[Federal Register Volume 77, Number 172 (Wednesday, September 5, 2012)]
[Proposed Rules]
[Pages 54499-54511]
[FR Doc No: 2012-21843]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 725

[EPA-HQ-OPPT-2011-0740; FRL-9348-1]
RIN 2070-AJ65

Microorganisms; General Exemptions From Reporting Requirements;
Revisions to Recipient Organisms Eligible for Tier I and Tier II
Exemptions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA received petitions to add Trichoderma reesei and Bacillus
amyloliquefaciens to the list of microorganisms that may be used as
recipient microorganisms in order to qualify for the exemption from
full notification and reporting procedures under the Toxic Substances
Control Act (TSCA) for new microorganisms that are being manufactured
for introduction into commerce. Based on EPA's evaluation of these
petitions, EPA has made a preliminary determination that certain
strains of both microorganisms will not present an unreasonable risk of
injury to health or the environment when used as a recipient
microorganism provided that certain criteria for the introduced genetic
material and the physical containment conditions are met. Therefore,
EPA is proposing to add two additional microorganisms to the list of
recipient microorganisms that are eligible for exemptions from full
reporting for the manufacture (including import) of new microorganisms.

DATES: Comments must be received on or before November 5, 2012.
    You may submit a request for an opportunity to present oral
comments in writing on or before October 5, 2012, and if a written
request is received by EPA, an informal public hearing will be held on
this proposed rule in Washington, DC. For further information on the
informal public hearing, see Unit I.C.

ADDRESSES: Submit your written request for an opportunity to present
oral comments, identified by docket identification (ID) number EPA-HQ-
OPPT-2011-0740, to the mailing or hand delivery addresses in this unit.
    Submit your comments, identified by docket ID number EPA-HQ-OPPT-
2011-0740, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments.
     Mail: Document Control Office (7407M), Office of Pollution
Prevention and Toxics (OPPT), Environmental Protection Agency, 1200
Pennsylvania Ave. NW., Washington, DC 20460-0001.
     Hand Delivery: OPPT Document Control Office (DCO), EPA
East Bldg., Rm. 6428, 1201 Constitution Ave., NW., Washington, DC.
Attention: Docket ID Number EPA-HQ-OPPT-2011-0740. The DCO is open from
8 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the DCO is<PHONE_NUMBER>. Such deliveries are
only accepted during the DCO's normal hours of operation, and special
arrangements should be made for deliveries of boxed information.
    Instructions: Direct your comments to docket ID number EPA-HQ-OPPT-
2011-0740. EPA's policy is that all comments received will be included
in the docket without change and may be made available online at http://www.regulations.gov, including any personal information provided,
unless the comment includes information claimed to be Confidential
Business Information (CBI) or other information whose disclosure is
restricted by statute. Do not submit information that you consider to
be CBI or otherwise protected through regulations.gov or email. The
regulations.gov Web site is an ``anonymous access'' system, which means
EPA will not know your identity or contact information unless you
provide it in the body of your comment. If you send an email comment
directly to EPA without going through regulations.gov, your email
address will be automatically captured and included as part of the
comment that is placed in the docket and made available on the
Internet. If you submit an electronic comment, EPA recommends that you
include your name and other contact information in the body of your
comment and with any disk or CD-ROM you submit. If EPA cannot read your
comment due to technical difficulties and cannot contact you for
clarification, EPA may not be able to consider your comment. Electronic
files should avoid the use of special characters, any form of
encryption, and be free of any defects or viruses.
    Docket: 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., CBI or other
information whose disclosure is restricted by statute. Certain other
material, such as copyrighted material, will be publicly available only
in hard copy. Publicly available docket materials are available
electronically at http://www.regulations.gov, or, if only available in
hard copy, at the OPPT Docket. The OPPT Docket is located in the EPA
Docket Center (EPA/DC) at Rm. 3334, EPA West Bldg., 1301 Constitution
Ave. NW., Washington, DC. The EPA/DC Public Reading Room hours of
operation are 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding
legal holidays. The telephone number of the EPA/DC Public Reading Room
is<PHONE_NUMBER>, and the telephone number for the OPPT Docket is
(202) 566-0280. Docket visitors are required to show photographic
identification, pass through a metal detector, and sign the EPA visitor
log. All visitor bags are processed through an X-ray machine and
subject to search. Visitors will be provided an EPA/DC badge that must
be visible at all times in the building and returned upon departure.

FOR FURTHER INFORMATION CONTACT: For technical information contact:
Brian Lee, Chemical Control Division (7405M), Office of Pollution
Prevention and Toxics, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(202) 564-6293; email address<EMAIL_ADDRESS>    For general information contact: The TSCA-Hotline, ABVI-Goodwill,
422 South Clinton Ave., Rochester, NY 14620; telephone number: (202)
554-1404; email address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you produce,
import, process, or use either intergeneric Trichoderma reesei or
intergeneric Bacillus amyloliquefaciens. Potentially affected entities
may include, but are not limited to:

     Basic Chemical Manufacturing (NAICS code 3251).
     Pesticide, Fertilizer and other Agricultural Chemical
manufacturing (NAICS code 3253).
     Other Chemical Product and Preparation Manufacturing
(NAICS code 3259).
    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 technical person listed under FOR FURTHER
INFORMATION CONTACT.

B. What should I consider as I prepare my comments for EPA?

    1. Submitting CBI. Do not submit this information to EPA through
regulations.gov or email. Clearly mark the part or all of the
information that you claim to be CBI. For CBI information in a disk or
CD-ROM that you mail to EPA, mark the outside of the disk or CD-ROM as
CBI and then identify electronically within the disk or CD-ROM the
specific information that is claimed as CBI. In addition to one
complete version of the comment that includes information claimed as
CBI, a copy of the comment that does not contain the information
claimed as CBI must be submitted for inclusion in the public docket.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2.
    2. Tips for preparing your comments. When submitting comments,
remember to:
    i. Identify the document by docket ID number and other identifying
information (subject heading, Federal Register date and page number).
    ii. Follow directions. The Agency may ask you to respond to
specific questions or organize comments by referencing a Code of
Federal Regulations (CFR) part or section number.
    iii. Explain why you agree or disagree; suggest alternatives and
substitute language for your requested changes.
    iv. Describe any assumptions and provide any technical information
and/or data that you used.
    v. If you estimate potential costs or burdens, explain how you
arrived at your estimate in sufficient detail to allow for it to be
reproduced.
    vi. Provide specific examples to illustrate your concerns and
suggest alternatives.
    vii. Explain your views as clearly as possible, avoiding the use of
profanity or personal threats.
    viii. Make sure to submit your comments by the comment period
deadline identified.

C. Can I request an opportunity to present oral comments to the agency?

    You may submit a request for an opportunity to present oral
comments. This request must be made in writing and be identified by
docket ID number EPA-HQ-OPPT-2011-0740. This written request must be
submitted to the mailing or hand delivery addresses provided under
ADDRESSES. If such a request is received on or before October 5, 2012,
EPA will hold an informal public hearing on this proposed rule in
Washington, DC. If such a request is received, EPA will announce the
scheduling of the informal public hearing in a subsequent document in
the Federal Register. If an informal public hearing is announced, and
if you are interested in attending or presenting oral and/or written
comments at the informal public hearing, you should follow the
instructions provided in the subsequent Federal Register document
announcing the informal public hearing.

II. Background

A. What action is the agency taking?

    EPA received petitions to add Trichoderma reesei and Bacillus
amyloliquefaciens to the list of recipient microorganisms at Sec.
725.420 that are eligible for the regulatory exemptions applicable to
new microorganisms that are manufactured for introduction into commerce
(Refs. 1-3). EPA has made a preliminary determination that both of the
microorganisms, with certain limitations, meet the criteria for
addition to the list--i.e., they will not present an unreasonable risk
of injury to health or the environment provided that the other
conditions of the exemptions at 40 CFR part 725, subpart G, relating to
the introduced genetic material, and the physical containment of the
new microorganisms, have been met. Therefore, this document proposes to
grant the exemption petition for these two microorganisms.
    EPA is proposing to restrict the exemption for Trichoderma reesei
to the Trichoderma reesei strain QM6a and its derivatives (hereafter,
T. reesei QM6a). In addition, EPA is proposing to restrict the T.
reesei QM6a exemption to use under submerged standard industrial
fermentation conditions; as described in this proposed rule, these
conditions are typical throughout industry and would also meet the
existing physical containment and control requirements for the tiered
exemptions under Sec.  725.422. EPA would also restrict the T. reesei
QM6a exemption to fermentation operations in which no solid plant
material or insoluble substrate is present in the fermentation broth.
EPA is also proposing to require that any fermentation of solid plant
material or insoluble substrate may only be initiated after the
inactivation of T. reesei QM6a by a procedure that meets the existing
requirements in Sec.  725.422(d), i.e., by a procedure that has been
demonstrated and documented to be effective in reducing the viable
microbial population by at least 6 logs.
    Additionally, EPA is proposing to limit the exemption for B.
amyloliquefaciens to only industrial strains of Bacillus
amyloliquefaciens that would fall into the subspecies Bacillus
amyloliquefaciens subsp. amyloliquefaciens (hereafter, B.
amyloliquefaciens).

B. What is the agency's legal authority for taking this action?

    This action is being taken under the authority of TSCA section
5(h)(4) (15 U.S.C. 2604(h)(4)).
    Section 5(a)(1) of TSCA requires that persons notify EPA at least
90 days before they manufacture (the term ``manufacture'' includes
import under TSCA) for commercial purposes a ``new'' chemical
substance, or manufacture (including import) or process a chemical
substance for a ``significant new use.'' TSCA defines ``chemical
substance'' broadly and in terms that cover intergeneric microorganisms
as well as traditional chemical substances. Therefore, for the purposes
of TSCA, a ``new microorganism,'' like a ``new chemical substance,'' is
one that is not listed on the TSCA Chemical Substances Inventory (TSCA
Inventory) compiled under TSCA section 8(b). Section 5(h)(4) of TSCA
authorizes EPA, upon application and by rule, to exempt the
manufacturer or importer of any new chemical substance from part or all
of the provisions of TSCA section 5, if EPA determines that the
manufacture, processing, distribution in commerce, use, or disposal of
the new chemical substance will not present an unreasonable risk of
injury to human health or the environment.

