Details

Autor(en) / Beteiligte

• Bégin, R
• Massé, S
• Rola-Pleszczynski, M
• Boctor, M
• Drapeau, G
• Geoffroy, M
• Côté, Y
• Fabi, D
• Couin, S
• Desmarais, Y
• Martel, M

Titel

Asbestos Exposure Dose - Bronchoalveolar Milieu Response in Asbestos Workers and the Sheep Model: Evidences of a Threshold for Chrysotile-Induced Fibrosis

Ist Teil von

• Drug and chemical toxicology (New York, N.Y. 1978), 1987, Vol.10 (1-2), p.87-107

Ort / Verlag

United States: Informa UK Ltd

Erscheinungsjahr

1987

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• ABSTRACT Epidemiological studies of asbestos workers have proposed a linear dose-response relationship between asbestos cumulative exposure indices and the incidence of asbestos-related lung diseases. However, for chrysotile, several studies have not observed such a linear relationship in low exposure workers. To further study the relationship of chrysotile exposure dose - lung tissue response, we designed in the sheep model one experiment of one exposure at variable intensity and one experiment with variable rates of individual exposures. In the first study, 6 groups of 6 sheep were exposed to either 0, 1, 10, 25, 50 or 100 mg chrysotile in 100 ml saline and lung lavage analyses carried out at day 0, 12, 24, 40 and 60 after. Histopathology was done at day 60. In the second experiment, 4 groups of 12 sheep were exposed to 100 ml saline every week or every two weeks, 100 mg chrysotile in 100 ml saline every week or every two weeks. In the second experiment, lung damage was assessed by changes in vital capacity (VC), lung compliance (Cst) and profusion of chest radiographic opacities (PO). On BAL in the control sheep, there were small and transient early increases in total cells/ml, macrophages/ml, neutrophils/ml, lactate dehydrogenase (LDH)/ml, alkaline phosphatase (AK)/ml, β-glucuronidase (βG)/ml and procollagen III/ml. In the 1, 10, 25, and 50 mg asbestos sheep groups, there were no significant differences. However, in the 100 mg asbestos sheep, there were significant sustained increases in total cells/ml (3-6 times controls), macrophages/ml (2-6 times controls), neutrophils/ml (60 - 600 times controls), LDH/ml (5 - 10 times controls), AK/ml (1.5 - 2 times controls), BC/ml (3-5 times controls), procollagen III/ml (2 times controls) and IgC (1.5 - 3 times controls). These data were correlated with histopathological findings. In the sheep exposed weekly to chrysotile, significant changes in VC, Cst and PO occurred at mean cumulative exposure dose of 1.2 9 whereas in the sheep exposed every 2 weeks, similar changes in VC, CSt and PO occurred at the cumulative exposure dose of 3.6 g (P < 0.05). In conclusion, our data suggest that there is a threshold for chrysotile-induced fibrosis. This level cannot be considered adequately in term of cumulative exposure dose but must take into account intensity and rate of individual exposures.