Dose and exposure route analyses inform relationships between liver steatosis and 2-amino-2-methyl-1-propanol: Implications for hazard characterization.
AMP
dermal exposure
exposure assessment
liver steatosis
margin of exposure
personal care products
risk assessment
Journal
Journal of applied toxicology : JAT
ISSN: 1099-1263
Titre abrégé: J Appl Toxicol
Pays: England
ID NLM: 8109495
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
18
02
2022
received:
12
12
2021
accepted:
19
02
2022
pubmed:
25
2
2022
medline:
15
11
2022
entrez:
24
2
2022
Statut:
ppublish
Résumé
2-Amino-2-methyl-1-propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP-containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP-choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low-density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.
Substances chimiques
2-amino-2-methyl-1-propanol
LU49E6626Q
Choline
N91BDP6H0X
Adenosine Monophosphate
415SHH325A
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1873-1889Subventions
Organisme : ANGUS Chemical Company
Informations de copyright
© 2022 John Wiley & Sons, Ltd.
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