C. Existing EPA Regulatory Requirements and Exemption Standard

    Manufacturers are required to report certain information to EPA 90
days

before commencing the manufacture of intergeneric microorganisms that
are not listed on the TSCA Inventory. EPA regulations at 40 CFR part
725 establish the mechanisms for reporting this information.
    Any manufacturer of a living intergeneric microorganism who is
required to report under TSCA section 5 must file a Microbial
Commercial Activity Notice (MCAN) with EPA, unless the activity is
eligible for one of the specific exemptions. The general procedures for
filing MCANs are described in 40 CFR part 725, subpart B.
    EPA regulations establish two exemptions for new microorganisms,
after the research and development stage, which are being manufactured
for introduction into commerce: The Tier I and Tier II exemptions.
    Under the Tier I exemption, if three criteria are met,
manufacturers are only required to notify EPA that they are
manufacturing a new microorganism that qualifies for this exemption 10
days before commencing manufacture, and to keep certain records. 40 CFR
725.400. To qualify for the Tier I exemption, a manufacturer must use
one of the recipient organisms listed in Sec.  725.420, and must
implement specific physical containment and control technologies. In
addition, the genetic material introduced into the recipient
microorganism must be well-characterized, limited in size, poorly
mobilizable, and free of certain sequences. 40 CFR 725.421.
    A manufacturer who otherwise meets the conditions of the Tier I
exemption may modify the specified containment restrictions, but must
submit a Tier II exemption notification. 40 CFR 725.428. The Tier II
exemption requires manufacturers to submit an abbreviated notification
describing the modified containment, and provides for a 45 day period,
during which EPA would review the proposed containment. 40 CFR 725.450
and 725.470. The manufacturer may not proceed under this exemption
until EPA approves the exemption. 40 CFR 725.470.
    EPA established a petition process at Sec.  725.67 to provide a
mechanism for the public to propose additional microorganisms as
candidates for the tiered exemptions.
    Section 725.67 directs a petitioner to submit information to
demonstrate that ``any activities affected by the requested exemption
will not present an unreasonable risk of injury to health or the
environment.'' 40 CFR 725.67(a)(2). In addition, a petitioner is
responsible to provide supporting information for this determination in
four general categories:
    1. The effects of the new microorganism on health and the
environment.
    2. The magnitude of exposure of human beings and the environment to
the new microorganism.
    3. The benefits of the new microorganism for various uses and the
availability of substitutes for such uses.
    4. The reasonably ascertainable economic consequences of granting
or denying the petition, including effects on the national economy,
small business, and technological innovation.
    Section 725.67 also specifies that when applying to list a
recipient microorganism for the tiered exemption under Sec.  725.420,
petitioners should include information addressing six specified
criteria, which EPA will use to evaluate the microorganism for listing.
40 CFR 725.67(a)(3)(iii). The six criteria are:
     Identification and classification of the microorganism
using available genotypic and phenotypic information.
     Information to evaluate the relationship of the
microorganism to any other closely related microorganisms which have a
potential for adverse effects on health or the environment.
     A history of safe commercial use for the microorganism.
     Commercial uses indicating that the microorganism products
might be subject to TSCA.
     Studies which indicate the potential for the microorganism
to cause adverse effects to health or the environment.
     Studies which indicate the survival characteristics of the
microorganism in the environment.

III. EPA's Evaluation of Available Information on the Proposed
Microorganisms for the Criteria Delineated in Sec.  725.67

    Pursuant to Sec.  725.67, Genencor International, Inc.,
(subsequently supported by the Enzyme Technical Association (ETA)) and
Novozymes North America, Inc., submitted Letters of Application to EPA
requesting that Trichoderma reesei and Bacillus amyloliquefaciens
(Refs. 1 and 2) be added to Sec.  725.420 as candidate recipient
microorganisms for the tiered exemptions. The letters of application
provided information that the submitters believed demonstrate that
activities affected by the requested exemptions would not present an
unreasonable risk of injury to health or the environment. Information
regarding the criteria specified in Sec. Sec.  725.67(a)(2) and
725.67(a)(3)(iii) were addressed in these letters of application to
list Trichoderma reesei and Bacillus amyloliquefaciens as recipient
microorganisms under Sec.  725.420.
    EPA has made a preliminary determination based on the information
provided in the Letters of Application (Refs. 1 and 2), supplemental
information provided by ETA (Refs. 4 and 5), and other information
available to EPA that T. reesei QM6a, with certain restrictions, and B.
amyloliquefaciens will not present an unreasonable risk of injury to
health or the environment when used as a recipient microorganism
provided the existing criteria for the introduced genetic material and
for physical containment conditions at Sec.  725.422 are met. EPA's
Risk Assessments for these two microorganisms (Refs. 6 and 7) are
available in the docket. This unit presents a summary of EPA's
evaluation of the available information pertinent to the six criteria
delineated in Sec.  725.67(a)(3)(iii) for both microorganisms. These
criteria follow:
     Identification and classification of the microorganism
using available genotypic and phenotypic information.
     Information to evaluate the relationship of the
microorganism to any other closely related microorganisms that have a
potential for adverse effects on health or the environment.
     A history of safe commercial use for the microorganism.
     Commercial uses indicating that the microorganism products
might be subject to TSCA.
     Studies which indicate the potential for the microorganism
to cause adverse effects to health or the environment.
     Studies which indicate the survival characteristics of the
microorganism in the environment.
    Units V. and VI. summarize EPA's evaluation of the information
relating to the criteria delineated in Sec.  725.67(a)(2) that address
hazard, exposure, benefits, and economic consequences. Specifically:
     The effects of the new microorganism on health and the
environment.
     The magnitude of exposure of human beings and the
environment to the new microorganism.
     The benefits of the new microorganism for various uses and
the availability of substitutes for such uses.
     The reasonably ascertainable economic consequences of
granting or denying the exemption, including effects on the national
economy, small business, and technological innovation.
    Unit V. provides a summary of EPA's assessments of the risks to
health and

the environment for both microorganisms. EPA's Risk Assessment
documents (Refs. 6 and 7) provide more detailed information, and
supporting references, for EPA's evaluation of the available
information and the potential risks to health and the environment. Unit
VI. provides a summary of EPA's assessments of the economic benefits
and consequences of adding both microorganisms to Sec.  725.420.

A. Evaluation of Available Information Relevant to the Criteria at
Sec.  725.67 for T. reesei QM6a as a Recipient Microorganism With
Specified Conditions of Growth

