Review, Discussion, and Summary: Toxicology

Abstract

The research presented in the toxicology session of the Symposium on the Health Effects of Acid Aerosols significantly advances our understanding of the health effects of acid aerosols and clearly illustrates the importance of animal inhalation toxicology to risk assessment. The description of the effects of acid on airway mucus buffering capacity and viscosity helps explain some of the mechanisms responsible for the effects of sulfuric acid on mucociliary clearance and pulmonary function observed in man and animals. Several of the papers illustrate that other pollutants interact with sulfuric acid (H2SO4), causing concern about exposure risks and helping in elucidating the effects observed in epidemiology studies that have not yet been duplicated in a laboratory. For example , H2SO4 absorbed on zinc oxide (ZnO) particles appears to be about a log more potent than H2SO4 alone in causing pulmonary function decrements. Low levels of H2SO4 and 03 were found to be synergistic in increasing collagen synthesis, implying a risk in development of lung fibrosis. More complex mixtures containing H2SO4 cause a variety of interactions, depending upon the end points examined and the chemistry of the mixture. Other reports indicate that dose rate and length of exposure issues are critical to toxicological outcomes. Animal data on mucociliary clearance, which parallels that of human data, was extended to show that concentration of exposure was more important than time of exposure in eliciting a response, although time played a significant role. A recent chronic study showed that H2SO4 caused effects that also can occur in the development of chronic bronchitis. Although the causal relationship between H2SO4 and chronic bronchitis remains to be proven, this chronic animal study, interpreted in context with shorter term human and animal studies of H2SO4 and with findings in the effects of cigarette smoke, raises concern. It is noteworthy that even after the H2SO4 chronic exposure ceased, there were some progressive changes, implying irreversible effects.

The Role of Airway Mucus in Pulmonary Toxicology

“…These include changes in pulmonary function, diminished lung defense and impaired mucociliary clearance, as well as obstructive, inflammatory, and neoplas-tic disease. These topics have been the subjects of several excellent recent reviews (128)(129)(130)(131)(132). This section will focus on specific effects of air pollutants on airway mucus function, secretion, and biosynthesis, as they pertain to the development of pulmonary toxicology and disease.…”

Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures.

“…This severe constraint raises a host of methodologic problems, but the potential value of morphometric measurements argues in favor of further exploring this promising technique. For example, morphometry has been used to study postnatal lung growth (1), an outcome relevant to ETS-NO2 exposur; and numerous morphometric studies have found pulmonary changes in animals exposed to single pollutants and pollutant mixtures (10). Limited studies of air pollution using morphometry with human autopsy specimens point to the feasibility of moving from animal to human tissues.…”