Toxicology databases and the concept of thresholds of toxicological concern as used by the JECFA for the safety evaluation of flavouring agents.
Since 1996 the FAO/WHO Joint Expert Committee on Food Additives (JECFA) has evaluated the safety of 1259 flavouring substances, based on a decision tree that incorporates a series of thresholds of toxicological concern. Safety conclusions are based on the predicted consequences of metabolism and whether the estimated intake is above or below a threshold of toxicological concern that is relevant to that compound. Compounds are allocated to one of three structural classes, and the intake compared with a threshold of toxicological concern derived using data from chronic and sub-chronic toxicity studies on compounds in the same structural class. If the substance is predicted to be metabolised to innocuous products there is no safety concern if the intake is below the threshold, but suitable toxicity data on the compound or structural analogues are required if the intake exceeds the threshold. If the substance is not predicted to be metabolised to innocuous products, and the intake is below the appropriate threshold, safety evaluation is based on data on the compound or structural analogues. An additional threshold of 1.5 microg per day, derived from doses of investigated chemicals giving a calculated cancer risk of one in a million, is applied when appropriate toxicity data are not available.
Renwick
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AG
Clinical Pharmacology Group, Allergy and Inflammatory Sciences Research Division, School of Medicine, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK. agr@soton.ac.uk
D000818:Animals; D016208:Databases, Factual; D003663:Decision Trees; D004032:Diet; D005421:Flavoring Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D013329:Structure-Activity Relationship; D014116:Toxicology / Q000295:instrumentation*; D014944:World Health Organization
D005421:Flavoring Agents