Elevated Concentrations of Ethinylestradiol, 17β-Estradiol, and Medroxyprogesterone have Little Effect on Reproduction and Survival of Ceriodaphnia dubia

Jukosky, James A.; Watzin, Mary C.; Leiter, James C.

doi:10.1007/s00128-008-9462-1

Cited by 15 publications

(9 citation statements)

References 35 publications

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“…Concerning invertebrates such as the amphipod Hyalella azteca it was observed that at sub-lethal concentrations of EE2 (0.1-10 µg L −1 ) sexual development of males was affected [158]. On the other hand, the estrogens E2 and EE2 did not show significant effects on reproduction or survival of C. dubia even at concentrations of 1 and 0.5 mg L −1 , respectively [159]. According to many authors, the concentrations of estrogens detected in the environment may not post a threat to humans.…”

Section: Sex Hormonesmentioning

confidence: 98%

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

Santos

Araújo

Fachini

et al. 2010

Journal of Hazardous Materials

1,304

533

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Pharmaceuticals are biologically active and persistent substances which have been recognized as a con-tinuing threat to environmental stability. Chronic ecotoxicity data as well as information on the current distribution levels in different environmental compartments continue to be sparse and are focused on those therapeutic classes that are more frequently prescribed and consumed. Nevertheless, they indicate the negative impact that these chemical contaminants may have on living organisms, ecosystems and ultimately, public health. This article reviews the different contamination sources as well as fate and both acute and chronic effects on nontarget organisms. An extensive review of existing data in the form of tables, encompassing many therapeutic classes is presented.Keywords: Pharmaceuticals, Sources, Environmental fate, Ecotoxicological effects

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Section: Sex Hormonesmentioning

confidence: 98%

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

Santos

Araújo

Fachini

et al. 2010

Journal of Hazardous Materials

1,304

533

View full text Add to dashboard Cite

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“…However, the LC 50 values obtained in the acute mortality tests on fish are in the range of mg L −1 [10]. In contrast to fish, no receptors for EE2 have been found in crustaceans, in which the observed effects of EE2 are minor [11], [12]. Compared to vertebrates, invertebrates have fewer identified orthologs to human drug targets.…”

Section: Introductionmentioning

confidence: 96%

Are Pharmaceuticals with Evolutionary Conserved Molecular Drug Targets More Potent to Cause Toxic Effects in Non-Target Organisms?

et al. 2014

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The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L−1, respectively) followed by promethazine (1.6 and 0.18 mg L−1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L−1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals.

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“…For example, although the estrogen receptor (ER) is well conserved across vertebrate species (Baker 2011), a functional ortholog has not been found in invertebrate species (Baker et al 2008; Thomson et al 2009). Therefore, chemicals that bind to the ER should affect vertebrates more than invertebrates, regardless of dose—a prediction confirmed in comparative studies (Goto and Hiromi 2003; Jukosky et al 2008; Santos et al 2007). …”

Section: Use Of Alternative Species and In Vitro Assays In An Aop Framentioning

confidence: 63%

Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

Perkins

Ankley

Crofton

et al. 2013

Environ Health Perspect

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Background: Traditional animal toxicity tests can be time and resource intensive, thereby limiting the number of chemicals that can be comprehensively tested for potential hazards to humans and/or to the environment.Objective: We compared several types of data to demonstrate how alternative models can be used to inform both human and ecological risk assessment.Methods: We reviewed and compared data derived from high throughput in vitro assays to fish reproductive tests for seven chemicals. We investigated whether human-focused assays can be predictive of chemical hazards in the environment. We examined how conserved pathways enable the use of nonmammalian models, such as fathead minnow, zebrafish, and Xenopus laevis, to understand modes of action and to screen for chemical risks to humans.Results: We examined how dose-dependent responses of zebrafish embryos exposed to flusilazole can be extrapolated, using pathway point of departure data and reverse toxicokinetics, to obtain human oral dose hazard values that are similar to published mammalian chronic toxicity values for the chemical. We also examined how development/safety data for human health can be used to help assess potential risks of pharmaceuticals to nontarget species in the environment.Discussion: Using several examples, we demonstrate that pathway-based analysis of chemical effects provides new opportunities to use alternative models (nonmammalian species, in vitro tests) to support decision making while reducing animal use and associated costs.Conclusions: These analyses and examples demonstrate how alternative models can be used to reduce cost and animal use while being protective of both human and ecological health.Citation: Perkins EJ, Ankley GT, Crofton KM, Garcia-Reyero N, LaLone CA, Johnson MS, Tietge JE, Villeneuve DL. 2013. Current perspectives on the use of alternative species in human health and ecological hazard assessments. Environ Health Perspect 121:1002–1010; http://dx.doi.org/10.1289/ehp.1306638

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Elevated Concentrations of Ethinylestradiol, 17β-Estradiol, and Medroxyprogesterone have Little Effect on Reproduction and Survival of Ceriodaphnia dubia

Cited by 15 publications

References 35 publications

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

Are Pharmaceuticals with Evolutionary Conserved Molecular Drug Targets More Potent to Cause Toxic Effects in Non-Target Organisms?

Current Perspectives on the Use of Alternative Species in Human Health and Ecological Hazard Assessments

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