References of "Toxicology Letters"
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See detailEstimated daily intake and cumulative risk assessment of phthalate diesters in a Belgian general population
Dewalque, Lucas ULg; Charlier, Corinne ULg; PIRARD, Catherine ULg

in Toxicology Letters (in press)

The daily intakes (DI) were estimated in a Belgian general population for 5 phthalates, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate ... [more ▼]

The daily intakes (DI) were estimated in a Belgian general population for 5 phthalates, namely diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP) and di-2-ethylhexyl phthalate (DEHP), based on the urinary measurements of their corresponding metabolites. DI values ranged between <LOD and 59.65 μg/kg bw/day depending on the congener, and were globally higher for children than adults. They were compared to acceptable levels of exposure (tolerable daily intakes) to evaluate the hazard quotients (HQ), which highlight an intake above the dose considered as safe for values greater than 1. If very few of our Belgian participants exceeded this threshold for phthalates considered individually, 6.2% of the adults and 25% of the children showed an excessive hazard index (HI) which took into account the cumulative risk of adverse anti-androgenic effects. These results are of concern since these HI were based on only 3 phthalates (DEHP, DiBP and DnBP), and showed a median of 0.55 and 0.29 for children and adults respectively. The comparison with previously determined dietary intakes demonstrated that for DEHP, food intake was nearly the only route of exposure while other pathways occurred mainly for the other studied phthalates. [less ▲]

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See detailModulation of CYP1A1 activity by a Ginkgo biloba extract in the human intestinal Caco-2 cells
Ribonnet, Laurence; Callebaut, Alfons; Nobels, Ingrid et al

in Toxicology Letters (2011), 202(3), 193-202

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See detailEndocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis.
Frizzell, C; Ndossi, D; Verhaegen, S et al

in Toxicology Letters (2011), 206(2), 210-217

The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays ... [more ▼]

The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays incorporating natural steroid receptors and the H295R steroidogenesis assay have been implemented to assess the endocrine disrupting activity of ZEN and its metabolites alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). alpha-ZOL exhibited the strongest estrogenic potency (EC(50) 0.022+/-0.001 nM), slightly less potent than 17-beta estradiol (EC(50) 0.015+/-0.002 nM). ZEN was ~70 times less potent than alpha-ZOL and twice as potent as beta-ZOL. Binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of ZEN, alpha-ZOL or beta-ZOL. ZEN, alpha-ZOL or beta-ZOL increased production of progesterone, estradiol, testosterone and cortisol hormones in the H295R steroidogenesis assay, with peak productions at 10 muM. At 100 muM, cell viability decreased and levels of hormones were significantly reduced except for progesterone. beta-ZOL increased estradiol concentrations more than alpha-ZOL or ZEN, with a maximum effect at 10 muM, with beta-ZOL (562+/-59 pg/ml)>alpha-ZOL (494+/-60 pg/ml)>ZEN (375+/-43 pg/ml). The results indicate that ZEN and its metabolites can act as potential endocrine disruptors at the level of nuclear receptor signalling and by altering hormone production. [less ▲]

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See detailOtotoxic drugs: difference in sensitivity between mice and guinea pigs.
Poirrier, Anne-Lise ULg; Van den Ackerveken, P.; Kim, T. S. et al

in Toxicology Letters (2010), 193(1), 41-9

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to ... [more ▼]

The development of experimental animal models has played an invaluable role in understanding the mechanisms of neurosensory deafness and in devising effective treatments. The purpose of this study was to develop an adult mouse model of ototoxic drug-induced hearing loss and to compare the ototoxicity in the adult mouse to that in the well-described guinea pig model. Mice are a powerful model organism, especially due to the large availability of antibodies, probes and genetic mutants. In this study, mice (n=114) and guinea pigs (n=35) underwent systemic treatment with either kanamycin or cisplatin. Auditory brainstem responses showed a significant threshold shift in guinea pigs 2 weeks after the beginning of the ototoxic treatment, while there was no significant hearing impairment recorded in mice. Hair cells and neuronal loss were correlated with hearing function in both guinea pigs and mice. These results indicate that the mouse is not a good model for ototoxicity, which should be taken into consideration in all further investigations concerning ototoxicity-induced hearing loss. [less ▲]

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See detailModulation of cytochrome P450 1A1 expression and activity in intestinal Caco-2 cells by components of Ginkgo biloba-based dietary supplements
Ribonnet, Laurence; Callebaut, Alfons; Scippo, Marie-Louise ULg et al

in Toxicology Letters (2009), 189

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See detailCYP1A1 induction and CYP3A4 inhibition by the fungicide imazalil in the human intestinal Caco-2 cells-Comparison with other conazole pesticides
Sergent, Thérèse; Dupont, Isabelle; Jassogne, Coralie et al

in Toxicology Letters (2009), 184(3), 159-168

Imazalil (IMA) is a widely used imidazole-antifungal pesticide and. therefore. a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ... [more ▼]

