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“Since the time of Hippocrates the growth of scientific medicine has in reality been based on the study of the manner in which what he called ‘Nature’ of the living body expresses itself in response to changes in the environment, and reasserts itself in face of disturbances and injury”

—John Scott Haldane (Haldane, 1922)


Toxic substances can disrupt the respiratory system and distant organs after chemicals enter the body by means of inhalation. Blood-borne agents also can cause pathological changes in the respiratory tract. Inhalation toxicology refers to the route of exposure, whereas respiratory toxicology refers to target organ toxicity. This chapter reviews the toxic responses of the respiratory system.

Historically, respiratory toxicology is a keystone of medicine, dating back to Hippocrates. In his medical thesis On Airs, Waters, and Places, Hippocrates recommended that physicians evaluate local atmospheres to discover the causes of diseases (Adams, 1849). In 1661, John Evelyn appealed to the English King and Parliament for relief from the poor air quality of London that was a result of the burning of “sea-coale” (a brown coal likely enriched in sulfur that washed up on the banks of the River Thames (Evelyn, 1661). This situation continued and became worse in the 19th century when the Industrial Revolution quickened awareness of respiratory toxicology due to air pollutions (see Chap. 31).

Later, Bernardino Ramazzini proposed that clinicians evaluate the relationships between occupational atmospheres and disease pathogenesis, starting a long history of respiratory toxicology in occupational medicine. He observed that “corruption of the atmosphere” can be at the origin of many respiratory diseases. In his work De Morbis Artificum Diatriba (Diseases of Workers) (1713), he writes: “Miners who maintain an almost daily contact with evil powders in the earth's depths … have lungs which absorb mineral exhalations and must be the first to suffer the attack of poisonous fumes …. The mortality rate of miners is very high and, as a proof of this, we remember that their wives re-marry many times.” Supporting the concept of exposure, he continues: “It is not only miners working in mines who run the risk of dying from diseases due to metals: so do many others working around mines.” He also supported the concept of prevention over treatment stating “Prevention is better than cure, just as it is better, on seeing storm arrive, to get under cover than to suffer its damages” (Bisetti, 1988).

During the 19th century the relationship between dusty trades and bronchitis (Thackrah, 1832), and silica dust and pneumoconiosis (Holland, 1843) became well recognized. In 1873, excessive bronchitis deaths were attributed to London fogs (smog) (British Medical Journal, 1880). In a report on London fogs (smog) in 1880 that lead to 1817 excessive deaths, Russell (Russel, 1880) states “And smoke in London ...

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