The Experts below are selected from a list of 1950 Experts worldwide ranked by ideXlab platform
Lisa Baumann - One of the best experts on this subject based on the ideXlab platform.
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Prochloraz causes irreversible masculinization of zebrafish danio rerio
Environmental Science and Pollution Research, 2015Co-Authors: Lisa Baumann, Susanne Knorr, Susanne Keiter, Tina Nagel, Helmut Segner, Thomas BraunbeckAbstract:The aim of the present study was to investigate the persistence of endocrine effects by Prochloraz, a fungicide known to have multiple effects on the endocrine system of vertebrates. Since discontinuous exposure is particularly relevant in aquatic ecosystems, an exposure scenario with an exposure phase and a subsequent recovery period was chosen to assess the potential for reversibility of effects by Prochloraz on the sexual development of zebrafish (Danio rerio). Zebrafish were exposed to different concentrations of Prochloraz (10–300 μg/L) until 60 days post hatch (dph), which includes the period of sexual differentiation. For the subsequent 40 days, fish were either held in clean water for depuration or under further continuous exposure. Histological investigations of the gonads revealed persistent effects on sexual differentiation. The sex ratio was skewed towards males and significantly more intersex individuals were found after exposure to Prochloraz at 60 dph. No intersex fish, but masculinized sex ratios were still present after the depuration period, documenting that Prochloraz irreversibly affects the sexual development of zebrafish.
Helmut Segner - One of the best experts on this subject based on the ideXlab platform.
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Prochloraz causes irreversible masculinization of zebrafish danio rerio
Environmental Science and Pollution Research, 2015Co-Authors: Lisa Baumann, Susanne Knorr, Susanne Keiter, Tina Nagel, Helmut Segner, Thomas BraunbeckAbstract:The aim of the present study was to investigate the persistence of endocrine effects by Prochloraz, a fungicide known to have multiple effects on the endocrine system of vertebrates. Since discontinuous exposure is particularly relevant in aquatic ecosystems, an exposure scenario with an exposure phase and a subsequent recovery period was chosen to assess the potential for reversibility of effects by Prochloraz on the sexual development of zebrafish (Danio rerio). Zebrafish were exposed to different concentrations of Prochloraz (10–300 μg/L) until 60 days post hatch (dph), which includes the period of sexual differentiation. For the subsequent 40 days, fish were either held in clean water for depuration or under further continuous exposure. Histological investigations of the gonads revealed persistent effects on sexual differentiation. The sex ratio was skewed towards males and significantly more intersex individuals were found after exposure to Prochloraz at 60 dph. No intersex fish, but masculinized sex ratios were still present after the depuration period, documenting that Prochloraz irreversibly affects the sexual development of zebrafish.
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effects of Prochloraz and nonylphenol diethoxylate on hepatic biotransformation enzymes in trout a comparative in vitro in vivo assessment using cultured hepatocytes
Aquatic Toxicology, 2001Co-Authors: Armin Sturm, J P Cravedi, E Perdu, M Baradat, Helmut SegnerAbstract:Abstract The suitability of cultured rainbow trout hepatocytes as a model system for the assessment of xenobiotic effects on hepatic biotransformation enzymes in fish was examined. Two model water pollutants, the imidazole fungicide Prochloraz and the alkylphenolic compound nonylphenol diethoxylate (NP2EO), were investigated in a comparative in vitro/in vivo approach. Biotransformation enzymes were measured in cultured rainbow trout hepatocytes following exposure to xenobiotics in vitro, or in the liver of juvenile rainbow trout ( Oncorhynchus mykiss ) exposed in vivo. The patterns of biochemical responses to the model pollutants were generally similar between in vitro and in vivo investigations. Levels of cytochrome P4501A (CYP1A) protein and the catalytic activity of the CYP1A-dependent enzyme 7-ethoxyresorufin- O -deethylase (EROD) were induced in vitro after 24 h of exposure to 1.0 μM Prochloraz. In vitro, higher Prochloraz concentrations induced only the levels of CYP1A above control levels, but not EROD activity. In vivo exposure of juvenile trout to 0.27 μM Prochloraz resulted in an induction of CYP1A and EROD after 7 and 14 days, while 0.027 μM Prochloraz had no effects. In vitro, the 6β- and 16β-hydroxylation of testosterone was significantly decreased by 1.0–3.0 μM Prochloraz, while in vivo these variables were significantly inhibited after exposure to 0.27 μM Prochloraz for 7 and 14 days. NP2EO did not affect EROD activity in vitro. In vivo, EROD activity and CYP1A remained unchanged following 7 days of exposure to 0.32 or 1.30 μM NP2EO. NP2EO (15–50 μM) inhibited the 16β-hydroxylation and glucuronidation of testosterone in vitro. In vivo, 7 days of exposure to 0.32 or 1.30 μM NP2EO resulted in a significant inhibition of the 6β- and 16β-hydroxylation of testosterone. The good qualitative correspondence between in vitro and in vivo results indicates that studies using trout hepatocytes allow the identification of biochemical targets of xenobiotic effects in fish liver. However, more research is needed before quantitative predictions, e.g. of effective concentrations, can be made from in vitro investigations.
