Tissue-specific distribution and maternal transfer of polybrominated diphenyl ethers (PBDEs) and their metabolites in adult common sole (Solea solea L.) over an entire reproduction cycle.

Tissue-specific accumulation and distribution of polybrominated diphenyl ethers (PBDEs) and their debrominated metabolites were studied in common sole (Solea solea) over an entire reproduction cycle. The fish were dietary-exposed to selected PBDEs in laboratory-controlled conditions for one year. Fish of both sexes were sampled throughout the reproduction cycle and their muscle, liver, viscera, carcass, skin and gonads (female) were analysed for total lipid content, PBDEs and their debrominated metabolites. On a wet weight basis, the concentrations of most spiked congeners showed an increase at the end of the exposure time in the whole body of fish of both sexes. Conversely, BDE-99 and BDE-209 - the two most highly metabolized congeners - did not show a similar increase, while their debrominated metabolites exhibited a linear increase over time. Biomagnification factors (BMFs) calculated in whole body were > 1 for all PBDEs except BDE-99 (0.89 ± 0.22) and BDE-209 (0.013 ± 0.006). BMFs were strongly correlated to apparent assimilation efficiencies, which ranged from 1.6% ± 0.7% (BDE-209) to 88% ± 11% (BDE-100). Fish carcass was the most predominant storage compartment for all PBDEs except BDE-209 in both male and female fish, followed by skin, muscle, female gonads, liver and visceral tissue. BDE-209 showed a different distribution and was stored more predominantly in the liver, viscera and female gonads than other congeners, probably due to its transport with lipoproteins. All PBDEs except BDE-209 showed equilibrium partitioning between the liver and other studied compartments, while BDE-209 showed a higher affinity with blood-enriched tissues, leading to higher liver / carcass, skin and muscle concentration ratios. Visceral tissue and liver exhibited the most pronounced differences in terms of concentration variations between sexes and over time. In females, both tissues showed a significant decrease in most PBDE concentrations (ww) and TLC in March during the spawning season, with low inter-individual variability, reflecting the striking utilisation of lipids by females for reproduction at this time. In males, no differences were found in concentrations in these compartments over time and a high inter-individual variability was observed. Maternal transfer of PBDEs from gonad to eggs was constant, regardless of spawn rank in the spawning season. Egg / gonad PBDE concentration ratios (in lw) were 1.3 ± 0.7 for all congeners and 2.6 ± 0.3 for BDE-209, suggesting a higher transfer of this congener from gonads to eggs.

Safety results from OCAPI: a European Observational Cohort Study of insulin glulisine-treated children aged 6-12 years with type 1 diabetes.

OBJECTIVE: Data on the safety of insulin glulisine for type 1 diabetes are limited in paediatric populations. The European post-marketing Observational prospective Cohort study of children with type 1 diabetes treated with APIDRA(®) (OCAPI) study evaluated the safety of insulin glulisine in children aged 6-12 years in real-life clinical practice, with a particular focus on the 6-8 years age group. RESEARCH DESIGN AND METHODS: OCAPI was an international, multicentre, observational, non-interventional, prospective cohort study, in which 94 participants with type 1 diabetes (6-8 years age group: n=31; 9-12 years age group: n=63) received insulin glulisine for 6 months under normal, local conditions. The primary objective was the incidence of severe hypoglycaemia in all participants. RESULTS: Overall incidence of severe hypoglycaemia was 6.6 events per 100 persons/year (7.2 and 6.3 events per 100 persons/year in the 6-8 and 9-12 years age groups, respectively). 12 participants (all aged 9-12 years) experienced transient injection-site reactions. No systematic hypersensitivity reactions were reported. Only 1 participant (9-12 years age group) experienced a serious class-effect risk possibly related to insulin glulisine (severe hypoglycaemia requiring an Emergency Department visit). Glycated haemoglobin levels did not change markedly throughout the study, and were inversely proportional to the risk of hypoglycaemia. CONCLUSIONS: Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions. These results are encouraging for its use in paediatric populations.

PCBs contamination does not alter aerobic metabolism and tolerance to hypoxia of juvenile sole (Solea solea L. 1758).

