[Federal Register Volume 62, Number 131 (Wednesday, July 9, 1997)]
[Proposed Rules]
[Pages 36749-36752]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-17797]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 101
[Docket No. 97P-0206]
Food Labeling: Health Claims; Dietary Sugar Alcohols and Dental
Caries
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the regulation that authorized a health claim on sugar alcohols and
dental caries to include the sugar alcohol erythritol. FDA is proposing
this action in response to a petition filed by the Cerestar Holding
B.V., Mitsubishi Chemical Corp., and Nikken Chemicals Co. The agency
has tentatively concluded that, based on the totality of publicly
available scientific evidence presented in the petition, erythritol
does not promote dental caries. Therefore, FDA is proposing to amend
the sugar alcohol and dental caries health claim to include erythritol.
DATES: Written comments by September 22, 1997. The agency is proposing
that any final rule that may issue based upon this proposal become
effective upon its publication in the Federal Register.
ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: Joyce J. Saltsman, Center for Food
Safety and Applied Nutrition (HFS-165), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-205-5483.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of August 23, 1996 (61 FR 43433), the
agency adopted a final rule to authorize the use, on food labels and in
food labeling, of health claims on the association between sugar
alcohols and dental caries (hereinafter referred to as the sugar
alcohol final rule) (Sec. 101.80 (21 CFR 101.80)). FDA adopted this
regulation in response to a petition filed under section
403(r)(3)(B)(i) of the Federal Food, Drug, and Cosmetic Act (the act)
(21 U.S.C. 343(r)(3)(B)(i)). Section 403(r)(3)(B)(i) of the act states
that the Secretary of Health and Human Services (and, by delegation,
FDA) shall issue regulations authorizing health claims only if he or
she determines, based on the totality of publicly available scientific
evidence (including evidence from well-designed studies conducted in a
manner which is consistent with generally recognized scientific
procedures and principles), that there is significant scientific
agreement, among experts qualified by scientific training and
experience to evaluate such claims, that the claim is supported by such
evidence (see also Sec. 101.14(c) (21 CFR 101.14(c))).
The sugar alcohol final rule sets out the circumstances in which a
sugar alcohol is eligible to be the subject of a health claim
(Sec. 101.80(c)(2)(ii)). Section 101.80(c)(2)(ii)(A) states that the
food must meet the requirement for a sugar free food defined in 21 CFR
101.60(c)(1)(i). Section 101.80(c)(2)(ii)(B) lists the sugar alcohols
that are eligible to bear the claim, xylitol, sorbitol, mannitol,
maltitol, isomalt, lactitol, hydrogenated starch hydrolysates,
hydrogenated glucose syrups, or a combination of these. Section
101.80(c)(2)(ii)(C) states that:
[W]hen fermentable carbohydrates are present in the sugar
alcohol-containing food, the food shall not lower plaque pH below
5.7 by bacterial fermentation either during consumption, or up to 30
minutes after consumption as measured by the indwelling plaque pH
test found in ``Identification of Low Caries Risk Dietary
Components,'' * * * which is incorporated by reference * * *.
In the sugar alcohol final rule, the agency stated that for other
sugar alcohols to be included in Sec. 101.80(c)(2)(ii)(B), a petitioner
must show how the substance conforms to the requirements of
Secs. 101.14(b) and 101.80 (61 FR 43433 at 43442). FDA stated:
For those substances that are to be consumed at other than
decreased dietary levels, the petitioner must demonstrate to FDA's
satisfaction that the substance is safe and lawful under the
applicable food safety provisions of the act
(Sec. 101.14(b)(3)(ii)). Likewise, the petitioner would need to
provide evidence that the sugar alcohol will not lower plaque pH
below 5.7. Therefore, before a claim can be made for a new sugar
alcohol, it must be shown to meet the requirements for Sec. 101.80.
When this is demonstrated, FDA will take action to add the substance
to the list in this regulation, which has been renumbered as
Sec. 101.80(c)(2)(ii)(B).