Thomas Braunbeck - One of the best experts on this subject based on the ideXlab platform.
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Prochloraz causes irreversible masculinization of zebrafish danio rerio
Environmental Science and Pollution Research, 2015Co-Authors: Lisa Baumann, Susanne Knorr, Susanne Keiter, Tina Nagel, Helmut Segner, Thomas BraunbeckAbstract:The aim of the present study was to investigate the persistence of endocrine effects by Prochloraz, a fungicide known to have multiple effects on the endocrine system of vertebrates. Since discontinuous exposure is particularly relevant in aquatic ecosystems, an exposure scenario with an exposure phase and a subsequent recovery period was chosen to assess the potential for reversibility of effects by Prochloraz on the sexual development of zebrafish (Danio rerio). Zebrafish were exposed to different concentrations of Prochloraz (10–300 μg/L) until 60 days post hatch (dph), which includes the period of sexual differentiation. For the subsequent 40 days, fish were either held in clean water for depuration or under further continuous exposure. Histological investigations of the gonads revealed persistent effects on sexual differentiation. The sex ratio was skewed towards males and significantly more intersex individuals were found after exposure to Prochloraz at 60 dph. No intersex fish, but masculinized sex ratios were still present after the depuration period, documenting that Prochloraz irreversibly affects the sexual development of zebrafish.
Poul Bjerregaard - One of the best experts on this subject based on the ideXlab platform.
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effects of the fungicide Prochloraz on the sexual development of zebrafish danio rerio
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2007Co-Authors: Karin Lund Kinnberg, Henrik Holbech, Gitte I Petersen, Poul BjerregaardAbstract:Abstract Some chemicals have the potential to adversely affect sexual development through multiple endocrine actions. Prochloraz is an imidazole fungicide that displays diverse mechanisms of action, including inhibition of aromatase activity, inhibition of androgen synthesis, and antagonism of the androgen receptor. The objective of this study was to assess the effects of Prochloraz on the sexual development of zebrafish ( Danio rerio ) in the Fish Sexual Development Test (FSDT) proposed as an OECD test guideline for detection of endocrine disruptors. Zebrafish were exposed to Prochloraz (0, 16, 64 or 202 μg/L) for 60 days from 24 h post fertilization. Fish exposed to 202 μg/L Prochloraz showed an increased proportion of males. Furthermore, the incidence of intersex and the stages of the gonads were altered in the treated fish compared to the control fish. A significant vitellogenin decrease was observed in both female and male zebrafish at an exposure concentration of 202 μg/L Prochloraz. However, in the male fish, significantly increased vitellogenin concentrations were observed in the groups exposed to 16 or 64 μg/L Prochloraz. This study serves as a part of the validation of the FSDT and indicates that the FSDT is suitable in detecting compounds with multiple endocrine actions. This is of importance in the assessment of the potential risk of existing and new chemicals.
Helle Raun Andersen - One of the best experts on this subject based on the ideXlab platform.
