Weight Of Evidence Assessment Research Articles

Hypothesis-driven weight of evidence analysis to determine potential endocrine activity of MTBE

Endocrine-related endpoints in animals have been reported to respond to high doses of methyl tertiary-butyl ether (MTBE), however, a systematic and transparent evaluation of endocrine potential has not been published. Resolving whether MTBE exhibits endocrine activity is important given regulatory and public interest in endocrine disrupting substances and their potential for causing adverse effects in humans or wildlife. A weight-of-evidence (WoE) analysis was conducted, focusing on hypotheses related to the potential for MTBE to interact with estrogen, androgen, and thyroid pathways, and steroidogenesis. To reach scientifically justified conclusions based on the totality of evidence, this WoE procedure involved a semi-quantitative relevance weighting of each endpoint for each hypothesis and systematic consideration of each endpoint in various study designs. This procedure maximized use of an extensive body of relevant and reliable literature on MTBE with evidence supporting or opposing a given mode of action hypothesis. Evaluating the strength and consistency of observations from many MTBE studies also provided a way to assess whether high doses used in experiments with MTBE confound identification of direct endocrine system responses. Based on results of studies using mammalian and fish models and in vitro screening assays, this WoE assessment reveals that MTBE lacks direct endocrine activity.

Insights from a multi-year program designed to test the impact of ingredients on mainstream cigarette smoke toxicity

Context: Cigarette tobacco ingredients may alter the distribution of chemical constituents present in smoke. When considering the toxicological relevance of potential ingredient-related effects on chemical and biological measurements assessing cigarette smoke toxicity, it is critical to understand the intrinsic variability of tobacco and cigarette smoke that is influenced by the environmental conditions during growing, agricultural practices during preparation, cigarette manufacturing tolerances, and stability of the assay methods.Objective: To understand possible effects of ingredients on cigarette smoke toxicity, various chemical and biological endpoints were measured in smoke from experimental cigarettes (added ingredient) to the intrinsic variability of control cigarettes (no added ingredient).Materials and methods: Data were collected during a multi-year program testing a variety of cigarette ingredients from several chemical classes. Chemical analysis of mainstream cigarette smoke,and biological procedures (Salmonella mutagenicity, cytotoxicity, and smoke inhalation) were performed using validated and controlled laboratory methods. The within-study and temporal variation of control cigarettes manufactured in parallel with experimental cigarettes was calculated and used to measure intrinsic variability.Results: The overwhelming majority of data generated from experimental cigarettes fell within the experiment variability represented by the pooled standard error of the entire multi-year dataset for the control cigarettes.Conclusion: The results of this evaluation add to a growing body of the literature regarding a weight of evidence assessment of cigarette ingredient toxicity. When assessed against the variability of assay methodology, natural agricultural change, and manufacturing control, the ingredients studied here demonstrated little relevant influence on the mainstream cigarette smoke toxicity endpoints measured.

Determining when contamination is pollution — Weight of evidence determinations for sediments and effluents

Contamination is simply the presence of a substance where it should not be or at concentrations above background. Pollution is contamination that results in or can result in adverse biological effects to resident communities. All pollutants are contaminants, but not all contaminants are pollutants. Differentiating pollution from contamination cannot be done solely on the basis of chemical analyses because such analyses provide no information on bioavailability or on toxicity. Effects-based measures such as laboratory or field toxicity tests and measures of the status of resident, exposed communities provide key information, but cannot be used independently to determine pollution status. Laboratory studies can be predictive, but are rarely realistic. Measures of resident communities include innate natural variability and cannot easily distinguish between adaptation to contamination (a genetic process) and acclimation (a physiological process that may decrease energy reserves, possibly reducing such critical population-level parameters as reproduction). Finally, contaminant effects may not only be direct but also indirect; predicting such effects requires knowledge of the system under study as well as appropriate use of lines of evidence (LOE) such as toxicity tests directed to key species. Consequently, in sediments, effluents or other inputs/environmental compartments, determining when contamination is or may in future become pollution, requires a weight of evidence (WOE) assessment using different LOE appropriate to the situation under investigation. WOE investigations provide two different types of information: definitive conclusions regarding pollution; or, information as to what additional, investigative studies are necessary for definitive conclusions. Effectively, a WOE assessment comprises an initial screening-level ecological risk assessment (ERA), which may be followed by a detailed-level ERA if key uncertainties need to be resolved.

A Weight of Evidence Approach to the Aquatic Hazard Assessment of Bisphenoi A

Bisphenol A (BPA; 4,4-isopropylidene diphenol) is a chemical intermediate used primarily in the production of epoxy resins and polycarbonate products. BPA has been identified in surface waters and, hence, has been the subject of considerable research into its potential effects on aquatic organisms. Available literature on the aquatic toxicity of BPA was reviewed for quality against European Union TGD and Organization of Economic Cooperation and Development GLP principles. From this review, studies of suitable quality covering numerous ecologically relevant endpoints were identified to evaluate the survival, growth, and reproductive success of aquatic organisms exposed to BPA. Those studies yielded approximately 70 no observed effect concentrations (ranging from 16 to 3640 μg/L) and lowest observed effect concentrations (160 to 11,000 μg/L) that were considered in this weight of evidence assessment. Across all data, adverse effects on survival, growth, and reproduction occurred only at concentrations of 160 μg/L and above. Secondary biochemical (e.g., vitellogenin induction) and morphological (e.g., gonad histology) data provide insight into mechanisms of action, but do not correlate with apical endpoints related to survival, growth, and reproduction. Comparing the weight of the evidence of the aquatic toxicity data that showed chronic effects at 160 μg/L and higher with typical surface water concentrations in the range of 0.001 to 0.10 μg/ L, BPA is unlikely to cause adverse effects on aquatic populations or ecosystems.