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Biomedical subjects

H Muhle

Publications and source records attributed to H Muhle.

At least 37 records · Page 2Linked to original sources
PubMed1995

Neoplastic lung lesions in rat after chronic exposure to crystalline silica.

Groups of 100 SPF Fischer-344 rats were exposed 6 h a day, 5 d a week for 24 months to crystalline silica (1 mg center dot m-3, DQ 12 quartz) or titanium dioxide (5 mg center dot m-3) or air only. The animals were kept without further exposure for an additional 1.5 months. In the group exposed to crystalline silica a significantly increased incidence of 20 primary lung tumors was observed among 19 animals. The distribution of tumor types consisted of 3 adenomas, 11 adenocarcinomas, 4 benign cystic keratinizing squamous-cell tumors, 1 adenosquamous carcinoma, and 1 squamous-cell carcinoma. There were also 13 nodular hyperplasia lesions, which were interpreted to be borderline cases of adenomas. Approximately half of the adenoid tumors and all of the nodular hyperplasia lesions were characterized by moderate central fibrosis. The principal nonneoplastic findings in the silica-exposed group were lipoproteinosis, inflammation, epithelial hyperplasia, and fibrosis. The results can be considered significant due to the increased lung tumor incidence at a relatively low exposure level.

Administration, Inhalation↗
PubMed1994

Comparative investigations of the biodurability of mineral fibers in the rat lung.

The biodurability of various glass fibers, rockwool, and ceramic fibers was examined in rat lungs and compared with natural mineral fibers. Experiments were based on studies that have shown that the biodurability of fibers is one of the essential factors of the carcinogenic potency of these materials. Sized fractions of fibers were instilled intratracheally into Wistar rats. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM) or careful examination of the fiber suspension before treatment. After serial sacrifices up to 24 months after treatment, the fibers were analyzed by SEM following low temperature ashing of the lungs. Parameters measured included number of fibers, diameter, and length distribution at the various sacrifice dates, so that analyses could be made of the elimination kinetics of fibers from the lung in relation to fiber length (FL). Size selective plots of the fiber elimination correlated with fiber diameters enables the mechanism of the fiber elimination (dissolution, fiber breakage, physical clearance) to be interpreted. The half-time of fiber elimination from the lung ranges from about 10 days for wollastonite to more than 300 days for crocidolite. The biodurability of man-made vitreous fibers (MMVF) is between these values and is dependent on the chemical composition of the fibers and the diameter and length distribution. Results indicate that the in vivo durability of glass fibers is considerably longer than expected from extrapolation of published data on their in vitro dissolution rates.

Animals↗
PubMed1994

Investigation on the durability of man-made vitreous fibers in rat lungs.

Two types of sized stonewool with median lengths of 6.7 and 10.1 microns and median diameters of 0.63 and 0.85 microns, and crocidolite with fibers of median length of 4.8 microns and median diameter of 0.18 microns were instilled intratracheally into female Wistar rats. A single dose of 2 mg in 0.3 ml saline was used for the stonewool samples and 0.1 mg in 0.3 ml saline for crocidolite. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM). Five animals per group were sacrificed after 2 days, 1, 3, 6, and 12 months. After low-temperature ashing of the lungs about 200 fibers per animal were analyzed by SEM for length and diameter. The number and mass of fibers in the total lung were calculated. For the stonewool samples the decrease in the number of fibers in the lung ash followed approximately first order kinetics resulting in half-times of 90 and 120 days. The analysis of fiber number and diameter of different length fractions was used to estimate the contribution of three processes of fiber elimination: transport by macrophages for short fibers, breakage of fibers, and dissolution of fibers. (The process of transport by macrophages was found fastest for fibers with length < 2.5 microns). For the elimination of critical fibers with length > 5 microns, the breakage and dissolution were the most important processes. The breakage of fibers was predominant for one of the stonewool samples. The preferential type of the mechanism of fiber elimination is dependent on chemical composition and size distribution.

Animals↗
PubMed1994

Investigation of the biodurability of wollastonite and xonotlite.

The in vivo durability of wollastonite materials, coated and uncoated, and of xonotlite was tested. Wollastonite is an anhydrous natural silicate and xonotlite is a hydrated synthetic calcium silicate. UICC crocidolite was used as a positive control with high durability. Using a dry-sizing technique, fractions from the stock materials were prepared according to the definition of "thoracic particulate mass" and "respirable particulate mass" of the American Conference of Governmental Industrial Hygienists. Fibers were instilled intratracheally into female Wistar rats, and the evenness of their distribution in the lung was checked by scanning electron microscopy (SEM). After serial sacrifices at 2 and 14 days, 1, 3, and 6 months, and low temperature ashing of the lung, the fibers were analyzed by SEM. The number and size distribution of fibers were investigated. The total number of crocidolite fibers decreased with a half-time of 240 days, but the number of fibers > 5 microns in length was unchanged after 6 months. The elimination kinetics of wollastonite fibers from the lung were relatively fast, with half-times of 15 to 21 days. The coating of wollastonite in Wollastocoat had no effect on this elimination process. For the thoracic fraction of wollastonite, the elimination from the lung was as fast as for the respirable particulate fraction. The elimination kinetics of xonotlite from the lung was very fast. This material consisted of single crystals of acicular morphology with a median length of 1.3 micron and of agglomerates of these crystals. More than 99% of single crystals and about 85 to 89% of the agglomerates were already eliminated 2 days after instillation.

