[Federal Register Volume 70, Number 92 (Friday, May 13, 2005)]
[Proposed Rules]
[Pages 25496-25502]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-9608]


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Proposed Rules
                                                Federal Register
________________________________________________________________________

This section of the FEDERAL REGISTER contains notices to the public of 
the proposed issuance of rules and regulations. The purpose of these 
notices is to give interested persons an opportunity to participate in 
the rule making prior to the adoption of the final rules.

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Federal Register / Vol. 70, No. 92 / Friday, May 13, 2005 / Proposed 
Rules

[[Page 25496]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 101

[Docket No. 2004P-0294]


Food Labeling; Health Claims; Dietary Noncariogenic Carbohydrate 
Sweeteners 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 authorizing a health claim on noncariogenic carbohydrate 
sweeteners and dental caries, i.e., tooth decay, to include sucralose, 
a nonnutritive sweetener. Similar to the sweeteners currently 
authorized to make a health claim, sucralose is used as a sugar 
substitute that is minimally fermented, relative to sugar, by oral 
microorganisms and thus does not contribute to production of organic 
acids by plaque bacteria as do the fermentable sugars for which it is a 
substitute. FDA is taking this action in response to a health claim 
petition filed by McNeil Nutritionals. The agency previously concluded 
that there was significant scientific agreement for the relationship 
between slowly fermented carbohydrate sugar substitutes, specifically 
certain sugar alcohols, and the nonpromotion of dental caries. Based on 
the totality of publicly available scientific evidence, FDA now has 
determined that the nonnutritive sweetener sucralose, like the sugar 
alcohols, is not fermented by oral bacteria to an extent sufficient to 
lower dental plaque pH to levels that would contribute to the erosion 
of dental enamel. Therefore, FDA has concluded that sucralose does not 
promote dental caries, and it is proposing to amend the regulation 
authorizing a health claim relating certain noncariogenic sweeteners 
and nonpromotion of dental caries to include sucralose as a substance 
eligible for the claim.

DATES: Submit written or electronic comments by July 27, 2005. See 
section XII of this document for the proposed effective date of a final 
rule based on this document.

ADDRESSES: You may submit comments, identified by the Docket Number 
2004P-0294, by any of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
     E-mail: [email protected]. Include Docket No. 2004P-
0294 and/or RIN number ------ in the subject line of your e-mail 
message.
     FAX: 301-827-6870
     Mail/Hand delivery/Courier [for paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket Number or Regulatory Information Number (RIN) for this 
rulemaking. All comments received will be posted without change to 
http://www.fda.gov/ohrms/dockets/default.htm, including any personal 
information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow prompts and/or go to the 
Division of Dockets Management, 5630 Fishers Lane, room 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: James E. Hoadley, Center for Food 
Safety and Applied Nutrition (HFS-830), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 301-436-1450.

SUPPLEMENTARY INFORMATION:

I. Background

    The Nutrition Labeling and Education Act of 1990 (the 1990 
amendments) (Public Law 101-535) amended the Federal Food, Drug, and 
Cosmetic Act (the act) in a number of important respects. One aspect of 
the 1990 amendments was that they clarified FDA's authority to regulate 
health claims on food labels and in food labeling.
    FDA issued several new regulations in 1993 that implemented the 
health claim provisions of the 1990 amendments. Among these were Sec.  
101.14 Health claims: general requirements (21 CFR 101.14) (58 FR 2478, 
January 6, 1993) and Sec.  101.70 Petitions for health claims (21 CFR 
101.70) (58 FR 2478), which established a process for petitioning the 
agency to authorize health claims about substance-disease relationships 
and set out the types of information that a health claim petition must 
include. These regulations became effective on May 8, 1993.
    The final rule that established Sec.  101.80 (21 CFR 101.80) (61 FR 
43433, August 23, 1996), relating sugar alcohols to the nonpromotion of 
dental caries (the dental caries health claim), completed the first 
rulemaking that we conducted in response to a health claim petition 
(Docket No. 1995P-0003).\1\ Section 101.80(a) describes the role of 
fermentable carbohydrates, i.e., dietary sugars and starches, in the 
development of dental caries. The fermentation of these carbohydrates 
by microorganisms produces organic acids on the surface of teeth, which 
contribute to the development of dental caries through erosion of tooth 
enamel. Section 101.80(b) explains that noncariogenic carbohydrate 
sweeteners are fermented by oral microorganisms more slowly than 
fermentable carbohydrates. Consequently, the rate of acid production is 
lower than that from fermentable carbohydrates. Noncariogenic 
carbohydrate sweeteners, when used in place of fermentable sugars, are 
therefore useful in that they do not promote dental caries as do the 
sugars they replace. Section 101.80(c) describes the specific 
requirements of the dental caries health claim, including

[[Page 25497]]

the requirement that the food bearing the claim be ``sugar free'' 
(Sec.  101.80(c)(2)(iii)(A)). This section also specifies 10 
noncariogenic carbohydrate sweeteners (xylitol, sorbitol, mannitol, 
maltitol, isomalt, lactitol, hydrogenated starch hydrolysates, 
hydrogenated glucose syrups, erythritol, and D-tagatose) that are 
eligible for the claim (Sec.  101.80(c)(2)(ii)). Section 
101.80(c)(2)(iii)(C) further states that:
---------------------------------------------------------------------------

    \1\Section 101.80 was subsequently amended, to expand the 
substances which are the subject of the claim, to include 
noncariogenic carbohydrate sweeteners other than sugar alcohols (67 
FR 71461, December 2, 2002).
---------------------------------------------------------------------------

