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Health impacts of estrogens in the environment, considering complex mixture effects.

ABSTRACT: 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 [17 alpha-ethinyl-estradiol (EE2)], and to EE2 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 EE2 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.

SUBMITTER: Filby AL

PROVIDER: S-EPMC2137123 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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Health impacts of estrogens in the environment, considering complex mixture effects.

Filby Amy L AL Neuparth Teresa T Thorpe Karen L KL Thorpe Karen L KL Owen Richard R Galloway Tamara S TS Tyler Charles R CR

Environmental health perspectives 20071201 12

<h4>Background</h4>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.<h4>Objectives</h4>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 ...[more]

PMID: 18087587

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Project description:BackgroundThe role of sex hormones on cellular function is unclear. Studies show androgens and estrogens are protective in the CNS, whereas other studies found no effects or damaging effects. Furthermore, sex differences have been observed in multiple oxidative stress-associated CNS disorders, such as Alzheimer's disease, depression, and Parkinson's disease. The goal of this study is to examine the relationship between sex hormones (i.e., androgens and estrogens) and oxidative stress on cell viability.MethodsN27 and PC12 neuronal and C6 glial phenotypic cell lines were used. N27 cells are female rat derived, whereas PC12 cells and C6 cells are male rat derived. These cells express estrogen receptors and the membrane-associated androgen receptor variant, AR45, but not the full-length androgen receptor. N27, PC12, and C6 cells were exposed to sex hormones either before or after an oxidative stressor to examine neuroprotective and neurotoxic properties, respectively. Estrogen receptor and androgen receptor inhibitors were used to determine the mechanisms mediating hormone-oxidative stress interactions on cell viability. Since the presence of AR45 in the human brain tissue was unknown, we examined the postmortem brain tissue from men and women for AR45 protein expression.ResultsNeither androgens nor estrogens were protective against subsequent oxidative stress insults in glial cells. However, these hormones exhibited neuroprotective properties in neuronal N27 and PC12 cells via the estrogen receptor. Interestingly, a window of opportunity exists for sex hormone neuroprotection, wherein temporary hormone deprivation blocked neuroprotection by sex hormones. However, if sex hormones are applied following an oxidative stressor, they exacerbated oxidative stress-induced cell loss in neuronal and glial cells.ConclusionsSex hormone action on cell viability is dependent on the cellular environment. In healthy neuronal cells, sex hormones are protective against oxidative stress insults via the estrogen receptor, regardless of sex chromosome complement (XX, XY). However, in unhealthy (e.g., high oxidative stress) cells, sex hormones exacerbated oxidative stress-induced cell loss, regardless of cell type or sex chromosome complement. The non-genomic AR45 receptor, which is present in humans, mediated androgen's damaging effects, but it is unknown which receptor mediated estrogen's damaging effects. These differential effects of sex hormones that are dependent on the cellular environment, receptor profile, and cell type may mediate the observed sex differences in oxidative stress-associated CNS disorders.

Project description:BackgroundDisparities in clinical research participation perpetuate broader health disparities. Recruitment registries are novel tools to address known challenges in accrual to clinical research. Registries may accelerate accrual, but the utility of these tools to improve generalizability is unclear.ObjectiveTo examine the diversity of a local on-line recruitment registry using the Area Deprivation Index (ADI), a publicly available metric of neighborhood disadvantage.DesignRetrospective analysis.SettingData were collected in the University of California Irvine Consent-to-Contact Registry.ParticipantsWe categorized N=2,837 registry participants based on the ADI decile (collapsed into quintiles) using a state-based rankings.MeasurementsWe examined the proportion of enrollees per ADI quintile and quantified the demographics of these groups. We assessed willingness to participate in studies involving unique research procedures among the ADI groups.ResultsAlthough registry enrollees represented the full spectrum of the ADI, they disproportionately represented less disadvantaged neighborhoods (lowest to highest quintiles: 42%, 30%, 15%, 6%, 7%). Compared to participants from less disadvantaged neighborhoods, participants from more disadvantaged neighborhoods were more often female, of non-white race, and Hispanic ethnicity. Despite demographic differences, ADI groups were observed to have similar willingness to participate in research studies.ConclusionsPeople from more disadvantaged neighborhoods may be underrepresented in recruitment registries, increasing the risk that they will be underrepresented when using these tools to facilitate prospective recruitment to clinical research. Once enrolled in registries, participants from more disadvantaged neighborhoods may be equally willing to participate in research. Efforts to increase representation of participants from disadvantaged neighborhoods in registries could be an important first step toward increasing the generalizability of clinical research.

Project description:Background:The clobetasol propionate cream formulations (CLB Cr ) belong to the "strongest" group, and are used widely. In addition, those formulations are often used as a mixture with moisturizer. Recently, we evaluated pharmaceutical properties of the CLB Cr using near infrared (NIR) spectroscopy, and characteristic NIR spectra depending on the formulation were observed. In the present study, we attempted to evaluate the more diverse pharmaceutical properties of CLB Cr , including the stability of mixture of CLB Cr and moisturizer. Method:Pharmaceutical properties of CLB Cr were evaluated using from rheological characteristics, microscopic observation, dye permeability observations, electrical conductivity method, thermogravimetry-differential thermal analysis (TG-DTA) and near infrared (NIR) spectroscopy. Stability of mixtures of CLB Cr and moisturizer were evaluated using from dye method and NIR spectroscopy. Results:The hardness of Dermovate® (DRM), Glydil® (GDL), and Myalone® (MYA) was greater than that of CLB Cr . High concentrations of white beeswax were considered the reason for the hardness of DRM and GDL. On the other hand, the hardness of MYA may be due to the presence of macrogol 6000. After storage of the cream formulations discharged from the tube at room temperature, mass reduction and attenuation of the peak reflecting water of NIR spectroscopy occurred in a time-dependent manner, except for GDL and MYA. Only GDL was shown to be a w/o-type formulation by dye and electric conductivity measurements, which suggested that this was the reason for the lack of changes in the mass or NIR spectrum of samples after storage. In the NIR spectrum of MYA, the peak reflecting water slightly increased in a time-dependent manner, suggesting the water absorption of macrogol 6000. TG-DTA provided curves indicating the presence of water in each formulation, except for MYA, which was consistent with water quantification previously reported. Finally, when mixing the CLB Cr with a moisturizer, in any CLB Cr , the stability of the mixture with w/o-type moisturizer varies greatly depending on the each CLB Cr . Conclusion:Thus, even for cream formulations with the same active pharmaceutical ingredient, pharmaceutical properties and stability of mixture with moisturizer may different significantly.

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Health impacts of estrogens in the environment, considering complex mixture effects.

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Health impacts of estrogens in the environment, considering complex mixture effects.

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