Toxicity of 13C-labeled linoleic and linolenic acids for diagnostic breath tests

Abstract

Noninvasive stable isotope breath tests allow highly accurate and safe estimation of liver and biliary tract function. The aim of this study was to test 13C-labeled linoleic and linolenic acids intended for diagnostic use for acute and subchronic toxicity. The acids were synthesized using the patented method. A single intragastric administration of the tested compounds to experimental BALB/c mice and Wistar rats in the amounts exceeding clinical doses 500 to 2500-fold did not cause animal death. In the subchronic toxicity test, the rats received 5 to 25 times higher doses than recommended for clinical use in humans. In a 14-day follow-up period no significant differences were observed between the main and the control groups in terms of weight, blood count (red blood cells, white blood cells, platelets), and blood biochemistry (hemoglobin, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, bilirubin). The studied compounds are safe at doses intended for oral administration and are recommended for further preclinical and clinical trials.