    When carbohydrates other than those listed in paragraph 
(c)(2)(ii) of this section are present in the 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 * * *.''
    In the dental caries health claim final rule, the agency stated 
that for other noncariogenic carbohydrate sweeteners to be included in 
the list of sweeteners eligible for the health claim, a petitioner must 
show how the substance conforms to the requirements of Sec. Sec.  
101.14(b) and 101.80 and must provide evidence that the new 
noncariogenic carbohydrate sweetener will not lower dental plaque pH 
below 5.7 (61 FR 43433 at 43442).
    In 1997, the agency amended the dental caries health claim to 
include erythritol as an additional noncariogenic carbohydrate 
sweetener eligible for the claim (62 FR 63653, December 2, 1997). The 
health claim petition to add erythritol to Sec.  101.80 (Docket No. 
1997P-0206) presented scientific data from a rodent cariogenicity study 
and from a clinical indwelling plaque pH test of erythritol. The agency 
was satisfied that the results of these two studies were consistent 
with the results of the studies that investigated the cariogenic 
potential of the substances previously listed in Sec.  
101.80(c)(2)(ii)(A) and that erythritol met the requirements of Sec.  
101.14(b). Therefore, erythritol was added to the list of sugar 
alcohols eligible as a noncariogenic carbohydrate sweetener. In 2002, 
the agency again amended Sec.  101.80 (67 FR 71461) to add D-tagatose, 
a non-fermentable sugar, to the list of substances eligible for the 
health claim. This action was based upon clinical evidence that 
ingestion of D-tagatose would not lower plaque pH below 5.7 as measured 
by the indwelling plaque pH method. Because the sweetener added to the 
health claim in the 2002 amendment was not a sugar alcohol, the 2002 
amendment also changed the substance in the title of the regulation 
from ``sugar alcohols'' to ``noncariogenic carbohydrate sweeteners.''

II. Petition and Grounds

A. The Petition

    On April 2, 2004, McNeil Nutritionals, of New Brunswick, NJ 
(petitioner) submitted a petition under section 403(r)(4) of the act 
(21 U.S.C. 343(r)(4)) (Ref. 1). The petition requested that we amend 
Sec.  101.80 to include the nonnutritive sweetener sucralose as one of 
the substances eligible to bear the dental caries health claim. On July 
9, 2004, we notified the petitioner that we had completed our initial 
review of the petition and that the petition had been filed for further 
action in accordance with section 403(r)(4) of the act. If the agency 
does not act, by either denying the petition or issuing a proposed 
regulation to authorize the health claim, within 90 days of the date of 
filing for further action, the petition is deemed to be denied unless 
an extension is mutually agreed upon by the agency and the petitioner 
(section 403(r)(4)(A)(i) of the act and Sec.  101.70(j)(3)(iii)). On 
April 5, 2005, FDA and the petitioner mutually agreed to extend the 
deadline to publish a proposed regulation until October 7, 2005.

B. Nature of the Substance

    The petition has identified the substance, which is the subject of 
the petitioned health claim, to be sucralose (CAS Reg. No. 56038-13-2), 
a substituted carbohydrate in which there is a selective replacement of 
three hydroxyl groups on a sucrose molecule with chlorine atoms. The 
food additive use of sucralose is as a general purpose sweetener in 
both conventional foods and dietary supplements (Sec.  172.831 (21 CFR 
172.831)). Sucralose, used as a general purpose sweetening food 
additive, is a specific component of food. The term ``substance'' 
within the meaning of a health claim includes ``* * * a specific food 
or component of food * * *'' (Sec.  101.14(a)(2)). As such, FDA 
concludes that sucralose is a ``substance'' as defined in Sec.  
101.14(a)(2) for the purpose of a food label statement which 
characterizes the relationship of any substance to a disease or health-
related condition.

C. Review of Preliminary Requirements for a Health Claim

1. The Substance Is Associated With a Disease for Which the U.S. 
Population Is at Risk
    The petition noted that the scientific literature establishing the 
relationship between dental caries and fermentable carbohydrates is 
described and referenced in the final rule for the dental caries health 
claim (61 FR 43433). When authorizing the health claim relating 
noncariogenic carbohydrate sweeteners and dental caries, the agency 
recognized that, although the prevalence of dental caries among 
children in the United States had been declining since the early 1970s, 
the overall prevalence of dental caries remained widespread throughout 
the U.S. population (Sec.  101.80(a)(3)). Currently, the Department of 
Health and Human Services' Healthy People 2010 Objectives recognizes 
dental caries as the single most common chronic disease of childhood, 
and states that 30 percent of adults have untreated dental decay (Ref. 
2). Based on these facts, FDA concludes that, as required in Sec.  
101.14(b)(1), dental caries is a disease for which the general U.S. 
population is at risk.
2. The Substance is a Food
    When a health claim involves consumption of a substance at other 
than decreased dietary levels, the substance that is the subject of the 
health claim must contribute taste, aroma, or nutritive value, or any 
other technical effect listed in Sec.  170.3(o) (21 CFR 170.3(o)) to 
the food, and must retain that attribute when consumed at the levels 
that are necessary to justify a claim (Sec.  101.14(b)(3)(i)). As noted 
by the petition, the use of sucralose as a nonnutritive sweetener in 
conventional foods and dietary supplements is prescribed by the food 
additive regulation under Sec.  172.831. The sweetness intensity of 
sucralose is approximately 600 times that of sucrose (Ref. 3), as such 
the amount of sucralose used as a sugar substitute is in milligrams per 
serving and the caloric contribution of sucralose to a food is 
insignificant. The food additive use of sucralose is as a ``non-
nutritive sweetener,'' one of the technical effects listed in Sec.  
170.3(o) for which human food ingredients may be added to foods. 
Because sucralose contributes to food taste, one of the technical 
effects listed in Sec.  170.3(o), the agency concludes that the 
preliminary requirement of Sec.  101.14(b)(3)(i) is satisfied.
3. The Substance is Safe and Lawful
    The petition notes that FDA has evaluated the use of sucralose in 
the food supply and has issued a food additive regulation setting out 
the conditions of its safe use in foods. The safe use of sucralose as a 
general purpose sweetener in foods in accordance with current good 
manufacturing practice in an amount not to exceed that reasonably 
required to accomplish the intended effect is

