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REFLEX MODIFICATION: AN APPROACH TO INCORPORATE INTO A DEVELOPMENTAL NEUROTOXICITY (DNT) STUDY DESIGN WITH COMMERCIAL EQUIPMENT.
Citation:
Crofton, K M. AND L. P. Sheets. REFLEX MODIFICATION: AN APPROACH TO INCORPORATE INTO A DEVELOPMENTAL NEUROTOXICITY (DNT) STUDY DESIGN WITH COMMERCIAL EQUIPMENT. Presented at Society of Toxicology, San Francisco, CA, 3/25-28/2001.
Description:
Reflex modification (RM) of the startle response is a very useful tool for testing sensory function and the integrity of a well-defined complement of neural circuits. Advantages of this procedure include the ability to rapidly acquire objective measurements and differentiate sensory from motor impairment, the potential to test multiple sensory modalities, and a high potential for interspecies extrapolation. Furthermore, this can be done without the need for prior training or invasive surgery. In the context of regulatory guidelines for a DNT study, RM is recommended, but not required, by the U.S. EPA (OPPTS 870.6300) and the OECD (draft guideline number 426). Compared to the test of auditory startle habituation, which is presently required in both guidelines, RM demands specialized equipment and additional expertise, including a knowledge of acoustical psychophysics. In particular, technical demands and equipment needs increase substantially if ultrasonic frequencies (i.e., > 20 kHz) are included in the selection of prepulse stimuli. Frequencies in the range of 30 to 40 kHz are typically included in such a battery because high-frequency hearing is the most sensitive to certain chemicals. This additional level of complexity, in combination with limitations associated with commercial equipment, represents a potential barrier to industry labs that want to incorporate RM into a DNT study. This paper examines the issues involved with incorporating this test into a DNT study using pure tones as prepulse stimuli and assesses what can be accomplished with a reasonable effort using commercial equipment. This abstract does not necessarily reflect the policy of the U.S. EPA.