Toxicological evaluation of the ketogenic ester bis hexanoyl (R)-1,3-butanediol: Subchronic toxicity in Sprague Dawley rats
| Autor: | Brianna J. Stubbs, Gopi S. Gadupudi, Donald G. Stump, Andrey I. Nikiforov, John C. Newman, Nancy Higley, Sari L. Weston, Marisa O. Rihner, Gregory A. Krane, Eric Verdin |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Physiology Toxicology Oral gavage Drug Administration Schedule Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Random Allocation 0404 agricultural biotechnology medicine Sprague dawley rats 1 3-Butanediol Animals Glandular stomach Butylene Glycols 030304 developmental biology 0303 health sciences Molecular Structure business.industry Stomach Toxicity Tests Subchronic 04 agricultural and veterinary sciences General Medicine medicine.disease 040401 food science Subchronic toxicity Rats medicine.anatomical_structure chemistry Toxicity Female Ketosis business Food Science |
| Zdroj: | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 150 |
| ISSN: | 1873-6351 |
| Popis: | 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 Crl:CD(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. |
| Databáze: | OpenAIRE |
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