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Biomedical subjects

C E Ulrich

Publications and source records attributed to C E Ulrich.

13 recordsLinked to original sources

Two-week aerosol inhalation study in rats of ethylene oxide/propylene oxide copolymers.

Previous studies have shown that aerosols of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100) produced an inflammatory response in lungs of rats in short-term repeated exposures at relatively low concentrations. This study was carried out on related polyalkylene glycols (EO/PO copolymers) to determine if similar effects would occur upon short-term repeated exposure. Rats were treated by whole body liquid droplet aerosol exposures of six hours per day, five days per week for two consecutive weeks to each of five EO/PO copolymers. The exposure level for the positive control (UCON 50-HB-5100) was 55 mg/m3, while the remaining 4 test copolymers were evaluated at 100 mg/m3. Each exposure group consisted of ten male albino rats. After three exposures, nine of ten rats exposed to UCON 50-HB-5100, and six of ten rats exposed to UCON 50-HB-2000 had died. At necropsy, congestion, consolidation and red discoloration of the lungs were noted. A moderate to severe alveolitis, characterized by intraalveolar edema, hemorrhage and fibrin deposition, was observed after five days of exposure. At necropsy, these rats exhibited elevated lung weights and similar macroscopic and microscopic lesions. Rats exposed to the other test materials (UCON 75-H-1400, Pluronic L17R1, Pluronic L31, and Pluronic L64) survived with essentially no signs of toxicity through the ten exposure days. Body weights, organ weights, hematological evaluation, pharmacotoxic signs, and macroscopic and microscopic evaluation after necropsy were similar between groups and when compared to the negative control group. Only a slight alveolitis was noted after two weeks of exposure which subsided by two-weeks post exposure.

Administration, Inhalation

Inhalation toxicity of chromium dioxide dust to rats after two years exposure.

Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 (stabilized and unstabilized, respectively) or 25 mg m-3 (stabilized) for 6 h day-1, 5 days week-1 for 2 years. No dust-exposure-related pathological changes were observed, other than lung lesions, in all exposed rats. There were no significant differences in pulmonary response between unstabilized and stabilized CrO2 at the 0.5 mg m-3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg m-3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, six developed keratin cysts and two had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization in the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally-induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of ths type of lung tumor appears to be negligible.

Administration, Inhalation

Inhalation developmental toxicity study of propylene oxide in Fischer 344 rats.

The developmental toxicity potential of propylene oxide (PO) was evaluated in Fischer 344 rats following inhalation exposure. Four groups of 25 mated female rats were exposed to 0, 100, 300, and 500 ppm of PO for 6 hr per day on Gestation Days 6 through 15, inclusive. Cesarean sections were performed on all females on Gestation Day 20 and the fetuses removed for morphological evaluation. Exposure to propylene oxide did not adversely affect survival, appearance, or behavior at any of the exposure levels tested. Maternal body weight gain and food consumption were reduced significantly among the females at the 500 ppm level during the exposure period. No exposure-related effects were noted with respect to maternal water consumption, organ weights, cesarean section, or fetal morphological observations with the sole exception of increased frequency of seventh cervical ribs in fetuses at the maternally toxic exposure level of 500 ppm. In summation, the no-observable-adverse-effect level (NOAEL) of propylene oxide, when administered to Fischer 344 rats via whole-body inhalation exposure, was considered to be 300 ppm.

Administration, Inhalation

Effects of inhaled chromium dioxide dust on rats exposed for two years.

Rats were exposed by inhalation to chromium dioxide (CrO2) dust at design concentrations of 0, 0.5 mg/m3 (stabilized and unstabilized, respectively), or 25 mg/m3 (stabilized) for 6 hr/day, 5 days/week for 2 years. No dust-exposure-related pathological changes other than lung lesions were observed in all exposed rats. There were no significant differences in pulmonary responses between unstabilized and stabilized CrO2 at the 0.5 mg/m3 exposure level. The lungs showed minute dust deposition in the alveoli adjacent to the alveolar ducts, but maintained an intact general architecture. The pulmonary responses satisfied the biological criteria for a nuisance dust. At 25 mg/m3, dust deposition was sharply confined to the alveoli in the alveolar duct region. Alveolar walls enclosing dust-laden macrophage (dust cell) aggregates were thickened with hyperplastic Type II pneumocytes and slightly collagenized fibrosis. Alveoli adjacent to the terminal bronchioles were lined with bronchiolar epithelium (alveolar bronchiolarization). In addition, lungs showed foamy macrophage response, cholesterol granulomas, alveolar proteinosis, and minute fibrotic pleurisy. These pulmonary lesions occurred predominantly in female rats. Of 108 female rats, 6 developed keratin cysts and 2 had cystic keratinizing squamous cell carcinoma (CKSCC). None of 106 male rats had either a keratin cyst or a CKSCC. The lung tumors developed from metaplastic squamous cells in the areas of alveolar bronchiolarization at the alveolar duct region. The lung tumors were well differentiated and devoid of characteristics of true malignancy. The CKSCC is an experimentally induced, unique tumor type and is different from the type of spontaneous lung tumor seen in man or animals. The relevance to man of this type of lung tumor appears to be negligible.

