Éditeur(s) : Elsevier Science Bv
Résumé : The biodynamic and saturation models offer promising lines of enquiry to predict the bioaccumulation of metals by aquatic organisms. However, in order to construct these models, the accumulation strategies have to be defined for each metal/organism couple in controlled conditions. This study aims at modelling the waterborne bioaccumulation of Ni and the influence of the water's geochemical properties on this process in a crustacean that is widely distributed in Europe, Gammarus pulex. In the laboratory, G. pulex was exposed to several Ni concentrations (from 0.001 to 100 mg L(-1)) in aquatic microcosms. Our results show that G. pulex is very tolerant to Ni (LC50(48 h) = 477 mg L(-1) Ni). Time course experiments enabled the construction of a biodynamic model by determining the uptake (k(u)) and elimination (k(e)) rate constants. When the exposure concentration exceeded 1 mg L(-1) Ni, the metal uptake reached a maximum due to a limited number of binding sites for Ni. Therefore, the organism's maximal capacity to accumulate the metal (B(max)) and the half-saturation constant (K) were determined to establish the saturation model. We showed that the two models are comparable for the lowest exposure concentrations (<1 mg L(-1) Ni), with k(u)/k(e) = B(max)/K. Then, the bioaccumulation of Ni was recorded in waters exhibiting various concentrations of three major ions (Na(+), Mg(2+) and Ca(2+)). Only Ca had an inhibitory effect on the Ni uptake. This study reports for the first time the bioaccumulation of Ni in G. pulex. Because of its high tolerance to Ni and its high capacity to accumulate this metal, this crustacean could be used as an indicator of Ni bioavailability in freshwaters. (C) 2011 Elsevier B.V. All rights reserved.
Aquatic Toxicology (0166-445X) (Elsevier Science Bv), 2011-08 , Vol. 104 , N. 3-4 , P. 161-167

Droits : 2011 Elsevier B.V. All rights reserved.
http://archimer.ifremer.fr/doc/00041/15217/18005.pdf
DOI:10.1016/j.aquatox.2011.04.011
http://archimer.ifremer.fr/doc/00041/15217/

Éditeur(s) : Elsevier
Résumé : Dissolved and particulate Hg fluxes in the Lot-Garonne-Gironde fluvial-estuarine system were obtained from observation of daily discharge and suspended particulate matter (SPM) concentrations. In addition to the measurements of the total dissolved (< 0.45 gm) and particulate Hg (> 0.45 gm), called HgTD and HgTp respectively, the dissolved inorganic Hg species (HgRD) were determined monthly. Geochemical background values for HgTp in sediments and SPM were similar to crustal values and to typical concentrations in SPM of non-contaminated river systems, respectively. The Riou Mort watershed already known as the origin of important historical polymetallic (e.g., Cd, Zn) pollution was identified as an important Hg point source. In the downstream Lot River, Hg concentrations were clearly higher than those in other moderately contaminated systems. The mean relative contribution of HgRD to HgTD in the Lot River and in the Garonne River was close to 25% and 50%, respectively, and showed no correlation with water discharge or SPM concentration. Depending on the origin and nature of SPM, HgTp concentrations were correlated or not with particulate organic C (POC). Maximum HgTp concentrations were measured in samples containing low POC concentrations and were attributed to sediment resuspension. In contrast, high POC concentrations (6-17%) during algal blooms were associated with low/moderate HgTp concentrations (< 0.5 mg kg(-1)) at different sites, suggesting that Hg concentrations in fluvial phytoplankton may be limited by bioavailability of dissolved Hg and/or physiologically controlled Hg accumulation. Mercury was mostly (up to 98%) transported in the particulate phase with estimated annual Hg fluxes at the outlet of the Lot River system ranging from 35 to 530 kg a(-1) for the past decade. The minimum anthropogenic component (58-84% of total Hg fluxes) could not be explained by present Riou Mort point source contributions, suggesting important Hg release from contaminated sediment as a major source and from downstream point sources (e.g., coal-fired power plants and/or metal processing industries). HgTp concentrations and fluxes were strongly related to hydrologic variations and were clearly increased by riverbed dredging during lock construction. Therefore, the estimated Hg stocks in the Lot River sediment (5-13 tons) represent an important potential Hg source for the downstream fluvial-estuarine system.
Applied Geochemistry (0883-2927) (Elsevier), 2006-03 , Vol. 21 , N. 3 , P. 515-527

