[Federal Register Volume 59, Number 230 (Thursday, December 1, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-29518]


[[Page Unknown]]

[Federal Register: December 1, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 172

[Docket No. 92F-0030]

 

Food Additives Permitted for Direct Addition to Food for Human 
Consumption; Acesulfame Potassium

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the food 
additive regulations to provide for the safe use of acesulfame 
potassium as a nonnutritive sweetener available to the consumer in 
bulk-packaged form. This action is in response to a petition filed by 
Hoechst Celanese Corp.

DATES: Effective December 1, 1994; written objections and requests for 
a hearing by January 3, 1995.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, rm. 1-23, 12420 Parklawn Dr., 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Patricia A. Hansen, Center for Food 
Safety and Applied Nutrition (HFS-206), Food and Drug Administration, 
200 C St. SW., Washington, DC 20204, 202-254-9523.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of February 21, 1992 (57 FR 6227), FDA announced that a food 
additive petition (FAP 2A4309) had been filed by Hoechst Celanese 
Corp., Rt. 202-206 North, Somerville, NJ 08876, proposing that 
Sec. 172.800 Acesulfame potassium (21 CFR 172.800) be amended to 
provide for the safe use of acesulfame potassium as a nonnutritive 
sweetener available to the consumer in bulk-packaged form.

I. Determination of Safety

    Under Section 409(c)(3)(A) of the Federal Food, Drug, and Cosmetic 
Act (the act) (21 U.S.C. 348(c)(3)(A)), the so-called ``general safety 
clause,'' a food additive cannot be listed for a particular use unless 
a fair evaluation of the evidence establishes that the additive is safe 
for that use. The concept of safety embodied in the Food Additives 
Amendment of 1958 is explained in the legislative history of the 
provision: ``Safety requires proof of a reasonable certainty that no 
harm will result from the proposed use of the additive. It does not--
and cannot--require proof beyond any possible doubt that no harm will 
result under any conceivable circumstance.'' (H. Rept. 2284, 85th 
Cong., 2d sess. 4 (1958)). This concept of safety has been incorporated 
into FDA's food additive regulations (21 CFR 170.3(i)).
    The food additives anticancer, or Delaney, clause (section 
409(c)(3)(A) of the act) further provides that no food additive shall 
be deemed to be safe if it is found to induce cancer when ingested by 
man or animal. Importantly, however, the Delaney clause applies to the 
additive itself and not to constituents of the additive. Thus, where an 
additive has not been shown to cause cancer, even though it contains a 
carcinogenic impurity, the additive is not subject to the legal effect 
of the Delaney clause. Rather, the additive is properly evaluated under 
the general safety clause using risk assessment procedures to determine 
whether there is a reasonable certainty that no harm will result from 
the proposed use of the additive (Scott v. FDA, 728 F.2d 322 (6th Cir. 
1984)).

II. Evaluation of Safety of the Petitioned Use of the Additive

     In its original review of acesulfame potassium in 1988, FDA 
concluded that a review of animal feeding studies showed that there is 
no association between neoplastic disease (cancer) and consumption of 
this additive (53 FR 28379 at 28380 and 28381, July 28, 1988). No new 
information has been received that would change that conclusion. 
Therefore, FDA has evaluated the safety of the petitioned use of 
acesulfame potassium under the general safety clause, considering all 
available data.
     In determining whether the proposed use of an additive is safe, 
FDA considers, among other things, whether an individual's estimated 
daily intake of the additive will be less than the acceptable daily 
intake established from toxicological information. The agency has 
established an acceptable daily intake for acesulfame potassium of 15 
milligrams (mg) per kilogram of body weight per day (or 900 mg per 
person per day). The agency described its analysis of the data that led 
to the establishment of the acceptable daily intake in its original 
decision on the use of acesulfame potassium (53 FR 28379). The agency 
has considered consumer exposure to acesulfame potassium resulting from 
uses listed in this regulation, as well as all currently regulated uses 
and other petitioned uses, including those that are the subject of 
regulations published elsewhere in this issue of the Federal Register. 
FDA has calculated the 90th percentile estimated daily intake from 
these combined uses to be 180 mg per person per day, which is well 
below the acceptable daily intake.

A. Special Considerations Relevant to Use as a Sugar Substitute 
Available to the Consumer in Bulk-Packaged Form

    The petitioner requested the use of acesulfame potassium as a sugar 
substitute available to the consumer in various forms, including 
granulated, powdered, and liquid forms. The availability of acesulfame 
potassium in bulk-packaged form will allow it to be conveniently used 
as a sugar substitute in a wide variety of home-prepared foods and 
beverages. FDA has evaluated data in the petition and other information 
regarding the stability of acesulfame potassium under a variety of 
conditions (pH, moisture content, and temperature) that reflect both 
the requested forms of the bulk-packaged additive and the wide range of 
foods that are prepared in the home and in which the additive, if 
available in bulk-packaged form, may be used. The agency concludes that 
acesulfame potassium is stable under the proposed conditions of use.

