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Biomedical subjects

E F Stula

Publications and source records attributed to E F Stula.

11 recordsLinked to original sources
PubMed1993

Inhalation studies in rats exposed to dimethylacetamide (DMAc) from 3 to 12 hours per day.

Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen.

Acetamides↗
PubMed1990

2-week inhalation study of N-monomethylformamide in rats.

N-Monomethylformamide (MMF) is a chemical intermediate with potential for inhalation exposure in humans. Human exposures to MMF have occurred in cancer chemotherapy but have been limited due to liver damage. To assess the toxicity of MMF, groups of 15 male rats each were exposed by nose-only inhalation, 6 hr/day, 5 days/week, for 2 weeks to either 0 (control), 50, 130, or 400 ppm MMF. Five rats per group were killed following the 10th exposure, five were killed after a 14-day postexposure recovery period, and five rats were used to determine urinary MMF excretion. Parameters investigated were clinical observations and body weights, clinical pathology, and gross and microscopic pathology including organ weights. Liver damage occurred in rats exposed to either 130 or 400 ppm. This was detected both by increases in serum enzyme activity indicative of liver injury and by microscopic changes in the liver. The changes were more severe in the 400-ppm rats and were partially reversible. Other organs were not adversely affected by inhalation of MMF. The amount of MMF excreted in the urine was dependent on the exposure concentration and MMF was present 14 days postexposure at the higher exposure levels. The no-observed-effect level under the conditions of this experiment was 50 ppm.

Administration, Inhalation↗
PubMed1978

Pulmonary pathology from inhalation of a complex mineral oil mist in dogs, rats, mice and gerbils.

Dogs, rats, mice, and gerbils were exposed for 6 hours per day, 5 days per week, for periods up to 2 years, to an atmosphere containing a complex mineral oil-base mist at concentrations of 5 and 100 mg/M3. The mass median diameter of the oil droplets was approximately that found in textile plants ( approximately 1.0 mu). In addition, these test atmospheres contained 1000 ppm acetone,an acetate fiber solvent, in order to simulate fiber plant conditions. Evidence of oil mist was detectable within lung macrophages of all species tested and at both concentrations. Only at the higher concentration (100 mg/M3),, in dogs and rats, but not in mice and gerbils, was a retention of oil of such a magnitude so as to result in the development of oil microgranulomas. Rats given a 10-month recovery period following 12 months of exposure did not completely recover from the oil microgranuloma. These results indicate that the presence of typical textile fiber adjuvants in mineral oil and the concurrent presence of 1000 ppm acetone in the atmosphere do not significantly alter the inhalation toxicity of pure white mineral oil mist.

Acetone↗
PubMedDate not supplied

Thyroid tumors in rats from tetramethylthiourea.

Tetramethylthiourea (TMTU) was added to the diet of male and female ChR-CD rats for up to 2 years at levels of 0, 30 and 300 ppm. Fifty rats of each sex were used at each dietary level. High-level males and females and low-level males had a lower body weight and consumed less diet than did the controls. A slight anemia was found in the high-level males and females. Polyuria of a low osmolality was found in high level males and females. Serum thyroxine was lower in high-level males and females than in controls. TMTU-related gross and histologic changes were detected only in the thyroids of high-level males and females. After 3 months on test, the thyroids were enlarged and dark on gross examination. Histologically, there was an increase in follicle lumen size, loss of colloid staining, hypertrophy and hyperplasia of follicular cells, together with hyperemia. These early lesions were diffuse in distribution. Eight (28 percent) of 29 female high level rats, 18 to 24 months on test, developed follicular cell carcinomas with no such tumors in 26 comparable controls (p less than 0.005, Fisher's Exact Test, one tail). Although no metastases were found, capsular and vascular invasion by tumor cells was seen. TMTU was considered to be carcinogenic for the female rat under the conditions of this test.

Animals↗
PubMedDate not supplied

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.

Animals↗
PubMedDate not supplied

Kidney and liver tumors in rats from 4,4'-methylene bis (2-carbomethoxyaniline).

4,4'-Methylene bis (2-carbomethoxyaniline), also known as methylene-bis methyl anthranilate (MBMA), was added to the diet of male and female ChR-CD rats for up to two years at levels of 0, 1500, and 15,000 ppm. Fifty rats of each sex were used at each dietary level. Female rats at both dietary levels of MBMA had a lower body weight gain and lower food efficiency values than did the controls. High-level males and females showed a slight anemia; all other clinical laboratory tests were within normal limits. MBMA caused slight degenerative histologic changes in the liver and kidney of both sexes at both dietary levels. High-level males developed a statistically significant increase in kidney and liver tumors when compared to controls (p less than 0.05, Fisher's Exact Test, one tail). High-level females had an elevated kidney tumor incidence compared with controls (p less than 0.10). There was a statistically significant lower incidence in pituitary tumors in high-level males (p less than 0.05) and in high-level females (p less than 0.10) than in controls. High-level females had a lower incidence of mammary tumors (p less than 0.05) compared to controls. MBMA was considered to be a carcinogen of moderate potency in rats, since tumors were not found until 18 months on test using a comparative large dose (1.5% of diet).

Animals↗
PubMedDate not supplied

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).

Animals↗
PubMedDate not supplied

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).

3,3'-Dichlorobenzidine↗