VOL.: 71 (1999) (p. 319)
CAS No.:5.1 Exposure data
Exposure to acetaldehyde may occur in its production, and in the production of acetic acid and various other chemical agents. It is a metabolite of sugars and ethanol in humans and has been detected in plant extracts, tobacco smoke, engine exhaust, ambient and indoor air, and in water.
5.2 Human carcinogenicity data
An increased relative frequency of bronchial and oral cavity tumours was found among nine cancer cases in one study of chemical workers exposed to various aldehydes. Oesophageal tumours have been associated with genetically determined, high metabolic levels of acetaldehyde after drinking alcohol.
Three case–control studies assessed the risk of oral, pharyngeal, laryngeal and oesophageal cancer following heavy alcohol intake, according to genetic polymorphism of enzymes involved in the metabolism of ethanol to acetaldehyde (alcohol dehydrogenase 3) and in the further metabolism of acetaldehyde (aldehyde dehydrogenase 2 and glutathione S-transferase M1). Despite limitations in the study design and the small size of most of the studies, these studies consistently showed an increased risk of alcohol-related cancers among subjects with the genetic polymorphisms leading to higher internal doses of acetaldehyde following heavy alcohol intake as compared to subjects with other genetic polymorphisms.
5.3 Animal carcinogenicity data
Acetaldehyde was tested for carcinogenicity in rats by inhalation exposure and in hamsters by inhalation exposure and by intratracheal instillation. It produced tumours of the respiratory tract following inhalation, particularly adenocarcinomas and squamous-cell carcinomas of the nasal mucosa in rats and laryngeal carcinomas in hamsters. In hamsters, it did not cause an increased incidence of tumours following intratracheal instillation. Inhalation of acetaldehyde enhanced the incidence of respiratory-tract tumours produced by intratracheal instillation of benzo[a]pyrene.
5.4 Other relevant data
Acetaldehyde is metabolized to acetic acid. During inhalation exposure of rats, degeneration of nasal epithelium occurs and leads to hyperplasia and proliferation.
Acetaldehyde causes gene mutations in bacteria and gene mutations, sister chromatid exchanges, micronuclei and aneuploidy in cultured mammalian cells, without metabolic activation. In vivo, it causes mutations in Drosophila melanogaster but not micronuclei in mouse germ cells. It causes DNA damage in cultured mammalian cells and in mice in vivo. Acetaldehyde–DNA adducts have been found in white blood cells from human alcohol abusers.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of acetaldehyde.
There is sufficient evidence in experimental animals for the carcinogenicity of acetaldehyde.
Overall evaluation
Acetaldehyde is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluations: Vol. 36 (1985); Suppl. 7 (1987)
Synonyms
See Also:
Toxicological Abbreviations
Acetaldehyde (EHC 167, 1995)
Acetaldehyde (HSG 90, 1995)
Acetaldehyde (ICSC)
ACETALDEHYDE (JECFA Evaluation)