In the application of the Threshold of Toxicological Concern (TTC) concept to non-cancer endpoints, the decision tree proposed by Cramer, Ford and Hall in 1978, commonly referred to as the Cramer scheme, is probably the most widely used approach for classifying and ranking chemicals according to their expected level of oral systemic toxicity. The decision tree categorises chemicals, mainly on the basis of chemical structure and reactivity, into three classes indicating a high (Class III), medium (Class II) or low (Class I) level of concern. Each Cramer class is associated with a specified human exposure level, below which chemicals are considered to present a negligible risk to human health. In the absence of experimental hazard data, these exposure threshold (TTC) values have formed the basis of priority setting in the risk assessment process. To facilitate the application of the TTC approach, the original Cramer scheme, and an extended version, have been implemented in Toxtree, a freely available software tool for predicting toxicological effects and mechanisms of action. Building on previous work by Patlewicz and coworkers, this report provides some suggestions for improving the Cramer scheme based on a review of the scientific literature, a survey of Toxtree users, and an analysis of lists of body and food components incorporated in Toxtree.JRC.DG.I.6-Systems toxicolog
