Journal of Toxicology and Environmental Health
ISSN: 0098-4108 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/uteh19
Induction of pulmonary carcinoma in rats by chronic inhalation of dust from pulverized asbestos pipe covering B. K. J. Leong , R. J. Kociba , H. C. Pernell , R. W. Lisowe & L. W. Rampy To cite this article: B. K. J. Leong , R. J. Kociba , H. C. Pernell , R. W. Lisowe & L. W. Rampy (1978) Induction of pulmonary carcinoma in rats by chronic inhalation of dust from pulverized asbestos pipe covering, Journal of Toxicology and Environmental Health, 4:4, 645-659, DOI: 10.1080/15287397809529687 To link to this article: http://dx.doi.org/10.1080/15287397809529687
Published online: 20 Oct 2009.
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Date: 07 November 2015, At: 22:11
INDUCTION OF PULMONARY CARCINOMA IN RATS BY CHRONIC INHALATION OF DUST FROM PULVERIZED ASBESTOS PIPE COVERING B. K. J. Leong, R. J. Kociba, H. C. Pernell, R. W. Lisowe, L. W. Rampy
Downloaded by [University of Florida] at 22:11 07 November 2015
Toxicology Research Laboratory, Health and Environmental Research, Dow Chemical U.S.A., Midland, Michigan
Rats and hamsters were exposed to the dust of pulverized asbestos pipe covering at an average concentration of 85 mg/m3 for 6 h/d, 5 d/wk, for 7 mo, followed by a lifetime observation period. In rats, the pulmonary responses were alveolar adenomatous proliferation, nonprogressive fibrosis, squamous metaplasia, and a substantial incidence of pulmonary carcinoma formation. A smaller group of hamsters exposed under these conditions experienced an earlier onset of mortality than control hamsters, which were not subjected to the exposure regimen. Although this prevented conclusive evaluation of the pulmonary response in this species, no pulmonary neoplasms were noted in the surviving hamsters.
INTRODUCTION Asbestos materials, primarily chrysotile, crocidolite, and amosite, are used extensively for thermal insulation (Hendry, 1965). Many industrial products worldwide depend increasingly on asbestos and the variety of its uses. At the same time, asbestos is also being perceived as a major health hazard. Asbestos dust exposure is now widely recognized as an important etiologic factor in pulmonary fibrosis (Cooke, 1927; Merewether, 1949; Murphy et al., 1971), respiratory cancers (Selikoff et al., 1965a, 1968, 1970; Hammond et al., 1965; Shettigara and Morgan, 1975), and malignant mesothelial tumors (Cooper, 1967; Selikoff et al., 1965b; Newhouse and Thompson, 1965; Smith et al., 1965; Wagner and Berry, 1969; Berry and Wagner, 1969; Stanton and Wrench, 1972). However, the precise mechanisms of the causal relationships have not yet been clarified, although many theories have been proposed. Several factors in the carcinogenic response to asbestos have been identified: (1) the action of the fiber itself because of its particular geometry (Stanton and Wrench, This paper was presented in part at the American Industrial Hygiene Conference, Atlanta, Georgia, May 1976. Requests for reprints should be sent to B. K. J. Leong, International Research and Development Corporation, 500 North Main Street, Mattawan, Michigan 49071.
645 Journal of Toxicology and Environmental Health, 4:645-659,1978 Copyright © 1978 by Hemisphere Publishing Corporation 0098-4108/78/0404-064512.25
646
B. K.J. LEONG ETAL.
Downloaded by [University of Florida] at 22:11 07 November 2015
1972; Gross and Harley, 1973), (2) trace metals associated with the fiber, some of which are known to be carcinogenic themselves (Cralley and Lainhart, 1973; Dixon et al., 1970), (3) polycyclic aromatic hydrocarbons associated with the fiber (Shabad et al., 1974), (4) other carcinogenic agents adsorbed onto the asbestos during milling, handling, mining, and so on and carried on the asbestos fiber into the body (Dixon et al., 1970), and (5) cigarette smoking in conjunction with asbestos exposure (Selikoff et al., 1970). Considering these factors, the asbestos fiber is basically viewed as a carcinogen or as a carrier of a carcinogen. Most asbestos inhalation experiments to date were conducted with relatively pure mineralogical types of dust. Findings in rats and hamsters exposed to dusts generated from prefabricated asbestos pipe covering (PAPC) are presented in this paper. The duration of exposure was 6 h/d, 5d/wk, for 7 mo, followed by observation for the life of the animals.
