Detection of a Hemoglobin Adduct of the Food Contaminant Furfuryl Alcohol in Humans: Levels of N‐((Furan‐2‐yl)methyl)‐valine in Two Epidemiological Studies

Abstract

Scope: Furfuryl alcohol is a heat-induced food contaminant, classified as possibly carcinogenic to humans. The proximal carcinogen 2-sulfoxymethylfuran leads to adduct formation in DNA and proteins (e.g., N-((furan-2-yl)methyl)-Val (FFA-Val) in hemoglobin). Methods and results: This study analyzed human erythrocyte samples from two studies for the presence of FFA-Val: the Risks and Benefits of a Vegan Diet study (RBVD; 72 adults) and the ENVIRonmental influence ON early AGEing birth cohort study (ENVIRONAGE; 100 mother-newborn pairs). In the RBVD study, FFA-Val levels are lower in vegans compared to omnivores (median 13.0 vs 15.8 pmol g −1 hemoglobin, p = 0.008), and lower in non-smokers compared to smokers (median 14.1 vs 17.0 pmol g −1 hemoglobin, p = 0.003). In the birth cohort, FFA-Val levels are distinctly higher in maternal compared to newborn samples (median 15.2 vs 2.2 pmol g −1 hemoglobin, p < 0.001). Conclusions: FFA-Val, hitherto detected only in blood samples of mice, is quantifiable in all human samples, indicating a general exposure to furfuryl alcohol. The low adduct levels in blood samples from newborn children suggested that the placenta is a barrier to furfuryl alcohol. Dietary habits and tobacco smoking are two main influencing factors on the formation of FFA-Val, which may be of use as a biomarker of exposure to furfuryl alcohol.

A comparison of the exposure system of glycidol‐related chemicals on the formation of glycidol‐hemoglobin adducts

“…Thus, various Hb adducts derived from many chemicals have been found in human blood (Carlsson et al., 2014 ; Degner et al., 2018 ; Goel et al., 2013 ). Other Hb adducts have been identified from substances other than glycidol, including ethylene oxide, glyoxal, methyl vinyl ketone, acrylamide, acrylic acid, methyl glyoxal, ethyl vinyl ketone, glycidamide (Carlsson et al., 2019 ), and furfuryl alcohol (Monien et al., 2021 ). Glycidol administration to mice or rats resulted in the formation of a hydroxypropanoic acid valine adduct ( m/z 577) from glycidic acid, a minor metabolite of glycidol (Vryonidis et al., 2022 ).…”

Non-innocuous Consequences of Metabolic Oxidation of Alkyls on Arenes

“…In contrast, regio­isomeric furan-3-methanol was only weakly mutagenic in all strains, independent of SULT expression. Both furfuryl alcohol and 5-hydroxy­methyl­furfural are considered mutagenic and carcinogenic via sulfate formation (and are rodent carcinogens); furfuryl alcohol has been shown to give rise to hemoglobin adducts in vivo in both humans and mice . Certain SULT subtypes were shown to play a large role for adduct formation in transgenic mice …”

“…However, it appears that most primary benzylic alcohols are not overly labile at neutral pH and will have to be sulfated in vivo to generate FQMs by an elimination reaction within a relevant time frame. For example, the widespread preservative and antioxidant BHT (19) can also be detected via the presence of its oxidation product BHT-OH (Chart 1, 20) in the environment, in amounts up to around 1 μg/g in indoor dust in the U.S. and several Asian countries. 22 This might point to half-lives in the range of days for many benzylic alcohols that, in principle, can generate QMs (see Scheme 6,below).…”

“…Both furfuryl alcohol and 5-hydroxymethylfurfural are considered mutagenic and carcinogenic via sulfate formation (and are rodent carcinogens); 20 furfuryl alcohol has been shown to give rise to hemoglobin adducts in vivo in both humans and mice. 105 Certain SULT subtypes were shown to play a large role for adduct formation in transgenic mice. 106 2-Methylnaphthalene is an industrial chemical that is teratogenic, carcinogenic, and cytotoxic.…”

“…The benzylic sulfate, a RM, can of course also alkylate directly. One example, shown in Scheme D, is furfuryl alcohol ( 10 ), a ubiquitous food contaminant, which has been studied in vitro and in vivo . , …”