Health risks resulting from dermal or inhalational exposures are frequently assessed based on rodent oral toxicity information due to a lack of species- or route-specific toxicity data. Default uncertainty factors (UFs; e.g., 10-fold) are also applied during risk assessments to account for variability such as inter-species, intra-species, exposure duration, dose–response, and route-to-route extrapolations. However, whether rodent oral data and a default UF approach can provide adequate protection for other mammalian species under dermal or inhalational exposure scenarios remains understudied, particularly for cleaning product ingredients. Therefore, we collated and examined publicly available median lethal dose (LD₅₀), no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values from different types of standard mammalian toxicity studies for rats (dermal and inhalational), mice, rabbits, guinea pigs, and dogs (oral, dermal and inhalational) using the Cleaning Product Ingredient Safety Initiative (CPISI) database. Probabilistic hazard assessments using chemical toxicity distributions (CTDs) were subsequently conducted, and threshold concentrations (TCs) and 95% confidence intervals (95% CIs) were derived to identify thresholds of toxicological concern (TTCs). Relative sensitivities among or between mammalian species, exposure routes, and chemical classes were also compared based on calculated TC₅s and 95% CIs to support future toxicology studies and hazard and risk assessments. We then identified uncertainty factors (UFs) using both CTD comparisons and individual UF probability distributional approaches. Based on available rodent inhalational data, chemical category-specific UFs were derived for ethers. Additionally, we also determined whether default UFs of 10 or 100 would be protective for various distributions of cleaning product ingredients. Our novel observations among these routes of exposure and common mammalian model organisms appear particularly useful for read across and screening-level health hazard and risk assessments when limited data exists for specific chemicals.

由于缺乏物种或途径特定的毒性数据，皮肤或吸入暴露导致的健康风险经常根据啮齿动物的口服毒性信息进行评估。在风险评估期间还应用默认不确定性因子（UF；例如，10 倍）以说明变异性，例如种间、种内、暴露持续时间、剂量反应和路径到路径外推。然而，啮齿动物的口腔数据和默认的超滤方法能否在皮肤或吸入暴露情况下为其他哺乳动物物种提供足够的保护仍有待研究，特别是对于清洁产品成分。因此，我们整理并检查了公开可用的半数致死剂量 (LD ₅₀)、未观察到不良反应水平 (NOAEL) 和最低观察到不良反应水平 (LOAEL) 值来自不同类型的标准哺乳动物毒性研究对大鼠（皮肤和吸入）、小鼠、兔、豚鼠和使用清洁产品成分安全倡议 (CPISI) 数据库的狗（口腔、皮肤和吸入）。随后使用化学毒性分布 (CTD) 进行概率危险评估，并推导出阈值浓度 (TC) 和 95% 置信区间 (95% CI) 以确定毒理学关注阈值 (TTC)。还根据计算的 TC ₅比较了哺乳动物物种、接​​触途径和化学类别之间或之间的相对敏感性s 和 95% CI 以支持未来的毒理学研究以及危害和风险评估。然后，我们使用 CTD 比较和单个 UF 概率分布方法确定了不确定性因素 (UF)。根据现有的啮齿动物吸入数据，可以得出醚的特定化学类别的 UF。此外，我们还确定了 10 或 100 的默认 UF 是否可以保护清洁产品成分的各种分布。当特定化学品的数据有限时，我们对这些接触途径和常见哺乳动物模型生物的新观察似乎对阅读和筛选级别的健康危害和风险评估特别有用。