Comparative influences of dermal and inhalational routes of exposure on hazards of cleaning product ingredients among mammalian model organisms

Abstract

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.

Keywords: Chemical toxicity distribution; Health hazard and risk assessment; Routes of exposure; Threshold of toxicological concern; Uncertainty factor.