title: Paired acute inhalation test reveals that acetaldehyde toxicity is higher in aldehyde dehydrogenase 2 knockout mice than in wild-type mice.
abstract: Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2); acute inhalation toxicity of acetaldehyde has not been evaluated in these populations. We compared the toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice by using the paired acute inhalation test modified from the acute toxic class method (OECD TG433). Blood acetaldehyde level was measured 4 hr after the inhalation. A pair of Aldh2+/+ and Aldh2-/- mice was put into a chamber and was exposed to 5000 ppm of acetaldehyde. At the start of the inhalation, the mice exhibited hypoactivity and closing of the eyes. Subsequently, symptoms such as crouching, bradypnea, and piloerection were observed. Flushing was observed only in the Aldh2+/+ mice. Symptoms such as tears, straggling gait, prone position, pale skin, abnormal deep respiration, dyspnea, and one case of death were observed only in the Aldh2-/- mice. The symptoms did not change 1 hr after inhalation in the Aldh2+/+ mice. In contrast, in the Aldh2-/- mice, the symptoms became more severe until the end of the inhalation. The blood acetaldehyde level in the Aldh2-/- mice was approximately twice that in the Aldh2+/+ mice 4 hr after inhalation. The Aldh2-/- mice evidently showed more severe toxicity as compared with the Aldh2+/+ mice due to acute inhalation of acetaldehyde at a concentration of 5000 ppm. Acetaldehyde toxicity in Aldh2+/+ and Aldh2-/- mice was estimated and classified one class different. Based on this study, acetaldehyde inhalations were inferred to pose a higher risk to ALDH2-inactive human individuals.
authors.affiliation: Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. isse@med.uoeh-u.ac.jp
authors.forename: Toyohi
authors.initials: T
authors.lastname: Isse
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Oyama
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuno
authors.forename: Masanori
authors.initials: M
authors.lastname: Ogawa
authors.forename: Rie
authors.initials: R
authors.lastname: Narai-Suzuki
authors.forename: Tetsunosuke
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Tomoe
authors.initials: T
authors.lastname: Murakami
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kinaga
authors.forename: Iwao
authors.initials: I
authors.lastname: Uchiyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawamoto
mesh_terms: D000079:Acetaldehyde / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D000280:Administration, Inhalation; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007527:Isoenzymes / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D013997:Time Factors; D023382:Toxicity Tests, Acute
chemical_list: D007527:Isoenzymes; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde