Implementation of reduction and refinement-related parameters in repeated dose toxicity studies

The OECD’s test guidelines programme provides internationally recognized standard methods for non-clinical health and environmental safety testing of chemicals. They act as a harmonization mechanism and can support the replacement, reduction and refinement of regulatory tests using animals. We reviewed the reports of 300 repeated dose tests using rats conducted for chemical safety purposes to determine the extent to which current reduction- and refinement-related param­eters in TG 407 and 408 had been taken up. We found strong adherence to minimum group size and number of dose groups and strong adherence to the maximum dose level and dose volume. There was, however, very low uptake of the use of a limit test as a reduction method in both TGs, and some evidence of continued use of individual housing and larger than the minimum group sizes in the 28-day studies (TG 407). There are other opportunities to improve the TGs with respect to reduction and refinement, and we recommend that there is a systematic review by the OECD test guidelines programme to ensure their guidelines comply with the aims of the 3Rs.