### Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 

### For Table of Contents, see home page: http://ntp.niehs.nih.gov/go/roc13 

## Acetaldehyde
CAS No. 75-07-0 Reasonably anticipated to be a human carcinogen First listed in the Sixth Annual Report on Carcinogens (1991) Also known as ethanal

C H 3 C O

H 

### Carcinogenicity Acetaldehyde is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in ex

perimental animals. Cancer Studies in Experimental Animals Exposure to acetaldehyde by inhalation caused tumors in two ro

dent species and at two different tissue sites. In rats of both sexes, it caused cancer of the nasal mucosa (squamous-cell carcinoma and adenocarcinoma), and in hamsters of both sexes, it caused cancer of the larynx (carcinoma) (IARC 1985, 1987). Inhalation of acetal

dehyde also promoted the induction of respiratory-tract tumors by intra tracheal instillation of the known carcinogen benzo[ a ]pyrene in hamsters of both sexes. Since acetaldehyde was listed in the Sixth Annual Report on Car

cinogens, an additional study in rats has been identified. Administra

tion of acetaldehyde in drinking water increased the incidences of hemolymphoreticular cancer (leukemia and lymphoma combined), benign tumors of the pancreas (islet-cell adenoma), and cancer of the bone (osteosarcoma) and nasal cavity (carcinoma) in males and be

nign mammary-gland tumors (fibroma or fibroadenoma) in females (Soffritti et al. 2002). Increased incidences of tumors observed at other sites occurred only at one of the lower doses tested.

Cancer Studies in Humans The data available from epidemiological studies are inadequate to evaluate the relationship between human cancer and exposure spe

cifically to acetaldehyde. A survey of workers producing acetaldehyde and other aldehydes in Germany reported 9 cases of cancer, includ

ing 5 of lung cancer and 2 of oral-cavity cancer, among an unspec

ified number of workers; these incidences reportedly were higher than expected, but the observations were confounded by the fact that all cases of cancer occurred in tobacco smokers (IARC 1985, 1987). Since acetaldehyde was listed in the Sixth Annual Report on Car

cinogens, additional epidemiological studies have been identified, pri

marily case-control studies of populations exposed to acetaldehyde (the main initial metabolite of alcohol) following consumption of al

coholic beverages. Alcoholic beverage consumption is listed in the Report on Carcinogens as known to be a human carcinogen . In its 1999 review, the International Agency for Research on Cancer notedthat three small case-control studies found increased risks of alcoholrelated cancer (of the oral cavity, pharynx, larynx, and esophagus) among individuals with genetic variations (polymorphisms) that re

sult in increased levels of acetaldehyde after alcohol consumption. However, IARC concluded that the data available were inadequate to evaluate the carcinogenicity of acetaldehyde (IARC 1999). Since then, a number of review articles and meta-analyses have summa

rized the results of subsequent studies that found dose-response rela

tionships between alcohol consumption and cancer of the oral cavity, pharynx, larynx, and esophagus, and possibly the stomach and col

orectum, among individuals with genetic polymorphisms that in

crease blood or salivary levels of acetaldehyde (Bagnardi et al. 2001, Zeka et al. 2003, Boffetta and Hashibe 2006, Baan et al. 2007, Boccia et al. 2009, Salaspuro 2009). In 2009, IARC concluded that acetalde

hyde associated with alcohol consumption was carcinogenic to hu

mans (Secretan et al . 2009). Few studies have been conducted on the association of these polymorphisms with cancer at other tissue sites, and the role of acetaldehyde in pancreatic, liver, bladder, or breast cancer is not clear (van Dijk et al. 2001, Terry et al. 2006, Seitz and Becker 2007, Visvanathan et al. 2007, Druesne-Pecollo et al. 2009). Studies on Mechanisms of Carcinogenesis Alcohol is metabolized to acetaldehyde by alcohol dehydrogenases (ADH), and acetaldehyde is metabolized to acetic acid by aldehyde de

hydrogenases (ALDH). In some individuals, genetic polymorphisms in these enzymes can result in either higher rates of acetaldehyde production from alcohol or lower rates of acetaldehyde metabolism to acetic acid, resulting in higher blood acetaldehyde levels after a given level of alcohol intake than in individuals without these poly

morphisms. Five ADH genes have been identified in humans, two of which have been shown to be polymorphic. The variant allele of the ALDH2 gene, which is prevalent in Asians, encodes an enzyme that has almost no ability to detoxify acetaldehyde (IARC 1999). 

