[Federal Register Volume 68, Number 134 (Monday, July 14, 2003)]
[Rules and Regulations]
[Pages 41535-41541]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-17726]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2003-0138; FRL-7311-6]


Aspergillus flavus AF36; Exemption from the Requirement of a 
Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an exemption from the requirement 
of a tolerance for residues of the microbial antifungal agent 
Aspergillus flavus AF36, a non-aflatoxin-producing member of the 
naturally-occurring genus of fungi Aspergillus, in or on the food/feed 
commodity cotton, when the pesticide is used according to its label 
instructions as a prebloom application. The Interregional Research 
Project Number 4 (IR-4), on behalf of the Arizona Cotton Research and 
Protection Council, submitted a petition to EPA under the Federal Food, 
Drug, and Cosmetic Act (FFDCA), as amended by the Food Quality 
Protection Act of 1996 (FQPA), requesting an exemption from the 
requirement of a tolerance. This regulation eliminates the need to 
establish a maximum permissible level for residues of Aspergillus 
flavus AF36 in or on cotton and its food/feed commodities.

DATES: This regulation is effective July 14, 2003. Objections and 
requests for hearings, identified by docket ID number OPP-2003-0138, 
must be received on or before September 12, 2003.

ADDRESSES: Written objections and hearing requests may be submitted by 
mail or through hand delivery/courier. Follow the detailed instructions 
as provided in Unit IX. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Shanaz Bacchus, Biopesticides and 
Pollution Prevention Division (7511C), Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8097; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0138. The 
official public docket is intended to serve as a repository for 
materials (i.e.,documents and other information) submitted to the 
Agency in connection with this action and/or relied upon by the Agency 
in

[[Page 41536]]

taking this action. Although a part of the official docket, the public 
docket does not include Confidential Business Information (CBI) or 
other information whose disclosure is restricted by statute. The 
official public docket is available for public viewing at the Public 
Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 
2, 1921 Jefferson Davis Hwy., Arlington, VA. This docket 
facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays. The docket telephone number is (703) 305-
5805. To the extent that a particular document is not located in the 
official public docket, consult the person listed under FOR FURTHER 
INFORMATION CONTACT.
    The legacy docket for this case is OPP-2003-0020, which was set up 
in connection with the Notice of Filing of this pesticide petition, 
8E5001. It contains the Federal Register Notice dated February 14, 
2003, (68 FR 7554), which was published to announce this petition, 
other relevant Federal Register documents associated with the exemption 
from temporary tolerance which preceded this permanent exemption from 
tolerance, and comments received in response to the publication of this 
petition.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180--00.html, a 
beta site currently under development. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Once in the system, select ``search,'' 
then key in the appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of February 14, 2003 (68 FR 7554) (FRL-
7289-9), EPA issued a notice pursuant to section 408 of the FFDCA, 21 
U.S.C. 346a, as amended by FQPA (Public Law 104-170), announcing the 
filing of a pesticide tolerance petition (PP 8E5001) by Interregional 
Research Project Number 4 (IR-4), New Jersey Agricultural Experiment 
Station, Technology Center of New Jersey, 681 U. S. Highway 1 
South, North Brunswick, NJ 08902-3390, on behalf of the Arizona Cotton 
Research and Protection Council, 3721 East Wier Avenue, Phoenix, AZ 
85040-2933. This notice included a summary of the petition prepared by 
the petitioner, IR-4, on behalf of the Arizona Cotton Research and 
Protection Council. In response to the notice of filing of this 
petition, comments in favor of the use of the pesticide were received 
from cotton growers, processors and ginners, mainly from Arizona and 
Texas.
    The petition requested that 40 CFR 180.1206 be amended by 
establishing an exemption from the requirement of a tolerance for 
residues of Aspergillus flavus AF36 in or on cotton and its food/feed 
commodities.
    Section 408(c)(2)(A)(i) of the FFDCA allows EPA to establish an 
exemption from the requirement of a tolerance (the legal limit for a 
pesticide chemical residue in or on a food) only if EPA determines that 
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of the FFDCA 
defines ``safe'' to mean that ``there is a reasonable certainty that no 
harm will result from aggregate exposure to the pesticide chemical 
residue, including all anticipated dietary exposures and all other 
exposures for which there is reliable information.'' This includes 
exposure through drinking water and in residential settings, but does 
not include occupational exposure. Section 408(b)(2)(C) of the FFDCA 
requires EPA to give special consideration to exposure of infants and 
children to the pesticide chemical residue in establishing a tolerance 
and to ``ensure that there is a reasonable certainty that no harm will 
result to infants and children from aggregate exposure to the pesticide 
chemical residue. . . .'' Additionally, section 408(b)(2)(D) of the 
FFDCA requires that the Agency consider ``available information'' 
concerning the cumulative effects of a particular pesticide's residues 
and ``other substances that have a common mechanism of toxicity.''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. First, EPA determines the 
toxicity of pesticides. Second, EPA examines exposure to the pesticide 
through food, drinking water, and through other exposures that occur as 
a result of pesticide use in residential settings.

