The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment

Abstract

The "totality" of the human exposure is conceived to encompass life-associated endogenous and exogenous aggregate exposures. Process-related contaminants (PRCs) are not only formed in foods by heat processing, but also occur endogenously in the organism as physiological components of energy metabolism, potentially also generated by the human microbiome. To arrive at a comprehensive risk assessment, it is necessary to understand the contribution of in vivo background occurrence as compared to the ingestion from exogenous sources. Hence, this review provides an overview of the knowledge on the contribution of endogenous exposure to the overall exposure to putative genotoxic food contaminants, namely ethanol, acetaldehyde, formaldehyde, acrylamide, acrolein, α,β-unsaturated alkenals, glycation compounds, N-nitroso compounds, ethylene oxide, furans, 2- and 3-MCPD, and glycidyl esters. The evidence discussed herein allows to conclude that endogenous formation of some contaminants appears to contribute substantially to the exposome. This is of critical importance for risk assessment in the cases where endogenous exposure is suspected to outweigh the exogenous one (e.g. formaldehyde and acrolein).

Keywords: Endogenous exposure; Exposome; Genotoxins; Process-related contaminants.

Fig. 1

Acetaldehyde-derived DNA adducts; for details and references see text

Fig. 2

Formation of hydroxymethyl DNA adducts induced by formaldehyde and discrimination between endogenous and exogenous sources (Adapted from Swenberg et al. 2011)

Fig. 3

Molecular dosimetry of N²-hydroxymethyl-dG adducts in the nasal epithelium of rats exposed to formaldehyde via inhalation (6 h) (Adapted from Swenberg et al. 2011)

Fig. 4

Heat-induced acrylamide formation in food

Fig. 5

Biotransformations of acrylamide. AAMA N-acetyl-S-(2-carboxamidoethyl) cysteine, GAMA isomeric GA N-acetylcysteine adducts, N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)-l-cysteine) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine

Fig. 6

Structural formulas of the different type of α,β-unsaturated aldehydes detected in the study reported by Grootveld et al. (2014) in thermally stressed oils and fats

Fig. 7

Selected glycation compounds formed during different stages of the Maillard reaction. (adapted from unpublished work, T. Henle, Institute of Food Chemistry, Technische Universität Dresden, Germany). CML Nε-(carboxylmethyl)-l-lysine, MG-H1 Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-l-ornithine

Fig. 8

Pathways of endogenous formation of glyoxal, reaction with cellular nucleophiles, and detoxification via the glyoxalase system (Adapted from WHO 2004)

Fig. 9

Metabolic activation of N-nitroso compounds

Fig. 10

Nitrosation of secondary amines by nitrous acid

Fig. 11

Main metabolic pathways for ethylene oxide (Adapted from Thier and Bolt 2000)

Fig. 12

Proposed formation pathways from the most important precursors of furan (Adapted from Yaylayan 2006)

Fig. 13

Possible endogenous formation pathway and formation from exogenous exposure of the protein-lysine-derived furan metabolites NAcLys-BDA and NAcCys-BDA-NAcLys (Adapted from Chen et al. ; Karlstetter and Mally 2020)

Fig. 14

Chemical structure of 3-MCPD, 3-MCPD-esters, glycidol and glycidylesters

Fig. 15

Biomarkers of glycidol/glycidylester exposure including 2,3-dihydroxypropylmercapturic acid (DHPMA) and N-(2,3-dihydroxypropyl)valine (2,3-diOHPr-Val) and several DNA adducts. dA deoxyadenosine, dC deoxycytidine, dG deoxyguanosine (Adapted from Rietjens et al. 2018)