DEVELOPMENTAL TOXICOLOGY STRUCTURE-ACTIVITY EQUATIONS

RECENT ASSESSMENTS OF THE STATUS OF DEVELOPMENTAL TOXICOLOGYBY THE REGULATORY AND SCIENTIFIC COMMUNITIES HAVE IDENTIFIEDA NEED TO APPLY STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) TO EXISTING TEST STRATEGIES. HEALTH DESIGNS, INC. HAS DEVELOPED A STATISTICAL SAR MODEL OF TERATOGENICITY BASED ON THE LITERATURE ON FRANK MALFORMATIONS IN MAMMALS. THIS MODEL IS BEING USED TO ESTIMATE THE PROBABILITY OF MALFORMATIONS FOR CHEMICALS THAT HAVE NOT YET BEEN TESTED. THE PURPOSE OF THE PROPOSED RESEARCH IS TO IMPROVE ON THE PRIOR WORK BY ASSEMBLING A MORE COHERENT AND DETAILED DATABASE OF DEVELOPMENTAL EFFECTS. SAR MODELS OF RELATED SETS OF CHEMICALS, CHEMICALS WITH COMMON PHARMACOLOGIC ACTIVITY, AND COMMON BIOCHEMICAL ACTIVITY WILL ALSO BE DEVELOPED. THE DATABASE AND THE SAR MODELS THUS DERIVED WOULD MATERIALLY ENHANCE THE ARMAMENTARIUM OF INDUSTRIAL TOXICOLOGISTS, HYGIENISTS, AND REGULATORS IN PINPOINTING EXPOSURES OF CONCERN. THE ESTIMATES OF DEVELOPMENTAL TOXICITY POTENTIAL COULD ALSO LEAD TO MORE FOCUSED DEVELOPMENTAL EFFECTS-TESTING OF POTENTIALLY HARMFUL CHEMICALS. THE PROPOSED RESEARCH COULD ALSO LEAD TO A REDUCTION IN THE NUMBERS OF ANIMALS USED IN REPRODUCTIVE EFFECTS-TESTING.