[Federal Register: November 29, 2007 (Volume 72, Number 229)]
[Rules and Regulations]
[Page 67572-67576]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29no07-7]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 173
[Docket No. 2006F-0409]
Secondary Direct Food Additives Permitted in Food for Human
Consumption
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 expand the conditions for the safe use of
cetylpyridinium chloride (CPC) as an antimicrobial agent in a pre-
chiller or post-chiller solution for application to raw poultry
carcasses. This action is in response to a petition filed by Safe Foods
Corp. (Safe Foods).
DATES: This rule is effective November 29, 2007. Submit written or
electronic objections and requests for a hearing by December 31, 2007.
See section VIII of the SUPPLEMENTARY INFORMATION of this document for
information on the filing of objections. 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 certain
publications in 21 CFR 173.375(a) as of November 29, 2007.
ADDRESSES: You may submit written or electronic objections and requests
for a hearing, identified by Docket No. 2006F-0409, by any of the
following methods:
Electronic submissions
Submit electronic objections in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written objections in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
[[Page 67573]]
To ensure more timely processing of objections, FDA is no longer
accepting objections submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic objections by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and docket number for this rulemaking. All objections received may be
posted without change to http://www.fda.gov/ohrms/dockets/default.htm,
including any personal information provided. For detailed instructions
on submitting objections, see the ``Objections'' heading of the
SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
objections received, go to http://www.fda.gov/ohrms/dockets/default.htm
and insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Raphael A. Davy, Center for Food
Safety and Applied Nutrition (HFS-265), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1272.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice published in the Federal Register of October 25, 2006
(71 FR 62475), FDA announced that a food additive petition (FAP 6A4767)
had been filed by Safe Foods Corp., 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. 173.375 Cetylpyridinium
chloride (21 CFR 173.375) to expand the conditions for the safe use of
CPC as an antimicrobial agent applied in a pre-chiller or post-chiller
solution to raw poultry carcasses.
CPC is currently approved under Sec. 173.375 for use as an
antimicrobial agent to treat the surface of raw poultry carcasses prior
to immersion in a chiller when applied as a fine mist spray at a level
not to exceed 0.3 grams CPC per pound of raw poultry carcass. As
conditions of safe use, the solution must contain food grade propylene
glycol (PG) at a concentration of 1.5 times that of the CPC, and the
solution must be used in systems that collect and recycle solution that
is not carried out of the system with the treated poultry carcasses.
Safe Foods initially petitioned for the use of a solution
containing up to 1 percent CPC and PG at a level 1.5 times that of CPC
as a liquid aqueous stream for either pre- or post-chiller application
without a limit on the amount of CPC applied per carcass. When
application of the CPC solution is not followed by immersion in a
chiller, the treatment would be followed by a potable water rinse of
the carcass. Safe Foods subsequently amended their petition by
decreasing the maximum concentration of CPC in the treatment solution
from 1 percent to 0.8 percent. As discussed in section II of this
document, to mitigate concerns associated with residual PG in the
treated poultry becoming a component of animal feed, in particular cat
food, Safe Foods also proposed a maximum limit of 5 gallons of solution
per carcass and a minimum of 99 percent recovery of the applied
solution.\1\
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\1\While typical application volumes would be on the order of
0.5 gallon per carcass, the 5 gallon maximum limit is to account for
infrequent occasions during processing when the line speed may
temporarily be slowed down or stopped (e.g., to accommodate
inspection of the processing line by U.S. Department of Agriculture
(USDA) personnel).
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II. Determination of Safety
Under the general safety standard in section 409 of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 348), 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.''
To establish with reasonable certainty that a food additive is not
harmful under its intended conditions of use, FDA considers the
projected human dietary intake of the additive, existing toxicological
data, and other relevant information (such as published literature)
available to the agency. FDA compares an individual's estimated daily
intake (EDI) of the additive from all food sources to an acceptable
intake level established by toxicological data. The EDI is determined
by projections based on the amount of the additive proposed for use in
particular foods and on data regarding the amount consumed from all
sources of the additive. The agency commonly uses the EDI for the 90th
percentile consumer of a food additive as a measure of high chronic
dietary intake.