[[Page 25498]]

prescribed by the food additive regulation under Sec.  172.831. This 
food additive regulation establishes the food use of sucralose under 
conditions prescribed by the regulation to be safe and lawful under 
section 409 of the act (21 U.S.C. 348). Therefore, FDA concludes that 
the petitioner has satisfied the requirement of Sec.  101.14(b)(3)(ii) 
to demonstrate, to FDA's satisfaction, that the use of sucralose as a 
sweetener is safe and lawful under the provisions of the act.

III. Review of Scientific Evidence of the Substance-Disease 
Relationship

A. Basis for Evaluating the Relationship Between Sucralose and Dental 
Caries

    In the preamble to the 1996 dental caries health claim final rule, 
the agency concluded that there was significant scientific agreement 
among qualified experts to support the relationship between certain 
sugar alcohols and the nonpromotion of dental caries (61 FR 43433 at 
43443). The agency noted that it would take action to add additional 
sugar alcohols to this regulation when presented with evidence that the 
additional sugar alcohols would not lower plaque pH (i.e., raise plaque 
acidity) below 5.7, and that the substance conformed to the 
requirements of Sec.  101.14(b) (61 FR 43433 at 43442).
    The substance that is the subject of the current petition, 
sucralose, is a chlorine-substituted sugar rather than a sugar alcohol. 
However, like the sugar alcohols, the intended food ingredient use of 
sucralose is as a sugar substitute. Also, as is the case with the sugar 
alcohols, the potential dental health benefit from sucralose derives 
from its lower fermentability relative to traditional sugars. 
Consequently, the criteria that were used to evaluate the sugar 
alcohols in the existing dental caries health claim can be applied to 
assess whether sucralose also qualifies for such a claim.

B. Review of Scientific Evidence

1. Evidence Considered in Reaching the Decision
    In the initial proposal to authorize a health claim relating 
noncariogenic carbohydrate sweeteners and nonpromotion of dental caries 
(60 FR 37507, July 20, 1995), FDA considered evidence from long-term 
controlled human caries studies, in vivo and in vitro plaque acidity 
studies, tooth decalcification and remineralization studies, and 
experimental rat caries studies for the noncariogenic potential of 
several specific sugar alcohols. FDA's review focused on the scientific 
evidence from studies evaluating changes in human dental plaque pH, 
plaque acid production, decalcification or remineralization of tooth 
enamel, and the incidence of dental caries. FDA limited its review to 
these types of studies because previous reviews by the Federal 
Government and other authorities had focused on these areas, and the 
majority of research efforts have also focused on these areas (60 FR 
37507 at 37523). The well established role of sucrose in the etiology 
of dental caries is related to the ability of sucrose to be metabolized 
by oral bacteria into extracellular polymers that adhere firmly to the 
tooth surfaces (i.e., plaque), and at the same time to form acids that 
can demineralize tooth enamel. FDA had previously concluded that human 
studies show sugar alcohols are associated with reduced rate of acid 
production in dental plaque and, in some studies, a reduced incidence 
of dental caries, in comparison to sucrose (60 FR 37507 at 37523).
    In consideration of the amendment requested in the current 
petition, FDA compared scientific evidence regarding the cariogenic 
potential of sucralose from three human studies which investigated the 
rate of acid production in dental plaque resulting from exposure to 
sucralose-containing solutions. This is the same type of clinical 
evidence that the agency previously reviewed regarding the cariogenic 
potential of certain sugar alcohols and of D-tagatose. As discussed in 
section II.C of this document, FDA has concluded that sucralose 
satisfies the requirements of Sec.  101.14(b).
    Sucralose is used as a nonnutritive food additive in processed 
foods. Sucralose is also marketed directly to consumers in several 
formulations for use in sweetening foods and beverages (Splenda Packet, 
Splenda Sugar Blend for Baking, and Splenda Granular). Splenda Packet 
is a formulation of sucralose dispersed in a dextrose/maltodextrin 
blend containing greater than 0.5 gram (g) dextrose sugar per labeled 
serving, and packaged in single serving packets for consumer use as a 
``table top'' sweetener. Splenda Sugar Blend for Baking is a 
formulation of sucralose dispersed in sucrose, containing 2 g sugar per 
labeled serving, and packaged for consumer use as a sugar replacement 
in cooking and baking. The dental caries health claim regulation 
requires that a food bearing the claim be ``sugar-free'' as defined in 
the regulations, except that the food may contain D-tagatose (see Sec.  
101.80(c)(2)(iii)(A) and Sec.  101.60(c)(1)(i) (21 CFR 
101.60(c)(1)(i)). Neither Splenda Packet nor Splenda Sugar Blend for 
Baking meet the definition of ``sugar-free'' as set out in Sec.  
101.60(c)(1)(i). Therefore, neither of these two sucralose formulations 
are eligible for use of the health claim, and the dental plaque pH data 
provided in the petition for Splenda Packet has not been considered as 
evidence for amending the health claim regulation. The petition did not 
include dental plaque pH data for Splenda Sugar Blend for Baking.
    There are three primary methods used for measuring the impact of 
foods on plaque acidity in humans: Plaque sampling, micro-touch, and 
indwelling electrode methods (Ref. 4). The plaque sampling method 
involves the scraping of plaque from tooth surfaces, dispersing the 
collected plaque in distilled water, and in vitro pH measurement of the 
plaque suspension. The micro-touch method involves measurements of 
plaque pH in situ, at the plaque surface, by touching a small pH 
electrode against tooth surfaces. The indwelling electrode method 
involves mounting a small pH electrode in a removable partial denture 
such that it is positioned adjacent to a natural tooth crown, allowing 
in situ pH measurements under the plaque layer that accumulates on the 
electrode. Since these three methods measure pH at different locations 
and at different depths in the plaque, they yield somewhat different pH 
values. Both the micro-touch and indwelling electrode methods have been 
reported to satisfactorily identify relative differences in acidogenic 
foods compared to a positive control (Refs. 4 and 5). However, in 
studies which directly compare the absolute pH values obtained from the 
different plaque pH measurement methods, the indwelling electrode 
method consistently yields lower minimum pH values than do either the 
plaque sampling or micro-touch methods (Refs. 4 to 6).
    When initially authorizing the dental caries health claim, FDA 
noted that it would take action to add other sweeteners to the list of 
substances eligible for this health claim when presented with a 
petition that included, in part, evidence that the substance would not 
lower plaque pH below 5.7 (61 FR 43433 at 43442). FDA did not specify a 
specific method to be used in measuring plaque pH for considering the 
addition of other sweeteners to the list of eligible substances for 
this health claim. On the other hand, in order for foods that contain 
both noncariogenic sweeteners and fermentable carbohydrates to qualify 
for this health claim, Sec.  101.80(c)(2)(iii)(C) specifies that

