Skip to main content
SpringerLink
Log in
Book cover

Teratogenicity Testing pp 275–294Cite as

Historical Control Data in Reproductive and Developmental Toxicity Studies

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 947))

Abstract

Reproductive and developmental toxicity studies in laboratory animals are conducted as part of the process of evaluating the risk of pharmaceuticals and chemicals to human reproduction and development. In these studies, comparison of data from groups dosed with the test article to a concurrent control group is considered the most relevant approach for the interpretation of adverse effects. However, differences between the concurrent control and treated groups may arise by chance alone, and in some instances may even appear to be dose-related. These limitations of the concurrent control group are of particular concern when interpreting fetal malformation data because malformations are rare events that can be better characterized when incidences in both concurrent control and treated groups are compared to a larger set of control values. Historical control data can be useful not only to understand the range of normal for a given endpoint but also to monitor the biological variability over time due to various external factors (e.g., genetic changes in a strain, changes at the breeding facility). It can also serve to track the performance of the laboratory and identify any changes in the data that may be the result of internal factors at the performing laboratory due to modification in animal diet, seasonal changes, or even the proficiency of the technicians in handling animals and recording fetal and offspring observations. This chapter will provide the reader with guidance on building a laboratory historical control database and applying it to the scientific interpretation of reproductive and developmental toxicity data. Information on sources of external historical control data will be provided and some perspective given on the utility of this data. A discussion of the presentation of historical control data with descriptive statistics will be accompanied by examples of tabulation of the data. Supernumerary rib will be used as an example of how historical control data can be used for data interpretation.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. US FDA (Food and Drug Administration) (1994) ICH Harmonized tripartite guideline, Detection of toxicity to reproduction for medicinal products & toxicity to male fertility S5(R2). Fed Regist 59:48746–48752

    Google Scholar 

  2. US EPA (Environmental Protection Agency), OPPTS (Office of Prevention, Pesticides and Toxic Substances). (1998) Health effects test guidelines. OPPTS 870.3800. Reproduction and fertility effects

    Google Scholar 

  3. US EPA (Environmental Protection Agency), OPPTS (Office of Prevention, Pesticides and Toxic Substances). (1998) Health effects test guidelines. OPPTS 870.3700, Prenatal developmental toxicity study

    Google Scholar 

  4. Charles River Laboratories (1996) Historical control data (1992–1994) for developmental and reproductive toxicity studies using the Crl:CD® (SD)BR rat. Compiled by MARTA (Middle Atlantic Reproduction and Teratology Association) and MTA (Midwest Teratology Association). http://www.criver.com/sitecollectiondocuments/rm_rm_r_tox_studies_crlcd_sd_br_rat.pdf. Accessed 4 Jan 2012

  5. Charles River Laboratories (1993) Historical control data for developmental and reproductive toxicity studies using the Crl:CD® BR rat. Compiled by MARTA (Middle Atlantic Reproduction and Teratology Association). Edited by Lang, P.L. http://www.criver.com/sitecollectiondocuments/rm_rm_r_tox_studies_crlcd_br_rat.pdf. Accessed 4 Jan 2012

  6. MARTA (Middle Atlantic Reproduction and Teratology Association) (1993) Historical control data for developmental and reproductive toxicity studies using the New-Zealand White rabbit. Edited by Lang, P.L. HRP Inc.

    Google Scholar 

  7. Palmer AK (1972) Sporadic malformations in laboratory animals and their influence on drug testing. In: Klingberg AA, Chemke J (eds) Drugs and fetal development. Plenum Press, New York, pp 45–60

    Chapter  Google Scholar 

  8. Perraud J (1976) Levels of spontaneous malformations in the CD rat and the CD-1 mouse. Lab Anim Sci 26:293–300

    PubMed  CAS  Google Scholar 

  9. Palmer AK (1972) Sporadic malformations in laboratory animals and their influence on drug testing. Adv Exp Med Biol 27:45–60

    Article  PubMed  CAS  Google Scholar 

  10. Wilson JG (1973) Environment and birth defects. Academic, New York

    Google Scholar 

  11. Harris SB et al (1980) Evaluation of the Upj: TUC (ICR) strain of mice for use in teratology tests. J Toxicol Environ Health 6:155–165

    Article  PubMed  CAS  Google Scholar 

  12. Marty MS et al (2009) Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test. Birth Defects Res B Dev Reprod Toxicol 86:470–489

    Article  PubMed  CAS  Google Scholar 

  13. Tyl RW, Marr MC (2006) Developmental toxicity testing—Methodology. In: Hood RD (ed) Developmental and reproductive toxicology. CRC, Boca Raton, FL, pp 201–261

    Google Scholar 

  14. Tyl RW, Chernoff N, Rogers JM (2007) Altered axial skeletal development. Birth Defects Res B Dev Reprod Toxicol 80:451–472

    Article  PubMed  CAS  Google Scholar 

  15. Holson JF et al (2006) Significance, reliability, and interpretation of developmental and reproductive toxicity study findings. In: Hood R (ed) Developmental and reproductive toxicology, 2nd edn. CRC, Boca Raton, FL, pp 329–424