III. Toxicological Profile

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action and considered its validity, completeness, and 
reliability, and the relationship of this information to human risk. 
EPA has also considered available information concerning the 
variability of the sensitivities of major identifiable subgroups of 
consumers, including infants and children.
    Aspergillus flavus AF36 (also referred to as AF36) is a non-
aflatoxin-producing or atoxigenic strain of Aspergillus flavus, whose 
species are ubiquitous around the world. Some members of the genus 
Aspergillus produce mycotoxins, such as aflatoxin, a potent carcinogen 
produced by toxigenic strains of A. flavus. Other members of the genus 
Aspergillus have been domesticated for commercial use, such as 
Aspergillus niger for production of enzymes (e.g., alpha-galactosidase 
found in beano, a dietary supplement) and Aspergillus oryzae for 
production of soy sauce. The subject strain of this final rule, 
Aspergillus flavus AF36, is characterized as an atoxigenic strain by 
its lack of production of aflatoxin. It is not vegetatively compatible 
with the toxigenic strains of A. flavus, a feature which limits cross-
over potential to, and, thus, further proliferation of, the toxigenic 
strains. Starter cultures, selected on the basis of the vegetative 
incompatibility with aflatoxin-producing strains, are to be monitored 
by standard thin layer chromatography (TLC) procedures, and 
visualization via scanning fluorescence densitometry scanning [Master 
Record Identification Number (MRID) 44626101; BPPD Data Evaluation 
Report of Analysis of Samples, dated March 29, 1999 (hereinafter 
referred to as ``BPPD review - March 29, 1999''); BPPD Review of 
Supplementary Information dated May 14, 1999 (hereinafter referred to 
as ``BPPD review - May 14, 1999'')]. In this manner, the applicant 
proposes to maintain batches free of aflatoxin contamination during 
production. Batches contaminated with aflatoxin, or human pathogens, or 
unintentional ingredients above regulatory levels are to be destroyed. 
Thus, use of AF36 is not likely to add to the environmental burden of 
the aflatoxin-producing strains of A. flavus.
    The pesticide is proposed for a single prebloom application once a 
year to cotton fields to displace the aflatoxin-producing strains of 
Aspergillus flavus from cotton. Sterilized wheat seeds, colonized with 
Aspergillus flavus AF36,

[[Page 41537]]

are to be applied at 10 lb of end-use product (EP) (equivalent to the 
low rate of less than 0.01 lb active ingredient (ai) per acre). Within 
3 days of application of the pesticide, the fields are furrow irrigated 
to promote germination of AF36, which apparently colonizes the cotton 
crop and soil, before the aflatoxin-producing strains of A. flavus 
proliferate. This competitive exclusion of the aflatoxin-producing 
strains does not increase the total Aspergillus population in the 
environment above background levels as demonstrated in soil and air 
monitoring studies. [MRIDs 45307201, 45307202; BPPD Review of Soil and 
Air Monitoring Studies and Product Performance Testing (Efficacy), 
dated May 15, 2003 (hereinafter referred to as ``BPPD Review - May 15, 
2003'')]. The displacement of the toxigenic strain of Aspergillus 
flavus by AF36 may reduce aflatoxin contamination of cotton seed.
    The toxicology and pathogenicity data generated by the petitioner 
in support of this tolerance exemption, and reviewed by the Agency, are 
summarized below. The following discussion of the evaluations of the 
submitted studies and information indicates that exposure to the 
pesticide is not likely to be greater than that which occurs normally 
to other ubiquitous A. flavus strains. Submitted data also indicate no 
toxicity or infectivity of AF36 in test mammalian systems. More 
detailed analyses of these studies can be found in the specific Agency 
reviews of the studies that are cited below.
    1. Acute oral toxicity/pathogenicity (OPPTS Harmonized Guideline 
885.3050; MRID 43972403). Agency evaluation of submitted acute oral 
study indicates no toxicity/infectivity effects of the pesticide. Five 
male, and five female Sprague Dawley rats were treated orally with the 
microbial pesticide (500 milligrams/milliliter (mg/mL) or 6.3 x 
103 cfu/mL) by gavage. No clinical signs or abnormalities 
were noted during the study, and the pesticide was considered to be 
neither toxic nor infective following oral administration of a single 
dose. The acute oral test resulted in a Toxicity Category IV 
classification with a lethal dose (LD)50 greater than 5,000 
milligrams/kilogram (mg/kg) body weight [MRID 43972403; BPPD Data 
Evaluation Report, Acute Oral Toxicity Study in Rats, dated April 23, 
1996 (hereinafter referred to as ``BPPD Review - April 23, 1996'')].
    2. Acute pulmonary toxicity/pathogenicity (OPPTS Harmonized 
Guideline 885.3150; MRID 45798201). The Agency required an 
intratracheal pulmonary infectivity/pathogenicity study. This test 
involves intratracheal instillation of the test material and post 
mortem examination of lungs and other organs for clearance.
    Three studies were submitted in support of the mammalian acute 
infectivity/pathogenicity pulmonary guideline: A range finding study 
and two complete acute pulmonary studies. The dose-range study 
concluded that 108 cfu/rat would be a suitable test dose 
level for the acute pulmonary studies [MRID 45739101; BPPD Data 
Evaluation Report, dated April 02, 2003a (hereinafter referred to as 
``BPPD Review - April 02, 2003a'')]. In the first acute pulmonary 
study, conducted with Tween 80 as a surfactant in the test material, 26 
male and 26 female Sprague Dawley rats (approximately 8 to 10 weeks 
old) each were dosed with a single intratracheal dose of 1.2 mL/kg at 
5.30 x 108 cfu/mL (or 1.28 to 1.63 x 108 cfu/
animal). Results from this study indicated that the test organism was 
neither infective nor pathogenic, in spite of rat mortality, which is 
believed to have been due to a severe acute inflammatory response to 
the Tween 80 [MRID 45798101; BPPD Data Evaluation Report, dated April 
02, 2003a (hereinafter referred to as ``BPPD Review - April 02, 
2003b'')].
    In the second acute pulmonary study, which was a repetition of the 
first acute pulmonary test, but was conducted without Tween 80, 25 male 
and 25 female Sprague Dawley rats (approximately 8 to 10 weeks old) 
each received a single intratracheal dose of approximately 1.2 mL/kg. 
Mortality of 4 rats by day 2 appeared to be attributable to an initial 
dosing effect. The rest of the test animals showed an initial response, 
followed by a rapid recovery indicating no toxicity. Although some 
surviving rats lost weight intermittently, all surviving rats gained 
weight prior to scheduled sacrifice. No clinical signs that were 
considered to be due to the test organism were observed in the test 
rats. Organs were examined post mortem as previously described. 
Aspergillus flavus AF36 was detected in the lungs with clearance by day 
8 after dosing. No test organisms were detected in any samples from the 
shelf control or inactivated test organism treated rats. Based on the 
presented/submitted data, including the clearance data, the test 
organism, Aspergillus flavus AF36, was considered not toxic, infective, 
or pathogenic to the rat pulmonary system. The study is acceptable.
    3. Acute inhalation (OPPTS Harmonized Guideline 152-32). The inert 
is sterilized wheat seeds, comprising approximately 99% of this 
pesticidal product. It acts as a matrix and nutrient source for the 
germinating AF36. Because this constitutes the majority of the 
pesticide and does not contain respirable particles of less than 10 
microns, an inhalation study was not required pursuant to 40 CFR 
158.740(c). In addition, based on the results obtained through the 
acute pulmonary toxicity/pathogenicity studies summarized immediately 
above, AF36 is considered not toxic, infective, or pathogenic to the 
rat pulmonary system. On the basis of this study and the nature of the 
inert ingredients present, the pesticide was considered Toxicity 
Category III for acute inhalation effects. [MRID 45798201; BPPD Data 
Evaluation Report, dated April 02, 2003c (hereinafter referred to as 
``BPPD Review - April 02, 2003c'')].
    4. Hypersensitivity incidents (OPPTS Harmonized Guideline 152-37; 
MRID 45739104). The registrant submitted information (MRID 45739104) to 
demonstrate the lack of hypersensitivity to workers who have been 
exposed during the manufacture, application, and use of the pesticide 
in the research and experimental phases. No adverse hypersensitivity 
reaction to AF36 was recorded or reported by a state council or six 
companies during use for 3 or 6 years [MRID 45739104; BPPD Data 
Evaluation Report, dated April 02, 2003d (hereinafter referred to as 
``BPPD Review - April 02, 2003d'')]. However, to comply with the 
Agency's requirements under section 6(a)(2), any incident of 
hypersensitivity associated with the use of this pesticide must be 
reported to the Agency.
    5. Data waivers. Data waivers were requested for the following 
studies:
    i. Acute dermal toxicity/pathogenicity (OPPTS Harmonized Guideline 
885.3100)
    ii. Primary dermal irritation (OPPTS Harmonized Guideline 870.2500)
    iii. Primary eye irritation (OPPTS Harmonized Guideline 870.2400)
    iv. Intravenous, intracerebral, intraperitoneal injection (OPPTS 
Harmonized Guideline 885.3200)
    v. Hypersensitivity study (40 CFR 152-36)
    vi. Immune response (40 CFR 152-38)
    With regards to the dermal and eye irritation guideline tests, it 
was impractical to apply the end-use product, sterilized wheat seeds 
inoculated with Aspergillus flavus AF36, as test material. Furthermore, 
non-occupational dermal and eye exposures, or exposures via any of the 
routes in Unit III.5.i.--vi., are not likely to be above naturally-
occurring background levels for the following reasons.
    First, Aspergillus flavus, a saprophytic fungus, is a normal