Droits : 2006 Elsevier Ltd All rights reserved
http://archimer.ifremer.fr/doc/2006/publication-1343.pdf
DOI:10.1016/j.apgeochem.2005.12.004
http://archimer.ifremer.fr/doc/00000/1343/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Children are exposed to toxic metals and metalloids via their diet and environment. Our objective was to assess the aggregate chronic exposure of children aged 3–6 years, living in France, to As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V present in diet, tap water, air, soil and floor dust in the years 2007–2009. Dietary data came from the French Total Diet Study, while concentrations in residential tap water, soil and indoor floor dust came from the ‘Plomb-Habitat’ nationwide representative survey on children's lead exposure at home. Indoor air concentrations were assumed to be equal to outdoor air concentrations, which were retrieved from regulatory measurements networks. Human exposure factors were retrieved from literature. Data were combined with Monte Carlo simulations. Median exposures were 1.7, 0.3, 10.2, 34.1, 60.3, 0.7, 0.1, 44.3, 1.5 and 95th percentiles were 4.4, 0.5, 15.8, 61.3, 98.3, 2.5, 0.1, 111.1, 2.9 μg/kg bw/d for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. Dietary exposures dominate aggregate exposures, with the notable exception of Pb - for which soils and indoor floor dust ingestion contribute most at the 95th percentile. The strengths of this study are that it aggregates exposures that are often estimated separately, and uses a large amount of representative data. This assessment is limited to main diet and residential exposure, and does not take into account the relative bioavailability of compounds. These results could be used to help target prevention strategies.
ISSN: 0160-4120

inserm-01404061
http://www.hal.inserm.fr/inserm-01404061
http://www.hal.inserm.fr/inserm-01404061/document
http://www.hal.inserm.fr/inserm-01404061/file/rev1%20-%20MS%20Expo%20metals.pdf
DOI : 10.1016/j.envint.2016.10.009

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
BACKGROUND: Differences in circulating steroid hormone levels have been hypothesized to explain ethnic differences in steroid-related diseases. The aim of this study was to determine the serum levels of a wide panel of steroid hormones, both androgens and estrogens, in healthy middle-aged African-Caribbean and European men. DESIGN AND METHODS: Serum steroid hormone levels were determined in men participating in a systematic public health study funded by the French National Health Insurance system. Blood was collected in the morning from 304 healthy African-Caribbean and European men aged between 40 and 69 years. Serum steroids were measured by mass spectrometry-gas chromatography, except for DHEAS and sex hormone-binding globulin, which were determined by RIA. Data were analyzed in 10-year age intervals by analysis of covariance, with adjustment for age, body mass index, waist-to-hip ratio, tobacco and alcohol consumption, and season of sampling. RESULTS: Compared with Europeans, African-Caribbean men presented significantly higher serum levels of measured bioavailable testosterone, 4-androstenedione (4-dione), and estrone (E1) regardless of the age group, of 5-androstenediol (5-diol) in those aged 40-49 and 50-59 years, and of testosterone (TT) and dihydrotestosterone in those aged 40-49 years. In contrast, European men aged 40-69 years showed significantly higher serum levels of DHEA and DHEAS. CONCLUSIONS: Significant differences in serum steroid hormone levels were observed in middle-aged African-Caribbean and European men. Whether such differences could contribute to ethnic differences in disease risk in adult men remains to be investigated. Some steroids, such as bioavailable TT, 4-dione, 5-diol, and E1, deserve particular attention.
ISSN: 0804-4643

hal-00876034
https://hal.archives-ouvertes.fr/hal-00876034
DOI : 10.1530/EJE-11-0551
PUBMED : 21951700

