[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]


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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.

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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