Malignant Mesothelioma - Pleural Tumors
Respirable fiber size: Although the draft report notes that a respirable fiber has a diameter of 3-4 µm this is for fibers with a density of 1. Talc has a specific gravity of 3 and, consequently the equivalent aerodynamic diameter of respirable talc fibers would be 1/3 of this, on the order of 1 µm (Wylie, et al. 1993). This finding is particularly important in that the fibers in asbestiform talc are primarily wider than 1 µm with only 10-11% of fibers in commercial talcs being <1 µm in diameter.
Fiber size and cancer risk: There are excellent animal models for the relationship between fiber dimension and risk of both mesothelioma and lung cancer. For mesothelioma risk, fibers with a dimension of £0.25 µm in diameter and >8 µm long appear to present the greatest risk (Stanton, et al., 1981; Oehlert, 1991) with almost no risk presented by short fibers (Davis, et al. 1986). Most amphibole fibers in a asbestiform talc mine are shorter than 10 µm (Kelse and Thompson, 1989) and would not be expected to present a risk of mesotheliomas. Similarly, lung cancer risk also depends on fiber dimensions. Based on asbestos inhalation studies, Berman et al (1995) found that potency for lung cancer rested with fibers that were longer than 10 µm and less than 0.3 µm in diameter. Their model found that fibers that were <10 µm long and had widths from 0.3-5.0 µm were not associated with a lung cancer risk. Lippmann (1988) performed as similar analysis. He found that fiber retention drops rapidly as fiber diameter increases from 0.8 to 2.0 µm. No lung cancer risk was associated with fiber length less than 5 µm. Lung cancer risk was associated with fibers with a diameter of 0.3-0.8 µm and a substantial fraction >10 µm in length.
Animal Studies: Although IARC considered a number of studies involving the carcinogenicity of talc in experimental animals, they did not have access to identification information concerning several of the fibrous talcs. This is particularly important because talcs form the Grouvenor Talc Company (GTC), the mine most studied for cancer risk, have been examined in a number of animal models and have been found to be non-carcinogenic. Stanton, et al. (1981) examined two asbestiform talcs from the Grouvenor talc district including one from GTC (Stanton talc #6) in their pleural implantation rat model. Neither of these talcs induced mesotheliomas although based on particle dimensions, a 60% incidence of mesotheliomas would have been expected with the GTC talc. Oehlert (1991) re-analyzed the Stanton data, breaking out potency assessments not only by particle size but by mineral type. When compared to asbestos, the author found that talcs were 1/135,000 as potent for causing pleural tumors. This re-analysis included both the asbestiform talcs and 5 non-asbestiform talcs studied by Stanton, et al. Smith, et al. (1979) also studied one GTC talc (FD14) in their hamster pleural malignant mesothelioma model. This talc, as well as another talc containing amphibole fibers, was negative in their model.
Wylie, et al. (1997) studied the FD14 talc from the Smith et al. study in an in vitro system. It was not cytotoxic and did not induce cell proliferation. Talc samples not containing quartz were not cytotoxic where asbestos was both cytotoxic and induced proliferation.--