Saturday, May 14, 2005

Is there something special about silica?

BrooklynDodger grew up when we wondered why asbestos caused fibrosis and cancer, but silica only fibrosis, and other dusts were non-toxic. We knew why tobacco smoke was carcinogenic [PAH's absorbed on carbon particles] even those tobacco smoke was not carcinogenic in rats by inhalation.

Now, silica is a Class 1 human carcinogen, based on epidemiology and bioassay data. Tobacco smoke has been shown carcinogenic in the rat [but not the mouse], but about 50 fold less potent than silica. Many other dusts, including the "non-carcinogenic" control titanium dioxide, are carcinogenic in the rat. [The strongest epidemiological study of titanium dioxide exposed workers is inadequate to measure carcinogenicity of titanium dioxide, and is not as null as the authors content.] Carbon black and diesel particulate matter are similarly potent in the rat, and similarly more potent than tobacco smoke.

Back in the day, the theory of silica fibrosis was that the silica particles killed pulmonary macrophages, leading to fibrosis. BrooklynDodger will look for a bibliography on in vitro and in vivo comparative toxicity to macrophage studies. Comparing behavior of various dusts in various systems is valuable to probe whether all particles should be treated similarly.

The paper below involves techniques the Dodger thinks appeared after the Dodger left the lab. Paraphrasing the abstract, ... the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology...evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. ...Mice were exposed intranasally...Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers...... bone marrow-derived macrophages (BMDM)... in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO2). ... These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis.

The problem with this paper is the titanium dioxide particle control. The investigators tell us the silica particles are 1.5-2 microns, and the "Treatments included saline alone, 1 mg crystalline silica in saline, or 0.5 mg TiO2 (as a control particle) in saline." There were some effects, not statistically significant from titanium dioxide [given at half the dose], and particle size is a big deal for titanium dioxide and the that's not given. So the study is inadequate to draw strong, if any conclusions about the contrast between silica and titanium dioxide. So, we still don't know if there is something special about silica.

Why the referees and editors let this get by, the Dodger is mystified. TAP is a top of the line journal.


Toxicology and Applied Pharmacology Volume 205, Issue 2 , 1 June 2005, Pages 168-176

Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

Christopher T. Migliaccio, , Raymond F. Hamilton, Jr. and Andrij Holian Center for Environmental Health Sciences, Biomedical and Pharmaceutical Sciences, University of Montana, 155 Skaggs Building, Missoula, MT 59812, USA Received 17 August 2004; accepted 2 November 2004. Available online 21 January 2005.

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