At a maximum CPC application concentration of 0.8 percent and
assuming the worst-case maximum application volume of 5 gallons of
solution per carcass, FDA estimates that the mean EDI of CPC from the
petitioned use is 27.5 micrograms per person per day (microg/p/d) and
the intake at the 90th percentile is 65 microg/p/d (Ref. 1). These EDIs
subsume the exposure from the currently regulated use. As part of FDA's
safety evaluation, the agency reviewed data submitted with the petition
from two sub-chronic (90-day) toxicity studies on CPC fed to rats and
dogs. FDA concluded that the no-observable-effect level (NOEL) for the
dog, which was the most sensitive species tested, is 8.00 milligrams
per kilogram body-weight per day (mg/kg-bw/day). By applying a 1,000-
fold safety factor to this NOEL, the agency calculated the acceptable
daily intake (ADI) for CPC for a 60 kilogram human as 0.48 mg/p/d.
Therefore, taking into account the available safety information and the
conservative estimates of intake of CPC, the agency concludes that the
proposed use of CPC to treat raw poultry carcasses is safe for humans
(Ref. 2).
FDA also considered the safety of the proposed use of PG, which is
used in the CPC solution to maintain the solubility and stability of
the solution and reduce absorption of CPC on the treated poultry. PG is
generally recognized as safe as an ingredient in human food for
multiple uses and as a processing aid provided that it is used in
accordance with good manufacturing practices (21 CFR 184.1666). The
agency does not have any safety concerns regarding the proposed use of
PG in the CPC solution for treating poultry for human consumption.
Because it is common for poultry and poultry byproducts to be used in
animal feed, including cat food, the agency considered potential animal
exposure from the petitioned use of the CPC solution. As part of the
agency's evaluation of the first CPC petition that established Sec.
173.375 (FAP 2A4736), FDA considered the safety of CPC-treated poultry
and poultry byproducts used in animal feed. Because PG is toxic to
cats, the substance is prohibited from use in cat food unless the use
has been authorized by FDA through the issuance of a regulation
providing for its safe use as a food additive (21 CFR 589.1001). FDA
has previously stated in its rulemaking declaring PG for use in cat
food not generally recognized as safe that PG levels at or below 0.02
percent (200 parts per million (ppm)) in cat food is safe (61 FR 19542,
May 2, 1996). To
[[Page 67574]]
mitigate any potential concerns associated with the possibility of
residual PG becoming a component of cat food, should it become
authorized as a food additive for such use, the petitioner has proposed
a maximum limit of 5 gallons of solution per carcass and a minimum of
99 percent recovery of the applied solution. FDA concludes that
potential PG residues in cat food from CPC solution containing a
maximum level of 0.8 percent CPC, applied at a maximum volume of 5.0
gallons of solution per carcass, and a minimum of 99 percent of the
applied CPC solution captured and recovered will ensure that the 200
ppm PG limit will not be exceeded (Ref. 3).
III. Updating of Specifications for CPC
The agency is updating Sec. 173.375 by citing the specifications
for CPC in the 30th edition of the United States Pharmacopeia/National
Formulary (USP 30/NF 25) that are incorporated by reference rather than
the 24th edition (USP 24/NF 19). We compared the specifications for CPC
in the 24th and 30th editions of the USP and found them to be
identical. Therefore, the agency is making this editorial change.
IV. Comments
The agency received several comments in response to the notice
announcing the filing of the petition. One comment expressed concern
that some microorganisms washed free from the treated carcasses will
continue to thrive in the recovered solution and could potentially
contaminate poultry as the solution is reused.
The agency agrees that microbes washed off the treated carcasses
may be present in the recovered solution. However, the agency believes
that the growth of these organisms will be controlled by CPC present in
the recovered solution. Furthermore, as part of good manufacturing
practices, the user of the CPC solution for treating poultry is
expected to take appropriate steps to maintain an application solution
of acceptable microbiological quality, including sampling and analysis
of the solution to ascertain the microbiological quality of the
treatment solution and to determine when the solution in the treatment
tank needs to be changed.
