Search

International audience; The ceasing of industrial activities often reduces the emission of pollutants but also often leaves disturbed areas without remediation and with persistent pollutants that can still be transferred along the food chain. This study examines the potential relationships between non-essential trace metals and histopathology in target tissues of wood mice (Apodemus sylvaticus) collected along a gradient of contamination around the former smelter, Metaleurop Nord (northern France). Cadmium and lead concentrations were measured, and histological alterations attributable to chronic trace metal exposure were assessed in the liver and the kidneys of 78 individuals. Metal concentrations quantified in the present study were among the highest observed for this species. Some histological alterations significantly increased with Cd or Pb concentrations in the soil and in the organs. Sixteen mice from polluted sites were considered at risk for metal-induced stress because their Cd and/or Pb tissue concentrations exceeded the LOAELs for single exposure to these elements. These mice also exhibited a higher severity of histological alterations in their organs than individuals with lower metal burdens. These results indicate that the Metaleurop smelter, despite its closure in 2003, still represents a threat to the local ecosystem because of the high levels and high bioavailability of Cd and Pb in the soil. However, among the mice not considered at risk for metal-induced stress based on the metal levels in their tissues, a large percentage of individuals still exhibited histological alterations. Thus, the present study suggests that the evaluation of toxic effects based only on the LOAELs for single metal exposure may result in the underestimation of the real risks when specimens are exposed to multiple stressors.

9 pages; International audience; Despite the dramatic decrease of atmospheric lead (Pb) concentrations in urban areas of most industrialised countries, we hypothesised that urban common blackbirds (Turdus merula) may still be contaminated by Pb concentrations of toxicological concern due to transfer from soil through the food chain. We sampled blackbirds and earthworms, one of their main preys, in Besan?, a middle-size city of Eastern France (where atmospheric Pb concentrations decreased from 0.5 microg/m(3) in 1987 to nearly 0 in 2002) and in a rural reference site. Lead concentrations were determined in the tissues of the different functional groups of earthworms (anecic, epigeous and endogeous) and in blood, washed and unwashed outermost tail feathers and breast feathers of blackbirds. Fresh masses and an index of individual body condition were measured in the two blackbird populations as biomarkers of possible toxic effects. Lead concentrations in earthworms did not differ among functional groups but were significantly higher in urban individuals than in rural ones. Concentrations in outermost tail feathers, breast feathers and blood were significantly higher in urban blackbirds (7.75+/-4.50, 3.15+/-1.77 and 0.15+/-0.09 microg/g, respectively) than in rural individuals. In urban blackbirds, concentrations in washed and unwashed outermost tail feathers allowed estimating the external contamination (probably due to deposition of dusts and/or to excretion of the uropygial gland) at 37% of the total Pb concentration of the unwashed feathers. Remaining 63% should be linked to food chain transfer of persistent Pb from urban soils. Among the 23 sampled blackbirds, 4 of them (3 in the urban site and 1 in the rural site) exhibited blood Pb concentrations higher than the benchmark value (0.20 microg/g) related to subclinical and physiological effects in birds. Variations in body condition index were not correlated to Pb concentrations in blackbird tissues. Present results suggest that Pb may still be of environmental concern for blackbirds in urban areas because of the persistence of Pb in soils and its transfer through the food chain.

International audience; Lead in homes is a well-known source of childhood lead exposure, which is still of concern due to the health effects of low lead doses. This study aims to describe lead contamination in the homes of children aged 6 months to 6 years in France (without overseas). Between October 2008 and August 2009, 484 housing units were investigated. Lead in tap water and total and leachable lead levels from floor dust, outdoor soils and paint chips were measured. X-ray fluorescence measurements were carried out on non-metallic and metallic substrates. Nationwide results are provided. The indoor floor dust lead (PbD) geometric mean (GM) was 8.8 μg/m² (0.8 μg/ft²) and 6.8 μg/m² (0.6 μg/ft²) for total and leachable lead respectively; 0.21% of homes had an indoor PbD loading above 430.5 μg/m² (40 μg/ft²). The outdoor play area concentration GM was 33.5 mg/kg and 21.7 mg/kg in total and leachable lead respectively; 1.4% of concentrations were higher than or equal to 400 mg/kg. Outdoor floor PbD GM was 44.4 μg/m² (4.1 μg/ft²) that was approximately 3.2 times higher than the GM of indoor PbD. Lead-based paint (LBP) was present in 25% of dwellings, LBP on only non-metallic substrates was present in 19% of homes and on metallic substrates in 10% of dwellings. The GM of lead concentrations in tap water was below 1 μg/L; 58% of concentrations were lower than 1 μg/L and 2.9% were higher than or equal to 10 μg/L. The age cut-off for homes with lead would be 1974 for paint and 1993 for indoor floor dust. This study provides, for the first time, a look at the state of lead contamination to which children are exposed in French housing. Moreover, it provides policy makers an estimate of the number of French dwellings sheltering children where abatement should be conducted.