Aerosols

A 6-month multispecies inhalation study with maleic anhydride.

This study was initiated to assess the safety of atmospheres containing maleic anhydride. Accordingly, rats (15/sex/group), hamsters (15/sex/group), and monkeys (3/sex/group) were treated 6 hr a day 5 days a week for 6 months. Atmospheres were generated by subliming maleic anhydride and were monitored using Tenax collection columns and gas chromatography to detect total maleic; i.e., maleic anhydride plus maleic acid. The mean analytical concentrations were 0, 1.1, 3.3, and 9.8 mg/m3 of total maleic. Dose-related signs of nasal and ocular irritation were observed at each test level in all three species; signs included discharge, sneezing, gasping, and coughing. No significant treatment-related mortality was observed in any species. While reduced weight gains were observed only in mid- and high-dose rats, their terminal body weights were greater than 90% of control values. No treatment-related effects were observed in hematology, clinical chemistry, urinalysis, and pulmonary function tests. Although microscopic evaluation of tissue revealed evidence of nasal irritation in all species, there was no evidence of systemic toxicity which was directly attributed to maleic anhydride. While the results of this study support the current ACGIH TLV and OSHA PEL of 1 mg/m3 regarding systemic toxicity, continuous exposure at this level during the day may produce some signs of irritation.

Administration, Inhalation

Chronic inhalation of short asbestos fibers.

An animal inhalation study was initiated to study the chronic biological effects of inhalation of short chrysotile asbestos fibers. Rats and monkeys were exposed for 18 months, 7 hr/day, 5 days/week to a specially prepared, chrysotile asbestos aerosol. Based upon daily chamber measurements, the mean concentration of fibers in the chamber air was 1.0 mg/m3. By phase contrast microscopy, the number of fibers greater than 5 micron in length was determined to be 0.79 fiber per cubic centimeter. Rats were autopsied for pathological and histochemical examination at 1, 3, 6, 12, 18, and 24 months after initiating exposures. No significant differences in the histochemical data were seen between the exposed and control groups. Gross and histopathologic examination of exposed and control groups of rats indicated no compound-related lesions, including fibrosis. Open lung biopsies were performed on the chrysotile-exposed and the control monkeys 28 months after initiating exposures. Histopathologic evaluation of the lung biopsy tissue showed the presence of asbestos bodies adjacent to the terminal bronchioles of the asbestos-exposed monkeys. There was no observed fibrosis in pulmonary tissue. All monkeys are being maintained for an indefinite period and observed for signs of latent pulmonary disease.

Aerosols

Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol--I. Introduction, experimental design, and aerosol generation methods.

A brief literature review on manganese toxicity is presented; as related to designing a chronic inhalation study for evaluating methylcyclopentadienyl manganese tricarbonyl when utilized as a motor fuel additive. The experimental design of this study is described. The generation system utilized to simulate the manganese aerosol produced by an internal combustion engine is described in detail. This generation system operated twenty-four hours per day, seven days per week producing aerosols at 11.6, 112.5, and 1152 micrograms Mn/m3 with an aerodynamic diameter of approximately 0.11 micron.

Aerosols

Evaluation of the chronic inhalation toxocity of a manganese oxide aerosol. II. Clinical observations, hematology, clinical chemistry and histopathology.

Monkeys and rats were exposed to 11.6, 112.5, or 1152 microgram Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various serum biochemical, and hematologic evaluations were conducted on both specie. Body weight gain was accelerated in rats exposed to 1152 microgram Mn/m3. Hemoglobin concentrations were slightly elevated for both sexes and both specie exposed to 1152 microgram Mn/m3; however, the effect may not be directly related to Mn. Some evidence of hypophosphatemia was observed. No exposure related effects were demonstrated by organ weight or histopathologic observations.

Aerosols

Evaluation of the chronic inhalation toxicity of a manganese oxide aerosol. III. Pulmonary function, electromyograms, limb tremor, and tissue manganese data.

