[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