg/l, respectively. In terms of measured 4-nonylphenol (4-NP), the LOECs of R-11 and TPA were 20 mg/l and 9.5 mg/l, respectively. Binary mixtures of TPA and 2,4-D showed a greater than additive estrogenic response at the lowest concentrations tested, but a less than additive response at the highest combined concentrations. Binary mixtures of TPA with triclopyr also caused greater than additive Vtg responses in two middle concentrations when compared to TPA or triclopyr alone. When trout were exposed to water collected from a site where triclopyr was used in combination with TPA, a concentrationdependent increase in Vtg expression was observed. Measured values of 4-NP were 3.7 mg/l, and triclopyr concentrations were below detection (<5 ng/l). Estradiol equivalents (EEQs) of the lake water were calculated from an estradiol concentration-response curve and were similar (8.5 ± 7.7 ng/l) to the mean values for the combined triclopyr + TPA treatments (9.9-12.2 ng/l) in the laboratory, suggesting the estrogenicity of the water may have been due to the treatment. These results demonstrated the binary mixture of alkylphenol ethoxylate-containing surfactants with two aquatic pesticides possessed greater than additive estrogenic responses in fish under laboratory conditions and in a field setting.
Environmental Science & Technology, 2001
Experiments were conducted to assess the in vivo potency of binary mixtures of estrogenic chemicals using plasma vitellogenin (VTG) concentrations in juvenile rainbow trout (Oncorhynchus mykiss) as the endpoint. The estrogenic potencies of estradiol-17 (E2), 4-tertnonylphenol (NP), and methoxychlor (MXC) were determined following 14 day exposures to the individual chemicals and binary mixtures of these chemicals. E2, NP, and MXC all induced concentration dependent increases in plasma VTG, with lowest observed effect concentrations of 4.7 and 7.9 ng L -1 for E2, 6.1 and 6.4 µg L -1 for NP, and 4.4 and 6.5 µg L -1 for MXC. Concentration-response curves for fixed ratio binary mixtures of E2 and NP (1:1000), E2 and MXC (1: 1000), and NP and MXC (1:1) were compared to those obtained for the individual chemicals, using the model of concentration addition. Mixtures of E2 and NP were additive at the concentrations tested, but mixtures of E2 and MXC were less than additive. This suggests that while NP probably acts via the same mechanism as E2 in inducing VTG synthesis, MXC may be acting via a different mechanism-(s), possibly as a result of its conversion to HPTE which is an estrogen receptor R agonist and an estrogen receptor antagonist. It was not possible to determine whether mixtures of MXC and NP were additive using VTG induction, because the toxicity of MXC restricted the effect range for which the expected response curve for the binary mixture could be calculated. The data presented illustrate that the model of concentration addition can accurately predict effects on VTG induction, where we know that both chemicals act via the same mechanism in mediating a vitellogenic response.
Collapse of a fish population after exposure to a synthetic estrogen
Proceedings of the National Academy of Sciences, 2007
Municipal wastewaters are a complex mixture containing estrogens and estrogen mimics that are known to affect the reproductive health of wild fishes. Male fishes downstream of some wastewater outfalls produce vitellogenin (VTG) (a protein normally synthesized by females during oocyte maturation) and early-stage eggs in their testes, and this feminization has been attributed to the presence of estrogenic substances such as natural estrogens [estrone or 17β-estradiol (E2)], the synthetic estrogen used in birth-control pills [17α-ethynylestradiol (EE2)], or weaker estrogen mimics such as nonylphenol in the water. Despite widespread evidence that male fishes are being feminized, it is not known whether these low-level, chronic exposures adversely impact the sustainability of wild populations. We conducted a 7-year, whole-lake experiment at the Experimental Lakes Area (ELA) in northwestern Ontario, Canada, and showed that chronic exposure of fathead minnow ( Pimephales promelas ) to low ...
We utilized a 21D reproduction protocol to determine the effects of EE2 and NH 3 . Exposure to a mixture of EE2 and NH 3 at their respective NOAEC induced mortality. Exposure to EE2, NH 3 and their mixture at their NOAEC did not affect reproduction. a b s t r a c t Aquatic organisms are exposed to a multitude of contaminants and to fully understand the impact of multiple stressors on fish populations, we must first understand the mechanism of action for each toxicant and how the combined effects manifest at the level of the individual. 17a-ethinylestradiol (EE2) has been known to cause adverse reproductive effects including reduced fecundity and fertility, intersex and skewed sex ratios in fish by mimicking naturally produced estrogen at low concentrations. Ammonia can cause adverse reproductive and mortality effects in individual fish through effects or damage to the central nervous system. Both EE2 and ammonia are found in most municipal effluents in various concentrations. A flow-through diluter system was used to test the individual effects of these two contaminants at their respective no observable adverse effect concentration (NOAEC) as well as their combined effects on fathead minnow, (Pimephales promelas) reproduction in a mixture exposure. While neither contaminant nor their mixture altered reproduction in terms of fecundity, their mixture resulted in significant fathead minnow mortality during a 21 d exposure. This study demonstrated the need to consider mixture effects when assessing risk for toxicity testing with multiple stressors.