[[Page 25499]]

the indwelling electrode method is the procedure that the agency will 
use.
2. Review of Sucralose Studies
    The petition included published reports from three separate 
randomized, double-blind studies of the effect of sucralose on dental 
plaque pH in humans (Refs. 7 to 9). Each study was conducted with 
essentially the same experimental protocol, and in each study 
interdental plaque pH was measured with a hand-held miniature pH 
electrode (the micro-touch method). Exposure to sucralose was 
accomplished by a 1 minute rinsing of the mouth with the test sweetener 
substances dissolved in water (Ref. 7), hot coffee (Ref. 8), or iced 
tea (Ref. 9).
    Each study recruited subjects older than 18 years of age and with 
high caries susceptibility as demonstrated by: (1) Greater than seven 
decayed, missing, or filled teeth, and (2) a plaque pH measurement 
below 5.7 when challenged with a 4.7 percent sucrose rinse. Subjects 
refrained from oral hygiene procedures for 48 hours prior to each test 
and refrained from smoking and all food and drink, except for water, 
for at least 4 hours prior to each test to allow for the development of 
an undisturbed resting plaque layer. At each test session, pre-rinse 
baseline pH was measured at the mesiobuccal surface of six teeth, after 
which subjects rinsed with a test sweetener solution for 1 minute, and 
then pH measurements at the same six sites were repeated at timed 
intervals over 60 minutes.
    Each study included test solutions of: (1) Sucralose alone, (2) 
sucralose with maltodextrin (Splenda Granular), (3) sucralose with a 
dextrose-maltodextrin blend (Splenda Packet), and (4) sucrose alone. 
The sucrose rinse served as a positive control. The sweetness of the 
sucralose solutions (0.007 percent by weight) and sucrose solution (4.7 
percent by weight) were equivalent to 2 teaspoons of sucrose in 6 fluid 
ounces. A fifth test solution (unsweetened coffee or iced tea) was 
included in two of the reported studies (Refs. 8 and 9). Test sessions 
were conducted at 1-week intervals, and at approximately the same time 
of day for each individual. One sweetener solution was tested per test 
session and each individual tested all test solutions for the study 
they were enrolled in.
    The reported mean minimum plaque pH values following a sucralose 
rinse were 6.56  0.23 (water), 6.04  0.44 
(coffee), and 6.73  0.34 (iced tea). The reported mean 
minimum plaque pH values following a Splenda Granular rinse were 6.15 
 0.36 (water), 5.59  0.35 (coffee), and 6.20 
 0.31 (iced tea). The reported mean minimum plaque pH 
values following a Splenda Packet rinse were 5.84  0.47 
(water), 5.34  0.29 (coffee), and 6.02  0.42 
(iced tea). The reported mean minimum pH values following a sucrose 
rinse were 5.29  0.30 (water), 5.35  0.37 
(coffee), and 5.46  0.33 (iced tea). The reported mean 
minimum pH values following a rinse with unsweetened beverage were 5.92 
 0.41 (coffee), and 6.79  0.31 (iced tea). 
These results show that exposure to sucralose alone by an oral rinse 
did not result in a increase in plaque acidity as measured by the 
micro-touch pH method. As such, these data are evidence that sucralose 
will not lower plaque pH below 5.7. However, exposure by an oral rinse 
to Splenda Granular and Splenda Packet did, in some instances, lower 
plaque pH below 5.7. For instance, when the oral rinse medium was 
coffee, mean plaque pH was reduced below pH 5.7 for both Splenda 
Granular and Splenda Packet.
    The human in situ plaque pH evidence for non-fermentability of 
sucralose is supported by pre-clinical study evidence submitted with 
the petition. The petitioner submitted reports from in vitro studies of 
sucralose metabolism by oral bacteria. These data indicate that 
sucralose does not support the growth of Streptococcus mutans nor of 
other strains of acidogenic plaque bacteria, nor do the bacteria 
produce acid from sucralose (Refs. 10 and 11). Studies with 
experimental rat models for caries development indicate that sucralose 
is noncariogenic in rats (Refs. 12 and 13). The preclinical data taken 
in total support a conclusion that sucralose is not a substrate for 
cariogenic bacteria and is not a contributor to caries development.