MATERIALS AND METHODS Material A section of an unused prefabricated asbestos air-cell pipe, which was produced by a major manufacturer in the fifties, was used. The PAPC dust was prepared by pulverizing the pipe covering into coarse powder with an industrial hammer mill. The duration of pulverization was brief (5 min) in order to minimize the possible contamination of the asbestos material by the metals of the hammer mill. The coarse powders were further reduced to extremely fine powders in a ceramic ball mill running for 48 h. The final dust sample consisted of 30-40% noncrystalline and approximately 60% crystalline materials as determined by X-ray diffraction analysis. On a whole dust basis, the crystalline components consisted of approximately 50% of a hydrated magnesium silicate having the crystalline structure of chrysotile, 5% Fe 3 O 4 , 5% Mg(OH) 2 , and 5% MgO. Atomic emission spectrographic analysis of a representative sample revealed the presence of various elemental components, as shown in Table 1. Dust Atmosphere Generation The PAPC dust atmosphere was generated by using an air elutriator, as shown in Fig. 1. The elutriator consisted of a 90 X 10 cm Pyrex tube, the bottom of which was sealed with a rubber diaphragm attached to an air vibrator. The powder was poured through the opening at the top of the tube onto the rubber diaphragm. It was then churned up by the vibrating diaphragm and was carried upward by a swirling air current emerging from two air nozzles located just above the diaphragm. The quantity of fine dust to be introduced into the exposure chamber could be regulated by adjusting the vibration frequency of the diaphragm and the volume of air ejecting through the dust cloud. For a 6-h exposure period 20 g of powder
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Downloaded by [University of Florida] at 22:11 07 November 2015
TABLE 1, Atomic Emission Spectrographic Analysis of Elements Present in the Ball-Milled Asbestos Pipe-Covering Sample Used in Inhalation Exposure of Rats and Hamsters
Element
Amount in sample (wt. %)
AI Ba B Ca Cd Co Cu Cr Fe Mg Mn Ni Pb Si Sn Sr Na K Ti V Zn
8.0 0.008
ISSN: 0098-4108 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/uteh19
Induction of pulmonary carcinoma in rats by chronic inhalation of dust from pulverized asbestos pipe covering B. K. J. Leong , R. J. Kociba , H. C. Pernell , R. W. Lisowe & L. W. Rampy To cite this article: B. K. J. Leong , R. J. Kociba , H. C. Pernell , R. W. Lisowe & L. W. Rampy (1978) Induction of pulmonary carcinoma in rats by chronic inhalation of dust from pulverized asbestos pipe covering, Journal of Toxicology and Environmental Health, 4:4, 645-659, DOI: 10.1080/15287397809529687 To link to this article: http://dx.doi.org/10.1080/15287397809529687
Published online: 20 Oct 2009.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=uteh20 Download by: [University of Florida]
Date: 07 November 2015, At: 22:11
INDUCTION OF PULMONARY CARCINOMA IN RATS BY CHRONIC INHALATION OF DUST FROM PULVERIZED ASBESTOS PIPE COVERING B. K. J. Leong, R. J. Kociba, H. C. Pernell, R. W. Lisowe, L. W. Rampy
Downloaded by [University of Florida] at 22:11 07 November 2015
Toxicology Research Laboratory, Health and Environmental Research, Dow Chemical U.S.A., Midland, Michigan
Rats and hamsters were exposed to the dust of pulverized asbestos pipe covering at an average concentration of 85 mg/m3 for 6 h/d, 5 d/wk, for 7 mo, followed by a lifetime observation period. In rats, the pulmonary responses were alveolar adenomatous proliferation, nonprogressive fibrosis, squamous metaplasia, and a substantial incidence of pulmonary carcinoma formation. A smaller group of hamsters exposed under these conditions experienced an earlier onset of mortality than control hamsters, which were not subjected to the exposure regimen. Although this prevented conclusive evaluation of the pulmonary response in this species, no pulmonary neoplasms were noted in the surviving hamsters.