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endocrine disrupting effects in vitro of conazole antifungals used as pesticides and pharmaceuticals
Reproductive Toxicology, 2010Co-Authors: Mia Birkhoj Kjaerstad, Camilla Taxvig, Christine Nellemann, Anne Marie Vinggaard, Helle Raun AndersenAbstract:Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, Prochloraz) were more potent than the triazoles (epoxiconazole, propiconazole, tebuconazole). The critical mechanism seems to be disturbance of steroid biosynthesis. In the H295R cell assay, the conazoles decreased the formation of estradiol and testosterone, and increased the concentration of progesterone, indicating inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole ∼ miconazole > ketoconazole > tebuconazole > epoxiconazole > propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase inhibition, since they inhibited the response induced by both 17β-estradiol (miconazole > econazole ∼ ketoconazole > Prochloraz > tebuconazole > epoxiconazole > propiconazole) and testosterone (econazole > miconazole > Prochloraz > ketoconazole > tebuconazole > epoxiconazole > propiconazole). The triazoles were anti-androgenic in an androgen receptor reporter gene assay (epoxiconazole ∼ tebuconazole > propiconazole). This effect could not be evaluated for the pharmaceutical imidazoles due to cytotoxicity.
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Prochloraz an imidazole fungicide with multiple mechanisms of action
International Journal of Andrology, 2006Co-Authors: Anne Marie Vinggaard, Helle Raun Andersen, Sofie Christiansen, Peter Laier, Majken Dalgaard, Ulla Hass, Eva Cecilie Bonefeldjorgensen, Mette Erecius PoulsenAbstract:Prochloraz is an imidazole fungicide that is widely used in Europe, Australia, Asia and South America within gardening and agriculture. Screening studies have shown that Prochloraz elicits multiple mechanisms of action in vitro, as it antagonizes the androgen and the oestrogen receptor, agonizes the Ah receptor and inhibits aromatase activity. In vivo Prochloraz acts as an antiandrogen in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions in the prostate and increasing luteinizing hormone levels. In order to investigate the developmental effects of Prochloraz, pregnant Wistar dams were dosed perinatally with 30 mg/kg Prochloraz. Results showed that Prochloraz significantly reduced plasma and testicular testosterone levels in gestational day 21 male foetuses, whereas testicular progesterone was increased. Gestational length was increased by Prochloraz. In male pups a significant increase in nipple retention was found, and the weight of the bulbourethral glands was decreased. Behavioural studies showed that the activity level and sweet preference of adult males were significantly increased, indicating that exposure during gestation and lactation causes permanent effects in adulthood. Overall, these results indicate that Prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis. Thus, a novel endocrine disruptor has been identified that is mechanistically interesting as it elicits dual mechanisms of action and acts as an antiandrogen both by blocking the androgen receptor and by inhibiting fetal steroidogenesis. That a fungicide with such effects is so widely used is a cause for concern, and its use should be reduced, thereby minimizing the risk of human exposure.
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antiandrogenic effects in vitro and in vivo of the fungicide Prochloraz
Toxicological Sciences, 2002Co-Authors: Anne Marie Vinggaard, Christine Nellemann, Majken Dalgaard, Eva Cecilie Bonefeld Jorgensen, Helle Raun AndersenAbstract:: The commonly used imidazole fungicide Prochloraz was tested for antiandrogenic effects in vitro and in vivo. Prochloraz, but not the metabolites 2,4,6-trichlorophenoxyacetic acid or 2,4,6-trichlorophenol, inhibited the R1881-induced response in an androgen receptor reporter gene assay. In the Hershberger assay, Prochloraz exposure at all dose levels (50, 100, and 200 mg/kg) given orally to castrated testosterone (T)-treated males markedly reduced weights of ventral prostate, seminal vesicles, musc. levator ani/bulbocavernosus, and bulbourethral gland. These effects were accompanied by an increase in LH and a reduction of the T(4) and TSH level. The effects on seminal vesicles, LH, T(4), and TSH were also evident in intact Prochloraz-exposed young adult rats. Body weights were unaffected whereas liver weights were increased in Prochloraz-treated animals. Changes in androgen-regulated gene expression were determined in ventral prostates by real-time RT-PCR. A pronounced decrease of ornithin decarboxylase and PBP C3 mRNA levels was observed for both Prochloraz and flutamide. These results indicate that Prochloraz antagonizes the peripheral androgen receptors resulting in decreased growth of androgen-dependent tissues and that it antagonizes central androgen receptors blocking the negative feed-back mechanism of testosterone resulting in increased LH secretion from the pituitary. The antiandrogenic effects of Prochloraz were in many ways qualitatively comparable, although weaker, to the effects of flutamide. However, differential effects on levels of FSH, T(4), and TSH indicate that other modes of action apart from the pure AR antagonism might play a role in vivo.