[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Rules and Regulations]
[Pages 20542-20546]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-8712]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2010-0274; FRL-8868-4]


Escherichia coli O157:H7 Specific Bacteriophages; Temporary 
Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a temporary exemption from the 
requirement of a tolerance for residues of lytic bacteriophages that 
are specific to Escherichia coli O157:H7, sequence negative for shiga 
toxins I and II, and grown on atoxigenic host bacteria when applied/
used on food contact surfaces in food processing plants in accordance 
with the terms of Experimental Use Permit (EUP) No. 74234-EUP-2. 
Intralytix, Inc. submitted a petition to EPA under the Federal Food, 
Drug, and Cosmetic Act (FFDCA), requesting the temporary tolerance 
exemption. This regulation eliminates the need to establish a maximum 
permissible level for residues of lytic bacteriophages that are 
specific to Escherichia coli O157:H7, sequence negative for shiga 
toxins I and II, and grown on atoxigenic host bacteria. The temporary 
tolerance exemption expires on April 1, 2013.

[[Page 20543]]


DATES: This regulation is effective April 13, 2011. Objections and 
requests for hearings must be received on or before June 13, 2011, and 
must be filed in accordance with the instructions provided in 40 CFR 
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: EPA has established a docket for this action under docket 
identification (ID) number EPA-HQ-OPP-2010-0274. All documents in the 
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is 
not publicly available, e.g., Confidential Business Information (CBI) 
or other information whose disclosure is restricted by statute. Certain 
other material, such as copyrighted material, is not placed on the 
Internet and will be publicly available only in hard copy form. 
Publicly available docket materials are available in the electronic 
docket at http://www.regulations.gov, or, if only available in hard 
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac 
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket 
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The Docket Facility telephone number is (703) 
305-5805.

FOR FURTHER INFORMATION CONTACT: Tracy Lantz, Antimicrobials Division 
(7510P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-6415; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 180 through the Government Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation in accordance with the instructions provided 
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify 
docket ID number EPA-HQ-OPP-2010-0274 in the subject line on the first 
page of your submission. All objections and requests for a hearing must 
be in writing, and must be received by the Hearing Clerk on or before 
June 13, 2011. Addresses for mail and hand delivery of objections and 
hearing requests are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing that does not contain any CBI for inclusion in the public 
docket. Information not marked confidential pursuant to 40 CFR part 2 
may be disclosed publicly by EPA without prior notice. Submit a copy of 
your non-CBI objection or hearing request, identified by docket ID 
number EPA-HQ-OPP-2010-0274, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Mail: Office of Pesticide Programs (OPP) Regulatory Public 
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
     Delivery: OPP Regulatory Public Docket (7502P), 
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South 
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only 
accepted during the Docket Facility's normal hours of operation (8:30 
a.m. to 4 p.m., Monday through Friday, excluding legal holidays). 
Special arrangements should be made for deliveries of boxed 
information. The Docket Facility telephone number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of May 5, 2010 (75 FR 24692) (FRL-8820-7), 
EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 
346a(d)(3), announcing the filing of a pesticide tolerance petition (PP 
9G7585) by Intralytix, Inc., 701 East Pratt Street, Baltimore, MD 
21202. The petition requested that 40 CFR part 180 be amended by 
establishing a temporary exemption from the requirement of a tolerance 
for residues of Escherichia coli O157:H7 Specific Bacteriophages. This 
notice referenced a summary of the petition prepared by the petitioner 
Intralytix, Inc., which is available in the docket, http://www.regulations.gov. There were no comments received in response to the 
notice of filing.
    Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an 
exemption from the requirement for a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if EPA determines that 
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of FFDCA defines 
``safe '' to mean that ``there is a reasonable certainty that no harm 
will result from aggregate exposure to the pesticide chemical residue, 
including all anticipated dietary exposures and all other exposures for 
which there is reliable information.'' This includes exposure through 
drinking water and in residential settings, but does not include 
occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in 
establishing or maintaining in effect an exemption from the requirement 
of a tolerance, EPA must take into account the factors set forth in 
section 408(b)(2)(C) of FFDCA, which require EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. * * 
*'' Additionally, section 408(b)(2)(D) of FFDCA requires that the 
Agency consider ``available information concerning the cumulative 
effects of a particular pesticide's residues'' and ``other substances 
that have a common mechanism of toxicity.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other

