Finally, we characterized uncertainties around the surrogate PODs from intra- and interstudy variability and derived probabilistic toxicity values using a standardized workflow. We hypothesized that a quantile of the BMDh distribution could serve as a surrogate POD and determined the appropriate quantile by calibration to regulatory PODs. Effect levels were adjusted to chronic human equivalent benchmark doses (BMDh). We developed a curated data set restricted to effect levels, exposure routes, study designs, and species relevant for deriving toxicity values. Environmental Protection Agency's Toxicity Value Database, we developed a semiautomated approach to determine surrogate oral route PODs, and corresponding toxicity values where regulatory assessments are unavailable. Using in vivo experimental animal data from the U.S. However, regulatory assessments are only available for a small fraction of chemicals. Regulatory toxicity values used to assess and manage chemical risks rely on the determination of the point of departure (POD) for a critical effect, which results from a comprehensive and systematic assessment of available toxicity studies. Our framework is applicable for evaluating chemical emissions and product-related exposure in life cycle assessment, chemical alternatives assessment and chemical substitution, consumer exposure and risk screening, and high-throughput chemical prioritization. Next steps are to test the new characterization framework in additional case studies and to close remaining research gaps. The recommended methodological advancements address several key limitations in earlier approaches. All proposed aspects have been consistently implemented into the original USEtox framework. Factors reflecting disease severity are proposed to distinguish cancer from non-cancer effects and within the latter to discriminate reproductive/developmental and other non-cancer effects. This approach allows for explicitly considering both uncertainty and human variability in toxicity effect factors. On the effect side, a probabilistic dose-response approach combined with a decision tree for identifying reliable points of departure is proposed for non-cancer effects, following recent guidance from the World Health Organization. Case study results illustrate that product use–related exposure dominates overall life cycle exposure. Consumer exposure is addressed via sub-models for each product type to account for product type-specific characteristics and exposure settings. On the exposure side, a matrix system is proposed and recommended to integrate far-field exposure from environmental emissions with near-field exposure from chemicals in various consumer product types. The proposed updated USEtox framework was tested in an illustrative rice production and consumption case study. Dedicated efforts have led to a set of recommendations to address these aspects in an update of USEtox, while ensuring consistency with the boundary conditions for characterizing life cycle toxicity impacts and being aligned with recommendations from agencies that regulate chemical exposure. This taskforce evaluated scientific advances since the original release of USEtox and identified two major aspects that required refinement, namely integrating near-field and far-field exposure, and improving human dose-response modeling. In response, we elaborate the methodological framework and present recommendations for advancing near-field/far-field exposure and toxicity characterization, and for implementing these recommendations into the scientific consensus model USEtox.Īn expert taskforce was convened by the Life Cycle Initiative hosted by UN Environment to expand existing guidance for evaluating human toxicity impacts from exposure to chemical substances. Guidelines for deriving globally applicable, life cycle–based indicators are required to consistently quantify toxicity impacts from chemical emissions as well as from chemicals in consumer products. Reducing chemical pressure on human and environmental health is an integral part of the global sustainability agenda.
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