Lung tumours

NT087 Hoffmann, D., M. V. Djordjevic, A. Rivenson, E. Zang, D. Desai, and S. Amin. A study of tobacco carcinogenesis. LI. Relative potencies of tobacco-specific N-nitrosamines as inducers of lung tumours in A/J mice. Cancer Lett 1993 71(1-3) 25-30. 

Cinnamyl anthranilate was tested for carcinogenicity in one experiment in mice and in one experiment in rats by oral administration in the diet. In mice, a dose-related increase in the incidence of hepatocellular tumours was found, but there was no increased incidence of tumours in rats. In a mouse lung tumour bioassay, an increased multiplicity of lung tumours was found. 

Coumarin has been adequately tested by oral administration in two experiments in mice and in one experiment in rats. In mice of one strain, it produced increases in lung tumours (adenomas and carcinomas) in both males and females and in hepatocellular adenomas in females. There was no increase in tumour incidences in another strain of mouse. In one study in rats, coumarin produced a low incidence of renal tubule adenomas in males, seen only after step-sectioning of the kidney. Three other studies in rats could not be evaluated. 

In a mouse lung screening assay, TV-nitrosodiethanolamine increased the incidence and multiplicity of lung tumours. 

Nitromethane was tested for carcinogenicity by inhalation in one experiment in mice and in two experiments in rats. In mice, it increased the incidence of Harderian gland and lung tumours in males and females as well as of hepatocellular adenomas in females. In one experiment in rats, nitromethane increased the incidence of benign and malignant mammary gland tumours in females, but produced no increase in the incidence of tumours in a second study in a different strain of rat. 

L-Diepoxybutane was administered by intraperitoneal injection (12 injections thrice weekly) to male and female strain A mice at total doses ranging from 1.7 to 192 mg/kg bw in water or tricaprylin. It increased the incidence and multiplicity of lung tumours (Shimkin et al., 1966). 

Activated -ras oncogenes have been detected in lymphomas and in liver and lung tumours induced in mice by 1,3-butadiene. Mutations in thep53 tumour-suppressor gene have been detected in mouse lymphomas. 

Groups of 50 male and 50 female Swiss mice, nine weeks of age, were administered 100 (low-dose) or 500 (high-dose) mg/kg bw dichloromethane (purity, > 99.9%) in olive oil by gavage once per day on four to five days per week for 64 weeks. Groups of 60 mice of each sex were given olive oil (vehicle-control). Animals were then kept under observation for their lifespan. Excess mortality was observed in male and female mice exposed to the high dose p < 0.01). An increase in mortality appeared after 36 weeks of treatment and led to withdrawal of the treatment at 64 weeks. In mice that died by 78 weeks, the incidence of lung tumours in males was 1/14 control, 4/21 low-dose and 7/24... 

NTP) mouse bioassay, the GST pathway would predominate and liver and lung tumour incidence was increased. Conversely, in the mouse drinking-water study where, presumably, lower blood levels of dichloromethane would be reached than in the inhalation bioassay, the dichloromethane would have been metabolized primarily via cytochrome P450, while GST-mediated metabolism would have been minimal (predicted by pharmacokinetic modelling to be two orders of magnitude lower than at the high dose used in the NTP study Andersen et al., 1987), and no increased incidence of tumours was observed. 

The available data suggest a plausible mechanism for the development of liver and lung tumours which occur in mice but not in rats exposed to dichloromethane. 

Green, T. (1997) Methylene chloride induced mouse liver and lung tumours An overview of the role of mechanistic studies in human safety assessment. Hum. exp. Toxicol., 16, 3-13... 

Aziridine has been tested for carcinogenicity in two strains of mice by oral administration, producing an increased incidence of liver-cell and pulmonary tumours. Subcutaneous injection of single doses in suckling mice produced an increased incidence of lung tumours in males. In one experiment in rats, aziridine increased the incidence of tumours at the injection site following its subcutaneous injection in oil (lARC, 1975). 

Benzotrichloride was tested in three studies by skin application to female mice. It produced squamous cell carcinomas of the skin and lung tumours in all three experiments upper digestive tract tumours were also observ ed in two of the three experiments. Increases in the incidence of tumours at other sites were reported. In a strain A mouse lung tumour bioassay, benzotrichloride increased the incidence of lung adenomas (lARC, 1982, 1987a). 

Groups of female ICR-Jcl mice were exposed to air or to benzoyl chloride vaporized at 50°C [concentration not stated] for 30 min per day on two days per week for five months. They were then observed for a further seven to nine months (12-14 months total). In the control and exposed groups, respectively, lung tumours were observ ed in 3/30 (3 adenomas) and 3/28 (1 adenoma and 2 adenocarcinomas) mice and skin papillomas in 0/30 and 2/28 mice. The differences in incidence were not significant (Yoshimura et al., 1986). [The Working Group noted the short duration of exposure and observation time, allowing only comparison with mice simultaneously exposed to benzotrichloride.]... 

Mouse. In a strain A lung adenoma assay, intraperitoneal injection of total doses of 20, 50 or 100 mg/kg bw epichlorohydrin given three times per week for eight weeks significantly increased the number of lung tumours per mouse in males treated with the highest dose (0.80 0.68, compared with 0.47 0.63 in controls p < 0.01) but not in other groups (Stoner et al., 1986). 

Epichlorohydrin was tested in rats by oral administration, inducing papillomas and carcinomas of the forestomach, and by inhalation, inducing papillomas and carcinomas of the nasal cavity. It was also tested in mice by skin application and by subcutaneous and intraperitoneal injection it gave negative results after continuous skin painting but was active as an initiator on skin. It produced local sarcomas after subcutaneous injection and was active in a mouse-lung tumour bioassay by intraperitoneal injection. 

Mouse-. Groups of 16 male and 16 female A/J mice, six to eight weeks of age, were given 2,4,6-trichlorophenol (reagent grade) by intraperitoneal injection three times per week for eight weeks for total doses of 240, 600 or 1200 mg/kg bw. No increase in the incidence of lung tumours was found (Stoner et al., 1986). 

Trichlorophenol was tested in one study in mice and in one study in rats by oral administration and in one study in mice in a screening test for lung tumours. In mice, it increased the incidences of benign and malignant tumours of the liver and in rats mononuclear cell leukaemia. It did not induce lung adenomas in mice. 

Hydrazine was tested for carcmogenicity by oral administration to mice in several experiments, producing mammary and lung tumours. When tested by oral administration or inhalation exposure in rats, it produced lung, liver and nasal tumours and a few colon tumours. In hamsters, it produced liver tumours and thyroid adenomas following oral or inhalation exposure. 

Polymeric 4,4 -methylenediphenyl diisocyanate containing 44.8-50.2% monomeric 4,4 -mcthylcncdiphcnyl diisocyanate was tested for carcinogenicity by inhalation in rats. An increased incidence of lung tumours was observed. 

Bis(2,3-epoxycyclopentyl)ether was tested for carcinogenicity by skin application in one experiment in tw o strains of mice. A small number of skin tumours w as observ ed in both strains and an increased incidence of lung tumours in females of one strain. Another experiment with skin application in mice was inadequate for evaluation (lARC, 1989). 

---