[[Page 41538]]

constituent of the microflora in air and soil. The naturally occurring 
soil and plant colonizer is also found on living and dead plant 
material throughout the world. Aflatoxin-producing strains of 
Aspergillus flavus are particularly prominent in hot, dry climates 
supplemented with irrigation and are ubiquitous components of the 
natural Arizona desert ecosystem. Quantities of A. flavus typically 
increase during crop production and the fungus occurs widely on crop 
debris left in the soil. Shortly after application, AF36 germinates, 
apparently displaces the aflatoxin-producing strains from cotton and 
the soil, and spore levels return to normal background, without 
increase of total A. flavus. This was demonstrated in soil and air 
monitoring studies submitted over multiple years of experimental usage 
[BPPD Review - May 15, 2003]. Thus exposures to AF36 are not likely to 
increase above those normally associated with the naturally occurring 
A. flavus background levels.
    Second, the application rate is low, being less than 0.01 lb active 
ingredient per acre, and agricultural sites are treated, thus 
minimizing non-occupational and residential exposure. The proposed 
label rate is less than 0.01 pound of active ingredient in 10 pounds 
end-use product, or approximately 1.34 x 107 colony forming 
units (cfu) per acre.
    Finally, drift is not expected during application based on the 
large granular nature of the pesticide (i.e., sterilized inoculated 
wheat seeds). In addition, only one prebloom application is made, and 
cultivation is not recommended after application. Thus, once again, the 
potential for non-occupational dermal and residential exposure is 
unlikely.
    The acute oral toxicological study demonstrated an LD50 
of greater than 5,000 mg/kg with no toxicity/infectivity effects, and 
demonstrable clearance from organs examined post mortem [MRID 43972403; 
BPPD Review - April 23, 1996]. This rationale supported the request to 
waive the acute intraperitoneal study.
    A hypersensitivity study was waived since hypersensitivity 
incidents were not reported from maximally exposed workers and 
researchers during the research and experimental phases associated with 
the use of the active ingredient, A. flavus AF36 [BPPD Review - April 
02, 2003d]. Nevertheless, reports of hypersensitivity incidents 
associated with the use of the pesticide are still required to comply 
with FIFRA section 6(a)(2) requirements.
    Submitted toxicity/pathogenicity studies in the rodent (required 
for microbial pesticides) also indicate that following oral and 
pulmonary routes of exposure [BPPD Review - April 23, 1996; BPPD Review 
- April 02, 2003c], the immune system is still intact and able to 
process and clear the active ingredient. Thus, the request to waive the 
immune response study was granted.
    On the basis of the foregoing rationales, and there being no 
documented problems associated with the non-aflatoxin producing strain, 
Aspergillus flavus AF36, data waivers for the studies listed in Unit 
III.5.i.--vi., were granted to the applicant for the proposed use of 
Aspergillus flavus AF36 on cotton.
    6. Subchronic, chronic toxicity and oncogenicity, and residue. 
Based on the data generated in accordance with the Tier I data 
requirements set forth in 40 CFR 158.740(c), the Tier II and Tier III 
data requirements were not triggered and, therefore, not required in 
connection with this action. In addition, because the Tier II and Tier 
III data requirements were not required, the residue data requirements 
set forth in 40 CFR 158.740(b) also were not required.

