Feron VJ, Til HP, de Vrijer F, Woutersen RA, Cassee FR, van Bladeren PJ. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutat Res 1991;259:363-85.
Wotld Health Organization (WHO). Formaldehyde. Concise international chemical assessment document 40. Geneva: WHO; 2002.
National Toxicology Program (NTP). Final report on carcinogens background document for formaldehyde. Rep Carcinog Backgr Doc 2010;(10-5981):i-512.
Soffritti M, Belpoggi F, Lambertin L, Lauriola M, Padovani M, Maltoni C. Results of long-term experimental studies on the carcinogenicity of formaldehyde and acetaldehyde in rats. Ann N Y Acad Sci 2002;982:87-105.
Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V; WHO International Agency for Research on Cancer Monograph Working Group. A review of human carcinogens - Part F: chemical agents and related occupations. Lancet Oncol 2009;10:1143-4. [CrossRef]
Wotld Health Organization (WHO). Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropan-2-ol. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 88. Geneva: WHO; 2006.
US Environmental Protection Ageny (US EPA). Formaldehyde (CASRN 50-00-0). Integrated Risk Information System. Document 0419. Washington (DC): US EPA; 1998.
Penteado JCP, Sobral AC, Masini JC. Evaluation of monolithic columns for determination of formaldehyde and acetaldehyde in sugar cane spirits by high-performance liquid chromatography. Anal Lett 2008;41:1674-81. [CrossRef]
Sampaio OM, Reche RV, Franco DW. Chemical profile of rums as a function of their origin. The use of chemometric techniques for their identification. J Agric Food Chem 2008;56:1661-8.
Lachenmeier DW, Schoeberl K, Kanteres F, Kuballa T, Sohnius E-M, Rehm J. Is contaminated unrecorded alcohol a health problem in the Europeab Union? A review of existing and methodological outline for future sdudies. Addiction 2011;106(Suppl 1):20-30. [CrossRef]
Jendral JA, Monakhova YB, Lachenmeier DW. Formaldehyde in alcoholic beverages: large chemical survey using purpald screening followed by chromotropic Acid spectrophotometry with multivariate curve resolution. Int J Anal Chem 2011;2011:1-11.
Lachenmeier DW, Haupt S, Schulz K. Defining maximum levels of higher alcohols in alcoholic beverages and surrogate alcohol products. Regul Toxicol Pharmacol 2008;50:313-21.
Lachenmeier DW, Kanteres F, Rehm J. Carcinogenicity of acetaldehyde in alcoholic beverages: risk assessment outside ethanol metabolism. Addiction 2009;104:533-50.
EFSA. Ethyl carbamate and hydrocyanic acid in food and beverages. EFSA J 2007;551:1-44.
European Food Safety Authority (EFSA). Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA J 2005;282:1-31.
Kerns WD, Pavkov KL, Donofrio DJ, Gralla EJ, Swenberg JA. Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res 1983;43:4382-92. [PubMed]
Monticello TM, Swenberg JA, Gross EA, Leininger JR, Kimbell JS, Seilkop S, Starr TB, Gibson JE, Morgan KT. Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res 1996;56:1012-22.
Kamata E, Nakadate M, Uchida O, Ogawa Y, Suzuki S, Kaneko T, Saito M, Kurokawa Y. Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher-344 rats. J Toxicol Sci 1997;22:239-54. [CrossRef]
Til HP, Woutersen RA, Feron VJ, Hollanders VHM, Falke HE, Clary JJ. 2-Year drinking-water study of formaldehyde in rats. Food Chem Toxicol 1989;27:77-87.
Tobe M, Naito K, Kurokawa Y. Chronic toxicity study on formaldehyde administered orally to rats. Toxicology 1989;56:79-86.
Takahashi M, Hasegawa R, Furukawa F, Toyoda K, Sato H, Hayashi Y. Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen-peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. Jpn J Cancer Res 1986;77:118-24.
US Environmental Protection Agency (US EPA). The use of the benchmark dose approach in health risk assessment. EPA/630/R-94/007. Washington (DC): US EPA; 1995.
Skog E. A toxicological investigation of lower aliphatic aldehydes. I. Toxicity of formaldehyde, acetaldehyde, propionaldehyde and butyraldehyde; as well as acrolein and crotonaldehyde. Acta Pharmacol Toxicol 1950;6:299-318.
Trezl L, Csiba A, Juhasz S, Szentgyorgyi M, Lombai G, Hullan L. Endogenous formaldehyde level of foods and its biological significance. Z Lebensm Unters Forsch A 1997;205:300-4.
Cui X, Fang G, Jiang L, Wang S. Kinetic spectrophotometric method for rapid determination of trace formaldehyde in foods. Anal Chim Acta 2007;590:253-9.
Wang S, Cui X, Fang G. Rapid determination of formaldehyde and sulfur dioxide in food products and Chinese herbals. Food Chem 2007;103:1487-93.
