Abstract
Abstract Commission Regulation (EU) No. 283/2013 sets out the data requirements for pesticide active substances and includes short‐term oral toxicity testing in rodents (90‐day rat study) and non‐rodents (90‐day dog study) to support human health hazard assessment for pesticide active substances in the European Union (EU). However, the relevance of the 90‐day dog study for such assessments has been increasingly questioned. In this context, the EFSA Panel on Plant Protection Products and their Residues (PPR Panel) initiated a self‐task mandate to evaluate the contribution of the 90‐day dog study to hazard assessment and to explore whether dog studies may be waived from a scientific perspective. This work included a retrospective analysis for the role of dog data in the derivation of health‐based guidance values (HBGVs, i.e. acceptable daily intake (ADI) and acceptable operator exposure level (AOEL)) for pesticide active substances in the EU and the development of a tiered assessment strategy to support regulatory decision‐making for new active substances. The evidence obtained in the retrospective analysis showed that, in 97% of the cases for ADI and 95% for AOEL, observed interspecies differences in established no observed adverse effect levels (NOAELs) were attributable to experimental and biological variability, differences in study design and/or allometric scaling, rather than reflecting a genuine dog‐specific sensitivity. Further analyses of modes of action (MoA); absorption, distribution, metabolism and excretion (ADME); and toxicokinetic (TK) profiles across species were conducted. Based on the retrospective analysis, a tiered assessment strategy was defined to decide whether for a new active substance, the 90‐day dog study can be waived. A minimum data set and scientific criteria were defined for this assessment strategy, which includes integration of physiologically based kinetic (PBK) modelling and human‐relevant data. The PPR Panel concludes that this strategy provides a robust basis to support the waiving of dog studies when scientifically justified and supports the implementation of new approach methodologies (NAMs) in the regulatory risk assessment of pesticide active substances.