title: Implementing the extended one-generation reproductive toxicity study (EOGRTS): important points to consider.
abstract: The hallmark of the extended one-generation reproductive toxicity study (EOGRTS) is that, based on certain criteria or triggers, selected offspring are assigned at weaning to different cohorts for further investigation of sexual maturation, reproductive organ integrity and function, neuropathological and behavioral endpoints, and/or immune function. The triggers allow for a more customizable design based directly on the data, while minimizing animal usage. Compared to the two-generation reproductive toxicity study, the EOGRTS design increases the number, extent, and duration of F1-offspring assessments resulting in more thorough and efficient utilization of the first generation while excluding the second generation of offspring unless triggered. Therefore, the EOGRTS has the potential to reduce the number of rats required by nearly 1200 animals per study. When performing the EOGRTS, the complexity of this study should not be underestimated and experienced flexible testing laboratories with sufficient resources and historical control data for all parameters are essential. The aim of this review is to discuss the important aspects of this challenging study design and to share our knowledge on the implementation of this study in our laboratories. In addition, we elaborate on the type of criteria for expansion of the study and logistical considerations. Altogether, this review can be used as guidance by other labs, study monitors, and registration officers.
authors.affiliation: a WIL Research Europe , Den Bosch , the Netherlands ;
authors.forename: Manon
authors.initials: M
authors.lastname: Beekhuijzen
authors.affiliation: a WIL Research Europe , Den Bosch , the Netherlands ;
authors.forename: Helma
authors.initials: H
authors.lastname: Barentsen
authors.affiliation: b WIL Research Europe , Lyon , France ;
authors.forename: Edward
authors.initials: E
authors.lastname: Marsden
authors.affiliation: a WIL Research Europe , Den Bosch , the Netherlands ;
authors.forename: Amy
authors.initials: A
authors.lastname: Zmarowski
authors.affiliation: b WIL Research Europe , Lyon , France ;
authors.forename: Michel
authors.initials: M
authors.lastname: Aujoulat
authors.affiliation: c WIL Research US , Hillsborough , NC , USA ;
authors.forename: Catherine
authors.initials: C
authors.lastname: Picut
authors.affiliation: d WIL Research US , Ashland , OH , USA.
authors.forename: Eddie
authors.initials: E
authors.lastname: Sloter
mesh_terms: D000818:Animals; D015331:Cohort Studies; D005062:European Union; D033161:Government Regulation; D017408:Guidelines as Topic; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods* / Q000592:standards
keywords: 3R’s; Developmental immunotoxicity; EU B.56; OECD 443; developmental neurotoxicity; extended one-generation reproductive toxicity study (EOGRTS); triggers