IV. Aggregate Exposures

    In examining aggregate exposure, section 408 of the FFDCA directs 
EPA to consider available information concerning exposures from the 
pesticide residue in food and all other non-occupational exposures, 
including drinking water from ground water or surface water and 
exposure through pesticide use in gardens, lawns, or buildings 
(residential and other indoor uses).
    There is a potential for aggregate exposure of adult humans, 
infants and children to the microbe because of the ubiquitous 
distribution of Aspergillus fungal strains in the environment. The 
Agency has considered the incremental exposure and risk associated with 
the proposed application of this strain of Aspergillus flavus, AF36, as 
summarized below, and concludes that use of AF36 is not likely to add 
an incremental risk above that posed by the normal exposure of adults, 
infants and children to Aspergillus flavus strains present in the 
environment. In fact, use of the pesticide, AF36, may decrease 
potential environmental aflatoxin exposure to exposed populations.

A. Dietary Exposure

    1. Food. Based on submitted studies, the end-use product, 
Aspergillus flavus AF36, demonstrates low acute oral toxicity category 
IV potential [BPPD Review - April 23, 1996]. No toxicity endpoints were 
indicated to justify setting a numerical tolerance for the fungal 
active ingredient, Aspergillus flavus AF36. An LD50 greater 
than 5,000 mg/kg body weight, in the acute oral studies discussed 
above, indicates that consumption of food commodities treated with AF36 
poses no incremental risk via dietary exposure. Indeed, the submitted 
data indicate no toxicity or infectivity of AF36 in the acute oral test 
mammalian systems.
    Cotton itself is not a food commodity. Residues of A. flavus AF36, 
the microbial active ingredient, are not likely to survive the heating 
and pressure associated with the processing of cottonseed into 
cottonseed meal. Moreover, A. flavus AF36 will not separate into the 
edible fraction, cotton seed oil. Thus, potential transfer of residues 
of A. flavus AF36 to edible cotton food/feed commodities is not 
expected. Consequently, human dietary exposure to A. flavus AF36 via 
cottonseed oil, or by secondary transfer of A. flavus AF36 residues to 
meat and milk via cottonseed meal, is not expected. Therefore, the 
Agency has determined that dietary exposure to A. flavus AF36 is not 
likely to result in any undue health effects and risk.
    While the Agency has concluded that AF36 is not likely to add to 
the dietary burden, any potential contribution by AF36 to aflatoxin 
contamination was also considered, for a conservative estimate of the 
health effects of this pesticide. This is because aflatoxin is 
considered a public health hazard (see Unit VII.D.) and AF36 is 
proposed as a biocontrol agent for aflatoxin-producing strains of A. 
flavus. Even if AF36 does not control aflatoxin levels in the treated 
cotton food/feed commodities, a safety net exists in the screening of 
cotton and its by-products for aflatoxin prior to their introduction 
into the channels of commerce. For instance, FDA does not allow cotton 
seed products containing aflatoxin above 20 parts per billion (ppb) to 
be used in dairy rations or above 300 ppb to be used for feeding beef 
cattle. As previously stated, the registrant claims that quality 
control and selection procedures will not allow aflatoxin production in 
the starter cultures for pesticide manufacture [BPPD review - March 29, 
1999; BPPD review - May 14, 1999]. Any batches with aflatoxin are to be 
destroyed. For these reasons, the Agency has determined that use of 
AF36 will not add to the dietary burden of aflatoxin, but is rather 
more likely to ameliorate aflatoxin levels in treated cotton food/feed 
commodities. Therefore, dietary exposure to aflatoxin, as a result of 
AF36 use, is not likely to be greater, and may even be less, than that 
which currently exists.

