The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Ken Donaldson - One of the best experts on this subject based on the ideXlab platform.
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Bromo-deoxyuridine (BRDU) uptake in the lungs of rats inhaling Amosite asbestos or vitreous fibres at equal airborne fibre concentrations
Experimental and Toxicologic Pathology, 2011Co-Authors: Ken Donaldson, David M Brown, Brian G. Miller, Arnold R. BrodyAbstract:Rats were exposed, by inhalation, to target airborne fibre concentrations of 1000 f/ml (PCOM fibres by WHO criteria) of a long Amosite asbestos sample and a vitreous fibre sample; the target was closely attained for both fibre samples. The size distributions of the two fibre samples was closely similar. Rats were placed in the chambers for 7 hours and then, following a further 16 hours in room air, were injected with bromo-deoxyuridine (BRDU). The presence of BRDU-positive cells in terminal bronchioles/alveolar ducts was assessed in blocks taken from various parts of the left lung, from apex to base. There were significant differences in the proliferative responses between animals but there were also significant differences between the treatments. Lungs from rats exposed to vitreous fibres showed no greater response than the controls, but there was a markedly greater proliferative response in the lungs of rats inhaling long Amosite. There was a decreasing gradient of proliferative response from the apex of the lung to the base with all treatments. This could be explained by different degrees of deposition in different areas of the lung. Similar amounts of fibre accumulated in the lungs of rats exposed to the two fibre types and it is unlikely that dissolution could be important over the timescale used here. We conclude that, when Amosite asbestos deposits in the lungs of rats it stimulates a proliferative response and that deposition of an equal number of similar-sized vitreous fibres has no effect.
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the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to Amosite asbestos following short term inhalation exposure interim results
Inhalation Toxicology, 2010Co-Authors: D M Bernstein, P Kunzendorf, Rick A Rogers, Ken Donaldson, Rosalinda Sepulveda, D Schuler, S Gaering, Jorg Chevalier, S E HolmAbstract:The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to Amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and Amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or Amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 µm) cleared rapidly (T1/2 of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response ...
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influence of fibre length dissolution and biopersistence on the production of mesothelioma in the rat peritoneal cavity
Annals of Occupational Hygiene, 1999Co-Authors: Brian G. Miller, R. E. Bolton, Ken Donaldson, R. T. Cullen, D. Buchanan, Alison Searl, J. M. G. Davis, C A SoutarAbstract:A range of respirable man-made mineral fibres were tested for evidence of carcinogenicity by injection into the peritoneal cavity of male SPF Wistar rats; and diAerences in carcinogenicity were related to the dimensions and biopersistence of the injected fibres. The fibres tested included an Amosite asbestos, a silicon carbide whisker, a special purpose glass microfibre, and a range of other man-made vitreous fibres (MMVFs) and refractory ceramic fibres (RCFs) from the TIMA fibre repository. The injected dose of each was designed as the estimated mass required to contain 10 9 fibres >5 mm in length, as determined by optical microscopy. The numbers of long fibres (>15 mm) contained in these doses ranged across fibres from 0.110 9 to 0.810 9 fibres; the number of long fibres thinner than 0.95 mm ranged from 0.01510 9 to 0.4 10 9 . The treatment groups contained between 18 and 24 animals. Animals were killed when they showed signs of debilitation. At autopsy, the diagnosis of mesothelioma was usually obvious macroscopically. Otherwise, histological examination of peritoneal organs was used to search for early tumour development. Judged by median survival time, four of the fibre types, in the doses administered, presented higher mesothelioma activity than Amosite asbestos. The other fibres tested were less carcinogenic than the Amosite. Only a ceramic material derived by extreme heating to simulate the eAect of furnace or oven conditions, produced no mesotheliomas. Attempts were made, using regression models, to relate these diAerences to fibre dimensions and to measures of durability from separate experiments. The results pointed principally to a link with the injected numbers of fibres >20 m mm in length and with biopersistence in the rat lung of fibres longer than 5 mm. Improved quantification of the relative importance of fibre dimensions and biopersistence indices requires experimentation with a range of doses. # 1999 British Occupational Hygiene Society. Published by Elsevier Science Ltd. All rights reserved.
