This proposal for a program project represents a continuing effort on the part of a multidisciplinary team in studying the basic biological effects of a variety of environmental chemicals. The research team consists of professionals trained in the field of biochemistry, chemistry, physiology, microbiology, engineering, pharmacology, toxicology, morphology and pathology, oncology, and medicine. Included in the proposal are 13 separate research projects dealing with the question of mechanisms and determinants of toxicity induced by environmental chemicals. There are 4 projects dealing with neuro- and behavioral toxicity of compounds such as lead, manganese, methyl butyl ketone, organophosphates and carbon monoxide. Of particular importance in these projects are questions of in utero and neonatal exposure, of simutaneous exposures to multiple agents, and of effects of cerebral blood flow. Three projects deal with pulmonary toxicology of agents such as acrolein, paraquat, cadmium, asbestos and fiberglass and deal specifically with effects on lung defense mechanisms and deposition of fibers. One project deals with the effects of carbon monoxide on the cardiovascular system in hypertensive and/or atherosclerotic animals; another involves studies on the interrelationship between xenobiotic metabolism and O2 transport in the placenta and lung. One project deals with the toxicology of the phthalic acid esters with emphasis on the lung, liver, and mutagenic potential; another with the toxicokinetics and lung toxicity of cadmium. Two projects deal with genetic toxicology and the potential mutagenicity/carcinogenicity of SO2, nickel, cadmium, and benzene. The objective of all these studies are (1) to evaluate hazard so as to prevent disease (2) to develop predictive assays, and (3) to lead to the development of rational therapeutic agents to reverse or prevent toxic effects.