A tiered approach to threshold of regulation.
This paper presents methods for extending the principle of a single "threshold of regulation" to a range of dietary concentrations between 0.5 and 15 parts per billion by using structure-activity relationships, genotoxicity, and short-term toxicity data. The database used to develop the FDA's threshold of regulation was examined to determine whether structural parameters or the result of certain short-term toxicity tests could be used to define a subset of less potent substances that supports higher threshold levels. In addition, results of reproductive toxicity tests for 3306 compounds and other multidose toxicity tests for 2542 compounds were compared with the database of carcinogenic potencies to establish that carcinogenic endpoints are the most conservative toxicity endpoint for establishing thresholds of regulation.
Food and Drug Administration, Center for Food Safety and Applied Nutrition, Washington, DC 20204, USA.
M A
MA
Cheeseman
E J
EJ
Machuga
A B
AB
Bailey
D000818:Animals; D004032:Diet; D006801:Humans; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000235:genetics; D013329:Structure-Activity Relationship; D018675:Toxicity Tests; D014481:United States; D014486:United States Food and Drug Administration