The present rulemaking is in response to a petition to amend
Sec. 101.80(c)(2)(ii)(B) to include erythritol as one of the sugar
alcohols that is eligible to bear the sugar alcohol and dental caries
health claim.
II. Petition for Health Claim on Erythritol and the Nonpromotion of
Dental Caries
A. The Petition
On April 4, 1997, the petitioners submitted a petition to FDA
requesting that the agency amend Sec. 101.80(c)(2)(ii)(B) to authorize
a claim to authorize a noncariogenicity dental health claim for the
sugar alcohol erythritol. On May 16, 1997, the agency sent the
petitioner a letter stating that it had completed its initial review of
the petition, and that the petition would be filed in accordance with
section 403(r)(4) of the act (see Docket 97P-0206, Letter 1). The
following is a review of the health claim petition and of whether
erythritol satisfies the requirements of Secs. 101.80(c)(2)(ii) and
101.14(b) and (c) of FDA's regulations.
B. Preliminary Requirements
1. The Substance That Is the Subject of the Petition
Erythritol is a 4-carbon, monosaccharide polyhydric alcohol. It
occurs naturally in a wide variety of plants (e.g., watermelons,
melons, grapes, and mushrooms) and animals (e.g., humans, dogs, and
cows). Erythritol is also a product of the fermentation by yeasts and
molds of sugars (Ref. 1, p. 27).
2. The Substance Is Associated With a Disease for Which the U.S.
Population Is at Risk
In the preamble to the proposed sugar alcohol and dental caries
rule (60 FR 37507 at 37509, July 20, 1995) and in the regulation
authorizing the claim on sugar alcohols and dental caries
(Sec. 101.80(a)(3)), FDA established that dental caries is a disease
for which the U.S. population is at risk. The agency stated:
Dental caries is recognized in The Surgeon General's Report on
Nutrition and Health * * * as a disease or health-related condition
for which the United States population is at risk * * *. The overall
prevalence of dental caries imposes a substantial burden on
Americans. Of the 13 leading health
[[Page 36750]]
problems in the United States, dental diseases rank second in direct
costs * * *.
Dental caries continues to affect a large proportion of
Americans. Although there has been a decline in the prevalence of
dental caries among children in the United States, the disease
remains widespread throughout the population * * *.
Based on these facts, FDA concludes that, as required in
Sec. 101.14(b)(1), dental caries is a disease for which the U.S.
population is at risk.
3. The Substance Is a Food
In the preamble to the sugar alcohols proposed rule (60 FR 37507 at
37509) and in the final regulation itself (Sec. 101.80(a)(4)), the
agency states that sugar alcohols can be used as sweeteners to replace
dietary sugars, such as sucrose and corn sweeteners, in foods such as
chewing gums and certain confectioneries. Therefore, FDA concludes that
erythritol satisfies the preliminary requirement in
Sec. 101.14(b)(3)(i).
4. The Substance Is Safe and Lawful
The petitioner has submitted a petition requesting that FDA affirm
that the use of erythritol is generally recognized as safe (GRAS) (62
FR 10285, March 6, 1997). The agency notes that this GRAS affirmation
petition (GRASP 7G0422) is still under review, and that authorization
of a health claim should not be interpreted as affirmation that the
proposed uses of erythritol are GRAS. Such a determination can be made
only after the agency has completed its review of the GRAS petition. A
preliminary review of the GRAS affirmation petition, however, reveals
that it contains significant evidence supporting the safety of the use
of this substance at the levels necessary to justify a health claim.