[[Page 41539]]

    2. Drinking water exposure. Exposure to AF36 via drinking water is 
not likely to be greater than current/existing exposures to A. flavus 
strains. Potential risks via exposure to drinking water or runoff are 
adequately mitigated by, among other things, percolation through soil. 
Thus, exposure via drinking water from the proposed use of this non-
aflatoxin-producing strain of Aspergillus flavus is not likely to pose 
any incremental risk to adult humans, infants and children. In fact, 
displacement of the toxigenic strains of A. flavus by AF36 may decrease 
exposure and risk to the toxigenic strains of A. flavus in the 
environment.

B. Other Non-Occupational Exposure

    1. Dermal exposure. The potential for non-occupational dermal 
exposure to AF36 is unlikely because the potential use sites, are 
commercial and agricultural, and because of the granular nature of the 
pesticide, which minimizes spray drift. As discussed earlier (see Unit 
III.), lack of hypersensitivity incidents, low application rates, and 
return of levels of Aspergillus flavus to background shortly after 
germination, poses minimal risk to populations via dermal, non-
occupational exposure. Thus, dermal non-occupational exposure to the 
non-aflatoxin strain is not likely to be greater than the existing 
exposure to A. flavus at current levels.
    2. Inhalation exposure. For the reasons stated immediately above, 
non-occupational inhalation exposure to AF36 is not expected to be 
greater than that which currently exists for A. flavus strains.

V. Cumulative Effects

    Section 408(b)(2)(D)(v) of the FFDCA requires the Agency to 
consider the cumulative effect of exposure to Aspergillus flavus AF36 
and to other substances that have a common mechanism of toxicity. These 
considerations include the possible cumulative effects of such residues 
on infants and children. Aspergillus flavus AF36 does not appear to be 
toxic or pathogenic to humans. There is no indication that the fungus 
A. flavus AF36 shares any common mechanisms of toxicity with other 
registered pesticides. In addition, there are no other registered 
pesticide products containing Aspergillus flavus AF36, and other A. 
flavus strains abound naturally in the environment. Moreover, the 
displacement of the toxigenic strain of A. flavus by AF36 may reduce 
aflatoxin contamination of cottonseed. Based on the low toxicity 
potential of AF36, the fact that it is non-aflatoxigenic, and the 
safety net already in place to monitor for aflatoxin, no cumulative or 
incremental effect is expected from the use of AF36 on cotton.

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

    There is reasonable certainty that no harm will result from 
aggregate exposures to residues of A. flavus AF36, in its use as an 
antifungal agent, to the U. S. population, including infants and 
children. This includes all anticipated dietary exposures and all other 
exposures for which there is reliable information. As discussed 
previously, there appears to be no potential for harm, from this fungus 
in its use as an antifungal agent via dietary exposure since the 
organism is non-toxic and non-pathogenic to animals and humans. The 
Agency has arrived at this conclusion based on the very low levels of 
mammalian toxicity for acute oral and pulmonary effects with no 
toxicity or infectivity at the doses tested (see Unit III above). 
Moreover, non-occupational inhalation or dermal exposure is not 
expected above background levels (see Unit V).
    FFDCA section 408(b)(2)(C) provides that EPA shall apply an 
additional ten-fold margin of exposure (safety) for infants and 
children in the case of threshold effects to account for prenatal and 
postnatal toxicity and the completeness of the data base unless EPA 
determines that a different margin of exposure (safety) will be safe 
for infants and children. Margins of exposure (safety) are often 
referred to as uncertainty (safety) factors. In this instance, based on 
all the available information, the Agency concludes that the fungus, A. 
flavus AF36, is non-toxic to mammals, including infants and children. 
Because there are no threshold effects of concern to infants, children 
and adults when A. flavus AF36 is used as labeled, the provision 
requiring an additional margin of safety does not apply. As a result, 
EPA has not used a margin of exposure (safety) approach to assess the 
safety of A. flavus AF36.

