[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