[Federal Register Volume 64, Number 104 (Tuesday, June 1, 1999)]
[Rules and Regulations]
[Pages 29224-29227]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-13670]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 173
[Docket No. 97F-0450]
Secondary Direct Food Additives Permitted in Food for Human
Consumption; Boiler Water Additives
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 sorbitol anhydride
esters, an emulsifier blend of sorbitan monostearate, polyoxyethylene
(20) sorbitan monostearate (polysorbate 60), and polyoxyethylene (20)
sorbitan monolaurate (polysorbate 20) as an anticorrosive agent in
boilers where steam may contact food. This action is in response to a
petition filed by Nalco Chemical Co.
DATES: This regulation is effective June 1, 1999; written objections
and requests for a hearing by July 1, 1999. The Director of the Office
of the Federal Register approves the incorporation by reference in
accordance with 5 U.S.C. 552(a) and 1 CFR part 51 of a certain
publication in Sec. 173.310 (21 CFR 173.310), effective June 1, 1999.
ADDRESSES: Submit written objections to the Dockets Management Branch
(HFA-305), Food and Drug Administration,
[[Page 29225]]
5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Martha D. Peiperl, Center for Food
Safety and Applied Nutrition (HFS-215), 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 November 13, 1997
(62 FR 60903), FDA announced that a food additive petition (FAP 7A4540)
had been filed by Nalco Chemical Co., One Nalco Center, Naperville, IL
60568-1198. The petition proposed to amend the food additive
regulations in Sec. 173.310 Boiler water additives to provide for the
safe use of an emulsifier blend containing sorbitan monostearate,
polyoxyethylene (20) sorbitan monostearate, and polyoxyethylene (20)
sorbitan monolaurate as an anticorrosive agent in boilers where steam
may contact food. The emulsifier blend is a simple mixture of these
three substances, each of which is an ester of sorbitol anhydride. For
convenience of listing of the mixture, the agency chooses to use the
name sorbitol anhydride esters (SAHE) for this additive.
Sorbitan monostearate is currently approved in Sec. 73.1001 (21 CFR
73.1001) as a diluent in color additive mixtures for drug use exempt
from certification; in Sec. 172.515 (21 CFR 172.515) as a synthetic
flavoring substance and adjuvant; in 21 CFR 172.842 as an emulsifier;
and in Sec. 173.340 (21 CFR 173.340) as a defoaming agent.
Polyoxyethylene (20) sorbitan monostearate (polysorbate 60) is
currently approved in Sec. 73.1001 as a diluent in color additive
mixtures for drug use exempt from certification; in Sec. 172.515 as a
synthetic flavoring substance and adjuvant; in 21 CFR 172.836 as an
emulsifier, foaming agent, dough conditioner, dispersing agent, and
surfactant and wetting agent; and in Sec. 173.340 as a defoaming agent.
Polyoxyethylene (20) sorbitan monolaurate (polysorbate 20) is currently
approved in Sec. 172.515 as a synthetic flavoring substance and
adjuvant.
In its evaluation of the safety of SAHE, FDA has reviewed the
safety of the three esters and the chemical impurities that may be
present in them resulting from their manufacturing process. Because
these three esters have similar chemical structures, which do not react
with each other, FDA has determined that its safety review for each of
the three esters would be the same as that for the SAHE mixture.
Therefore, FDA refers to each ester, rather than the additive as a
whole, in its evaluation of the safety of SAHE in this final rule.
Although none of the esters have been shown to cause cancer, two of
them (polysorbate 20 and polysorbate 60) may contain minute amounts of
unreacted 1,4-dioxane (DX) and ethylene oxide (EO), which are
carcinogenic impurities resulting from their manufacture. Residual
amounts of impurities are commonly found in chemical products,
including food additives.
II. Determination of Safety
Under the general safety standard section 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)).
III. Safety of Petitioned Use of the Additive
FDA estimates that the petitioned use of SAHE will result in a
maximum daily dietary exposure to each ester of approximately 0.8 part
per million. This corresponds to an estimated daily intake (EDI) of 2.5
milligrams per person per day (/p/d) of each ester (Ref. 1).
The agency has reviewed the available toxicological data on the
three sorbitol anhydride esters. Based on the available toxicology data
for sorbitan monostearate and polysorbate 60 and the fact that their
additional dietary exposure from the proposed use would be small
compared to that from their currently regulated uses, the agency
concludes that the estimated dietary exposure resulting from the
petitioned use of these two esters is safe. The agency also finds that
polysorbate 60 and polysorbate 20 would hydrolyze to similar breakdown
products under the proposed conditions of use, the only difference
being the chain length of the fatty acid residue (C12 for
polysorbate 20 and C16 or C18 for polysorbate
60). Based on the chemical similarities between polysorbate 60 and
polysorbate 20, the agency concludes that the toxicology data for
polysorbate 60 can be used to support the safety of polysorbate 20
under their limited exposure anticipated from the petitioned use of
SAHE. Moreover, based on the agency's review of the estimated dietary
exposure from all three esters in SAHE, the agency concludes that the
estimated small dietary exposure resulting from the proposed use of
this additive is safe.
