Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate.
Autor: | Clarke K; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK. kieran.clarke@dpag.ox.ac.uk, Tchabanenko K, Pawlosky R, Carter E, Knight NS, Murray AJ, Cochlin LE, King MT, Wong AW, Roberts A, Robertson J, Veech RL |
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Jazyk: | angličtina |
Zdroj: | Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2012 Jul; Vol. 63 (2), pp. 196-208. Date of Electronic Publication: 2012 Apr 11. |
DOI: | 10.1016/j.yrtph.2012.04.001 |
Abstrakt: | (R)-3-Hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester) has been developed as an oral source of ketones, which may be utilized for energy. In a 28-day toxicity study, Crl:WI (Wistar) rats received diets containing, as 30% of the calories, ketone monoester (12 and 15 g/kg body weight/day for male and female rats, respectively). Control groups received either carbohydrate- or fat-based diets. Rats in the test group consumed less feed and gained less weight than control animals; similar findings have been documented in studies of ketogenic diets. Between-group differences were noted in selected hematology, coagulation, and serum chemistry parameters; however, values were within normal physiological ranges and/or were not accompanied by other changes indicative of toxicity. Upon gross and microscopic evaluation, there were no findings associated with the ketone monoester. In a developmental toxicity study, pregnant Crl:WI (Han) rats were administered 2g/kg body weight/day ketone monoester or water (control) via gavage on days 6 through 20 of gestation. No Caesarean-sectioning or litter parameters were affected by the test article. The overall incidence of fetal alterations was higher in the test group; however, there were no specific alterations attributable to the test substance. The results of these studies support the safety of ketone monoester. (Copyright © 2012 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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