Coastal habitats play a major role as nurseries for many fish species; however, they are also submitted to pollutants and oxygen fluctuations. Fry's concept of metabolic scope for activity was used to evaluate the effect of polychlorinated biphenyls (PCBs) on the aerobic metabolism in juvenile common sole (0-1 year old). Aerobic metabolic scope (AMS) in control and PCB-contaminated fish via food pathway was determined using respirometry techniques. Furthermore, the hypoxia tolerance in control and PCB-contaminated fish was evaluated by assessing their critical oxygen concentration (O(2crit)). Our results showed that while PCB-contaminated fish were able to maintain a constant AMS and O(2crit), PCBs tend to affect their aerobic metabolism by acting on maximal oxygen consumption (MO(2max)) in hypoxia and standard metabolic rate, but only at the highest PCB concentration between 30 and 60 days of exposure. In conclusion, we can hypothetise that the tested PCB-exposures may not impair the tolerance to hypoxia and the survival of common sole in their natural environment.

Influences of bioavailability, trophic position, and growth on methylmercury in hakes (Merluccius merluccius) from Northwestern Mediterranean and Northeastern Atlantic.

Methylmercury (MeHg) determinations in hake, its food-chain, and the surrounding waters and sediments allowed us to show that the higher length or age normalized mercury concentrations of Northwestern Mediterranean (Gulf of Lions: GoL) muscle hakes compared to its Northeastern Atlantic (Bay of Biscay: BoB) counterpart are due to both biotic and abiotic differences between their ecosystems. Bioenergetic modeling reveals that the slower growth rate of Mediterranean hake favors the MeHg bioaccumulation in the fish muscle and explains most of the difference between GOL and BoB hake populations. In addition, the waters of the Mediterranean hake habitat favor a higher MeHg exposition, due to the upper position of the thermohalocline, where MeHg is formed. Furthermore, we show that, within the Mediterranean hake population, a major increase in the biomagnification power (the slope of the relationships between logMeHg and δ(15)N), from 0.36 up to 1.12, occurs when individuals enter adulthood, resulting from the combined effects of lowering growth rate and change in feeding habits. Finally, δ(15)N normalized Hg concentrations indicate that the highest Hg concentrations are for hake from the shelf edge and the lowest are for hake from the Rhône prodelta area, suggesting a lower Hg bioavailability in inshore environments, consistent with MeHg distributions in water, sediment, and preys.

Relationship between PAH biotransformation as measured by biliary metabolites and EROD activity, and genotoxicity in juveniles of sole (Solea solea).

Polycylic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in the marine environment. Their toxicity is mainly linked to the ability of marine species to biotransform them into reactive metabolites. PAHs are thus often detected at trace levels in animal tissues. For biomonitoring purposes, this findings have two main consequences, (i) the determination of the PAH tissue concentration is not suitable for the evaluation of individual exposure to PAHs (ii) it can explain sometimes the lack of correlations obtained with relevant markers of toxicity such as genotoxicity biomarkers. The aim of the present study was to better investigate the link between PAH exposure and genotoxicity in marine flatfish. During a laboratory experiment, juvenile soles were exposed for four weeks to a mixture of three PAHs, namely benzo[a]pyrene, fluoranthene and pyrene, followed by one week of depuration. Fish were exposed via the trophic route to a daily PAH concentration of 120 µg/g food. Fish were sampled at different time points. The bioavailability and the biotransformation of PAHs were assessed by the measurement of biliary metabolites using a sensitive UPLC MS/MS method. The 7-ethoxyresorufine-O-deethylase was also measured in liver subcellular fractions as a biomarker of phase I biotransformation activities. Genotoxicity was assessed in parallel by the measurement of DNA strand breaks in fish erythrocytes by the alkaline comet assay. During this study, the high amount of PAH metabolites produced in sole demonstrated the bioavailability of PAHs and their biotransformation by fish enzymes. A positive correlation was observed between the level of hydroxylated PAH metabolites and genotoxicity as measured by the alkaline comet assay.

Congener-specific accumulation and trophic transfer of polychlorinated biphenyls in spider crab food webs revealed by stable isotope analysis.

Polychlorobiphenyls (PCB) and stable isotopes (delta15N and delta13C) were analyzed in the spider crab (Maja brachydactyla) food web from the Iroise Sea (Western Brittany) and the Seine Bay (Eastern English Channel). PCB concentrations were all significantly higher in organisms from the Seine Bay than those from the Iroise Sea. PCB patterns were strongly related to the feeding mode of the species, and increased influence of higher chlorinated congeners was highlighted with trophic position of the organisms. PCB concentrations (lipid normalized) were significantly related to the isotopically derived trophic level (TL) in spider crab food webs. The highest trophic magnification factors (TMFs) were calculated for the congeners with 2,4,5-substitution, and were lower in the Seine Bay compared to the Iroise Sea. The confrontation of PCB and TL data also revealed biotransformation capacity of decapod crustaceans for specific congeners based on structure-activity relations.

