[Federal Register Volume 61, Number 104 (Wednesday, May 29, 1996)]
[Rules and Regulations]
[Pages 26785-26788]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-13303]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 172
[Docket No. 94F-0189]
Food Additives Permitted for Direct Addition to Food for Human
Consumption; Dimethyl Dicarbonate
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 dimethyl
dicarbonate (DMDC) as a yeast inhibitor in sports drinks and fruit or
juice sparklers. This action is in response to a petition filed by
Miles, Inc. (now Bayer Corp.).
DATES: Effective May 29, 1996; written objections and requests for a
hearing by June 28, 1996.
ADDRESSES: Written objections may be sent to the Dockets Management
Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm.
1-23, Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Martha D. Peiperl, Center for Food
Safety and Applied Nutrition (HFS-217), Food and Drug Administration,
200 C St. SW., Washington, DC 20204, 202-418-3077.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of June 28, 1994 (59
FR 33299), FDA announced that a food additive petition (FAP 4A4420) had
been filed by Miles, Inc., Mobay Rd., Pittsburgh, PA 15205-9741 (now
Bayer Corp., 100 Bayer Rd., Pittsburgh, PA 15205-9741), proposing that
the food additive regulations in Sec. 172.133 Dimethyl dicarbonate (21
CFR 172.133) be amended to provide for the safe use of DMDC as a yeast
inhibitor in sports drinks and fruit or juice sparklers. The petition
defines sports drinks as carbonated or noncarbonated, nonjuice-
containing (less than or equal to 1 percent juice), flavored or
unflavored beverages containing added electrolytes (5-20
milliequivalents (meq)/liter sodium ion (Na+) and 3-7 meq/liter
potassium ion (K+)). Fruit or juice sparklers are defined as
carbonated, dilute beverages containing juice, fruit flavor, or both,
with juice content not to exceed 50 percent.
DMDC is currently approved in Sec. 172.133 for use as a yeast
inhibitor in wine, dealcoholized wine, and low alcohol wine (53 FR
41325, October 21, 1988; and 58 FR 6088, January 26, 1993) and in
ready-to-drink tea beverages (59 FR 5317, February 4, 1994)
(hereinafter referred to as the October 1988 final rule, the January
1993 final rule, and the February 1994 final rule, respectively).
As discussed below, FDA has evaluated data in the petition and
other relevant material and concludes that DMDC is efficacious in
preventing the growth of yeasts and molds in sports drinks and fruit or
juice sparklers and that the proposed use of DMDC is safe.
II. Determination of Safety
Under the so-called ``general safety clause'' in section
409(c)(3)(A) of the Federal Food, Drug, and Cosmetic Act (the act) (21
U.S.C. 348(c)(3)(A)), a food additive cannot be approved for a
particular use unless a fair evaluation of the data available to FDA
establishes that the additive is safe for that use. FDA's food additive
regulations (21 CFR 170.3(i)) define safe as ``a reasonable certainty
in the minds of competent scientists that the substance is not harmful
under the intended conditions of use.''
The food additive anticancer or Delaney clause in section
409(c)(3)(A) of the act (21 U.S.C. 348(c)(3)(A)) 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 the impurities
in the additive. That is, where an additive itself has not been shown
to cause cancer, but contains a carcinogenic impurity, 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).
III. Safety of DMDC in Sports Drinks and Fruit or Juice Sparklers
DMDC is currently permitted as a yeast inhibitor in wine and wine
substitutes (dealcoholized wine and low-alcohol wine) and in ready-to-
drink tea beverages under Sec. 172.133. In the October 1988, January
1993, and February 1994 final rules, the agency concluded that, because
DMDC decomposes almost immediately after addition to aqueous beverages,
there will be virtually no exposure to the additive from the
consumption of the above-listed beverages.
Data submitted in the petition to support the proposed use of the
additive at levels up to 250 parts per million (ppm) in sports drinks
and fruit or juice sparklers are consistent with these findings.
Specifically, data from a study of sparkling juice drink formulated
with 250 ppm DMDC showed no detectable amount of the additive (limit of
detection (LOD) = 40 parts per billion (ppb)) after 4 hours (Ref. 1). A
study of water with 250 ppm DMDC added yielded the same result (Ref.
1). Based on these data and data incorporated from the petition that
resulted in the October 1988 final rule (FAP 2A3636), the agency
concludes that there will be virtually no consumer exposure to DMDC,
per se, from the use of the additive in sports drinks and fruit or
juice sparklers. Therefore, FDA concludes that DMDC itself presents no
hazard to the consumer.
IV. Safety of Substances That May be Present in Sports Drinks and
Fruit or Juice Sparklers Due to the Use of the Additive
DMDC is unstable in aqueous solution and breaks down almost
immediately after addition to beverages. In aqueous liquids, the
principal breakdown products are methanol and carbon dioxide. Dimethyl
carbonate (DMC) may be present as an impurity in DMDC. Section 172.133
sets a specification of 0.2 percent DMC in DMDC. DMDC also may react
with traces of ammonium ions in beverages to produce methyl carbamate
(MC), a known carcinogen.
In previous evaluations of DMDC, the agency, in accordance with
Sec. 171.1 (21 CFR 171.1), reviewed the safety not only of DMDC but
also of its decomposition products in aqueous beverages. The results of
the agency's analysis of the additive's use in wine and wine
substitutes were discussed extensively in the October 1988 and January
1993 final rules, and its use in ready-to-drink tea beverages was
discussed in the February 1994 final rule. The agency applied the same
type of analysis as in past reviews to its review of the petitioned use
of DMDC. Aspects of the safety evaluation that were not previously
addressed in final rules for other uses of DMDC are discussed below.
