Cleaners such as dishwashing liquids contain various chemicals that cause skin damage. Alkaline agents used in cleaners alter the lipid composition of the skin and damage the skin barrier. However, little is known about the effects of acids used in cleaners on the skin. Here, we investigated the effects of acidic pH on the skin and evaluated the skin irritation of acids commonly used in cleaners with a 3D-reconstructed human epidermis model, KeraSkin^TM, according to OECD TG439. First, to examine the effects of acidic pH, we evaluated the skin irritation of citrate buffers (0.1 M, McIlvaine buffer) prepared in a wide pH range (pH 1.5–6.0). Surprisingly, cell viability was not significantly affected even at pH 1.5, reflecting that the acidity alone may not be sufficient to induce skin irritation. Even after longer exposure (180 min), the cell viability was not reduced below 50%, a cutoff to determine an irritant. To examine the effect of the anionic part, several organic acids used in cleaners (citric acid, glycolic acid, lactic acid, malic acid, and succinic acid) were examined. These organic acids also failed to reduce viability at 0.1 M. However, at 1 M, most of the acids tested, except lactic acid, were determined to be skin irritants. Histology further supported the skin irritancy of acids at 1 M. Similarly, inorganic acids (hydrogen bromide, hydrogen chloride, nitric acid, and sulfuric acid) were determined to be irritants only at 1 M. In the case of alkaline agents, pH and concentrations were also important factors to determine the skin irritancy, although the epidermal structure and lipids were more damaged than acids. Collectively, we demonstrated that both the pH and concentration are important factors for the skin irritancy of acids, shedding an important insight into the mechanism of skin irritation.

Evaluating the safety of botanical extracts for cosmetics has become mandatory, but it is often challenging because of their phytochemical complexity and limited toxicological data. In this study, the safety of aqueous Sophora flavescens root extract (SFRE), widely used in cosmetics, was assessed using an integrated approach combining in vitro, in silico, margin of safety (MoS), threshold of toxicological concern (TTC), and history of safe use (HSU). Chemical characterization was performed by literature review and LC–MS/MS analysis. SFRE was classified as non-irritant in in vitro skin and eye irritation tests conducted according to OECD TG439 and 492. Whole-extract and constituent-level in silico analysis and literature evaluation were conducted to assess genotoxicity and skin sensitization potential. For systemic toxicity, a 13-week oral repeat dose no-observed-adverse-effect level (NOAEL) of 10 mg/kg bw/day for a decocted Sophorae radix extract was employed without compositional adjustment to calculate the acceptable systemic exposure dose of 0.10 mg/kg bw/day, which was slightly lower than the current usage of SFRE in cosmetics (up to 0.13 mg/kg/day). The TTC approach revealed that many bioactive constituents fell outside the applicability domain due to steroid moieties. HSU data from dietary supplements (32–64.67 mg/kg/day) could support the safety of the current use of SFRE in cosmetics. The findings highlight that a combined, case-by-case application of MoS, TTC, and HSU is essential for the robust safety assessment of complex botanical ingredients.