Methylene Diphenyl Diisocyanate

The report provides the comprehensive risk assessment of the substance Methylenediphenyl diisocyanate (MDI). It has been prepared by Belgium in the frame of Council Regulation (EEC) No. 793/93 on the evaluation and control of the risks of existing substances, following the principles for assessment of the risks to humans and the environment, laid down in Commission Regulation (EC) No. 1488/94. Part I - Environment This part of the evaluation considers the emissions and the resulting exposure to the environment in all life cycle steps. Following the exposure assessment, the environmental risk characterisation for each protection goal in the aquatic, terrestrial and atmospheric compartment has been determined. The environmental risk assessment concludes that there is no concern. Part II ¿ Human Health This part of the evaluation considers the emissions and the resulting exposure to human populations in all life cycle steps. The scenarios for occupational exposure, consumer exposure and humans exposed via the environment have been examined and the possible risks have been identified. The human health risk assessment concludes that there is concern for workers and consumers with regard to irritation of skin, eye and respiratory tract, skin sensitisation and lung effects induced by repeated inhalation exposure. There is a need for further information and for testing (on hold) on the toxicity for fertility for workers and consumers. For humans exposed via the environment and for human health (physico-chemical properties) there is no concern. The conclusions of this report will lead to risk reduction measures to be proposed by the Commission¿s committee on risk reduction strategies set up in support of Council Regulation (EEC) N. 793/93.JRC.DDG.I.2-Chemical assessment and testin

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Some technical problems of feeding rate measurements in rotifers with fluorescently labelled algae.

Grazing of metazooplankton on phytoplankton and protozooplankton has been widely studied using the radiotracer technique. An interesting alternative to radioactive label is the use of fluorescent dies. Indeed, the use of fluorescently labelled algae (FLA) or protozoans does not imply particular security measures or equipment; moreover they allow the visualisation of the labelled prey in the predator sometimes providing useful informations on the variability between individuals and on the mechanism of feeding processes. Prior to the use of this method in ingestion rate measurements with Brachionus calyciflorus discrimination experiments were performed. The FLAs were Chlorella-like algae (Dictyosphaerium ehrenbergianum) labelled with DTAF (5-(4,6-dichlorotriazin-2-yl) aminofluorescein). The ingestion rate of the rotifer on the FLAs was 3 to 15 times lower than the ingestion rate on non labelled. Evidence was gathered that the staining procedure (heat-killing of the algae) was mainly responsible for the discrimination of the rotifer rather than the dye itself. Other technical considerations will be discussed like the occurrence of crashed algae in the rotifers gut and the inter-individual variability

Feeding of Brachionus calyciflorus on Tetrahymena pyriformis using

This study was carried out in the wider frame of the quatitative evaluation of trophic transfers occurring in large rivers between metozooplankton and protozooplankton. Since the rotifer B. calyciflorus is dominant in the river Meuse (Belgium) its feeding on the widespread ciliate T. pyriformis was studied. Grazing rates were either determined through monitoring of cell number variations in experimental media or through use of fluorescently labeled ciliates. The labeling procedure consisted in allowing the ciliates to ingest fluorescent microspheres (0.5 µm in diameter) for short period of time; since number of ingested fluorescent spheres are very stabl

Investigating apical adverse effects of four endocrine active substances in the freshwater gastropod Lymnaea stagnalis

The hermaphroditic gastropod Lymnaea stagnalis is proposed as a candidate species for the development of OECD guidelines for testing of the reprotoxicity of chemicals, including endocrine active substances (EASs). Up to now, only a few putative EASs have been tested for their reproductive toxicity in this species. In this study, we investigate the effects of four EASs with different affinities to the vertebrate estrogen and androgen receptors (chlordecone as an estrogen; cyproterone acetate, fenitrothion and vinclozolin as anti-androgens) on the reproduction of L stagnalis in a 21-day semi-static test. Testosterone and 17 alpha-ethinylestradiol (EE2) were used as the reference compounds. The tested EASs had no significant effect on growth and survival at the tested concentration ranges (ng to mu g/L. Classical reproduction endpoints (i.e., oviposition and fecundity) were not responsive to the tested chemicals, except for chlordecone and 17 alpha-ethinylestradiol, which hampered reproduction from 19.6 mu g/L and 17.6 mu g/L, respectively. The frequency of polyembryonic eggs, used as an additional endpoint, demonstrated the effects of all compounds except EE2. The molecular pathways, which are involved in such reproduction impairments, remain unknown. Our results suggest that egg quality is a more sensitive endpoint as compared to other reproductive endpoints commonly assessed in mollusk toxicity tests. (C) 2014 Elsevier B.V. All rights reserved

Modeling chlordecone toxicokinetics data in growing pigs using a nonlinear mixed-effects approach

International audienc

Workshop on rotifers in ecotoxicology

The aim of the workshop on rotifers in ecotoxicology was to stimulate discussions on new developments in the field. Discussions about the use of biomolecular tools indicate that gene expression analysis with rotifers should be available in the next few years. Such analyses will be a great asset as they enable ecotoxicologists to study molecular mechanisms of toxicity. Rotifers also appear as useful tools in the risk assessment of pharmaceuticals and their metabolites that find their way into aquatic ecosystems because their sensitivity to some of these substances is higher than that of cladocerans and algae. The nature and extent of the impact of potential endocrine disruptors on aquatic invertebrates is another poorly resolved issue for which rotifers are a promising tool. Indeed, rotifers seem to be particularly sensitive to androgenic and anti-antiandrogenic substances, whereas copepods and cladocerans are typically more affected by estrogens and juvenile hormone-like compounds. Besides their usefulness in these emerging fields of aquatic ecotoxicology, it was emphasized that research with rotifers on basic issues like, e.g., toxicant interference with predation, competition, or interspecific and interclonal variation in ecotoxicological tests is still needed