In response to this comment, it should be noted that the trials
that were conducted with recycled spray solution showed that aerobic
plate counts (APC) from the carcasses treated with recycled spray
solution were extremely low compared to those from the untreated
carcasses. If bacteria were continuing to thrive in the recycled
solution, the APC from the treated carcasses would have increased.
However, this was not the case. For these reasons, FDA has no concerns
about contamination of poultry from the recycled solution.
One comment concerned an efficacy trial conducted by the petitioner
in which carcasses were tested post-chiller and after neutralizing CPC
on the treated carcasses with activated carbon. The comment expressed
concern that bacteria may have been trapped by the activated carbon
producing a ``false negative'' result for the treated carcasses.
However, the petitioner has stated that all 2,300 samples in the trial
were ``neutralized'' with activated carbon whether or not the sample
was treated with the CPC solution. The Salmonella incidence for the
samples not treated with the CPC solution ranged from 20-22 percent
positive, while the Salmonella incidence was only 4 percent positive
for the CPC-treated samples. If the activated carbon was ``trapping''
the bacteria, the incidence levels in the untreated and treated samples
would be expected to be more similar. That is, the fact that the
positive incidence rate was significantly lower in the treated samples
than in the untreated samples shows the effectiveness of the CPC
treatment, not the trapping of the bacteria, which would be expected to
occur to a similar extent in both CPC-treated and untreated carcasses.
Thus, the available data confirm that the results from this efficacy
study were not adversely affected by the use of activated carbon to
neutralize CPC on the samples.
One comment was from a user of the product who claims that when CPC
was used in their plant for the currently-regulated use, they received
customer complaints about discoloration of their poultry product. Data
from the petitioner showed that CPC does not provide a lasting
technical effect and that its use would not result in any organoleptic
changes to treated poultry. Furthermore, this customer experienced
problems with discoloration of products that were not treated with a
CPC solution. Therefore, it is unlikely that CPC was causing the
discoloration. In addition, the petitioner stated that CPC solution is
being used in similar applications in seven other poultry plants
without any complaints of discoloration that can be attributed to CPC.
Therefore, FDA does not believe that CPC used in accordance with the
conditions in the regulation will cause discoloration of the treated
poultry.
One comment expressed concern with potential occupational hazards
posed by CPC and concentration of CPC in wastewater effluent,
specifically: (1) Over complaints from inspectors for the USDA Food
Safety and Inspection Service (FSIS) about the impact of other approved
antimicrobial agents on the health of meat and poultry plant employees,
and about increased respiratory problems from introduction of
antimicrobials into the production process; (2) that the Material
Safety Data Sheet (MSDS) identified physical hazards if CPC is not used
properly (i.e., irritation to the skin, eye, respiratory and digestive
systems); and (3) that CPC is a synthetic enzyme that does not break
down easily and will accumulate in recycled water systems used by
poultry processing facilities.
The agency's response to the first two concerns is that the USDA's
New Technology Staff is responsible for reviewing new technologies that
companies employ to ensure that their use is consistent with agency
regulations and will not adversely affect product safety, inspection
procedures, or the safety of FSIS inspectors. USDA is not aware of any
health-related complaints from inspection personnel regarding the use
of CPC in federally-inspected poultry plants. Furthermore, complaints
or potential health issues associated with the use of one particular
antimicrobial agent (e.g., tri-sodium phosphate) are not necessarily
applicable to every other antimicrobial agent used for the same
purpose. The physical hazards listed on the MSDS for CPC (i.e., severe
skin irritation, severe eye irritation, severe irritation to the
respiratory system, harmful if swallowed, may cause severe irritation
to the digestive system) are physical hazards listed on MSDSs for
numerous chemical compounds that are used routinely and safely everyday
throughout the United States both in industry and by consumers. The
physical hazards that are listed on an MSDS inform the user of the
potential damaging effects to tissues and organs associated with direct
exposure to the compound and remind the user of that substance of
precautions that should be taken to avoid these adverse effects.
Furthermore, as noted by the petitioner, the CPC solution is applied in
a specially designed and fully automated cabinet, which limits worker
exposure.