Background Lead exposure remains a public health concern due to its serious adverse effects, such as cognitive and behavioral impairment: children younger than six years of age being the most vulnerable population. In Europe, the lead-related economic impacts have not been examined in detail. We estimate the annual costs in France due to childhood exposure and, through a cost benefit analysis (CBA), aim to assess the expected social and economic benefits of exposure abatement. Methods Monetary benefits were assessed in terms of avoided national costs. We used results from a 2008 survey on blood-lead (B-Pb) concentrations in French children aged one to six years old. Given the absence of a threshold concentration being established, we performed a sensitivity analysis assuming different hypothetical threshold values for toxicity above 15 μg/L, 24 μg/L and 100 μg/L. Adverse health outcomes of lead exposure were translated into social burden and economic costs based on literature data from literature. Direct health benefits, social benefits and intangible avoided costs were included. Costs of pollutant exposure control were partially estimated in regard to homes lead-based paint decontamination, investments aiming at reducing industrial lead emissions and removal of all lead drinking water pipes. Results The following overall annual benefits for the three hypothetical thresholds values in 2008 are: €22.72 billion, €10.72 billion and €0.44 billion, respectively. Costs from abatement ranged from €0.9 billion to 2.95 billion/year. Finally, from a partial CBA of lead control in soils and dust the estimates of total net benefits were € 3.78 billion, € 1.88 billion and €0.25 billion respectively for the three hypothesized B-Pb effect values. Conclusions Prevention of childhood lead exposure has a high social benefit, due to reduction of B-Pb concentrations to levels below 15 μg/L or 24 μg/L, respectively. Reducing only exposures above 100 μg/L B-Pb has little economic impact due to the small number of children who now exhibit such high exposure levels. Prudent public policies would help avoiding future medical interventions, limit the need for special education and increase future productivity, and hence lifetime income for children exposed to lead.

International audience; BACKGROUND: Environmental prenatal exposure to potentially neurotoxic metals poses a particular challenge with regard to the study of early toxic effects. Monoamine oxidase activity, shown to be influenced by metals in experimental studies, could be a useful biomarker in humans. OBJECTIVE: To examine the relationship between blood metal concentrations at delivery and placenta MAO activity. METHODS: The study was performed in 163 pregnancies. Maternal and cord blood samples were obtained for manganese (Mn), lead (Pb), and cadmium (Cd) determination. Mercury (Hg) was also analysed in maternal hair. Placental samples were stored immediately after expulsion and total MAO activity was measured. RESULTS: MAO activity was significantly positively correlated with maternal and cord blood Mn concentrations in subjects with high MAO activity. In subjects with low MAO activity, maternal hair Hg was negatively correlated with MAO. CONCLUSION: Our results suggest the use of placental MAO as a potential surrogate marker of Mn toxicity in the newborn and its correlation with psychomotor development should be further investigated.

International audience; Enzymatic probing and lead(II)-induced cleavages have been developed to study the secondary structure of RNA molecules either free or engaged in complex with different ligands. Using a combination of probes with different specificities (unpaired vs. paired regions), it is possible to get information on the accessibility of each nucleotide, on the binding site of a ligand (noncoding RNAs, protein, metabolites), and on RNA conformational changes that accompanied ligand binding or environmental conditions (temperature, pH, ions, etc.). The detection of the cleavages can be conducted by two different ways, which are chosen according to the length of the studied RNA. The first method uses end-labeled RNA molecules and the second one involves primer extension by reverse transcriptase. We provide here an experimental procedure that was designed to map the structure of mRNA and mRNA-sRNA interaction in vitro.

