[Federal Register Volume 75, Number 131 (Friday, July 9, 2010)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-16771]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Homobrassinolide; Exemption from the Requirement of a Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of homobrassinolide in or on all food
commodities when applied/used as a plant growth regulator in accordance
with good agricultural practices. Repar Corporation submitted a
petition to EPA under the Federal Food, Drug, and Cosmetic Act (FFDCA),
requesting an exemption from the requirement of a tolerance. This
regulation eliminates the need to establish a maximum permissible level
for residues of homobrassinolide under the FFDCA.
DATES: This regulation is effective July 9, 2010. Objections and
requests for hearings must be received on or before September 7, 2010,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2007-1187. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the Office of Pesticide Programs (OPP) Regulatory Public
Docket in Rm. S-4400, One Potomac Yard (South Bldg.), 2777 S. Crystal
Dr., Arlington, VA. The Docket Facility is open from 8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays. The Docket
Facility telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: John Fournier, Biopesticides and
Pollution Prevention Division (7511P), Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 308-0169; e-mail address: [email protected].
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
B. How Can I Get Electronic Access to Other Related Information?
You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr.
C. How Can I File an Objection or Hearing Request?
Under FFDCA section 408(g), 21 U.S.C. 346a(g), any person may file
an objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2007-1187 in the subject line on
the first page of your submission. All objections and requests for a
hearing must be in writing, and must be received by the Hearing Clerk
on or before September 7, 2010. Addresses for mail and hand delivery of
objections and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket. Information not marked confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA without prior notice. Submit a copy of
your non-CBI objection or hearing request, identified by docket ID
number EPA-HQ-OPP-2007-1187, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: OPP Regulatory Public Docket (7502P), Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of February 13, 2008 (73 FR 8312) (FRL-
8349-2), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide tolerance
petition (PP 7F7296) by Repar Corporation, 8070 Georgia Avenue, Suite
209, Silver Spring, MD 20910. The petition requested that 40 CFR part
180 be amended by establishing an exemption from the requirement of a
tolerance for residues of homobrassinolide. This notice referenced a
summary of the petition prepared by the petitioner, Repar Corporation,
which is available in the docket, http://www.regulations.gov. Comments
were received on the notice of filing. EPA's response to these comments
is discussed in Unit VII.C.
Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the exemption is ``safe.'' Section 408(c)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Pursuant to section 408(c)(2)(B) of FFDCA, in
establishing or maintaining in effect an exemption from the requirement
of a tolerance, EPA must take into account the factors set forth in
section 408(b)(2)(C) of FFDCA, which require EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical
residue....'' Additionally, section 408(b)(2)(D) of FFDCA requires that
EPA 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 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.
A. Overview of Homobrassinolide
The active ingredient, homobrassinolide, is a plant growth
regulator that is a synthesized homologue of brassinolide, a naturally
occurring brassinosteroid. Brassinosteroids are a group of steroidal
plant hormones that were discovered in 1973, when it was shown that
pollen from rapeseed (Brassica napus) could promote stem elongation and
cell division and that the biologically active molecule was a steroid.
Brassinosteroids are ubiquitously distributed in the plant kingdom.
Since their discovery, over 70 brassinosteroids have been isolated from
plants. The occurrence of these steroids has been demonstrated in
various plant parts, such as pollen, flower buds, fruit seeds, vascular
cambium, leaves, shoots, and roots. Studies on higher plants suggest
that these steroids play a critical role in a range of developmental
processes (i.e., stem elongation, root growth, floral initiation,
B. Biochemical Pesticide Human Health Assessment Data Requirements
1. Acute Toxicity. Tier I acute toxicity studies showed that
homobrassinolide is a Toxicity Category IV (low toxicity) compound via
oral and inhalation routes of exposure and a Toxicity Category III
(slightly toxic) compound for dermal and eye exposures. Moreover,
homobrassinolide is neither a skin irritant nor a dermal sensitizer.
Given the results of these studies, no additional toxicity (i.e., Tiers
II or III) or residue data are required to support food uses of this
biochemical active ingredient.
i. The acute oral median lethal doses (LD50s) for
homobrassinolide in rats and mice were greater than 5,000 milligrams
per kilogram (mg/kg) and confirmed negligible toxicity through oral
exposure (Master Record Identification Numbers [MRID Nos.] 47185118 and
47208903). Homobrassinolide is classified as Toxicity Category IV for
acute oral toxicity.
ii. The acute dermal median lethal dose (LD50) for
homobrassinolide in rats was over 2,000 mg/kg, which confirmed low
dermal toxicity (Master Record Identification Number [MRID No.]
