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MOTOR ACTIVITY IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA.
Citation:
Raffaele, K. C., W. F. Sette, S. L. Makris, V C. Moser, AND K M. Crofton. MOTOR ACTIVITY IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
The USEPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for a battery of functional and neuropathological assessments in offspring during and following maternal exposure. The battery includes measurement of motor activity on post-natal days (PND) 13, 17, 21, and 60?2; the inclusion of three time points during lactation allows assessment of the pattern of overall activity levels during this time and of the development of habituation. Although the Guideline specifies use of an automated motor activity recording apparatus, and provides general guidance on conduct of motor activity testing, the type of device or duration of the testing period are not specified. As a result, many devices and session lengths are seen among the roughly two dozen studies that have been submitted to the Agency. In order to evaluate whether some types of devices/testing conditions yield more reliable data than others, we have compared motor activity data generated in control animals from 21 studies. Data were evaluated in terms of: 1) variability of the data within a given study, across time points; 2) variability of the data across studies within a given laboratory, separately by time point; 3) stability of the mean baseline motor activity counts across studies within a given laboratory, for each time point; 4) variability for particular devices, across laboratories. Data from ten laboratories were evaluated; the number of studies available from a single laboratory varied from 1 to 5. We noted a large variability in motor activity data for some studies. Preliminary analysis indicated that there is higher variability for the earlier lactation time points than for the later lactation time points in most laboratories. Variability for the adult time point was usually lower than for the lactation time points. The variability did not consistently correlate with the type of device used or with session duration. The stability of mean baseline activity counts across studies varied among laboratories. For all laboratories, mean baseline activity counts were higher on PND17 than on PND13; for most laboratories, mean counts on PND21 were lower than on PND17. Further consideration of how to reduce variability of these motor activity measurements is warranted. This abstract does not necessarily reflect the policy of the US Environmental Protection Agency.