    1. Identification and classification of the microorganism using
available genotypic and phenotypic information. T. reesei is a fungus
originally isolated in the Solomon Islands in 1944. T. reesei is a
hypercellulolytic fungus found on deteriorating military fabrics such
as tents and clothing. This isolate, designated as QM6a, was initially
named Trichoderma viride. Approximately 20 years later, QM6a was re-
classified as Trichoderma reesei.
    Trichoderma reesei is the species name given to the anamorphic form
(this form reproduces asexually) of the fungus whose telemorphic form
(this form reproduces sexually) is now understood to be Hypocrea
jecorina.
    Recent taxonomic studies have shown that the species T. reesei
consists only of this single isolate QM6a and its derivatives. Many
other strains called T. reesei isolated elsewhere have now been
proposed as belonging to a newly named species, T. parareesei, based on
differences in habitat, sporulation, and metabolic versatility. T.
reesei has been shown to belong to a single species now referred to as
H. jecorina/T. reesei (QM6a) which reflects its relationship to its
teleomorph H. jecorina. The only anamorphic strains within the species
H. jecorina/T. reesei are those of QM6a and its derivatives. The
petition to add T. reesei to the list of microorganisms at Sec.
725.420 requested that EPA include all strains of T. reesei. However,
given these recent taxonomic publications, all fungal strains correctly
named T. reesei are, by definition, QM6a or a derivative.
    Adequate genotypic and phenotypic information is available for
classification of T. reesei QM6a and its derivatives. The American Type
Culture Collection (ATCC) designation for this original strain of T.
reesei QM6a is ATCC 13631.
    2. Information to evaluate the relationship of the microorganism to
any other closely related microorganisms that have a potential for
adverse effects on health or the environment. The petition to add T.
reesei to the list of microorganisms at Sec.  725.420 requested that
EPA include all strains of T. reesei. Closely related members of
section Longibrachiatum do not have a potential for adverse effects;
other less closely related Trichoderma species have a potential to
cause adverse effects as pathogens of commercially produced mushrooms.
These less closely related species include various species of the
Harzianum clade, T. aggressivum, T. pleuotrophilum, and T. fulvidum
that are responsible for significant loss of the mushroom crops of
Agaricus bisporus and Pleurotus ostreatus.
    T. reesei/H. jecorina can be distinguished from other Trichoderma
species by a comprehensive approach employing criteria of the
Genealogical Concordance Phylogenetic Species Recognition (GCPSR)
concept, which commonly requires the use of genealogies of three or
four genes, not just the sequences of spacer regions as previously
utilized for identification. Use of the GCPSR protocol will separate T.
reesei (sensu lato) from the opportunistic pathogens within the section
Longibrachiatum, including T. longibrachiatum and T. citronoviridae/H.
schweinitzii, as well as the mold disease pathogens of mushrooms.
    3. A history of safe commercial use for the microorganism. T.
reesei QM6a has a long history of safe use producing a variety of
commercial enzymes. T. reesei QM6a cellulases, beta-glucanases, and
xylanases are used by the animal feed, baking, beverages, textile
processing, detergent, pulp and paper, industrial chemicals, and
biofuels industries.
    For industrial enzyme production, T. reesei is generally grown in a
closed, submerged fermentation system. In submerged fermentation,
growth of the microorganism occurs beneath the surface of the liquid
growth medium. As described in this unit, this type of fermentation
system appears to be typical throughout the industry, based on EPA's
review of MCAN submissions over the years. This type of fermentation
system would also comply with the existing tiered exemption
requirements relating to physical containment and control technologies,
which are laid out in Sec.  725.422.
    Under this type of fermentation system, the fermentation broth is a
defined mixture of carbon and nitrogen sources, minerals, salts, and
other nutrients, is maintained at optimal pH and temperature, and is
typically aerated and mixed with no solid plant material or insoluble
substrate present. These conditions support the active growth and
productivity of the organisms. Submerged fermentation systems reduce
the potential for exposure of workers to the production organism and
fermentation broth aerosols, reduce the potential for contamination of
the culture and make the collection of extracellular enzyme simpler and
less costly. The fermentation process is terminated before the T.
reesei QM6a organisms go into the stationary growth phase (i.e., before
secondary metabolism begins). At the end of the fermentation process,
the production organisms are separated from the fermentation broth and
inactivated. Throughout the SUPPLEMENTARY INFORMATION section, EPA
refers to this process as ``submerged standard industrial
fermentation.''
    The Food and Drug Administration (FDA) has determined that several
enzymes produced by T. reesei QM6a are Generally Recognized As Safe
(GRAS). This determination supports the Agency's preliminary conclusion
that commercial use of T. reesei QM6a as a recipient microorganism for
commercial enzyme production will not present an unreasonable risk of
injury to health or the environment. T. reesei QM6a enzymes used in
foods that have been granted GRAS status include cellulase,
hemicellulase, transglucosidase, pectin lyase, acid fungal protease,
and a chymosin enzyme preparation. Data supporting the GRAS petitions
included the results of pathogenicity tests for the T. reesei QM6a
production organisms and toxicity tests for the enzyme products. The
data showed that the production strains are not pathogenic and did not
produce toxins during enzyme fermentation.
    4. Commercial uses indicating that the microorganism products might
be subject to TSCA. EPA has reviewed several MCANs involving
intergeneric T. reesei QM6a production organisms. More detailed
information on MCANs submitted to EPA can be viewed on EPA's TSCA
Biotechnology Program Web page: http://www.epa.gov/oppt/biotech/pubs/submain.htm.
    Intergeneric T. reesei QM6a strains could also be used to
manufacture industrial chemicals other than enzymes such as surfactants
or specialty chemicals.
    5. Studies which indicate the potential for the microorganism to
cause adverse effects to health or the environment--a. Human health
hazards--i. Pathogenicity. Trichoderma reesei QM6a is not pathogenic to
humans. Due to its long history of use for production of enzymes used
in food

applications, the potential for the fungus and its products to be
pathogenic or toxic to humans has been evaluated numerous times.
Various studies have been conducted assessing T. reesei QM6a's
pathogenic potential in healthy and immunocompromised laboratory
animals. Most studies have shown a lack of pathogenicity of T. reesei
QM6a. Pathogenicity studies have been conducted as part of submissions
submitted to FDA for GRAS petitions for several different enzymes used
in the food industry. Studies using intraperitoneal (ip) injection of
T. reesei QM6a in rats, using intravenous (IV) injection of T. reesei
QM6a in both healthy and immunosuppressed rats, and using ip injection
of viable and heat-killed cells of T. reesei QM6a in rats have all
demonstrated a lack of potential pathogenicity to humans.
    T. reesei QM6A is not known to possess any virulence factors
associated with colonization or disease such as adherence factors,
penetration factors, necrotic factors, toxins, or the ability to grow
at human body temperature, 37 [deg]C. There are no reports in the
literature on infection in healthy humans by T. reesei QM6A. There are
no reports of harmful effects associated with the use of or exposure to
T. reesei QM6A strains given decades of commercial use for enzyme
production. The body of evidence indicates that T. reesei QM6A does not
pose concerns regarding human pathogenicity.
    ii. Toxicity. Available data indicate that T. reesei QM6a strains
used in submerged standard industrial fermentation operations in which
no solid plant material or insoluble substrate is present in the
fermentation broth do not present human toxicity concerns. A number of
studies have been conducted assessing the potential for T. reesei QM6a
to produce toxins during submerged fermentation for production of
enzymes for food, pharmaceutical, or industrial uses. A cellulase
enzyme known as celluclast produced by T. reesei QM6a has been tested
for general oral toxicity and inhalation toxicity. Acute oral toxicity
studies conducted in mice, rats, and dogs showed that T. reesei QM6a
cellulase was not toxic to any of the test animals. Subchronic toxicity
studies showed no evidence of systemic effects in dogs or rats.
Additional toxicity studies have been conducted on other enzymes
produced by T. reesei QM6a, the results of which have been presented in
various GRAS petitions. Acute oral toxicity tests on two endoglucanases
and a glucoamylase showed a lack of toxins. Subchronic feeding studies
conducted on a cellulase, two xylanases, two endoglucanases, a
protease, and a glucoamylase also showed a lack of toxicity in rats.
    Industrial strains of T. reesei QM6a are routinely checked by the
enzyme producers to confirm the absence of antibiotic activity and
toxins including aflatoxin B, ochratoxin A, sterigmatocystin, T-2
toxin, and zearalenone according to the recommendations of the Joint
Food and Agriculture Organization and the World Health Organization
(FAO/WHO) Expert Committee on Food Additives. Relying on the data that
show T. reesei QM6a has a long history of safe use in the production of
food enzymes where there is a need to routinely check for the absence
of toxins, EPA has preliminarily concluded that strains used
industrially would not be expected to produce these compounds under the
growth conditions used for enzyme fermentation.
    iii. Mycotoxins and other secondary metabolites. The only health
concern associated with T. reesei QM6a is its ability to produce a
secondary metabolite called paracelsin, which is a peptaibol.
Peptaibols are small linear peptides of 1,000-2,000 daltons
characterized by a high content of the non-proteinogenic amino acid
[alpha]-amino-isobutyric acid (Aib), with an N-terminus that is
typically acetylated, and a C-terminus that is linked to an amino
alcohol, which is usually phenylalaninol, or sometimes valinol,
leucinol, isoleucinol, or tryptophanol. Peptaibols are associated with
a wide variety of biological activities and have antifungal,
antibacterial, sometimes antiviral, antiparasitic, and neurotoxic
activity. Paracelsin has been shown to have toxicity toward mammalian
cells such as hemolytic activity on human erythrocytes and cytotoxicity
to rat adrenal medulla PC12 cells. Paracelsin showed toxicity to PC12
cells (a cell line derived from a pheochromocytoma of the rat adrenal
medulla) with a CC50 (cytotoxicity concentration of 50%) of
21.8 micromolar ([micro]M) (Ref. 6). The in vitro hemolytic activity of
paracelsin has been reported to be C50 = 3.7 x
10-5 mole/liter (mol/L) (Ref. 6).
    Paracelsin has not been detected in the use of T. reesei QM6a under
submerged standard industrial fermentation operations in which no solid
plant material or insoluble substrate is present in the fermentation
broth; numerous toxicity studies on enzyme products of T. reesei QM6a
have demonstrated a lack of toxicity to laboratory animals. EPA
therefore generally expects that paracelsin production will be of
insignificant concern with submerged standard industrial fermentation
operations in which no solid plant material or insoluble substrate is
present in the fermentation broth.
    However, under non-standard conditions of fermentation, such as
with extended duration of fermentation, or fermentation in the presence
of insoluble carbon sources such as cellulose or in the presence of
solid plant material, paracelsin may be produced (Ref. 6). Neither the
information submitted with the petition, nor the information that is
otherwise available is sufficient to allow EPA to determine the extent
of paracelsin formation under these non-standard conditions.
Consequently, EPA is unable to determine whether the use of the microbe
under these non-standard conditions will pose an unreasonable risk to
human health and/or the environment (Ref. 6).
    b. Environmental hazards--i. Hazards to animals. T. reesei QM6a is
not pathogenic to domesticated animals or wildlife. However, the
secondary metabolite paracelsin produced by T. reesei QM6a has been
shown to exhibit toxicity to aquatic species. Twenty-four hour exposure
of paracelsin to Artemia salina (brine shrimp) suggested a lethal
concentration of 50% (LC50) of 21.26 [micro]M (40.84
micrograms per milliliter ([micro]g/ml)) which decreased to 9.66
[micro]M (18.56 [micro]g/ml) with a 36-hour (hr) exposure. With Daphnia
magna, paracelsin was found to be moderately toxic, with an
LC50 of 7.70 [micro]M (14.79 [micro]g/ml) with a 24-hr
exposure, and 5.60 [micro]M (10.76 [micro]g/ml) with a 36-hr exposure.
    ii. Hazards to plants. Trichoderma reesei QM6a is not a pathogen of
plants. Although it is capable of degrading cellulose and hemicellulose
due to the copious quantities of the enzymes it can produce, it cannot
be a primary colonizer on plant tissue as genetic studies have shown
that it does not contain any genes for ligninases that are required for
initial breakdown of plant material. This species is known as a wood
rot fungus, but it apparently attacks only decaying plant material, not
live plants.
    iii. Effects on other organisms. Peptaibols are toxic to Gram-
positive bacteria and various fungi. The inhibitory action of
peptaibols on various fungi is the reason that many species of
Trichoderma are used as biocontrol agents of plant pathogenic fungi. T.
reesei QM6a, which is known to produce only the peptaibol paracelsin,
has been shown to be inhibitory to one particular fungus, Phoma
destructiva.

