Toxic Effects Of Asbestos Exposure And Disease Causation

Mesothelioma is a rare form of cancer that is caused by asbestos exposure. One of the main risk factors for developing this disease is occupational exposure. A lot of excellent research has been on asbestos and its wide reaching impact. One interesting study is called, In vitro cytotoxicity of asbestos and man-made vitreous fibers: roles of fiber length, diameter and composition by G.A. Hart, L.M. Kathman and T.W. Hesterberg - Carcinogenesis Volume 15, Number 5 Pp. 971-977. Here is an excerpt: The present study investigated (i) the impact of various fiber parameters on in vitro toxicity to cells and (ii) the validity of an in vitro test system as a toxic screen for fibrous materials. Chinese hamster ovary cells were exposed in vitro to a series of size-selected inorganic test fibers that represented a range of different diameters, lengths and compositions (glass, refractory ceramic, mineral wool, asbestos). Toxic end-points included inhibition of proliferation, induction of micronuclei and polynudei and viability. For all compositions tested, toxic effects were similar: a concentration-dependent decrease in proliferation and increase in incidence of morphologically abnormal nuclei with minor decreases in viability. Diameter-dependent differences in toxicity were slight or absent for fiber diameters ranging from 0.37 m when concentration was expressed as number of fibers/cm Length-dependent differences in toxicity were, however, striking. EC50 values (concentration in fibers/cm that reduced cell proliferation to 50% of unexposed control cultures) plotted against fiber length produced a hyperbolic curve, demonstrating that toxicity increases with fiber length up to 20 m. All fibers tested fell on this hyperbola. These data suggest that: (a) the primary toxic effect of fibers on CHO cells is the induction of nudear morphologic alterations resulting in cytostasis; (b) fiber diameter has little or no impact on in vitro toxicity when concentration is calculated as fibers/cm (c) fiber length is directly proportional to in vitro toxicity; and (d) toxicity of asbestos and vitreous fibers to CR0 cells is not affected by composition. The lack of compositional effect in CHO cells does not correlate with findings from recent rodent inhalation studies using the same test fibers. Thus CHO cells may not be an appropriate in vitro model of fiber pathogenesis and would not constitute a valid toxicologic screening system for fibers.

Another interesting study is called, Asbestos exposure as a risk factor for retroperitoneal fibrosis by T.Uibu, P.Oksa, A.Auvinen, E.Honkanen, K.Metsrinne, H.Saha, J.Uitti, P.Roto - The Lancet, Volume 363, Issue 9419, Pages 1422-1426. Here is an excerpt: Abstract Background - Retroperitoneal fibrosis (RPF) is an uncommon disease with unknown causation in most cases. The pathognomonic finding is a fibrous mass covering the abdominal aorta and the ureters. Our aim was to clarify the possible role of asbestos exposure in the development of RPF. The hypothesis was based on the ability of asbestos to cause fibrosis in pulmonary and pleural tissue. Methods - We undertook a case-control study of 43 patients with the disease (86% of eligible cases) treated in three university hospital districts of Finland in 19902001. For every patient, five population-based controls were selected, matched by age, sex, and central hospital district. We assessed asbestos exposure and medical history using a postal questionnaire and a personal interview. Of the 215 eligible controls, 179 (83%) participated in the study.

Findings - The age-standardised incidence of RPF was 010 (95% CI 007014) per 100000 person-years. The disease was strongly associated with asbestos exposure. The odds ratio (OR) was 554 (1641865) for less than 10 fibre-years of asbestos exposure and 884 (2033850) for 10 or more fibre-years, the attributable fraction being 82% and 89%, respectively. Other risk factors were previous use of ergot derivates (OR 992 [1636026]), abdominal aortic aneurysm (OR 673 [0815608]), and smoking for more than 20 pack-years (OR 473 [1281741]). Interpretation - Our results show that occupational asbestos exposure is an important causal factor for RPF. For patients with work-related asbestos exposure, RPF should be considered an occupational disease.

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