Search

International audience; Pesticides are now recognised to interact with drug transporters, but only few data are available on this issue for carbamate pesticides, a widely-used class of agrochemicals, to which humans are highly exposed. The present study was therefore designed to determine whether four representative carbamate pesticides, i.e., the insecticides aminocarb and carbofuran, the herbicide chlorpropham and the fungicide propamocarb, may impair activities of main drug transporters implicated in pharmacokinetics.The interactions of carbamates with solute carrier and ATP-binding cassette transporters were investigated using cultured transporter-overexpressing cells, reference substrates and spectrofluorimetry-, liquid chomatography/tandem mass spectrometry- or radioactivity-based methods.Aminocarb and carbofuran exerted no or minimal effects on transporter activities, whereas chlorpropham inhibited BCRP and OAT3 activities and propamocarb decreased those of OCT1 and OCT2, but cis-stimulated that of MATE2-K. Such alterations of transporters however required chlorpropham/propamocarb concentrations in the 5-50 µM range, likely not relevant to environmental exposure. Trans-stimulation assays and propamocarb accumulation experiments additionally suggested that propamocarb is not a substrate for OCT1, OCT2 and MATE2-K.These data indicate that some carbamate pesticides can interact in vitro with some drug transporters, but only when used at concentrations higher than those expected to occur in environmentally-exposed humans.

International audience; Several industries manufacture and process large quantities of engineered nanomaterials, thus increasing the potential for their environmental release during waste management and disposal. Herein, we quantified the release and spatial distribution of titanium dioxide nanomaterials (TiO2 NMs) emitted from an industrial waste stream that flows into a nearby river. Two sampling campaigns were carried out on the river in fall 2017 and spring 2018 at selected sites upstream and downstream of the Industrial Effluent and an urban wastewater treatment plant (WWTP). Significant Ti accumulation was detected in the sediments at the Industrial Effluent and WWTP sites for both fall and spring samples, with measured Ti concentrations of 75–193 mg Ti/kg reaching 21–55× that of the local background upstream. X-ray diffraction analysis confirmed the anatase and rutile mineralogy of the inputs. River surface waters were filtered on-site to distinguish between particulate (>0.20 μm), colloidal (0.02–0.20 μm), and dissolved and/or small nanoparticulate (NP) (0.20 μm), and that the particles sediment rapidly near the emission source and accumulate in the sediment.

TiO 2 nanomaterials (NM) have a wide range of industrial applications, including their use in food products. The incorporation of these NMs in consumer products represents a clear concern for public health safety agencies and consumers, and further investigation of the potential impact of these products on human health is necessary. Indeed, since human oral exposure to TiO 2 NMs is expected to increase in the years to come, there exist legitimate concerns about the risk assessment of these nanomaterials present in food products. A considerable amount of studies investigating the adverse effects of TiO 2 NMs have focused on the genotoxic effects of these NMs, and more recently they have been classified by the International Agency for Research on Cancer (IARC) as carcinogen group 2B following inhalation studies (IARC, 2010). While numerous data are available for anatase or mixes of anatase/rutile forms, the toxicity and the genotoxicity of rutile TiO 2 NMs have been rarely investigated. The aim of our study was therefore to investigate the cytotoxic and genotoxic effects of two rutile TiO 2 NMs, differing in surface coating, NM103 (hydrophobic) and NM104 (hydrophilic), on intestinal and hepatic cell models. Following 3 or 24 h treatments with concentrations of TiO 2 NMs from 1.2 to 80 μg/cm 2 , we have assessed the genotoxicity of these NMs with γH2AX, alkaline comet assay and micronucleus (MN) assays. Cellular viability and effects on oxidative stress were also evaluated. Although TEM imaging demonstrated the presence of the two TiO 2 NMs within the cytoplasm, no significant cytotoxic or genotoxic were observed in either cell model. We have also evaluated and taken into account a variety of potential sources of interference of NMs with cellular assays. TiO 2 NMs present in the cytoplasm introduce uncertainty in the scoring of micronuclei, and therefore this assay is not recommended for the evaluation of the genotoxicity of TiO 2 NMs, or other NMs demonstrating similar interference. The unique properties of TiO 2 NMs introduce additional complexity for genotoxicity testing, and caution must be taken in order to obtain reliable results necessary for accurate hazard assessment.

A recent survey by EDHEC-Risk Institute indicates that 45.2% of European institutional investors have already adopted alternative weighting schemes, 1.1% are not familiar with them, and 24.7% see their current cap-weighted indexes as problematic. The same survey in North America puts these figures at respectively 53.2%, 4.8%, and 42.1%. Replicating an index offers a great equity diversification if it is large enough. The idiosyncratic risk being thus eliminated, only remains the systematic risk, beta, at least on the surface. Indeed, to suit to passive investment, indexes have not only to offer a sufficient return, which absorbs trading cost involved by the index turnover, but also to be enough liquid in order to avoid an important counterparty risk. The sector allocation is also essential, since if the biggest weights are assigned to financial companies for example, a debt crisis like in Europe would lead to important capital losses. We talk about index style, with a value, core or growth orientation. Passive investors show thus a real appetite for these new forms of indexation, but they are not the only users of equity indexes. Active managers use them as benchmarks. Those showing superior performance are hotly pursued by investors, while those falling short of their target can be fired. Abnormal returns are obtained through the managers' ability to successfully time their portfolio weightings or/and select securities that outperform average stocks of similar type. Consequently, this is a crucial issue for managers, but also for the Capital Asset Pricing Model (CAPM). Indeed, the model assumes that a major stock market index can be used as market proxy for mean (return) - variance (risk) efficient portfolio to predict the required rate of return. Cap-weighted indexes have thus long been perceived as reasonable proxies. Literature has however made reservations, considering that a non-optimized proxy may lead to an invalid test of the CAPM, even if we are now aware of its tautological functioning and its empirical problems invalidating a real application. Even more serious, the CAPM can be used to evaluate managers' investment performance. In this case, a nonoptimized proxy would lead to benchmark errors and thus a mismeasurement. Also, given the variety of building methods, which equity index would be the most appropriate for each purpose?

Zinc therapies exert beneficial effects in several cutaneous pathologies through their antiinflammatory properties, but target cells and mechanisms of action are still uncertain. We wondered whether markers of the keratinocyte activation state, such as the expression of immune surface antigens (ICAM-1 and HLA-DR) and the production of TNF-alpha, frequently detected in inflammatory reactions, may be reduced by zinc. For this purpose, we used normal human keratinocytes derived from plastic skin surgery and cultured in low-calcium medium (MCDB153). We studied the effects of ZnSO4 (12.5 to 50 microM) alone or in combination with IFN-gamma (5 U/ml), a mediator of inflammation produced by activated T-cells, or nickel (5-10 micrograms/ml), a sensitizing metal hapten. Using FACS analysis, we showed that the combination of zinc with nickel or the addition of ZnSO4 24 h before IFN-gamma or NiSO4 treatments reduced ICAM-1 expression on the keratinocyte surface (p0.01). However, zinc did not modify the IFN-gamma induced expression of HLA class II antigen on keratinocytes. Zn2+ could also reduce the TNF-alpha secretion of keratinocytes stimulated by IFN-gamma or Ni2+ during 48 h. Taken together, these data indicate that zinc can directly reduce some keratinocyte activation markers frequently observed in vivo; this action may be involved in the antiinflammatory effect of Zn(2+)-associated therapies in cutaneous inflammatory reactions.