Question: What types of toxicity data must be submitted?
Answer: Where the cumulative estimated dietary intake:
- Is below 0.5 ppb? - no toxicity data need be generated, but all relevant known toxicity data available must be submitted;
- Is between 0.5 ppb and 50 ppb? - two genotoxicity studies (a bacterial mutagenicity assay plus an in vitro cytogenetic damage or mouse lymphoma assay) must be submitted;
- Exceeds 50 ppb but is below 1 ppm? - a third genotoxicity study (in addition to the two noted above) in the form of an in vivo chromosomal aberration study is recommended, as well as two subchronic studies (two different species) are required for these exposures;
- Is in excess of 1 ppm? - a full range of toxicity studies is generally required, including chronic (two-year) toxicity/carcinogenicity studies in rats and mice, a one-year feeding study in dogs, and multigeneration reproductive studies in rats.
Where cumulative dietary exposure exceeds this 1 ppm level, FDA may request the filing of a Food Additive Petition instead of an FCN. |