[[Page 20544]]

exposures that occur as a result of pesticide use in residential 
settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of FFDCA, EPA has reviewed the 
available scientific data and other relevant information in support of 
this action and considered its validity, completeness and reliability 
and the relationship of this information to human risk. EPA has also 
considered available information concerning the variability of the 
sensitivities of major identifiable subgroups of consumers, including 
infants and children.
    Phages are naturally occurring viruses infecting bacteria. They are 
found in soil and water and in association with plants and animals, 
including humans. Bacteriophages are obligate parasites of bacteria, 
which means they attach to, infect, and reproduce in bacteria. Phages 
are host-specific for bacteria, with specific bacteriophages attacking 
only one bacterial species and most frequently only one strain within a 
bacterial species. As such, phages do not attack other beneficial 
bacteria. In addition, there is no evidence for bacteriophages 
infecting any other life form, including humans, except bacteria. Thus, 
non-target organisms, such as mammals, birds, fish, plants, and other 
wildlife, are not affected by exposure to bacteriophages. Humans and 
other animals commonly consume bacteriophages as they are abundantly 
found in water, on plant surfaces, and in foods such as ground beef, 
pork sausage, chicken, oysters, cheese, fresh mushrooms, and lettuce. 
In addition, phages are common commensals of the human gut and likely 
play an important role in regulating populations of various bacteria in 
the gastrointestinal tract. As cited in public literature, phages have 
been used for more than 80 years as therapeutic agents with no ill 
effects and are active against bacteria that cause many infections and 
human diseases.
    Since bacteriophage do not infect humans, there is not a human 
health risk concern from the bacteriophages themselves. The potential 
concerns for human health risk from bacteriophages relate to their 
interaction with the bacteria they infect. If bacteriophage do not lyse 
(i.e., break open) the bacterial cell they infect, there is a 
possibility the cell will survive the infection and incorporate any DNA 
carried by the bacteriophage in its genome (i.e. lysogenize). If genes 
for shigatoxins I and II, often associated with pathogenic strains of 
Escherichia coli O157:H7, are carried by a lysogenized bacteriophage 
into an atoxigenic Escherichia coli, there is a possibility, in theory, 
to convert a commensal and harmless bacterium into a pathogen. This 
theoretical risk is handled in three ways for this tolerance exemption: 
(1) Only lytic bacteriophage are used; (2) bacteriophage covered by 
this tolerance exemption are DNA sequenced to ensure they do not have 
the ability to convey shigatoxins I and II; and (3) host bacteria used 
to grow bacteriophage also are atoxigenic in that they do not carry DNA 
sequences capable of shigatoxin production.
    To address the infectivity and toxicity endpoints for oral, 
pulmonary, and injection exposures, the petitioner provided publicly 
available information documenting a lack of mammalian toxicity or 
infectivity associated with bacteriophages due to the specificity of 
bacteriophages attachment and attack to a narrow range of bacterial 
strains. As a result, the public literature demonstrates that phages 
pose little to no risk to humans even with the known wide exposure in 
food and the environment.
    Based on the published literature and information submitted in 
accordance with the Tier I toxicology data requirements set forth in 40 
CFR 158.2140(c), the Tier II and Tier III toxicology data requirements 
also set forth therein were not triggered and, therefore, not required 
in connection with this action.

IV. Aggregate Exposures

    In examining aggregate exposure, section 408 of FFDCA directs EPA 
to consider available information concerning exposures from the 
pesticide residue in food and all other non-occupational exposures, 
including drinking water from ground water or surface water and 
exposure through pesticide use in gardens, lawns, or buildings 
(residential and other indoor uses).