Bianchi F, Careri M, Musci M, Mangia A. Fish and food safety: Determination of formaldehyde in 12 fish species by SPME extraction and GC-MS analysis. Food Chem 2007;100:1049-53.
Lawrence JF, Iyengar JR. The determination of formaldehyde in beer and soft drinks by HPLC of the 2,4-dinitrophenylhydrazone derivative. Int J Environ Anal Chem 1983;15:47-52.
de Oliveira EA, de Andrade JB. Simultaneous determination of formaldehyde and acetaldehyde and their respective hydroxyalkylsulfonic acids by HPLC. Quimica Nova 1994;17:13-6.
de Andrade JB, Reis JN, Rebouças MV, Pinheiro HLC, Andrade MV. Determination of formaldehyde and acetaldehyde in drinking water and alcoholic beverages by high performance liquid chromatography (HPLC). Quimica Anal 1996;15:144-7.
Nascimento RF, Marques JC, Neto BSL, De Keukeleire D, Franco DW. Qualitative and quantitative high-performance liquid chromatographic analysis of aldehydes in Brazilian sugar cane spirits and other distilled alcoholic beverages. J Chromatogr A 1997;782:13-23.
Ebeler SE, Spaulding RS. Characterization and measurement of aldehydes in wine. In: Waterhouse AL, Ebeler SE, editors. Chemistry of wine flavor. Washington (DC): American Chemical Society; 1998. p. 166-79.
Lau MN, Ebeler JD, Ebeler SE. Gas chromatographic analysis of aldehydes in alcoholic beverages using a cysteamine derivatization procedure. Am J Enol Vitic 1999;50:324-33.
Wardencki W, Sowinski P, Curylo J. Evaluation of headspace solid-phase microextraction for the analysis of volatile carbonyl compounds in spirits and alcoholic beverages. J Chromatogr A 2003;984:89-96.
Burini G, Coli R. Determination of formaldehyde in spirits by high-performance liquid chromatography with diode-array detection after derivatization. Anal Chim Acta 2004;511:155-8.
Curylo J, Wardencki W. HS-SPME-CGC-PID determination of aldehydes in rectified spirits and vodkas after derivatisation with 2,4,6-trichlorophenylhydrazine (TCPH). Chem Anal (Warsaw) 2005;50:735-48.
Anonymous. Chinese brewing industry defend use of formaldehyde. Modern Brewery Age 2005 July 18.
Rodríquez DM, Wrobel K, Wrobel K. Determination of aldehydes in tequila by high-performance liquid chromatography with 2,4-dinitrophenylhydrazine derivatization. Eur Food Res Technol 2005;221:798-802.
Sowinski P, Wardencki W, Partyka M. Development and evaluation of headspace gas chromatography method for the analysis of carbonyl compounds in spirits and vodkas. Anal Chim Acta 2005;539:17-22.
Curylo J, Wardencki W. Application of single drop extraction (SDE) gas chromatography method for the determination of carbonyl compounds in spirits and vodkas. Anal Lett 2006;39:2629-42. [CrossRef]
Park YS, Lee YJ, Lee KT. Analysis of formaldehyde and acetaldehyde in alcoholic beverage. J Korean Soc Food Sci Nutr 2006;35:1412-9.
Wu QJ, Lin H, Fan W, Dong JJ, Chen HL. Investigation into benzene, trihalomethanes and formaldehyde in Chinese lager beers. J Inst Brew 2006;112:291-4.
de Oliveira FS, Sousa ET, de Andrade JB. A sensitive flow analysis system for the fluorimetric determination of low levels of formaldehyde in alcoholic beverages. Talanta 2007;73:561-6.
Miyakawa H, Fujinuma K, Kamata K. Determination of formaldehyde in beer. Ann Rep Tokyo Metropol Inst Public Health 2007;58:185-8.
Elias RJ, Laurie VF, Ebeler SE, Wong JW, Waterhouse AL. Analysis of selected carbonyl oxidation products in wine by liquid chromatography with diode array detection. Anal Chim Acta 2008;626:104-10.
Zhao XQ, Zhang ZQ. Rapid and sensitive determination of formaldehyde in some beverages and foods by flow-injection fluorimetric analysis. Int J Food Sci Technol 2009;44:216-21. [CrossRef]
International Agency for Research on Cancer (IARC). Acetaldehyde. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 71. Lyon: IARC; 1999.
Bradley EL, Boughtflower V, Smith TL, Speck DR, Castle L. Survey of the migration of melamine and formaldehyde from melamine food contact articles available on the UK market. Food Addit Contam 2005;22:597-606. [CrossRef] [PubMed]
Wong JW, Ngim KK, Shibamoto T, Mabury SA, Eiserich JP, Yeo HCH. Determination of formaldehyde in cigarette smoke. J Chem Educ 1997;74:1100-3. [CrossRef]
Appel K, Bernauer U, Herbst U, Madle S, Schulte A, Richter-Reichhelm H, Gundert-Remy, U. Kann für Formaldehyd eine "sichere" Konzentration abgeleitet werden? - Analyse der Daten zur krebserzeugenden Wirkung [Can a "safe" concentration be established for formaldehyde? - Analysis of carcinogenicity data, in German]. Forsch Prax 2006;11:347-61.