In the GRAS affirmation petition, the petitioner relied heavily on
published animal subchronic and chronic toxicity studies and
reproduction studies (GRASP 7G0422, App. IV: C4, C12, D5, D7, D8, D17,
D20, D27, and D30), on human toleration and absorption studies (GRASP
7G0422, App. IV: C9, C19, C27, E2, E6, E8, and E11), and on the
conclusions about the safety of erythritol by a panel of independent
experts qualified by scientific training and experience to evaluate the
safety of foods. The panel of independent scientists based their
conclusions on their review of various published and unpublished
scientific studies which included animal toxicological studies and
clinical studies. In their report entitled, ``Erythritol: A Review of
Biological and Toxicological Studies'' (GRASP 7G0422, App. I-1), the
panel concluded that:
The large body of published data supports the conclusion that
the intake of erythritol would not be expected to cause adverse
effects in humans under the conditions of use in food and that other
qualified food safety experts would agree that erythritol is
generally recognized as safe (GRAS) under the conditions of its
intended use in food.
The petitioner also asserted that erythritol occurs endogenously
and naturally in the diet, and that it has a history of safe use in
foods. The petitioner further argued that the safety of erythritol is
supported by its chemical structure, i.e., it is positioned in the
homologous series of sugar alcohols, between glycerol and xylitol, a
series that also includes other common food ingredients such as
sorbitol and mannitol.
Based on the totality of the evidence, the agency is not prepared,
at this time, to take issue with the petitioner's view that the use of
erythritol is safe and lawful. Therefore, FDA tentatively concludes
that the petitioner has provided evidence that satisfies the
requirement in Sec. 101.14(b)(3)(ii) that use of erythritol at the
levels necessary to justify a claim is safe and lawful.
III. Review of Scientific Evidence
The petitioner submitted two scientific studies evaluating the
relationship between erythritol and dental caries: A human study and an
animal study that included an in vitro evaluation.
The human study included an interdental plaque pH telemetry test,
one of the methods described in the text entitled ``Identification of
Low Caries Risk Dietary Components,'' which the agency incorporated by
reference in the sugar alcohol regulation (see
Sec. 101.80(c)(2)(ii)(C)). The test was conducted at the Bioelectronic
Unit of the Clinic of Preventive Dentistry, Periodontology, and
Cariology of the University Dental Institute of Zurich, Switzerland
(Ref. 1, Appendix B-2).
For this test, each subject had a mandibular telemetric prosthesis
incorporating a miniaturized glass pH-electrode placed directly
opposite the interproximal area of an adjacent abutment tooth. Once the
prosthesis was inserted into the subject's mouth, the subject was asked
not to alter his or her eating habits. The prostheses were worn
throughout the 3-to 4-day test period to allow an undisturbed growth of
interdental plaque over the tips of the electrodes. With the exception
of water rinses, the subjects were also asked to refrain from all oral
hygiene measures.
At the end of the 3-to 4-day plaque buildup period, the interdental
plaque pH telemetry test was conducted. Baseline plaque pH was measured
over a 15-minute period after the subjects chewed a piece of paraffin
for 3 minutes. The subjects then sucked on the sugar-free throat
lozenge containing erythritol, followed by plaque pH measurements over
a 30-minute period. The same test procedure was then repeated using a
10-percent sucrose rinse as the control substance in place of the
erythritol lozenge.
The results of this test showed that after the first paraffin chew,
baseline plaque pH measured between 6.9 to 7.0, values that were
similar to earlier tests with the same subjects and plaque ages (Ref.
1, Appendix B-2). Following consumption of erythritol, plaque pH
measured 6.0 to 6.65. The sucrose rinse caused plaque pH to drop to a
range of 4.25 to 4.9, levels that were significantly lower than pH of
plaque during the erythritol period and well below the critical pH
value of 5.7, the level at which demineralization of enamel occurs. The
key finding for this proceeding is that there were no significant
differences in plaque pH between the paraffin and erythritol periods.
Kawanabe and coworkers evaluated the cariogenicity of erythritol in
vitro and in pathogen-free rats (Ref. 1, Appendix B-3). The authors
used microorganisms of various Streptococcus, Lactobacillus, and
Actinomyces species to determine whether the organisms could use
erythritol as a substrate for lactic acid production and plaque
formation. The results of this study showed that erythritol was not
utilized as a substrate for lactic acid production or for plaque
formation by Streptococcus mutans or certain other oral microorganisms.