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detection of surface free radical activity of respirable industrial fibres using supercoiled φx174 rf1 plasmid dna
Carcinogenesis, 1995Co-Authors: Peter S Gilmour, P H Beswick, David M Brown, Ken DonaldsonAbstract:The ability of a number of respirable industrial fibres, Amosite and crocidolite asbestos, refractory ceramic fibres (RCFs) and man-made vitreous fibres (MMVFs), to cause free radical injury to plasmid ?X174 RFI DNA was assessed. The oxidative DNA damage was observed as depletion of supercoiled DNA after fibre treatment and was quantified by scanning laser densitometry. The mechanism of fibre-mediated damage was determined by the use of the specific hydroxyl radical scavenger mannitol and the iron chelator desferrioxamine-B. The Amosite and crocidolite asbestos caused substantial damage to DNA that was dose-related. The free radicals responsible for the asbestos-mediated DNA damage were hydroxyl radicals, as determined by inhibition with mannitol. Asbestos fibre-mediated damage to DNA was completely ameliorated by the chelation of fibre-associated iron with desferrioxamine-B. The amount of Fe(II) and Fe(III) released by equal numbers of the different fibre types at equal fibre number was determined. The fibres released very small amounts of Fe(II) and there were no significant differences between the fibre types. The fibres released substantial amounts of Fe(III) ; MMVF 21 released significantly more Fe(III) than any of the other fibres and short fibre Amosite also released more Fe(III) than three of the MMVFs and two of the RCFs. When ability to release Fe(II) and Fe(III) was compared with ability to cause DNA damage there was not a good correlation, because only the long Amosite and crocidolite caused substantial free radical injury to DNA ; this contrasts with MMVF 21 and short Amosite being the two fibres that released the greatest amounts of iron. The loss of ability to damage DNA in DSF-B-treated asbestos fibres shows that iron at the surface of asbestos fibres definitely has a role in generating hydroxyl radicals. However, it is clear that some fibres, such as short Amosite and MMVF 21, release large quantities of iron without causing free radical damage, whilst neither long Amosite nor crocidolite released more iron than the other fibres. The exact role of iron in fibre reactivity therefore remains unresolved, but fibre-bound iron not released from the surface of asbestos could be important. Further research is under way to investigate this possibility.
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Cytogenetic and pathogenic effects of long and short Amosite asbestos.
The Journal of Pathology, 1995Co-Authors: Ken Donaldson, Nadya GolyasnyaAbstract:This study utilized two samples of Amosite asbestos which differ in their length, but not in their diameter and which have been shown previously to have very different abilities to cause pathology in rats exposed by instillation or inhalation. The activity of these Amosite samples in causing chromosomal aberrations in Chinese hamster ovary cells in culture was examined, along with the effect of the glutathione (GSH) synthesis-inhibiting agent buthionine sulphoximine. The incidence of chromosomal aberrations in cells treated with the short fibre sample was similar to control levels; the long Amosite sample caused significantly more chromosomal aberrations than the short fibre sample. When cells were treated with buthionine sulphoximine to decrease the levels of intracellular glutathione, the incidence of chromosomal aberrations was increased in the control cells, but also on treatment with both short and long Amosite, the long sample again being considerably more active than the short. The pathogenicity of the long Amosite may result from the ability of the fibres to cause chromosome damage, while the enhancement of this damage caused by decreasing intracellular glutathione suggests that the asbestos fibres may impose an oxidant stress on the cells which contributes to these aberrations.
Heinrich Ernst - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the exposure dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 1 exper
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and Amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and Amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; Amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; Amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & Amosite exposures (BD 470–715; chrysotile 495–614; crocidolite 415; Amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and Amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10–13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and Amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.
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evaluation of the dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 2 histopathologi
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and Amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1–3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and Amosite, compared to that from the brake dust and chrysotile. Both crocidolite and Amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
D M Bernstein - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the exposure dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 1 exper
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and Amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and Amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; Amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; Amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & Amosite exposures (BD 470–715; chrysotile 495–614; crocidolite 415; Amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and Amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10–13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and Amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.
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evaluation of the dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 2 histopathologi
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and Amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1–3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and Amosite, compared to that from the brake dust and chrysotile. Both crocidolite and Amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
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the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to Amosite asbestos following short term inhalation exposure interim results
Inhalation Toxicology, 2010Co-Authors: D M Bernstein, P Kunzendorf, Rick A Rogers, Ken Donaldson, Rosalinda Sepulveda, D Schuler, S Gaering, Jorg Chevalier, S E HolmAbstract:The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to Amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and Amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or Amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 µm) cleared rapidly (T1/2 of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response ...
P Kunzendorf - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the exposure dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 1 exper
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and Amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and Amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; Amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; Amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & Amosite exposures (BD 470–715; chrysotile 495–614; crocidolite 415; Amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and Amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10–13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and Amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.
