Publications by authors named "Keyvin Darney"

This updated risk assessment evaluated evidence on potential adverse health effects of fluoride related to all sources of oral exposure as mandated by the European Commission. Fluoride benefit assessment was not included. Effects on the central nervous system, thyroid and bone were prioritised.

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The European Commission mandated EFSA to assess the toxicity of bromide, the existing maximum residue levels (MRLs), and possible transfer from feed into food of animal origin. The critical effects of bromide in experimental animals are on the thyroid and central nervous system. Changes in thyroid hormone homeostasis could result in neurodevelopmental toxicity, among other adverse effects.

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The new challenges in toxicology demand novel and innovative in vitro approaches for deriving points of departure (PODs) and determining the mode of action (MOA) of chemicals. Therefore, the aim of this original study was to couple in vitro studies with untargeted metabolomics to model the concentration-response of extra- and intracellular metabolome data on human HepaRG cells treated for 48 h with three pyrrolizidine alkaloids (PAs): heliotrine, retrorsine and lasiocarpine. Modeling revealed that the three PAs induced various monotonic and, importantly, biphasic curves of metabolite content.

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The open source database "OpenCYP database" has been developed based on the results of extensive literature searches from the peer-reviewed literature. OpenCYP provides data on human variability on baseline of activities and polymophism frequencies for selected cytochrome P-450 isoforms (CYP1A2, CYP2A6, CYP2D6, CYP3A4/3A5 and CYP3A7) in healthy adult populations from world populations. CYP enzymatic activities were generally expressed as the metabolic ratio (MR) between an unchanged probe drug and its metabolite(s) in urine or plasma measured in healthy adults.

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Article Synopsis
  • * It presents new findings on the variability of GST activities in healthy humans, highlighting the high inter-individual differences, tissue localization, and genetic polymorphisms of GSTs based on a comprehensive literature review and meta-analysis.
  • * The study emphasizes the importance of GSTs in responding to chemical stressors and calls for more research to identify specific substrates and quantitatively assess individual variations in GST activity, as current data is limited and often uncertain.
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In chemical risk assessment, default uncertainty factors are used to account for interspecies and interindividual differences, and differences in toxicokinetics and toxicodynamics herein. However, these default factors come with little scientific support. Therefore, our aim was to develop an in vitro method, using acetylcholinesterase (AChE) inhibition as a proof of principle, to assess both interspecies and interindividual differences in toxicodynamics.

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The French Nutrition and Health Survey (ENNS) reported higher biomarker levels of exposure to pyrethroids than those observed in North American and German biomonitoring studies. The authors therefore investigated aggregate exposure to permethrin as an initial case study because this compound is one of the most widely-used pyrethroid insecticides. We assessed several contamination sources-such as indoor and outdoor air, settled dust and diet-and several pathways, including oral, inhalation and dermal routes.

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