Abstract
Glycidol fatty acid esters that are present in foods are degraded in vivo to the animal carcinogen glycidol, which binds to the N-terminal valine of hemoglobin (Hb) to form N-(2,3-dihydroxypropyl)valine (diHOPrVal) adducts. The existence of other chemicals that are converted to glycidol is unknown. To determine the effect of different exposure conditions on the formation of diHOPrVal adducts, several glycidol-related chemicals (3-monochloropropane-1,2-diol; 3-MCPD, epichlorohydrin, glyceraldehyde, acrylic acid, and 1,2-propanediol) were evaluated using in vitro and in vivo (single/repeated dose) methods. In vitro, the reaction of 3-MCPD or epichlorohydrin with human Hb produced 17% and 0.7% of diHOPrVal, as compared to equimolar glycidol, respectively. Following a single administration of glycidol-related compounds to ICR mice, diHOPrVal formation was observed only in the epichlorohydrin-treated group after day 5 of exposure. After 14 days of repeated dosing, the amounts of diHOPrVal produced by epichlorohydrin and 3-MCPD in vivo were <1% of diHOPrVal produced by an equal molar concentration of glycidol. Furthermore, glyceraldehyde group produced 0.2% of diHOPrVal at the same molar concentration of glycidol equivalents, in which diHOPrVal formation could not be confirmed by the in vitro assay. The results indicate the usefulness of diHOPrVal as an exposure marker for glycidol; however, the contribution of its formation in vivo by exposure to various chemicals will be necessary to validate and interpret the results.