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
ISSN: 1932-6203

hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025/document
https://hal.archives-ouvertes.fr/hal-00876025/file/Persistent_Organochlorine-accepted.pdf
DOI : 10.1371/journal.pone.0066460

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed. Significant interactions occur by inhibition or induction of CYP450 3A4 which is the main metabolic pathway of TKIs. However, minor metabolic pathways should also be paid attention to. Interactions involving efflux and influx transporters should also be considered occurring for some TKIs. Genetic polymorphism in drug metabolism as well as in drug transport is a factor of variability in drug exposure, which could modulate the magnitude of drug-drug interactions (DDIs). It should be noticed that TKIs can also be at the origin of drug interactions by altering the pharmacokinetics of coprescribed drugs. Since cancer patients are given many drugs either for supportive care or for the treatment of drug toxicity, and to the fact that the oldest patients are polymedicated, a clear understanding of DDIs with TKIs is of interest. The objectives of this review are to provide an overview of the mechanisms of DDIs with TKIs and to provide to physicians and pharmacists recommendations to manage these DDIs in their clinical practice.
ISSN: 0278-0232

hal-01616064
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616064
DOI : 10.1002/hon.2335
PUBMED : 27925256

Éditeur(s) : Communication, ICES Conference and Meeting (CM), 2010, Nantes
Résumé : Chlordecone is a very persistent insecticide used in banana plantations of the French West Indies between 1972 and 1993. Chlordecone residues were found in inland water, in agricultural and freshwater products, and in marine organisms. This pollution has become of great concern in 2007. Therefore, a governmental action Plan was launched to better assess the pollution and to improve the consumer’s protection. Within this plan, 1048 samples from 69 different species of marine fishes and crustaceans were collected all around both the Guadeloupe and the Martinique Islands and analyzed. The results confirm the presence of chlordecone in marine organisms, with highly variable concentrations (from the detection limit to 1000 μg.kg-1). In 17.9 % of the samples, concentrations exceeded 20 μg.kg-1, the maximum acceptable level in fish according to the French regulation (Anon, 2008). Two main features of this contamination were characterized. 1) Because of the sedimentation of contaminated suspended soil particles, the sheltered bays are more exposed to chlordecone than the open coast where terrigenous flux are dispersed. 2) Species biology, particularly their lifestyle and diet, appear to influence contamination levels. Thus, the more contaminated species live in relation with sediment or are at high trophic level. These results have directly supported political decisions in order to prevent too high exposure of consumers to chlordecone. Fishing activities in sheltered bays have been forbidden for potentially highly contaminated species like benthic crustaceans and top predators. Further studies are under way to assess the importance of the trophic transport of chlordecone within the foodweb, and to evaluate the historical deposition of this insecticide in sediment and its further bioavailability.