Monkeys and rats were exposed to 11.6, 112.5, and 1152 micrograms Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various evaluations of pulmonary function, electromyographic activity, limb tremor, and tissue manganese levels were conducted. No exposure related effects on pulmonary function, limb tremor, or electromyographic activity were observed. After nine months of exposure Mn levels were elevated in a near dose related manner in kidney, lung, spleen, and blood. However, by six months postexposure there were no differences as compared to the control group in tissue Mn levels which could be attributed to the exposure conditions.

Aerosols

Pulmonary deposition of aerosols in individual and group caged rats.

There has long been a need to define differences in the amount of aerosol inhaled by group caged rodents as compared to the theoretically ideal individually caged rodent. Therefore, an experiment was designed and conducted to gain insight into this problem. Three groups of animals were evaluated for the degree of pulmonary deposition following a single six hour exposure to a 3 mu aerosol of dodecyl alcohol. One group contained individually caged rats, while the other two groups contained rats caged either in groups of three or seven. Analyzing lungs and trachea for the dodecyl alcohol indicated 25.6 micrograms/g, 27.1 microbrams/g, and 23.1 micrograms/g for rats caged individually, in threes, or in sevens, respectively. There was no statistically significant difference between the amount of dodecyl alcohol found in group caged rat lungs as compared to individually caged rats. Thus group housing does not appear to reduce the amount of aerosol inhaled by rats during a six hour whole body exposure.

Aerosols

Effects in rats and guinea pigs of short-term exposures to sulfuric acid mist, ozone, and their combination.

Ozone and the oxides of sulfur are common environmental pollutants. The acute pulmonary lesions caused by ozone and sulfuric acid mist in rats and guinea pigs have been characterized. Rats are not affected by sulfuric acid mist in concentrations up to 100 mg/m3 except for reduced body weight at the higher doses. A true alveolitis develops in guinea pigs exposed to more than 20 mg/m3 sulfuric acid mist. The ozone lesion is primarily confined to the terminal bronchioles and proximal alveoli. In combination studies with up to 2 ppm ozone and up to 10 mg/m3 sulfuric acid mist, the pulmonary lesion and lung/body weight data were essentially the same as in exposure to ozone alone, and the number of statistically significant synergistic effects in rats and guinea pigs was about what one would expect to observe by chance alone.

Aerosols

Baseline pulmonary physiologic values for the squirrel monkey (Saimiri sciureus).

Baseline pulmonary physiologic values were determined on 43 (421-910 g) male and 47 (425-604 g) female squirrel monkeys (Saimiri sciureus). Respiratory rate was found to be 55 +/- 1.9 (SE) breaths per minute for males and 58 +/- 1.7 breaths per minute for females. Tidal volume was 8.9 +/- 0.37 ml for males and 7.5 +/- 0.28 ml for females. Airway resistance for the male was 0.052 +/- 0.006 cm H2O/ml/second; while for the female it was 0.086 +/- 0.011 cm H2O/ml/second. Dynamic compliance was found to be 1.78 +/- 0.15 ml/cm H2O for males and 1.48 +/- 0.124 ml/cm H2O for females. An index of distribution of ventilation was 48 +/- 2.5 breaths for males and 42 +/- 1.7 breaths for females.

Airway Resistance

Subchronic inhalation toxicity of nitromethane and 2-nitropropane.

Nitromethane (NM) and 2-nitropropane (2-NP) and versatile compounds employed in a wide variety of industrial applications, thus providing ample opportunity for occupational exposure. The purpose of this study was to determine the subchronic inhalation toxicity of NM and 2-NP in order to recommend acceptable exposure levels in the workplace. Fifty male rats and 15 male rabbits were exposed to either 98 ppm or 745 ppm of NM or 27 or 207 ppm of 2-NP 7 hours/day, 5 days/week, for periods up to 24 weeks. Fifty rats and 15 rabbits were exposed to filtered air for similar lengths of time and served as controls. Ten rats from each exposure and control group were sacrificed following 2 days, 10 days, 1 month, 3 months, and 6 months of exposure. Five rabbits from each exposure or control group were sacrificed at 1, 3, and 6 months of exposure. Effects relatable to exposure to NM were decreased body weight gain in rats following 8 weeks of exposure to 745 ppm, and a thyroid effect evidenced by an increased thyroid weight and decreased serum thyroxin levels, most notable in rabbits. Liver weights were significantly elevated in rats exposed to 207 ppm of 2-NP for 1, 3, and 6 months. No exposure-related gross or microscopic alterations were seen in any of the tissues examined for rats and rabbits exposed to 745 and 98 ppm of NM and 27 ppm of 2-NP or in tissues of rabbits exposed to 207 ppm of 2-NP. Liver neoplasms were seen in all 10 rats killed following 6 months of exposure to 207 ppm of 2-NP, indicating that 2-NP is a potent carcinogen in the rat.

Animals