Generally recognised as safe and effective

Absence of carcinogenity, genotoxicity, developmental and reproductive toxicity and of chronic toxicity effects at low exposure levels are indispensable prerequisites for food additive approvals. All substances approved in the European Union or the USA or deemed generally recognised as safe (GRAS) in the USA fulfil this requirement. 

As enacted in 1938, the FD C Act defined a new drug as any drug that was not generally recognised as safe. Section 505 of the 1938 Act provided that an NDA must be submitted for every new drug, and authorised FDA to permit an NDA to become effective or to disapprove it, but not affirmatively to approve an NDA. If FDA took no action within 60 days after the filing of an NDA, the NDA automatically became effective and the drug could lawfully be marketed. 

The effective but volatile 2,6-di-ferf.butyl-4-methyIphenol (11) was replaced for most applications by various mononuclear (12), binuclear (13), trinuclear (14) and tet-ranuclear phenols (15, 16). Recently, synthetic DL-a-tocopherol (17) was introduced for effective melt stabilization of PO. This antioxidant may be listed among the stabilizers generally recognised as safe (GRAS). 

The Congress described the term safety as reasonable certainty that no harm will result from the proposed use of an additive , recognising that it is not possible to prove that no harm will result under any conceivable circumstances. However, it was generally interpreted to mean that if an additive is safe, there is no risk associated with it. Accordingly, the amendment directed FDA to consider consumption patterns, the cumulative effect of the ingredient in the diet of man or animals, and appropriate safety factors. 

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