    Some species of Trichoderma, specifically T. aggressivum, T.
pleuotrophilum, and T. fulvidum are pathogens of mushrooms. However, T.
reesei QM6a is not a pathogen of mushrooms.
    6. Studies which indicate the survival characteristics of the
microorganism in the environment. The species T. reesei is known only
from the single original isolate QM6a from the Solomon Islands.
Therefore, there is little information on its prevalence or behavior in
the environment. Microcosm studies have been conducted that suggest it
would survive in the environment if inadvertently released in the plant
rhizosphere and in bulk soils.
    Although T. reesei was originally isolated from a tropical climatic
region, it would be expected to persist in soils for extended periods
of time, even after cold temperatures.

B. Evaluation of Available Information Relevant to the Criteria at
Sec.  725.67 for B. amyloliquefaciens as a Recipient Microorganism

    1. Identification and classification of the microorganism using
available genotypic and phenotypic information. Bacillus
amyloliquefaciens was initially proposed as a unique species in 1943.
The name Bacillus amyloliquefaciens lost standing when it was not
included on the Approved List of Bacterial Names with Standing in
Nomenclature in 1980. Since classical phenotypic tests could not
differentiate it as a species unique from Bacillus subtilis, it was
regarded as a subspecies of B. subtilis for several decades. However,
molecular evidence from various subsequent studies led to the
conclusion that Bacillus amyloliquefaciens did indeed deserve
independent status. The DNA homology between B. subtilis and B.
amyloliquefaciens is only about 15%. In addition, there were several
phenotypic properties that differed between the two species.
Chemotaxonomic studies revealed additional capability of separating
strains of B. amyloliquefaciens from the other related species, B.
subtilis, B. licheniformis, and B. pumilus. The species has remained
within the genus Bacillus sensu stricto since it was last established
as a separate species.
    Recently, it has been proposed that there are two subspecies within
the species B. amyloliquefaciens, B. amyloliquefaciens subsp.
amyloliquefaciens and B. amyloliquefaciens subsp. plantarum. The former
subspecies includes the type strain and likely most, if not all, of the
industrial strains of B. amyloliquefaciens used for enzyme production.
The latter subspecies consists of plant-associated strains used as
biocontrol agents since they produce a number of antifungal lipopeptide
and antibacterial polyketide toxins. This proposed exemption would be
restricted to the subspecies B. amyloliquefaciens subsp.
amyloliquefaciens which contains the industrial strains used for enzyme
production. Adequate genotypic and phenotypic information is available
to accurately identify B. amyloliquefaciens subsp. amyloliquefaciens.
    2. Information to evaluate the relationship of the microorganism to
any other closely related microorganisms which have a potential for
adverse effects on health or the environment. There are several species
in the genus Bacillus that are known pathogens. These include B.
anthracis, which is pathogenic to humans and other animals, and B.
cereus, which is a common cause of food poisoning. B. thuringiensis, B.
larvae, B. lentimorbus, B. popilliae, and some strains of B. sphaericus
are pathogenic or toxigenic to certain insects. The new subspecies B.
amyloliquefaciens subsp. plantarum has been shown to exhibit toxicity
mainly to plant pathogenic fungi, but can also be cytotoxic to
mammalian cells. It is possible, using polyphasic approaches, to
differentiate between Bacillus amyloliquefaciens subsp.
amyloliquefaciens and these other species and subspecies that have the
potential to adversely affect humans or other organisms. B.
amyloliquefaciens can be distinguished from the very similar B.
subtilis by a few phenotypic traits and DNA dissimilarity.
    3. A history of safe commercial use for the microorganism. Bacillus
amyloliquefaciens has been used to produce commercial enzymes for more
than 50 years. It produces carbohydrases, proteases, nucleases,
xylanases, and phosphatases that have applications in the food,
brewing, distilling, and textile industries.
    For commercial enzyme production, B. amyloliquefaciens is grown in
a closed, submerged fermentation system. In submerged fermentation,
growth of the microorganism occurs beneath the surface of the liquid
growth medium. The fermentation broth is a defined liquid growth medium
(with no solid plant material or insoluble substrate) of carbon and
nitrogen sources, minerals, salts, and other nutrients that is
maintained at optimal pH and temperature. These conditions support the
active growth and productivity of the organisms. Submerged fermentation
systems reduce the potential for exposure of workers to the production
organism and fermentation broth aerosols, reduce the potential for
contamination of the culture, and make the collection of extracellular
enzyme simpler and less costly. The fermentation process is terminated
before the B. amyloliquefaciens organisms go into the stationary growth
phase (i.e., before secondary metabolism begins). At the end of the
fermentation process, the production organisms are separated from the
fermentation broth and inactivated. The enzyme preparation may also be
subjected to other purification processes.
    B. amyloliquefaciens has a long history of safe use for the
production of enzymes with both food and industrial uses with no
incidences associated with human pathogenicity. In response to a
petition from the ETA, FDA affirmed that carbohydrase enzyme
preparations and protease enzyme preparations derived from either B.
subtilis or B. amyloliquefaciens are GRAS for use as direct food
ingredients. The European Food Safety Authority (EFSA) has put B.
amyloliquefaciens on their list of bacteria that have a ``qualified
presumption of safety'' (QPS) because of a long history of apparent
safe use in food and feed production. However, it was put on the list
with a qualifier that only strains of B. amyloliquefaciens that do not
have toxigenic potential be used.
    One strain of B. amyloliquefaciens also has been used as a
biopesticide. A naturally occurring strain of B. amyloliquefaciens
subsp. plantarum was registered in 2000 as a biopesticide active
ingredient under the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA). It can only be used on certain ornamental, non-food plants
in greenhouses and other closed structures.
    4. Commercial uses indicating that the microorganism products might
be subject to TSCA. It is expected that intergeneric strains of B.
amyloliquefaciens will be used to produce enzymes and to manufacture
other industrial chemicals subject to TSCA. Many enzymes produced by B.
amyloliquefaciens, particularly [alpha]-amylase, are used in laundry
detergents and in textile processing. B. amyloliquefaciens also makes a
surfactant known as surfactin which functions as an antibiotic.
    5. Studies which indicate the potential for the microorganism to
cause adverse effects to health or the environment--a. Human health
hazards--i. Pathogenicity.
    Bacillus amyloliquefaciens is not pathogenic to humans. There are
no reports in the literature associating B. amyloliquefaciens with
infection or disease in humans. B. amyloliquefaciens

