Scientific Ignorance and Reliable Patterns of Evidence in Toxic Tort Causation: Is There a Need for Liability Reform?

As a first step to preserving the central aims of tort law, courts will need to recognize the wide variety of respectable, reliable patterns of evidence on which scientists themselves rely for drawing inferences about the toxicity of substances. Courts may also need to take further steps to address the woeful ignorance about the chemical universe. This may necessitate changes in the liability rules

Scientific Ignorance and Reliable Patterns of Evidence in Toxic Tort Causation: Is There a Need for Liability Reform?

As a first step to preserving the central aims of tort law, courts will need to recognize the wide variety of respectable, reliable patterns of evidence on which scientists themselves rely for drawing inferences about the toxicity of substances. Courts may also need to take further steps to address the woeful ignorance about the chemical universe. This may necessitate changes in the liability rules

Mutagenicity testing for chemical risk assessment: update of the WHO/IPCS Harmonized Scheme

Since the publication of the International Programme on Chemical Safety (IPCS) Harmonized Scheme for Mutagenicity Testing, there have been a number of publications addressing test strategies for mutagenicity. Safety assessments of substances with regard to genotoxicity are generally based on a combination of tests to assess effects on three major end points of genetic damage associated with human disease: gene mutation, clastogenicity and aneuploidy. It is now clear from the results of international collaborative studies and the large databases that are currently available for the assays evaluated that no single assay can detect all genotoxic substances. The World Health Organization therefore decided to update the IPCS Harmonized Scheme for Mutagenicity Testing as part of the IPCS project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals. The approach presented in this paper focuses on the identification of mutagens and genotoxic carcinogens. Selection of appropriate in vitro and in vivo tests as well as a strategy for germ cell testing are describe

Birds and bioenergy within the americas: A cross‐national, social–ecological study of ecosystem service tradeoffs

Although renewable energy holds great promise in mitigating climate change, there are socioeconomic and ecological tradeoffs related to each form of renewable energy. Forest‐related bioenergy is especially controversial, because tree plantations often replace land that could be used to grow food crops and can have negative impacts on biodiversity. In this study, we examined public perceptions and ecosystem service tradeoffs between the provisioning services associated with cover types associated with bioenergy crop (feedstock) production and forest habitat‐related supporting services for birds, which themselves provide cultural and regulating services. We combined a social survey‐based assessment of local values and perceptions with measures of bioenergy feedstock production impacts on bird habitat in four countries: Argentina, Brazil, Mexico, and the USA. Respondents in all countries rated birds as important or very important (83–99% of respondents) and showed lower enthusiasm for, but still supported, the expansion of bioenergy feedstocks (48–60% of respondents). Bioenergy feedstock cover types in Brazil and Argentina had the greatest negative impact on birds but had a positive impact on birds in the USA. In Brazil and Mexico, public perceptions aligned fairly well with the realities of the impacts of potential bioenergy feedstocks on bird communities. However, in Argentina and the USA, perceptions of bioenergy impacts on birds did not match well with the data. Understanding people’s values and perceptions can help inform better policy and management decisions regarding land use changes

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Dose-Response Analysis of Bromate-Induced DNA Damage and Mutagenicity Is Consistent With Low-Dose Linear, Nonthreshold Processes

Mutagenic agents have long been inferred to act through low-dose linear, nonthreshold processes. However, there is debate about this assumption, with various studies interpreting datasets as showing thresholds for DNA damage and mutation. We have applied rigorous statistical analyses to investigate the shape of dose-response relationships for a series of in vitro and in vivo genotoxicity studies using potassium bromate (KBrO3), a water ozonation byproduct that is bioactivated to a reactive species causing oxidative damage to DNA. We analyzed studies of KBrO3 genotoxicity where no-effect/threshold levels were reported as well as other representative datasets. In all cases, the data were consistent with low-dose linear models. In the majority of cases, the data were fit either by a linear (straight line) model or a model which was linear at low doses and showed a saturation- like downward curvature at high doses. Other datasets with apparent upward curvature were still adequately represented by models that were linear at low dose. Sensitivity analysis of datasets showing upward curvature revealed that both low-dose linear and nonlinear models provide adequate fits. Additionally, a simple biochemical model of selected key processes in bromate- induced DNA damage was developed and illustrated a situation where response for early primary events suggested an apparent threshold while downstream events were linear. Overall, the statistical analyses of DNA damage and mutations induced by KBrO3 are consistent with a low-dose linear response and do not provide convincing evidence for the presence of a threshold