### Properties Acetaldehyde is an aliphatic aldehyde that exists at room temperature as a colorless gas with a fruity, pungent odor. It is miscible with water, ether, benzene, gasoline, solvent naphtha, toluene, xylene, turpentine, and acetone. It is very flammable and is unstable in air (Akron 2009, HSDB 2009). Physical and chemical properties of acetaldehyde are listed in the following table. Property Information Molecular weight 44.0 a Specific gravity 0.79 at 16°C/4°C a Melting point –124°C a Boiling point 21°C a Log K
ow –0.34 b Water solubility 1,000 g/L at 25°C a Vapor pressure 902 mm Hg at 25°C a Vapor density relative to air 1.5 a Dissociation constant (p K
a ) 13.6 at 25°C a
Sources: a HSDB 2009, b ChemIDplus 2009. 

### Use Acetaldehyde is used primarily as a chemical intermediate in the pro

duction of acetic acid, pyridine and pyridine bases, peracetic acid, pentaerythritol, butylene glycol, and chloral. It is also used in the synthesis of crotonaldehyde, flavor and fragrance acetals, acetalde

hyde 1,1-dimethylhydrazone, acetaldehyde cyanohydrin, acetalde

hyde oxime, various acetic acid esters, paraldehyde, metaldehyde (a mollusci cide widely used to kill slugs and snails), polymers, and var

ious halogenated derivatives (IARC 1985, 1999). Acetaldehyde has been used in the manufacture of aniline dyes, plastics, and synthetic rubber, to silver mirrors, and to harden gelatin fibers. It has also been used in the production of polyvinyl acetal resins, in fuel compositions, to inhibit mold growth on leather, and in the manufacture of disin

fectants, pesticides, drugs, explosives, lacquers and varnishes, photo

graphic chemicals, phenolic and urea resins, and rubber accelerators and antioxidants (EPA 1994). Acetaldehyde is considered by the U.S. Food and Drug Adminis

tration to be generally recognized as safe for use as a flavoring agent and adjuvant (Furia and Bellanca 1975, HSDB 2009). It is an important component of food flavorings and is added to milk products, baked

### Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 2 go ods, fruit juices, candy, desserts, and soft drinks; it is especially useful for imparting orange, apple, and butter flavors. The concentra

tion of acetaldehyde in food generally is up to 0.047%. In 1976, about 8,600 kg (19,000 lb) of acetaldehyde was used as food additives. Acet

aldehyde is also used in the manufacture of vinegar and as a fruit and fish preservative. It is approved for use in phenolic resins in molded containers for contact with non-acidic foods. Acetaldehyde is no lon

ger registered as an active ingredient in any pesticide. When it was used as a fumigant for storage of apples and strawberries, it was ex

empted from a residue tolerance (IARC 1985, EPA 1994, HSDB 2009). 

### Production Acetaldehyde was first produced commercially in 1916 (IARC 1985). U.S. production was 63.5 million kilograms (140 million pounds) in 1940 and 408 million kilograms (899 million pounds) in 1960. Pro

duction peaked in 1969 at 748 million kilograms (1.65 billion pounds), decreasing to 281 million kilograms (619 million pounds) in 1982. In 2009, acetaldehyde was produced by 50 manufacturers worldwide (17 in China, 12 in India, 6 in East Asia, 5 in Europe, 5 in Central and South America, 2 in Mexico, 2 in the Middle East, and 1 in the United States) (SRI 2009) and was available from 49 suppliers, in

cluding 21 U.S. suppliers (ChemSources 2009). U.S. imports of ac

etaldehyde increased from 1,000 kg (2,200 lb) in 1989 to 414,000 kg (913,000 lb) in 2006 (USITC 2009). U.S. exports of acetaldehyde were 19 million kilograms (42.6 million pounds) in 1989, decreasing to 1.6 million kilograms (3.5 million pounds) in 2003 and remaining near this level from 2004 through 2008 (USITC 2009). Reports filed under the U.S. Environmental Protection Agency’s Toxic Substances Con

trol Act Inventory Update Rule indicated that U.S. production plus imports of acetal dehyde totaled 500 million to 1 billion pounds in 1986 and 1990 and 100 million to 500 million pounds in 1994, 1998, and 2002 (EPA 2004). 

