Inclusion of seasonal variation in river system microbial communities and phototroph activity increases environmental relevance of laboratory chemical persistence tests

Regulatory tests assess crop protection product environmental fate and toxicity before approval for commercial use. Although globally applied laboratory tests can assess biodegradation, they lack environmental complexity. Microbial communities are subject to temporal and spatial variation, but there is little consideration of these microbial dynamics in the laboratory. Here, we investigated seasonal variation in the microbial composition of water and sediment from a UK river across a two-year time course and determined its effect on the outcome of water-sediment (OECD 308) and water-only (OECD 309) biodegradation tests, using the fungicide isopyrazam. These OECD tests are performed under dark conditions, so test systems incubated under non-UV light:dark cycles were also included to determine the impact on both inoculum characteristics and biodegradation. Isopyrazam degradation was faster when incubated under non-UV light at all collection times in water-sediment microcosms, suggesting that phototrophic communities can metabolise isopyrazam throughout the year. Degradation rate varied seasonally between inoculum collection times only in microcosms incubated in the light, but isopyrazam mineralisation to 14CO2 varied seasonally under both light and dark conditions, suggesting that heterotrophic communities may also play a role in degradation. Bacterial and phototroph communities varied across time, but there was no clear link between water or sediment microbial composition and variation in degradation rate. During the test period, inoculum microbial community composition changed, particularly in non-UV light incubated microcosms. Overall, we show that regulatory test outcome is not influenced by temporal variation in microbial community structure; however, biodegradation rates from higher tier studies with improved environmental realism, e.g. through addition of non-UV light, may be more variable. These data suggest that standardised OECD tests can provide a conservative estimate of pesticide persistence end points and that additional tests including non-UV light could help bridge the gap between standard tests and field studies

Water flow plays a key role in determining chemical biodegradation in water-sediment systems

Before agrochemicals can be registered and sold, the chemical industry is required to perform regulatory tests to assess their environmental persistence, using defined guidelines. Aquatic fate tests (e.g. OECD 308) lack environmental realism as they are conducted under dark conditions and in small-scale static systems, which can affect microbial diversity and functionality. In this study, water-sediment microflumes were used to investigate the impact of these deficiencies in environmental realism on the fate of the fungicide, isopyrazam. Although on a large-scale, these systems aimed to retain the key aspects of OECD 308 tests. Tests were carried out under both a non-UV light-dark cycle and continuous darkness and under both static and flowing water conditions, to investigate how light and water flow affect isopyrazam biodegradation pathways. In static systems, light treatment played a significant role, with faster dissipation in illuminated compared to dark microflumes (DT50s = 20.6 vs. 47.7 days). In flowing systems (DT50s = 16.8 and 15.3 days), light did not play a significant role in dissipation, which was comparable between the two light treatments, and faster than in dark static microflumes. Microbial phototroph biomass was significantly reduced by water flow in the illuminated systems, thereby reducing their contribution to dissipation. Comprehensive analysis of bacterial and eukaryotic community composition identified treatment specific changes following incubation, with light promoting relative abundance of Cyanobacteria and eukaryotic algae, and flow increasing relative abundance of fungi. We conclude that both water velocity and non-UV light increased isopyrazam dissipation, but the contribution of light depended on the flow conditions. These differences may have resulted from impacts on microbial communities and via mixing processes, particularly hyporheic exchange. Inclusion of both light and flow in studies could improve the extent they mimic natural environments and predict chemical environmental persistence, thus bridging the gap between laboratory and field studies

Scientific concepts and methods for moving persistence assessments into the 21st century

34 páginas.- 2 figuras.- 3 tablas.- 225 referenciasThe evaluation of a chemical substance's persistence is key to understanding its environmental fate, exposure concentration, and, ultimately, environmental risk. Traditional biodegradation test methods were developed many years ago for soluble, nonvolatile, single-constituent test substances, which do not represent the wide range of manufactured chemical substances. In addition, the Organisation for Economic Co-operation and Development (OECD) screening and simulation test methods do not fully reflect the environmental conditions into which substances are released and, therefore, estimates of chemical degradation half-lives can be very uncertain and may misrepresent real environmental processes. In this paper, we address the challenges and limitations facing current test methods and the scientific advances that are helping to both understand and provide solutions to them. Some of these advancements include the following: (1) robust methods that provide a deeper understanding of microbial composition, diversity, and abundance to ensure consistency and/or interpret variability between tests; (2) benchmarking tools and reference substances that aid in persistence evaluations through comparison against substances with well-quantified degradation profiles; (3) analytical methods that allow quantification for parent and metabolites at environmentally relevant concentrations, and inform on test substance bioavailability, biochemical pathways, rates of primary versus overall degradation, and rates of metabolite formation and decay; (4) modeling tools that predict the likelihood of microbial biotransformation, as well as biochemical pathways; and (5) modeling approaches that allow for derivation of more generally applicable biotransformation rate constants, by accounting for physical and/or chemical processes and test system design when evaluating test data. We also identify that, while such advancements could improve the certainty and accuracy of persistence assessments, the mechanisms and processes by which they are translated into regulatory practice and development of new OECD test guidelines need improving and accelerating. Where uncertainty remains, holistic weight of evidence approaches may be required to accurately assess the persistence of chemicals. Integr Environ Assess Manag 2022;1–34. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).Peer reviewe

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

The endogeneity bias in the relation between cost-of-debt capital and corporate disclosure policy

Abstract The purpose of this paper is twofold. First, we provide a discussion of the problems associated with endogeneity in empirical accounting research. We emphasize problems arising when endogeneity is caused by (1) unobservable firm-specific factors and (2) omitted variables, and discuss the merits and drawbacks of using panel data techniques to address these causes. Second, we investigate the magnitude of endogeneity bias in Ordinary Least Squares (OLS) regressions of cost-of-debt capital on firm disclosure policy. We document how including a set of variables which theory suggests to be related with both cost-of-debt capital and disclosure and using fixed effects estimation in a panel data-set reduces the endogeneity bias and produces consistent results. This analysis reveals that the effect of disclosure policy on cost-of-debt capital is 200% higher than what is found in OLS estimation. Finally, we provide direct evidence that disclosure is impacted by unobservable firm-specific factors that are also correlated with cost of capital.