Nasal cavity carcinomas

Carcinogenicity of NDELA. Our special interest in NDELA as a constituent of tobacco products and as an environmental agent relates to the observation that this nitrosamine induces carcinoma of the liver as well as of the kidney in rats (21,22) and carcinoma of the nasal cavity and papillomas of the trachea in hamsters (23). Recently, Lijinsky reported that NDELA admini-... 

Hamster s.c. Trachea (Papilloma) Nasal Cavity (Carcinoma) 23,45... 

Rat s.c. Nasal Cavity (Carcinoma) Liver Lung (Adenoma, Carcinoma) 44... 

High doses of dioxane by oral administration produced malignant tumors of the nasal cavity and liver in rats, and mmors of the liver and gallbladder in guinea pigs." Rats administered either 0.5% or 1.0% (vol/vol) in the drinking water had squamous cell carcinomas of the nasal turbinates hepatocellular adenomas were seen in the dosed females." In another study, inhalation of 111 ppm, 7 hours/day, 5 days/week for 2 years did not result in any increased tumor incidence in rats. ... 

Rats exposed for 2 years to 400 ppm had increased incidence of papillary adenomas of the nasal cavity the incidences of alveolar/ bronchiolar adenomas or carcinomas (combined) were also increased in the male rats, but not in the females. Nonneoplastic lesions of the nasal cavity included inflammation, epithelial hyperplasia, and squamous metaplasia of the nasal epithelium, as well as atrophy of the olfactory sensory epithelium. Mice exposed at 50 or lOOppm for 2 years had no significant increases in the incidence of neoplastic lesions... 

Nasal tumors were induced in rats by inhalation exposure to HMPA for 6-24 months at levels of 50, 100, 400, and 4000 ppb, 6 hours/ day, 5 days week, but not in rats exposed to 10 ppb for 24 months. Most nasal mmors were epidermoid carcinomas and developed from the respiratory epithelium or subepithelial nasal glands, both of which revealed squamous metaplasia or dysplasia in the anterior nasal cavity. 

Chronic exposure of rats to 1 or 12 ppm 6 hours/day, 5 days/week for 2 years caused an increased incidence of rhinitis, squamous metaplasia, and epidermal carcinomas of the nasal cavity. The lARC has determined that there is sufficient evidence for the carcinogenicity of PGE in animals and that it is possibly carcinogenic to humans. ... 

It has been postulated that wood dust carcinoma results from a multistep process Exposure causes loss of cilia and hyperplasia of the goblet cells and initiation of cuboidal cell metaplasia, followed (after a quiescent period) by squamous cell metaplasia. Decades later, cellular aplasia leads to nasal adenocarcinoma. The time between first occupational exposure to wood dust and the development of nasal cavity adenocarcinoma averages 40 years. Other cancers, including lung cancer, Hodgkin disease, multiple myeloma, stomach cancer, and colorectal cancer and lymphosarcoma, have been mentioned in relation to wood... 

Chronic 2-year studies showed a significant increase in the incidences of adenomas and carcinomas of the nasal cavity in high-dose rats fed diets containing 3000ppm of 2,6-xylidine. The carcinomas were highly invasive and frequently destroyed the nasal turbinates and nasal septum. Rhabdomyosarcomas, a rare tumor of the nasal cavity were also observed in the high-dose male and females. The nonneo-plastic lesions observed in the nasal cavity included acute inflammation, epithelial hyperplasia, and squamous metaplasia. In addition, subcutaneous fibromas and fibrosarcomas occurred in both males and females and there was an increased incidence of neoplastic nodules in the livers of female rats. 

A group of 100 male Syrian golden hamsters, eight weeks of age, was exposed by inhalation to 1 ppm [4.4 mg/m- ] dimethylcarbamoyl chloride for 6 h per day on five days per week for life. Two groups of 50 and 120 male hamsters served as sham-exposed and untreated controls, respectively. Neoplastic lesions of the nasal cavity were observed from 406 to 770 days. Squamous-cell carcinomas of the nasal cavity occurred in 50/99 hamsters in the treated group. No such tmnour occurred in controls (Sellakumar et al., 1980). 

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. 

Hexamethylphosphoramide was tested for carcinogenicity in rats, the only species tested, by inhalation in this study, which was reported as a preliminary note, it produced squamous-cell carcinomas of the nasal cavity. It has also been inadequately tested in rats by oral administration (lARC, 1977). 

Rat. Four groups of 120 male and 120 female Sprague-Dawley rats were exposed to 0 (control), 50,400 and 4000 ppb [0, 0.37,2.9 and 29 mg/m- ] hexamethylphosphoramide vapour for 6 h per day on five days per week for periods ranging from nine months to two years. In an additional study, four groups of 100 male and 100 female rats were similarly exposed to 0, 10, 50 and 100 ppb [0, 73, 370 and 730 pg/m ] atmospheres. Nasal tumours were first found after approximately seven months of exposure at 400 and 4000 ppb, after nine months at 100 ppb and after 12 months at 50 ppb. No exposure-related tumours were found at 10 ppb. Tumour incidences at 24 months were 50 ppb, 15% (12 months of exposure) and 25% (24 months of exposure) 100 ppb, 19% (six months of exposure) and 56% (13 months of exposure) 400 ppb, 82% (10 months of exposure) 4000 ppb, 83% (nine months of exposure). Most tumours developed in the squamous or respiratory epithelium and nasal glands, all of which showed squamous metaplasia or dysplasia in the anterior nasal cavity. Exposure concentrations correlated with tumour incidence and latency, but not with tumour type. The total of 473 nasal tumours included 72% epidermoid carcinomas, 15% adenoid squamous carcinomas and 8% papillomas. Most tumours (59%) developed in the anterior nasal cavity and then progressed to the posterior nasal cavity (41%) (Lee Trochimowicz, 1982a). 

Pure phenyl glycidyl ether was tested for carcinogenicity by inhalation exposure in male and female rats of one strain, producing carcinomas of the nasal cavity in animals of each sex (lARC, 1989). 

Among 4 cases of nasal carcinoma in men who worked for 19 and 32 years in a Japanese chromate factory, 1 patient was diagnosed with squamous cell carcinoma of the left nasal cavity 11 years after retirement (Satoh et al. 1994). The other three patients underwent lobectomy for lung cancer, and 6-15 years later, all three contracted nasal cancer, two in the nasal cavity and one in the nasopharynx. The period for the appearance of nasal cancer was about 39 years after first being exposed to chromium. No mention was made of the possibility of metastasis of lung cancer to the nasal region. 

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