Air Pollutants↗
PubMed1992

Atypical malignant mesotheliomas with osseous and cartilaginous differentiation after intraperitoneal injection of various types of mineral fibres in rats.

The histopathological appearance of malignant mesotheliomas with osseous and cartilaginous differentiation is described in detail. Bone and cartilage occurred in mixed and sarcomatoid mesotheliomas which were induced by intraperitoneal injection of various types of asbestos fibres (asbestos cement, crocidolite, UICC-amosite, UICC-chrysotile B, Calidria-chrysotile). Bone or cartilage were found in 32.7% of mixed mesothelioma and in 12.8% of sarcomatoid mesotheliomas.

Abdominal Neoplasms↗
PubMed1992

Irreversible pulmonary changes induced in rat lung by dust overload.

The objective of this study was to investigate whether the effects of dust overload are reversible upon cessation of subchronic exposure to test toner. Female rats were exposed 6 hr/day, 5 days/week for 3 months to a test toner at 0, 10, and 40 mg/m3. The retained quantity of test toner in the lungs at the end of exposure was 0.4 and 3.0 mg for the low and high exposure groups, respectively. Fifteen months later, the corresponding values were 0.12 and 2.65 mg in the lungs. Alveolar clearance of tracer aerosols as well as cytologic and enzymatic parameters in the bronchoalveolar fluid was investigated at the end of exposure and subsequently up to 15 months later. The alveolar clearance of 59Fe2O3, 51Cr-polystyrene, and 85Sr-polystyrene tracer aerosols was slightly retarded at the low and substantially impaired at the high exposure level. At the low exposure level, there was some recovery in the clearance behavior up to 6 months after exposure. In contrast, at the high exposure level there was no indication of a reversal of the impaired clearance. For the beta-glucuronidase activity and the number of polymorphonuclear cells, the pattern of the effects was similar to the effects on the half-time tracer particle clearance. In conclusion, the dust overload at a lung burden of 3 mg test toner in rats was persistent for at least 15 months after termination of exposure.

Animals↗
PubMed1991

Pulmonary response to toner upon chronic inhalation exposure in rats.

A chronic inhalation study of a test toner was conducted by exposure of groups of F-344 rats for 6 hr/day, 5 days/week for 24 months. The test toner was a special Xerox 9000 type xerographic toner, enriched in respirable-sized particles compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The target test aerosol exposure concentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high) mg/m3. Titanium dioxide (5 mg/m3) and crystalline silicon dioxide (1 mg/m3), used as negative and positive controls for fibrogenicity, were also evaluated. Inhalation of the test toner or the control materials showed no signs of overt toxicity. Body weight, clinical chemistry values, food consumption, and organ weights were normal in the toner- and TiO2-exposed groups, except for a 40% increase in lung weight in the toner high-exposure group. All of the changes in the toner-exposed groups were restricted to the lungs or associated lymph nodes. A chronic inflammatory response was evident from the bronchoalveolar lavage parameters for the toner high-exposure group. The incidence of primary lung tumors was comparable among the three toner-exposed groups and the TiO2-exposed, and air-only controls, as well as consistent with historical background levels. A mild to moderate degree of lung fibrosis was observed in 92% of the rats in the toner high-exposure group, and a minimal to mild degree of fibrosis was noted in 22% of the animals in the toner middle-exposure group. The pulmonary changes in the toner high-exposure group were smaller in magnitude than those found in the crystalline silica-exposed group. The comparative fibrogenic potency of TiO2, toner, and SiO2 was estimated to be 1:5:418 using a dosimetric model and assuming a common mechanistic basis. There were no pulmonary changes of any type at the toner low-exposure level, which is most relevant in regard to potential human exposures. The lung alterations in the toner high-exposure group are interpreted in terms of "lung overloading," a generic response of the respiratory system to saturation of its detoxification capacity. The maximum tolerated dose (MTD) criterion was met at the toner high (16 mg/m3)-exposure level.

Administration, Inhalation↗
PubMed1991

Lung clearance and retention of toner, utilizing a tracer technique, during chronic inhalation exposure in rats.

