Safety Assessment of Butyric Acid-Rich Triglyceride Oil: A Novel Palatable Formulation of Butyrate for the Pediatric Population.

A novel, palatable butyric acid-rich triglyceride oil has been developed and is available as a food supplement for adults in the United States and Canada. A program of safety studies was conducted with butyric acid-rich triglyceride oil for the pediatric population. The oil was tested in a microbial reverse mutation assay Ames Test OECD471 (Organisation for Economic Co-operation and Development) in which all bacterial strains showed negative responses over the complete dose range in two independently repeated experiments. All values were within the laboratory historical control data ranges. Further, data from the human lymphocyte micronucleus assay (OECD487) in the presence or absence of a metabolic activator (S9-mix), the oil did not induce a biologically relevant increase in the number of binucleated cells with micronuclei; therefore, the oil is considered not to be clastogenic or aneugenic. In a 90-day rat repeat dose toxicity study (OECD408), there were no unscheduled deaths, no treatment-related clinical signs, or effects on body weight and body weight gain, food consumption, ophthalmology, FOB parameters (including motor activity), clinical chemistry including thyroid hormones, and sperm parameters. There were no related organ weight changes, macroscopic or microscopic findings. In an extended one-generation reproductive toxicology study (EOGRTS) OECD443, there were no biologically important changes in body weight or body weight gain observed in the P generation male rats during the dosing period. At the end of the dosing period, the mean body weights in the male rats were 98% and 98% of the control group value in the 3720 and 4650 mg/kg/day dose groups, respectively. No biologically important changes in maternal body weights or body weight gains were observed during the premating, gestation, or lactation periods at dose levels up to and including 4650 mg/kg/day. Clinical signs observed in the P generation males and females were within the historical data ranges and not test substance related. There were no test substance-related changes in any other tested outcomes analyzed in the P generation males and females at doses up to and including 4650 mg/kg/day. In the F1 Generation, preweaning clinical signs observed in the males and females were within the historical data ranges and not test article related. There were no statistically significant or biologically relevant abnormalities in any of the parameters analyzed throughout the preweaning period at maternal dose levels up to and including 4650 mg/kg/day. In the postweaning period, there were also no clinical signs observed in males and females; all were within the historical data ranges and not test article related. There were no statistically significant or biologically relevant abnormalities in any of the parameters analyzed throughout the postweaning period at maternal dose levels up to and including 4650 mg/kg/day including body weights. Taken together, data from these toxicity studies show that butyric acid-rich triglyceride oil is extremely safe with a "no observed adverse effect level" (NOAEL) considered to be 4650 mg/kg/day, the highest dose tested.