Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher-344 rats.
Male F-344 rats were exposed by inhalation to gaseous formaldehyde at 0.3, 2, and 15 ppm 6 h/day, 5 days/week for 28 months. Nasal tumors were macroscopically evident in the 15 ppm group from the 14th month and 8 of 32 rats bore such tumors at the 24th month. Histopathological examination revealed both squamous cell papillomas and carcinomas. No nasal tumors were observed in the lower exposure groups (0.3 and 2 ppm groups). In the high exposure group (15 ppm group), frequent face washing, coughing and/or crouching position, lacrimation, nasal discharge, and yellow discoloration of the haircoat were observed. Significant decrease in food consumption and body weight was noted, and 20 (88.3%) rats died by the 24th month. Reduced triglyceride levels and liver weights, presumed to be related to the drop in food intake, were also seen in the 15 ppm group. Epithelial cell hyperplasia, hyperkeratosis, and the squamous metaplasia were apparent in all exposure groups. Inflammatory cell infiltration, erosion or edema were evident in all groups, including the 0 ppm and room (RC group) controls. In this study, a no effect level of formaldehyde vapor could not be obtained because toxicological signs were obvious even with the low exposure group. The benchmark doses for squamous metaplasia and epithelial hyperplasia were 0.25 and 0.24 ppm, respectively.
Kamata
E
E
Division of Risk Assessment, National Institute of Health Sciences, Tokyo, Japan.
Nakadate
M
M
Uchida
O
O
Ogawa
Y
Y
Suzuki
S
S
Kaneko
T
T
Saito
M
M
Kurokawa
Y
Y
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005557:Formaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D005740:Gases; D008297:Male; D009669:Nose Neoplasms / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010212:Papilloma / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D005740:Gases; D005557:Formaldehyde