47185120). Homobrassinolide is classified as Toxicity Category III for
acute dermal toxicity.
iii. The acute inhalation median lethal concentration
(LC50) was greater than 2.26 milligrams per liter (mg/L) in
rats and showed practically no inhalation toxicity or irritation (MRID
No. 47185121). Homobrassinolide is classified as Toxicity Category IV
for acute inhalation toxicity.
iv. An acute eye study showed that exposure to homobrassinolide
will cause temporary mild eye irritation (MRID No. 47185122). As such,
EPA has determined that homobrassinolide is Toxicity Category III for
acute eye irritation. Acute dermal irritation and skin sensitization
studies showed that homobrassinolide is non-irritating and not a
sensitizer to the skin (MRID Nos. 47185123 and 47185124). EPA has
determined that homobrassinolide is Toxicity Category IV for both
dermal irritation and dermal sensitization.
These acute toxicity studies, submitted to support the registration
of one manufacturing-use product containing homobrassinolide, confirm a
low toxicity profile.
2. Subchronic Toxicity. i. The submitted 90-day oral toxicity (MRID
No. 47208906) study showed that test animals did not exhibit any
clinical signs of toxicity that were statistically different from
untreated controls. There were no significant changes in organ weights
(e.g., thymus and spleen) or differential white blood cell counts of
the treated animals during the 90-day study period, which would
indicate potential interference with normal immune function. The 90-day
oral feeding no observable effect level (NOEL) for Homobrassinolide
Technical was 1,000 milligrams per kilogram per day. Based on the
review of these data, EPA concluded that no subchronic oral toxicity is
expected to occur when this compound is used in accordance with good
ii. Submission of 90-day dermal toxicity data was waived by EPA
(MRID No. 47185136) for primarily two reasons. First, dermal metabolism
of homobrassinolide is not expected to differ from its oral metabolism.
Acute guideline studies demonstrated that homobrassinolide has a low
dermal toxicity (LD50 >2,000 mg/kg), was not a dermal
irritant, and was not a dermal sensitizer. In addition, prolonged human
dermal exposure is remote as brassinosteroids are readily metabolized
by plants to inactive forms and, therefore, the application of
homobrassinolide to crop plants as a plant growth stimulant is unlikely
to increase levels of brassinosteroids in the treated plants.
Brassinosteroids are present in all plants, resulting in ubiquitous
exposure to humans and other organisms though the food chain without
iii. Submission of 90-day inhalation data was also waived. The
acute inhalation toxicity study demonstrates homobrassinolide's lack of
toxicity (Toxicity Category IV) and there is no anticipated repeated
inhalation exposure under the conditions of product use at a
concentration that could be toxic (MRID No. 47185137).
3. Developmental Toxicity and Mutagenicity. Based on in vivo
studies using oral applications of homobrassinolide, the active
ingredient did not have the potential to induce chromosome aberrations
in mice treated up to a single oral dose of 2,000 mg/kg body weight.
The active ingredient did not have micronucleus induction potential in
mice after two days of oral dosing up to a level of 2,000 mg/kg body
weight. Thus, homobrassinolide is non-mutgenic to mice (MRID No.
In vitro studies demonstrated that treatment with 100 and 1,000 mg/
kg body weight of homobrassinolide did not result in mortality or overt
signs of toxicity for pregnant rats during the observation period. Body
weight changes in the groups of test substance treated dams were
statistically similar to controls and no significant changes were
observed in the weights of ovary and fetuses. The test further showed
that there were no significant changes in the uterine weights, as well
as, no test related recurrent visceral and skeletal malformations when
compared to controls. Based on these findings it appears that
homobrassinolide is non-teratogenic to Wistar rats at the dose levels
of 100 and 1000 mg/kg of bodyweight (MRID No. 47185132).
As a result of the findings in these studies, EPA concludes that
homobrassinolide is not mutagenic or genotoxic.
Bajguz, A., 2000. Effect of brassinosteroids on nuclear acids and
protein content in cultured cells of chlorella vulgaris. Plant Physiol.
Biochem. 38, 209-215.
Catterou, M., F. Dubois, H. Schaller, L. Aubanella, B. Vilcol, B. S.
Sangwan-Norrel, R.S. Sangwan, 2001. Brassinosteroids microtubules and
cell elongation in Arabidopsis thaliana. II. Effects of
brassinosteroids on microtubules and cell elongation in the bull
mutant. Planta, 212, 673-683.
IECVI.I - Individual Effects Chance Model Version 1.1. 2004. USEPA/OPP/
EFEDSeeta S.R.R., B.V.Vardhini, E. Sujatha, S. Anuradha. 2002.
Brassinosteroids-A new class of phytohormones. Current Science,
IV. Aggregate Exposures
In examining aggregate exposure, section 408 of FFDCA directs EPA
to consider available information concerning exposures from the
pesticide residue in food and all other non-occupational exposures,
including drinking water from ground water or surface water and
exposure through pesticide use in gardens, lawns, or buildings
(residential and other indoor uses).
A. Dietary Exposure
1. Food. The primary route of homobrassinolide exposure to the
general population is expected to be through consumption of food.