Droits : 2010 ICES/CIEM ; Ifremer
http://archimer.ifremer.fr/doc/00014/12511/9361.pdf
http://archimer.ifremer.fr/doc/00014/12511/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In addition to dietary exposure, children are exposed to metals via ingestion of soils and indoor dust, contaminated by natural or anthropogenic outdoor and indoor sources. The objective of this nationwide study was to assess metal contamination of soils and dust which young French children are exposed to. A sample of 484 children (6 months to 6 years) was constituted in order to obtain representative results for young French children. In each home indoor settled dust was sampled by a wipe in up to five rooms. Outdoor playgrounds were sampled with a soil sample ring (n=315) or with a wipe in case of hard surfaces (n=53). As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V were measured because of their potential health concern due to soil and dust ingestion. The samples were digested with hydrochloric acid, and afterwards aqua regia in order to determine both leachable and total metal concentrations and loadings by mass spectrometry with a quadrupole ICP-MS. In indoor settled dust most (total) loadings were below the Limit of Quantification (LOQ), except for Pb and Sr, whose median loadings were respectively 9 and 10 μg/m². The 95th percentile of loadings were 2 μg/m² for As, <0.8 for Cd, 18 for Cr, 49 for Cu, <64 for Mn, 63 for Pb, 2 for Sb, 56 for Sr, and <8 for V. Median/95th percentile of loadings in settled dust on outdoor playgrounds were 2/16, <0.8/1.3, 17/53, 49/330, 99/424, 32/393, 2/13, 86/661 and 10/37 μg/m² for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. In outdoor playground soil median/95th percentile of concentrations (μg/g) were 8/26, <0.65/1, 25/52, <26/53,391/956, 27/254, 0.7/4, 54/295, 23/57 for As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V respectively. These results are comparable with those observed in other countries. Because of their representative nature, we can assess children's exposures to these metals via soil and dust and the associated risks in urban and rural environments. Ratios of leachable/total concentrations and loadings, calculated on >LOQ measurements, differed among metals. To a lesser extent, they were also affected by type of matrix, with (except for Cd) a greater leachability of dust (especially indoor) compared to soils.
ISSN: 0160-4120

hal-00732136
https://hal.archives-ouvertes.fr/hal-00732136
PUBMED : 22613504
DOI : 10.1016/j.envint.2012.04.010

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Metalloproteases involved in extracellular matrix remodeling play a pivotal role in cell response by regulating the bioavailability of cytokines and growth factors. Recently, the disintegrin and metalloprotease, ADAMTS1 has been demonstrated to be able to activate the transforming growth factor TGF-β, a major factor in fibrosis and cancer. The KTFR sequence from ADAMTS1 is responsible for the interaction with the LSKL peptide from the latent form of TGF-β, leading to its activation. While the atomic details of the interaction site can be the basis of the rational design of efficient inhibitory molecules, the binding mode of interaction is totally unknown. In this study, we show that recombinant fragments of human ADAMTS1 containing KTFR sequence keep the ability to bind the latent form of TGF-β. The recombinant fragment with the best affinity is modeled to investigate the binding mode of LSKL peptide with ADAMTS1 at the atomic level. Using a combined approach with molecular docking and multiple independent molecular dynamics (MD) simulations, we provide the binding mode of LSKL peptide with ADAMTS1. The MD simulations starting with the two lowest energy model predicted by molecular docking shows stable interactions characterized by 3 salt bridges (K3-NH3+ with E626-COO−; L4-COO− with K619-NH3+; L1-NH3+ with E624-COO−) and 2 hydrogen bonds (S2-OH with E623-COO−; L4-NH with E623-COO−). The knowledge of this interaction mechanism paves the way to the design of more potent and more specific inhibitors against the inappropriate activation of TGF-β by ADAMTS1 in liver diseases
ISSN: 1476-9271

hal-01269916
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01269916
DOI : 10.1016/j.compbiolchem.2016.01.012
PUBMED : 26878129

