Chemical Specific Adjustment Factor: A Shift From Default/Refined Toward Hybrid Uncertainty Publisher



Daghighi SM¹ ; Baeeri M¹ ; Nodeh HR² Show Affiliations
Source: Encyclopedia of Toxicology# Fourth Edition: Volume 1-9 Published:2023

Abstract

For a decade, the chemical-specific adjustment factor has been developed based on the chemical-specific data obtained from the risk assessment of chemicals toxicity. The traditional methodology of evaluating chemical toxicity relied on animal experiments and default uncertainty analysis with particular attention to the interspecies and interindividual differences. The current knowledge about the determination of chemical-specific adjustment factor (CSAF) concerning the uncertainty for chemicals and biological risk assessment has been reviewed. Due to the lack of knowledge in hazard and exposure uncertainty analysis, a refinement process is needed to reduce the default uncertainty to a minimum level. Refinement processes are developing based on a combination of the current CSAF (common structural characteristics, common mode of action, and physiologically based toxicokinetic) and new data (in vitro, in silico, in vivo, clinical, and epidemiological data), resulting in more precise uncertainty analysis and an increased tier of initial data from a lower to a higher level. Thus, the influence of default, refined, and, a combination of both, hybrid uncertainty analysis on the development of CSAF methodology is updated regarding the present state of knowledge. © 2024 Elsevier Inc. All rights reserved.