GRAS determination scientific procedures and possible alternatives

Regul Toxicol Pharmacol. 2016 Aug;79 Suppl 2:S105-11. doi: 10.1016/j.yrtph.2016.06.015. Epub 2016 Jun 18.


The use of a food substance is Generally Recognized as Safe (GRAS) through scientific procedures or experience based on common use in food. The pivotal data used for GRAS determination must be of common knowledge and should include evidence for safety under the conditions of intended use of the substance. Such evidence includes data on the identity and specifications of the substance, its properties of absorption, distribution, metabolism and excretion, and depending on the level of concern, data on genotoxicity, acute and subchronic toxicity, reproductive and developmental toxicity and carcinogenicity. Several alternative procedures can be used as the replacement for standard scientific procedures in order to improve the GRAS process.

Keywords: Accelerated carcinogenicity bioassay(ACB); Alternatives; Carcinogenicity; GRAS determination scientific procedures; Generally Recognized as Safe (GRAS); In Ovo assay; Safety; Scientific procedures; Toxicity.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenicity Tests
  • Consumer Product Safety* / legislation & jurisprudence
  • Consumer Product Safety* / standards
  • Dose-Response Relationship, Drug
  • Food Additives / adverse effects*
  • Food Additives / standards
  • Food Industry / legislation & jurisprudence
  • Food Industry / methods*
  • Food Industry / standards
  • Food Safety / methods*
  • Government Regulation
  • Health Policy
  • Humans
  • Nutritive Value
  • Policy Making
  • Recommended Dietary Allowances
  • Risk Assessment
  • Toxicity Tests / methods*
  • United States
  • United States Food and Drug Administration


  • Food Additives