Biomedical subjects

B M Ulland

Publications and source records attributed to B M Ulland.

18 recordsLinked to original sources

PubMed1989

Thirteen-week toxicity studies of 3,3'-dimethoxybenzidene and C.I. Direct Blue 15 in the Fischer 344 rat.

The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination.

Animals↗

PubMed1989

Transplantation studies of preputial gland and epithelial skin neoplasms derived from benzidine-based dye carcinogenicity assays in Fischer 344 male rats.

Neoplasms of preputial gland and skin were obtained from Fischer 344 male rats on lifetime drinking water studies of the benzidine congener 3,3'-dimethoxybenzidine, C.I. Direct Blue 15 or C.I. Acid Red 114, bisazobiphenyl dyes derived from 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine. Portions of these well differentiated neoplasms were implanted into the left mammary fat pad of Fischer 344 male recipients. The rate of growth, presence of local invasion and distant metastases, and morphologic features were observed following 4 serial transplantations. All implants appeared early, grew rapidly, and were histomorphologically similar to the original neoplasms. Metastases from transplants were observed with both preputial gland and skin tumor lines in serial passages. The transplantation results confirm the malignant nature of these neoplasms.

Animals↗

PubMed1986

A two-year drinking-water study of dichloromethane in rodents. I. Rats.

In order to evaluate its toxicity and carcinogenic potential, dichloromethane (DCM) at levels of 0, 0, 5, 50, 125 and 250 mg/kg body weight/day was administered in deionized water to a total of 500 Fischer 344 rats of each sex for 104 wk. An additional group received a level of 250 mg/kg body weight/day for 78 wk followed by a 26-wk recovery period during which only deionized water was presented. Kills were performed at 26-wk intervals. Statistically significant effects on body weight, water consumption and food consumption were observed at the two highest dose levels. Minimal effects were noted on the haematological and serum chemistry parameters monitored. Treatment-related hepatic changes were observed histomorphologically in both sexes after 78 wk of treatment. These changes consisted of an increased incidence of foci/areas of cellular alteration and of fatty change at all dose levels except the lowest. A decrease in the severity of fatty change was observed in the recovery group, but no difference was noted in the incidence of cellular alteration. An increased incidence of hepatic tumours noted in females treated at 50 and 250 mg/kg/day was within the range of historical control incidences. In view of an unusually low incidence of similar tumours in the concurrent control groups and the absence of an increased incidence of hepatic tumours in the group treated at 125 mg/kg/day, the effect seen at 50 and 250 mg/kg/day was not considered to be attributable to DCM treatment. Under the experimental conditions of this study, there was a no-observable-effect level of 5 mg/kg/day in both males and females.

Administration, Oral↗

PubMed1986

A two-year drinking-water study of dichloromethane in rodents. II. Mice.

To investigate its carcinogenic potential, dichloromethane (DCM) was administered at levels of 0, 0, 60, 125, 185 and 250 mg/kg body weight/day to a total of 1000 B6C3F1 mice in deionized drinking-water for 104 wk. The high-dose male and female mice showed a transitory increase in mean leucocyte counts. Treatment-related toxic changes were noted in both male and female livers at the highest dose. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose-related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no-observable-effect level (NOEL) for DCM of 185 mg/kg body weight/day in both sexes.

Administration, Oral↗

PubMed1983

Chronic effects of dietary exposure to amosite asbestos and tremolite in F344 rats.

Carcinogenesis bioassays of blocky (nonfibrous) tremolite and amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted with male and female Fischer 344 rats. The minerals were administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats starting with the dams of the test animals. One group of amosite rats also received chrysotile asbestos via gavage during lactation. Group sizes varied from 100 to 250 animals. The offspring from mothers exposed to tremolite or amosite asbestos were smaller at weaning than those from untreated mothers and remained smaller throughout their life. The administration of dimethylhydrazine (DMH) did not affect body weight gain, either in amosite-exposed or nonexposed animals. Survival was comparable in the tremolite and control groups. The amosite-exposed rats showed enhanced survival compared to the untreated controls. DMH exposure reduced survival by approximately one year, although the amosite plus DMH groups survived slightly better than the DMH alone groups. No toxicity or increase in neoplasia was observed in the tremolite-exposed rats compared to the controls. Significant increases (p less than 0.05) in the rates of C-cell carcinomas of the thyroid and monocytic (mononuclear cell) leukemia in male rats were observed in amosite-exposed groups. However, the biological significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and the positive effect was not observed in the amosite plus preweaning gavage group. The biological significance of an increased incidence of mononuclear cell leukemia is questionable, because of a lack of statistical significance in the amosite group when evaluated using life table analysis, lack of significance when compared to the tremolite control group, and the fact that no toxic or neoplastic lesions were observed in the target organs, i.e., gastrointestinal tract and mesothelium. DMH caused a high rate of (62-74%) of intestinal neoplasia in amosite and nonamosite-exposed groups. Neither an enhanced carcinogenic nor protective effect was demonstrated by exposure to amosite asbestos.

