Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test

M. S. Marty, B. Allen, R. E. Chapin, R. Cooper, G. P. Daston, J. A. Flaws, P. M D Foster, S. L. Makris, E. Mylchreest, D. Sandler, R. W. Tyl

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)470-489
Number of pages20
JournalBirth Defects Research Part B - Developmental and Reproductive Toxicology
Volume86
Issue number6
DOIs
StatePublished - Dec 2009
Externally publishedYes

Fingerprint

Reproduction
Fertility
Guidelines
Spermatozoa
Rats
Animals
Fertility Agents
Weights and Measures
Thymus
Spermatids
Environmental Health
Biological Science Disciplines
Sample Size
Toxicology
Thymus Gland
Sprague Dawley Rats
Toxicity
Wistar Rats
Prostate
Organisation for Economic Co-Operation and Development

Keywords

  • Endocrine
  • Fertility
  • Multi-generation
  • Regulatory
  • Reproduction
  • Reproductive toxicity
  • Test guideline

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test. / Marty, M. S.; Allen, B.; Chapin, R. E.; Cooper, R.; Daston, G. P.; Flaws, J. A.; Foster, P. M D; Makris, S. L.; Mylchreest, E.; Sandler, D.; Tyl, R. W.

In: Birth Defects Research Part B - Developmental and Reproductive Toxicology, Vol. 86, No. 6, 12.2009, p. 470-489.

Research output: Contribution to journalArticle

Marty, MS, Allen, B, Chapin, RE, Cooper, R, Daston, GP, Flaws, JA, Foster, PMD, Makris, SL, Mylchreest, E, Sandler, D & Tyl, RW 2009, 'Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test', Birth Defects Research Part B - Developmental and Reproductive Toxicology, vol. 86, no. 6, pp. 470-489. https://doi.org/10.1002/bdrb.20208
Marty, M. S. ; Allen, B. ; Chapin, R. E. ; Cooper, R. ; Daston, G. P. ; Flaws, J. A. ; Foster, P. M D ; Makris, S. L. ; Mylchreest, E. ; Sandler, D. ; Tyl, R. W. / Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test. In: Birth Defects Research Part B - Developmental and Reproductive Toxicology. 2009 ; Vol. 86, No. 6. pp. 470-489.
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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.",
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AU - Allen, B.

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AU - Cooper, R.

AU - Daston, G. P.

AU - Flaws, J. A.

AU - Foster, P. M D

AU - Makris, S. L.

AU - Mylchreest, E.

AU - Sandler, D.

AU - Tyl, R. W.

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