How far does ozone penetrate into the pulmonary air/tissue boundary before it reacts?

A simple method is suggested for calculating the time it takes ozone to traverse a biological region, such as a bilayer or a cell, and comparing this time to the halflife of ozone within that region. For a bilayer the calculations suggest that most of the ozone reacts within a bilayer, but a fraction may exit unreacted. For the lung lining fluid layer (LLFL), the calculations show that ozone cannot cross this layer without reacting where the LLFL is thicker than about 0.1 microns. However, since the LLFL varies from 20 to 0.1 microns in thickness with patchy areas in the lower airways that are virtually uncovered, some ozone could reach underlying cells, particularly in the lower airways. For cells (such as alveolar type I epithelial cells), the calculations show that ozone reacts within the cell too rapidly to pass through and exit unreacted from the other side. These calculations have implications for ozone toxicity. In vivo, the toxicity of ozone is suggested to result from the effects of a cascade of products that are produced in the reactions of ozone with primary target molecules that lie close to the air/tissue boundary. These products, which have a lower reactivity and longer lifetime than ozone itself, can transmit the effects of ozone beyond the air/tissue interface. The variation in thickness of the LLFL may modulate the species causing damage to the cells below it. In the lower airways, where the LLFL is thin and patchy, more cellular damage may be caused by ozone itself; in the upper airways where the LLFL is thicker, secondary products (such as aldehydes and hydrogen peroxide) may cause most of the damage. In vitro studies must be designed in an attempt to model the lung physiology. For example, if cells in culture are studied, and if the cells are exposed to ozone while under a supporting medium solution that contains ozone-reactive substances, then the cells may be damaged by products that are formed in the reactions of ozone with the cell medium rather than by ozone itself.