Two-year drinking-water study of formaldehyde in rats

Food Chem Toxicol. 1989 Feb;27(2):77-87. doi: 10.1016/0278-6915(89)90001-x.


Formaldehyde was administered in the drinking-water to groups of 70 male and 70 female Wistar rats for up to 24 months. Survivors of subgroups of ten rats/sex/group each were killed after 12 or 18 months. The mean formaldehyde doses administered were 0, 1.2, 15 or 82 mg/kg body weight/day for males, and 0, 1.8, 21 or 109 mg/kg/day for females. There were no adverse effects on general health, survival or haematological or clinical chemistry parameters. Body weight and food intake were decreased in the high-dose group. Liquid intake was decreased by 40% in the high-dose group in both sexes in comparison with the controls. There was a slight temporary increase in the density of urine, whereas there was a tendency towards lower urine production in the high-dose group. The relative kidney weights were increased in the high-dose females. Gross examination at autopsy revealed a raised and thickened limiting ridge of the forestomach in most high-dose rats. In addition, several rats in the high-dose group showed irregular mucosal thickenings in the fore- and/or glandular stomach. Treatment-related histopathological gastric changes seen in most of the animals of the high-dose group included papillary epithelial hyperplasia frequently accompanied by hyperkeratosis and focal ulceration in the forestomach and focal chronic atrophic gastritis, occasionally accompanied by ulceration and/or glandular hyperplasia, in the glandular stomach. A higher incidence and/or degree of renal papillary necrosis occurred in the high-dose rats. From this study it appeared that the 'no-observed-adverse-effect level' of formaldehyde was 15 and 21 mg/kg body weight/day for male and female rats, respectively. Oral administration of formaldehyde at doses of 82 and 109 mg/kg/day to male and female rats, respectively, caused severe damage to the gastric mucosa but did not result in gastric tumours or tumours at other sites. The study did not provide any evidence of carcinogenicity of formaldehyde after oral administration.

MeSH terms

  • Administration, Oral
  • Animals
  • Carcinogenicity Tests
  • Carcinogens*
  • Eating / drug effects
  • Female
  • Formaldehyde / administration & dosage
  • Formaldehyde / toxicity*
  • Hyperplasia
  • Kidney / drug effects
  • Kidney / pathology
  • Male
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred Strains
  • Stomach / drug effects
  • Stomach / pathology
  • Urination / drug effects


  • Carcinogens
  • Formaldehyde