Following a request from the European Commission, the Scientific Committee developed principles and guidance for the establishment of protocols for 90-day whole food/feed studies in rodents. The guidance complements the OECD Test guideline 408 and provides specific advice for performing and reporting experiments carried out with whole food/feed. The conduct of the study and documentation should follow good laboratory practice. Preparation of appropriate test diets is a key element of the experiment with respect to the choice of the diet type, nutritional balance and necessary adjustments, processing, and storage. Since it is often not possible to include whole foods in high amounts in the test diet, fewer dose levels but more animals in control and top dose groups should be used to maximise the power of the study. In accordance with the European Directive 2010/063, the test animals should be housed socially. The guidance recommends that animals of the same sex are housed in pairs. A comprehensive set of endpoints as set out in the OECD TG 408 should be measured during and at the end of the 90-day period, as appropriate. The use of a power analysis to estimate a sample size capable of detecting a pre-specified biologically relevant effect size with a specified power and significance level is described. A randomised block design is recommended for 90-day toxicity studies when testing whole food/feed.