IV. Decision to Authorize a Health Claim Relating Sucralose to the 
Nonpromotion of Dental Caries

    FDA previously concluded that there is significant scientific 
agreement among qualified experts to support the relationship between 
certain noncariogenic carbohydrate sweeteners (e.g., some sugar 
alcohols and D-tagatose) and the nonpromotion of dental caries. The 
principal evidence, which substantiates this relationship, is in situ 
human plaque pH data showing that the metabolism of sugar alcohols and 
D-tagatose by oral bacteria is significantly less than the metabolism 
of sucrose and other fermentable carbohydrates, and therefore does not 
contribute to the loss of minerals from tooth enamel (Sec.  101.80(b)). 
The current petition evaluated the cariogenic potential of sucralose 
based on three studies which measured the acidogenic potential of 
sucralose with in situ plaque pH tests. As discussed previously, these 
plaque pH tests demonstrate that rinsing of the mouth with sucralose 
did not result in decreases in plaque pH below pH 5.7 and, therefore, 
does not promote demineralization of dental enamel. The results of 
these studies are consistent with the results of the studies that 
investigated the cariogenic potential of the sugar alcohols originally 
listed in Sec.  101.80(c)(2)(ii), and are consistent with the evidence 
relied upon by the agency when adding erythritol (62 FR 63653) and D-
tagatose (67 FR 71461) to this list. Therefore, based on the totality 
of publicly available evidence pertaining to the cariogenicity of 
sucralose and to the relationship between dental plaque pH and dental 
caries, we conclude that there is significant scientific agreement that 
sucralose does not promote dental caries. Accordingly, we are proposing 
to amend Sec.  101.80 to authorize extending the dental caries health 
claim to include sucralose.
    Section 101.80(c)(2)(iii) contains requirements for the nature of 
the food bearing the dental caries health claim. Section 
101.80(c)(2)(iii)(A) states ``The food shall meet the requirement in 
Sec.  101.60(c)(1)(i) with respect to sugars content, except that the 
food may contain D-tagatose.'' That is, one criterion of the health 
claim is that the food be ``sugar free,'' i.e., the food contains less 
than 0.5 grams of sugar per reference amount customarily consumed and 
per labeled serving. The agency notes that ``Splenda Packet'' contains 
in excess of 0.5 g of dextrose per serving and as such does not meet 
the ``sugar free'' requirement of Sec.  101.80 and thus is ineligible 
to bear the dental caries health claim. The petition does not request 
amendments to the ``sugar-free'' requirement in Sec.  101.80(c)(2)(iii) 
in order to accommodate use of the dental caries health claim by 
Splenda Packet, nor has the agency considered amending this paragraph.
    The predominant ingredient, by weight, of Splenda Granular is 
maltodextrin, a fermentable carbohydrate. The data provided by the 
petitioner indicates that rinsing with one serving of Splenda Granular 
(sweetness equivalent to 2 teaspoons of sucrose) resulted in plaque 
acidity between pH 5.6 and 6.2, depending on the beverage in which it 
was suspended, as measured by the micro-touch plaque pH measurement 
method. As mentioned in section III.B.1 of this document, plaque pH 
values measured by the indwelling electrode pH measurement method are 
consistently lower than are

[[Page 25500]]

the pH values obtained by the micro-touch method.
    A provision of the Sec.  101.80 health claim regulation requires 
that when carbohydrates other than those eligible for the claim are 
present in a food bearing the dental caries health claim, bacterial 
fermentation of the food must not lower plaque pH below 5.7, either 
during consumption or up to 30 minutes after consumption, as measured 
by an indwelling electrode pH method (see Sec.  101.80(c)(2)(iii)(C)). 
The petitioner's micro-touch pH measurement method data do not satisfy 
the pH evidence requirement of Sec.  101.80(c)(2)(iii)(C) for Splenda 
Granular (i.e., plaque pH remains above pH 5.7 as measured by the 
indwelling electrode method). Therefore, FDA concludes that the use of 
the dental caries health claim on the label of Splenda Granular would 
not be appropriate.

V. Description of Modifications to Sec.  101.80

A. Requirements

    Specific requirements for use of the dental caries health claim are 
provided in Sec.  101.80(c)(2). The noncariogenic carbohydrate 
sweeteners now eligible for the health claim are listed within the 
nature of the substance paragraph (Sec.  101.80(c)(2)(ii)). FDA is 
proposing to amend Sec.  101.80(c)(2)(ii) to include sucralose as an 
additional eligible noncariogenic carbohydrate sweetener.