In response to the comment that CPC is a synthetic enzyme that does
not degrade easily, first, the agency notes that CPC is not classified
as an enzyme; it is a quaternary ammonium compound. Second, data
provided in the environmental assessment for FAP 2A4736 demonstrated
that any CPC that enters poultry facility water systems will quickly
bind to organic solids suspended in the water and will not
[[Page 67575]]
remain solubilized in the water. To support this fact, the petitioner
provided results of an experiment in which a solution containing 22.3
ppm CPC was added to publicly owned treatment works sludge material. In
less than 1 minute, CPC was not detectable at a sensitivity of
approximately 10 parts per billion (ppb) in the water with the treated
sludge. Based on the data submitted in that environmental assessment,
it was concluded that CPC would be present in poultry plant wastewater
at levels below 0.01 ppb. Therefore, the available data do not indicate
a potential for CPC to accumulate in recycled poultry plant water
systems.
One comment expressed concern that the petitioner: (1) Did not
provide adequate data that demonstrate the expanded use of CPC meets
the requirements of a secondary direct food additive; (2) did not
provide sufficient data such as a material balance that accounts for
the CPC that is applied; and (3) did not provide sufficient
requirements (flow rate, spray pressure, time, temperature, and spray
distance) for the potable water rinse requirements following CPC
application. The comment also suggested that the regulation provide
details on the recovery system depending on line speed.
The agency notes that, regarding CPC's ongoing technical effect,
the petitioner presented data in FAP 6A4767 to demonstrate that the
food additive does not have an ongoing technical effect in poultry
treated with the CPC solution. Because the technical effect of CPC on
treated poultry occurs during processing but not after processing, it
is considered a processing aid. Therefore, FDA has determined that it
is appropriate to regulate the petitioned use of CPC as a secondary
direct food additive rather than as a direct food additive.
FDA disagrees with the comment about insufficient data to account
for the CPC that may enter the environment from use of the additive.
Information submitted in the environmental assessment for this
petition, which included mass balance information, was used by FDA to
estimate environmental introductions from the proposed use of the
additive. Based on this information, FDA estimated that environmental
concentrations of CPC will be in the low ppb level. The comment
contains no information that would cause the agency to change its
conclusion that there will be no significant impact to the environment
resulting from the petitioned use of the additive.
Regarding the comment about insufficient details for ensuring an
adequate potable water rinse of CPC-treated poultry, FDA believes that
it is sufficient for such requirements to be provided by each company
that markets CPC to each poultry processor that uses the product.
Because of plant-to-plant variation in processing conditions and
equipment, a single set of specific parameters for the potable water
rinse would not be appropriate in all processing facilities.
The petitioner further noted that testing described in the current
petition indicates that the CPC residues remaining on the treated
poultry carcass are not significantly affected by the duration or
volume of the water rinse. Thus, the comment appears to overstate the
effect of these variables on the efficiency of CPC removal and its
potential introduction to the environment. As is clear from the
agency's review of the data in FAP 2A4736 and in the current petition,
the residual levels of CPC in treated carcasses are minimal and do not
raise a health or safety concern.
Regarding the suggestion of including the details of the recovery
system in the regulation, FDA strongly disagrees with this comment. FDA
has determined that the petitioned use of the CPC solution containing a
maximum level of 0.8 percent CPC, applied at a maximum volume of 5.0
gallons of solution per carcass, and a 99 percent recovery of the
applied solution is safe. FDA does not believe it is necessary to
include details of recovery system design in order to meet these
conditions of safe use. Therefore, the agency concludes that it would
be overly prescriptive to have such equipment requirements in a food
additive regulation.
V. Conclusion
FDA reviewed data in the petition and other available relevant
material to evaluate the safety of the use of CPC as an antimicrobial
agent in a solution applied to raw poultry carcasses either pre- or
post-chiller. Based on this information, the agency concludes that the
proposed use of the additive is safe. Therefore, the conditions of use
listed in Sec. 173.375 should be amended as set forth 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 will be made available for inspection
at the Center for Food Safety and Applied Nutrition by appointment with
the information contact person (see FOR FURTHER INFORMATION CONTACT).
