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Toxicology Requirements

How is the safe intake of an additive determined by FDA?

Mar 2001

Question: How is the safe intake of an additive determined by FDA?

Answer: The level of safe intake of an additive is determined by the lowest ?no-observed effect level? (NOEL) established in the feeding studies. If two subchronic (but not two-year) studies have been conducted, FDA typically divides the lowest NOEL by a factor of 1,000 to yield the ?acceptable daily intake? (ADI), the highest intake level that may be cleared based on the available data. When chronic feeding studies have been conducted, the NOEL is divided by 100 to determine the ADI.

FDA does not determine an ADI based on feeding studies having a duration of less than approximately 90 days, or from genetic toxicity test results; generally, the agency merely determines that intake below 50 ppb is negligible and, thus, that extensive toxicity data are not required to establish safety.

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