Recommendations on dose level selection for repeat dose toxicity studies

Prior to their registration and release on the market,  pharmaceuticals, (agro)chemicals and food ingredients must be tested and selecting the correct dose to administer to animals is a key factor to establish their safety for humans. While advise is given in test guidelines, this is often not harmonised, especially when it comes to the highest dose.

The manuscripts expands on a report from ECETOC, which suggests practical ways to choose doses that respect both regulations and animal welfare. Instead of leaving it to different sectors to choose the appropriate dose selection levels, experts from this ECETOC Task Force argue in favour recognizing systemic exposure and combining toxicokinetics with toxicity results to reach sensible dose decisions. The highest dose should induce mild toxicity to animals, yet avoid causing severe harm. Advancements in predicting human exposure will offer innovative opportunities for more relevant dose level selection approaches in the future.