Genetic Toxicity Studies of the Ketogenic Ester Bis Hexanoyl (R)-1,3-Butanediol

Abstract

A series of studies was conducted to assess the genetic toxicity of a novel ketone ester, bis hexanoyl (R)-1,3-butanediol (herein referred to as BH-BD), according to Organization for Economic Co-operation and Development testing guidelines under the standards of Good Laboratory Practices. In bacterial reverse mutation tests, there was no evidence of mutagenic activity in any of the Salmonella typhimurium strains tested or in Escherichia coli strain WP2 uvrA, at dose levels up to 5,000 μg/plate in the presence or absence of Aroclor 1254-induced rat liver (S9 mix) for metabolic activation. In the in vitro micronucleus test using human TK6 cells, BH-BD did not show a statistically significant increase in the number of cells containing micronuclei when compared with concurrent control cultures at all time points and at any of the concentrations analyzed (up to 100 μg/mL, final concentration in culture medium), with and without S9 mix activation. In the in vivo micronucleus test using Sprague Dawley rats, BH-BD did not show a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes relative to the vehicle control group. Therefore, BH-BD was concluded to be negative in all 3 tests. These results support the safety assessment of BH-BD for potential use in food.

Ketone ester-what’s in a name? Ambiguity begets uncertainty

“…Categories 1 through 6 shown below, along with Figures 1 – 4 , are “ketone esters”, or compounds used to synthesize ketone esters, which are independently capable of elevating circulating ketone bodies-those compounds being 1,3-butanediol and mid-chain carboxylic acids and alcohols. Six ketone esters cover the bulk of studies performed to date, those coming from the Brunengraber group, category 3A.ii ( Desrouchers et al, 1995 ), the Veech/Clarke groups, category 3A.i ( Clarke et al, 2012 ), the Hashim group, category 4A.i ( Hashim, 2014 ) and the Buck Institute, categories 2C.iii.2 and 3B.iii ( Newman et al, 2017 ), ( Stubbs et al, 2021 ) along with medium chain triglycerides, category 4A.ii. Immediately obvious from the structures shown in Figures 1 – 4 are the additional number of compounds possible.…”