A critical review on toxicological safety of 2-alkylcyclobutanones

• Mutagenicity 2-ACBs on the microorganisms was not observed.
• Several in vitro studies demonstrated the cytotoxicity of 2-ACBs.
• Genotoxicity of 2-ACBs was suggested, but elucidation of the mechanism is needed.
• 2-dDCB was metabolized into cyclic alcohol and excreted in feces.
• Further studies for toxicity of 2-ACBs following international guidelines are needed.

2-Alkylcyclobutanones (2-ACBs) are known as unique radiolytic products generated from the major fatty acids and triglycerides in food through only irradiation. Since 1990, studies on the toxicological safety of 2-ACBs have been conducted extensively with synthetic compounds. Mutagenicity tests of 2-ACBs on the microorganisms reviewed in this study clearly indicate that no evidence was observed, while several in vitro studies demonstrated the cytotoxicity of 2-ACBs through cell death. Moreover, the genotoxicity of 2-ACBs was suggested as DNA strand breaks were observed. However, these findings should be interpreted with caution because genotoxicity may result from cytotoxicity, which causes DNA damage or from cell membrane destruction and indirect oxidative DNA damage. Therefore, elucidation of the mechanism of genotoxic effects is needed. With regards to the suggestion of Raul et al. (2002) who showed the promoting effect of colon cancer by the administration of 2-ACBs, further studies are needed to correct some experimental design errors. Moreover, an in-vivo experiment that evaluated the metabolism of 2-ACBs has revealed that 2-dDCB was metabolized into cyclic alcohol and excreted through fecal discharge. In conclusion, it is considered that the ingestion of 2-ACBs through irradiated foods is unlikely to affect the human health. However, more specific studies are required to identify the fate of 2-ACBs in body and the LD50 values. The determination of chronic toxicity by long-term exposure to low concentrations of 2-ACBs has to be evaluated more clearly to determine if these compounds are safe to human.