Male and female F-344 rats were exposed to 6 hr/day, 5 days/week for up to 24 months to a special test toner at 0, 1, 4, and 16 mg/m3, TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3 by the inhalation route. 59Fe-labeled iron oxide and 85Sr-labeled polystyrene particles were periodically inhaled by the nose-only route and used to measure alveolar clearance rates during the course of the study. This method was used to describe a maximum functionally tolerated dose (MFTD). Pulmonary retention of toner and control materials (TiO2 and SiO2) was measured after 3, 9, 15, 21, and 24 months of exposure. The quantity of all three materials retained in the lungs and lung-associated lymph nodes increased with exposure duration and level. The final pulmonary burdens of toner at the three exposure levels were 0.22, 1.73, and 15.6 mg/lung, respectively. Alveolar clearance of both tracers was substantially impaired at the toner high-exposure level, and moderately slowed at the toner middle-exposure level. The excessive quantity of toner retained and the substantially retarded clearance in the toner high-exposure group are indicative of "lung overloading." Alveolar clearance of 85Sr-polystyrene particles was slightly slowed in the TiO2-exposed group and substantially impaired in the SiO2-exposed group. The alveolar clearance of the unexposed rats decreased about 30% during the study, a change ascribed to aging. For a general description of the toxicokinetics of the various dusts, a semiempirical kinetic model was developed, which could generally be useful for the extrapolation of lung retention of insoluble particles from a subchronic to a chronic inhalation study. Both the maximum tolerated dose (MTD) and the MFTD were exceeded at the toner high-exposure level during the study in rats.

Aerosols↗
PubMed1990

[The persistence of chemically different glass fibers in rat lungs].

The half-times of glass fibre samples of different chemical composition and size was analysed in the rat lung. Up to two years after intratracheal instillation the number of fibres in the ashed lungs was determined by SEM. Half-times of fibre clearance of 40 to 240 days were calculated.

Animals↗
PubMed1989

Reversibility of clearance impairment after subchronic test toner inhalation.

In a chronic study of a test toner in F-344 rats an impairment of alveolar clearance and increased toner retention were observed at the high and, to a lesser degree, at the middle exposure level throughout the study. The objectives of the present study were: 1. To investigate the nature and the time course of test toner and surrogate tracer alveolar clearance and toner retention behaviour following a subchronic exposure interval. 2. To investigate the dependence of the response upon the pulmonary burden of the test toner.

Administration, Inhalation↗
PubMed1989

Lung response to test toner upon 2-year inhalation exposure in rats.

SPF F-344 rats were exposed 6 h/day 5 days/wk for up to 24 months to a special test toner at 0, 1, 4 and 16 mg/m3 or TiO2 at 5 mg/m3, or SiO2 at 1 mg/m3, by the inhalation route. The animals were kept for an additional 6 weeks in filtered air. Surviving animals were sacrificed at 25.5 months after start of exposure. Life-span and causes of death were independent of treatment and in accordance with published values. No evidence for systemic toxicity or any upper-respiratory system effects were found in the toner-exposed groups. The incidence of lung tumors was comparable in the control, 3 toner and TiO2-exposed groups. An incidence of 18%, combined benign and malignant tumors was observed in the quartz-treated rats. A slight to moderate degree of fibrosis was observed at the toner high exposure level in all animals, while a very slight degree of fibrosis was noted in 20% of the animals at the toner middle (4 mg/m3) exposure level. The fibrogenic potency of the test toner was calculated to be comparable to TiO2. No pulmonary changes were seen at the toner low (1 mg/m3) and environmentally most relevant exposure level.

Administration, Inhalation↗
PubMed1989

Reversibility of biochemical and cytological alterations in broncho-alveolar lavagate upon cessation of dust exposure.

The objectives of the present study were: 1. To investigate the nature and time course of the biochemical and cytological changes following acute and subchronic exposure intervals. 2. To investigate the dependence of the response upon the pulmonary burden of the test material. Alveolar clearance measurements were performed in parallel and are presented in a separate poster (1).

Animals↗
PubMed1987

Comparative study of bronchoalveolar lavage fluid: effect of species, age, and method of lavage.

The analysis of bronchoalveolar lavage fluid has been used as a probe to detect lung injury in toxicological studies and to diagnose the disease state of the lung in humans. To determine how variable the content of lavage fluid from different species is, bronchoalveolar lavage fluids from normal individuals of four species (hamster, rat, guinea pig, and rabbit) were compared for enzymatic and cellular content as well as total protein and sialic acid. In addition, lavage fluid from young adult rats and hamsters was compared to that from older animals. Finally, the effect of the method of lavage on lavage fluid content was evaluated by comparing lavage fluid obtained from an excised lung with that from a lavage performed in vivo. In general, lavage fluids from the four species were similar. However, lavage fluid from guinea pigs had higher numbers of granulocytes and higher mean beta-glucuronidase activities than fluids from other species. Rats had higher mean alkaline phosphatase activities, reflecting higher serum values of this enzyme. Older hamsters had more protein in their lavage fluid than younger animals, and older rats had lower elastase inhibitory activity than young rats. Performing lavage in vivo, as compared to in vitro, did not greatly alter the lavage fluid except for a trend toward a higher level of sialic acid in fluid taken from the living animal.

Aging↗