VII. Other Considerations

A. Endocrine Disruptors

    EPA is required under the FFDCA, as amended by FQPA, to develop a 
screening program to determine whether certain substances (including 
all pesticide active and other ingredients) ``may have an effect in 
humans that is similar to an effect produced by a naturally-occurring 
estrogen, or other such endocrine effects as the Administrator may 
designate.'' Following the recommendations of its Endocrine Disruptor 
Screening and Testing Advisory Committee (EDSTAC), EPA determined that 
there was scientific basis for including, as part of the program, the 
androgen-and thyroid systems, in addition to the estrogen hormone 
system. EPA also adopted EDSTAC's recommendation that the program 
include evaluations of potential effects in wildlife. For pesticide 
chemicals, EPA will use FIFRA and, to the extent that effects in 
wildlife may help determine whether a substance may have an effect in 
humans, FFDCA authority, to require the wildlife evaluations. As the 
science develops and resources allow, screening of additional hormone 
systems may be added to the Endocrine Disruptor Screening Program 
(EDSP).
    The Agency is not requiring information on the endocrine effects of 
this active ingredient, Aspergillus flavus AF36, at this time. The 
Agency has considered, among other relevant factors, available 
information concerning whether the microorganism may have an effect in 
humans similar to an effect produced by a naturally occurring estrogen 
or other endocrine effects. There is no known metabolite that acts as 
an ``endocrine disrupter'' produced by this microorganism. The 
submitted toxicity/infectivity or pathogenicity studies in the rodent 
(required for microbial pesticides) indicate that, following oral and 
pulmonary routes of exposure, the immune system is still intact and 
able to process and clear the active ingredient (see Unit III.). In 
addition, based on the low potential exposure level associated with the 
proposed single, seasonal, prebloom application of the pesticide, the 
Agency expects no adverse effects to the endocrine or immune systems.

B. Analytical Method

    The Agency proposes to establish an exemption from the requirement 
of a tolerance without any numerical limitation. Accordingly, the 
Agency has concluded that for an exemption from tolerance, analytical 
methods are not needed for enforcement purposes for residues of 
Aspergillus flavus AF36 on treated cotton. Nonetheless, and for 
purposes of clarification, analytical methods are still required for 
product characterization, quality control, and quality assurance for 
manufacturing purposes [BPPD review - March 29, 1999; BPPD review - May 
14, 1999]. Vegetative compatibility tests are used to screen starter 
cultures to identify the non-aflatoxin-producing Aspergillus flavus 
AF36 strain. Starter cultures of AF36 are also selected on the basis of

[[Page 41540]]

the lack of aflatoxin as monitored by standard thin layer 
chromatography (tlc) procedures and visualization via scanning 
fluorescence densitometry scanning. Other appropriate methods are 
required for quality control to assure product characterization, the 
control of human pathogens and other unintentional metabolites or 
ingredients within regulatory limits, and to ascertain storage 
stability and viability of the pesticidal active ingredient.

C. Codex Maximum Residue Level

    There is no Codex maximum residue level for residues of Aspergillus 
flavus AF36.

D. Efficacy Data

    PR Notice 2002-1 lists aflatoxin as a public health hazard, for 
which product performance or efficacy data are required according to 40 
CFR 158.202(i). To demonstrate that this pesticide may reduce 
aflatoxin-producing strains and does not increase A. flavus populations 
above background levels, the applicant provided product performance or 
efficacy data from multiple years of soil and air monitoring studies.
    Aflatoxin, one of the most potent human carcinogens, is the 
metabolite of concern produced by the target pest, aflatoxin-producing 
strains of Aspergillus flavus. As such, the Agency considers aflatoxin 
a public health hazard. In the soils of cotton-producing areas of 
Arizona and south Texas, especially in the dry regions, the toxigenic 
strains are prominent. Few alternatives, if any, exist to displace 
aflatoxin-producing A. flavus strains from cotton and other crops. 
Decontamination of crops via ammoniation is costly, not available 
universally, and decreases the value of the crop. Other methods to 
reduce aflatoxin formation include manipulation of harvest date, costly 
irrigation practices, and different methods of harvesting and storage 
practices.
    Efficacy data submitted to the Agency include monitoring of soil 
and air levels of the toxigenic and non-aflatoxin-producing strains of 
A. flavus AF36 in the field and on the crops. Results from the 
environmental expression and population monitoring studies, during the 
experimental program, demonstrate that a single seasonal application of 
AF36 on cotton fields may incite significant changes in the incidence 
of toxigenic A. flavus strains resident in the agroecosystem, without 
altering the overall quantity of A. flavus. Soil and air population 
counts of A. flavus from treated fields were associated with 
concomitant decreases in incidences of toxigenic A. flavus, for many of 
the treated areas [BPPD review - May 15, 2003]. Reducing the aflatoxin-
producing populations of fungi, and the concomitant reduction of 
aflatoxin, a potent carcinogen, is in the public interest.