B. Methylene Chloride

    The manufacturing process referred to in the petition for 
acesulfame potassium differs from that described in the petition that 
was the basis for the promulgation of Sec. 172.800. In the new process, 
methylene chloride is used as a solvent in the initial step in the 
process. Subsequently, the product is neutralized, stripped of 
methylene chloride, and recrystallized from water. Data were submitted 
by the petitioner showing that methylene chloride could not be detected 
in the final product at a limit of detection of 40 parts per billion 
(ppb).
    FDA, in its evaluation of the safety of the petitioned uses of 
acesulfame potassium, reviewed both the safety of the additive and of 
the chemical impurities that may be present in the additive as a result 
of the manufacturing process. Residual amounts of reactants and 
manufacturing aids are commonly found as contaminants in chemical 
products, including food additives.
    The agency has used risk assessment procedures to estimate the 
upper-bound limit of risk presented by methylene chloride, a 
carcinogenic chemical, that may be present as an impurity in the 
additive. This risk evaluation has two aspects: (1) Assessment of the 
human exposure to the impurity from the proposed use of the additive; 
and (2) extrapolation of the risk observed in the animal bioassays to 
the conditions of probable human exposure.
    FDA has estimated the hypothetical worst-case exposure to methylene 
chloride from both the currently regulated and the petitioned uses of 
acesulfame potassium to be 3.6 nanograms per person per day (ng/p/day) 
(Ref. 1). This estimate is based on the assumption that methylene 
chloride is present in acesulfame potassium at a level of 20 ppb, one-
half its detection limit (Ref. 2). Because it is a volatile compound 
that is removed from the additive prior to further purification, FDA 
does not expect it to be present even at that very low level (Ref. 1).
    Using risk assessment procedures, FDA used data from the National 
Toxicology Program (NTP) report (Ref. 3) of a bioassay on methylene 
chloride to calculate the potency, or unit risk, from exposure to this 
chemical (Ref. 4). The results of the bioassay on methylene chloride 
demonstrated that the material was carcinogenic for mice under the 
conditions of the study. The test material induced benign and malignant 
neoplasms in both the liver and lung of both sexes when administered by 
the inhalation route.
    The agency also evaluated data from a second study, in mice of the 
same strain as used in the inhalation study, in which methylene 
chloride was administered in the drinking water (Ref. 5). In this 
second study, there was no significant increase in the incidence of 
neoplasms at any site examined. However, assuming that methylene 
chloride would induce neoplasia at a dose just above the highest level 
tested in the drinking water study, a maximum potency for ingested 
methylene chloride can be estimated. This estimate is approximately the 
same as the potency calculated from the data of the inhalation study, 
providing confidence that using the inhalation study for upper-bound 
risk assessment is not likely to underestimate any potential risk due 
to ingested methylene chloride (Ref. 4).
    Based on a potential exposure of 3.6 ng/p/day, FDA estimates that 
the upper-bound limit of individual lifetime risk from the potential 
exposure to methylene chloride resulting from the use of acesulfame 
potassium is 2.6x10-11, or less than 3 in 100 billion (Ref. 6). 
Because of the numerous conservative assumptions used in calculating 
the exposure estimate, actual lifetime averaged individual daily 
exposure to methylene chloride is expected to be substantially less 
than the estimated worst-case exposure, and therefore, the estimated 
upper-bound limit of risk would be substantially greater than any 
actual risk. Thus, the agency concludes that there is a reasonable 
certainty of no harm from the exposure to methylene chloride that might 
result from the proposed use of acesulfame potassium.
    The agency has also considered whether a specification is necessary 
to control the amount of methylene chloride impurity in the food 
additive. While FDA would ordinarily establish a specification for a 
carcinogenic constituent in a direct food additive, the agency finds 
that specifications are not needed in this case for the following 
reasons: (1) Methylene chloride is a volatile material that is used 
early in the manufacturing process for the additive and then removed 
from the additive. Several steps occur after methylene chloride is 
removed and before the additive is added to food. Therefore, the agency 
would not expect this impurity to become a component of food at other 
than an extremely low level. (2) Methylene chloride has not been 
detected in any samples tested even at a limit of detection of 40 ppb, 
a level that is several orders of magnitude below levels that would 
present any public health concerns. (3) Finally, the upper-bound limit 
of lifetime risk from exposure to this impurity, even under worst-case 
assumptions, is very low, less than 3 in 100 billion. Thus, FDA 
believes that there is no reasonable possibility that methylene 
chloride will be present in amounts that present a health concern and 
sees no justification for requiring manufacturers to monitor compliance 
with a specification.

