Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk

Abstract

The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 μg/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/10⁵) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels.

Keywords: Hb adduct; N-(2.3-dihydroxypropyl)valine; UPLC/MS/MS; cancer risk; glycidol; in vivo.

Figure 1

Glycidol is formed in vivo by hydrolysis of glycidyl fatty acid esters [3], where R represents different ester side chains. Glycidol reacts with the N-terminal valine in hemoglobin (Hb) to form N-(2,3-dihydroxypropyl)valine (diHOPrVal) as N-terminal.

Figure 2

Ion chromatogram from a human sample and exact mass spectrum for the fluorescein thiohydantoin (FTH) derivative (diHOPrVal-FTH) of the N-terminal valine adduct formed by glycidol (6.6 pmol/g Hb at 3 ppm mass tolerance). The m/z fragments 503, 460 and 447 were used for quantification of the adduct diHOPrVal-FTH (m/z 563).

Figure 3

N-(2,3-Dihydroxypropyl)valine adduct levels in blood from children (n = 50) and, non-smoking (n = 6) and smoking (n = 6) adults. The mean values are marked as horizontal bars. The higher level observed in the smokers is likely due to presence of glycidol in tobacco smoke (see Section 4).

Figure 4

Determination of the second-order reaction rate constant, k_val, for the formation of the N-(2,3-dihydroxypropyl)valine adduct in Hb. The data points represent the adduct levels from 1-hour incubations of glycidol with fresh human blood from triplicate samples at each dose level from four individuals, where each point corresponds to the mean from two m/z transitions. One replicate at the highest dose for individual 2 (data point in parenthesis) was excluded in the analyses as it was judged as an outlier (Grubbs test).

Figure 5

Examples of possible precursors to N-(2,3-dihydroxypropyl)valine c.f. [29,30].