has been categorized as a Biosafety 1 microorganism by the Centers for
Disease Control and Prevention (CDC). Biosafety 1 microorganisms are
well-characterized agents not known to consistently cause disease in
immunocompetent adult humans, and which present minimal potential
hazard to laboratory personnel and the environment. Animal toxicity
studies were performed with B. amyloliquefaciens strain FZB24 to
support its registration as a biopesticide. Tests for acute oral
toxicity/pathogenicity, acute pulmonary toxicity/pathogenicity, and
acute injection toxicity/pathogenicity showed little to no adverse
effects, which indicated low mammalian toxicity and a lack of
pathogenicity/infectivity.
    ii. Toxins and other secondary metabolites. Although another
species in the genus Bacillus, B.cereus, has the potential to produce
food poisoning toxins which cause both emetic and diarrheal syndromes,
and a variety of local and systemic infections, the risk of food-borne
disease caused by bacilli other than B. cereus is generally considered
to be negligible because usually only B. cereus has the genes that
encode food poisoning toxins. Industrial strains of Bacillus species
belonging to the B. subtilis group, which includes B.
amyloliquefaciens, do not express B. cereus toxins. In addition, there
are no reported cases of food poisoning being caused by B.
amyloliquefaciens.
    Some strains of B. amyloliquefaciens have been shown to produce
bioactive cyclic lipopeptide metabolites such as iturin, surfactin,
fengycin, and bacillomycin D. These are cyclical lipoprotein
biosurfactants produced by non-ribosomal peptide synthesis. They have a
low mammalian toxicity as demonstrated by a lethal dose of 50%
(LD50) of >2,500 milligram/kilogram (mg/kg) in an acute
toxicity test of surfactin C, and a No Observed Adverse Effect Level
(NOAEL) of 500 mg/kg-day in a repeat dose oral gavage study. Some
strains of B. amyloliquefaciens may also produce the polyketide toxins
macrolactin, bacillanene, and difficidin. B. amyloliquefaciens also
produces the protein toxin barnase and the antifungal protein baciamin.
    There are several reports of the isolation of B. amyloliquefaciens
from water-damaged buildings in which occupants were suffering ill
health symptoms. Extracts from biomass of isolated strains of Bacillus
exhibiting antifungal properties were assessed for the toxicity
endpoints. All of the isolated B. cereus and B. amyloliquefaciens
strains studied showed cytotoxicity as evidenced by inhibition of boar
spermatozoa motility; however, the B. amyloliquefaciens strains
affected boar spermatozoa differently from the indoor B. cereus
isolates and the reference food-poisoning strain.
    The isolation of cytotoxic strains of B. amyloliquefaciens from
water-damaged buildings is of little concern in relation to this
exemption of B. amyloliquefaciens subsp. amyloliquefaciens. It is
important to note that all of the B. amyloliquefaciens strains studied
in water-damaged buildings were specifically selected for further study
because the isolates exhibited antifungal activity. Some of the
secondary metabolites produced by these biocontrol-type strains of B.
amyloliquefaciens apparently also exhibit cytotoxicity to mammalian
cells (i.e., boar spermatozoa). However, industrial strains of B.
amyloliquefaciens that would fall into the classification as B.
amyloliquefaciens subsp. amyloliquefaciens have been shown not to
produce most, if not all, of the antifungal and antibacterial
lipopeptides and polyketides produced by the biocontrol-type strains.
The genome of the type strain of B. amyloliquefaciens DSM 7\T\ (now B.
amyloliquefaciens subsp. amyloliquefaciens) is very similar to the
genome of the biocontrol strain FZB42 (B. amyloliquefaciens subsp.
plantarum). However, the latter subspecies had genomic islands carrying
prophage sequences, transposases, integrases, and recombinases that the
DSM 7\T\ type strain did not have. The DSM 7\T\ type strain was shown
to have a diminished capacity to non-ribosomally synthesize secondary
metabolites with antifungal and antibacterial activities. The DSM 7\T\
type strain could not produce the polyketides difficidin or
macrolantin, and could not produce lipopeptide such as iturin,
macrolantin, and other compounds except for the compound surfactin.
    The only other reported instance of mammalian toxin production by
B. amyloliquefaciens was during the 1980s with the commercial
production of tryptophan, by a genetically engineered strain of B.
amyloliquefaciens, strain IAM 1521. The consumption of the tryptophan
food supplement from various retail lots produced by one specific
company resulted in an epidemic of a disease known as eosinophilia-
myalgia syndrome (EMS) in which 1,511 were sickened, and 37 people
died. Although this disease incidence was widely studied, the cause of
the disease was never confirmed. It was thought to be due to the
consumption of a chemical constituent that was associated with specific
tryptophan manufacturing processes. This included the combination of
using reduced quantities of powdered carbon for a purification step
with the use of a ``new'' strain of B. amyloliquefaciens called Strain
V. There purportedly was a chemical substance produced as a result of
the genetic engineering of this certain strain, but the toxin was not
attributable to the parental strain of B. amyloliquefaciens as not all
production batches were toxic.
    Although there are isolated reports of toxin production in several
antifungal, environmental isolates of B. amyloliquefaciens, the larger
body of studies available on the safety and toxicity of B.
amyloliquefaciens strains used industrially for enzyme production (Ref.
6) indicate that these strains are safe and non-toxic. For example, the
toxicity of industrial strains of B. amyloliquefaciens, B. subtilis,
and B. licheniformis used for large-scale enzyme production has been
studied. The industrial strains did not exhibit any cytotoxicity in
Chinese hamster ovary tests. In Europe, the toxicity of two strains of
B. amyloliquefaciens used for the production of [alpha]-amylase and
bacillolysin for the product Kemzyme W Dry was assessed by the EFSA's
Scientific Panel on Additives and Products or Substances used in Animal
Feed. The panel concluded that the B. amyloliquefaciens production
strains DSM9553 and DSM9554 when used as a source of extracellular
enzyme do not present a toxigenic risk. Given its widespread
distribution in the environment, its long history of safe use in
industrial fermentation, the absence of reports on pathogenicity to
humans, and the limited reports of cytotoxicity, all indicate that the
use of B. amyloliquefaciens in fermentation facilities for production
of enzymes or specialty chemicals does not present a human health
concern.
    b. Environmental hazards--i. Hazards to animals. There are no
reports suggesting that B. amyloliquefaciens is pathogenic to
domesticated animals or wildlife. The cytotoxicity of antifungal
secondary metabolites to mammalian cells by biocontrol stains of B.
amyloliquefaciens is discussed in this unit.
    ii. Hazards to plants. B. amyloliquefaciens is not pathogenic to
plants. There are plant-associated strains of B. amyloliquefaciens that
are beneficial to plants because they inhibit the growth of fungal
plant pathogens. Various antifungal and antibacterial secondary
metabolites produced by

strains of B. amyloliquefaciens such as various iturins, surfactins,
fengycin, bacillomycins, and azalomycin have been shown to inhibit the
growth of Rhizoctonia solani, Xanthomonas campestris pv. campestris,
Alternaria brassicae, Botyris cinerea, Leptosphaeria maculans,
Verticillium longisporum, Pythium ultimatum, Aspergillus spp., Fusarium
spp., Bipolaris sorokiniana, and Fusarium oxysporum.
    In addition to the ability of B. amyloliquefaciens to produce
antifungal and antibacterial compounds, the bacterium is known as a
plant growth-promoting rhizobacterium. Some of the biological control
strains of B. amyloliquefaciens produce the phytohormone indole-3-
acetic acid (IAA).
    6. Studies which indicate the survival characteristics of the
microorganism in the environment. Using polymerase chain reaction (PCR)
techniques, it has been found that populations of viable B.
amyloliquefaciens inoculated at high densities to intact soil-core
microcosms decreased to below the detection limit within 1 month.
Survival was longer for a genetically modified B. amyloliquefaciens
strain on leaf surfaces; vegetative cells were still detected for over
2 months in the phylloplane. Viable cells were not detectable in plant
roots after 1 month or in soils after a few days. Given that the
natural habitat for B. amyloliquefaciens is typically in soil, on plant
roots, or as an endophyte within the roots or stems of plants, the
bacterium is likely to survive for a least some period of time if
inadvertently released to the environment. However, like other bacilli,
survival in soil may occur predominately as the resistant endospore
state, whereas in the rhizosphere, it may exist as active vegetative
cells.

IV. Physical Containment and Control Technologies

A. Release and Exposure Assessment in Support of Proposed TSCA Section
5(h)(4) Exemption for T. reesei QM6a

    The estimated releases of the microorganism from an enzyme
manufacturing facility and exposures of the microorganisms to workers,
the general population, and the environments are based on a generic
scenario developed by EPA for large-scale closed system fermentation.
Assumptions in the generic scenario are that the facility operates 350
days/year, produces 100 batches/year, and the maximal cell
concentration in the fermentation broth is 1 x 10\7\ colony-forming
units (cfu)/ml, and the volume of the fermentation broth is 70,000 L.
The process consists of the main steps of laboratory propagation,
fermentation and then recovery where filtration operations separate out
the biomass from the concentrated desired product. The operations,
sources of exposure and release are described in more detail in EPA's
Release and Exposure Assessments (Ref. 8).

B. Release and Exposure Assessment in Support of Proposed TSCA 5(h)(4)
Exemption for B. amyloliquefaciens

    The estimated releases of the microorganism from an enzyme
manufacturing facility and exposures of the microorganisms to workers,
the general population, and the environments are based on a generic
scenario developed by EPA for large-scale closed system fermentation.
Assumptions in the generic scenario are that the facility operates 350
days/year, produces 100 batches/year, and the maximal cell
concentration in the fermentation broth is 1 x 10\11\ cfu/ml and the
volume of the fermentation broth is 70,000 L. The process consists of
the main steps of laboratory propagation, fermentation and then
recovery where filtration operations separate out the biomass from the
concentrated desired product. The operations, sources of exposure and
release are described in more detail in EPA's Release and Exposure
Assessments (Ref. 9).
    Additionally, containment and control technologies are delineated
in the Sec.  725.422 for Tier I and Tier II exemptions.

V. Risk Assessment

A. Risk Assessment for T. reesei QM6a

    There is only one potential concern for human health and
environmental hazards associated with T. reesei QM6a, and that is for
paracelsin production. Paracelsin production is not expected to occur
in submerged standard industrial fermentation operations in which no
solid plant material or insoluble substrate is present in the
fermentation broth. There is no concern for potential pathogenicity of
T. reesei QM6a to humans, plants, domesticated animals, or wildlife.
Pathogenicity test data on various industrial strains typically do not
show adverse effects. Toxicity testing on a number of enzymes produced
by T. reesei indicates that the fungus does not produce toxins under
the standard conditions used for enzyme production.
    T. reesei has a long history of safe use and would be expected to
present low hazard to workers, the general public, and the environment.
Although direct monitoring data are unavailable, worst-case estimates
of potential exposures made by EPA in its assessment of potential risks
(Ref. 6) do not indicate high levels of exposure of T. reesei to either
workers or the public resulting from the submerged industrial enzyme
fermentation operations that are standard throughout the industry.
Standard industrial hygiene management practices currently used in the
fermentation industry reduce the potential for adverse health effects
in the workplace. The standard use of engineering controls (closed
fermentation systems), appropriate work practices, personal protective
equipment, and personal hygiene reduce the potential for worker
exposure. Thus, current practices reduce the potential for the dermal
and respiratory exposures estimated by EPA.
    EPA has made a preliminary determination based on worst-case
exposure scenarios and toxicity of the microorganism that the potential
risk to workers, the general public, and to the environment resulting
from the use of T. reesei QM6a in submerged standard industrial
fermentation as a recipient microorganism is low, provided the
additional criteria of the tiered exemptions for the introduced genetic
material and the physical containment conditions are met (Ref. 6).

B. Risk Assessment for B. amyloliquefaciens

    Industrial strains of Bacillus amyloliquefaciens that would fall
into the subspecies Bacillus amyloliquefaciens subsp. amyloliquefaciens
are not pathogenic to humans, plants, domesticated animals, or
wildlife, and do not produce many of the toxic secondary metabolites
found in biological control strains of B. amyloliquefaciens subsp.
plantarum. The long history of safe use of enzymes produced by
industrial strains of B. amyloliquefaciens in food is evidence that the
bacterium does not produce toxins under standard conditions used for
enzyme production.
    Current practices in the fermentation industry reduce the potential
for adverse health effects in the workplace. The use of engineering
controls (closed fermentation systems), appropriate work practices,
personal protective equipment, and personal hygiene reduce the
potential for worker exposure. Thus, current practices reduce the
potential for dermal and respiratory exposures.
    Industrial strains of B. amyloliquefaciens have a long history of

safe use and would be expected to present low hazard to workers, the
general public, and the environment. Although direct monitoring data
are unavailable, worst-case estimates do not suggest high levels of
exposure of B. amyloliquefaciens to either workers or the public
resulting from the submerged industrial enzyme fermentation operations
that are standard throughout the industry.
    EPA has made a preliminary determination based on worst-case
exposure scenarios and toxicity of the microorganism, that the
potential risk to workers, the general public, and the environment,
associated with the use of industrial strains of B. amyloliquefaciens
subsp. amyloliquefaciens in submerged standard industrial fermentation
as a recipient microorganism is low provided the additional criteria of
the tiered exemptions for the introduced genetic material and the
physical containment conditions are met (Ref. 7).