International audience; To understand bioaccumulation kinetics of metals within biota inhabiting industrially contaminated soils, toxicokinetic dynamics and subcellular fractionation were carried out with the terrestrial snail Helix aspersa in a long-term (six-month) laboratory experiment. Accumulation and elimination kinetics were determined for Cd, Pb, and Zn in both viscera and foot of snails and were described accurately by one-compartment models. The subcellular fractions were obtained by sequential centrifugations and were analyzed by isolating metal-rich granules, tissue fragments, and cytosolic fractions. Different fractions showed metal-specific binding capacities that might be useful in identifying the biological significance of accumulated metal levels in snails. Cadmium was retrieved mainly from the cytosolic fraction, where it was stored in the long term and not excreted, thus explaining the linear accumulation patterns. Most of the accumulated Pb was found in the granular fraction, and snails appeared able to excrete these concretions, leading to achievement of a steady state in internal Pb body burdens. Significant levels of Pb, however, were retrieved at the end of the depuration phase and retained in the cell debris fraction. Zinc showed affinities for both cytosolic and granular fractions, leading to intermediate uptake and excretion patterns. The dynamics of the different sequestration forms at the subcellular level support the observed kinetics of metal body burdens and, in association with the determination of uptake fluxes, allow precise assessment of metal accumulation in snails.

Objectives: Emissions of lead into the environment (and thus its environmental concentrations) have decreased in recent years. We sought to estimate the overall lead exposure of children aged 6 months to 6 years (the population group most exposed and most sensitive to lead) in France through the various media (air, food, water, soils, and dust) and the respective contributions of each medium to the total dose. We have focused on the general population, leaving aside specific risk factors such as deteriorated lead paints. Methods: We used the most recent French intake data for food and water, and a daily ingested quantity selected from the literature for soils and dust. Contamination data came from the first total diet study of contaminant levels in France (2000–2001), from regulatory testing of tap water (2004), a literature review of lead in urban soils, and a pilot study (2005) of lead in dust. Air quality monitoring measurements showed that the contribution of air could now be safely ignored. Weekly exposure doses were estimated with Monte Carlo simulations. Results: Median weekly exposure dose was 7.5 μg/kg bw.week for children aged 6 months to 3 years and 4.7 for those aged from 3–6 years. 95th percentiles were 13.5 and 8.7 μg/kg bw.week. Exposure came mainly from food. The principal uncertainties are associated with quantification limits in food and water, representativeness and traceability of tap water samples, and absence of recent data about urban soil contamination. Conclusions: These results differ quite notably from earlier estimates and highlight the need, especially for policy-making purposes, to update exposure measurements for this metal. Keywords: Environmental exposure, Environmental health, Exposure assessment, Probabilistic exposure assessment, Lead

International audience; Despite a considerable amount of data, evaluation of the potential genotoxicity and cancer proneness of lead compounds remains unclear, probably due to the plethora of experimental procedures, biological endpoints and cellular models used. In parallel, the understanding in DNA damage formation, repair and signaling has considerably progressed all along these last years, notably for DNA double-strand breaks (DSBs). Here, were examined DNA damage formation and repair in human cells exposed to lead nitrate (Pb(NO(3))(2)) and their consequences upon the ATM-dependent stress signaling, cell cycle progression and cell death. As observed with anti-pH2AX immunofluorescence, exposure to Pb(NO(3))(2) results in formation of late DSBs, that would not originate from conversion of nucleotide damage but likely by a direct production of single-strand breaks. Lead contamination inhibits non-homologous end-joining repair process by preventing the DNA-PK kinase activity whereas the MRE11-dependent repair pathway is exacerbated. Lead contamination triggers successive synchronization of cells in G2/M phase in which the RAD51-dependent homologous recombination was found to be activated. Altogether, our findings support that lead contamination generates late unrepairable DSBs that impact upon the ATM-dependent stress signaling pathway by favoring propagation of errors. Such findings should help to consider more carefully the biological action of lead compounds in the frame of public and occupational exposures.