In the animal study, the rats were randomly divided into six
groups. Three groups of animals were fed modified diets for 5 days.
These diets contained either starch alone, with no sugars or sugar
alcohol; starch plus sucrose; or starch plus erythritol. Then the
animals were infected with Streptococcus sobrinus, after which they
continued to consume the modified diet for an additional 50 days. In a
similar experiment, the other three groups of animals were fed diets
that contained starch chocolate; sucrose chocolate, or erythritol
chocolate, and the animals were infected with Streptococcus mutans.
Mandibular caries scores were determined at 70 days of age in all
groups.
The results of this study showed that the group fed starch plus
erythritol experienced significantly fewer caries compared to the
starch and starch plus sucrose groups. The total caries scores for
groups fed diets of starch, starch
[[Page 36751]]
plus sucrose, and starch plus erythritol were 12.5, 60.5, and 3.1,
respectively. Similarly, the group consuming erythritol chocolate
experienced significantly fewer caries compared to the starch chocolate
and sucrose chocolate groups. The caries scores for the starch
chocolate, sucrose chocolate, and erythritol chocolate groups were
18.5, 82.8, and 6.7, respectively. There were no significant
differences in the body weights of the rats between groups.
The authors stated that, although the group fed starch usually
experienced the least dental caries, the caries score for the group fed
starch was significantly higher than that of the group fed starch plus
erythritol. The same trend was reported in the animals consuming the
chocolate diets. The authors suggested that the cariogenicity of starch
in these experiments may be explained by the contamination of mono- and
disaccharides. The main conclusion from this study is that erythritol
did not induce dental caries.
IV. Decision to Propose a Health Claim Relating Erythritol to the
Nonpromotion of Dental Caries
The petition set out the results of an indwelling plaque pH test
and the results of an in vitro and animal study that evaluated the
cariogenicity of erythritol. FDA reviewed this information and has
tentatively concluded that there is significant scientific evidence to
demonstrate that erythritol does not promote dental caries. The results
of the plaque pH test clearly demonstrate that erythritol does not
lower plaque pH below 5.7, and that, therefore, it does not promote the
demineralization of dental enamel. The results of the in vitro and
animal study are consistent with the results of the indwelling plaque
pH study and show that erythritol does not support the growth of oral
microorganisms responsible for producing the acid in plaque and has
little to no cariogenic potential. The results of these studies are
consistent with the results of the studies that investigated the
cariogenic potential of the sugar alcohols listed in
Sec. 101.80(c)(2)(ii)(B). Therefore, FDA tentatively finds that
erythritol has satisfied the requirements set forth in Secs. 101.14(d)
and 101.80, and the agency is proposing to add erythritol to the list
of eligible sugar alcohols.
V. Description of Modifications to Sec. 101.80
Section 101.80(c)(2)(ii)(B) lists the sugar alcohols that are
eligible to be the subject of a dental claim. FDA is proposing to amend
Sec. 101.80(c)(2)(ii)(B) to state ``[T]he sugar alcohol in the food
shall be xylitol, sorbitol, mannitol, maltitol, isomalt, lactitol,
hydrogenated starch hydrolysates, hydrogenated glucose syrups,
erythritol, or a combination of these.''
The agency is not specifying a level of erythritol in the food
product because, like the other sugar alcohols, erythritol is being
used as a substitute for sugars. Therefore, the amount of the substance
required is that needed to achieve a desired level of sweetness.
VI. Environmental Impact
The agency has determined under 21 CFR 25.24(a)(11) that this
action is of a type that does not individually or cumulatively have a
significant effect on the human environment. Therefore, neither an
environmental assessment nor an environmental impact statement is
required. This finding is based on information submitted by the
petitioner in an environmental assessment prepared using the format
described in 21 CFR 25.31a(b)(5).