VI. Economic Impacts

    EPA's economic assessment (Ref. 10) evaluates the potential for
significant economic impacts as a result of the addition of two
microorganisms (Trichoderma reesei (Strain QM6a) and Bacillus
amyloliquefaciens subsp. amyloliquefaciens) to Sec.  725.420 which
lists recipient microorganisms eligible for Tier I and Tier II
exemptions. Over the course of the first 10 years after the effective
date of the final rule, if finalized as proposed, EPA estimates that
the proposed addition of the two microorganisms to the list in Sec.
725.420 would generate a total cost savings to society of $5.68
million. Industry would save approximately $1.98 million and the Agency
would save approximately $3.68 million. The equivalent, annualized cost
savings are expected to be $552,000 and $535,000 at a 3% and 7%
discount rate, respectively. EPA estimates that there will be a net
decrease in burden to society of 72,500 hr over this 10-year period.

VII. Rationale for Proposed Regulatory Action

A. Statutory Background

    Pursuant to TSCA section 5(h)(4), EPA is authorized to exempt the
manufacturer of any new chemical substance from all or part of the
requirements of TSCA section 5 if EPA determines that the manufacture,
processing, distribution in commerce, use, or disposal of the chemical
substance, or any combination of such activities, will not present an
unreasonable risk of injury to human health or the environment. Section
26(c) of TSCA provides that any action authorized under TSCA for an
individual chemical substance may be taken for a category of such
chemical substances.
    While TSCA does not contain a definition of ``unreasonable risk,''
the legislative history indicates that the determination of
unreasonable risk requires a balancing of the considerations of both
the severity and the probability that harm will occur against the
effect of the final regulatory action on the availability to society of
the benefits of the chemical substance (Ref. 11). This analysis can
include an estimate of factors such as market potential, the effect of
the regulation on promoting or hindering the economic appeal of a
chemical substance, environmental effects, and many other factors which
are difficult to define and quantify precisely. EPA may rely not only
on data available to it, but also on its professional judgment.
Congress recognized that the implementation of the unreasonable risk
standard ``will vary on the specific regulatory authority which the
Administrator seeks to exercise'' [Ibid.].

B. EPA's Approach

    In determining whether T. reesei QM6a and Bacillus
amyloliquefaciens subsp. amyloliquefaciens will not present an
unreasonable risk of injury to human health or the environment, the
Agency considers more than just the inherent risks presented by the two
microorganisms. The Agency also considers the full range of societal
benefits associated with the exemption; for example, as discussed in
more detail in Unit V., EPA considers not only the cost savings to the
users of the microorganism, but also the societal benefits that flow
from promotion of the use of low-risk recipient microorganisms, while
allowing the Agency to direct its resources toward higher risk
microorganisms.
    EPA is only proposing to revise one aspect of the existing tiered
exemptions at Sec.  725.420; specifically, EPA is proposing to expand
the exemption to apply to two specific microorganisms. EPA is not
reconsidering or otherwise reopening any other aspect of those
exemptions. The narrow scope of this action necessarily affects the
scope of EPA's cost-benefit analysis. This means, for example, that EPA
compares the risks and benefits of the two microorganisms being
considered for an exemption with the risks that would have resulted if
those same two microorganisms remained subject to full MCAN submission
requirements and 90-day EPA review. But EPA does not compare the risks
and benefits that would result from use of these two microorganisms in
the absence of any regulation.
    It is also significant that the standard applicable to this
proposed rule is that the microorganisms will present ``no unreasonable
risk,'' rather than ``no risk.'' It is not possible to eliminate all
risks associated with the manufacture, processing, distribution in
commerce, use, and disposal of any new microorganism nor was this
Congress' intent. The standard embodied by a TSCA section 5(h)(4)
exemption does not require the Agency to ensure absolute safety from
the activities associated with an exempted chemical substance.

C. Application of No Unreasonable Risk Factors

    The following is an explanation of the factors and their analyses
relevant to the no unreasonable risk finding.
    1. Risks associated with microorganisms. EPA's evaluation of the
available information concerning T. reesei QM6a and B.
amyloliquefaciens subsp. amyloliquefaciens against these criteria is
presented in detail in Unit III., and is summarized again here for the
readers' convenience.
    The Agency developed specific criteria in Sec.  725.67 that the
Agency uses in determining the extent of a potential recipient
microorganism's risks, and consequently, its eligibility for listing at
Sec.  725.420. These criteria were explained in detail in the proposed
``biotech'' rule (Ref. 12) and final ``biotech'' rule (Ref. 13), and
are discussed again in Units II. and III. EPA's conclusions regarding
the low-risk potential for these two microorganisms are based on the
available data and EPA's scientific professional judgment based on 14
years experience reviewing notifications for new intergeneric
microorganisms submitted in accordance with the regulations at 40 CFR
part 725.
    T. reesei QM6a is not pathogenic to humans, plants, domesticated
animals, or wildlife and the fungus does not produce toxins under
standard industrial conditions used for enzyme production. T. reesei
QM6a has a long history of safe use and is generally expected to
present low risk to workers, the general public, and the environment
resulting from submerged standard industrial enzyme fermentation
operations that are standard throughout the industry. Under non-
standard conditions of fermentation, such as with extended duration of
fermentation, or fermentation in the presence of insoluble carbon
sources such as

cellulose or other solid surfaces, paracelsin may be produced. The
risks associated with the production of paracelsin may be significant
due to the toxicity of paracelsin to mammalian cells, aquatic species,
Gram-positive bacteria, and various fungi. However, the potential risk
associated with any paracelsin production would be significantly
reduced by this proposed rule, which proposes to limit the exemption to
fermentation operations using submerged standard industrial
fermentation operations, and in which no solid plant material or
insoluble substrate is present in the fermentation broth.
    Industrial strains of Bacillus amyloliquefaciens that would fall
into the subspecies Bacillus amyloliquefaciens subsp. amyloliquefaciens
are not pathogenic to humans, plants, domesticated animals, or
wildlife, and do not produce toxins under standard conditions used for
enzyme production. Industrial strains of B. amyloliquefaciens subsp.
amyloliquefaciens used in fermentation facilities for the production of
enzymes have a long history of safe use and are expected to present low
hazards to human health and the environment resulting from standard
industrial submerged fermentation operations. Consistent with the
proposed restrictions on Trichoderma reesei discussed in Unit II.A.,
only strains of Bacillus amyloliquefaciens that would fall into the
subspecies Bacillus amyloliquefaciens subsp. amyloliquefaciens were
considered as the eligible recipient microorganism at Sec.  725.420.
EPA is proposing to exclude other strains/subspecies of these two
species for which:
     The Agency still has insufficient data and review
experience to find that they will not present an unreasonable risk of
injury or
     The Agency has found that, under certain conditions, based
on data on the species in question, a strain or subspecies may present
an unreasonable risk, thereby requiring a closer examination of the
conditions of manufacturing, processing, distribution in commerce, use,
and disposal during a full 90-day Premanufacture Notice (PMN) review.
Consequently, additional information would be necessary to make an
appropriate determination about the organisms' potential risks and
benefits.
    The Agency believes that the requirement for submission of a MCAN
followed by a 90-day review period for new intergeneric microorganisms
that use T. reesei QM6a and Bacillus amyloliquefaciens subsp.
amyloliquefaciens as recipient microorganisms is not necessary to
address the risks associated with these microorganisms, and would not
result in any additional protection than would be achieved by this
proposed rule. In part, this conclusion is based on EPA's preliminary
findings regarding the intrinsically low level of hazard that these two
organisms pose to human health and the environment. In addition, the
existing requirements of the Tier I and Tier II exemptions, taken with
the proposed restrictions, would place sufficient constraints to
significantly limit the potential risks of injury to human health or
the environment that these two microorganisms may present.
    In sum, the Agency believes that the criteria set forth in this
proposed exemption would be sufficient to mitigate the identified risks
associated with these microorganisms.
    2. Costs. This proposed rule expands an existing exemption, and as
discussed in Unit VI., would significantly reduce costs to currently
regulated entities. The proposed rule would not otherwise impose any
additional cost or other burden on currently regulated entities, or
existing fermentation processes.
    EPA further believes that limiting the use of this proposed
exemption to the identified fermentation conditions would impose no
burden on affected entities. The restriction merely codifies existing
industrial fermentation procedures that are common practices for
manufacturing operations that currently seek to use tiered exemptions.
Consequently, EPA expects that most, if not all, manufacturers
currently using these microbes will already have the measures in place
to qualify for the exemption. Equally important, this limitation would
add no burden to any existing fermentation processes. Currently,
fermentation operations with either of these microbes are not eligible
for the tiered exemption, and thus a MCAN must be submitted. Any
company that chooses to use a different fermentation process could
continue to operate under the status quo and simply submit a MCAN. This
proposed rule would simply offer an additional, less costly option, to
facilities that choose to use the fermentation operations discussed in
this proposed rule.
    3. Benefits. The following discussion describes the benefits of
this proposed rule in a qualitative manner; for a more quantitative
approach, see the economic analysis prepared for this proposed rule
(Ref. 10). A summary of that economic analysis is also provided in Unit
VI.
    The benefits analyzed encompass more than the direct benefits
associated with submitting a Tier I or Tier II exemption for a new
intergeneric microorganism rather than a MCAN. Rather, EPA's benefit
analysis included a consideration of the broader benefits to society.
EPA's unreasonable risk determination is based on broader benefits to
society as well as those benefits attributable to a reduction in the
burden associated with submission of Tier I and Tier II exemptions
rather than MCANs.
    EPA believes manufacturers of new intergeneric microorganisms based
on these low-risk microorganisms currently bear an unnecessary
regulatory burden in continuing to file MCANs. By adding T. reesei QM6a
and B. amyloliquefaciens to the list of eligible recipient
microorganisms in Sec.  725.420, the Agency removes unnecessary
regulatory impediments to the design, manufacture, and
commercialization of these low risk new intergeneric microorganisms,
and of the chemical substances that can be produced by these safer
microorganisms. This action would also substantially reduce the costs
associated with industry's reporting burden, including the costs
associated with the preparation of the submission, and with the delay
in the commercial market introduction of the new intergeneric
microorganism. Some of the cost-savings benefits may accrue to small
businesses, either as developers of the exempt microorganisms, as
producers of fermentation chemicals using the live microorganisms, or
as customers for enzymes or other products made using the
microorganisms.
    There would also be a reduction in the Agency review resources
currently allocated to reviews of MCANs for these two microorganisms.
These Agency resources would be shifted to the review of new
intergeneric microorganisms or chemical substances of greater concern.
    There would be cost savings to both the industry and the Agency.
The proposed rule is expected to positively impact the rate of
innovation in the industry. It is reasonable to assume that a new
intergeneric microorganism will either possess a new function or serve
an existing function more efficiently or less expensively. The
reduction in delay for that new intergeneric microorganism to be
introduced into commerce is a benefit to both manufacturers and the
general public who will have access to the substance more quickly. The
expected benefits to innovation have not been quantified but include:
Reduced time to develop and commercialize organisms; decreased cost of
some downstream industrial products, such as fuel ethanol; improved
consumer appeal of some products, such as certain

