Application of a unified probabilistic framework to the dose-response assessment of acrolein.

BACKGROUND: In quantitative chemical risk assessment, a reference value is an estimate of an exposure to a chemical that is "likely to be without appreciable risk." Because current "deterministic" approaches do not quantitatively characterize the likelihood or severity of harm, the National Academies has recommended using reference values derived from a risk-specific dose that are treated as random variables, with probability distributions characterizing uncertainty and variability. OBJECTIVES: In order to build familiarity and address issues needed for routine and standardized derivation of probabilistic risk-specific dose distributions, a case example applying the unified probabilistic framework presented in Chiu and Slob (2015) is developed for acrolein. This case study is based on an updated systematic evidence map of literature (Keshava et al., 2020) identifying nasal lesions reported in Dorman et al. (2008) as the most appropriate endpoint and study for reference value derivation. METHODS: The probability distribution was calculated for the risk-specific dose, which in this implementation of the approach was calculated for the dose at which 1% of the human population is estimated to experience minimal lesions, and a probabilistic reference value was computed as the 5th percentile of this distribution. A deterministic reference value was also derived for comparison, and a sensitivity analysis of the probabilistic reference value was conducted investigating alternative assumptions for the point of departure type and exposure duration. RESULTS: The probabilistic reference value of 6 × 10-4 mg/m3 was slightly lower than the deterministic reference value of 8 × 10-4 mg/m3, and the risk-specific dose distribution had an uncertainty spanning a factor of 137 (95th-5th percentile ratio). Sensitivity analysis yielded slightly higher probabilistic reference values ranging between 9 × 10-4 mg/m3 and 2 × 10-3 mg/m3. CONCLUSIONS: Using a probabilistic approach for deriving a reference value allows quantitative characterization of the severity, incidence, and uncertainty of effects at a given dose. The results can be used to inform risk management decisions and improve risk communication.

Sparking connections: toward better linkages between research and human health policy-an example with multiwalled carbon nanotubes.

Risk assessment and subsequent risk management of environmental contaminants can benefit from early collaboration among researchers, risk assessors, and risk managers. The benefits of collaboration in research planning are particularly evident in light of (1) increasing calls to expand upon the risk assessment paradigm to include a greater focus on problem formulation and consideration of potential tradeoffs between risk management options, and (2) decreasing research budgets. Strategically connecting research planning to future decision making may be most critical in areas of emerging science for which data are often insufficient to clearly direct targeted research to support future risk assessment and management efforts. This article illustrates an application of the comprehensive environmental assessment approach to inform research planning for future risk assessment and management of one emerging material, multiwalled carbon nanotubes (MWCNTs). High-priority research areas identified for MWCNTs in flame-retardant coatings applied to upholstery textiles included the following: release across the product life cycle; environmental transport, transformation and fate in air, wastewater and sediment; exposure in human occupational and consumer groups; kinetics in the human body; impacts on human health and aquatic populations; and impacts on economic, social, and environmental resources. This article focuses on specific research questions related to human health and how these may connect to future risk assessments and risk management efforts. Such connections will support more effective collaborations across the scientific community and may inform the prioritization of research funding opportunities for emerging materials like MWCNTs.