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evaluation of the dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 2 histopathologi
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and Amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1–3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and Amosite, compared to that from the brake dust and chrysotile. Both crocidolite and Amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
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the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to Amosite asbestos following short term inhalation exposure interim results
Inhalation Toxicology, 2010Co-Authors: D M Bernstein, P Kunzendorf, Rick A Rogers, Ken Donaldson, Rosalinda Sepulveda, D Schuler, S Gaering, Jorg Chevalier, S E HolmAbstract:The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to Amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and Amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or Amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 µm) cleared rapidly (T1/2 of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response ...
Rick A Rogers - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the exposure dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 1 exper
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract This 90-day repeated-dose inhalation toxicology study of brake-dust (BD) (brakes manufactured with chrysotile) in rats provides a comprehensive understanding of the biokinetics and potential toxicology in the lung and pleura. Exposure was 6 h/d, 5d/wk., 13wks followed by lifetime observation (~20 % survival). Control groups included a particle control (TiO2), chrysotile, commercial crocidolite and Amosite asbestos. Aerosol fiber distributions of the chrysotile, crocidolite and Amosite were similar (fibers L > 20 μm/cm3: chrysotile-Low/High 29/72; crocidolite 24; Amosite 47 fibers/cm3; WHO-fibers/cm3: chrysotile-Low/High 119/233; crocidolite 181; Amosite 281 fibers/cm3). The number of particles/cm3 in the BD was similar to that in the chrysotile, crocidolite & Amosite exposures (BD 470–715; chrysotile 495–614; crocidolite 415; Amosite 417 particles/cm3). In the BD groups, few fibers L > 20 μm were observed in the lungs at the end of exposure and no fibers L > 20 μm at 90d post exposure. In the chrysotile groups, means of 204,000 and 290,000 fibers(L > 20 μm)/lung were measured at 89d. By 180d, means of 1 and 3.9 fibers were counted on the filter corresponding to 14,000 and 55,000 fibers(L > 20 μm)/lung. In the crocidolite and Amosite groups mean lung concentrations were 9,055,000 and 11,645,000 fibers(L > 20 μm)/lung at 89d. At 180d the means remained similar with 8,026,000 and 11,591,000 fibers(L > 20 μm)/lung representing 10–13% of the total lung fibers. BAL determined the total number of macrophages, lymphocytes, neutrophils, eosinophils, epithelial-cells and IL-1 beta, TNF-alpha and TGF-beta. At the moderate aerosol concentrations used in this study, neutrophil counts increased ~5 fold in the amphibole asbestos exposure groups. All other groups and parameters showed no important differences at these exposure concentrations. The exposure and lung burden results provide a sound basis for assessing the potential toxicity of the brake dust in comparison to the TiO2 particle control and the chrysotile, crocidolite and Amosite asbestos control groups. The BAL results provide an initial indication of the differential response. Part 2 presents the presentation and discussion of the histopathological and confocal microscopy findings in this study through 90 days post exposure.
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evaluation of the dose response and fate in the lung and pleura of chrysotile containing brake dust compared to tio2 chrysotile crocidolite or Amosite asbestos in a 90 day quantitative inhalation toxicology study interim results part 2 histopathologi
Toxicology and Applied Pharmacology, 2020Co-Authors: D M Bernstein, P Kunzendorf, D E Kling, J. I. Phillips, B. Toth, Rick A Rogers, Heinrich ErnstAbstract:Abstract The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and Amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1–3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and Amosite, compared to that from the brake dust and chrysotile. Both crocidolite and Amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
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the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to Amosite asbestos following short term inhalation exposure interim results
Inhalation Toxicology, 2010Co-Authors: D M Bernstein, P Kunzendorf, Rick A Rogers, Ken Donaldson, Rosalinda Sepulveda, D Schuler, S Gaering, Jorg Chevalier, S E HolmAbstract:The pathological response and translocation of a commercial chrysotile product similar to that which was used through the mid-1970s in a joint compound intended for sealing the interface between adjacent wall boards was evaluated in comparison to Amosite asbestos. This study was unique in that it presents a combined real-world exposure and was the first study to investigate whether there were differences between chrysotile and Amosite asbestos fibers in time course, size distribution, and pathological response in the pleural cavity. Rats were exposed by inhalation 6 h/day for 5 days to either sanded joint compound consisting of both chrysotile fibers and sanded joint compound particles (CSP) or Amosite asbestos. Subgroups were examined through 1-year postexposure. No pathological response was observed at any time point in the CSP-exposure group. The long chrysotile fibers (L > 20 µm) cleared rapidly (T1/2 of 4.5 days) and were not observed in the pleural cavity. In contrast, a rapid inflammatory response ...
