Laboratory of Environmental Toxicology: Summary Statement

The scientific efforts of the Laboratory of Environmental Toxicology (LET) are directed toward the prevention of environmentally related diseases through understanding mechanisms of toxicity. Special emphasis is placed upon environmental factors which may adversely affect reproduction and development. Toxicologic phenomena are studied from the descriptive to the molecular level in search of a better understanding of mechanisms. This increased understanding contributes to the development of better and more effective test procedures to predict toxicity in humans. Available scientific expertise is broad and includes biochemistry, reproductive physiology, teratology, pharmacology, cell biology, pathology, and behavior. Test systems are likewise diverse and range from molecular biochemistry and electron microscopy, through in vitro cell, organ, and embryo cultures, to whole animals. Whether their study be molecular and/or biochemical mechanisms of toxic action, phar-macology and pharmacokinetics in developing systems , the identification of sensitive biochemical indicators which predict specific organ damage, or some other area of toxicology, scientists in LET are in a unique position to develop and utilize basic scientific information for resolving critical environmental health problems. The research goals of the Laboratory are supported by both intramural scientists and contracted research. The scope of the overall effort is broad involving both national and international programs and adjunct appointments. Recognizing training as one of its primary responsibilities, the Laboratory supports graduate students at nearby universities, offers training opportunities for foreign postdoc-toral scientists and American scientists on sabbatical leave. In short, the Laboratory of Environmental Toxicology integrates research and training into a program that is both worldwide in scope and one of the strongest multidisciplinary efforts in toxicology in this country. Experimental Teratogenesis The research of this group seeks a better understanding of teratogenic compounds, particularly their molecular mechanisms of action. Scientists are currently testing the hypothesis that certain drugs and environmental chemicals interfere with embryogenesis by irreversibly combining with critical molecules in the fetus. As a first step to investigate this possibility, known acylating agents of simple chemical structure, including anhydrides and imides, are being used as test compounds. To determine the teratogenicity and embryotoxicity of these agents, each is administered to pregnant CD-1 mice. One day prior to full term, fetuses are removed and examined for gross visceral or skeletal abnormalities. All of the acylating agents thus far tested have produced malformations in the offspring of treated dams. In order to correlate teratogenic potential with chemical reactivity, the interaction of acylating agents with …