[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: 94-29520]
[[Page Unknown]]
[Federal Register: December 1, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
21 CFR Part 172
[Docket No. 90F-0443]
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 in baked goods and baking mixes,
including icings, frostings, toppings, and fillings. 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 October 30, 1990 (55 FR 45657), FDA announced that a food
additive petition (FAP 0A4225) 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 in baked goods and
baking mixes. In a second notice published in the Federal Register of
November 19, 1993 (58 FR 61093), FDA announced that it was amending the
filing notice for the petition to reflect that the petitioner had also
proposed that Sec. 172.800 be amended to provide for the safe use of
acesulfame potassium in icings, frostings, toppings, and fillings for
baked goods.
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 uses 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 Conditions Relevant to Use in Baked Goods
The sweetener has been previously shown to be stable at normal
temperatures and moderate pH. The use of acesulfame potassium in baked
goods will subject the additive to elevated temperatures and other
conditions different from those that were considered when Sec. 172.800
was originally promulgated. FDA has evaluated data in the petition
regarding the stability of acesulfame potassium under conditions of
elevated temperature in foods of different moisture content and pH
value. Even under conditions of exaggerated baking time and
temperature, no detectable amounts of decomposition products were
found. Thus, 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 (ng) per person per 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 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 per person per 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 2.6 x 10-11, 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
calculated estimate of the upper-bound limit of risk would be
substantially higher 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 uses of acesulfame potassium
in baked goods, baking mixes, and frostings, icings, toppings, and
fillings for baked goods are safe. Therefore, the agency concludes that
Sec. 172.800 should be amended as set forth below.
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 Review 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. l-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 adding new paragraph (c)(8) to
read as follows:
Sec. 172.800 Acesulfame potassium.
* * * * *
(c) * * *
(8) Baked goods and baking mixes, including frostings, icings,
toppings, and fillings for baked goods.
* * * * *
Dated: November 18, 1994.
William K. Hubbard,
Interim Deputy Commissioner for Policy.
[FR Doc. 94-29520 Filed 11-30-94; 8:45 am]
BILLING CODE 4160-01-F