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Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats

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Author: Appelman, L.M. · Woutersen, R.A. · Feron, V.J. · Hooftman, R.N. · Notten, W.R.F.
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Journal of Applied Toxicology, 5, 6, 331-336
Identifier: 230021
Keywords: Acetaldehyde · Animal experiment · Inhalation · Intoxication · Lung alveolus macrophage · Lung toxicity · Nonhuman · Nose mucosa · Olfactory epithelium · Olfactory system · Phagocytosis · Rat · Respiratory system · Acetaldehyde · Administration, Inhalation · Animal · Drug Administration Schedule · Lung · Male · Nasal Mucosa · Phagocytosis · Rats · Rats, Inbred Strains


The effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4-week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3-h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold. Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound-related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde or interruptedly exposed to 110 ppm with peak loads of 660 ppm. As a consequence 150 ppm acetaldehyde can be considered a 'no-toxic-effect level' in male rats exposed for 6 h/day, 5 days/week, during a 4-week period. It was concluded that the interruption of daily exposure by 1.5 h exposure-free period or by the superimposition of six times 5 min peak exposure periods did not appreciably influence the nasocytotoxic potency of acetaldehyde. Furthermore for inhalation toxicity testing of irritants such as acetaldehyde the use of variable exposure patterns does not seem to produce more relevant toxicity data than the use of uninterrupted daily exposure to a fixed concentration. Chemicals/CAS: acetaldehyde, 75-07-0; Acetaldehyde, 75-07-0