Exercising animal models in inhalation toxicology: interactions with ozone and formaldehyde

Exercise during exposure to inhaled toxicants increases inhaled dose rate and alters dose distribution within the respiratory tract, and exercise has long been recognized as a critical exposure variable. While modern inhalation exposure studies with human subjects routinely use an exercise protocol, most investigations with animal models are performed with resting subjects. Animal inhalation exposures under exercising conditions frequently induce respiratory toxic effects well beyond that expected from the simple increase in ventilation dose rate. Different classes of irritants can induce different reflex breathing patterns, and small mammals have different capacities for hypothermic or hyperthermic responses to rest or exercise exposure. Respiratory tract injury and breathing pattern responses of rats to upper and lower airway irritants ozone and formaldehyde were measured under conditions of rest and exercise to illustrate the complexities of comparison to human exposures. In addition to the exercise effects on dose and dose distribution and the possibility of hypo- or hyperthermic responses, exercise enhancement of inhalation injury may also be related to a combination of toxicant-induced disruption of the pulmonary epithelial permeability barrier and exercise-induced pulmonary capillary stress failure.