Science Inventory

Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls

Citation:

NAROTSKY, M. G. Comparison of Birth-and Conception-Based Definitions of Postnatal Age in Developmental and Reproductive Rodent Toxicity Studies: lnfluence of Gestation Length on Measurements of Offspring Body Weight and Puberty in Controls. Presented at Teratology Society Annual Meeting, San Diego, CA, June 25 - 29, 2011.

Impact/Purpose:

Two of these studies defined PND 0 as the DOB; the other studies defined PND 0 to coincide with gestation day (GO) 22. Litters were examined at birth and at various times postnatally.

Description:

Most laboratories conducting developmental and reproductive toxicity studies in rodents assign age by defining postnatal day (PND) 0 or 1 as the day of birth (DOB); i.e., gestation length affects PND and the timing of postnatal measurements. Some laboratories, however, define age based on a particular day of gestation; i.e., PND is standardized by time postcoitus, independent of gestation length. Here, where possible, both approaches were applied retrospectively to control data to assess body weight and pubertal measurements independent of treatment effects. Analyses focused on the influence of gestation length on these endpoints.. Data from four reproductive toxicity studies using Sprague-Dawley rats were examined. Two of these studies defined PND 0 as the DOB; the other studies defined PND 0 to coincide with gestation day (GO) 22. Litters were examined at birth and at various times postnatally. Weanlings were maintained past puberty and examined for onset of vaginal opening (VO) and preputial separation (PPS). All control litters were delivered on GD 21 (n=53) or 22 (n=44). Using OOB-based age, animals born on GD21 remained significantly lighter than GD22-born counterparts at all time points examined, from birth to PNO 38 in females and PI\JD 46 in males (p<0.004 for all DOB-based pup weight analyses; p0.6 for all GD-based pup weight analyses, p>O.l at PND38 and PND46). The GD-based age of VO or PPS was also unaffected by gestation length (p=0.9 and 0.2, respectively). Independent of protocol, body weight on the day of VO or PPS was uninfluenced by gestation length. Thus, with DOB-based age, gestation length strongly and consistently influenced offspring body weight; typical data analyses rarely account for this. In contrast, the GD-based approach, which defines age independent of gestation length, effectively removed the influence of gestation length on offspring body weight measurements. [This abstract does not necessarily reflect EPA policy.]

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 06/29/2011
Record Last Revised: 03/12/2012
OMB Category: Other
Record ID: 233452