Sustained Human Background Exposure to Acrolein Evidenced by Monitoring Urinary Exposure Biomarkers

Abstract

Scope: This study investigates a potential correlation between the intake of heat-processed food and the excretion of the acrolein (AC) biomarkers N-acetyl-S-(3-hydroxypropyl)-l-cysteine (HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) based on two human studies. Methods and Results: Human exposure to AC is monitored using the AC-related mercapturic acids HPMA and CEMA in the urine of a) non-smoking volunteers under defined living conditions and b) of non-smoking volunteers on unrestricted or vegan diet under free living conditions. Free living volunteers in part show markedly enhanced urinary excretions of HPMA and CEMA. The intake of heat-processed food does not influence AC-related biomarker excretion. Incidentally enhanced urinary exposure biomarker levels appear to suggest AC exposure possibly from open fire, barbecuing, or tobacco smoke. However, kinetics of urinary biomarkers related to tobacco and other potential smoke exposure, do not correlate with those observed for HPMA and CEMA. Conclusion: This study is the first to convincingly show a sustained and substantial background exposure to AC in non-smoking humans, clearly independent from uptake of heat-processed foods. The data strongly point to endogenous AC generation by pathways of mammalian and/or microbial metabolism as yet not taken into consideration.

Mode of action-based risk assessment of genotoxic carcinogens

“…This endogenous baseline exposure is estimated to account for about 0.2-0.4 µg AA/kg bw/day, quite close to the average dietary exposure level. The source of this endogenous background is not clear at present but it may well originate from the metabolism of the intestinal microbiota, as has recently been reported for acrolein that appears to be generated at about tenfold higher level than acrylamide (Goempel et al 2017;Goerke et al 2019;Ruenz et al 2016;Ruenz et al 2019).…”

Revisiting the evidence for genotoxicity of acrylamide (AA), key to risk assessment of dietary AA exposure

“…For AA, this endogenous background exposure has been estimated to be relatively close to the average dietary exposure. Moreover, human endogenous exposure to the close AA analogue, acrolein (AC), has recently been reported to be even more than tenfold higher than that to endogenous AA (Goempel et al 2017 ; Goerke et al 2019 ; Ruenz et al 2016 , 2019 ). It may be presumed that such endogenous exposure may be variable, depending on as yet largely unknown factors of influence.…”

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

“…AC exposure has been assessed based on a daily HPMA excretion (200–1000 μg/24 h) in urine of non-smokers or former smokers on abstinence and assuming 20% urinary excretion of ingested AC, in analogy to data obtained from rats. As mentioned above, this resulted in a total AC exposure estimate of 300–1400 μg/day, suggesting an intake of 5–24 μg/kg bw/day (Ruenz et al 2019 ).…”

“…On the assumption that about 20% of a given AC intake is excreted as 3-HPMA, a total exposure of about 300–1400 μg/day or 5–24 μg/kg bw/day has been estimated (SKLM 2013 ). Stringently controlled human biomarker studies arrived at similar estimates of about 10–12 μg/kg bw/day, based on monitoring of urinary 3-HPMA, supposedly excreted at 20% of the total AC dose (Ruenz et al 2019 ).…”

“…AC may be formed endogenously from carbohydrates, triacylglycerides, and certain amino acids. Non-microbial endogenous formation routes of AC include myeloperoxidase catalysed formation of AC from threonine, amine oxidase catalysed formation from spermine and spermidine, and formation as a by-product of lipid peroxidation (Ruenz et al 2019 ).…”