PCB, PCDD/F and PBDE levels and profiles in crustaceans from the coastal waters of Brittany and Normandy (France).

Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analysed in the muscle of various edible marine crustaceans (spider crab, edible crab, velvet swimming crab and Norway lobster) from the Brittany and Normandy coasts (France). The highest concentrations were measured in species collected from Antifer (Seine Bay). PCB and PBDE patterns in crustacean muscles were similar and independent of the geographical area with the predominance of the high chlorinated PCBs (CB153, 138, 118 and 180), and of a few PBDE congeners (BDE47, BDE99, BDE100 and BDE28). Oppositely, dioxin contamination differed with site. The major component in crustaceans from the Seine Bay was 2378-TCDF, whereas specimens from cleaner areas had higher relative concentrations of OCDD. Finally, the comparison of the spider crab contaminant profiles to those measured in mussel and sea bass highlighted two different trends: decapod crustaceans possess relatively strong capacity to metabolise PCBs and PBDEs; however these species might be used as bioindicators for dioxin pollution monitoring in the marine coastal environment.

Organochlorinated contaminants in decapod crustaceans from the coasts of Brittany and Normandy (France).

The contamination and distribution of organochlorinated compounds were considered in three crustacean species (edible crab, Cancer pagurus; spider crab, Maja brachydactyla; velvet swimming crab, Necora puber) from five sites along the coasts of Brittany and Normandy (Western and North-Western France). PCBs (16 single congeners), pp'-DDE and HCB were measured in hepatopancreas, gonads and muscle: in all, 175 samples were analysed. The spider crab was the only species found in the five sampling sites, thus enabling comparison between areas. Specimens from Antifer were much more contaminated (summation operator 16 PCBs in hepatopancreas=2000-4000 ng g(-1) dry weight) than those from other sites (50-1000 ng g(-1) d.w.). Among all the three species, the spider crab appeared more contaminated by PCBs than the edible crab, by a factor 2-3, probably in relation with specific differences in their life cycle. There was no difference due to the gender of the species. Within the different analysed tissues, contamination levels increased from muscle to gonads and hepatopancreas in relation with the fat content. A very similar PCB composition was observed in all samples, PCB fingerprints being characterised by the relative importance of the more persistent PCB congeners: CB153, 138, 180, 187, and 118. Finally, these results were compared to recent food regulations first of maximum marker PCB intake and secondly of maximum dioxin-like PCB intake. By considering the muscle, all samples were far below the regulatory limits; for hepatopancreas and gonads, however, some samples were unfit for human consumption.

A model of PCB bioaccumulation in the sea bass food web from the Seine Estuary (eastern English Channel).

A bioaccumulation model was developed to simulate the PCB contamination in the sea bass food web from the Seine Estuary. The model relies upon a contaminant mass balance budget for each biological species. Biological processes determine the extent of bioaccumulation: respiration and feeding rates control the uptake of contaminants whereas excretion, spawning, and growth act on the chemicals removal. A step-by-step modelling approach was followed. A first version was a steady-state model validated for the bioaccumulation processes. In the second version seasonal variation was taken into account, and finally in the third version, the model was coupled with a population dynamics model to describe PCB contamination in each age class.

Validation of an analytical procedure for polychlorinated biphenyls, coplanar polychlorinated biphenyls and polycyclic aromatic hydrocarbons in environmental samples.

This work describes an efficient analytical procedure for the analysis of PCBs (polychlorinated biphenyls), coplanar PCBs and PAHs (polycyclic aromatic hydrocarbons) from the same sample. The method includes a solvent extraction followed by a combined purification-separation step on an alumina-silica column. Coplanar PCBs are isolated from the first fraction (PCBs) by a further high-performance liquid chromatography (HPLC) fractionation on a PYE [2-(1-pyrenyl)ethyldimethylsilylated silica gel] column. PCBs are identified and quantified by gas chromatography (GC) with electron-capture detection whereas GC with flame ionization detection or mass spectrometry are used for PAH determinations. This method allows the measurement of these contaminants in biota and sediment at trace levels as low as 1 pg g(-1) for coplanar PCBs with a precision better than 20%.