Principles and key elements of the evidence base formation within assessment and classification of hazards posed by chemical substances

The demand for creating an evidence base in preventive toxicology is caused by the necessity to implement the criteria for assessing the hazard of chemical substances and mixtures for all types of exposure in the states of the Eurasian Economic Union. This should be done in accordance with the Globally Harmonized System of Classification and Labelling of Chemicals. The aim of this study is to develop a scientifically substantiated unified action algorithm for creating an evidence base of the accepted assessments based on an integrated approach and transparency. We analyzed international approaches to evidence base formation in toxicology by the WHO, the OECD, the European Union, as well as national methodological documents on assessment and classification of hazards posed by mutagens, endocrine disruptors, reprotoxicants, and skin and respiratory sensitizers. The weight of evidence was ranked based on the Klimish approach. A unified decision-making algorithm has been developed and scientifically substantiated. It is a formalized scheme for systematic assessment of a set of evidence (both confirming and refuting the presence of an effect), taking their weight into account. The algorithm is based on key criteria: reliability, consistency, biological plausibility, dose-response relationship, and the comparability of animal studies with potential human health effects. The weight of evidence is assessed using a three-point scale based on the Klimisch approach. Priority is given to data with the lowest number of points, which helps increase objectivity and transparency in assessment and classification of chemical hazards. The proposed algorithm will contribute to improving the quality, reliability, and transparency of toxicological research, as well as the effectiveness and efficiency of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing ensuring sanitary and epidemiological welfare.