B. Model Health Claims

    Section 101.80(e) provides examples of statements that meet the 
requirements to make a health claim about nonpromotion of dental 
caries. FDA emphasizes that these ``model health claims'' are only 
illustrative. These model claims illustrate both the elements of the 
health claim statement required under Sec.  101.80(c)(2)(i) and some of 
the optional elements permitted under Sec.  101.80(d). Because the 
agency is proposing to amend Sec.  101.80 to add sucralose as an 
additional noncariogenic carbohydrate sweetener eligible for the health 
claim, and is not approving specific claim wording, manufacturers will 
be free to design their own claim so long as it is consistent with 
agency regulations.
    Current Sec.  101.80(e)(1) consists of examples of the full claim, 
and Sec.  101.80(e)(2) consists of examples of the shortened claim for 
use on packages with less than 15 square inches of surface area 
available for labeling. The petition recommends amending Sec.  
101.80(e) to include examples of both the full claim and the shortened 
claim specific for sucralose. One of the requirements of the dental 
caries health claim is that the claim statement specify the substance 
as ``sugar alcohol,'' ``sugar alcohols,'' or by the name of the 
substance, e.g., sorbitol or tagatose (Sec.  101.80(c)(2)(i)(C)). The 
health claim regulation provides that packages with less that 15 square 
inches of surface area available for labeling are exempt from the Sec.  
101.80(c)(2)(i)(C) requirement of specifying the substance in the claim 
statement (Sec.  101.80(c)(2)(i)(G)). As such, the shortened claim 
provided for by Sec.  101.80(c)(2)(i)(G) need not specify the substance 
and therefore FDA is not proposing to amend Sec.  101.80(e)(2) to add 
examples of the shortened claim specific for sucralose. FDA notes that 
the lack of a model shortened claim specifying ``sucralose'' in Sec.  
101.80(e)(2) does not preclude a manufacturer from using, on packages 
with less that 15 square inches of surface area available for labeling, 
a shortened claim that mentions sucralose specifically, as was proposed 
by the petition. We are proposing to amend Sec.  101.80(e)(1) to add 
the model claim for sucralose proposed by the petition. The added 
example of the full claim will state: ``Frequent eating of foods high 
in sugars and starches as between-meal snacks can promote tooth decay. 
Sucralose, the sweetening ingredient used to sweeten this food, unlike 
sugars, does not promote tooth decay.'' (proposed Sec.  
101.80(e)(1)(v)).

VII. Analysis of Impacts

A. Regulatory Impact Analysis

    FDA has examined the economic implications of this proposed rule as 
required by Executive Order 12866. Executive Order 12866 directs 
agencies to assess 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). 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, adversely affecting a sector of the economy in a material way, 
adversely affecting competition, or adversely affecting jobs. A 
regulation is also considered a significant regulatory action if it 
raises novel legal or policy issues. FDA has determined that this 
proposed rule is not a significant regulatory action as defined by 
Executive Order 12866.
    FDA has identified three options regarding this petition: (1) Deny 
the petition; (2) add sucralose to the dental caries health claim using 
the standards previously applied for making that claim; or (3) add 
sucralose to the dental caries health claim using different standards 
from those standards previously applied for making that claim, so that 
the claim could be applied to products such as Splenda Granular and 
Splenda Packet. This rule will affect three sets of stakeholders: 
Consumers, producers using sucralose, and producers not using 
sucralose. The agency will evaluate each of the three options with 
respect to their effect on each of these three sets of stakeholders.
    Option one: FDA's denial of the petition would mean no change in 
the dental caries health claim. This option generates no new costs and 
benefits and is the point of comparison for all other options. 
Producers using sucralose would not change labels to provide more 
information on sucralose and dental caries. Producers not using 
sucralose would not be affected by changes in the information given to 
consumers about sucralose and dental caries or changes in the relative 
prices of sweeteners or products using sweeteners. Consumers would 
continue to experience dental caries unaffected by information on 
sucralose and dental caries.
    If we deny the petition, then the state of treatment of dental 
caries would not be affected. Dental caries is the most common chronic 
childhood disease and 94 percent of adults have either untreated decay 
or fillings in the crowns of their teeth, with an average of 22 
affected surfaces, according to the National Oral Health Survey, part 
of the National Health and Nutrition Examination Survey (Ref. 14). The 
cost of dental caries includes the costs of dental treatment as well as 
the value of lost productivity and pain and suffering associated with 
dental caries. There are several risk factors for developing dental 
caries: Genetic factors, eating behaviors, and types and 
characteristics of foods eaten (Ref. 15). Specifically, consumption of 
dietary sugars and starches have been linked to development of dental 
caries.
    Option two: The option chosen by the agency under certain 
conditions permits producers who use sucralose to place the dental 
caries health claim in their labeling. If these producers decide to do 
so they will have to pay to redesign and replace their labels. If they 
voluntarily make this choice, then their choice reveals that they value 
the ability to place the health claim on their products more highly 
than they value the cost they must bear to make the labeling change. 
Producers who use sucralose

