Incidence of tumours

A study of 148000 subjects by Lanza and colleagues (1987) reported 36 individuals with myeloperoxidase deficiency, 10 of whom were completely deficient a further 2 individuals with total deficiency were identified from familial studies. Of the 12 patients with total deficiency, 7 had either benign or malignant tumours, but none was undergoing radio- or chemotherapy at the time of analysis hence, the myeloperoxidase deficiency could not be attributed, in these cases, to the therapy used for treatment of the malignant disease. These findings imply either that the tumour somehow affects the expression of myeloperoxidase in these patients, or that myeloperoxidase-deficient individuals perhaps have an increased incidence of tumours. Much follow-up work is needed for these studies on myeloperoxidase-deficient neutrophils in order to evaluate these proposals. 

There is a continuing debate as to whether inbred or outbred strains of rodents should be used. In theory, inbred strains are preferable because a more accurate knowledge of back-grormd tumour incidence is available. It may be, however, that a particular inbred strain may metabolise the test material in a certain way or have a genetic resistance to the development of a specific tumour type. Usually outbred strains of rat or hamster are used, but occasionally inbred mice strains are included. An FI hybrid mouse strain is frequently employed. In some circumstances outbred Syrian hamsters may be the species of choice. The most important factor is to have a sound knowledge of the background incidence of tumours in the species or strain selected. This information complements the concurrent control data and provides information on the susceptibility of the strain to rare tumour t)rpes. Modif)dng factors, such as diet, cage density, etc., must be kept as constant as possible to enable correct interpretation of the results. ... 

Groups of 50 male and 50 female Fischer 344 rats, six weeks of age, were given 2-ethylhexanol by gavage, five times weekly, at doses of 0, 50, 150 or 500 mg/kg bw for 104 weeks. A dose-related depression of body weight gain in male and female rats and increased mortality in high-dose female rats were observed. There was no increase in the incidence of tumours in any treated group (Astill et al, 1996). 

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. 

Chloro-ort/70-toluidine or its hydrochloride was tested for carcinogenicity by oral administration in two experiments in mice and in two experiments in rats. The compounds increased the incidence of haemangiosarcomas in the spleen and adipose tissue in both male and female mice, but no increase in the incidence of tumours was observed in rats. 

Diethanolamine was tested for carcinogenicity by dermal application in one study in mice and in one study in rats. In the mouse study, there was a treatment-related increase in the incidences of both hepatocellular adenomas and carcinomas in both males and females, as well as an increase in the incidence of hepatoblastomas in males. There was also a marginal increase of renal tubule adenomas in males. In rats, no treatment-related increase in the incidence of tumours was seen in either males or females. 

Table 2. Incidence of tumours in B6C3Fi mice exposed by inhalation to nitromethane...

Rat. Groups of 10, 20, 30 or 40 male and 10, 20, 30 or 40 female Fischer 344/N rats, four weeks of age, were injected subcutaneously with 0, 3, 10, 30 or 100 mg/kg bw pyridine (commercial product) in physiological saline twice a week for 52 weeks. The animals were observed for a further six months. Body weights were similar in treated and untreated animals. Distributed across all groups, only three animals died by 12 months and eight by 18 months. There was no increase in the incidence of tumours either at the injection site or at any other site (Mason et al., 1971). 

In two studies with genetically modified mice, there was no treatment-related increase in the incidence of tumours. 

In one inhalation study in rats, 1,3-butadiene increased the incidence of tumours at several sites. The tumour increases were mainly in organs in which tumours develop spontaneously. The response was seen mainly at 8000 ppm [17 700 mg/m ]. 

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. 

Acetaldehyde was tested for carcinogenicity in rats by inhalation exposure and in hamsters by inhalation exposure and intratracheal instillation. Following inhalation exposure, an increased incidence of carcinomas was induced in the nasal mucosa of rats, and laryngeal carcinomas were induced in hamsters. In another inhalation study in hamsters, using a lower exposure level, and in an intratracheal instillation study, no increased incidence of tumours was observed. In hamsters, inhalation of acetaldehyde enhanced the incidence of respiratory-tract tumours produced by intratracheal instillation of benzo a -pyrene (lARC, 1985). 

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). 

Benzyl chloride, benzal chloride, benzotrichloride and benzoyl chloride have been studied by skin application to mice. Small numbers of skin tumoms were produced by benzyl chloride and benzoyl chloride, while clear increases in skin tumours were produced by benzal chloride and benzotrichloride. Following subcutaneous injections to rats, benzyl chloride produced some injection site tumours. Administration by gavage of benzyl chloride to mice and rats produced forestomach tumours in mice and a few neoplasms of the forestomach were observed in male rats. Benzotrichloride administered by gavage to mice produced tumours of the forestomach and lungs. In addition, benzotrichloride and benzoyl chloride were administered by inhalation to mice benzotrichloride produced increases in the incidences of tumours of the lung and skin, whereas no significant increase in tumour incidence was observed after benzoyl chloride administration. 

Groups of 50 male and 50 female Fischer 344 rats, five to six weeks of age, were administered l,2-dibromo-3-chloropropane (96% pure), containing small amounts of epichlorohydrin (0.6%) and 1,2-dibromoethane (0.07%), by whole-body inhalation at concentrations of 0 (control), 0.6 or 3 ppm [0,4 or 29 ing/nr for 6 h per day on five days per week for 84-103 weeks. Survival of high-dose rats was reduced and all surviving rats were killed at week 84. Increased incidence of tumours of the nasal cavity and of the tongue in both sexes and of the pharynx in females was observed, as shown in Table 2 (United States National Toxicology Program, 1982). 

Groups of 50 female weanling Wistar rats were administered 0, 2 or 10 mg/kg bw epichlorohydrin (purity, 99.5%) daily by gavage on five days per week for two years. All surviving animals were killed. The incidence of forestomach hyperplasia, papilloma and carcinoma was increased in both sexes (Table 1). The incidence of tumours at other sites was not increased (Wester et al., 1985). 

Table 1. Incidence of tumours in mice exposed to ethylene dibromide by...

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