[Federal Register Volume 63, Number 214 (Thursday, November 5, 1998)]
[Rules and Regulations]
[Pages 59707-59709]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29616]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 176

[Docket No. 98F-0054]


Indirect Food Additives: Paper and Paperboard Components

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 octadecanoic acid, 
reaction products with 2-[(2-aminoethyl)amino]ethanol and urea, and the 
acetate salts thereof, which may be emulsified with ethoxylated tallow 
alkyl amines, for use in the manufacture of paper and paperboard 
intended for use in contact with dry food. This action is in response 
to a petition filed by Sequa Chemicals, Inc.

DATES: The regulation is effective November 5, 1998; submit written 
objections and requests for a hearing by December 7, 1998.

ADDRESSES: Submit written objections to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Vir D. Anand, Center for Food Safety 
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C 
St. SW., Washington, DC 20204, 202-418-3081.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of February 9, 1998 (63 FR 6571), FDA announced that a food 
additive petition (FAP 8B4576) had been filed by Sequa Chemicals, Inc., 
c/o Keller and Heckman, 1001 G St. NW., suite 500 West, Washington, DC 
20001). The petition proposed to amend the food additive regulations in 
Sec. 176.180 Components of paper and paperboard in contact with dry 
food (21 CFR 176.180) to provide for the safe use of octadecanoic acid, 
reaction products with 2-[(2-aminoethyl)amino]ethanol and urea, and the 
acetate salts thereof, which may be emulsified with ethoxylated tallow 
alkyl amines, for increasing opacity and thickness, employed prior to 
the sheet forming operation in the manufacture of paper and paperboard 
intended for use in contact with dry food.
    In its evaluation of the safety of this additive, FDA has reviewed 
the safety of the additive itself and the chemical impurities that may 
be present in the additive resulting from its manufacturing process. 
Although the additive itself has not been shown to cause cancer, it has 
been found to contain minute amounts of ethylene oxide, a carcinogenic 
impurity resulting from the manufacture of the additive. Residual 
amounts of reactants and manufacturing aids, such as ethylene oxide, 
are commonly found as contaminants in chemical products, including food 
additives.

I. Determination of Safety

    Under the so-called ``general safety clause'' 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 of the act (21 
U.S.C. 348(c)(3)(A)) provides that no food additive shall be deemed 
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 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 
standard using risk assessment procedures to determine whether there is 
a reasonable certainty that no harm will result from the intended use 
of the additive (Scott v. FDA, 728 F.2d 322 (6th Cir. 1984)).

II. Safety of Petitioned Use of the Additive

    FDA estimates that the petitioned use of the additive, octadecanoic 
acid, reaction products with 2-[(2-aminoethyl)amino]ethanol and urea, 
and the acetate salts thereof, which may be emulsified with ethoxylated 
tallow alkyl amines, will result in exposure to no greater than 50 
parts per billion (ppb)

[[Page 59708]]

of the additive in the daily diet (3 kilogram (kg)), or an estimated 
daily intake (EDI) of 0.15 milligram per person per day (mg/p/d) (Ref. 
1).
    FDA does not ordinarily consider chronic toxicological studies to 
be necessary to determine the safety of an additive whose use will 
result in such low exposure levels (Ref. 2), and the agency has not 
required such testing here. However, the agency has reviewed the 
available toxicological data on the additive and concludes that the 
estimated small dietary exposure resulting from the proposed use of 
this additive is safe.
    FDA has evaluated the safety of this additive under the general 
safety standard, considering all available data and using risk 
assessment procedures to estimate the upper-bound limit of lifetime 
human risk presented by ethylene oxide, the carcinogenic chemical that 
may be present as an impurity in the additive. The risk evaluation of 
ethylene oxide has two aspects: (1) Assessment of exposure to the 
impurity from the proposed use of the additive; and (2) extrapolation 
of the risk observed in the animal bioassay to the conditions of 
exposure to humans.

A. Ethylene Oxide

    FDA has estimated the exposure to ethylene oxide from the 
petitioned use of the additive in the manufacture of paper and 
paperboard to be no more than 6.9 parts per trillion (ppt) in the daily 
diet (3 kg), or 6.3 nanograms (ng)/p/d (Ref. 1). The agency used data 
from a carcinogenesis bioassay on ethylene oxide conducted by the 
Institute of Hygiene, University of Mainz, Germany (Ref. 3), to 
estimate the upper-bound limit of lifetime human risk from exposure to 
ethylene oxide resulting from the proposed use of the additive. The 
results of the bioassay on ethylene oxide demonstrated that ethylene 
oxide was carcinogenic for female rats under the conditions of the 
study. The test material caused significantly increased incidence of 
squamous cell carcinomas of the forestomach and carcinomas in situ of 
the glandular stomach.
    Based on the estimated exposure to ethylene oxide of 6.3 ng/p/d, 
FDA estimates that the upper-bound limit of lifetime human risk from 
the proposed use of the subject additive is 1.1 x 10-8, or 
1.1 in 100 million (Ref. 4). Because of the numerous conservative 
assumptions used in calculating the exposure estimate, the actual 
lifetime-averaged individual exposure to ethylene oxide is likely to be 
substantially less than the estimated exposure, and therefore, the 
probable lifetime human risk would be less than the upper-bound limit 
of lifetime human risk. Thus, the agency concludes that there is 
reasonable certainty that no harm from exposure to ethylene oxide would 
result from the proposed use of the additive.