III. Conclusion of Safety

    FDA has evaluated the data in the petition and other relevant 
material and concludes that the proposed use of acesulfame potassium as 
a nonnutritive sweetener (sugar substitute) available to the consumer 
in bulk-packaged form is safe. Therefore, the agency concludes that 
Sec. 172.800 should be amended as set forth below.
    The current regulation authorizes two forms of acesulfame potassium 
to be offered directly to the consumer: (1) Dry, free-flowing sugar 
substitutes in individual serving packages (Sec. 172.800(c)(1)); and 
(2) sugar substitute tablets (Sec. 172.800(c)(2)). This final rule, 
which permits additional forms of acesulfame potassium for such use, 
removes the need for specifying each individual form in which the 
nonnutritive sweetener (sugar substitute) might be offered to the 
consumer. Therefore, FDA is revising the regulations prescribing the 
listed forms of acesulfame potassium directly available to the consumer 
for use as a sugar substitute, both to add the additional form that is 
the subject of this rulemaking and to simplify the regulation by 
grouping all such permitted forms into a single paragraph.
    In accordance with Sec. 171.1(h) (21 CFR 171.1(h)), the petition 
and the documents that FDA considered and relied upon in reaching its 
decision to approve the petition are available for inspection at the 
Center for Food Safety and Applied Nutrition by appointment with the 
information contact person listed above. As provided in 21 CFR 
171.1(h), the agency will delete from the documents any materials that 
are not available for public disclosure before making the documents 
available for inspection.

IV. Environmental Impact

    The agency has carefully considered the potential environmental 
effects of this action. FDA has concluded that the action will not have 
a significant impact on the human environment, and that an 
environmental impact statement is not required. The agency's finding of 
no significant impact and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

V. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before January 3, 1995, file with the Dockets Management 
Branch (address above) written objections thereto. Each objection shall 
be separately numbered, and each numbered objection shall specify with 
particularity the provisions of the regulation to which objection is 
made and the grounds for the objection. Each numbered objection on 
which a hearing is requested shall specifically so state. Failure to 
request a hearing for any particular objection shall constitute a 
waiver of the right to a hearing on that objection. Each numbered 
objection for which a hearing is requested shall include a detailed 
description and analysis of the specific factual information intended 
to be presented in support of the objection in the event that a hearing 
is held. Failure to include such a description and analysis for any 
particular objection shall constitute a waiver of the right to a 
hearing on the objection. Three copies of all documents shall be 
submitted and shall be identified with the docket number found in 
brackets in the heading of this document. Any objections received in 
response to the regulation may be seen in the Dockets Management Branch 
between 9 a.m. and 4 p.m., Monday through Friday.

VI. References

    The following references have 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. Memorandum from M. DiNovi, Chemistry Review Branch, to P. 
Hansen, Biotechnology Policy Branch, dated August 14, 1992.
    2. Memorandum from M. Dinovi, Chemistry Branch, to P. Hansen, 
Biotechnology Policy Branch, dated November 9, 1994.
    3. ``Technical Report on the Toxicology and Carcinogenesis 
Studies of Dichloromethane (Methylene Chloride) in F344/N Rats and 
B6C3F1 Mice,'' NTP Draft Report, NTP-TR-306, National Institute of 
Health Publication No. 1-85-2562, 1985.
    4. Memorandum from the Quantitative Risk Assessment Committee, 
dated November 15, 1985.
    5. National Coffee Association, ``24-Month Oncogenicity Study of 
Methylene Chloride in Mice--Final Report; vol. 1,'' Hazelton 
Laboratories America, Inc., Vienna, VA, November 30, 1983.
    6. Memorandum from P. Hansen, Biotechnology Policy Branch, to S. 
Henry, Quantitative Risk Assessment Committee, dated June 24, 1993.

List of Subjects in 21 CFR Part 172

    Food additives, 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 
172 is amended as follows:

PART 172--FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR 
HUMAN CONSUMPTION

    1. The authority citation for 21 CFR part 172 continues to read as 
follows:

    Authority: Secs. 201, 401, 402, 409, 701, 721 of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 342, 348, 371, 
379e).

    2. Section 172.800 is amended by revising paragraph (c)(1) and by 
removing and reserving paragraph (c)(2) to read as follows:


Sec. 172.800  Acesulfame potassium.

* * * * * *
    (c) * * *
    (1) Sugar substitute, including granulated, powdered, liquid, and 
tablet form.
    (2) [Reserved]
* * * * *

    Dated: November 22, 1994.
William K. Hubbard,
Interim Deputy Commissioner for Policy.
[FR Doc. 94-29518 Filed 11-30-94; 8:45 am]
BILLING CODE 4160-01-F