Animal studies that focused on the biological effects of chronic inhalation exposure to Mount St. Helens volcanic ash or quartz, under controlled laboratory conditions, indicate significant dose-response to both materials. The quartz that came from the volcano was found to be markedly toxic and fibrogenic; by contrast, the volcanic ash was much less toxic. Similar results were noted in other animal studies, suggesting that quartz is a much more potent pulmonary toxicant than volcanic ash. However, the presence of volcanic ash in the inhaled air did increase the "histamine sensitivity" of the epithelial irritant receptors as well as inhibit the ability of alveolar macrophages to protect against infection. The toxicity of volcanic ashes has been evaluated in rats that were dosed once by intratracheal instillation. Ashes that were obtained from the San Francisco volcano field in Arizona (lunar dust simulant) and from a Hawaiian volcano (martian dust simulant) were compared to the toxicity of titanium dioxide and quartz. Lungs of mice that have been harvested 90 days after receiving a dose of 1 mg of lunar simulant showed chronic inflammation, septal thickening, and some fibrosis. No changes were seen at the low dose of 0.1 mg/mouse. The martian dust simulant elicited a response that was similar to that of the lunar simulant, except that there was an inflammatory and fibrotic response even at a dose of 0.1 mg/mouse. The response of the mouse lungs to 0.1-mg quartz was comparable to the response to the martian dust simulant. In another study, the effect of these same simulants was assessed on human alveolar macrophages. The lunar dust simulant was comparable in cell viability reduction and apoptosis induction to the TiO2 (titanium dioxide) negative control. Both were less toxic than the quartz positive control. Both simulants showed a dose-dependent increase in cytotoxicity. Inhalation of freshly ground quartz, when compared to inhalation of aged quartz, results in a significant increase in animal lung injury. Freshly ground quartz has increased reactive silicon-based oxygen radicals, and animals that are exposed to freshly ground quartz have been found to have decreased concentrations of antioxidant enzymes. Activated quartz particles decay with age in ambient air. Quartz dusts containing surface iron as an impurity have been shown to deplete cellular glutathione, contributing to the oxidative damage that is caused by particle and cell-derived ROS.