Toxicity Investigations of (R)-3-Hydroxybutyrate Glycerides In Vitro and in Male and Female Rats

Abstract

TCN006, a formulation of (R)-3-Hydroxybutyrate glycerides, is a promising ingredient for enhancing ketone intake of humans. Ketones have been shown to have beneficial effects on human health. To be used by humans, TCN006 must be determined safe in appropriately designed safety studies. The results of a bacterial reverse mutation assay, an in vitro mammalian micronucleus study, and 14-and 90-day repeat dose toxicity studies in rats are reported herein. In the 14- and 90-day studies, male and female Wistar rats had free access to drinking water containing 0, 75,000, 125,000 or 200,000 ppm TCN006 for 92 and 93 days, respectively. TCN006 tested negative for genotoxicity and the no observed adverse effect level (NOAEL) for toxicity in the 14- and 90-day studies was 200,000 ppm, the highest dose administered. In the longer term study, the mean overall daily intake of TCN006 in the 200,000 ppm groups was 14,027.9 mg/kg bw/day for males and 20,507.0 mg/kg bw/day for females. At this concentration, palatability of water was likely affected, which led to a decrease in water consumption in both males and females compared to respective controls. This had no effect on the health of the animals. Although the rats were administered very high levels of (R)-3-Hydroxybutyrate glycerides, there were no signs of ketoacidosis.

Toxicity and Toxicokinetics of a Four-Week Repeated Gavage of Levamisole in Male Beagle Dogs: A Good Laboratory Practice Study

“…Although a statistical difference in CHOL levels was observed between the 15 and 30 mg/kg groups compared to the negative control group, it appears that the increase approaching the clinical range was attributable to the rise in HDL, or ‘good’ cholesterol. This suggests that LVM may exert some influence on the CHOL values in beagle dogs without toxicological significance [ 18 ]. Also, blood indicators combined with organ coefficient indexes, we found that continuous administration of LVM did not affect liver and kidney indexes and weights, and it did not produce accumulation effects and toxicological effects in the kidneys and liver of beagle dogs [ 19 ].…”