1,2-Dimethylhydrazine↗

PubMed1981

Effects of aging on the induction of angiosarcoma.

Adult, Sprague-Dawley albino rats of four different ages (6, 18, 32 and 52 weeks) were exposed to 940 ppm vinyl chloride by inhalation for 24 weeks, 5 days/week, 7 hr/day. In each age group, there were 110 to 128 males and the same number of females. The similarly housed control group, which was not exposed to vinyl chloride, consisted of the same number of males and females in each age group. All animals that died spontaneously, or were sacrificed moribund, or were killed at scheduled times (3, 6 and 9 months after initial exposure) were autopsied. All organs were examined grossly, and several tissues from each animal were examined microscopically. The older the rats were when they were first exposed, the greater the incidence of angiosarcomas. The incidences of angiosarcomas in the four age groups (from youngest to oldest) in the exposed males in the nonscheduled sacrifice groups were: 0/37 (0%); 0/44 (0%); 3/45 (6.7%); and 13/55 (24%). Similarly, for the females, these incidences were: 2/38 (5.3%); 7/47 (15%); 23/49 (47%); and 11/54 (20%). Most of the angiosarcomas were highly anaplastic, primary tumors in the livers that metastasized to the lungs. Only one angiosarcoma was seen in all the control rats; that occurred in subcutaneous tissue. This study demonstrated that older adult animals and females are more susceptible to the angiosarcoma-inducing effects of vinyl chloride than young adult animals and males, respectively.

Aerosols↗

PubMed1981

Carcinogenicity tests of certain environmental and industrial chemicals.

Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions.

2-Acetylaminofluorene↗

PubMed1979

Chronic exposure to low concentrations of halothane-nitrous oxide: lack of carcinogenic effect in the rat.

The effects of prolonged exposure to low-concentration combinations of halothane and nitrous oxide on tumor incidence, especially with regard to the reticuloendothelial system, were studied. Three groups of 50 male and 50 female Fischer 344 rats each were studied. For seven hours/day, five days/week, for 104 weeks, Group I was exposed to filtered air (control); Group II, to halothane, 1 ppm, and nitrous oxide (N2O), 50 ppm; Group III, to halothane, 10 ppm, and N2O, 500 ppm. No evidence of exposure-related effects on body weight, appearance, behavior, survival, or hematologic findings was found. Histologic evaluation of the reticuloendothelial system and of other major organs revealed neither enhancement of the spontaneous tumor rate nor any unusual neoplasm. Thus, this study did not lend support to the hypothesis that these anesthetic agents in low concentrations are responsible for the reportedly higher than average incidence of reticuloendothelial malignancies in operating room personnel.

Animals↗

PubMed1978

Serum haptoglobin levels in mice with 7, 12-dimethylbenz[a]anthracene-induced tumors.

Serum haptoglobin (Hp) levels were determined periodically in mice treated with the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA). The magnitude and duration of the Hp response to tumors induced by DMBA were dependent on the tumor type; lymphocytic lymphomas elicted a minimal response, whereas mice bearing mammary carcinomas and stomach squamous cell carcinomas had high Hp levels which remained elevated throughout most of the period of tumor development. In the majority of mice with mammary carcinomas, the initial rise in serum Hp coincided fairly closely with the first appearance of palpable masses. Some variation in the magnitude of the Hp response was observed between individual mice bearing chemically-induced tumors of similar histological types.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1977

A carcinogenicity assay of Mirex in Charles River CD rats.

The long-term administration of 50 and 100 ppm of Mirex in the diets of male and female Charles River CD rats was associated with a spectrum of liver lesions, from foci or areas of cellular alteration and neoplastic nodules to hepatocellular carcinoma. Statistically significant numbers of neoplastic nodules were observed in the livers of male rats receiving the high dose. Neoplastic nodules and hepatocellular carcinomas were not observed in control rats.

Animals↗

PubMed1975

Carcinogenicity of three dose levels of 1,4-Bis(4-fluorophenyl)-2-propynyl-N-cyclooctyl carbamate in male Sprague-Dawley and F344 rats.

Feeding 1,4-bis(fluorophenyl)-2-propynyl-N-cyclooctyl carbamate to F344 or Sprague-Dawley male rats at 125-500 ppm in the diet led to many carcinomas of the small intestine and ear duct (Zymbal's gland tumors) in addition to lymphomas and leukemias. A high incidence of mammary adenocarcinomas was found in the Sprague-Dawley rats. Only a few colon or liver tumors were observed in each strain.

Adenocarcinoma↗

PubMed1973