International audience; BACKGROUND: Living around industrial sites may expose young children to lead and cause elevated blood lead levels (BLLs). Systematic screening for childhood lead poisoning is necessarily invasive but may be appropriate, depending on children's exposure levels. Our objective was to assess the performance of several decision support tools for determining the need for systematic BLL screening in children around industrial sites. METHOD: We used several exposure models to predict BLLs: the pharmacokinetic model IEUBK, the InVS dose model, and an empirical relation (Lewin, 1999) between soil concentrations and BLLs. We tested the BLLs (percentage of children with a BLL >100 micro g/l) that they predicted as well as threshold levels of soil pollution (200, 400, 500 ppm) for 71 situations for which the literature reports both environmental soil concentrations and BLLs in children aged 0-6 years. The tools' performance (sensitivity and specificity) was assessed by the rate of 'correct' (mass screening or not) decisions, judged retrospectively on the basis of measured BLLs, for different tolerated percentages of children with elevated BLLs. RESULTS: Decision support systems based on soil pollution levels were not adequately protective. The IEUBK and (updated) InVS mechanistic exposure models were the most effective in this setting. CONCLUSION: Exposure models may provide decision support if sufficient data about environmental contamination and dietary intake are available. Absolute performance measurement nonetheless remains difficult, in view of the limitations of the input data.

International audience; BACKGROUND: Children exposure to lead, even at low doses, can induce neurobehavioral and cognitive effects. In France, a consensus conference about lead poisoning in children has recently stated that exposure near an industrial site was a priority for blood lead screening. Selection criteria for industrial sites have therefore to be defined, especially because screening for lead poisoning requires a blood lead sample, that is an invasive procedure. METHODS: We propose here an operational procedure to select sites where systematic blood lead screenings have to be implemented. It is based on modeling blood lead levels of children aged 1-6 years. This is made by indirect dose estimation from environmental measurements, human exposure parameters and a dose/blood lead level relationship. Decision criteria are based on mean and extreme predicted blood lead level. The procedure is illustrated with a real life smelter case study. RESULTS: For the studied smelter, estimated blood lead levels are less than 100 microg(Pb)/l(blood) and therefore do not lead to recommend a systematic blood lead screening. CONCLUSIONS: Indirect dose estimation associated with blood lead level modeling is a useful tool for selecting where blood lead screenings have to be implemented around industrial sites. Possible improvements of the method are listed.

International audience; Exposure to lead is a special problem in children, because they are more highly exposed than adults and because this pollutant, which accumulates in the body, induces neurobehavioral and cognitive effects. The objective of this study was to determine the probability density of the lead exposure dose of a 2-year-old child around an old mine site and to analyze its uncertainties, especially those associated with the bioavailability of lead in soil. Children's exposure was estimated indirectly from environmental samples (soils, domestic dust, water, air) and parameters (volume inhaled, body weight, soil intake rate, water intake, dietary intake) from the literature. Uncertainty and variability were analyzed separately in a two-dimensional Monte Carlo simulation with Crystal Ball software. Exposure doses were simulated with different methods for accessing the bioavailability of lead in soil. The exposure dose per kilogram of body weight varied from 2 microg/kgday at the 5th percentile to 5.5 microg/kgday at the 95th percentile (and from 2 to 10 microg/kgday, respectively, when ignoring bioavailability). The principal factors of variation were dietary intake, soil concentrations, and soil ingestion. The principal uncertainties were associated with the level of soil ingestion and the bioavailability of lead. Reducing uncertainty about the bioavailability of lead in soil by taking into account information about the type of mineral made it possible to increase our degree of confidence (from 25% to more than 95%) that the median exposure dose does not exceed the Tolerable Daily Intake. Knowledge of the mineral very substantially increases the degree of confidence in estimates of children's lead exposure around an old mining site by reducing the uncertainty associated with lead's bioavailability.

Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5′ terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5′-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.

