Plenary Lectures (6 March 1981) AI)

1200-1220 Hal l 2 THE INFLUENCE OF THE ALUMINUM ON THE TOXICOLOGY OF RATS EXPOSED BY INHALATION

TO ALUMINUM CHLORIDE AND FLUORIDE

VINCENT N. FINELLI, Ph.D., SHANE S. QUE flEE, Ph.D. University of Cincinnati Medical Center, Cincinnati, Ohio 45367, U.S,A.

and R. NIEMEIER Biomedical and Behavioral Science Division, U.S. National Institute for Occupational Safety and Health, Cincinnati, Ohio 45227, U.S.A.

Workers in the aluminum reduction industry are heavily exposed to aluminum fluoride and also, in some cases, to aluminum chloride. This study was initiated to study whether the cation exerts any sigr ificant toxicological effect on selected physiological and biochemical parameters which might provide early warning of toxic effects. Male Sprague-Dawley rats were exposed by inhalation to aerosols of aluminum fluoride and chloride and potassium fluoride (~2 mg/m 3) in addition to a parailel control exposure involving only purified air, over a period of five months. The following parameters were monitored at each monthly sacrifice: lysozyme, glucose-6-phosphate dehydrogenase and alkaline phosphatase activities of lung lavage ; the leakage of previously injected 125I-serum albumin into the lung lavage and the amount of label retained in the blood circulatory system; total lavage protein; pulmonary alveolar macrophage number and viability; body and organ (kidney, lung, brain, and liver) weights; aluminum and 4-hydroxyproline levels in these organs, and general histopathology. Preliminary results indicate that significant increases proportional to exposure time were induced by alumin.u~_ chloride for lysozyme and alkaline phosphatase activities, total protein, Iz~I-leakags, and weights of kidney and liver. Aluminum chloride also increased liver weights and alkaline phosphatase activity. The significance of the above parameters will be discussed vis-a-vis cation versus anion toxicological

effects on the lung and other organs.

PLENARY LECTURES (6 March 1981)

0900-09~5 ALKYLATION AND PEROXIDATION IN CHEMICAL-INDUCED TISSUE INJURIES Hal l 1

3ERRY R. MITCHELL, M.D., Ph.D.

Departmont of Internal Medicine, Baylor College of Medicine, Houston, Texas, U.S.A.

Over the past two decades a common mechanism has been found to be

responsible for the initiation of many types of structural tissue

lesions: the metabolic activation by tissue enzymes of chemically

stable end unresetive compounds to highly toxic alkylating,

azTlating, acylating or peroxidizing metabolites. This major

advance has necessitated the development of new and unconventional

methodologies to investigate the potential pathogenetic role of these

reactive metabolites in many different types of tissue lesions.

The morphology and biochemical pattern of injury, the selectivity

of the target organ vulnerable to attack, and the respective

importance of giutathione, vitamin E, selenium, dietary lipid

content, and atmospheric oxygen concentration are often detemined

by two main factors: (I) the chemical nature of the reactive

metabolite and (2) the structure- toxic i ty-re lat ionship (STR) for

the given functional group. I l l u s t r a t i v e examples of toxins

initiating injury through two-electron addition resctionst by one-

electron (radical) attach or by generation of peroxidizing oxygen

species will be given, and methodologic approaches to solution

of ouch problems will be reviewed.