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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]

To mitigate the spread of COVID-19, face masks, including fabric face coverings, have been encouraged or mandated. To meet demand, traditional clothes-making fabrics have been redirected to face covering manufacture. It has been reported that phthalates may be present in textiles, posing a health risk consideration for the industry; however, the potential presence of and exposure to phthalates in fabric face coverings have not been evaluated. Consequently, this study 1) estimated the concentrations of phthalates in fabric face coverings, 2) estimated the potential consumer exposures, and compared them to health guidance values (HGVs), and 3) advised on voluntary phthalate testing in textiles and/or face coverings. Precautionary upper-bound phthalate mass in face coverings was estimated from phthalate concentrations in clothing articles. Exposure to phthalates was predicted to occur predominantly via inhalation and direct dermal contact; however, for both routes, the doses were below HGVs, indicating that, based on the limited materials characterized in the literature, a health risk was unlikely. Further, the limit of 0.1% (w/w) set for individual or sum of phthalates in child care articles in the U.S. and other countries was deemed protective for children and adult face coverings. We conclude that the establishment of industry-wide voluntary phthalate quality specifications and test data for commercial face coverings or textiles used to manufacture them is advisable to substantiate product safety given the limited data. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are the most commonly used metallic nanoparticles in industrial applications, including medical and consumer products. In the recent years, however, concerns regarding their environmental and health impacts have emerged. Aquatic organisms are of special concern since water bodies often serve as sinks for anthropogenic activities. This study assessed the effects of AgNPs on the activities of the gill Na+/K+-ATPase and erythrocyte acetylcholinestrase (AChE), as well as the plasma biochemistry in adult zebrafish (Danio rerio). In an acute exposure scenario the fish were exposed for 4d to 16.76mg/L AgNPs, which was the 96h LC50 value determined in preliminary experiments. In a prolonged exposure scenario the fish were exposed for 1, 2, or 3 weeks to AgNPs at concentrations of 2 and 4mg/L, corresponding to the 1/10th and 2/10th of the 96h LC50 value. Generally the activity of the gill Na+/K+-ATPase decreased, but this was only significant starting at 14d of the prolonged exposure scenario, whereas the activity of the erythrocyte AChE was significantly decreased in both exposure scenarios. Finally, the plasma electrolytes levels were reduced and the plasma glucose and cortisol levels were increased in exposed fish. This study demonstrates that AgNPs could inhibit the activities of Na+/K+-ATPase and AChE, thus interfering with the proper ionoregulation and neuroregulation, respectively, and act as stressors. [Copyright &y& Elsevier]

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/m 3 (or 0.07 μg/m 3 ) 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/m 3 (or 5.25 × 10 -6 and 2.77 × 10 -5 μg/m 3 ) for PFOA and PFOS, respectively., (© 2022 Society for Risk Analysis.)