Coal Miners and Lung Cancer: Can Mortality Studies Offer a Perspective on Rat Inhalation Studies of Poorly Soluble Low Toxicity Particles?

Inhalation studies involving laboratory rats exposed to poorly soluble particles (PSLTs), such as carbon black and titanium dioxide, among others, have led to the development of lung cancer in conditions characterized as lung overload. Lung overload has been described as a physiological state in which pulmonary clearance is impaired, particles are not effectively removed from the lungs and chronic inflammation develops, ultimately leading to tumor growth. Since lung tumors have not occurred under similar states of lung overload in other laboratory animal species, such as mice, hamsters and guinea pigs, the relevance of the rat as a model for human risk assessment has presented regulatory challenges. It has been suggested that coal workers' pneumoconiosis may reflect a human example of apparent "lung overload" of poorly soluble particles. In turn, studies of risk of lung cancer in coal miners may offer a valuable perspective for understanding the significance of rat inhalation studies of PSLTs on humans. This report addresses whether coal can be considered a PSLT based on its composition in contrast to carbon black and titanium dioxide. We also review cohort mortality studies and case-control studies of coal workers. We conclude that coal differs substantially from carbon black and titanium dioxide in its structure and composition. Carbon black, a manufactured product, is virtually pure carbon (upwards of 98%); TiO