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LEARNING AND MEMORY TESTS IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA.
Raffaele, K. C., M. E. Gilbert, K M. Crofton, S. L. Makris, AND W. A. Sette. LEARNING AND MEMORY TESTS IN DEVELOPMENTAL NEUROTOXICITY TESTING: A CROSS-LABORATORY COMPARISON OF CONTROL DATA. Presented at Society of Toxicology, Baltimore, MD, 3/21-25/2004.
The US EPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for functional tests to assess the impact of chemicals on cognitive function in offspring following maternal exposure. A test of associative learning and memory is to be conducted around the time of weaning and around 60 days of age, and flexibility is allowed in the choice of test. The present study was undertaken to: 1) survey the types of` learning and memory tests typically used by companies submitting DNT data to EPA, 2) evaluate the consistency of protocols for such tests across laboratories, 3) identify the variables routinely reported for any given test protocol, and 4) estimate the variability in control values on a number of test endpoints. Datasets from 15 laboratories were examined, comprising learning and memory tests for 35 test substances and 7 positive control treatments. The survey revealed a total of 8 learning and memory tests were employed. The two most common tests in both age groups were position discrimination in a 3 compartment water maze and passive avoidance conditioning. Preliminary findings reveal a range in the stimulus parameters and protocols for any given test. Similarly the dependent measures recorded and the format of the data report varied broadly, complicating efforts to evaluate control variability and limiting direct comparisons of proficiency among laboratories. A number of cases utilized the same animals for young and adult testing. Data presentation and statistical evaluation were often inadequate; incomplete reporting of individual animal and trial data limited our ability to re-analyze submitted data. More complete reporting of procedural information and inclusion of complete individual animal and trial data may help identify sources of variability and facilitate cross-laboratory comparisons. This abstract does not reflect official policy of the US EPA..