Conclusions of the French Food Safety Agency on the toxicity of bisphenol A

Since more than 10 years, risk assessment of bisphenol A (BPA) is debated at the international level. In 2008, the U.S. National Toxicology Program (NTP) expressed some concern for adverse effects, at current level of exposure to BPA, on developmental toxicity. In this context, the French Food Safety Agency (AFSSA) decided to review the toxicity data on BPA with a special focus on this endpoint at doses below 5mg/kg bw/day (the no observed adverse effect level set by different regulatory bodies). This paper summarizes the conclusions of a collective assessment conducted by an expert Working Group from AFSSA. Studies were classified into 3 groups: (i) finding no toxicity, (ii) reporting results not considered to be of concern and (iii) indicating warning signals. The term "warning signal" means that no formal conclusion can be drawn regarding the establishment of a health based guidance value but the study raises some questions about the toxicity of BPA at low doses. It was concluded that studies are needed to ascertain the significance for human health of these warning signals and to be able to propose new methodologies for assessing the risks associated with low doses of BPA and more generally of endocrine disruptors

Estimation of grass intake by lambs using n-alkanes as markers

International audienc

Absorption et stockage des hydrocarbures satures chez la truite arc-en-ciel

National audienc

Etude de l'impact de l'exposition à des mélanges de pesticides à faibles doses (caractérisation des effets sur des lignées cellulaires humaines et sur le système hématopoïetique murin)

Pesticides are a heterogeneous group of chemicals widely used for agricultural, domestic and industrial purposes. Omnipresent in the environment, these compounds are of major concern for public health. The general population exposure through food intake usually consists in a combination of many compounds at low doses. However, few studies have examined the effects of such exposure on biological systems. We tested the impact of pesticide mixtures at levels that mimic the consumer's real exposure through the diet, on human intestinal cells in vitro and on the hematopoietic system of mice exposed in vivo. The use of biochemical and biological (cell culture, flow cytometry, antibody array and western blot) assays and of statistical approaches (Meta-analysis) allowed us to argue possible correlation between pesticides and health. Moreover, many modes of action of pesticides in mixture are suggested and more studies are needed to investigate these effects in details.Les pesticides sont des composés chimiques utilisés pour lutter contre des organismes considérés nuisibles dans l'agriculture et également dans d'autres secteurs (industries, collectivités territoriales, usage domestique). Les pesticides sont omniprésents dans l'environnement et l'exposition à ces composés est suspectée d'augmenter l'incidence de certaines pathologies telles que les cancers. A l'heure actuelle, l'exposition du consommateur à des mélanges de pesticides via l'alimentation suscite un intérêt croissant. Cependant, les connaissances en matière d'effets combinés des pesticides à des faibles doses sont encore très lacunaires. Au cours de nos études, nous avons tenté d'apporter des éléments de réponse en testant l'effet de mélanges de pesticides à des faibles doses tels qu'ils peuvent être apportés via l'alimentation, d'une part in vitro sur des cellules d'origine intestinale humaine et d'autre part sur le système hématopoïétique de souris exposées in vivo. Le développement de techniques appropriées relevant de la biochimie (dosages protéiques et enzymatiques), de la biologie (culture cellulaire, comptages, cytométrie de flux, Antibody arrays, western blot) et également des approches statistiques (Méta-analyse) nous a permis d'apporter des arguments sur la plausibilité d'une relation entre l'exposition aux pesticides et la santé. De plus, nos travaux ont ouvert différentes pistes de recherches relatives aux possibles mécanismes d'action de ces substances en mélange.TOULOUSE-ENSAT-Documentation (315552324) / SudocSudocFranceF

Comparative in vitro study of the biotransformation of n-alkanes by liver and small intestine microsomes from different rat strains

National audienc

Comparative metabolism of clenbuterol by rat and bovine liver microsomes and slices. Drug Metab Dispos 26

This paper is available online at http://www.dmd.org ABSTRACT: The metabolism of clenbuterol by liver microsomal fractions and precision-cut liver slices was studied in rats and cattle using a 14 C-labeled molecule and radio-HPLC quantitation of the resulting metabolites. 4-N-Oxidation of clenbuterol was found to be an extensive in vitro metabolic pathway in both species. Clenbuterol hydroxylamine was by far the major metabolite characterized from microsomal and slice incubation media. Trace amounts of 4-nitroclenbuterol were also detected. Another important microsomal biotransformation of clenbuterol, resulting in the production of 4-amino-3,5-dichlorobenzoic acid, was observed only when the drug was incubated with bovine liver microsomes. The corresponding glycine conjugate, namely 4-amino-3,5-dichlorohippuric acid, was detected when clenbuterol was incubated with bovine or rat liver slices. Structural characterization of the major metabolites was performed using electrospray ionization-mass spectrometry, either coupled to liquid chromatography or with direct infusion of collected samples. In addition to these compounds, only quantitatively minor metabolites were detected in bovine (but not rat) microsomal incubation media. Analysis of incubation media from liver slices also allowed the quantitation of a few additional metabolites, some of which were shown to be conjugated compounds