Assessment of the genotoxicity of tert-butyl alcohol in an in vivo thyroid comet assay.
comet assay
genotoxicity
mode of action (MOA)
tert‐butyl alcohol (TBA)
thyroid
Journal
Environmental and molecular mutagenesis
ISSN: 1098-2280
Titre abrégé: Environ Mol Mutagen
Pays: United States
ID NLM: 8800109
Informations de publication
Date de publication:
08 May 2024
08 May 2024
Historique:
received:
02
04
2024
accepted:
15
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
8
5
2024
Statut:
aheadofprint
Résumé
Chronic exposure to high (20,000 ppm) concentrations of tert-butyl alcohol (TBA) in drinking water, equivalent to ~2100 mg/kg bodyweight per day, is associated with slight increases in the incidence of thyroid follicular cell adenomas and carcinomas in mice, with no other indications of carcinogenicity. In a recent toxicological review of TBA, the U.S. EPA determined that the genotoxic potential of TBA was inconclusive, largely based on non-standard studies such as in vitro comet assays. As such, the potential role of genotoxicity in the mode of action of thyroid tumors and therefore human relevance was considered uncertain. To address the potential role of genotoxicity in TBA-associated thyroid tumor formation, CD-1 mice were exposed up to a maximum tolerated dose of 1500 mg/kg-day via oral gavage for two consecutive days and DNA damage was assessed with the comet assay in the thyroid. Blood TBA levels were analyzed by headspace GC-MS to confirm systemic tissue exposure. At study termination, no significant increases (DNA breakage) or decreases (DNA crosslinks) in %DNA tail were observed in TBA exposed mice. In contrast, oral gavage of the positive control ethyl methanesulfonate significantly increased %DNA tail in the thyroid. These findings are consistent with most genotoxicity studies on TBA and provide mechanistic support for non-linear, threshold toxicity criteria for TBA. While the mode of action for the thyroid tumors remains unclear, linear low dose extrapolation methods for TBA appear more a matter of policy than science.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Uponor North America
Organisme : Rehau North America
Informations de copyright
© 2024 Environmental Mutagenesis and Genomics Society.
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