Urinary bladder tumors in dogs from 4,4'-methylene-bis (2-chloroaniline) (MOCA).

Six female beagle dogs were given a daily dose of 100 mg MOCA, by capsule, 3 days per week for the first 6 weeks and then 5 days per week continuously for periods up to 9.0 years. The dose varied from 8 to 15 mg/kg body weight/day among the dogs. Six female beagle dogs were kept as untreated controls. The test was terminated after 9.0 years of treatment. The average plasma glutamic-pyruvic transaminase activity of the dogs fed MOCA was higher than that of the controls during the first and last two years on test. During the eighth and ninth years the urine sediment from MOCA dogs contained excessive numbers of erythrocytes, leukocytes, and epithelial cells. Some epithelial cells contained abnormalities that suggested neoplasia in the genitourinary tract. One MOCA dog, sacrificed after 8.3 years on test was found to have a papillary transitional cell carcinoma of the urinary bladder. Of four MOCA dogs sacrificed after 9.0 years on test, three were found to have papillary transitional cell carcinomas of the urinary bladder and one had a combined transitional cell carcinoma and adenocarcinoma of the urethra. The urethral tumor had metastasized to the liver, but the papillary transitional cell carcinomas found in the other four dogs did not invade the muscle layers of the bladder wall and did not metastasize. Since no urinary bladder tumors were found in the six control dogs, MOCA was considered to be carcinogenic for the urinary bladder of dogs under the conditions employed (p less than 0.025, Fisher's Exact Test, one tail). Three of five MOCA dogs contained hyperplastic nodules in the liver with no such nodules in six control dogs (p greater than 0.05, Fisher's Exact Test, one tail). This was considered to be suggestive of an effect of MOCA treatment.

Liver and urinary bladder tumors in dogs from 3,3'-dichlorobenzidine.

Six female beagle dogs were given, by capsule, a daily oral dose of 100 mg of 3,3'-dichlorobenzidine (DCB), 3 times per week for 6 weeks, then 5 times per week continuously for periods up to 7.1 years. The DCB test was terminated after 7.1 years. Six untreated female beagle dogs served as controls for several tests and were sacrificed after 8.3 to 9.0 years on test. All 6 DCB dogs had an elevated plasma glutamic-pyruvic transaminase activity during the first 3 years on test; two dogs showed persistent elevation throughout the test. One DCB dog, sacrificed in extremis after 3.5 years on test, had no tumors. Another DCB dog, sacrificed in extremis after 6.6 years on test, developed an undifferentiated carcinoma of the liver with metastases to many organs; this dog also had a papillary transitional cell carcinoma of the urinary bladder. Of the 4 remaining DCB dogs sacrificed after 7.1 years on test, 3 developed hepatocellular carcinomas and all 4 had papillary transitional cell carcinomas of the urinary bladder. No liver or urinary bladder tumors were found in the 6 control dogs. DCB was found to be carcinogenic for the liver and urinary bladder in dogs under the conditions employed (p less than .025, Fisher's Exact Test, one tail).

Liver and lung tumors in dogs from 4,4'-methylene-bis(2-methylaniline).

Six female beagle dogs were given, by capsule, a daily dose of 100 mg 4,4'-methylene-bis(2-methylaniline) (MeMDA), 3 times per week for 6 weeks, then 5 times per week for 5 weeks, at which time the dose was reduced to 50 mg 5 times per week, continuously for periods up to 7.0 years. Six female beagle dogs were kept as untreated controls for several studies and were sacrificed after 8.3 to 9 years test. MeMDA dogs developed renal atrophy with an elevated blood urea nitrogen during an approximate six-month period prior to death or being sacrificed in extremis. As three of three MeMDA dogs that survived for 5.2 years to 7.0 years developed hepatocellular carcinomas and two of the three dogs also developed primary lung tumors, with no liver or lung tumor in six control dogs, MeMDA was considered to be carcinogenic for the dog (liver tumors: p less than .05; lung tumors: p less than 10; Fisher's Exact Test, one tail).

Ultrastructural alterations of rat lung exposed to pyrolysis products of polytetrafluoroethylene (PTFE, Teflon).

Ultrastructural changes of the lung tissues were evaluated in rats exposed to the pyrolysis products of Teflon at 380 degrees C., 400 degrees C;, and 450 degrees C., respectively, for 4 hours. At 450 degrees C. Teflon evolved numerous tiny particles (0.02 to 0.04 mum.), which were considered to be the toxic material, and at 550 degrees C., in addition to the tiny particles, large spherical particles (0.7 to 5.0 mum) were found. No particles were observed in the pyrolysis product produced at temperatures between 380 degrees C. and 425 degrees C. There were no clinical symptoms or lung alterations induced at temperatures below 425 degrees C colloidal carbon injected as a marker of increased vascular permeability did not pass through the alveolar capillary endothelium. At 450 degrees C. (approximate lethal temperature) rats revealed severe respiratory difficulty, pulmonary edema, hemorrhage, and necrosis of the tracheobronchial epithelium. The membranous pneumocytes appear to be vulnerable to the Teflon fume causing cytoplasmic swelling, bleb formation, fragmentation, and denudation. Similar changes were found in the endothelial cells, but to a much lesser extent. When Teflon fume generated at 450 degrees CnWAS FILTERED THROUGH A Millipore filter (pore size 0.2 mum.), rats revealed only slight degenerative changes in the superficial tracheobronchial epithelium, but no clinical signs.