A. Dietary Exposure

    1. Food. All phages, including those at issue in this action, are 
similar in nature in that they are host-specific, attacking only 
bacteria. Published literature submitted by the registrant, and other 
publically available literature, indicate that humans are exposed to 
phages daily, and these phages are commonly found in humans, having no 
known adverse effects. Indeed, humans and other animals routinely 
consume phages when they eat food such as raw produce and cheese. For 
example, it is reported that 1,000 (10\3\) to 5 x 10\5\ phages can be 
isolated routinely per gram (g) of high quality cheese. Pathogenic 
microorganisms are often found in foods; therefore, it is not 
surprising that one study found Escherichia coli and coliphages in 11 
of 12 foods purchased at retail markets. In this study, 10 purchases of 
each of the 12 foods were made. All 10 of the fresh ground beef 
purchases were contaminated with Escherichia coli, and all 10 contained 
coliphages. In addition to ground beef, Escherichia coli and coliphages 
were found in chicken, fresh pork, fresh oyster, fresh mushrooms, 
lettuce, chicken pot pie, biscuit dough, deli loaf, deli roasted 
turkey, and package roasted chicken. Another example of phages in food 
has been Propionibacterium freundenreichii phage found in 
concentrations as high as 1.4 x 10\6\/gm of swiss cheese.
    The use of the bacteriophages covered by this tolerance in food 
processing plants on food contact surfaces could result in some 
residues of these bacteriophages on food. The Agency anticipates that 
food coming into contact with these surfaces could get residues of the 
phages on them and foods with Escherichia coli O157:H7 may end up with 
more phages on them as the bacteriophages covered by this tolerance 
exemption infect the bacteria and produce progeny.
    2. Drinking water exposure. The Escherichia coli bacteriophages 
covered by this tolerance exemption are not intended for use in 
drinking water, nor are the approved uses likely to result in these 
bacteriophages reaching surface water or ground water that might be 
used as drinking water. Use sites are only for food processing 
facilities.

B. Other Non-Occupational Exposure

    Since Escherichia coli bacteriophages subject to this tolerance 
exemption are only intended to be applied to food contact surfaces in 
food processing plants, the potential for non-occupational, non-dietary 
exposures (i.e., dermal and inhalation exposures) to these phages by 
the general population, including infants and children, is highly 
unlikely.

V. Cumulative Effects From Substances With a Common Mechanism of 
Toxicity

    Section 408(b)(2)(D)(v) of FFDCA requires that, when considering 
whether to establish, modify, or revoke a tolerance, the Agency 
consider ``available information'' concerning the cumulative effects of 
a particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.''
    EPA has not found lytic bacteriophages that are specific to 
Escherichia coli O157:H7, sequence negative for shiga toxins I and II, 
and grown on atoxigenic host bacteria to

[[Page 20545]]

share a common mechanism of toxicity with any other substances. 
Moreover, bacteriophage that meet these conditions do not appear to 
produce a toxic metabolite produced by other substances. Therefore, for 
the purposes of this action, EPA has assumed that lytic bacteriophages 
that are specific to Escherichia coli O157:H7, sequence negative for 
shiga toxins I and II, and grown on atoxigenic host bacteria do not 
have a common mechanism of toxicity with other substances. For 
information regarding EPA's efforts to determine which chemicals have a 
common mechanism of toxicity and to evaluate the cumulative effects of 
such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

VI. Determination of Safety for U.S. Population, Infants and Children

A. U.S. Population

    Based on the fact that bacteriophages are host-specific and do not 
cause harm to human health, except in theoretical instances that the 
Agency is avoiding through its conditions on this exemption, there is 
reasonable certainty that no harm will result to the U.S. population, 
including infants and children, from aggregate exposure to residues of 
lytic bacteriophages that are specific to Escherichia coli O157:H7, 
sequence negative for shiga toxins I and II, and grown on atoxigenic 
host bacteria. This includes all anticipated dietary exposures and all 
other exposures for which there is reliable information.

B. Infants and Children

    FFDCA section 408 (b)(2)(C) provides that EPA shall apply an 
additional tenfold margin of exposure (MOE) for infants and children in 
the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and 
exposure, unless EPA determines that a different MOE will be safe for 
children. MOEs, which are often referred to as uncertainty (safety) 
factors, are incorporated into EPA risk assessments either directly, or 
through the use of a MOE analysis or by using uncertainty factors in 
calculating a dose level that poses no appreciable risk. As previously 
mentioned in the toxicological profile, humans, including infants and 
children, have been exposed to phages generally through food and water, 
where they are commonly found, and through decades of therapeutic use, 
with no known or reported adverse effects. Based on all available 
information, the Agency concludes that lytic bacteriophages that are 
specific to Escherichia coli O157:H7, sequence negative for shiga 
toxins I and II, and grown on atoxigenic host bacteria are non-toxic to 
mammals, including infants and children. Because there are no threshold 
effects of concern to infants, children, and adults when lytic 
bacteriophages that are specific to Escherichia coli O157:H7, sequence 
negative for shiga toxins I and II, and grown on atoxigenic host 
bacteria are used as labeled, the Agency concludes that the additional 
MOE is not necessary to protect infants and children and that not 
adding any additional MOE will be safe for infants and children.