### Exposure There is high potential for exposure of the general population to ac

etaldehyde through ingestion, inhalation, and dermal contact and of workers through inhalation and dermal contact. The main source of exposure of the general population is through consumption of alco

holic beverages and the subsequent metabolism of alcohol to form acet aldehyde (HSDB 2009). Because acetaldehyde may form in wine and other alcoholic beverages after exposure to air (Hagemeyer 2002), alcoholic beverages (including wines, beer, and spirits) also frequently contain acet aldehyde as a volatile component (HSDB 2009). Acetaldehyde is a product of most hydrocarbon oxidation reac

tions and is a normal intermediate in the respiration of most higher plants. It is found in trace amounts in many plant products, includ

ing apples, broccoli, coffee, grapefruit, grapes, lemons, mushrooms, onions, oranges, peaches, nectarines, pears, pineapples, raspberries, strawberries, cranberries, sour cherries, and mango. It has been de

tected in the essential oils of alfalfa, rosemary, balm, clary sage, daf

fodil, bitter orange, camphor, angelica, fennel, mustard, peppermint, and lychee, and in oak and tobacco leaves and cotton leaves and blos

soms (IARC 1985, Burdon et al. 1996, Gorny et al. 1999, Gunes et al. 2002, Bonerz et al. 2007, Mahattanatawee et al. 2007). Acetaldehyde has also been detected in breast milk. Consumers may be exposed to acetaldehyde in many milk products, including all types of cheese, yo

gurt, and milk of varying fat content (Mistry and Hassan 1992, Bar

bieri et al. 1994, Jandal 1996, Beshkova et al. 1998, Van Aardtet al. 2001, Kondyli et al. 2002, Boscaini et al. 2003, Di Cagno et al. 2004, Fernandez-Garcia et al. 2004, Blagden and Gilliland 2005, Gadaga et al. 2007, Kaminarides et al. 2007). Acetaldehyde has also been de

tected in cooked beef, chicken, and fish (HSDB 2009, Yasuhara and Shibamoto 1995) and is used as a synthetic flavoring ingredient in processed foods, especially margarine (HSDB 2009). According to EPA’s Toxics Release Inventory, environmental re

leases of acetaldehyde have increased slightly since 1988, when 9.5 million pounds was released, 73% to air, 23% to underground injec

tion wells, and the remainder to surface water and landfills. Since then, releases to underground injection wells have decreased, and re

leases to surface water have increased. In 2007, 11.4 million pounds of acetaldehyde was released from 336 facilities that processed, pro

duced, or used the chemical; 29 facilities each released more than 100,000 lb. Of the total amount, 94% was released to air, 3.1% to un

derground injection wells, and 2.8% to water (TRI 2009). Acetalde

hyde will volatilize rapidly from water or land, and it will leach into the ground, where it will biodegrade (HSDB 2009). Acetaldehyde is also degraded readily in soil, sewage, and natural waters by micro

organisms (EPA 1987). Acetaldehyde is a natural product of photooxidation of hydro

carbons commonly found in the atmosphere and occurs naturally as emissions from forest fires, volcanoes, and animal wastes. In the 1990s, annual emissions of acetaldehyde from all sources in the United States were estimated at 12.1 million kilograms (27 million pounds) (IPCS 1995). Burning wood produces acetaldehyde at ap

proximately 0.7 g/kg of wood, and fireplace emissions range from 0.083 to 0.20 g/kg of wood burned (HSDB 2009). In the 1990s, an

nual emissions from residential burning in the United States were estimated at 5,000 metric tons (11 million pounds) (IPCS 1995). Ac

