[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<SUP>-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<SUP>-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