VIII. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA, EPA will continue to use those procedures, with 
appropriate adjustments, until the necessary modifications can be made. 
The new section 408(g) of the FFDCA provides essentially the same 
process for persons to ``object'' to a regulation for an exemption from 
the requirement of a tolerance issued by EPA under new section 408(d) 
of the FFDCA, as was provided in the old sections 408 and 409 of the 
FFDCA. However, the period for filing objections is now 60 days, rather 
than 30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0138 in the subject line on the 
first page of your submission. All objections and hearing requests must 
be in writing, and must be mailed or delivered to the Hearing Clerk on 
or before September 12, 2003.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm. 104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is 
open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Office of the Hearing Clerk is 
(703) 603-0061.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit IX.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.1. Mail your 
copies, identified by docket ID number OPP-2003-0138, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit

[[Page 41541]]

I.B.1. You may also send an electronic copy of your request via e-mail 
to: [email protected]. Please use an ASCII file format and avoid the 
use of special characters and any form of encryption. Copies of 
electronic objections and hearing requests will also be accepted on 
disks in WordPerfect 6.1/8.0 or ASCII file format. Do not include any 
CBI in your electronic copy. You may also submit an electronic copy of 
your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

IX. Statutory and Executive Order Reviews

    This final rule establishes an exemption from the tolerance 
requirement under section 408(d) of the FFDCA in response to a petition 
submitted to the Agency. The Office of Management and Budget (OMB) has 
exempted these types of actions from review under Executive Order 
12866, entitled Regulatory Planning and Review (58 FR 51735, October 4, 
1993). Because this rule has been exempted from review under Executive 
Order 12866 due to its lack of significance, this rule is not subject 
to Executive Order 13211, Actions Concerning Regulations That 
Significantly Affect Energy Supply, Distribution, or Use (66 FR 28355, 
May 22, 2001). This final rule does not contain any information 
collections subject to OMB approval under the Paperwork Reduction Act 
(PRA), 44 U.S.C. 3501 et seq., or impose any enforceable duty or 
contain any unfunded mandate as described under Title II of the 
Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 104-4). Nor 
does it require any special considerations under Executive Order 12898, 
entitled Federal Actions to Address Environmental Justice in Minority 
Populations and Low-Income Populations (59 FR 7629, February 16, 1994); 
or OMB review or any Agency action under Executive Order 13045, 
entitled Protection of Children from Environmental Health Risks and 
Safety Risks (62 FR 19885, April 23, 1997). This action does not 
involve any technical standards that would require Agency consideration 
of voluntary consensus standards pursuant to section 12(d) of the 
National Technology Transfer and Advancement Act of 1995 (NTTAA), 
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of the FFDCA, such as the exemption from 
the tolerance requirement in this final rule, do not require the 
issuance of a proposed rule, the requirements of the Regulatory 
Flexibility Act (RFA) (5 U.S.C. 601 et seq.) do not apply. In addition, 
the Agency has determined that this action will not have a substantial 
direct effect on States, on the relationship between the national 
government and the States, or on the distribution of power and 
responsibilities among the various levels of government, as specified 
in Executive Order 13132, entitled Federalism (64 FR 43255, August 10, 
1999). Executive Order 13132 requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by State and local 
officials in the development of regulatory policies that have 
federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this rule does not have any ``tribal implications'' 
as described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
Order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

X. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. EPA will submit a report containing this rule and other 
required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of this final rule in the Federal Register. This final 
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

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

    Dated: July 2, 2003.
James Jones,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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

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

0
2. Section 180.1206 is revised to read as follows:


Sec.  180.1206  Aspergillus flavus AF36; exemption from the requirement 
of a tolerance.

    An exemption from the requirement of a tolerance is established for 
residues of the microbial pesticide Aspergillus flavus AF36 in or on 
cotton and its food/feed commodities.

[FR Doc. 03-17726 Filed 7-11-03; 8:45 am]
BILLING CODE 6560-50-S