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2‐Amino‐2‐methyl‐1‐propanol (AMP™) is a widely used pH stabilizer in personal care products (PCPs); thus, the safety implications of dermal AMP exposure remain of interest. We have previously reported that exposure to AMP in PCPs when used as intended is not anticipated to result in an increased risk of hepatotoxicity (primarily steatosis and altered phospholipid homeostasis). The current study focuses on AMP in PCP's potential for developmental and reproductive toxicity (DART) in humans, based on data from animal studies. Animal studies suggest that exposure to AMP can result in post‐implantation loss. However, such effects occur at maternally toxic doses, posing a challenge for determining appropriate hazard classifications in the context of relevant consumer use scenarios. Our assessment concluded that human exposure to AMP in PCPs is not anticipated to result in DART at non‐maternally toxic doses. Further, mode of action (MOA) analysis elucidated the potential biological pathways underlying DART effects observed in high‐dose animal studies, such that perturbation of uterine choline synthesis was the most well‐supported MOA hypothesis. Downstream uterine effects might reflect choline‐dependent changes in epigenetic control of pathways important for implantation maintenance and uterine cell energetics. Since AMP‐induced post‐implantation loss occurs at doses higher than pathology related to liver toxicity, maintaining AMP exposures from exceeding the onset dose for maternal liver effects will also be protective of DART effects. Furthermore, dermal exposure to AMP expected from the use of PCPs is highly unlikely to result in toxicologically significant systemic AMP concentrations; thus, DART is not anticipated. Animal studies suggest that exposure to 2‐amino‐2‐methyl‐1‐propanol [AMP™; a pH stabilizer in personal care products (PCPs)] can result in post‐implantation loss. Our evaluation indicated that perturbation of uterine choline synthesis was the most likely hypothesis for developmental and reproductive toxicity (DART). Importantly, we showed that DART was not anticipated following exposure to non‐maternally toxic doses, since dermal exposure in humans from PCPs was unlikely to yield toxicologically significant systemic AMP concentrations. [ABSTRACT FROM AUTHOR]

Per‐ and poly‐fluoroalkyl substances (PFAS) are ubiquitous in the environment and are detected in wildlife and humans. With respect to human exposure, studies have shown that ingestion is the primary route of exposure; however, in certain settings, exposure via inhalation could also be a significant source of exposure. While many studies examined toxicity of PFAS via ingestion, limited information is available for PFAS toxicity via the inhalation route, translating into a lack of exposure guidelines. Consequently, this article examined whether route‐to‐route extrapolation to derive guidelines for inhalation exposure is appropriate for PFAS. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were used as exemplary PFAS given the abundance of toxicity data for these two compounds. Our evaluation determined that available toxicity and toxicokinetic data support route‐to‐route extrapolation for PFAS in order to derive inhalation‐based standards. Results from this analysis suggest that an air concentration of 7.0 × 10−5 mg/m3 (or 0.07 μg/m3) would be an appropriate RfC for PFOA and PFOS assuming the 2016 EPA RfD of 0.00002 mg/kg‐day, whereas use of the interim RfDs proposed in 2022 of 1.5 × 10−9 and 7.9 × 10−9 mg/kg would yield much lower RfCs of 5.25 × 10−9 and 2.77 × 10−8 mg/m3 (or 5.25 × 10−6 and 2.77 × 10−5 μg/m3) for PFOA and PFOS, respectively. [ABSTRACT FROM AUTHOR]

Purpose/Aim: The U.S. Food and Drug Administration (FDA) does not require specific testing to demonstrate the safety of personal care and cosmetic products or their ingredients. Recently, there have been reports of skin irritation associated with the use of commercially available cleansing conditioners. The goal of this study was to implement a tier-based safety assessment to evaluate the skin irritation potential of six commercially available cleansing conditioners and their ingredients. Materials and Methods: The first tier of testing utilized the Organization for Economic Co-operation and Development (OECD) QSAR Toolbox to perform an in silico evaluation of the skin irritation potential of the product ingredients, and the second tier of testing utilized an OECD in vitro guideline test to evaluate the skin irritation potential of each product. Results: Thirty-two ingredients were evaluated using the OECD QSAR Toolbox profiler for the tier one analysis; nine ingredients received a structural alert for skin irritation/corrosion. In the tier two in vitro analysis, the evaluated cleansing conditioner products were all classified as non-irritants. Conclusions: These results provide evidence that use of the evaluated commercially available cleansing conditioners would not be expected to cause skin irritation among consumers. Additionally, this study demonstrates that the presence of structural alerts does not always accurately predict the safety of a product, as focused tier-based testing is necessary to comprehensively evaluate a product. This study illustrates a tier-based safety assessment approach, applicable to a wide variety of health endpoints, which efficiently and adequately evaluates the safety of personal care and cosmetic products and their ingredients. [ABSTRACT FROM AUTHOR]

Abstract: Coal combustion residuals (CCRs) are composed of various constituents, including radioactive materials. The objective of this study was to utilize methodology on radionuclide risk assessment from the Environmental Protection Agency (EPA) to estimate the potential cancer risks associated with residential exposure to CCR‐containing soil. We evaluated potential radionuclide exposure via soil ingestion, inhalation of soil particulates, and external exposure to ionizing radiation using published CCR radioactivity values for 232Th, 228Ra, 238U, and 226Ra from the Appalachia, Illinois, and Powder River coal basins. Mean and upper‐bound cancer risks were estimated individually for each radionuclide, exposure pathway, and coal basin. For each radionuclide at each coal basin, external exposure to ionizing radiation contributed the greatest to the overall risk estimate, followed by incidental ingestion of soil and inhalation of soil particulates. The mean cancer risks by route of exposure were 2.01 × 10−6 (ingestion), 6.80 × 10−9 (inhalation), and 3.66 × 10−5 (external), while the upper bound cancer risks were 3.70 × 10−6 (ingestion), 1.18 × 10−8 (inhalation), and 6.15 × 10−5 (external), using summed radionuclide‐specific data from all locations. The upper bound cancer risk from all routes of exposure was 6.52 × 10−5. These estimated cancer risks were within the EPA's acceptable cancer risk range of 1 × 10−6 to 1 × 10−4. If the CCR radioactivity values used in this analysis are generally representative of CCR waste streams, then our findings suggest that CCRs would not be expected to pose a significant radiological risk to residents living in areas where contact with CCR‐containing soils might occur. [ABSTRACT FROM AUTHOR]