[Federal Register Volume 63, Number 205 (Friday, October 23, 1998)]
[Rules and Regulations]
[Pages 56786-56789]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-28410]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 175
[Docket No. 98F-0433]
Indirect Food Additives: Adhesives and Components of Coatings
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
mono-isotridecyl ether sulfate, sodium
[[Page 56787]]
salt as a surfactant in adhesives intended for use in contact with
food. This action is in response to a petition filed by Servo Delden
BV.
DATES: This regulation is effective October 23, 1998; submit written
objections and requests for a hearing by November 23, 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 June 30, 1998 (63 FR 35603), FDA announced that a food
additive petition (FAP 8B4600) had been filed by Servo Delden BV, 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. 175.105 Adhesives (21 CFR 175.105) to provide for the safe use of
polyethylene glycol mono-isotridecyl ether sulfate, sodium salt as a
surfactant in adhesives intended for use in contact with 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 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 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 proposed 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, polyethylene
glycol mono-isotridecyl ether sulfate, sodium salt as a surfactant in
adhesives will result in exposure to no greater than 7 parts per
billion (ppb) of the additive in the daily diet (3 kilogram (kg)) or an
estimated daily intake of 21 microgram per person per day (g/
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
proposed 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 in adhesives to be 0.2 ppb of the daily diet (3 kg)
or 0.6 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
proposed use of the additive. The results of the bioassay on 1,4-
dioxane demonstrated that the test material caused 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 proposed 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 proposed use of the additive.
B. Ethylene Oxide
FDA has estimated the exposure to ethylene oxide from the
petitioned use of the additive in adhesives to be 5 parts per trillion
in the daily diet (3 kg) or 15 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. 5), 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 the test
material caused significantly increased incidence of squamous cell
carcinomas of the forestomach and carcinomas of the glandular stomach
in female rats.
Based on the agency's exposure estimate to ethylene oxide of 15 ng/
p/d, FDA estimates that the upper-bound limit of lifetime human risk
from the proposed use of the subject additive is 2.8 x 10-8
(or 2.8 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.
[[Page 56788]]
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 additives, 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
2.8 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. 175.105 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 8B4600 (June 30,
1998, 63 FR 35603). 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 November 23, 1998, 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.
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 from the Chemistry Review Team, FDA, to the file
concerning FAP 8B4600 (MATS No. 978, M2.0 & 2.1), Servo Delden BV,
use of polyethylene glycol mono-isotridecyl ether sulfate sodium
salt as a component of adhesives, dated July 16, 1998.
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 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 mono-isotridecyl ether
sulfate, sodium salt as a surfactant in adhesives: Food Additive
petition No. 8B4600 (Servo Delden BV),'' dated July 22, 1998.
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 175
Adhesives, 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
175 is amended as follows:
PART 175--INDIRECT FOOD ADDITIVES: ADHESIVES AND COMPONENTS OF
COATINGS
1. The authority citation for 21 CFR part 175 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348, 379e.
2. Section 175.105 is amended in the table in paragraph (c)(5) by
alphabetically adding an entry under the heading ``Substances'' to read
as follows:
Sec. 175.105 Adhesives.
* * * * *
(c) * * *
(5) * * *
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Substances Limitations
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* * * *
* * *
Polyethylene glycol mono-
isotridecyl ether sulfate, sodium
salt (CAS Reg. No. 150413-26-6).
* * * *
* * *
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[[Page 56789]]
Dated: October 15, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-28410 Filed 10-22-98; 8:45 am]
BILLING CODE 4160-01-F
