U.S. Food & Drug Administration
Center for Food Safety & Applied Nutrition
Office of Premarket Approval
1983; Updated 1997
(Effective June 18, 2001, Office of Premarket Approval is now Office of Food Additive Safety. See updated contact information)

Safety evaluation for a food additive involves assigning the additive to a concern level based on information on the additive's structural configuration and an estimation of exposure. This document has been prepared to recommend the minimum toxicity tests to be performed for safety evaluation of indirect and direct additives based on levels of concern.

Toxicological Testing of Food Additives

This document was reformatted in 1997. No substantive changes have been made.


Indirect Food Additives:

Virtually nil exposure
( < 0.05ppm):
A
Insignificant exposure
( > 0.05ppm):
A*** C I* K**
E J*
Significant exposure
( > ~ 1ppm):
A*** D*** F G
H I J* K**
L**
 
Direct Food Additives:
(Concern levels are listed below)

Concern Level I:
B K
Concern Level II:
A*** D E I
J* K
Concern Level III:
A*** D*** F G
H I J* K
L**
* if indicated by available data or information
** suggested
*** if needed as preliminary to further study


If carcinogenicity is suspected as a problem, carcinogenicity studies will be done no matter what the circumstances.

Key to Toxicological Studies

A. Acute oral study--rodent

B. Short-term feeding study (at least 28 days)--rodent

C. Subchronic feeding study (90-day)--rodent with in-utero exposure

D. Subchronic feeding study (90-day)--rodent

E. Subchronic feeding study (90-day)--non-rodent

F. Lifetime feeding study (ca 2-year)--rodent with in-utero exposure for carcinogenesis and chronic toxicity

G. Lifetime feeding study (ca 2-year)--rodent for carcinogenesis

H. Short-term feeding study (at least 1 year)--non-rodent

I. Multigenerational reproduction feeding study (minimum of 2 generations) with teratology phase--rodent

J. Teratology study

K. Short-term tests for carcinogenic potential

L. Metabolism studies

References to current guides on these toxicology studies are contained in the "Redbook"



CONCERN LEVEL from EXPOSURE AND STRUCTURE
for Direct Food Additives

Degree of Concern


HIGHER

|

LOWER

Structure C


C.L.* III

0.25 ppm**


C.L. II

0.0125 ppm


C.L. I

Structure B


C.L. III

0.5 ppm


C.L. II

0.025 ppm


C.L. I

Structure A


C.L. III

1.0 ppm


C.L. II

0.05 ppm


C.L. I

* C.L. = Concern Level
** ppm = parts per million dietary


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