INTRODUCTION Asbestos materials, primarily chrysotile, crocidolite, and amosite, are used extensively for thermal insulation (Hendry, 1965). Many industrial products worldwide depend increasingly on asbestos and the variety of its uses. At the same time, asbestos is also being perceived as a major health hazard. Asbestos dust exposure is now widely recognized as an important etiologic factor in pulmonary fibrosis (Cooke, 1927; Merewether, 1949; Murphy et al., 1971), respiratory cancers (Selikoff et al., 1965a, 1968, 1970; Hammond et al., 1965; Shettigara and Morgan, 1975), and malignant mesothelial tumors (Cooper, 1967; Selikoff et al., 1965b; Newhouse and Thompson, 1965; Smith et al., 1965; Wagner and Berry, 1969; Berry and Wagner, 1969; Stanton and Wrench, 1972). However, the precise mechanisms of the causal relationships have not yet been clarified, although many theories have been proposed. Several factors in the carcinogenic response to asbestos have been identified: (1) the action of the fiber itself because of its particular geometry (Stanton and Wrench, This paper was presented in part at the American Industrial Hygiene Conference, Atlanta, Georgia, May 1976. Requests for reprints should be sent to B. K. J. Leong, International Research and Development Corporation, 500 North Main Street, Mattawan, Michigan 49071.
645 Journal of Toxicology and Environmental Health, 4:645-659,1978 Copyright © 1978 by Hemisphere Publishing Corporation 0098-4108/78/0404-064512.25
646
B. K.J. LEONG ETAL.
Downloaded by [University of Florida] at 22:11 07 November 2015
1972; Gross and Harley, 1973), (2) trace metals associated with the fiber, some of which are known to be carcinogenic themselves (Cralley and Lainhart, 1973; Dixon et al., 1970), (3) polycyclic aromatic hydrocarbons associated with the fiber (Shabad et al., 1974), (4) other carcinogenic agents adsorbed onto the asbestos during milling, handling, mining, and so on and carried on the asbestos fiber into the body (Dixon et al., 1970), and (5) cigarette smoking in conjunction with asbestos exposure (Selikoff et al., 1970). Considering these factors, the asbestos fiber is basically viewed as a carcinogen or as a carrier of a carcinogen. Most asbestos inhalation experiments to date were conducted with relatively pure mineralogical types of dust. Findings in rats and hamsters exposed to dusts generated from prefabricated asbestos pipe covering (PAPC) are presented in this paper. The duration of exposure was 6 h/d, 5d/wk, for 7 mo, followed by observation for the life of the animals.
MATERIALS AND METHODS Material A section of an unused prefabricated asbestos air-cell pipe, which was produced by a major manufacturer in the fifties, was used. The PAPC dust was prepared by pulverizing the pipe covering into coarse powder with an industrial hammer mill. The duration of pulverization was brief (5 min) in order to minimize the possible contamination of the asbestos material by the metals of the hammer mill. The coarse powders were further reduced to extremely fine powders in a ceramic ball mill running for 48 h. The final dust sample consisted of 30-40% noncrystalline and approximately 60% crystalline materials as determined by X-ray diffraction analysis. On a whole dust basis, the crystalline components consisted of approximately 50% of a hydrated magnesium silicate having the crystalline structure of chrysotile, 5% Fe 3 O 4 , 5% Mg(OH) 2 , and 5% MgO. Atomic emission spectrographic analysis of a representative sample revealed the presence of various elemental components, as shown in Table 1. Dust Atmosphere Generation The PAPC dust atmosphere was generated by using an air elutriator, as shown in Fig. 1. The elutriator consisted of a 90 X 10 cm Pyrex tube, the bottom of which was sealed with a rubber diaphragm attached to an air vibrator. The powder was poured through the opening at the top of the tube onto the rubber diaphragm. It was then churned up by the vibrating diaphragm and was carried upward by a swirling air current emerging from two air nozzles located just above the diaphragm. The quantity of fine dust to be introduced into the exposure chamber could be regulated by adjusting the vibration frequency of the diaphragm and the volume of air ejecting through the dust cloud. For a 6-h exposure period 20 g of powder
ASBESTOS: CARCINOGENIC IN RATS
647
Downloaded by [University of Florida] at 22:11 07 November 2015
TABLE 1, Atomic Emission Spectrographic Analysis of Elements Present in the Ball-Milled Asbestos Pipe-Covering Sample Used in Inhalation Exposure of Rats and Hamsters
Element
Amount in sample (wt. %)
AI Ba B Ca Cd Co Cu Cr Fe Mg Mn Ni Pb Si Sn Sr Na K Ti V Zn
8.0 0.008