etaldehyde is also a combustion product of some plastics (e.g., poly

carbonate) and some hard and soft polyurethane foams. It also occurs in gasoline exhaust (1.4 to 8.8 mg/m 3 ) and diesel exhaust (0.05 to 6.4 mg/m 3 ); however, very little is emitted from small engines such as lawn mowers or leaf blowers (IARC 1985, Baldauf et al. 2006). Many individuals are exposed to acetaldehyde by inhalation. The highest ambient-air concentrations of acetaldehyde were reported for urban or suburban areas or near sources of combustion (HSDB 2009). In ambient air, concentrations of acetaldehyde generally av

eraged 5 μg/m 3 . Indoor air concentrations were higher than ambient concentrations in all locations where acetaldehyde air concentrations were measured, both in the United States and in other countries (Miguel et al. 1995, Mukund et al. 1996, Brickus et al. 1998, Mac

Intosh et al. 2000, Possanzini et al. 2002, Baez et al. 2003, Hellen et al. 2004, Hodgson et al. 2004, Park and Ikeda 2004, Saijo et al. 2004, Saxet al. 2004, Shendell et al. 2004, Gilbertet al. 2005, Cavalcante et al. 2006, Ohuraet al. 2006, Pang and Mu 2006, Sax et al. 2006, Hodg

son et al. 2007, Possanzini et al. 2007). Acetaldehyde is also found in tobacco and marijuana cigarette smoke (1,220 μg per cigarette) and tobacco cigarettes (980 to 1,370 μg per cigarette). In 1988–89, acetaldehyde was detected in 4 of 10 surveyed water supplies (EPA 1987). In surface water, concentrations generally are less than 0.1 μg/L, and the contribution from drinking water to hu

man exposure is considered negligible (IPCS 1995). The National Occupational Exposure Survey (conducted from 1981 to 1983) estimated that 216,533 workers, including 97,770 women, potentially were exposed to acetaldehyde (NIOSH 1990). Workers potentially exposed include those involved in the manufac

ture or use of industrial organic chemicals, dyes, fabricated rubber, plastics, urea-formaldehyde foam insulation, fuels, drugs, explo

sives, varnishes, pesticides, food additives, leather goods, and mir

rors (IARC 1985, EPA 1994). 

### Regulations Coast Guard, Department of Homeland Security Minimum requirements have been established for safe transport of acetaldehyde on ships and barges.

### Report on Carcinogens, Thirteenth Edition

National Toxicology Program, Department of Health and Human Services 3 Department of Transportation (DOT) Acetaldehyde is considered a hazardous material, and special requirements have been set for marking, labeling, and transporting this material. Environmental Protection Agency (EPA) Clean Air Act Mobile Source Air Toxics:Listed as a mobile source air toxic for which regulations are to be developed. National Emission Standards for Hazardous Air Pollutants:Listed as a hazardous air pollutant. New Source Performance Standards:Manufacture of acetaldehyde is subject to certain provisions for the control of volatile organic compound emissions. Prevention of Accidental Release:Threshold quantity (TQ) = 10,000 lb. Urban Air Toxics Strategy:Identified as one of 33 hazardous air pollutants that present the greatest threat to public health in urban areas. Clean Water Act Designated a hazardous substance. Comprehensive Environmental Response, Compensation, and Liability Act Reportable quantity (RQ) = 1,000 lb. Emergency Planning and Community Right-To-Know Act Toxics Release Inventory:Listed substance subject to reporting requirements. Resource Conservation and Recovery Act Listed Hazardous Waste:Waste code for which the listing is based wholly or partly on the presence of acetaldehyde = U001. Occupational Safety and Health Administration (OSHA) While this section accurately identifies OSHA’s legally enforceable PELs for this substance in 2010, specific PELs may not reflect the more current studies and may not adequately protect workers. Permissible exposure limit (PEL) = 200 ppm (360 mg/m 3 ). Considered a highly hazardous chemical: Threshold quantity (TQ) = 2,500 lb. 

### Guidelines American Conference of Governmental Industrial Hygienists (ACGIH) Threshold limit value – ceiling (TLV-C) = 25 ppm. National Institute for Occupational Safety and Health (NIOSH) Immediately dangerous to life and health (IDLH) limit = 2,000 ppm. Listed as a potential occupational carcinogen. 

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### Report on Carcinogens, Thirteenth Edition

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