Changes introduced with the new OECD 443 method and implications on the toxicological interpretation

OECD Guideline 443: ""Extended One-Generation Reproductive Toxicity Study"" was adopted 28 July 2011 as a discrete guideline within the system of other ones relevant for reproductive toxicology (e.g. 414, 415, 416). However, on the 13th March 2015, it was decided to replace the two-generation reproductive toxicity study (416) with the extended one-generation reproductive toxicity study. This replacement is critical, since it introduced significant changes in the study design also leading to implications on the toxicological interpretation of the study results. The presentation will focus on these changes, putting into perspective pros and cons of the new guideline. A few improvements (retention of more pups for postweaning developmental endpoints, reduction in animal numbers, additional information on developmental immunotoxicity and neurotoxicity) are faced by significant shortcomings (shortening of the premating treatment, restriction in fertility data, omission of the second generation, small group size of some cohorts, use of internal and sometimes inconsistent triggers in some regions, logistical problems). These differences will be discussed in detail, and an overview will be given how to improve study design using available alternatives and possible extensions to OECD 443.