Developmental and reproductive toxicity hazard characterization of 2-amino-2-methyl-1-propanol (AMP)

2-Amino-2-methyl-1-propanol (AMP & TRADE;) 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 & TRADE;; 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.

Automated summary

2-amino-2-methyl-1-propanol (AMP) is commonly used in personal care products as a pH stabilizer. Animal studies suggest that exposure to AMP can lead to post-implantation loss, but only at maternally toxic doses. Our assessment indicates that dermal exposure to AMP from personal care products is unlikely to result in toxicologically significant systemic concentrations, therefore developmental and reproductive toxicity (DART) is not anticipated.