Thresholds of toxicological concern - overview of ongoing scientific developments

Abstract

The Concept of the Threshold of Toxicological Concern (TTC) uses the principles of chemical grouping and read-across to screen chemicals at low levels of exposure for prioritization of follow-up testing. The approach incorporates consideration of chemical structure, metabolism, and animal toxicity data to establish chronic exposure thresholds below which there is no appreciable human health risk. The chemical groups and exposure thresholds were originally established based on the analysis by Rulis, Cramer and Munro. The TTC concept has recently been re-evaluated by several expert working groups and acknowledged for some applications by a number of regulatory bodies such as EFSA and JECFA. However, controversy still surrounds the use of the approach due to actual or perceived concerns such as imprecise structural groupings, old or non-validated datasets, impractically low thresholds, the use of 5th percentiles as cut-off. At the same time, safety and risk assessment scientists are striving to identify methods and approaches capable of achieving the vision to Refine, Replace and Reduce animal testing, whilst trying to improve the efficiency and throughput of low tier evaluations. Consequently, several activities have been initiated or performed by different research groups to update the TTC datasets with more, recent and structured data including improved study documentation and dose selection information. Activities on the different levels aiming to expand the chemical domain of the TTC concept and to refine the structural grouping applied will be presented and future research needs discussed