Following boron intake, multiple effects have been observed in animal experiments. However, human data is lacking, and no data is available on the ability of boron to accumulate in fetal tissues. Positive responses in animal species suggest that developmental toxicity may be an area of concern in humans, following exposure to boron. Two hypotheses have seemed to account for the multiple effects described in scientific findings. One hypothesis is that boron is a negative regulator that influences a number of metabolic pathways by competitively inhibiting some key enzyme reactions. The other hypothesis is that boron has a role in ionic membrane transport regulations. To better understand boron potential toxicity, the present study examined the relationship between boron exposure and some key enzymes, well-known for their affinity for mineral elements, such as delta-aminolevulinic acid dehydratase (ALA-D), and two fundamental enzymes having a role in ionic membrane transport regulations (Ca-pump and Na(+)K(+)-ATPase). We investigated the potential effects of an environmental boron exposure on the activity of these enzymes in an urban population of 197 "normal" newborns. Environmental boron exposure was assessed in placental tissue. Because of the well-known inhibiting effect of lead on these enzymes, cord blood and placental lead were also analyzed. After adjustment for potential confounders, including lead, placental boron levels were negatively significantly correlated to ALA-D activity while Ca-pump and Na(+)K(+)-ATPase activities did not seem to be affected by the level of boron exposure. Given boron's ability, as a Lewis acid, to complex with hydroxyl groups, we suggest that such a mechanism would explain the inhibiting effect of boron on ALA-D.

International audience; BACKGROUND: Lead exposure and total immunoglobulin E (IgE) have been shown to be positively related in animals and humans even at lead levels below those recognized as toxic. In the last decades, exposure to lead has become more frequent in urban areas of industrialized as well as of developing countries where IgE-mediated allergy prevalence has also increased. METHODS: We examined for the first time the relationship between in utero exposure to lead and cord blood total IgE in two samples of 137 and 237 mother-newborn pairs, respectively, recruited in Paris. RESULTS: Cord blood IgE was positively related to hair lead level at birth, providing an integrated measure of long-term exposure in utero, in each cohort (Spearman's coefficient r = 0.32, P < 0.001 and r = 0.19, P < 0.01, respectively) and in the combined cohort (r = 0.21; P < 0.01). The relationship appeared to be more pronounced in newborns of nonallergic mothers (r = 0.24; P < 0.01) than in those of allergic mothers (r = 0.12). This could be due to the fact that familial history of allergy, the strongest determinant of IgE development, may overshadow the influence of lead on IgE in the offspring. CONCLUSIONS: Our findings suggest a possible intervention of environmental exposure besides genetic factors in early life development of IgE production. Further studies are needed to confirm the finding.

International audience; Juvenile Helix aspersa snails exposed in field microcosms were used to assess the transfer of Cd, Cu, Ni, Pb and Zn from forest soils amended with liquid and composted sewage sludge. Zn concentrations and contents were significantly higher in snails exposed to liquid and composted sludge after 5 and 7 weeks of exposure, when compared with control. Trends were less clear for the other metals. Present results show that Zn, among the cocktail of metallic trace elements (MTE) coming from sewage sludge disposal, represents the principal concern for food chain transfer and secondary poisoning risks. The microcosm design used in this experiment was well suited for relatively long-term (about 2 months) active biomonitoring with H. aspersa snails. The snails quickly indicated the variations of MTE concentrations in their immediate environment. Therefore, the present study provides a simple but efficient field tool to evaluate MTE bioavailability and transfer.

International audience; Metal concentrations measured in the organs of beached whales are published regularly. Few of these, however, describe metal levels in nursing females. In the present study, mercury, lead, copper and zinc levels were measured in the milk and tissues of a female Bottlenose dolphin. Results reveal that metal pollutants pass from the tissue into the milk.

International audience; The cadmium, lead, copper, and zinc levels were measured in six organs (lung, liver, kidney, skin, muscle, and bone) from 18 specimens of toothed whales, belonging to five species, found stranded along the Corsican coast between November 1993 and December 1998. The five species examined were the bottlenose dolphin Tursiops truncatus, the common dolphin Delphinus delphis, the striped dolphin Stenella coeruleoalba, the pilot whale Globicephala melas, and the Risso's dolphin Grampus griseus. The values obtained demonstrate that there is a great variability in the accumulation of toxic metals. A comparison of the values with those obtained in other geographical regions also demonstrates an extensive variability in metal levels. The presence of metals in the stomach contents of three of the individuals studied shows that the food source is responsible for a significant input of pollutants to the whales. Measured pollutant levels in whales are thus the result of an accumulation occurring throughout the animal's life.