Inhalation toxicity of acetaldehyde in rats II. Carcinogenicity study: Interim results after 15 months

Woutersen, Ruud; Appelman, L.M.; Feron, V.J.; Heijden, C.A. van der

doi:10.1016/0300-483x(84)90004-0

Cited by 91 publications

(54 citation statements)

References 4 publications

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“…Focal changes, such as erosion and ulceration may also occur. Inflammatory changes are nonspecific but are dependent on exposure dose or concentration and degree of necrosis and are seen more frequently after administration of irritants such as acetaldehyde (11) and chlorine (17). However, 3-methylfuran (25) and 3-methylindole (34)-both of which are activated by mixed-function oxidases-induce acute, severe serofibrinous, necrotizing rhinitis.…”

Section: Inflammationmentioning

confidence: 99%

Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Gaskell¹

1990

Environmental Health Perspectives

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Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects.Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands.Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran-which are activated by mixed-function oxidases-the nerve bundles remain intact. Future work, including metabolism studies, will provide more information on the mode of action of these chemicals.

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Section: Inflammationmentioning

confidence: 99%

Nonneoplastic Changes in the Olfactory Epithelium. Experimental Studies

Gaskell¹

1990

Environmental Health Perspectives

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“…Special staining methods were applied when (12). Nasal discharge and mouth breathing were only rarely seen in rats with trichlorobutene-or vinyl chloride-induced carcinomas of the olfactory epithelium (4,8).…”

Section: Introductionmentioning

confidence: 99%

Upper Respiratory Tract Tumors in Cpb:WU (Wistar Random) Rats

Feron¹,

Woutersen²,

Garderen-Hoetmer³

et al. 1990

Environmental Health Perspectives

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A survey is given of upper respiratory tract tumors in Cpb:WU (Wistar random) rats. Data were collected from ten 24-to 30-month toxicity/carcinogenicity studies and from one 12-month study. Nasal tumors may lead to dyspnea, mouth breathing, and nasal discharge. These clinical signs mainly occurred in rats bearing squamous cell carcinomas. The large nasal tumors were often osteolytic, they invaded the subcutis over the premaxilla, resulting in swellings on the back of the nose, and extended into the brain. The incidence of nasal tumors in untreated male controls was 1.1% (7/661), the tumors invariably being squamous cell carcinomas. There were no nasal tumors found in untreated female controls. The type of compound-induced nasal tumor most frequently observed was adenocarcinoma (of the olfactory epithelium) followed, in order of decreasing incidence, by squamous cell carcinoma, carcinoma in situ, polypoid adenoma, Schwannoma, and carcinosarcoma. It was proposed that adenocarcinomas of the olfactory epithelium should be classified as neuroepitheliomas. It was also suggested that squamous cell carcinomas, seen in association with necrotizing inflammation of an incisor tooth, should be considered as part ofthe malocclusion syndrome. No spontaneous tracheal tumors were observed, and only one out of 422 untreated female controls (0.2 %) was seen to have a laryngeal tumor, an adenoma. Induced laryngeal tumors included carcinoma in situ, squamous cell carcinoma, and adenocarcinoma. Squamous cell carcinoma was the only type of treatment-related tracheal tumor found. The incidences of induced laryngeal and tracheal tumors were very low, and in no case were these tumors statistically significantly different from the respective incidences in controls.

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“…Alcohol metabolites can affect initiation. In rats, acetaldehyde, the result of metabolized ethanol, has been shown to cause mutations (Dellarco, 1988) and induce nasal tumors when inhaled in vapor form (Woutersen et al, 1984). Acetaldehyde has also been found to inhibit the activation of DNA repair enzyme that would return the DNA to its normal state (Espina et al, 1988).…”

Section: Alcohol and Cancer: Possible Biochemical Pathwaysmentioning

confidence: 98%