Chemicals assessment and management frameworks rely on regulatory toxicity values, which are based on points of departure (POD) identified following rigorous dose–response assessments. Yet, regulatory PODs and toxicity values for inhalation exposure (i.e., reference concentrations [RfCs]) are available for only ∼200 chemicals. To address this gap, we applied a workflow to determine surrogate inhalation route PODs and corresponding toxicity values, where regulatory assessments are lacking. We curated and selected inhalation in vivo data from the U.S. EPA’s ToxValDB and adjusted reported effect values to chronic human equivalent benchmark concentrations (BMC_h) following the WHO/IPCS framework. Using ToxValDB chemicals with existing PODs associated with regulatory toxicity values, we found that the 25th %-ile of a chemical’s BMC_h distribution (${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$) could serve as a suitable surrogate for regulatory PODs (Q² ≥ 0.76, RSE ≤ 0.82 log₁₀ units). We applied this approach to derive ${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$ for 2,095 substances with general non-cancer toxicity effects and 638 substances with reproductive/developmental toxicity effects, yielding a total coverage of 2,160 substances. From these ${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$, we derived probabilistic RfCs and human population effect concentrations. With this work, we have expanded the number of chemicals with toxicity values available, thereby enabling a much broader coverage for inhalation risk and impact assessment.

中文翻译：

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用于表征 2,160 种物质的吸入非癌症和发育/生殖效应的概率参考和 10% 效应浓度


化学品评估和管理框架依赖于监管毒性值，这些值基于严格的剂量反应评估后确定的出发点 (POD)。然而，吸入暴露的监管 POD 和毒性值（即参考浓度 [RfC]）仅适用于约 200 种化学品。为了解决这一差距，我们应用了一个工作流程来确定替代吸入途径 POD 和相应的毒性值，而这方面缺乏监管评估。我们从美国 EPA 的 ToxValDB 中策划和选择了吸入体内数据，并按照 WHO/IPCS 框架将报告的效应值调整为慢性人体等效基准浓度 (BMC _h )。将 ToxValDB 化学品与与监管毒性值相关的现有 POD 结合使用，我们发现化学品 BMC _h 分布 ( ${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$ ) 的 25%-ile 可以作为监管 POD 的合适替代品（Q ² ≥ 0.76，RSE ≤ 0.82 log ₁₀ 单位）。我们应用这种方法导出了 2,095 种具有一般非癌症毒性作用的物质和 638 种具有生殖/发育毒性作用的物质的 ${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$ ，总共覆盖了 2,160 种物质。从这些 ${\mathrm{POD}}_{p25{\mathrm{BMC}}_{\mathrm{h}}}$ 中，我们得出了概率 RfC 和人口效应浓度。通过这项工作，我们扩大了具有毒性值的化学品数量，从而扩大了吸入风险和影响评估的覆盖范围。