title: Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test.
abstract: BACKGROUND
  The U.S. EPA revised the Reproduction and Fertility Effects Test Guideline (OPPTS 870.3800/OECD 416) in 1998, adding numerous endpoints in an effort to incorporate new methodologies, improve the sensitivity for detecting reproductive toxicants, and more efficiently utilize study animals. Many of these new endpoints have not been used in regulatory reproductive toxicology studies prior to their inclusion in the test guidelines; thus, the Health and Environmental Sciences Institute (HESI) of the International Life Sciences Institute (ILSI) initiated the Reproductive Endpoints Project to examine the utility of these new endpoints.
  
  
  METHODS
  This report provides a retrospective analysis of 43 multi-generation studies (16 in Wistar rats, 27 in Sprague-Dawley rats) conducted according to the latest version of the test guidelines. It focuses on vehicle (negative) control values (means and ranges) for the various endpoints to examine inter-laboratory variability.
  
  
  RESULTS
  Based on the compiled data, the most variable endpoints across laboratories and their associated coefficients of variation (CV) for each generation were: percent abnormal sperm (166-205%), testicular spermatid concentration (126-147%), postimplantation loss (97-104%), primordial follicle counts (69%, only measured in P2 females), and epididymal sperm concentration (52-57%). Absolute and relative prostate and thymus weights, weanling uterine weights, and anogenital distance had CVs of 25-50%. Sources of variability included procedural differences between laboratories, inherent biological variability, and/or small sample sizes for some endpoints.
  
  
  CONCLUSIONS
  These inter-laboratory control data provide a means for laboratories to review their performance on reproductive toxicity measures, and provide perspective for interpreting their own control data and data from treated animals.
authors.affiliation: The Dow Chemical Company, Midland, Michigan 48674, USA. mmarty@dow.com
authors.forename: M S
authors.initials: MS
authors.lastname: Marty
authors.forename: B
authors.initials: B
authors.lastname: Allen
authors.forename: R E
authors.initials: RE
authors.lastname: Chapin
authors.forename: R
authors.initials: R
authors.lastname: Cooper
authors.forename: G P
authors.initials: GP
authors.lastname: Daston
authors.forename: J A
authors.initials: JA
authors.lastname: Flaws
authors.forename: P M D
authors.initials: PM
authors.lastname: Foster
authors.forename: S L
authors.initials: SL
authors.lastname: Makris
authors.forename: E
authors.initials: E
authors.lastname: Mylchreest
authors.forename: D
authors.initials: D
authors.lastname: Sandler
authors.forename: R W
authors.initials: RW
authors.lastname: Tyl
mesh_terms: D000818:Animals; D035061:Control Groups; D016208:Databases, Factual; D023381:Endpoint Determination; D005260:Female; D005298:Fertility / Q000502:physiology*; D017408:Guidelines as Topic; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000502:physiology; D017208:Rats, Wistar / Q000502:physiology; D012016:Reference Values; D012098:Reproduction / Q000502:physiology*; D012189:Retrospective Studies; D018675:Toxicity Tests / Q000379:methods*