Donald E. Gardner’s research while affiliated with Louisiana State University and other places

Health effects associated with the inhalation of airborne metals have been the subject of intense interest since the early days of pharmacology and toxicology. Many metals are ubiquitous in the environment, having multiple sources and routes of exposure. Metals represent the ultimate form of persistent environmental pollutants because they are chemically and biologically indestructible. The respiratory system is one of the primary target sites for metal toxicity. Inhalation exposure becomes critical when one considers that the mammalian respiratory system must not only maintain life by the exchange of gases but also perform a number of essential nonrespiratory functions such as the maintenance of an active immune system, metabolism of biologically active substances, and the clearance of viable and nonviable particles from the lung. The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the major components that comprise the respiratory toxicology of airborne metals.

Methodologies and technology for animal inhalation toxicology studies nasal structure, function, and toxicology gross morphometry of airways cell populations and structure-function relationships of cells in the airways morphometric analysis of the gas exchange region of the lung three- dimensional analysis of lung structure and its application to pulmonary Dosimetry Models Metabolism Of Xenobiotics The Respiratory Tract extrapolation of animal data to humans - homology of pulmonary physiological responses with ozone exposure biological markers of respiratory tract exposure quantitative clinical studies with defined exposure atmospheres the epidemiologic approach to investigating indoor and outdoor air pollution cellular approaches in respiratory tract toxicology pulmonary reactions and mechanisms of toxicity of inhaled fibres immunological responses within the lung after inhalation of airborne chemicals chemically-induced pulmonary hypersensitivity, airway hyperactivity and asthma chronic inhalation bioassays for respiratory tract carcinogenesis advances in physiological modelling approaches for understanding the disposition of inhaled vapours regional respiratory tract absorption of inhaled reactive gases approaches to modelling disposition of inhaled particles and fibres in the lung developing risk assessments for airborne materials.

A study was undertaken on the effect of inhalation exposure of an aćute dose of cadmium on mitochondrial enzymes in rat lungs. Citrate synthase, succinic dehydrogenase and cytochrome c oxidase were inhibited immediately after exposure and regained to near normal levels at the end of 336 hours. The cadmium level in the target tissue was not cleared effectively and the lung tissue showed histopathological changes such as focal thickening of alveolar septa with cuboidal cells lining alveoli.

The nitrogen dioxide (NO2) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO2 peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO2 exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO2 concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O3) and NO2, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO2 and O3, synergistic results were obtained for streptococcal-induced mortality.

The study reported herein evaluates the influence of a chronic exposure to an urban pattern of NO2 (continuous baseline exposure of 0.2 ppm, on which were superimposed two 1-h spikes of 0.8 ppm NO2, 5 d/wk) as compared to the baseline exposure to determine the contribution of the spikes to toxicity. Mice were exposed for up to 52 wk with interim examinations. Multivariate analysis of variance revealed a statistically significant treatment effect on infectivity (p = 0.05) and pulmonary function (p = 0.03) parameters. Infectivity mortality of mice in the spiked exposure regimen was significantly greater than that in either the NO2-background-exposed mice or in control mice. Four of the pulmonary function variables exhibited the greatest differences among the treatment groups: end expiratory volume, vital capacity, respiratory-system compliance, and multiple-breath nitrogen washout. Results from the pulmonary-function analyses indicate that the spiked exposures to 0.8 ppm NO2 may have induced a subtle lesion. The chronic study results indicate that the presence of spikes of NO2 is contributing significantly to effects on antibacterial lung defenses and pulmonary function of mice.

The ambient air consists of a multitude of air pollutants that differ geographically and temporarily by concentration and chemical identity. They can be classed as either gases or particles. Only a limited number of these pollutants has been studied for immunotoxic effects. Those chemicals that have been studied are relatively common, such as ozone (O3), nitrogen dioxide (NO2), sulfur dioxide, sulfates (including sulfuric acid), and fly ashes. Other chemicals which are common, but less widely distributed, such as metals, have also been investigated.

Pulmonary and extrapulmonary effects from a 2-h inhalation exposure to cadmium (850 micrograms Cd/m3) were studied in male rats. The effect of this chemical on mitochondrial enzyme activity in the lung, liver, kidney, and testis were investigated immediately after exposure and at 48, 144, and 336 h postexposure. In all tissues studied, mitochondrial citrate synthase activity was significantly increased immediately after the cessation of the exposure. This activity level began to decrease at 48 h postexposure. Succinic dehydrogenase activity was significantly decreased in the lungs and kidney at all periods tested, but increased activity was seen in the liver and testis. Cytochrome c oxidase activity in lungs and testis mitochondria was inhibited at all time periods studied. In the liver and kidney this activity was significantly increased immediately after the exposure ceased, and then a significant reduction began to appear at 48 h postexposure. This study demonstrates that inhaled cadmium, after deposition in the lungs, may alter various enzyme activities in other organs.