Guidance Document for the Extended One-Generation Reproduction Toxicity Study (OECD Test Guideline 443) (EOGRT)

Terms of Reference

  • Review the available literature on the sensitivity and specificity of including a second generation in reproductive toxicity testing.
  • Define, if possible, the triggers to include (or waive) a second generation.
  • Review available literature on the evidence indicating developmental neurotoxicity that is not identified in other required studies, such as the 90-day repeated dose toxicity studies.
  • Define, if possible, the triggers to include (or waive) the developmental neurotoxicity module.
  • Review available literature on the evidence indicating developmental immunotoxicity that is not identified in other required studies, such as the 90-day repeated dose toxicity studies.
  • Define, if possible, the triggers to include (or waive) the developmental immunotoxicity module.
  • Formulate triggers for conducting each of the three optional modules in the EOGRT, if possible in the form of a decision-tree.
  • Publish the results in an ECETOC Report and subsequently as a peer-reviewed publication

Outcome:

July 2016. The results from this Task Force have been published as:

Moore NP, Beekhuijzen M, Boogaard PJ, Foreman JE, North CM, Palermo C, Schneider S, Strauss V, van Ravenzwaay B, Poole A. 2016.
Guidance on the selection of cohorts for the extended one-generation reproduction toxicity study (OECD test guideline 443).
Regul Toxicol Pharmacol 80:32-40. (Open Access)

Available from this link: http://bit.ly/ecetoc-art-2016-moore-et-al

Abstract:

The extended one-generation reproduction toxicity study (EOGRTS; OECD test guideline 433) is a new and technically complex design to evaluate the putative effects of chemicals on fertility and development, including effects upon the developing nervous and immune systems. In addition to offering a more comprehensive assessment of developmental toxicity, the EOGRTS offers important improvements in animal welfare through reduction and refinement in a modular study design. The challenge to the practitioner is to know how the modular aspects of the study should be triggered on the basis of prior knowledge of a particular chemical, or on earlier findings in the EOGRTS itself, requirements of specific regulatory frameworks notwithstanding. The purpose of this document is to offer guidance on science-based triggers for these extended evaluations.

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