Effects of exposure to furfural vapour in hamsters simultaneously treated with benzo[alpha] pyrene or diethylnitrosamine.

Syrian golden hamsters were exposed to 0 or 250/400 ppm furfural vapour, 7 h/day, 5 days/week for a period of 52 weeks. Simultaneously, a proportion of the animals were given either intratracheal inslillations of benzo [alpha] pyrene (BP) or subcutaneous injections of diethylnitrosamine (DENA). All treatments were stopped after 52 weeks. The study was terminated after 81 weeks. Furfural exposure caused yellowish discolouration of the animals' coat, irritation of the nasal mucosa, growth retardation, atrophy and downward growth of sensory cells of the olfactory epithelium, degenerative changes in Bowman's glands, and the occurrence of cyst-like structures in the lamina propria beneath the olfactory epithelium. There was no evidence of furfural possessing carcinogenic activity. In a previous instillation experiment with furfural, slight indications had been obtained of furfural potentiating the carcinogenic effect of BP, but in the present study the carcinogenic effect of BP or DENA on the respiratory tract did not appear to be influenced by furfural exposure. It was concluded that little if any, significance can be attached to furfural as a co-factor in respiratory tract carcinogenesis.

One-year time sequence inhalation toxicity study of vinyl chloride in rats. I. Growth, mortality, haematology, clinical chemistry and organ weights.

Wistar rats were exposed to atmospheres containing O (control) or 5000 ppm vinyl chloride monomer (VCM), 7 h/day, 5 days/week, for a period of 52 weeks. After 4, 13, 26 and 52 weeks each time 10 rats/sex/group were killed and subjected to extensive examinations. The present paper deals with growth, mortality, haematology, clinical chemistry and organ weights. Slight growth retardation throughout the experimental period and high mortality in the second half of the study were observed in VCM-exposed animals. Some of the haematological parameters and biochemical blood parameters were slightly influenced by VCM after an experimental period of 52 weeks only. Blood clotting time was generally slightly shorter in VCM-exposed rats than in controls. There were minor indications of increased potassium contents of the blood serum in VCM-exposed animals during the first half of the test period. The kidneys were adversely affected by VCM as appeared from increased blood urea nitrogen levels and relative kidney weights. After 52 weeks increased weights of heart and spleen, and slight signs of anaemia were noticed in VCM-exposed rats. The present study did not produce obviously suitable parameters for early diagnosing "VCM-disease" in man.

Repeated exposure to butenolide vapour: subacute study in Syrian golden hamsters.

The subacute inhalation toxicity of butenolide was examined in hamsters by repeated exposure of 4 groups of 10 males and 10 females to butenolide vapour at concentrations of 0, 5.4, 25 and 130 ppm respectively (6 h/day, 5 days/week) for a period of 13 weeks. The effects found at 130 ppm included eye irritation, salivation, nasal discharge, growth retardation, decreased number of eosinophils, increased liver weight, and hyper- and metaplastic epithelium in the nasal cavity. At the 5.4 and 25 ppm levels no changes were observed which could be attributed to butenolide; 25 ppm was, therefore, considered the highest no-toxic effect level observed. The actual no-adverse effect level was placed at 75 ppm.

Repeated exposure to acrolein vapour: subacute studies in hamsters, rats and rabbits.

The subacute inhalation toxicity of acrolein was examined in 4 groups of 20 hamsters, 12 rats and 4 rabbits each, exposed repeatedly to acrolein vapour at concentrations of 0, 0.4, 1.4 and 4.9 ppm (6 h/day, 5 days/week) for a 13-week period. The most important effects found at the highest level included mortality in rats, ocular and nasal irritation, growth depression and histopathological changes of the respiratory tract in each of the animal species exposed. The aberrations in the airways consisted of destruction and hyper- and metaplasia of the lining epithelium accompanied by inflammatory alterations. Rats appeared to be the most susceptible of the species examined and showed treatment-related abnormalities even at 0.4 ppm, whereas this exposure level was found to be a no-toxic effect level in both hamsters and rabbits.

Repeated exposure to acetaldehyde vapor. Studies in Syrian golden hamsters.

The subacute inhalation toxicity of acetaldehyde was examined with four groups of 20 hamsters each, exposed repeatedly to acetaldehyde vapor at concentrations of 0, 390, 1,340, and 4,560 ppm (six hr day, five days/week) for a 90-day period. The highest level induced growth retardation, ocular and nasal irritation, increased numbers of erythrocytes, increased weights of heart and kidneys, and severe histopathological changes in the respiratory tract that mainly consisted of necrosis, inflammatory changes, and hyper- and metaplasia of the epithelium. The upper segments of the respiratory tract were much more severely injured than the lower parts. At 1,340 ppm treatment-releated changes included increased kidney weights in males and slight hyper- and metaplastic changes of the tracheal epithelium; 390 ppm was considered a no toxic effect level.

Repeated exposure to cyclopentenone vapour: long-term study in Syrian golden hamsters.

Effects of cyclopentenone inhalation were examined in a 78-week study with 420 hamsters evenly distributed over two inhalation chambers, one for exposure to air and the other for exposure to the test substance. Cyclopentenone was dosed at a level of 18 ppm (seven hr/day, five days/week) during the first 52 weeks, and at a level of 27 ppm during the last 26 weeks of the study. During the first 52 weeks, part of the animals in both chambers fortnightly received an intratracheal instillation of benzo(a)pyrene (BP) or diethylnitrosamine (DENA) in saline or saline alone. Exposure to cyclopentenone caused slight growth depression in both sexes, and slightly increased relative liver weights and enhanced development of renal amyloidosis in females only. There was no evidence of cyclopentenonne possessing carcinogenic activity or being a co-factor in respiratory tract carcinogenesis.

Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzo(a)pyrene or diethylnitrosamine.

Syrian golden hamsters were exposed to 0 or 2500-1650 ppm acetaldehyde vapour, 7 hr/day, 5 days/week for a period of 52 weeks. A proportion of the animals was given, simultaneously, either intratracheal instillations of benzo(a)pyrene (BP) or subcutaneous injections of diethylnitrosamine (DENA). All treatments were stopped after 52 weeks. The study was terminated after 81 weeks. Major effects attributed to acetaldehyde exposure included growth retardation, rhinitis, hyperplasia and metaplasia of the nasal, laryngeal and tracheal epithelium, nasal and laryngeal carcinomas, and a markedly increased incidence of BP-initiated tracheobronchial carcinomas. There was no evidence of acetaldehyde enhancing the development of DENA-initiated tumours of the respiratory tract. It was concluded that acetaldehyde is an irritant, as well as a carcinogen, for the respiratory tract of Syrian golden hamsters. Possible mechanisms of the carcinogenicity of this aldehyde are briefly discussed.

Repeated exposure to furfural vapour: 13-week study in Syrian golden hamsters.

The sub-acute inhalation toxicity of furfural was studied in Syrian golden hamsters. Four groups of ten males and ten females each were repeatedly exposed to furfural vapour at concentrations of 0, 20, 115 and 552 ppm (0, 77, 448 and 2165 mg/m3 air) respectively for 6 hours/day, 5 days/week during a period of 13 weeks. At the highest exposure level furfural induced irritation of the eyes and nose, slight growth retardation and atrophy along with hyperplasia of the olfactory epithelium in the nasal cavity. At 115 ppm atrophy and hyperplasia of the olfactory epithelium were the only adverse effects observed that could be attributed to furfural. No compound-related alterations were detected at the lowest exposure concentration of 20 ppm (77 mg/m3 air) which was, therefore, accepted as a no-toxic effect level.