Fibrogenic Irritants

The toxicity of exogenous agents leading to fibrosis in the respiratory system is described in this chapter. These agents interact with parenchymal cells through inhalation or systemic circulation. This chapter addresses a variety of agents that are known to cause long-lasting damage to respiratory tissues, resulting in parenchymal remodeling/fibrosis. Among the chosen agents are particulates (silica, asbestos, nanoparticles, particulate matter (PM)), heavy metals (cadmium, arsenic, cobalt, tungsten, uranium), ionizing radiation, pharmacological agents (bleomycin, amiodarone, nitrogen mustard), and herbicide agent (paraquat [1,19-dimethyl-4,49-bipyridilium]). Exposure results in a wide range of mechanisms of toxicity, including the formation of reactive electrophilic intermediates, sustained inflammation, and adduct (DNA, protein) formation. These compounds are toxic to nonciliated bronchiolar epithelial cells, alveolar epithelial cells (AECs) involved in gas exchange, resident alveolar macrophages (AM), as well as nasal epithelial or pulmonary endothelial cells. The purpose of this chapter is to provide chemical and biochemical insights into the generalized mechanisms of toxicity of fibrogenic circulating pneumotoxicants, through the enumeration and compilation of examples of well-documented, chemically induced lung damage.