VII. Analysis of Impacts
FDA has examined the economic implications of the proposed rule as
required by Executive Order 12866 and the Regulatory Flexibility Act (5
U.S.C. 601-612). Executive Order 12866 directs agencies to assess all
costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select the regulatory approach that
maximizes net benefits (including potential economic, environmental,
public health and safety effects; distributive impacts; and equity).
Executive Order 12866 classifies a rule as significant if it meets any
one of a number of specified conditions, including having an annual
effect on the economy of $100 million or adversely affecting in a
material way a sector of the economy, competition, or jobs, or if it
raises novel legal or policy issues. If a rule has a significant
economic impact on a substantial number of small entities, the
Regulatory Flexibility Act requires agencies to analyze regulatory
options that would minimize the economic impact of that rule on small
entities. FDA finds that this proposed rule is not a significant rule
as defined by Executive Order 12866 and finds under the Regulatory
Flexibility Act that the proposed rule will not have a significant
impact on a substantial number of small entities.
The establishment of this health claim results in benefits and in
costs only to the extent that food manufacturers elect to take
advantage of the opportunity to use the claim. This rule will not
require that any labels be redesigned, or that any product be
reformulated.
Some manufacturers are using FDA's approved health claim regarding
the benefits of sugar alcohols. This proposed health claim will allow
them to highlight the effects of another sugar alcohol, erythritol. The
benefit of establishing this health claim is to provide for new
information in the market regarding the relationship of erythritol and
dental caries, and to provide consumers with the assurance that this
information is truthful, not misleading, and scientifically valid.
Costs will be incurred by small entities only if they opt to take
advantage of the marketing opportunity presented by this regulation.
FDA cannot predict the number of small entities that will choose to use
the claim. However, no firm, including small entities, will choose to
bear the cost of redesigning labels unless they believe that the claim
will result in increased sales of their product. Therefore, this rule
will not result in either a decrease in revenues or a significant
increase in costs to any small entity. Accordingly, under the
Regulatory Flexibility Act, 5 U.S.C. 605(b), the agency certifies that
this proposed rule will not have a significant economic impact on a
substantial number of small entities.
VIII. Paperwork Reduction Act
FDA tentatively concludes that this proposed rule contains no
reporting, recordkeeping, labeling, or other third party disclosure
requirement. Thus, there is no ``information collection'' necessitating
clearance by the Office of Management and Budget. However, to ensure
the accuracy of this tentative conclusion, FDA is seeking comment on
whether this proposed rule to permit health claims on the association
between erythritol and the noncariogenicity of dental caries imposes
any paperwork burden.
IX. Effective Date
FDA is proposing to make these regulations effective upon
publication of a final rule based on this proposal.
X. Comments
Interested persons may, on or before September 22, 1997, submit to
the Dockets Management Branch (address above) written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday.
[[Page 36752]]
XI. Reference
The following reference has been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Cerestar Holding B. V., Mitsubishi Chemical Corp., and Nikken
Chemicals Co., ``Petition to amend the regulation for 21 CFR
Sec. 101.80 to authorize a noncariogenicity dental health claim for
the sugar alcohol erythritol (1,2,3,4-butanetetrol),'' April 4, 1997
[CP1].
List of Subjects in 21 CFR Part 101
Food and Drug Administration, Food labeling, Nutrition, Reporting
and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 101 be amended as follows:
PART 101--FOOD LABELING
1. The authority citation for 21 CFR part 101 continues to read as
follows:
Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342,
343, 348, 371).
2. Section 101.80 is amended by revising paragraph (c)(2)(ii)(B) to
read as follows:
Sec. 101.80 Health claims: dietary sugar alcohols and dental caries.
* * * * *
(c) * * *
(2) * * *
(ii) * * *
(B) The sugar alcohol in the food shall be xylitol, sorbitol,
mannitol, maltitol, isomalt, lactitol, hydrogenated starch
hydrolysates, hydrogenated glucose syrups, erythritol, or a combination
of these.
* * * * *
Dated: June 17, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-17797 Filed 7-8-97; 8:45 am]
BILLING CODE 4160-01-F
