Genotoxicity evaluation of kaurenoic acid.

Genotoxicity evaluations are essential components of the safety assessment for compounds intended for ingestion. Kaurenoic acid, a naturally occurring diterpene, is found in various plant species that are under investigation for potential therapeutic and sweetening properties. Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strain WP2uvrA were treated with kaurenoic acid using the Ames plate incorporation and pre-incubation methods. Up to eight dose levels were tested, with and without metabolic activation using 10 % rat liver S9 mix with standard co-factors. Kaurenoic acid did not induce an increase in revertant colony frequency at any dose level under either condition indicating a lack of mutagenic activity. Additionally, genotoxic potential was evaluated in human peripheral blood lymphocytes via the in vitro micronucleus assay. Duplicate cultures were treated with kaurenoic acid at four dose levels with exposure conditions including a 4-hour exposure with or without 2 % S9 and a 24-hour exposure without S9. While kaurenoic acid exhibited marked toxicity, it did not produce any statistically significant increase in micronucleated binucleate cells. The assay included a dose that induced approximately 55 ± 5 % cytostasis, consistent with current OECD guidelines. Under the conditions of these studies, kaurenoic acid demonstrated no evidence of mutagenicity, clastogenicity, or aneugenicity. When considered with existing literature, the current findings support the conclusion that kaurenoic acid does not pose a genotoxic risk.