[[Page 25501]]

are better off under option two than under option one because under 
option two they have additional ways to market their products to 
consumers.
    This option under certain conditions permits producers who use 
sucralose to give consumers more information about sucralose and dental 
carries. Some consumers may find this information valuable to them 
while choosing products. As stated previously, FDA has determined that 
this information has sufficient scientific support, and when provided 
in labeling under certain conditions is truthful and not misleading to 
consumers. Consumption of products containing sucralose, such as gum 
and soft drinks, can potentially reduce the risk of dental caries. This 
would lead to benefits in reduced expenditures and other health costs 
related to dental caries. It is possible that the health claim could 
draw some consumers to choose foods that are more expensive. If they 
voluntarily make this choice, they reveal that they value the more 
expensive products more highly than the they value the additional 
expenditure. It is also possible that the prices of products containing 
sucralose may rise and cause some consumers to seek other, less 
expensive products with less protection against dental caries. If they 
voluntarily make this choice, they reveal that they value the less 
expensive products more highly than the increased probability of 
bearing the consequences of dental caries. Regardless of their choices, 
consumers are better off under option two than under option one because 
they can have more information related to their health and can make the 
choices that seem best to them.
    If the agency under certain conditions permits producers who use 
sucralose to place the dental caries health claim in their labeling, 
products that do not contain sucralose may be affected. Some producers 
may be hurt if consumers choose to stop consuming their products and 
instead consume products containing sucralose. Some producers may be 
helped if changes in the prices of products using sucralose make their 
products look less expensive to consumers. Producers not using 
sucralose will be affected differently depending on the type of product 
that they produce, and it is impossible to tell beforehand how the 
approval of this health claim will affect different producers.
    Some producers not currently using sucralose may decide to 
reformulate their products to contain sucralose. Substitution of 
sucralose for sugars in some foods, such as gum and soft drinks can 
potentially reduce the risk of dental caries. This reformulation would 
lead to benefits to consumers in reduced costs associated with dental 
caries. If some producers voluntarily choose to reformulate their 
products, they reveal that they value the ability to place the health 
claim on their products more highly than they value the cost of 
reformulating their products. Whatever the effects of this option on 
producers not using sucralose, they will be the results of the product 
choices made by consumers who respond to the new information and make 
the choices that seem best to them.
    Option three: This option would relax some of the restrictions 
imposed by the agency in option two so that the claim could be applied 
to products such as Splenda Granular and Splenda Packet. Option three 
would use different standards for approving this claim than previously 
applied to other products.
    Option three would give producers using sucralose more 
opportunities to make the health claim than under option two. If, when 
given this option, producers decide to make the claims, they would have 
to pay to redesign and replace their labels, and they could decide to 
change more labels than under option two. However, if they voluntarily 
make this choice, they reveal that they value the ability to place the 
health claim on their product more highly than they value the cost of 
the label change regardless of how many labels they would change. 
Therefore, producers who use sucralose are better off under option 
three than under option two because they have additional opportunities 
for marketing their products to consumers using the health claim.
    Option three makes producers using sucralose better off while 
making consumers worse off. As stated above, the intended use of 
Splenda Granular is in the preparation of foods likely to lower plaque 
pH below 5.7 when measured by the indwelling electrode method. It also 
is designed to be used in the cooking and baking of many foods 
containing starch. Since foods containing starch are associated with 
increased plaque acidity and thus increased risk of dental caries, 
consumers would not benefit from seeing the health claim on products 
such as Splenda Granular. Also, as stated previously, Splenda Packet 
contains dextrose, and therefore is not ``sugar free'' and may promote 
tooth decay. Therefore, consumers would be made worse off under option 
three than under option two. Having the health claim on these 
additional types of products may mislead consumers and undo some of the 
benefit (reduced dental caries) of allowing the claim on products 
containing sucralose that meet the conditions set forth by the agency.
    For producers not using sucralose, the effect of option three is 
generally the same as for option two, though allowing the claim to 
appear on more products would likely make for larger effects.
    We can conclude that the option chosen by the agency (option two) 
is better for society than option one because the impact on consumers 
and on producers using sucralose is positive and the impact on 
producers not using sucralose is indeterminate and depends only on 
choices made by better informed consumers. We can also conclude that 
the option chosen by the agency (option two) is better for society than 
option three because under option three any advantage to producers 
using sucralose comes at the disadvantage of consumers.
    The petition also raises the issue of the effect the increased use 
of sucralose could have on weight loss in the U.S. population. We have 
not addressed that issue here because the products involved and the 
amounts consumed are so small that a health claim relating sucralose to 
reduced dental caries would not have an impact big enough to cause a 
noticeable change in weight.

B. Regulatory Flexibility Analysis

    FDA has examined the economic implications of this proposed rule as 
required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a 
rule has a significant impact on a substantial number of small 
entities, the Regulatory Flexibility Act requires the agency to analyze 
regulatory options that would minimize the economic impact of the rule 
on small entities.
    As previously explained, this proposed rule will not generate any 
compliance costs for any small entities, because it does not require 
small entities to undertake any new activity. No small business will 
choose to use the dental caries health claim authorized by this rule 
unless it believes that doing so will increase private benefits by more 
than it increases private costs. Accordingly, we certify that this 
proposed rule will not have a significant impact on a substantial 
number of small entities. Under the Regulatory Flexibility Act, no 
further analysis is required.

C. Unfunded Mandates

    Title II of the Unfunded Mandates Reform Act of 1995 (Public Law 
104-4) requires cost-benefit and other analyses before any rulemaking 
if the rule would include a ``Federal Mandate that may result in the 
expenditure by State, local, and tribal governments, in the aggregate,

[[Page 25502]]

or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any 1 year.'' FDA has determined that this proposed 
rule does not constitute a significant regulatory action under the 
Unfunded Mandates Reform Act.

VIII. Environmental Impact

    FDA has determined under 21 CFR 25.32(p) 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.

IX. Paperwork Reduction Act

    FDA concludes that this proposed rule contains no collection of 
information under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). Therefore, clearance by the Office of Management and Budget 
under the Paperwork Reduction Act of 1995 is not required.

X. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. We have determined that 
the rule does not contain policies that have substantial direct effects 
on the States or on the relationship between the National Government 
and the States, or on the distribution of power and responsibility 
among the various levels of government. Accordingly, FDA has concluded 
that the proposed rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

XI. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments in response to FDA's 
proposed rule. Submit a single copy of electronic comments or two paper 
copies of any mailed comments, except that individuals may submit one 
paper copy. Identify comments with the docket number found in brackets 
in the heading of this document. Received comments may be seen in the 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.

XII. Proposed Effective Date

    FDA proposes that any final regulation that may issue based on this 
proposal become effective 30 days after its date of publication in the 
Federal Register.

XIII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. McNeil Nutritionals, ``Petition to Amend 21 CFR 101.80 to 
Authorize a Noncariogenicity Dental Health Claim for Sucralose,'' 
CP-1, Docket No. 2004P-0294, April 2, 2004.
    2. U.S. Department of Health and Human Services, ``Oral 
Health,'' chapter 21, Healthy People 2010, volume II, part B, 2d 
ed., Washington, DC: U.S. Government Printing Office 
(www.health.gov/healthypeople/Document/HTML/Volume2/21Oral.htm, 
visited 03/17/2005), November 2000.
    3. G.A. Miller, ``Sucralose,'' Alternative Sweeteners, 2d ed. 
L.O. Nabors and R.C. Gelardi, eds. Marcel Dekker, Atlanta, pp. 173-
175, 1991.
    4. P. Lingstr[ouml]m, T. Imfeld, and D. Birkhed, ``Comparison of 
Three Different Methods for Measurement of Plaque-pH in Humans After 
Consumption of Soft Bread and Potato Chips,'' Journal of Dental 
Research, 72:865-870, 1993.
    5. D.S. Harper, R. Gray, J.W. Lenke, et al., ``Measurement of 
Human Plaque Acidity: Comparison of Interdental Touch and Indwelling 
Electrodes,'' Caries Research, 19:536-546, 1985.
    6. M.E. Jensen and C.F. Schachtele, ``Plaque pH Measurements by 
Different Methods on the Buccal and Approximal Surfaces of Human 
Teeth After Sucrose Rinse,'' Journal of Dental Research, 62:1058-
1061, 1983.
    7. L.M. Steinberg, F. Odusola, J. Yip, et al., ``Effect of 
Aqueous Solutions of Sucralose on Plaque pH,'' American Journal of 
Dentistry, 8:209-211, 1995.
    8. L.M. Steinberg, F. Odusola, J. Yip, et al., ``Effect of 
Sucralose in Coffee on Plaque pH in Human Subjects,'' Caries 
Research, 30:138-142, 1996.
    9. C. Meyerowitz, E.P. Syrrakov, and R.F. Raubertas, ``Effect of 
Sucralose--Alone or Bulked With Maltodextrin and/or Dextrose--on 
Plaque pH in Humans,'' Caries Research, 30:439-444, 1996.
    10. D.A. Young and W.H. Bowen, ``The Influence of Sucralose on 
Bacterial Metabolism,'' Journal of Dental Research, 69:1480-1484, 
1990.
    11. D.B. Drucker and J. Verron, ``Comparative Effects of the 
Substance Sweeteners Glucose, Sorbitol, Sucrose, Xylitol, and 
Trichlorosucrose on Lowering of pH by Two Oral Streptococcus Mutans 
Strains In Vitro,'' Archives of Oral Biology, 24:965-970, 1980.
    12. W.H. Bowen, D.A. Young, and S.K. Pearson, ``The Effects of 
Sucralose on Coronal and Root-Surface Caries,'' Journal of Dental 
Research, 69:1485-1487, 1990.
    13. W.H. Bowen, S.K. Pearson, and J.L. Falany, ``Influence of 
Sweetening Agents in Solution on Dental Caries in Desalivated 
Rats,'' Archives of Oral Biology, 35:839-844, 1990.
    14. Department of Health and Human Services, Results of National 
Oral Health Survey Results Released (press release) (http://www.hhs.gov/news/press/1996pres/960311.html, visited on 03/17/2005), 
March 11, 1996.
    15. U.S. Department of Health and Human Services, Oral Health in 
America: A Report of the Surgeon General--Executive Summary, 
Rockville, MD, U.S. Department of Health and Human Services, 
National Institute of Dental and Craniofacial Research, National 
Institutes of Health, (http://www2.nidcr.nih.gov/sgr/execsumm.htm, 
visited on 03/17/2005), 2000.

List of Subjects in 21 CFR Part 101

    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, 21 CFR part 
101 is proposed to be amended as follows:

PART 101--FOOD LABELING

    1. The authority citation for 21 CFR part 101 continues to read as 
follows:

    Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 342, 
343, 348, 371; 42 U.S.C. 243, 264, 271.
    2. Section 101.80 is amended by adding (c)(2)(ii)(C) and (e)(1)(v) 
to read as follows:


Sec.  101.80  Health claims: dietary noncariogenic carbohydrate 
sweeteners and dental caries.

* * * * *
    (c) * * *
    (2) * * *
    (ii) * * *
    (C) Sucralose.
* * * * *
    (e) * * *
    (1) * * *
    (v) Frequent eating of foods high in sugars and starches as 
between-meal snacks can promote tooth decay. Sucralose, the sweetening 
ingredient used to sweeten this food, unlike sugars, does not promote 
tooth decay.

    Dated: May 4, 2005..
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-9608 Filed 5-12-05; 8:45 am]
BILLING CODE 4160-01-S