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DEVELOPMENTAL NEUROTOXICITY TESTING GUIDELINES: VARIABILITY IN MORPHOMETRIC ASSESSMENTS OF NEUROPATHOLOGY.
Citation:
Crofton, K M., J. L. Sutton, S. L. Makris, K. Raffaele, AND W. F. Sette. DEVELOPMENTAL NEUROTOXICITY TESTING GUIDELINES: VARIABILITY IN MORPHOMETRIC ASSESSMENTS OF NEUROPATHOLOGY. Presented at Society of Toxicology, San Francisco, CA, March 25-28, 2000.
Description:
The USEPA Developmental Neurotoxicity (DNT) Study Test Guideline (OPPTS 870.6300) calls for neuropathological and morphometric assessments of rat pups on postnatal day (PND) 11 and at study termination (after PND 60). In recent discussions about conducting these studies on pesticides and the draft OECD DNT Study guideline, it was suggested that PND 11 testing results in excessive variation in morphometric assessments. To evaluate the variation in these measures, data were summarized from 24 DNT studies from 14 different labs; 13 pesticides, 3 positive controls, 6 toxics and 2 historical control studies. Morphometric data were available from 12 of these studies. Analogous measures of the cortex, cerebellum and hippocampus were chosen from each study. Body weight (20 studies) and brain weight (22 studies) data were summarized nd compared. Data variation for all assessments were compared by calculating the coefficients-of-variation (CV = SD/mean). Data were coded by postnatal day for analyses across different ages. Results clearly indicate that CVs for almost all morphometric and brain weight assessments were lower compared to body weights CVs. Overall, the mean CVs for the morphometric endpoints was between 5-20% for PND 11 pups and adults. Age was not a significant factor in the variation for morphometric endpoints. Mean CVs for brain weights ranged from 4-12% for pups and 3-6% for adults. Mean CVs for body weight ranged from 6-30% in pups, and 4-12% in adults. Brain and body weight CVs showed a trend towards lower variation as age increased. These data indicate that variability in the most common morphometric measures is modest, less than that associated with body weights, and not significantly greater at PND 11 than in young adults. This abstract does not necessarily reflect the policy of the US Environmental Protection Agency.