Long-term exposure of male rats to low-dose ethinylestradiol (EE2) in drinking water: Effects on ponderal growth and on litter size of their progeny

Vosges, Mélanie; Braguer, Jean-Claude; Combarnous, Yves

doi:10.1016/j.reprotox.2007.12.002

Cited by 29 publications

(13 citation statements)

References 46 publications

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“…In Germany, ethinylestradiol, the active ingredient in oral contraceptive pills, was detected in four out of 10 distribution water samples at the 0.15-0.50 ng/L level (Kuch and Ballschmiter, 2001). Ethinylestradiol may cause long-term endocrine disruption effects even at very low ng/L concentrations in distribution water (Vosges et al, 2008). The presence of various classes of pharmaceuticals in water may negatively affect the quality of drinking water and pose risks to human beings.…”

Section: Introductionmentioning

confidence: 99%

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Sun

Luo

Wang

et al. 2015

Ecotoxicology and Environmental Safety

125

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a b s t r a c tPharmaceuticals in drinking water sources (DWSs) have raised significant concerns for their persistent input and potential human health risks. Currently, little is known about the occurrence of pharmaceuticals in DWSs in China. In this study, a survey for multi-class pharmaceuticals in DWSs of five major river watersheds in China was conducted from 2012 to 2013. Samples were collected from 25 sampling sites in rivers and reservoirs. 135 pharmaceuticals were analyzed using solid-phase extraction and ultra-performance liquid chromatography tandem mass spectrometry. The results showed that a total of 70 pharmaceuticals were present in the samples, and the most frequently detected ones included sulfonamides, macrolides, antiepileptic drugs, anti-inflammatory drugs, and β-blockers, etc. Amongst these, maximum concentrations of lincomycin, sulfamethoxazole, acetaminophen and paraxanthine were between 44 ng/L and 134 ng/L, and those of metoprolol, diphenhydramine, venlafaxine, nalidixic acid and androstenedione were less than 1 ng/L. Concentrations of the two that were most persistent, DEET and carbamazepine, were 0.8-10.2 ng/L and 0.01-3.5 ng/L, respectively. Higher concentrations of cotinine were observed in warm season than in cold season, while concentrations of lincomycin were the opposite. In a causality analysis, the occurrence of pharmaceuticals in DWSs depends mainly on the detection limits of the methods, their usage and the persistence in the aquatic environment.

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Section: Introductionmentioning

confidence: 99%

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Sun

Luo

Wang

et al. 2015

Ecotoxicology and Environmental Safety

125

View full text Add to dashboard Cite

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“…Nevertheless, in both cases estrogens have been shown to interact with PDI and to inhibit its activities. Numerous EDC affecting reproduction are estrogenic molecules such as EE2, DES, BP-A etc… [17]–[19]. The observation of diminished PDI reductase activity in the presence of physiological concentrations of estrogens indicates that these hormones might have an inhibitory effect on the synthesis and secretion of proteins including by cells not expressing estrogen receptors.…”

Section: Discussionmentioning

confidence: 99%

Effect of Pharmaceutical Potential Endocrine Disruptor Compounds on Protein Disulfide Isomerase Reductase Activity Using Di-Eosin-Oxidized-Glutathion

Klett

Cahoreau²,

Villeret³

et al. 2010

PLoS ONE

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BackgroundProtein Disulfide Isomerase (PDI) in the endoplasmic reticulum of all cells catalyzes the rearrangement of disulfide bridges during folding of membrane and secreted proteins. As PDI is also known to bind various molecules including hormones such as estradiol and thyroxin, we considered the hypothesis that adverse effects of endocrine-disrupter compounds (EDC) could be mediated through their interaction with PDI leading to defects in membrane or secreted proteins.Methodology/Principal FindingsTaking advantage of the recent description of the fluorescence self quenched substrate di-eosin-oxidized-glutathion (DiE-GSSG), we determined kinetically the effects of various potential pharmaceutical EDCs on the in-vitro reductase activity of bovine liver PDI by measuring the fluorescence of the reaction product (E-GSH). Our data show that estrogens (ethynylestradiol and bisphenol-A) as well as indomethacin exert an inhibition whereas medroxyprogesteroneacetate and nortestosterone exert a potentiation of bovine PDI reductase activity.ConclusionsThe present data indicate that the tested EDCs could not only affect endocrine target cells through nuclear receptors as previously shown, but could also affect these and all other cells by positively or negatively affecting PDI activity. The substrate DiE-GSSG has been demonstrated to be a convenient substrate to measure PDI reductase activity in the presence of various potential EDCs. It will certainely be usefull for the screening of potential effect of all kinds of chemicals on PDI reductase activity.

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“…EE 2 is a synthetic estrogen commonly used in contraceptives, hormonal replacement therapies and livestock reproduction management (Zuo, Zhang, & Zhou, 2013). EE 2 is one of the top 15 most prescribed pharmaceuticals and approximately 1 ton of EE 2 is consumed annually worldwide (Vosges, Braguer, & Combarnous, 2008). EE 2 is a hydrophobic substance with low volatility (Yin, Kookana, & Ru, 2002) and is less prone to biodegradation than natural estrogenic steroids (Zuo et al, 2013) making it a persistent pollutant in the environment.…”

Section: Figurementioning

confidence: 99%

Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

Cosme

Lister

Kraak

2015

General and Comparative Endocrinology

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INHIBITION OF SPAWNING IN ZEBRAFISH (Danio rerio): ADVERSE OUTCOME PATHWAYS OF QUINACRINE AND ETHINYLESTRADIOL Madelyne CosmeAdvisor: University of Guelph, 2014Professor. Glen Van Der KraakThis study examined the effects of estrogen receptor agonist, ethinylestradiol, and the phospholipase A 2 inhibitor, quinacrine, on the pathways controlling follicular recruitment, steroidogenesis, oocyte maturation and ovulation and spawning success in the adult zebrafish. Ethinylestradiol and quinacrine both inhibit spawning but did so through different adverse outcome pathways. Ethinylestradiol affected follicular recruitment (reduced ovarian size and reduction in the proportion of cortical alveolus, vitellogenic and mature follicle stages), steroidogenesis (reduced expression of aromatase) maturation (reduced luteinizing hormone receptor expression) and ovulation (reduced expression of cytosolic phospholipase A2 and the nuclear progesterone receptor). Quinacrine targeted ovulation via a reduction of the steroid 17α, 20β dihydroxy-4-prenen-3-one and expression of the prostaglandin metabolizing enzyme cyclooxygenase 2. Collectively, these studies suggest that a targeted assessment of reproductive endpoints can be used effectively to identify the adverse outcome pathways by which toxicants can impact reproductive fitness.iii ACKNOWLEDGEMENTS

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Long-term exposure of male rats to low-dose ethinylestradiol (EE2) in drinking water: Effects on ponderal growth and on litter size of their progeny

Cited by 29 publications

References 46 publications

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Occurrences of pharmaceuticals in drinking water sources of major river watersheds, China

Effect of Pharmaceutical Potential Endocrine Disruptor Compounds on Protein Disulfide Isomerase Reductase Activity Using Di-Eosin-Oxidized-Glutathion

Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

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