[Federal Register Volume 64, Number 163 (Tuesday, August 24, 1999)]
[Rules and Regulations]
[Pages 46130-46132]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-21850]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 176
[Docket No. 98F-0871]
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 polyethylene glycol
monoisotridecyl ether sulfate, sodium salt as a component of coatings
on paper and paperboard intended for use in contact with dry food. This
action is in response to a petition filed by Servo Deldon BV.
DATES: This regulation is effective August 24, 1999; submit written
objections and requests for a hearing by September 23, 1999.
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: Mark A. Hepp, Center for Food Safety
and Applied Nutrition (HFS-215), Food and Drug Administration, 200 C
St. SW., Washington, DC 20204, 202-418-3098.
SUPPLEMENTARY INFORMATION: In a notice published in the Federal
Register of October 13, 1998, (63 FR 54717), FDA announced that a food
additive petition (FAP 8B4630) had been filed by Servo Deldon BV, c/o
Keller and Heckman LLP, 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 polyethylene
glycol monoisotridecyl ether sulfate, sodium salt as a component of
coatings on 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 unreacted 1,4-dioxane and
ethylene oxide, carcinogenic impurities resulting from the manufacture
of the additive. Residual amounts of reactants and manufacturing aids,
such as 1,4-dioxane and ethylene oxide, are commonly found as
contaminants in chemical products, including food additives.
I. Determination of Safety
Under the general safety standard 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 additives 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)).
[[Page 46131]]
II. Safety of Petitioned Use of the Additive
FDA estimates that the petitioned use of the additive,
polyethylene glycol monoisotridecyl ether sulfate, sodium salt as a
surfactant in coatings for paper and paperboard in contact with dry
foods, will result in exposure to no greater than 50 parts per billion
(ppb) of the additive in the daily diet (3 kilogram (kg)) or an
estimated daily intake (EDI) of 0.15 milligrams 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 petitioned use of
the 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 1,4-dioxane and ethylene oxide, the
carcinogenic chemicals that may be present as impurities in the
additive. This risk evaluation of 1,4-dioxane and ethylene oxide has
two aspects: (1) Assessment of the exposure to the impurities from the
petitioned use of the additive and (2) extrapolation of the risk
observed in the animal bioassays to the conditions of exposure to
humans.
A. 1,4-Dioxane
FDA has estimated the exposure to 1,4-dioxane from the petitioned
use of the additive as a surfactant in coatings for paper and
paperboard in contact with dry foods to be no more than 0.2 ppb of the
daily diet (3 kg) or 0.6 micrograms per person per day (g/p/d)
(Ref. 1). The agency used data from a carcinogenesis bioassay on 1,4-
dioxane, conducted by the National Cancer Institute (Ref. 3), to
estimate the upper-bound limit of lifetime human risk from exposure to
this chemical resulting from the petitioned use of the additive. The
authors reported that the test material caused a significantly
increased incidence of squamous cell carcinomas and hepatocellular
tumors in female rats. Based on the agency's estimate that exposure to
1,4-dioxane will not exceed 0.6 g/p/d, FDA estimates that the
upper-bound limit of lifetime human risk from the petitioned use of the
subject additive is 2.1 x 10-8 (or 2.1 in 100 million) (Ref.
4). Because of the numerous conservative assumptions used in
calculating the exposure estimate, the actual lifetime-averaged
individual exposure to 1,4-dioxane 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 1,4-dioxane would result from the petitioned use
of the additive.
B. Ethylene Oxide
FDA has estimated the exposure to ethylene oxide from the
petitioned use of the additive as a surfactant in coatings for paper
and paperboard in contact with dry foods to be no more than 3.9 parts
per trillion in the daily diet (3 kg) or 12 nanograms per person per
day (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. 5), to estimate the upper-bound
limit of lifetime human risk from exposure to ethylene oxide resulting
from the petitioned use of the additive. The authors reported that the
test material caused significantly increased incidence of squamous cell
carcinomas of the forestomach and carcinomas in situ of the glandular
stomach in female rats. Based on the agency's estimate that exposure to
ethylene oxide will not exceed 12 ng/p/d, FDA estimates that the upper-
bound limit of lifetime human risk from the petitioned use of the
subject additive is 2.24 x 10-8 (or 2.24 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
petitioned use of the additive.
C. Need for Specifications
The agency has also considered whether specifications are
necessary to control the amount of 1,4-dioxane and ethylene oxide as
impurities in the additive. The agency finds that specifications are
not necessary for the following reasons: (1) Because of the low level
at which 1,4-dioxane and ethylene oxide may be expected to remain as
impurities following production of the additive, the agency would not
expect the impurities to become components of food at other than
extremely small levels; and (2) the upper-bound limits of lifetime risk
from exposure to 1,4-dioxane and ethylene oxide is very low, 2.1 in 100
million and 2.24 in 100 million, respectively.
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 adhesives is safe, that the additive
will achieve its intended technical effect, and therefore, that the
regulations in Sec. 176.180 should be amended as set forth below in
this document.
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 previously. 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 8B4630 (October
13, 1998, 63 FR 54717). 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 September 23, 1999, 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
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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.
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. Memoranda, dated January 13, 1999, and March 8, 1999, from
the Chemistry Review Team, FDA, to the file concerning FAP 8B4630
(MATS No. 1011), Servo Delden BV, concerning the use of polyethylene
glycol monoisotridecyl ether sulfate sodium salt as a surfactant in
coatings in food-contact paper and paperboard,
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. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,''
National Cancer Institute, NCI-CG-TR-80, 1978.
4. Memorandum, dated January 25, 1999, from the Indirect
Additives Branch, FDA, to the Executive Secretary, Quantitative Risk
Assessment Committee, FDA, concerning estimation of upper-bound
lifetime risk from ethylene oxide and 1,4-dioxane in polyethylene
glycol monoisotridecyl ether sulfate, sodium salt (PGMES): food
additive petition No. 8B4630 (Servo Delden BV).
5. Dunkelberg, H., ``Carcinogenicity of Ethylene Oxide and 1,2-
propylene Oxide Upon Intragastric Administration to Rats,''British
Journal of Cancer, 46: pp. 924-933, 1982.
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 ``Lists 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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* * * *
* * *
Polyethylene glycol monoisotridecyl For use only as a surfactant at
ether sulfate, sodium salt (CAS Reg. levels not to exceed 3 percent
No. 150413-26-6). in latex formulations used in
pigment binders for paper and
paperboard.
* * * *
* * *
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Dated: August 5, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-21850 Filed 8-23-99; 8:45 am]
BILLING CODE 4160-01-F
