Variation of biological responses to different respirable quartz flours determined by a vector model

Background: The hypothesis of widely differing lung damage due to commonly used types of quartz was studied in 16 samples of respirable quartzes (> 99% silica) from sites of the European quartz industry, using an in vitro test, the vector model. Two samples with high and 2 with low biological activities were identified and subsequently examined for their in vivo lung toxicity (inflammation, fibrosis, genotoxicity) and surface characteristics. Alveolar macrophages (AM) are considered the target cells of primary dust effects. The vector model mimics some of the elemental dust cell effects such as cell toxicity, effects on the metabolism and stimulatory effects, e.g., TNF alpha and dust-induced ROS secretion. Methods: Doses of 15, 30, 60 and 120 mug dust per 10(6) AM were used together with the control dusts (quartz DQ12 and corundum). Testing parameters were LDH, glucuronidase, PMA forced ROS release, TNF alpha and dust induced ROS secretion. The main criterion for the selection of low or high activity samples was the secretion of TNF alpha. Results: (i) Apart from quartz samples with an activity close to that of DQ12, one also finds examples with a very low activity. (11) In comparison particular parameters are linked with a specific dose response relationship and different dose points for the leveling off of the effects. The levels of TNF alpha represent a conspicuously broad response pattern; some samples induce secretion at the lowest dose and others are not active even at the highest dose investigated at already apparent toxicity. (iii) Regarding various parameters the dust samples led to distinct dose response profiles considered as vectors. The current study indicates that within the particle type "quartz fine dust" varying harmful doses and different elements of damage must be present. (iv) The lung damage of the subchronic animal assay coincides with in vitro tests thus confirming the concept of the vector model. Conclusion: Threshold effects in the range of 15 - greater than or equal to 120 mug can be demonstrated for the discriminant vector TNF alpha, i.e. over 4 steps of dose doubling. These studies show very toxic quartzes but also quartzes of low biological activity comparable to corundum.