Toxicologists above a certain age will remember the arrival of the Cramer scheme, which enables chemicals to be placed into one of three classes (I, II or III in order of increasing likely toxicity), according to certain structural characteristics. Toxicological threshold of concern (TTC) values have been assigned to each Cramer class, for use in the risk assessment of chemicals of essentially unknown toxicity, with these TTC values representing a level of exposure below which substance-related adverse effects are considered unlikely. Toxtree, a software tool for predicting toxicological effects and mechanisms of action, implements this approach, and it is in the context of Toxtree that a recent JRC paper critically evaluates the Cramer scheme, and gives suggestions for improvement. Key criticisms of the Cramer class system are its age (the scheme is based on what was known in the late 1970s), its lack of power in discriminating between substances of different toxic potential, and the ill-defined nature of Cramer class II, said by JRC to be “of questionable added value”. In the short term, JRC suggests rewriting the Cramer scheme, possibly merging classes II and III into a single “high concern” class. Longer term changes involve either significant rewriting, or complete abandonment in favour of a modernised, purely structure-based classification system. JRC also concludes that, while the TTC values for non-cancer end-points (1800, 540 and 90 µg/person/day for Cramer classes I, II and III, respectively) have been proven to be robust and health-protective, a more extensive toxicity database and an up-to-date classification scheme could be used to derive an alternative set of threshold values.

[Lapenna S. and Worth A. (2011). Analysis of the Cramer classification scheme for oral systemic toxicity – implications for its implementation in Toxtree. Joint Research Centre of the European Commission. Institute for Health and Consumer Protection. JRC Scientific and Technical Reports: EUR 24898 EN – 2011. Electronic gremlins permitting, this report can be accessed by visiting online.] {188483}

The above item was taken from the October 2011 issue of Toxicology and Regulatory News which is sent automatically to members of bibra (click here for more details).

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