Imazalil (IMA) is a widely used imidazole-antifungal pesticide and. therefore. a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ingested drugs and pollutants, we have investigated the effects of IMA, at realistic intestinal concentrations, on xenobiotic-metabolizing enzymes and efflux pumps by using Caco-2 cells, as a validated in vitro model of the human intestinal absorptive epithelium. For comparison, other conazole fungicides, i.e. ketoconazole, propiconazole and tebuconazole. were also studied. IMA induced cytochrome P450 (CYP) 1A1 activity to the same extent as benzo(a)pyrene (B(a)P) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in a dose-and time-dependent manner. Cell-free aryl hydrocarbon receptor (AhR) binding assay and reporter gene assay suggested that IMA is not an AhR-ligand, implying that IMA-mediated induction should involve an AhR-independent pathway. Moreover, IMA strongly inhibited the CYP3A4 activity in 1,25-vitamin D-3-induced Caco-2 cells. The other fungicides had weak or nil effects on CYP activities. Study of the apical efflux pump activities revealed that ketoconazole inhibited both P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP-2) or breast cancer resistance protein (BCRP), whereas IMA and other fungicides did not. Our results imply that coingestion of IMA-contaminated food and CYP3A4- or CYP1A1-metabolizable drugs or chemicals could lead to drug bioavailability modulation or toxicological interactions, with possible adverse effects for human health. (C) 2008 Elsevier Ireland Ltd. All rights reserved. [less ▲]

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See detailCYP1A1 and CYP3A4 modulation by dietary flavonoids in human intestinal Caco-2 cells.
Sergent, Thérèse; Dupont, Isabelle; Van Der Heiden, Edwige ULg et al

in Toxicology Letters (2009), 191

Flavonoids have been proposed to exert beneficial effects in a multitude of disease states. However, evidence of potential toxic actions has also emerged. Since large doses of flavonoids can be ... [more ▼]

Flavonoids have been proposed to exert beneficial effects in a multitude of disease states. However, evidence of potential toxic actions has also emerged. Since large doses of flavonoids can be encountered in the intestine simultaneously with ingested drugs and pollutants, this study aimed at investigating nine individual flavonoid compounds and their interactions with the major intestinal isoforms of cytochrome P450, i.e. CYPs 1A1 and 3A4, using human intestinal Caco-2 cells cultivated in a serum-free medium. Genistein, quercetin and chrysin provoked a dose-dependent inducing effect on the CYP1A1 activity, measured with the EROD assay. However, they did not affect the CYP1A1 mRNA expression, suggesting they are not aryl hydrocarbon receptor-ligands in intestinal cells and act at a post-transcriptional level. Chrysin, at 50muM, was detected as a potent inhibitor of the TCDD-induced CYP1A1 activity, leading the activity to ca. 10% of the TCDD-control value (n=3), this effect involving, at least partly, direct interactions at the enzyme level. Quercetin was also shown to significantly inhibit the constitutive CYP3A4 activity, measured by the 6beta-(OH)-testosterone assay, and to impair its induction by 1,25-vitamin D(3). Chrysin, quercetin and genistein, were detected as significant inhibitors of the 1,25-vitamin D(3)-induced CYP3A4 activity. In vivo, these effects could result in reduced activation of procarcinogens and/or in drug bioavailability limitation. They underline the importance of intestinal studies to assess food safety and health risks linked to the ingestion of flavonoid-enriched supplements or functional foods. [less ▲]

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See detailA special year for Fusarium Head Blight and associated mycotoxins in Luxembourg
Giraud, Frédéric; Vrancken, Carine; El Jarroudi, Moussa ULg et al

in Toxicology Letters (2008), 180

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See detailSet up of an experimental tool in order to investigate food chemical contaminant toxicity at realistic concentrations
Ribonnet, Laurence; Sergent, Thérèse; Nobels, Ingrid et al

in Toxicology Letters (2007), 172

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See detailAlteration of the estrogen hormone pathway in hepatic cells after exposure to polycyclic aromatic hydrocarbons
Brasseur, Catherine ULg; Widart, Stéphane; Muller, Marc ULg et al

in Toxicology Letters (2007), 172

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See detailImazalil modulates CYPs 1A1 and 3A4 activities in the human Caco-2 cells as an intestinal model to assess food safety
Sergent, Thérèse; Ribonnet, Laurence; Jassogne, C. et al

in Toxicology Letters (2007), 172

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See detailAnti-laminin antibodies in workers exposed to mercury vapour.
Lauwerys, R.; Bernard, A.; Roels, H. et al

in Toxicology Letters (1983), 17(1-2), 113-6

In 62 male workers exposed to mercury vapour for 5.5 years on average, the results of several renal parameters were not significantly different from those found in a well-matched control group (n = 60 ... [more ▼]

In 62 male workers exposed to mercury vapour for 5.5 years on average, the results of several renal parameters were not significantly different from those found in a well-matched control group (n = 60). Circulating anti-laminin antibodies were found, however, in 8 workers exposed to mercury vapour but in none of the control workers. These results suggest that occupational exposure to mercury vapour may lead to immune dysfunction in a certain percentage of the exposed population. Whether such a finding is predictive of the occurrence of an immune glomerulonephritis remains to be evaluated. [less ▲]

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