Marvin Kuschner

Inhalation carcinogenicity of alpha halo ethers. III. Lifetime and limited period inhalation studies with bis(chloromethyl)ether at 0.1 ppm.

Rats and hamsters were exposed to 0.1 ppm bis(chloromethyl)ether (BCME) six hours per day, five days per week throughout their lifetime. Additional groups of rats were given 10, 20, 40, 60, 80, and 100 exposures to 0.1 ppm BCME and then held until death. Forty cancers originating in the respiratory tract were found in the 200 rats involved in these studies. These included 14 cancers of the lung and 26 cancers of the nasal cavity. They occurred in dose-related fashion. A single undifferentiated carcinoma of the lung was seen in a hamster.

Inhalation carcinogenicity of alpha halo ethers. I. The acute inhalation toxicity of chloromethyl methyl ether and bis(chloromethyl) ether.

A range of acute studies were performed with chloromethyl methyl either (CMME) and bis(chloromethyl)ether (BCME), including 14-day LC50s following single seven-hour inhalation exposures. The LC50s for CMME were 55 ppm for rats and 65 ppm for hamsters. The LC50s for BCME were 7 ppm for both species. All animals showed characteristic changes of acute irritation of the respiratory tract manifested by congestion, edema, and hemorrhage. Severe shortening of life span was seen in 30-day exposures of rats to CMME and in all studies with BCME. Incidences of mucosal changes, including atypia, were generally increased in a dose-related manner in both species. The carcinogenicity of BCME in these range finding experiments was demonstrated by a skin cancer in a rat after three exposures and a nasal tumor in a hamster after one exposure to 1 ppm BCME.

Inhalation carcinogenicity of alpha halo ethers. II. Chronic inhalation studies with chloromethyl methyl ether.

Rats and hamsters were exposed to 1 ppm of chloromethyl methyl ether six hours per day, five days per week, throughout their lifetime. Mortality and weight gain of the exposed animals paralleled that of the control animals. Malignant tumors of the respiratory tract were found in two rats. These were a squamous cell carcinoma of the lung with blood vessel invasion and an esthesloneuroepithelioma originating in the olfactory epithelium and invading the forebrain. One hamster was found to have an adenocarcinoma of the lung and another, a squamous papilloma of the trachea. A single exposed rat had a pituitary tumor of primitive cell type that may well have been coincidental.

The pathology of congestive heart failure

Abstract It may be stated that the newer techniques of electron microscopy and histochemistry appear ideal for the study of the ultimate pathogenesis of the failing myocardium. Investigations of the ultrastructure of myofilaments and mitochondria, together with changes in sulfhydryl groups, adenosinetriphosphatase activity, and magnesium, as well as variations in activity of the respiratory enzymes, promise new insight into the mechanisms of congestive failure