Éditeur(s) : Université de Paris 7
Résumé : The Seine estuary and its adjacent region Pays de Caux are two significant sources of mercury for coastal marine environments. It is carried through fluvial means for the Seine bay and through karstic fresh water emergences for Pays de Caux's coastal area. Mercury cycle in the Seine estuary and bay is affected by additional anthropical activities. The estuary's maximal turbidity area acts like a trap and a chemical reactor for fluvial mercury. Within this area, we can confirm: (i) the non conservative behaviour of dissolved mercury; (ii) mercury enrichment of particles when comparing the Seine's and marine environment and we suggest mercury particle redistribution from the organic fraction to the oxyhydroxydes fraction. A large fraction of mercury is exported in this state towards coastal areas. Mercury reduction in surface coastal waters and its atmospherical recycling are major phenomena. Photoreduction and biological reduction play quantitative roles equivalent to total mercury recycling via the atmosphere corresponding approximately to 30 % of fluvial exchanges. We are demonstrating that reactive forms of mercury are supporting photoreduction. Mercury behaviour within Pays de Caux's karst depends of the hydrogeological context of the system (time and flow speed, turbidity, flow); regardless of the speciation and/or partition in underground waters, the total amount of mercury in intertidal areas is quantitatively the same as in the Seine estuary. Mercury brought through intertidal emergences (karstic exudations) is not « filtered » by a maximal turbidity area and is more widely bio-available for mussels than in the Seine estuary. Even being free from growth factor influences through simple models, mussels found in Pays de Caux still show one of the highest mercury contamination on the French coast; for the first time this places the emphasis on how much mercury is brought from underground waters to the coastal environment. Surface complexation modelisation tests are able to reproduce the major part of mercury partition in the Seine estuary and bay if a very low mercury exchangeable fraction and minimum complexation parameters are taken into account; thermodynamic calculations also suggest that a strong or highly concentrated « dissolved » ligand must be present in the water in order to compete with chlorocomplex formations and explain our measures.
L'estuaire de la Seine et la région adjacente du Pays de Caux sont deux sources significatives en mercure pour le milieu marin côtier. Les apports sont d'une part fluviatiles en ce qui concerne la Baie de Seine et karstiques via des émergences d'eau douce pour la zone côtière du Pays de Caux. Le cycle du mercure en estuaire et baie de Seine est perturbé par les apports liés aux activités anthropiques. La zone de turbidité maximum de l'estuaire joue le rôle de piège et de réacteur chimique pour le mercure fluviatile. Au sein de cette zone, nous mettons en évidence : (i) un comportement non-conservatif du mercure dissous; (ii) un enrichissement en mercure des particules par rapport à celles de la Seine et du milieu marin et suggérons une redistribution du mercure particulaire de la fraction organique vers la fraction oxyhydroxydes. C'est sous cette forme qu'une fraction importante du mercure est exportée vers la zone côtière. La réduction du mercure dans les eaux côtières de surface et son recyclage atmosphérique sont des phénomènes majeurs. En effet, la photoréduction et la réduction biologique jouent des rôles quantitativement équivalents avec un recyclage total du mercure via l'atmosphère correspondant à environ 30% des apports fluviatiles. Nous montrons que les formes réactives du mercure constituent le substrat de la photoréduction. Le comportement du mercure au sein du karst du Pays de Caux dépend du contexte hydrogéologiques du système (temps et vitesse de circulation, turbidité, débit) ; quelle que soit la spéciation et/ou la partition dans les eaux souterraines, l'apport en mercure total à la zone intertidale est quantitativement du même ordre de grandeur que les apports de la Seine. Le mercure apporté par les émergences intertidales (exutoires karstiques) n'est pas « filtré » par une zone de turbidité maximale et se trouve plus largement biodisponible pour les moules qu'en estuaire de Seine. En s'affranchissant, par des modèles simples, de l'influences des facteurs de croissance, les moules du Pays de Caux affichent toujours une contamination par le mercure parmi les plus élevées du littoral français; ceci met pour la première fois l'emphase sur l'importance de l'apport en mercure par des eaux souterraines dans un environnement côtier. Les essais de modélisation de complexation de surface reproduisent la majeure partie de la partition du mercure dans l'estuaire et la baie de Seine si l'on tient compte d'une fraction échangeable en mercure très faible et de paramètres de complexation minimums ; les calculs thermodynamiques suggèrent aussi qu'un ligand « dissous » fort ou présent à de fortes concentrations doit être présent dans l'eau afin d'entrer en compétition avec la formation de chlorocomplexes et expliquer nos mesures.

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/2001/these-1842.pdf
http://archimer.ifremer.fr/doc/00000/1842/