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Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length and Timing of Neonatal Examinations on Litter Data in Controls
Citation:
NAROTSKY, M. G. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: Influence of Gestation Length and Timing of Neonatal Examinations on Litter Data in Controls. Presented at Teratology Society Annual Meeting, Baltimore, MD, June 23 - 27, 2012.
Impact/Purpose:
Thus, the GD-based approach effectively removed the influence of gestation length on subsequent offspring body weight measurements and reduces variance for this postnatal endpoint..
Description:
Laboratories conducting developmental and reproductive toxicity studies with rodents use varied protocols for determining the timing of neonatal litter examinations and subsequent measurements. Most laboratories determine timing based on the day of birth (DOB); l.e., gestation length affects the timing of data collection. Some laboratories, however, determine timing based on a particular day of gestation; i.e., examinations are standardized by time postcoitus, independent of gestation length. Here, three protocols were compared by retrospectively examining control neonatal litter data to assess the influences of methodology and gestation length on litter size, prenatal loss, and pup weight independent of treatment effects. Data from nine reproductive/developmental toxicity studies using Sprague-Dawley rats were examined. In five of these studies (n=81), litters were examined on the day coinciding with gestation day (GD) 22 (plug=GDO), regardless of the actual day of parturition, and 5 days later (i.e., GD22-based postnatal day 5) (Protocol 1). In the remaining studies, neonatal examinations were DOB based: in two studies (n=63), litters were examined as soon as practical after parturition and again 6 days after birth (DOB-based day 6) (Protocol 2); whereas in the other two studies (n=34), litters were examined the morning after parturition completion and 4 days after GD22 (Protocol 3). For all three protocols, litter size and prenatal loss per litter were comparable across gestation length, examination day, and parturition-examination interval; whereas neonatal pup weights increased significantly with these parameters. Thus, these protocols yielded comparable results for litter size, prenatal loss, and pup weight of neonates. In contrast, subsequent litter examinations on postnatal day 4-6 showed different results for pup weight depending on the definition of postnatal age. For Protocol 2 (DOBbased day 6), animals born on GD22 were significantly heavier than those born on GD21; whereas for Protocols 1 and 3 (GD22-based age), pup weights on day 4 or 5 were comparable for animals born on different gestation days. Thus, the GD-based approach effectively removed the influence of gestation length on subsequent offspring body weight measurements and reduces variance for this postnatal endpoint. [This abstract does not necessarily reflect EPA policy.]