6 research outputs found
Une approche pluridisciplinaire du processus de construction sociale de la prévention du risque CMR en entreprise -Rapport de synthèse de la recherche financée par l'Association de Recherche contre le Cancer (ARC)
Une approche pluridisciplinaire du processus de construction sociale de la prévention du risque CMR
International audienceThe aim of this symposium is to present a research project that has analysed the social process of the prevention of carcinogenic risks, in order to identify the actors involved in, and the form of knowledge, representation of risks and the use of carcinogenic products in industrial and agricultural activities.L'objectif général de ce symposium est de présenter un projet qui a cherché à caractériser le processus de la construction sociale de la prévention du risque CMR en entreprise. Il s'est agi d'identifier les acteurs qui y sont partie prenante, de même que les connaissances, les représentations (portant sur les produits, les process, les effets sur la santé, etc..) et les pratiques liées à l'usage des produits CMR dans le cadre des activités de travail des salariés. L'accès des différents acteurs d'entreprise aux connaissances hétérogènes portant sur les produits CMR a été analysé et comment les formes de construction sociale permettent ou pas un recouvrement voire un partage minimal « des mondes » des différents acteurs, pour nourrir une prévention des risques CMR perçue comme efficace. Cette analyse a montré comment ces connaissances, représentations et pratiques hétérogènes produites par des mondes de conception et d'usage cloisonnés ont la possibilité de se « rencontrer », de s'enrichir pour s'ouvrir à un monde commun
Risk assessment of dietary exposure to organophosphorus flame retardants in children by using HBM-data
Due to their extensive usage, organophosphorus flame retardants (OPFRs) have been detected in humans and in the environment. Human are exposed to OPFRs via inhalation of indoor air, dust uptake or dietary uptake through contaminated food and drinking water. Only recently, few studies addressing dietary exposure to OPFRs were published. In this study, we used human biomonitoring (HBM) data of OPFRs to estimate how much the dietary intake may contribute to the total exposure. We estimated by reverse dosimetry, the daily intake of tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP), tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) for children using HBM data from studies with sampling sites in Belgium, Denmark, France, Germany, Slovenia and Slovakia. For estimating the dietary exposure, a deterministic approach was chosen. The occurrence data of selected food categories were used from a published Belgium food basket study. Since the occurrence data were left-censored, the Lower bound (LB)—Upper bound (UB) approach was used. The estimated daily intake (EDI) calculated on the basis of urine metabolite concentrations ranged from 0.03 to 0.18 µg/kg bw/d for TDCIPP, from 0.05 to 0.17 µg/kg bw/d for TCIPP and from 0.02 to 0.2 µg/kg bw/d for TCEP. Based on national food consumption data and occurrence data, the estimated dietary intake for TDCIPP ranged from 0.005 to 0.09 µg/kg bw/d, for TCIPP ranged from 0.037 to 0.2 µg/kg bw/d and for TCEP ranged from 0.007 to 0.018 µg/kg bw/d (summarized for all countries). The estimated dietary intake of TDCIPP contributes 11–173% to the EDI, depending on country and LB-UB scenario. The estimated dietary uptake of TCIPP was in all calculations, except in Belgium and France, above 100%. In the case of TCEP, it is assumed that the dietary intake ranges from 6 to 57%. The EDI and the estimated dietary intake contribute less than 3% to the reference dose (RfD). Therefore, the estimated exposure to OPFRs indicates a minimal health risk based on the current knowledge of available exposure, kinetic and toxicity data. We were able to show that the dietary exposure can have an impact on the general exposure based on our underlying exposure scenarios
Harmonization of human biomonitoring studies in Europe : characteristics of the HBM4EU-aligned studies participants
Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies Participants
Spliceosome malfunction causes neurodevelopmental disorders with overlapping features
: Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including seven recurrent variants in 30 individuals) and six individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function of the Drosophila orthologs, U2af50 and Prp19, led to lethality, abnormal mushroom body (MB) patterning, and social deficits, differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50 deficient flies. Upon re-analysis of negative clinical exomes followed by data sharing, we further identified six NDD patients carrying RBFOX1 missense variants which, by in vitro testing, showed loss of function. Our study implicates three splicing factors as NDD causative genes and establishes a genetic network with hierarchy underlying human brain development and function