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Animal Studies
Rats
Woutersen et al. (1984, 1986) exposed groups of 105 male and female SPF-Wistar rats to
atmospheres containing acetaldehyde concentrations of 0, 750, 1500, or 3000/1000 ppm (0, 1350,
2700 or 5400/1800 mg/m 3 , respectively), 6 hours/day, 5 days/week for up to 28 months. The highest
concentration was gradually decreased from 3000 ppm (days 0 to 141) to 1000 ppm (from day 313
forward) because of severe growth retardation, loss of body weight, and early mortality.
Treatment-related nonneoplastic histopathological lesions were observed in the nose, larynx, and lungs,
with the most severe lesions seen in the nose and in the vocal cord region of the larynx.
Nasal tumors observed were mainly squamous cell carcinomas and adenocarcinomas originating from
the respiratory and olfactory epithelium, respectively. Tumor incidences are listed in Table 1. The
incidences of adenocarcinomas were significantly (p < 0.01) higher in both sexes of rats at all exposure
concentrations when compared to controls. Squamous cell carcinomas were significantly (p < 0.01)
increased in males in the mid- and high-dose groups and in females in the high-dose group. No
laryngeal or lung tumors were seen in male rats and tumors observed in the other organs of treated rats
were comparable to those in the controls. The presence of nasal tumors at all exposure levels suggested
that the latency period for nasal tumor induction was independent of the acetaldehyde concentration.
The authors concluded that under the conditions of this study, acetaldehyde was carcinogenic to the
nasal mucosa of rats.
Table 1:
Nasal tumor incidence in male and female Wistar rats exposed to acetaldehyde by
inhalation (Woutersen et al., 1986)
Sex Exposure Concentration (ppm) Nasal Tumor Incidence
males 0 1/49
750 17/52
1500 41/53
females 0 0/50
750 6/48
1500 36/53
In an extension of the above study, Woutersen and Feron (1987) examined the process of regeneration
of damaged nasal mucosa in rats exposed to acetaldehyde at concentrations as described above for 52
weeks. Animals were sacrificed after a recovery period of 26 weeks. The number of nasal tumors
observed was almost the same as in the lifetime study, which indicated that proliferative epithelial lesions
of the nose may develop into tumors even without continued acetaldehyde exposure.
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