B. Need for Specifications

     The agency has also considered whether specifications are 
necessary to control the amount of ethylene oxide present as an 
impurity in the additive. The agency finds that specifications are not 
necessary for the following reasons: (1) Because of the low level at 
which ethylene oxide may be expected to remain as an impurity following 
production of the additive, the agency would not expect the impurity to 
become a component of food at other than extremely low levels; and (2) 
the upper-bound limit of lifetime human risk from exposure to the 
impurity is very low, less than 1.1 in 100 million.

III. Conclusion

    FDA has evaluated the data in the petition and other relevant 
material. Based on this information, the agency concludes that the 
proposed use of the additive in the manufacture of paper and paperboard 
intended for use in contact with dry food is safe, and that the 
additive will achieve its intended technical effect. Therefore, the 
agency concludes that the regulations in Sec. 176.180 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 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.

IV. Environmental Impact

    The agency has previously considered the environmental effects of 
this rule as announced in the notice of filing for FAP 8B4576 (63 FR 
6571, February 9, 1998). No new information or comments have been 
received that would affect the agency's previous determination that 
there is no significant impact on the human environment and that an 
environmental impact statement is not required.

V. Paperwork Reduction Act of 1995

    This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

VI. Objections

    Any person who will be adversely affected by this regulation may at 
any time on or before December 7, 1998, file with the Dockets 
Management Branch (address above) written objection 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 objection 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.

VII. 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 dated May 8, 1998, from the Chemist, Special 
Project Team (HFS-246), to the file, concerning FAP 8B4576: dietary 
concentrations of the additive and the impurity (ethylene oxide).
    2. Kokoski, C. J., ``Regulatory Food Additive Toxicology,'' in 
Chemical Safety Regulation and Compliance, edited by F. Homburger 
and J. K. Marquis, published by S. Karger, New York, NY, pp. 24-33, 
1985.
    3. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
Propylene Oxide Upon Intragastric Administration of to Rats,'' 
British Journal of Cancer, 46:924-933, 1982.
    4. Memorandum from the Indirect Additives Branch, FDA, to the 
Executive Secretary, Quantitative Risk Assessment Committee, FDA, 
concerning: Assessment of upper-bound lifetime risk from exposure to 
ethylene oxide from the use of octadecanoic acid, reaction product 
with 2-[(2-aminoethyl)amino]ethanol and urea, and the acetate salts 
which may be emulsified with

[[Page 59709]]

ethoxylated tallow alkyl amines, in the manufacture of paper and 
paperboard. Subject of Food Additive Petition 8B4576 (Sequa 
Chemicals, Inc.), dated May 21, 1998.

List of Subjects in 21 CFR Part 176

    Food additives, Food packaging.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
176 is amended as follows:

PART 176--INDIRECT FOOD ADDITIVES: PAPER AND PAPERBOARD COMPONENTS

    1. The authority citation for 21 CFR part 176 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 342, 346, 348, 379e.

    2. Section 176.180 is amended in the table in paragraph (b)(2) by 
alphabetically adding an entry under the headings ``List of 
substances'' and ``Limitations'' to read as follows:

Sec. 176.180  Components of paper and paperboard in contact with dry 
food.

* * * * *
    (b) * * *
    (2) * * *

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                   List of substances                                          Limitations
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  *                    *                    *                    *                    *                    *
                                                             *
Octadecanoic acid, reaction products with 2-[(2-         For use prior to sheet forming at levels not to exceed
 aminoethyl)amino]ethanol and urea (CAS Reg. No. 68412-   12 pounds per ton of paper.
 14-6), and the acetate salts thereof (CAS Reg. No.
 68784-21-4), which may be emulsified with ethoxylated
 tallow alkyl amines (CAS Reg. No. 61791-26-2).
  *                    *                    *                    *                    *                    *
                                                             *
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    Dated: October 21, 1998.
 William K. Hubbard,
 Associate Commissioner for Policy Coordination.
[FR Doc. 98-29616 Filed 11-4-98; 8:45 am]
BILLING CODE 4160-01-F