LINKING HUMAN AND ANIMAL NEUROTOXICOLOGY RESEARCH

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Behavioral research on the neurotoxic effects of environmental chemicals is conducted in two isolated worlds. Human performance tests are drawn from the traditions of achievement, aptitude and intelligence testing (e.g., Digit Symbol, Santa Ana). Behavioral testing in animals, emerging from a different tradition, employs techniques such as maze learning, reinforcement schedules, and complex stimulus discrimination to investigate potential neurotoxicants. Although the primary differences between these approaches are methodological rather than conceptual, efforts to bridge this chasm have been unsuccessful and there has been little practical or scientific contact between them. As a consequence, the generality of the extensive animal neurotoxicity literature has rarely been evaluated, few human-subjects studies acknowledge much less utilize the animal literature when selecting tests, and efforts to identify and characterize health effects advance along parallel paths with little indication they will intersect. The objective of this project is to implement frequently-used animal behavioral tests in an affordable, efficient, field-ready behavioral test battery on a laptop computer for human neurotoxicology research. Further, the proposed test system will replace language-based instructions through the utilization of shaping and modeling; techniques which been used to successfully teach complex tasks to animals, children, and a wide range of educationally-impaired adults. Newly available software will permit the presentation of motion pictures and animation on the computer screen to teach the behaviors needed for performance testing to supplement shaping methods which form the foundation of the training strategy for the new tests. These tests could thus be employed with virtually any person over 10 years of age, literate or not in English. Test development and availability, however, are insufficient to establish the needed linkage between the animal and human neurotoxicology research worlds. To provide the database needed to relate these new tests to the established tests in human subjects research, parametric testing of unimpaired males and females will explore the impact of sex, age, culture, and educational level on the new tests. Tests adopted from animal research and tests of the same function used in human research will be administered to the same subjects and the results correlated. Finally, validation studies with a human population exposed to a representative toxicant, using tests employed with analogously exposed and damaged animal groups, will provide the demonstration of significant, reliable relationships between species. Upon completion, this project will significantly improve the generalization potential between animal and human research on neurotoxic chemicals by making animal test methods available, accessible, and meaningful to neurotoxicologists studying humans.