Under the proposed conditions of use, any residual EO will
quantitatively react with the boiler water to form ethylene glycol
(Ref. 1). Thus, no EO will be present in the steam that contacts food.
Consequently, the exposure to EO from the petitioned use of SAHE will
be zero. Therefore, 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 DX, a carcinogenic chemical that may
be present as an impurity in two of the components of the additive
(polysorbate 20 and polysorbate 60). This risk evaluation of DX has two
aspects: (1) Assessment of the exposure to the impurity from the
petitioned use of the additive, and (2) extrapolation of the risk
observed in the animal bioassay to the conditions of exposure to
humans.
A. 1,4-Dioxane
FDA has estimated the exposure to DX from the petitioned use of the
additive as an anticorrosive agent in boilers where steam may contact
food to be no more than 17 parts per trillion in the daily diet (3
kilograms), or 50 nanograms (ng)/p/d (Ref. 1). The agency used data
from a carcinogenesis bioassay on DX, conducted by the National Cancer
Institute (Ref. 2), to estimate the upper-bound limit of lifetime human
risk from exposure to this chemical resulting from the petitioned use
of the additive. The results of the bioassay on DX demonstrated that
the material was carcinogenic for female rats under the conditions of
the study. The authors reported that the rodent bioassay showed that
the test material caused a significantly increased incidence of
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squamous cell carcinomas and hepatocellular tumors in female rats.
Based on the agency's estimate that exposure to DX will not exceed
50 ng/p/d, FDA estimates that the upper-bound limit of lifetime human
risk from the petitioned use of the subject additive is 1.8 x
10-9 or 1.8 in a billion (Ref. 3). Because of the numerous
conservative assumptions used in calculating the exposure estimate, the
actual lifetime-averaged individual exposure to DX 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 DX would result from
the petitioned use of the additive.
B. Need for Specifications
The agency has also considered whether specifications are necessary
to control the amount of DX present as an impurity in SAHE. The agency
finds that new specifications are not necessary for the following
reasons: (1) Because of the low levels at which DX may be expected to
remain as an impurity following production of SAHE, 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 DX is very low, 1.8 in a billion.
IV. Conclusion
FDA has evaluated data in the petition and other relevant material.
Based on this information, the agency concludes that the proposed use
of the additive as an anticorrosive agent in boilers where steam may
contact food is safe, that the additive will achieve its intended
technical effect, and therefore, that the regulations in Sec. 173.310
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.
V. 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.
VI. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
VII. Objections
Any person who will be adversely affected by this regulation may at
any time on or before July 1, 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 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, dated April 20, 1998, from the Division of
Product Manufacture and Use (HFS-246) to the Division of Petition
Control (HFS-215).
2. ``Bioassay of 1,4-Dioxane for Possible Carcinogenicity,''
National Cancer Institute, NCI-CG-TR-80, 1978.
3. Memorandum, dated June 19, 1998, from the Division of
Petition Control (HFS-215) to Executive Secretary, Quantitative Risk
Assessment Committee (QRAC) (HFS-308).
List of Subjects in 21 CFR Part 173
Food additives, Incorporation by reference.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
173 is amended as follows:
PART 173--SECONDARY DIRECT FOOD ADDITIVES PERMITTED IN FOOD FOR
HUMAN CONSUMPTION
1. The authority citation for 21 CFR part 173 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348.
2. Section 173.310 is amended in the table in paragraph (c) by
alphabetically adding an entry for ``sorbitol anhydride esters'' under
the headings ``Substances'' and ``Limitations'' to read as follows:
Sec. 173.310 Boiler water additives.
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(c) * * *
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Substances Limitations
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Sorbitol anhydride esters: a mixture consisting of The mixture is used as an anticorrosive agent in steam
sorbitan monostearate as defined in Sec. 172.842 of boiler distribution systems, with each component not
this chapter; polysorbate 60 ((polyoxyethylene (20) to exceed 15 parts per million in the steam.
sorbitan monostearate)) as defined in Sec. 172.836 of
this chapter; and polysorbate 20 ((polyoxyethylene
(20) sorbitan monolaurate)), meeting the
specifications of the Food Chemicals Codex, 4th ed.
(1996), pp. 306-307, which is incorporated by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR
part 51. Copies are available from the National
Academy Press, 2101 Constitution Ave. NW., Box 285,
Washington, DC 20055 (Internet http://www.nap.edu), or
may be examined at the Center for Food Safety and
Applied Nutrition's Library, Food and Drug
Administration, 200 C St. SW., rm. 3321, Washington,
DC, or at the Office of the Federal Register, 800
North Capitol St. NW., suite 700, Washington, DC.
* * * * * *
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Dated: May 22, 1999.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 99-13670 Filed 5-28-99; 8:45 am]
BILLING CODE 4160-01-F