A subchronic 90-day oral rat toxicity study and in vitro genotoxicity studies with a conjugated linoleic acid product

Conjugated linoleic acid (CLA) is the term given to a group of positional and geometric isomers of the essential fatty acid linoleic acid. CLA is found naturally in foods such as dairy and meat products. CLA is reported to have a number of beneficial effects including anticarcinogenic activity. However, safety data are limited. Clarinol™ G80 is a commercial preparation containing equal amounts of the 9cis,11trans and 10trans,12cis CLA isomers in the form of glycerides. In order to support the safety-in-use of Clarinol™ G80 as an ingredient in food, the preparation was tested in two in vitro mutagenicity assays, an Ames test and an in vitro cytogenetics assay, and a 90-day repeat-dose oral toxicity rat study. Clarinol™ G80 was non-mutagenic in both in vitro assays. In the 90-day study, Clarinol™ G80 produced hepatocellular hypertrophy in female rats at the highest dose level (15% w/w). This effect was an adaptive effect in response to feeding high levels of Clarinol™ G80 in the diet and was reversible upon withdrawal of test material. An increase in plasma insulin levels was also observed female rats fed 15% w/w Clarinol™ G80 but there was no effect on plasma glucose levels. A No Observed Adverse Effect Level of 2433 mg/kg bw/day for male and 2728 mg/kg bw/day female rats was identified in the study.