textiles; and reduced costs of some consumer products, such as
detergent and leather goods.
    4. Risk/benefit balance. Determining the presence or absence of an
unreasonable risk requires balancing of the benefits and risks posed by
a regulatory action. EPA has determined that the risks are generally
low based on the inherent properties and intended uses of T. reesei
QM6a and B. amyloliquefaciens, and would be adequately managed by the
restrictions in the proposed rule, combined with the existing
requirements of the Tier I and Tier II exemptions.
    As noted in this unit, EPA believes that this proposed rule would
impose no costs. This proposed rule expands an existing exemption, and
as such, would in fact reduce costs to currently regulated entities.
This proposed rule would not otherwise impose any additional cost or
other burden on currently regulated entities, or existing fermentation
processes. The limitation on the use of the proposed exemption to
certain fermentation conditions is not a cost that would be imposed by
this proposed rule but rather a limitation on the amount of regulatory
relief it would provide. The proposed conditions reflect industrial
fermentation procedures that are currently common practices for the
affected industry.
    EPA also believes that the benefits of this proposed rule are quite
significant. This proposed rule would reduce the overall regulatory
burden for affected entities by reducing the reporting requirements and
by eliminating the delay of these products into commerce. As a
consequence, this would benefit both regulated entities and the general
public by promoting the expedited manufacture and use of the chemical
substances produced using these low-risk organisms and manufacturing
processes. There is also the added benefit of concentrating limited EPA
resources on regulation of chemical substances which have a greater
potential to present significant risks, rather than on these two
microorganisms. While this is difficult to quantify, it is considered
substantial nonetheless.
    In sum, the Agency believes that the criteria set forth in this
proposed exemption are sufficient to mitigate the low level of
potential risks presented by these organisms, particularly when
compared to the benefits, in toto, of this proposed exemption, to
levels that are consistent with the statutory standard for an
exemption. Consequently, EPA has made a preliminary conclusion that
adding T. reesei QM6a and B. amyloliquefaciens as recipient
microorganisms to the list of recipient microorganisms at Sec.  725.420
is appropriate, as it would not present an unreasonable risk of injury
to human health or the environment when manufactured under the
conditions of this proposed exemption.

VIII. Request for Public Comment, Rulemaking Process, and Request for
an Informal Public Hearing

A. Rulemaking Process and Request for an Informal Public Hearing

    EPA is conducting this rulemaking under the notice and comment
rulemaking procedures of section 553 of the Administrative Procedure
Act (APA), 5 U.S.C. 553. Interested persons have the opportunity to
submit written comments by the methods identified under ADDRESSES. EPA
will carefully consider all such comments.
    EPA is also providing an opportunity for an informal public hearing
on the proposed rule. This hearing will be held only if EPA receives a
timely written request for such a hearing.
    As a general matter, EPA is not required to hold a public hearing
in informal notice and comment rulemaking conducted under APA section
553. However, use of TSCA section 5(h)(4) modifies the APA section 553
rulemaking requirements by referencing TSCA section 6(c)(2) and (c)(3)
rulemaking procedures. Under the TSCA section 6 procedures, EPA must
hold an informal public hearing, if requested, and, if properly
requested and granted by EPA, allow an opportunity to present rebuttal
submissions and conduct cross-examinations related to disputed issues
of material fact.
    EPA does not anticipate that, even if a hearing is held, there will
be a need for rebuttal submissions and cross-examination, because the
TSCA section 5(h)(4) portion of this proposed rulemaking is based
primarily on matters of science policy that do not yield disputed
factual issues.

B. Specific Comment Solicitation

    EPA is seeking public comment pertaining to several specific issues
regarding the proposed rule.
    1. Do the proposed rule and supporting documents adequately
address:
     The effects of the new microorganism on health and the
environment?
     The magnitude of exposure of human beings and the
environment to the new microorganism?
     The benefits of the new microorganism for various uses and
the availability of substitutes for such uses?
     The reasonably ascertainable economic consequences of
granting or denying the exemption, including effects on the national
economy, small business, and technological innovation?
    2. Does the proposed rule address taxonomy adequately (is the
Agency capturing and excluding the correct strains)?
    3. Does the proposed rule address the right description of typical
conditions for enzyme production (eliminating plant material/solid
surfaces)?
    4. Are the limitations on the use of T. reesei QM6a reasonable for
preventing paracelsin production (i.e., having no solid plant material
or insoluble substrate with the microorganism)?

IX. References

    As indicated under ADDRESSES, a docket has been established for
this proposed rule under docket ID number EPA-HQ-OPPT-2011-0740. The
following is a listing of the documents that have been placed in the
docket for this proposed rule. The docket includes information
considered by EPA in developing this proposed rule, including the
documents listed in this unit, which are physically located in the
docket. In addition, interested parties should consult documents that
are referenced in the documents that EPA has placed in the docket,
regardless of whether these referenced documents are physically located
in the docket. For assistance in locating documents that are referenced
in documents that EPA has placed in the docket, but that are not
physically located in the docket, please consult the technical contact
listed under FOR FURTHER INFORMATION CONTACT. The docket is available
for review as specified under ADDRESSES.
    1. Genencor International, Inc. Letter of Application to list
Trichoderma reesei as exempt under subpart G of 40 CFR Part 725--
Reporting Requirements and Review Processes for Microorganisms.
March 17, 2005.
    2. Novo Nordisk BioChem North America, Inc. Letter of
Application to list B.amyloliquefaciens as exempt under subpart G of
40 CFR Part 725--Reporting Requirements and Review Processes for
Microorganisms. November 7, 1997.
    3. EPA, OPPT. Email confirming Novo Nordisk BioChem North
America, Inc.'s letter of application to list B.amyloliquefaciens as
exempt under subpart G of 40 CFR Part 725--Reporting Requirements
and Review Processes for Microorganisms. August 3, 2009.
    4. ETA. Supplemental information on Trichoderma reesei. January
29, 2010.
    5. ETA. Supplemental information on Trichoderma reesei. June 16,
2011.
    6. EPA, OPPT. Risk Assessment of Trichoderma reesei for
Consideration of Addition to the List of Eligible Recipient

Microorganisms for the Tiered 5(h)(4) Exemptions from MCAN Reporting
Requirements. October 2011.
    7. EPA, OPPT. Risk Assessment of Bacillus amyloliquefaciens
subsp. amyloliquefaciens for Consideration of Addition to the List
of Eligible Recipient Microorganisms for the Tiered 5(h)(4)
Exemptions from MCAN Reporting Requirements. October 2011.
    8. EPA, OPPT. Release and Exposure Assessment in Support of
Proposed TSCA 5(h)(4) Exemption for Trichoderma reesei. June 2011.
    9. EPA, OPPT. Release and Exposure Assessment in Support of
Proposed TSCA 5(h)(4) Exemption for Bacillus amyloliquefaciens. June
2011.
    10. EPA, OPPT. Economic Analysis for the Proposed Biotechnology
Exemptions Rule for Trichoderma reesei and Bacillus
amyloliquefaciens. September 2011.
    11. Legislative History of the Toxic Substances Control Act, pp.
409-423. House Report 1341, 94th Congress, 2nd Session. 1976.
    12. EPA. Microbial Products of Biotechnology; Proposed
Regulation under the Toxic Substances Control Act. Federal Register
(59 FR 45526; September 1, 1994) (FRL-4774-4).
    13. EPA. Microbial Products of Biotechnology; Final Regulation
under the Toxic Substances Control Act. Federal Register (62 FR
17910; April 11, 1997) (FRL-5577-2).

X. Statutory and Executive Order Reviews

A. Executive Order 12866: Regulatory Planning and Review and Executive
Order 13563:

Improving Regulation and Regulatory Review
    This action is not a ``significant regulatory action'' under the
terms of Executive Order 12866 (58 FR 51735, October 4, 1993) and is
therefore not subject to review under Executive Orders 12866 and 13563
(76 FR 3821, January 21, 2011). EPA prepared an analysis of the
potential costs and benefits associated with this action, which is
summarized in Unit VI.