VII. Other Considerations

A. Analytical Enforcement Methodology

    An analytical method is not required for enforcement purposes since 
the Agency is establishing an exemption from the requirement of a 
tolerance without any numerical limitation.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and 
Agriculture Organization/World Health Organization food standards 
program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    The Codex has not established a MRL for lytic bacteriophages that 
are specific to Escherichia coli O157:H7, sequence negative for shiga 
toxins I and II, and grown on atoxigenic host bacteria.

C. Revisions to Petitioned-for Tolerances

    In its petition PP 9G7585, Intralytix requested that the Agency 
establish a tolerance exemption for residues of Escherichia coli 
O157:H7 specific bacteriophages. The Agency is narrowing the scope of 
the tolerance exemption to residues of lytic bacteriophages that are 
specific to Escherichia coli O157:H7, sequence negative for shiga 
toxins I and II, and grown on atoxigenic host bacteria because that is 
the category of bacteriophages for which the Agency can make a safety 
finding.

VIII. Conclusion

    The Agency concludes that there is a reasonable certainty that no 
harm will result to the U.S. population, including infants and 
children, from aggregate exposure to residues of lytic bacteriophages 
that are specific to Escherichia coli O157:H7, sequence negative for 
shiga toxins I and II, and grown on atoxigenic host bacteria, including 
all anticipated dietary exposures and all other exposures for which 
there is reliable information, when used according to label directions, 
as a microbial on food contact surfaces in food processing plants. 
Therefore, a temporary exemption is established for residues of lytic 
bacteriophages that are specific to Escherichia coli O157:H7, sequence 
negative for shiga toxins I and II, and grown on atoxigenic host 
bacteria.

IX. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this final rule has been 
exempted from review under Executive Order 12866, this final rule is 
not subject to Executive Order 13211, entitled Actions Concerning 
Regulations That Significantly Affect Energy Supply, Distribution, or 
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled 
Protection of Children from Environmental Health Risks and Safety Risks 
(62 FR 19885, April 23, 1997). This final rule does not contain any 
information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any 
special considerations under Executive Order 12898, entitled Federal 
Actions To Address Environmental Justice in Minority Populations and 
Low-Income Populations (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under section 408(d) of FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes,

[[Page 20546]]

nor does this action alter the relationships or distribution of power 
and responsibilities established by Congress in the preemption 
provisions of section 408(n)(4) of FFDCA. As such, the Agency has 
determined that this action will not have a substantial direct effect 
on States or tribal governments, on the relationship between the 
national government and the States or tribal governments, or on the 
distribution of power and responsibilities among the various levels of 
government or between the Federal Government and Indian tribes. Thus, 
the Agency has determined that Executive Order 13132, entitled 
Federalism (64 FR 43255, August 10, 1999) and Executive Order 13175, 
entitled Consultation and Coordination With Indian Tribal Governments 
(65 FR 67249, November 9, 2000) do not apply to this final rule. In 
addition, this final rule does not impose any enforceable duty or 
contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 
note).

X. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report to each House of the Congress and to 
the Comptroller General of the United States. EPA will submit a report 
containing this rule and other required information to the U.S. Senate, 
the U.S. House of Representatives, and the Comptroller General of the 
United States prior to publication of this final rule in the Federal 
Register. This final rule is not a ``major rule'' as defined by 5 
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: April 5, 2011.
Steven Bradbury,
Director, Office of Pesticide Programs.

    Therefore, 40 CFR part 180 is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.


0
2. Add Sec.  180.1301 to subpart D to read as follows:


Sec.  180.1301  Escherichia coli O157:H7 specific bacteriophages; 
temporary exemption from the requirement of a tolerance.

    A temporary exemption from the requirement of a tolerance is 
established for residues of lytic bacteriophages that are specific to 
Escherichia coli O157:H7, sequence negative for shiga toxins I and II, 
and grown on atoxigenic host bacteria when used/applied on food contact 
surfaces in food processing plants in accordance with the terms of 
Experimental Use Permit (EUP) No. 74234-EUP-2. This temporary exemption 
expires on April 1, 2013.

[FR Doc. 2011-8712 Filed 4-12-11; 8:45 am]
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