A. Methanol
As stated in previous final rules on DMDC, the tolerable (safe)
level of exposure to methanol is 7.1 to 8.4 milligrams per kilogram
body weight per day (mg/kg body weight/day), or approximately 426 to
504 mg/person/day for a 60 kg adult. FDA estimates that the cumulative
methanol exposure for a consumer at the 90th percentile from its
presence naturally in untreated fruit juice and wine and from all uses
of
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DMDC, including its currently regulated uses and the proposed use in
sports drinks and fruit or juice sparklers, is 59 mg/person/day (Ref.
2). This estimate is based on a maximum level of methanol that can be
derived from DMDC of 48.7 ppm methanol per 100 ppm DMDC used. This
level is less than one-seventh of the tolerable safe level. The agency,
therefore, concludes that there is an adequate margin of safety between
total methanol consumption from all sources, including the petitioned
use of DMDC, and the amount of methanol that can be safely ingested.
B. Methyl Carbamate
The reaction of ammonium ions in beverages with DMDC produces MC,
a known carcinogen. The petitioner provided data showing that MC was
detected at a level of 3.7 ppb in a fruit sparkler formulated with 250
ppm DMDC. MC was not detected in DMDC-treated sports drinks, using an
analytical method with an LOD of 0.5 ppb. Using the residual level of
3.7 ppb and the LOD of 0.5 ppb for MC in fruit sparklers and sports
drinks, respectively, the agency estimates the exposure to MC for all
ages from the petitioned use of DMDC to be 1.5 microgram/person/day at
the 90th percentile (Ref. 1). Using established procedures for
quantitative risk assessment, the agency estimates that the 90th
percentile upper-bound lifetime risk from potential exposure to MC from
the petitioned use of DMDC is 1.5 x 10-8, or less than 1 in 67
million, and the 90th percentile upper-bound lifetime risk from
exposure to MC from all approved and petitioned uses of DMDC is 1.8 x
10-8, or less than 1 in 56 million (Refs. 1 and 3).
Therefore, the agency concludes that there is a reasonable
certainty of no harm from the exposure to MC that may result from the
use of up to 250 ppm of DMDC in sports drinks and fruit or juice
sparklers.
V. Conclusion on Safety
FDA has evaluated all of the data in the petition pertaining to the
use of DMDC in sports drinks and fruit or juice sparklers, as well as
other data in its files, and concludes that the additive is safe for
its proposed use.
To ensure the safe use of the additive in sports drinks and fruit
or juice sparklers, FDA, under 21 U.S.C. 348(c)(1)(A), finds that it is
necessary to require directions on the food additive label limiting the
level of use of the additive in these beverages to 250 ppm.
In accordance with Sec. 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 Sec. 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.
VI. 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.
The agency received one comment on the environmental assessment in
response to the filing notice published in the Federal Register of June
28, 1994 (59 FR 33299). The comment states that approval of the subject
additive could have two environmental benefits due to switching from
hot-fill bottling of sports drinks and sparklers to cold-fill. The
comment claims that this switch could greatly reduce water usage in the
bottling process and could reduce cooling water flow into municipal
wastewater treatment plants. However, the comment did not provide
quantitative data on the magnitude of the claimed environmental
benefits of the approval of this petition. FDA has concluded that the
comment does not affect the agency's determination that the approval of
this petition will have no significant impact on the environment. This
comment can be seen at the Dockets Management Branch, along with the
petitioner's environmental assessment and the agency's finding of no
significant impact.
VII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before June 28, 1996, 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.
VIII. 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 the Chemistry Review Branch to the Direct
Additives Branch, ``FAP 4A4420-Dimethyl Dicarbonate as a Yeast
Inhibitor in Sports Drinks and in Fruit or Juice Sparkling
Beverages,'' dated July 8, 1994.
2. Memorandum from the Chemistry Review Branch to the Direct
Additives Branch, ``FAP 4A4420-DMDC as a Yeast Inhibitor in Sports
Drinks and Sparkling Fruit or Juice Beverages. Background Methanol
Exposure,'' dated May 8, 1996.
3. Memorandum from the Direct Additives Branch to the
Quantitative Risk Assessment Committee, ``Estimation of the Upper-
Bound Lifetime Risk from Methyl Carbamate (MC) Formed by the
Reaction of Ammonium Ions with Dimethyl Dicarbonate (DMDC) During
the Use of DMDC as Requested in FAP 4A4420 (Miles Inc.),'' dated May
23, 1995.
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 172.133 is amended by adding new paragraphs (b)(3) and
(b)(4)
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and by revising paragraph (c)(2) to read as follows:
Sec. 172.133 Dimethyl dicarbonate.
* * * * *
(b) * * *
(3) Inhibitor of yeast in carbonated or noncarbonated, nonjuice-
containing (less than or equal to 1 percent juice), flavored or
unflavored beverages containing added electrolytes (5-20
milliequivalents (meq)/liter sodium ion (Na+) and 3-7 meq/liter
potassium ion (K+)). The additive may be added to the beverage in an
amount not to exceed 250 ppm.
(4) Inhibitor of yeast in carbonated, dilute beverages containing
juice, fruit flavor, or both, with juice content not to exceed 50
percent. The additive may be added to the beverage in an amount not to
exceed 250 ppm.
(c) * * *
(2) Directions to provide that not more than 200 ppm of dimethyl
dicarbonate will be added to the wine, dealcoholized wine, or low
alcohol wine and not more than 250 ppm of dimethyl dicarbonate will be
added to the ready-to-drink tea or to the beverages described in parts
(b)(3) and (b)(4) of this section.
Dated: May 17, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-13303 Filed 5-28-96; 8:45 am]
BILLING CODE 4160-01-F