B. Paperwork Reduction Act (PRA)

    According to PRA, 44 U.S.C. 3501 et seq., an agency may not conduct
or sponsor, and a person is not required to respond to, a collection of
information that requires approval by the Office of Management and
Budget (OMB) under PRA, unless it has been approved by OMB and displays
a valid OMB control number. The OMB control numbers for EPA's
regulations in title 40 of the CFR, after appearing in the Federal
Register, are listed in 40 CFR part 9, and included on the related
collection instrument, or form, if applicable.
    The information collection requirements related to the submission
of Tier I and Tier II notification are already approved by OMB under
PRA, and have been assigned OMB control numbers 2070-0012 and 2070-
0038. This proposed rule does not impose any new requirements, or
otherwise increase burden such that additional OMB review or approval
is necessary. Instead, this proposed rule is expected to reduce the
amount of required reporting by allowing firms to submit less
information for qualifying microorganisms.
    The PRA requires agencies to estimate the potential recordkeeping
and reporting burden of a proposed rule. In this context, the term
``burden'' is defined in 5 CFR 1320.3(b). EPA estimates that this
proposed rule would result in a reduction of industry burden by 30,695
hr over 10 years. EPA also estimates that the proposed rule would cause
a total incremental Agency savings of 41,869 hr over 10 years. Submit
any comments related to these estimates to EPA. See ADDRESSES for
submission of comments.

C. Regulatory Flexibility Act (RFA)

    Pursuant to section 605(b) of the RFA, 5 U.S.C. 601 et seq., the
Agency hereby certifies that this proposed rule, if promulgated as
proposed, would not have a significant economic impact on a substantial
number of small entities. Under RFA, small entities include small
businesses, small organizations, and small governmental jurisdictions.
For purposes of assessing the impacts of this action on small entities,
small entity is defined as:
    1. A small business as defined by the Small Business
Administration's (SBA) regulations at 13 CFR 121.201 using either the
number of employees or annual receipts for the businesses affected by
the regulation, which for this action includes any business that is
conducting commercial research and development activities or persons
manufacturing, importing or processing products using intergeneric
microorganisms for biofertilizers; biosensors; enzyme, commodity, or
specialty chemical production; energy applications; waste treatment or
pollutant degradation; and other TSCA subject uses.
    2. A small governmental jurisdiction that is a government of a
city, county, town, school district, or special district with a
population of less than 50,000.
    3. A small organization that is any not-for-profit enterprise which
is independently owned and operated and is not dominant in its field.
    In making this determination, the impact of concern is any
significant adverse economic impact on small entities because the
primary purpose of regulatory flexibility analysis is to identify and
address regulatory alternatives ``which minimize any significant
economic impact of the rule on small entities.'' 5 U.S.C. 603 and 604.
Thus, an agency may certify under RFA when the rule relieves regulatory
burden, or otherwise has no expected economic impact on small entities
subject to the rule.
    This proposed rule is an exemption, and is therefore expected to
reduce the existing regulatory burden, which will benefit all
submitters regardless of the size of the entity. The factual basis for
the Agency's certification under RFA is presented in the small entity
impact analysis prepared as part of the Economic Analysis for this
proposed rule (Ref. 10), and is briefly summarized in Unit VI.
    We continue to be interested in the potential impacts of the
proposed rule on small entities and welcome comments on issues related
to such impacts.

D. Unfunded Mandates Reform Act (UMRA)

    EPA has determined that this action does not impose any enforceable
duty or contain any unfunded mandate for State, local, or Tribal
governments or the private sector, and does not otherwise have any
effect on small governments, such that it is subject to the
requirements of sections 202, 203, 204, or 205 of UMRA, 2 U.S.C. 1531-
1538. As indicated previously, this action is expected to reduce costs.
In addition, based on EPA's experience with past MCANs and Tier I and
II exemptions, State, local, and Tribal governments have not been
affected by these reporting requirements, and EPA does not have any
reason to believe that any State, local, or Tribal government will be
affected by this particular rulemaking. A search of past submissions to
EPA demonstrated that no State, local, or Tribal government have ever
submitted a MCAN, Tier I or Tier II notification to EPA. EPA has no
information to indicate that any State, local, or Tribal government
commercially manufactures the microorganisms covered by this action.

E. Executive Order 13132: Federalism

    For the same reasons presented in Unit X.D., the Agency has
determined that this action will not have a substantial direct effect
on State or local governments, on the relationship between the national
government and the States or local governments, or on the distribution
of power and responsibilities among the various

levels of government. Thus, the Agency has determined that Executive
Order 13132 (64 FR 43255, August 10, 1999) does not apply to this
action.

F. Executive Order 13175: Consultation and Coordination With Indian
Tribal Governments

    For the same reasons presented in Unit X.D., the Agency has
determined that this action will not have a substantial direct effect
on tribal governments, on the relationship between the national
government and Tribal governments, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes.
Thus, the Agency has determined that Executive Order 13175 (65 FR
67249, November 9, 2000) does not apply to this action.

G. Executive Order 13045: Protection of Children From Environmental
Health Risks and Safety Risks

    EPA interprets Executive Order 13045 (62 FR 19885, April 23, 1997)
as applying only to those regulatory actions that concern health or
safety risks, such that the analysis required under section 5-501 of
the Executive Order has the potential to influence the regulation. This
action is not subject to Executive Order 13045 because it does not
establish an environmental standard intended to mitigate health or
safety risks, nor is it an ``economically significant regulatory
action'' as defined by Executive Order 12866.

H. Executive Order 13211: Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use

    This action is not subject to Executive Order 13211 (66 FR 28355,
May 22, 2001), because it is not a significant regulatory action under
Executive Order 12866.

I. National Technology Transfer and Advancement Act (NTTAA)

    Section 12(d) of NTTAA, 15 U.S.C. 272 note, directs EPA to use
voluntary consensus standards in its regulatory activities unless to do
so would be inconsistent with applicable law or impractical. Voluntary
consensus standards are technical standards (e.g., materials
specifications, test methods, sampling procedures, etc.) that are
developed or adopted by voluntary consensus standards bodies. This
proposed rule does not impose any technical standards that would
require EPA to consider any voluntary consensus standards.

J. Executive Order 12898: Federal Actions To Address Environmental
Justice in Minority Populations and Low-Income Populations

    This action does not have disproportionately high and adverse human
health or environmental effects on minority or low-income populations
because it does not affect the level of protection provided to human
health or the environment. Therefore, this action does not involve
special consideration of environmental justice-related issues as
specified in Executive Order 12898 (59 FR 7629, February 16, 1994).

List of Subjects in 40 CFR Part 725

    Environmental protection, Administrative practice and procedure,
Biotechnology, Chemicals, Hazardous substances, Imports, Labeling,
Microorganisms, Occupational safety and health, Reporting and
recordkeeping requirements.

    Dated: August 28, 2012.
James Jones,
Acting Assistant Administrator, Office of Chemical Safety and Pollution
Prevention.
    Therefore, it is proposed that 40 CFR chapter I be amended as
follows:

PART 725--[AMENDED]

    1. The authority citation for part 725 continues to read as
follows:

    Authority:  15 U.S.C. 2604, 2607, 2613, and 2625.

    2. In Sec.  725.3, add in alphabetical order the definition below
to read as follows:

Sec.  725.3  Definitions.

* * * * *
    Submerged standard industrial fermentation for purposes of this
part, means a fermentation system that meets all of the following
conditions:
    (1) Submerged fermentation (i.e., growth of the microorganism
occurs beneath the surface of the liquid growth medium).
    (2) Any fermentation of solid plant material or insoluble
substrate, to which T. reesei fermentation broth is added after the
standard industrial fermentation is completed, may be initiated only
after the inactivation of the microorganism as delineated in Sec.
725.422(d).
* * * * *
    3. In Sec.  725.420, add new paragraphs (k) and (l) to read as
follows:

Sec.  725.420  Recipient microorganisms.

* * * * *
    (k) Trichoderma reesei strain QM6a used only in submerged standard
industrial fermentation operations in which no solid plant material or
insoluble substrate is present in the fermentation broth, fermentation
may only be initiated after the inactivation of T. reesei as delineated
in Sec.  725.422(d).
    (l) Bacillus amyloliquefaciens subsp. amyloliquefaciens.

[FR Doc. 2012-21843 Filed 9-4-12; 8:45 am]
BILLING CODE 6560-50-P


    RE: Revised Area Source Boiler Preamble and Rule    Higgins, Cortney    to:  Mary Johnson                                                                12/20/2012 12:14 PM                                                             12/20/2012 12:14 PM   Cc:  RobertJ Wayland, Thomas Gillis, Jim Eddinger

 From: "Higgins, Cortney"<EMAIL_ADDRESS>

 To: Mary Johnson/RTP/USEPA/US@EPA

 Cc: RobertJ Wayland/RTP/USEPA/US@EPA, Thomas Gillis/DC/USEPA/US@EPA, Jim Eddinger/RTP/USEPA/US@EPA

Hi Mary, We have no further edits the area source rule.  Can you send me the final clean version?

Thanks, Cortney

From<EMAIL_ADDRESS><EMAIL_ADDRESS>Sent: Wednesday, December 19, 2012 3:11 PM To: Higgins, Cortney Cc<EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS><EMAIL_ADDRESS>Subject: Revised Area Source Boiler Preamble and Rule

Cortney,

Attached is a redline version of the Area Source Boiler preamble/rule. It shows the changes made from the version sent to you on 12/17/2012.

(See attached file: EO 12866 NESHAP for Area Sources ICI Boilers 2060-AR14_Redline_121712_v_121912.docx)

Thanks.

Mary

Mary Johnson Environmental Engineer U.S. Environmental Protection Agency Office of Air Quality Planning and Standards Mail Code D 243-01 Research Triangle Park, NC 27711 Phone:<PHONE_NUMBER> Fax:<PHONE_NUMBER>