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Toxicity of fibers and particles report of the workshop held in Munich, Germany, October 26-27, 2000.

Greim-H; Borm-P; Schins-R; Donaldson-K; Driscoll-K; Hartwig-A; Kuempel-E; Oberdorster-G; Speit-G
Inhal Toxicol 2001 Sep; 13(9):737-754
Fibers and particles can have primary genotoxic effects and also induce inflammation, fibrosis, and cancer in experimental animals and humans. The intensities of these adverse effects are dose dependent where inflammation is known to induce cell proliferation and secondary genotoxicity. Secondary genotoxicity may arise as a result of inflammation and cell proliferation and will not occur at exposure concentrations that do not induce inflammation and do not overcome the antioxidant and DNA-repair capacity in the lung (Greim et al., 2000). Thus, fibers and particles may act through a threshold mechanism. The exposure and the dose that results in a lung burden without adverse effects (no-observed- effects level, NOEL) during long-term exposure have to be defined. Optimally this no-effect exposure should represent a steady-state lung burden at which the rates of deposition and clearance are equal so that no further increase in lung burden will occur. For primary genotoxicity caused by fibers and particles, the assumption is made that humans are at risk at any exposure, as any amount of a direct-acting carcinogen in theory can cause a mutation. For this reason, the exposure response relationship for direct-acting carcinogens is generally described as low-dose linear. In any case, exposure reduction will reduce the risk of adverse effects. Thus, for risk assessment of fibers and particles the mechanism of genotoxicity (primary, induced by the inherent genotoxicity of the material, secondary, e.g., as a consequence of inflammation), the dose response of the critical effects and their NOELs have to be understood. Unfortunately, such information usually is minimal for the many fibers and particles. To discuss the information necessary for a science-based risk assessment of fibers and particles, the MAK Commission, on behalf of the Deutsche Forschungsgemeinschaft, convened an international workshop, held in Munich on 26 - 27 October 2000. During the workshop the state of the art of fiber and particle toxicity was presented, research needs were identified, and the necessary information for risk assessment was discussed. The full length contributions to the workshop will be published in this journal at a later date. This communication presents summaries of the workshop discussions on specific issues, including any consensus views. It presents current scientific opinion, as conveyed by the workshop participants. This report is intended to provide guidance to the MAK Commission and other occupational health and safety organizations that interpret scientific data for the development of public health policy (e.g., exposure limits). Other interpretations may be possible, and conclusions could be modified in the future as new data are acquired.
Toxins; Toxic-effects; Particulates; Genotoxic-effects; Cancer; Cancer-rates; Fibrogenesis; Fibrogenicity
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Inhalation Toxicology