Threshold approaches to safety assessment

Begimiing in the 1980s, Flamm et al. (1987) and Rulis (1989) documented FDA s exploration of the use of large databases of toxicity data to address very low exposures to components of food contact materials more efficiently. Flamm et al. (1987) performed a probabilistic analysis of carcinogenic potency data in an attempt to discern a dietary level below which no specific toxicity testing data should be considered prerequisite to judge the safety of a compound used in a food contact material. 

FDA s threshold of 1.5 fig/p/d is an example of the threshold of toxicological concern approach. Below this threshold level of consumer exposure, FDA does not consider specific testing necessary to identify compounds with significant carcinogenic potential. This threshold of regulation is not meant to be a level below which no chemicals could be harmful. FDA s threshold 

Just as a threshold level can be set to address the toxicological concern for carcinogenic risk, other threshold levels for toxicity testing may be established in order to address the likelihood of other toxicological risks. Kroes proposed multiple thresholds of toxicological concern based on Munro s structural 

Collectively, the work by Mimro et al. (1996) and Kroes et al. (2000, 2004) proposed several thresholds of toxicological concern based on toxicological and structural classifications. Table 7.2 summarizes these thresholds, which are cumulative as dietary concentrations increase. These thresholds are based on the analysis of compounds grouped using the so-called Cramer decision tree and on the structural analysis of compounds testing positive for specific toxic endpoints. Maintenance of such a system depends upon maintenance of the decision tree and the ability to continue to discern relationships between toxicity effects and structural information and to then translate those relationships into a decision tree. 

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