Trace metal chemical speciation and acute toxicity to Pacific oyster larvae

Access to the full-text thesis is no longer available at the author's request, due to 3rd party copyright restrictions. Access removed on 28.11.2016 by CS (TIS).Metadata merged with duplicate record (http://hdl.handle.net/10026.1/2252) on 20.12.2016 by CS (TIS).Controlled laboratory studies showed that the toxicity induced by biologically relevant trace metal species of Cu, Cd, Pb and Zn on embryo-larval development occurred at concentrations in excess of those found in the natural environinent, except for Cu in metal perturbed areas. Average free ion concentrations inducing 50% abnormal development( EC50feew) ere determineda s 0.23 nM CU2+8, 8.0 rim Cd2+,1 28 nM Zn2+a nd 3 62 nM Pb 2+ . However, the response to some binary metal combinations indicated enhanced (synergy) toxicity at concentrations relevant for estuarine waters (e. g. EC5of'. for Cu2+i n the presenceo f C(ý: +, Zn2+a nd Pb2 +w as 0.004,0.02 and 0.04 nM, respectively). A comparison of voltarnmetric instrumentation (voltammetric in situ profiling (VIP) system versus Hanging Mercury Drop Electrode with potentiostat) highlighted the advantage of high resolution measurements (ca. 20-60 min intervals) for environmental studies and the minimisation of artefacts associated with discrete sampling methodologies. Field-based studies were carried out in two contrasting estuaries in SW England, one heavily impacted with metal contaminants (Fal Estuary) and another subject to greater variety of anthropogenic influences (Tamar Estuary). High resolution in situ trace metal speciationm easurementsc, arried out over tidal cycles, identified important information on the temporal and spatial distributions of biologically relevant dynamic (<4 nm) metal species of Cd, Pb and Cu. Variation in embryo-larval responses to discrete samples from these estuaries, effectively paralleled the metal speciation measurements showing enhanced toxicity when the marine water influence was at its lowest. In both systems, the results indicated that the combined effect of the metals studied was likely to have provided a significant contribution to the bioassay response. However, the difficulty in de-coupling the speciation measurements with biological responses was evident and supports the need for more comprehensive campaigns to study the impact of contaminants on ecosystem functioning. Bioassay and metal speciation analysis techniques were complementary, exhibiting high sensitivity and rapid responses, and would be considered effective screening tools for waters subject to intermittent inputs of metal contaminants and areas with recognised pressures. The integrated approach has extended our knowledge of trace metal speciation in estuarine environments and their effects on the developing embryos of the Pacific oyster. This approach has the potential for wider application

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Metal speciation and toxicity of Tamar Estuary water to larvae of the Pacific oyster, Crassostrea gigas

As part of the PREDICT Tamar Workshop, the toxicity of estuarine waters in the Tamar Estuary (southwest England) was assessed by integration of metal speciation determination with bioassays. High temporal resolution metal speciation analysis was undertaken in situ by deployment of a Voltammetric In situ Profiling (VIP) system. The VIP detects Cd (cadmium), Pb (lead) and Cu (copper) species smaller than 4 nm in size and this fraction is termed ‘dynamic’ and considered biologically available. Cadmium was mainly present in the dynamic form and constituted between 56% and 100% of the total dissolved concentration, which was determined subsequently in the laboratory in filtered discrete samples. In contrast, the dynamic Pb and Cu fractions were less important, with a much larger proportion of these metals associated with organic ligands and/or colloids (45–90% Pb and 46–85% Cu), which probably reduced the toxicological impact of these elements in this system. Static toxicity tests, based on the response of Crassostrea gigas larva exposed to discrete water samples showed a high level of toxicity (up to 100% abnormal development) at two stations in the Tamar, particularly during periods of the tidal cycle when the influence of more pristine coastal water was at its lowest. Competitive ligand-exchange Cu titrations showed that natural organic ligands reduced the free cupric ion concentration to levels that were unlikely to have been the sole cause of the observed toxicity. Nonetheless, it is probable that the combined effect of the metals determined in this work contributed significantly to the bioassay response

Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women

Background: The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors. Methods and Results: We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02-1.24; P=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00-1.23; P=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at P≤0.05. Conclusions: Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms

Characteristics of the sample by severity of coronary artery stenoses.

<p>Characteristics of the sample by severity of coronary artery stenoses.</p