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.
VI. 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 Division
of Dockets Management (see ADDRESSES) between 9 a.m. and 4 p.m., Monday
through Friday.
VII. 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.
VIII. Objections
Any person who will be adversely affected by this regulation may
file with the Division of Dockets Management (see ADDRESSES) written or
electronic objections. Each objection shall be separately numbered, and
each numbered objection shall specify with particularity the provisions
of the regulation to which the 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 are to be submitted and are to 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 Division of Dockets Management between 9 a.m. and 4 p.m.,
Monday through Friday.
Please note that in January 2008, the FDA Web site is expected to
transition to the Federal Dockets Management System (FDMS). FDMS is a
Government-wide, electronic docket management system. After the
transition
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date, electronic submissions will be accepted by FDA through the FDMS
only. When the exact date of the transition to FDMS is known, FDA will
publish a Federal Register notice announcing that date.
IX. References
The following references have been placed on display in the
Division of Dockets Management (see ADDRESSES) and may be seen by
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
1. Memorandum from Folmer, Chemistry Review Group, Division of
Petition Review, to Davy, Division of Petition Review, July 10,
2007.
2. Memorandum from Khan, Toxicology Review Group, Division of
Petition Review, to Davy, Division of Petition Review, July 25,
2007.
3. Memorandum from Benjamin, Animal Feed Safety Team, Division
of Animal Feeds, to Davy, Division of Petition Review, July 18,
2007.
List of Subjects in 21 CFR Part 173
Food additives, Incorporation by reference.
0
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 COUNSUMPTION
0
1. The authority citation for 21 CFR part 173 continues to read as
follows:
Authority: 21 U.S.C. 321, 342, 348.
0
2. Revise Sec. 173.375 to read as follows:
Sec. 173.375 Cetylpyridinium chloride.
Cetylpyridinium chloride (CAS Reg. No. 123-03-05) may be safely
used in food in accordance with the following conditions:
(a) The additive meets the specifications of the United States
Pharmacopeia (USP)/National Formulary (NF) described in USP 30/NF 25,
May 1, 2007, pp. 1700-1701, which is incorporated by reference. The
Director of the Office of the Federal Register approves this
incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR
part 51. You may obtain copies from the United States Pharmacopeial
Convention, Inc., 12601 Twinbrook Pkwy., Rockville, MD 20852, or you
may examine a copy at the Center for Food Safety and Applied
Nutrition's Library, Food and Drug Administration, 5100 Paint Branch
Pkwy., College Park, MD 20740, or at the National Archives and Records
Administration (NARA). For information on the availability of this
material at NARA, call 202-741-6030, or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html
.
(b) The additive is used in food as an antimicrobial agent as
defined in Sec. 170.3(o)(2) of this chapter to treat the surface of
raw poultry carcasses. The solution in which the additive is used to
treat raw poultry carcasses shall also contain propylene glycol (CAS
Reg. No. 57-55-6) complying with Sec. 184.1666 of this chapter, at a
concentration of 1.5 times that of cetylpyridinium chloride.
(c) The additive is used as follows:
(1) As a fine mist spray of an ambient temperature aqueous solution
applied to raw poultry carcasses prior to immersion in a chiller, at a
level not to exceed 0.3 gram cetylpyridinium chloride per pound of raw
poultry carcass, provided that the additive is used in systems that
collect and recycle solution that is not carried out of the system with
the treated poultry carcasses; or
(2) As a liquid aqueous solution applied to raw poultry carcasses
either prior to or after chilling at an amount not to exceed 5 gallons
of solution per carcass, provided that the additive is used in systems
that recapture at least 99 percent of the solution that is applied to
the poultry carcasses. The concentration of cetylpyridinium chloride in
the solution applied to the carcasses shall not exceed 0.8 percent by
weight. When application of the additive is not followed by immersion
in a chiller, the treatment will be followed by a potable water rinse
of the carcass.
Dated: November 12, 2007.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E7-23182 Filed 11-28-07; 8:45 am]
BILLING CODE 4160-01-S