Toxicological evaluation of the ketogenic ester bis hexanoyl (R)-1,3-butanediol: Subchronic toxicity in Sprague Dawley rats.
Food Chem Toxicol
; 150: 112084, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33621607
ABSTRACT
Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is novel ketone ester undergoing development as a food ingredient to achieve nutritional ketosis in humans. Male and female CrlCD(SD) rats were administered BH-BD twice daily at 9000, 12,000 or 15,000 mg/kg/day, by oral gavage in a 90-day toxicity study with 28-day recovery period; and an interim 28-day phase. Test substance-related early deaths occurred in four females at 15,000 mg/kg/day. A dose-dependent increase in acute transient postdose (1-3 h) observations of incoordination at ≥12,000 mg/kg/day and decreased activity at all dose levels were noted in both sexes. Postdose observations were likely associated with peak ketonemia and were considered adverse at 15,000 mg/kg/day. These daily observations decreased over the study without any persistent effects, as determined during weekly pre-dose observations. Adverse histopathological changes included ulceration/erosion in non-glandular stomach at ≥ 12,000 mg/k/day and in glandular stomach at 15,000 mg/kg/day. These histopathological findings were not noted after 28-days of recovery. Due to unlikely human relevance of the rat non-glandular stomach effects for BH-BD and test substance-related mortality at 15,000 mg/kg/day, the no-observed-adverse-effect level (NOAEL) for subchronic toxicity of BH-BD was determined to be 12,000 mg/kg/day.
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MEDLINE
Assunto principal:
Butileno Glicóis
Limite:
Animals
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2021
Tipo de documento:
Article