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Case Study: Occupational Health Risks from Crystalline Silica

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Quantitative Risk Analysis of Air Pollution Health Effects

Part of the book series: International Series in Operations Research & Management Science ((ISOR,volume 299))

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Abstract

Chapter 3 pointed out that chronic inflammation mediates an extraordinarily wide range of diseases. Recent progress in understanding intracellular inflammasome assembly, priming, activation, cytokine signaling, and interactions with mitochondrial reactive oxygen species (ROS), lysosome disruption, cell death, and prion-like polymerization and spread of inflammasomes among cells, has potentially profound implications for dose-response modeling. This chapter and Chaps. 5 and 6 further discuss biological mechanisms of exposure concentration and duration thresholds for NLRP3 inflammasome-mediated inflammatory responses, and develop and apply simple biomathematical models of the onset of exposure-related tissue-level chronic inflammation and resulting disease risks. This chapter focuses on respirable crystalline silica (RCS) and lung cancer risk as an example. It proposes an inflammation-mediated two-stage clonal expansion (I-TSCE) model of RCS-induced lung cancer that explains why relatively low estimated concentrations of RCS (e.g., <1 mg/m3) do not increase lung cancer risk and why even high occupational concentrations increase risk only modestly (typically RR < 2). The model of chronic inflammation implies a dose-response threshold for excess cancer risk, in contrast to traditional linear no-threshold (LNT) assumptions. If this implication is correct, then concentrations of crystalline silica (or amphibole asbestos fibers, or other environmental challenges that act via the NLRP3 inflammasome) below the threshold do not cause chronic inflammation and resulting elevated risks of inflammation-mediated diseases.

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    Louis Anthony Cox Jr.

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Cox Jr., L.A. (2021). Case Study: Occupational Health Risks from Crystalline Silica. In: Quantitative Risk Analysis of Air Pollution Health Effects. International Series in Operations Research & Management Science, vol 299. Springer, Cham. https://doi.org/10.1007/978-3-030-57358-4_4

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