Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach

Lachenmeier, Dirk W.; Przybylski, Maria C.; Rehm, Jürgen

doi:10.1002/ijc.27553

Cited by 98 publications

(80 citation statements)

References 28 publications

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“…The major risk, however, certainly comes from ethanol with a MOE of 1 or even smaller (55). Ethanol was also identifi ed as the most important carcinogen in alcoholic beverages in a comparative quantitative assessment of 15 carcinogenic compounds (56). This study fully confirms this finding and suggests prioritising general alcohol policy measures over more specifi c measures such as mitigative efforts to reduce the content of trace contaminants such as formaldehyde.…”

Section: Discussionsupporting

confidence: 67%

The Margin of Exposure to Formaldehyde in Alcoholic Beverages

Monakhova¹,

Jendral

Lachenmeier

2012

Archives of Industrial Hygiene and Toxicology

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Formaldehyde has been classifi ed as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the fi rst risk assessment of formaldehyde for consumers of alcoholic beverages. Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments. For tumours in male rats, a BMD of 30 mg kg -1 body weight per day and a "BMD lower confi dence limit" (BMDL) of 23 mg kg -1 d -1 were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10-5 mg kg -1 d -1. Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns. The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde. Monakhova Y B, et al. EXPOSURE TO FORMALDEHYDE IN ALCOHOLIC BEVERAGES Arh Hig Rada Toksikol 2012;63:227-237 Formaldehyde (methanal, CH 2 O, CAS # 50-00-0) is a colourless substance, which is widely present in foods, industry, and in the environment (1, 2) and may also be endogenously produced in humans and animals (3). The industrial use includes mainly the production of various types of resin, the use as intermediate in the manufacture of industrial chemicals, and the direct use in aqueous solutions (formalin) as a disinfectant and preservative (1-3). Epidemiological studies have demonstrated a causal relationship between formaldehyde and cancer in humans (3). Causality is indicated by consistent fi ndings of increased risks of nasopharyngeal cancer, sinonasal cancer, and myeloid leukaemia among individuals with high exposure to formaldehyde. The fi ndings are based on case-control studies of industrial workers and other professional groups in inhalatory contact with formaldehyde such as pathologists, funeral directors or embalmers (3). Biological mechanisms associated with formaldehydeinduced cancer are not completely understood, but potential carcinogenic modes of actions for formaldehyde include DNA reactivity (covalent Unauthenticated Download Date | 5/8/18 6:46 AM 228 binding), gene mutation, chromosomal breakage, aneuploidy, and epigenetic effects (3). However, the biological plausibility of an associa...

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Section: Discussionsupporting

confidence: 67%

The Margin of Exposure to Formaldehyde in Alcoholic Beverages

Monakhova¹,

Jendral

Lachenmeier

2012

Archives of Industrial Hygiene and Toxicology

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“…This classification relates to the last review of the subject in 1994 (IARC Working Group on (2010) and Lachenmeier et al (2012) with permission from John Wiley and Sons) a The compounds were selected as follows: the complete IARC list of known and suspected human carcinogens was compared with the list of compounds regularly occurring in alcoholic beverages (see Table 1.14, p. 113 in IARC Working Group on the Evaluation of Carcinogenic Risks to Humans 2010). From this summary, the compounds set into IARC group 1 (carcinogenic to humans), IARC group 2A (probably carcinogenic to humans) and IARC group 2B (possibly carcinogenic to humans) were chosen to be included.…”

Section: Acrylamidementioning

confidence: 99%

“…For Table 2 Occurrence of WHO International Agency for Research on Cancer (IARC) known and suspected human carcinogens in alcoholic beverages (updated from Lachenmeier et al (2012) Caramel coloured products: 9/28 µg/L in dark beer, Klejdus et al (2006); 0/0.14 mg/L in whisky, Yoshikawa and Fujiwara (1981) N-Nitrosodimethylamine 0.1/1.3 µg/kg (beer)…”

Section: Comparative Risk Assessment Of Compounds In Alcoholic Beveragesmentioning

confidence: 99%

“…The toxicological endpoints used for dose-response modelling and the chosen points of departure for MOE assessment are shown in Table 3. The full methodology for the comparative assessment is available in Lachenmeier et al (2012). For this review, the new IARC-evaluated carcinogens glyphosate, 3-MCPD and pulegone were included using exactly the same methodology.…”

Section: Comparative Risk Assessment Of Compounds In Alcoholic Beveragesmentioning

confidence: 99%

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Carcinogenic compounds in alcoholic beverages: an update

et al. 2016

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The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

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“…Human cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) is one of the major phase I enzymes, involved in the activation of carcinogens related to head and neck cancers, such as polycyclic aromatic hydrocarbon (PAH), heterocyclic amines, N-nitrosamine, alkaloids, polyphenols and tannins present in tobacco smoke and betel quid (Wu et al, 2004;Sharan et al, 2012). Ethanol and acetaldehyde of alcoholic drinks are important chemical agents related to various cancers (Lachenmeier et al, 2012). Therefore, modulation of CYP1A1 activity may be important in the aetiology of HNC.…”

Section: Introductionmentioning

confidence: 99%