    Google Scholar 

  16. US EPA (Environmental Protection Agency) FIFRA (Federal Insecticide, and Rodenticide Act), Good laboratory practice standard 40 CFR part 160

    Google Scholar 

  17. US FDA (Food and Drug Administration) Good laboratory practice regulations 21 CFR Part 58

    Google Scholar 

  18. Makris SL et al (2009) Terminology of developmental abnormalities in common laboratory mammals (version 2). Reprod Toxicol 28:371–434

    Article  PubMed  CAS  Google Scholar 

  19. Wise LD et al (1997) Terminology of developmental abnormalities in common laboratory mammals (version 1). Teratology 55:249–292

    Article  PubMed  CAS  Google Scholar 

  20. Chahoud I et al (1999) Classification terms in developmental toxicology: need for harmonisation. Report of the second workshop on the terminology in developmental toxicology Berlin, 27–28 Aug 1998. Reprod Toxicol 13:77–82

    Article  PubMed  CAS  Google Scholar 

  21. U.S. EPA (Environmental Protection Agency) (1991) Guidelines for developmental toxicity risk assessment. Fed Reg 56:63798–63824

    Google Scholar 

  22. Collins T et al (1999) Food and Drug Administration proposed testing guidelines for developmental toxicity studies. Reg Toxicol Pharmacol 30:38–44

    Google Scholar 

  23. European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) (2002) Guidance on evaluation of reproductive toxicity data, Monograph No. 31, ECETOC Brussels, Belgium

    Google Scholar 

  24. Weil CS (1970) Selection of the valid number of sampling units and a consideration of the combination in toxicological studies involving reproduction, teratogenesis, and carcinogenesis. Food Cosmet Toxicol 8:177–182

    Article  PubMed  CAS  Google Scholar 

  25. Gaylor DW (1978) Methods and concepts of biometrics applied to teratology. In: Wilson JG, Fraser FC (eds) Handbook of teratology, vol I. Plenum, New York, pp 429–444

    Google Scholar 

  26. Gad SC, Weil CS (1986) Data analysis applications in toxicology. In: Gad SC, Weil CS (eds) Statistics and experimental design for toxicologists. Telford, Caldwell, NJ, pp 429–444

    Google Scholar 

  27. Green EL (1962) Quantitative genetics of skeletal variations in the mouse. II. Crosses between four inbred strains (C3H, DBA, C57BL, BALB/c). Genetics 47:1085–1096

    PubMed  CAS  Google Scholar 

  28. Rogers JM et al (1991) Developmental toxicity of bromoxynil in rats and mice. Fundam Appl Toxicol 17:442–447

    Article  PubMed  CAS  Google Scholar 

  29. Wickramaratne GA (1988) The post-natal fate of supernumerary ribs in rat teratogenicity studies. J Appl Toxicol 8:91–94

    Article  PubMed  CAS  Google Scholar 

  30. Sawin PB, Gow M, Muehlke M (1967) Morphogenetic studies of the rabbit. XXXVII. Genome, gradient growth pattern and malformation. Am J Anat 121:197–216

    Article  PubMed  CAS  Google Scholar 

  31. Chernoff N, Rogers JM (2004) Supernumerary ribs in developmental toxicity bioassays and in human populations: incidence and biological significance. J Toxicol Environ Health B Crit Rev 7:437–449

    Article  PubMed  CAS  Google Scholar 

  32. Khera KS (1981) Common fetal aberrations and their teratologic significance: a review. Fundam Appl Toxicol 1:13–18

    PubMed  CAS  Google Scholar 

  33. Holson JF et al (1976) Teratological evaluation of FD&C Red No. 2-A collaborative government industry study. V. Combined findings and discussions. J Toxicol Environ Health 1:875–885

    Article  PubMed  CAS  Google Scholar 

  34. Holson JF et al (1981) Suitability of experimental studies for predicting hazards to human development. Proceedings of the 1981 annual winter meeting of the Toxicology Forum, Arlington, VA

    Google Scholar 

  35. Kimmel CA et al (1984) Reliability of experimental studies for predicting hazards to human development. NCTR technical report for experiment No. 6015 National Center for Toxicological Research, Jefferson, AR

    Google Scholar 

  36. Chernoff N et al (1991) Significance of supernumerary ribs in rodent developmental toxicity studies: Postnatal persistence in rats and mice. Fundam Appl Toxicol 17:448–453

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Southern Research, Birmingham, AL, USA

    Eve Mylchreest

  2. Stephen B. Harris Group, San Diego, CA, USA

    Stephen B. Harris

Authors
  1. Eve Mylchreest
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen B. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eve Mylchreest .

Editor information

Editors and Affiliations

  1. CiToxLAB, BP 563, Evreux, 27005, France

    Paul C. Barrow

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Mylchreest, E., Harris, S.B. (2013). Historical Control Data in Reproductive and Developmental Toxicity Studies. In: Barrow, P. (eds) Teratogenicity Testing. Methods in Molecular Biology, vol 947. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-131-8_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-131-8_22

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-130-1

  • Online ISBN: 978-1-62703-131-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation