[Federal Register Volume 61, Number 165 (Friday, August 23, 1996)]
[Rules and Regulations]
[Pages 43447-43450]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-21482]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Parts 182 and 184

[Docket No. 85N-0548]


Direct Food Substances Affirmed as Generally Recognized as Safe; 
High Fructose Corn Syrup

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending its 
regulations for substances that are generally recognized as safe (GRAS) 
to affirm that high fructose corn syrup (HFCS), prepared from high 
dextrose equivalent corn starch hydrolysate by partial enzymatic 
conversion of glucose (dextrose) to fructose utilizing one of several 
glucose isomerase enzyme preparations, is GRAS as a direct human food 
ingredient. This action is in response to six petitions filed by 
members of the food industry.
DATES: Effective August 23, 1996. The Director of the Office of the 
Federal Register approves the incorporation by reference in accordance 
with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain publication in 21 
CFR 184.1866, effective August 23, 1996.

FOR FURTHER INFORMATION CONTACT: James C. Wallwork, Center for Food 
Safety and Applied Nutrition (HFS-217), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204-0001, 202-418-3078.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of February 8, 1983 (48 FR 5716), FDA 
published a document that listed HFCS as GRAS for use in food 
(Sec. 182.1866 (21 CFR 182.1866)) and also affirmed that certain 
insoluble glucose isomerase enzyme preparations are GRAS for use in the 
manufacture of HFCS (Sec. 184.1372 (21 CFR 184.1372)) (hereinafter 
referred to as the 1983 final rule). The agency published this final 
rule in response to six industry petitions that requested GRAS 
affirmation for certain insoluble glucose isomerase enzyme preparations 
used to make HFCS and for the manufactured product itself.
    The basis for listing HFCS in 21 CFR part 182 was that HFCS is made 
with enzyme preparations that FDA has affirmed as GRAS; the saccharide 
composition (glucose to fructose ratio) of HFCS is approximately the 
same as that of honey, invert sugar, and the disaccharide sucrose; and 
the minor components (primarily higher saccharides of glucose) of HFCS 
are also found at similar levels in corn syrup and corn sugar which are 
already on the GRAS list. Therefore, FDA concluded that it was 
appropriate to list HFCS as GRAS for use in food while the agency fully 
evaluated it during the comprehensive safety review of corn sugar, corn 
syrup, invert sugar, and sucrose.
    In the 1983 final rule, the agency gave notice to all interested 
parties that when the agency completed its comprehensive safety review 
of corn sugar (dextrose), corn syrup, invert sugar, and sucrose, it 
would examine the data on these substances to determine whether those 
data provide an adequate basis to affirm that HFCS is GRAS. In the 
Federal Register of November 7, 1988 (53 FR 44862), the agency 
published a final rule affirming that the use of corn sugar, corn 
syrup, invert sugar, and sucrose in food is GRAS.

II. The Safety Review of High Fructose Corn Syrup

    In the Federal Register of November 7, 1988 (53 FR 44904), FDA 
proposed to affirm that the use of HFCS in food is GRAS (hereinafter 
referred to as the 1988 HFCS proposal). Included in the 1988 HFCS 
proposal was the agency's: (1) Evaluation of the data contained in the 
petitions and of their relationship to the safety of HFCS; (2) 
discussion of the relevancy of reports by the Select Committee on GRAS 
Substances of the Federation of American Societies for Experimental 
Biology entitled ``Evaluation of the Health Aspects of Corn Sugar 
(Dextrose), Corn Syrup, and Invert Sugar as Food Ingredients'' (Ref. 1) 
and ``Evaluation of the Health Aspects of Sucrose as a Food 
Ingredient'' (Ref. 2) to the safety assessment of HFCS; and (3) 
discussion of the relevancy of FDA's Sugars Task Force Report 
``Evaluation of the Health Aspects of Sugars Contained in Carbohydrate 
Sweeteners'' (Ref. 3) to the safety evaluation of HFCS.
    The agency made it clear during its safety evaluation of corn 
sugar, corn syrup, invert sugar, and sucrose that its exposure estimate 
for HFCS included exposure to HFCS containing 55 percent fructose 
(HFCS-55) (Ref. 3). Furthermore, FDA noted that most of the components 
found in HFCS

[[Page 43448]]

containing 43 percent fructose (HFCS-43) (approximately equimolar 
mixtures of glucose and fructose; residues from corn syrup; and 
residues from the glucose isomerase enzyme preparations) are also found 
in HFCS-55. Therefore, the agency noted that the safety evaluation of 
the major components in HFCS-43 is also applicable to HFCS-55, and it 
stated that it would consider including HFCS-55 in its rule affirming 
the GRAS status of HFCS if it received, as comments on the 1988 HFCS 
proposal, information on the production of HFCS-55 adequate to allow it 
to identify possible residues from processing materials and to ensure 
that the level of these residues in the final product is safe (53 FR 
44904 at 44907).
    The 1988 HFCS proposal did not include 90 percent fructose (HFCS-
90); however, HFCS-90 is also a commercially available product. This 
product contains a substantially different ratio of glucose to fructose 
than either HFCS-43 or HFCS-55. The HFCS-90 is not included in this 
rulemaking because the agency does not have adequate information to 
assess the safety of residual levels of the processing materials in the 
final product. Moreover, FDA did not include HFCS-90 in the agency's 
exposure estimate for HFCS, even though the agency was aware of minor 
uses of HFCS-90 as an ingredient in low-calorie foods. Finally, FDA's 
report on its safety review of the sugars contained in carbohydrate 
sweeteners did not include HFCS-90 primarily because HFCS-90 does not 
contain approximately equimolar amounts of glucose and fructose (53 FR 
44904 at 44907). Thus, additional data on the effects of fructose 
consumption that is not balanced with glucose consumption would be 
needed to ensure that this product is safe. Because HFCS-90 has not 
been included in this rulemaking, consideration of the GRAS status of 
this substance will need to proceed through the petition process in 
accordance with Sec. 170.35.

III. Comments on the 1988 HFCS Proposal

    The original comment period for the 1988 HFCS proposal ended on 
January 6, 1989. In the Federal Register of January 27, 1989 (54 FR 
4045), in response to requests from two trade associations, FDA 
extended the comment period until April 6, 1989, to allow sufficient 
time for interested persons to respond to the agency's request for 
information on the manufacturing process for HFCS-55. FDA received four 
submissions in response to the 1988 HFCS proposal, each containing one 
or more comments. One submission was from a diabetes research center, 
and the other three were from trade associations. In addition, recently 
a further comment was received from one of the trade associations. This 
comment modified some of the information that the association had 
submitted in its previous comment.
     1. The Diabetes Research Center stated its opinion that the safety 
of HFCS as it relates to diabetics has not been totally established. It 
suggested that the fact that its safety for diabetics had not been 
fully established should be stated somewhere on the product label. The 
comment did not provide any support for its conclusion or for the 
suggested labeling requirement.
    FDA does not agree with this comment. FDA's Sugars Task Force 
stated in its report (Ref. 3) that it could not find any basis in the 
scientific literature to conclude that there was the potential for an 
adverse effect in diabetics from increased fructose consumption. The 
comment did not present any evidence of any developments since the 
publication of the Task Force's report almost 10 years ago that would 
contradict the Task Force's finding.
    In a 1994 review of Nutrition Principles for the Management of 
Diabetes and Related Complications (Ref. 4), sponsored by the American 
Diabetes Association (ADA), a national expert body for diabetes, the 
effects of sucrose, fructose, and other nutritive sweeteners were 
discussed in detail. The fructose used in the studies that were 
discussed in the review was primarily crystalline fructose. HFCS, which 
has a saccharide composition similar to sucrose, was not separately 
considered. The overall findings that emerged from this review (Ref. 5) 
were that ``scientific evidence has shown that the use of sucrose as 
part of the meal plan does not impair blood glucose control in 
individuals with type I or type II diabetes,''and that ``dietary 
fructose produces a smaller rise in plasma glucose than isocaloric 
amounts of sucrose and most starchy carbohydrates.''
    Moreover, the ADA dietary guidelines for diabetics state that 
diabetics may consume a modest amount of sugars as long as metabolic 
control and desirable body weight are maintained (Ref. 5). The 
guidelines do not include a recommendation to avoid any specific 
sweetener because of safety concerns.
    FDA's policy in the case of food ingredients, such as FD&C Yellow 
No. 5 and sulfites, to which subpopulations are allergic or sensitive 
is to rely on the declaration of the presence of the substance in the 
ingredient list, rather than to require a special statement on the 
label. The agency considers that declaration of the ingredient will 
give the sensitive subpopulation an opportunity to avoid the food. 
HFCS, like any other ingredient, will have to be declared on the 
ingredient list when used in food. Thus, even if there were a basis for 
a safety concern about HFCS in diabetics, FDA finds no reason why it is 
not adequate to treat this ingredient like other ingredients of concern 
to particular subpopulations.
    Given the absence of any data supporting a safety concern for HFCS 
in diabetics, the agency finds no rational basis for requiring on 
products that contain this sweetener a label statement that advises 
that the safe use of HFCS by diabetics has not been fully established. 
The agency concludes that there is no evidence to suggest that HFCS is 
any less safe for diabetics than any other commonly used sweetener. 
Based on the foregoing, FDA concludes that no change in Sec. 184.1866 
in response to this comment is warranted.
     2. In three submissions, three trade associations strongly 
endorsed affirming the use of HFCS in food as GRAS. These comments 
asked that the final rule recognize that the item of commerce contains 
42 percent fructose (HFCS-42) on a dry weight basis, and that the 
reference to the 43 percent fructose dry weight product be deleted. The 
comments discussed in detail the manufacturing process for HFCS-55 and 
asked that the final rule be modified to allow manufacturers the 
flexibility to make HFCS-42 and HFCS-55 according to the identity and 
specifications described. Subsequently, one of these trade associations 
submitted a comment that amended its earlier submission regarding the 
identity and specifications for HFCS to read as follows:
    ``High Fructose Corn Syrup is a sweet, nutritive saccharide 
mixture prepared as a clear, aqueous solution from high-dextrose-
equivalent corn starch hydrolysate by the partial enzymatic 
conversion of glucose (dextrose) to fructose, using an insoluble 
glucose isomerase preparation that complies with 21 CFR 184.1372 and 
that has been grown in a pure culture fermentation that produces no 
antibiotics. It is a water-white to light yellow, somewhat viscous 
liquid that darkens at high temperatures. It is miscible in all 
proportions with water. This product has the following requirements:
    Assay, 42 Percent High Fructose Corn Syrup: Not less than 97.0 
percent total saccharides (dry weight), of which not less than 42.0 
percent consists of fructose (dry weight), not less than 92.0 
percent consists of monosaccharides, and not more than 8.0 percent 
(dry weight) of other saccharides. 55 Percent High Fructose Corn 
Syrup: Not less

[[Page 43449]]

than 95.0 percent total saccharides (dry weight), of which not less 
than 55.0 percent consists of fructose (dry weight), not less than 
95.0 percent consists of monosaccharides, and not more than 5.0 
percent (dry weight) of other saccharides. Arsenic (as As), not more 
than 1 milligram per kilogram. Color, within the range specified by 
the vendor. Heavy metals (as Pb), not more than 5 milligrams per 
kilogram. Lead, not more than 0.1 milligram per kilogram. Sulfur 
dioxide, not more than 0.003 percent. Total solids, 42 percent high 
fructose corn syrup: not less than 70.5 percent. 55 Percent high 
fructose corn syrup: not less than 76.5 percent.''
This information is similar to that published in Food Chemicals Codex, 
4th ed., p. 191 (1996), in the monograph entitled ``High-Fructose Corn 
Syrup.''
    FDA has reviewed the comments and acknowledges that the item of 
commerce is HFCS-42. The agency agrees with the identity and 
specifications recommended by the latter comment for HFCS (HFCS-42 or 
HFCS-43). FDA concludes that the identity and specifications that it is 
adopting are adequate to ensure that the public health is protected.
    The agency also has reviewed the comments from the three trade 
associations requesting the inclusion of HFCS-55 in the final rule. FDA 
notes that the comments provided detailed information on the 
manufacture of HFCS-55, including information on processing aids and 
residues of these materials in the final product. In addition, the 
comments provided information on the identity of, and specifications 
for, the HFCS-55 product.
    FDA concludes that the manufacturing process for HFCS-55 does not 
raise any safety concerns, and that the residues of the processing 
materials in this product are safe, because HFCS-55 is prepared from 
HFCS-42 using standard techniques. In addition, as noted earlier in 
this final rule, the agency has determined that the safety evaluation 
of the major components in HFCS-42 is also applicable to HFCS-55. Thus, 
FDA finds that information provided by the comments is sufficient for 
the agency to include HFCS-55 in the final rule. Accordingly FDA has 
modified the final rule to include HFCS-55.
    The agency has also reviewed the identity and specifications 
suggested for HFCS-55 in the comments. FDA concludes that the suggested 
identity and specifications are adequate to ensure that the public 
health will be protected.
    In addition, the agency has determined that because the components 
of HFCS-55 are similar to HFCS-42, and there are no safety concerns 
with these components, there is no need to differentiate between these 
two HFCS's on product labels for consumers.
    3. A comment from a trade association included a recommendation for 
FDA to adopt the Food Chemicals Codex (3d ed., 2d supplement) assay 
requirements for HFCS. The association also pointed out that the Food 
Chemicals Codex has published food grade specifications for HFCS.
    In the 1988 HFCS proposal, the agency stated that it would 
cooperate with the National Academy of Sciences to establish 
specifications for HFCS. The 1988 HFCS proposal also stated that when 
acceptable specifications are developed, the agency will incorporate 
them into the regulation. Recently, however, as stated above, industry 
submitted a comment suggesting new identities and specifications for 
HFCS-42 and HFCS-55 that are similar to those published in the Food 
Chemicals Codex, 4th ed., p. 191 (1996), in the monograph entitled 
``High-Fructose Corn Syrup.'' These identities and specifications, as 
discussed in response to comment 2 of this document, are acceptable to 
the agency and are therefore incorporated by reference.

IV. Conclusion

    Based on the conclusions of the Federation of American Societies 
for Experimental Biology on the safety evaluations of corn sugar, corn 
syrup, invert sugar, and sucrose (Refs. 1 and 2) and of FDA's Task 
Force Report on the health aspects of sugars contained in carbohydrate 
sweeteners (Ref. 3), in the 1988 HFCS proposal, the agency proposed to 
affirm that the use of HFCS in food is GRAS. FDA has considered all the 
comments received on the 1988 HFCS proposal and has found that no 
information has been submitted in response to the proposal that 
warrants a change in FDA's tentative conclusion about the safety of 
HFCS or about whether it is GRAS.
    The agency agrees with comments to the 1988 HFCS proposal that the 
item of commerce is HFCS containing not less than 42 percent fructose. 
Thus, FDA has included HFCS containing not less than 42 percent 
fructose dry weight in the description of the identity of HFCS in the 
final rule. In addition, FDA has incorporated by reference the other 
aspects of the identity and specifications for HFCS-42 that were 
published in the Food Chemicals Codex, 4th ed., p. 191 (1996), in the 
monograph entitled ``High-Fructose Corn Syrup'' and that are similar to 
industry comments to the 1988 HFCS proposal.
    Also, sufficient information was submitted in the comments to 
justify affirming HFCS-55 as GRAS and to provide specifications for 
this substance. Therefore, the agency has included HFCS containing not 
less than 55 percent fructose dry weight in the description of the 
identity of HFCS in the final rule. In addition, FDA has incorporated 
by reference the other aspects of the identity and specifications for 
HFCS-55 that were published in the Food Chemicals Codex, 4th ed., p. 
191 (1996), in the monograph entitled ``High-Fructose Corn Syrup,'' and 
that are similar to industry comments to the 1988 HFCS proposal. 
Furthermore, the agency is including a sentence in the regulation to 
characterize the manufacturing process that converts HFCS-42 to HFCS-
55, i.e., ``The product containing more than 50 percent (dry weight) 
fructose may be prepared through concentration of the fructose portion 
of the mixture containing less than 50 percent fructose.''
    Thus, FDA is including two types of HFCS in this final rule. HFCS-
42 contains at least 42 percent fructose, approximately 50 percent 
glucose, and not more than 8 percent other saccharides. HFCS-55 
contains at least 55 percent fructose, approximately 40 percent 
glucose, and not more than 5 percent other saccharides. HFCS-42 and 
HFCS-55 both contain similar saccharide compositions (glucose to 
fructose ratio) as honey, invert sugar, and the disaccharide sucrose, 
and the minor components (primarily higher saccharides of glucose) of 
HFCS-42 and HFCS-55 are also present at similar levels in corn syrup 
and corn sugar, which FDA has already found to be GRAS.
    FDA has previously considered the environmental effects of this 
rule as announced in the 1988 HFCS proposal. FDA did not receive any 
information or comments that would affect the agency's determination 
that there is no significant impact on the human environment and that 
an environmental impact statement is not required.

V. Analysis of Impacts

    FDA has examined the economic implications of the final rule 
affirming the GRAS status of HFCS, prepared from high dextrose-
equivalent corn starch hydrolysate by partial enzymatic conversion of 
glucose (dextrose) to fructose utilizing one of several glucose 
isomerase enzyme preparations, for use as a direct human food 
ingredient, under Executive Order 12866 and the Regulatory Flexibility 
Act. Executive Order 12866 directs agencies to assess

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all costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). The Regulatory Flexibility Act (Pub. L. 96-354) requires 
analyzing options for small businesses. FDA finds that this final rule 
is not a significant regulatory action as defined by Executive Order 
12866.
    Affirming that the use of HFCS that contains either not less than 
42 percent fructose or not less than 55 percent fructose in food is 
GRAS will expand the formulation possibilities for food manufacturers, 
including small businesses. Therefore, in accordance with the 
Regulatory Flexibility Act, FDA has also determined that this rule will 
have a positive impact on small businesses.
    Because no current activity is prohibited by this final rule, the 
compliance cost to firms is zero. Total costs are also zero because 
there will be no increase in the health risks faced by consumers 
resulting from this final rule. Potential benefits include the wider 
use of these substances to achieve intended technical effects and the 
savings that will result from not having to prepare any new petitions 
to affirm that the use of these substances in food is GRAS.

VI. Effective Date

    As this rule recognizes an exemption from the ``food additive'' 
definition in the Federal Food, Drug, and Cosmetic Act, and from the 
approval requirements applicable to food additives, no delay in 
effective date is required by the Administrative Procedure Act, 5 
U.S.C. 553(d). The rule will therefore be effective immediately (5 
U.S.C. 553(d)(1)).

VII. References

    The following references have been placed on display at the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 12420 
Parklawn Dr., rm. 1-23, Rockville, MD 20857, and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1.-``Evaluation of the Health Aspects of Corn Sugar (Dextrose), 
Corn Syrup, and Invert Sugar as Food Ingredients'' (SCOGS-50), 
Select Committee on GRAS Substances, Life Sciences Research Office, 
Federation of American Societies for Experimental Biology, 1976.
    2.-``Evaluation of the Health Aspects of Sucrose as a Food 
Ingredient'' (SCOGS-69), Select Committee on GRAS Substances, Life 
Sciences Research Office, Federation of American Societies for 
Experimental Biology, 1976.
    3. Glinsmann W. H., H. Irausquin, and Y. K. Park, ``Evaluation 
of Health Aspects of Sugars Contained in Carbohydrate Sweeteners,'' 
Report of Sugars Task Force 1986, Journal of Nutrition, 116(11S):S1-
S216, 1986.
    4. Franz, M. J. et al, ``Nutrition Principles for the Management 
of Diabetes and Related Complications,'' Diabetes Care, 17:490-518, 
1994.
    5. American Diabetes Association, ``Nutrition Recommendations 
and Principles for People with Diabetes Mellitus,'' Diabetes Care, 
17:519-522, 1994.

List of Subjects

21 CFR Part 182

    Food ingredients, Food packaging, Spices and flavorings.

21 CFR Part 184

    Food ingredients, Incorporation by reference.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, parts 182 
and 184 are amended as follows:

PART 182--SUBSTANCES GENERALLY RECOGNIZED AS SAFE

    1. The authority citation for 21 CFR part 182 continues to read as 
follow:

    Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).

Sec. 182.1866  [Removed]

    2. Section 182.1866 High fructose corn syrup is removed from 
subpart B.

PART 184--DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED 
AS SAFE

    3. The authority citation for 21 CFR part 184 continues to read as 
follows:

    Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).
    4. Section 184.1372 is amended by revising paragraph (a) to read as 
follows:


Sec. 184.1372  Insoluble glucose isomerase enzyme preparations.

    (a) Insoluble glucose isomerase enzyme preparations are used in the 
production of high fructose corn syrup described in Sec. 184.1866. They 
are derived from recognized species of precisely classified 
nonpathogenic and nontoxicogenic microorganisms, including Streptomyces 
rubiginosus, Actinoplanes missouriensis, Streptomyces olivaceus, 
Streptomyces olivochromogenes, and Bacillus coagulans, that have been 
grown in a pure culture fermentation that produces no antibiotics. They 
are fixed (rendered insoluble) for batch production with GRAS 
ingredients or may be fixed for further immobilization with either GRAS 
ingredients or materials approved under Sec. 173.357 of this chapter.
 * * * * *
    5. Section 184.1866 is added to subpart B to read as follows:


Sec. 184.1866  High fructose corn syrup.

    (a) High fructose corn syrup, a sweet, nutritive saccharide mixture 
containing either approximately 42 or 55 percent fructose, is prepared 
as a clear aqueous solution from high dextrose-equivalent corn starch 
hydrolysate by partial enzymatic conversion of glucose (dextrose) to 
fructose using an insoluble glucose isomerase enzyme preparation 
described in Sec. 184.1372. The product containing more than 50 percent 
fructose (dry weight) is prepared through concentration of the fructose 
portion of the mixture containing less than 50 percent fructose.
    (b) The ingredient shall conform to the identity and specifications 
listed in the monograph entitled ``High-Fructose Corn Syrup'' in the 
Food Chemicals Codex, 4th ed. (1996), pp. 191-192, which is 
incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR 
part 51. Copies are available from the Office of Premarket Approval, 
Center for Food Safety and Applied Nutrition (HFS-200), Food and Drug 
Administration, 200 C St. SW., Washington, DC 20204-0001, or may be 
examined at the Center for Food Safety and Applied Nutrition's Library, 
200 C St. SW., rm. 3321, Washington, DC, or at the Office of the 
Federal Register, 800 North Capitol St. NW., suite 700, Washington, DC.
    (c) In accordance with Sec. 184.1(b)(1), the ingredient is used in 
food with no limitation other than current good manufacturing practice.

    Dated: August 15, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-21482 Filed 8-22-96; 8:45 am]
BILLING CODE 4160-01-F