著者

長尾 美奈子 日本環境変異原学会臨時委員会

出版者

日本環境変異原学会

雑誌

環境変異原研究 (ISSN:09100865)

巻号頁・発行日

vol.26, no.2, pp.193-198, 2004 (Released:2005-12-21)

参考文献数

15

被引用文献数

2 2

---

Kojic acid (KA) , belonging to existing food additives for which compositions or usages are not clarified, had been used for prevention of enzymatic browning. In 1995, the food sanitation law was largely revised to harmonize with JECFA, OECD and FDA. Under the new law, reevaluation of existing food additives was required. In 1998, it was found that KA induced tumors in the thyroid and liver of mice. KA also showed genotoxicities; gene mutations in S. typhimurium, chromosome aberrations in CHO-K1 and CHL/IU cells in vitro, and micronuclei in the liver of mice and hematopoietic cells in rats. Although it has not been clarified whether liver or thyroid tumors were induced by genotoxic effects of KA or not, use of KA as a food additive was banned in 2003, based on the fact that KA was not used in any country at that time. The ad hoc committee which was set-up for a three-year task from 2003-2005 considered that KA was an appropriate model compound to re-evaluate the strategies presently used to detect genotoxicity in vitro and in vivo, and to re-evaluate the regulatory rules (use of genotoxic carcinogens as food additives should be totally avoided; genotoxic non-carcinogens in rodents can be used as food additives). First of all, we confirmed the genotoxicity of KA; we demonstrated that genotoxicity in S. typhimurium was due to KA itself, but not due to contaminants, KA induced TK mutations, micronuclei and DNA damage (Comet) in human lymphoblastoid cells, TK6 and WTK-1. These results support the finding that KA is genotoxic in vivo, although it is not clear yet whether KA induces tumors by its genotoxicity or not. Speculating that liver tumors induced by KA were due to its genotoxicity, human risks to KA to which humans are exposed by taking fermented food products was calculated to be 2×10-7 by the linearized multistage model.