Lachenmeier DW, Kanteres F, Rehm J. Epidemiology-based risk assessment using the benchmark dose/margin of exposure approach: the example of ethanol and liver cirrhosis. Int J Epidemiol 2011;40:210-8. [CrossRef] [PubMed]
Lachenmeier DW, Przybylski MC, Rehm J. Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach. Int J Cancer 2012, DOI: 10.1002/ijc.27553. [CrossRef] [PubMed]
Archives of Industrial Hygiene and Toxicology
The Journal of Institute for Medical Research and Occupational Health
4 Issues per year
IMPACT FACTOR increased in 2013: 0.727
5-year IMPACT FACTOR: 0.980
SCImago Journal Rank (SJR): 0.242
Source Normalized Impact per Paper (SNIP): 0.537
Volume 65 (2014)
Volume 64 (2013)
Volume 63 (2012)
Volume 62 (2011)
Volume 61 (2010)
Volume 60 (2009)
Volume 59 (2008)
Most Downloaded Articles
- Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model by Chaklader, Malay/ Das, Prosun/ Pereira, Jacintha Archana/ Chaudhuri, Samaresh and Law, Sujata
- A Systematic Review of Aluminium Phosphide Poisoning by Mehrpour, Omid/ Jafarzadeh, Mostafa and Abdollahi, Mohammad
- Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk by Božina, Nada/ Bradamante, Vlasta and Lovrić, Mila
- Contaminants of Medicinal Herbs and Herbal Products by Kosalec, Ivan/ Cvek, Josipa and Tomić, Siniša
- Low-grade chronic inflammation perpetuated by modern diet as a promoter of obesity and osteoporosis by Ilich, Jasminka Z./ Kelly, Owen J./ Kim, Youjin and Spicer, Maria T.
The Margin of Exposure to Formaldehyde in Alcoholic Beverages
Department of Chemistry, Saratov State University, Saratov, Russia1
Chemisches und Veterinäruntersuchungsamt (CVUA) Karlsruhe, Karlsruhe, Germany2
This content is open access.
Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 63, Issue 2, Pages 227–237, ISSN (Print) 0004-1254, DOI: 10.2478/10004-1254-63-2012-2201, June 2012
- Published Online:
The Margin of Exposure to Formaldehyde in Alcoholic Beverages
Formaldehyde has been classified 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 first 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 confidence 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.
Granica izlaganja formaldehidu u alkoholnim pićima
Formaldehid je kancerogen za ljude te je klasificiran u skupinu 1 prema WHO IARC-u. Uzrokuje leukemiju i nazofaringealni karcinom, a navodi se i kao redoviti sastojak alkoholnih pića. Međutim, rizik od izlaganja formaldehidu konzumacijom alkoholnih pića nije sustavno istražen pa će ovo istraživanje pružiti prvu takvu procjenu rizika. Količina formaldehida koju ljudi unose alkoholnim pićima u Europskoj je uniji procijenjena temeljem podataka Svjetske zdravstvene organizacije o konzumaciji alkohola i literature o sadržaju formaldehida u različitim skupinama alkoholnih pića (pivo, vino, jaka alkoholna pića i neregistrirani alkohol). Procjena rizika obavljena je korištenjem pristupa granice izlaganja (eng. margin of exposure, MOE) i graničnih doza (eng. benchmark doses, BMD) za 10 %-tni učinak koji se postiže modeliranjem odnosa doza-odgovor u ispitivanjima provedenima na životinjama. BMD od 30 mg kg-1 tjelesne težine na dan i BMD s nižom granicom pouzdanosti (BMDL) od 23 mg kg-1 d-1 izračunati su za tumore kod mužjaka štakora temeljem raspoloživih dugotrajnih ispitivanja provedenih na životinjama. Prosječno izlaganje ljudi formaldehidu u alkoholnim pićima procijenjeno je na 8·10-5 mg kg-1 d-1. U usporedbi s BMDL vrijednošću krajnji MOE je iznosio više od 200.000 u prosječnim situacijama. Čak i u najlošijim situacijama MOE nije nikada bio niži od 10.000, što se smatra graničnom vrijednošću za zdravlje ljudi. Procjena rizika pokazuje da je rizik od nastanka karcinoma uslijed izlaganja formaldehidu iz alkoholnih pića zanemariv te da je prioritet upravljanja rizikom u takvim slučajevima (npr. kako bi se smanjila kontaminacija) vrlo nizak. Najveći rizik proizlazi iz etanola i acetaldehida koji se također nalaze u alkoholnim pićima.