Dietary exposure to homobrassinolide from application/use as a plant
growth regulator is expected to be minimal, assuming use consistent
with the labeling and use of good agricultural practices. The approved
label allows a maximum application rate of 20 grams of active
ingredient per acre per application. In addition, homobrassinolide is
present in all plants, resulting in ubiquitous exposure to humans and
other organisms through the food chain without causing harm. The
endogenous levels of brassinosteroids are in parts per million or parts
per billion (e.g., brassinosteroid levels in pollen have been measured
at 200 parts per billion). The 20 grams per acre of homobrassinolide
from application/use as a plant growth regulator is not expected to
increase natural levels of brassinosteroids in treated plants. This is
because the homobrassinolide applied/used as a crop plant will be
metabolized as the plant grows.
2. Drinking water exposure. No significant drinking water exposure
or residues are expected to result from the use of homobrassinolide as
a plant growth regulator. The active ingredient is intended for use as
a foliar application on food commodities and is not to be applied
directly to water. If used in accordance with EPA-approved labeling and
good agricultural practices, homobrassinolide is not likely to
accumulate in drinking water. Furthermore, it is doubtful that
homobrassinolide concentrations in water would exceed levels that are
currently ubiquitous to plants. Although fate information is not
available on homobrassinolide, the compound is not soluble in water
(water solubility 3.18%), and the log Pow = 3.96 suggests both moderate
binding to soil and a low probability of ground water contamination.
Overall, drinking water exposure to residues of homobrassinolide is
expected to be minimal.
B. Other Non-Occupational Exposure
The potential for non-dietary exposure of the general population,
including infants and children, is limited based on the use patterns of
homobrassinolide. Non-dietary exposures would not be expected to pose
any quantifiable risk to the general population.
V. Cumulative Effects from Substances with a Common Mechanism of
Section 408(b)(2)(D)(v) of FFDCA requires that, when considering
whether to establish, modify, or revoke a tolerance, EPA consider
``available information concerning the cumulative effects of [a
residues and other substances that have a common mechanism of
EPA has not found homobrassinolide to share a common mechanism of
toxicity with any other substances, and homobrassinolide does not
appear to produce a toxic metabolite produced by other substances. For
the purposes of this tolerance exemption, therefore, EPA has assumed
that homobrassinolide does not have a common mechanism of toxicity with
other substances. For information regarding EPA's efforts to determine
which chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's website at http://www.epa.gov/pesticides/cumulative.
VI. Determination of Safety for the United States Population, Infants,
FFDCA section 408(b)(2)(C) provides that EPA shall assess the
available information about consumption patterns among infants and
children, special susceptibility of infants and children to pesticide
chemical residues, and the cumulative effects on infants and children
of the residues and other substances with a common mechanism of
toxicity. In addition, FFDCA section 408(b)(2)(C) provides that EPA
shall apply an additional tenfold margin of safety for infants and
children in the case of threshold effects to account for prenatal and
postnatal toxicity and the completeness of the database unless EPA
determines that a different margin of safety will be safe for infants
and children. Margins of exposure (safety), which are often referred to
as uncertainty factors, are incorporated into EPA risk assessments
either directly or through the use of a margin of exposure analysis, or
by using uncertainty (safety) factors in calculating a dose level that
poses no appreciable risk.
Based on the results of the toxicological data discussed in Unit
III., as well as all other available information, EPA concludes that
there is a reasonable certainty that no harm will result to the United
States population, including infants and children, from aggregate
exposure to the residues of homobrassinolide. This includes all
anticipated dietary exposures and all other exposures for which there
is reliable information. EPA has arrived at this conclusion based on
the low level of toxicity of the compound, the minimal exposure from
application/use of homobrassinolide as a plant growth regulator, the
ubiquitous nature of brassinosteroids in the plant kingdom, and the
already widespread exposure to these plant steroids without any
reported adverse effects on human health. Thus, there are no threshold
effects of concern and, as a result, the provision requiring an
additional margin of safety does not apply in this instance.
VII. Other Considerations
A. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has not established a MRL for homobrassinolide.
B. Response to Comments
A notice of receipt of the application for registration of a
pesticide product containing homobrassinolide (a new active ingredient)
was published in the Federal Register and opened a 30-day comment
period (73 FR 8312, February 13, 2008). Two comments were received
following this publication, but neither comment was related to the
registration of homobrassinolide as a new active ingredient (i.e., both
referenced a pesticide product apparently associated with another
active ingredient) nor provided any substantive basis, such as data or
other available information, supporting their respective positions or
calling into question any of EPA's risk assessments.
The Agency concludes that there is a reasonable certainty that no
harm will result to the United States population, including infants and
children, from aggregate exposure to residues of homobrassinolide
applied/used as a plant growth regulator in accordance with good
agricultural practices. Therefore, an exemption is established for
residues of homobrassinolide in or on all food commodities when
applied/used as a plant growth regulator in accordance with good
IX. Statutory and Executive Order Reviews
This final rule establishes a tolerance exemption under section
408(d) of FFDCA in response to a petition submitted to the Agency. The
Office of Management and Budget (OMB) has exempted these types of
actions from review under Executive Order 12866, entitled Regulatory
Planning and Review (58 FR 51735, October 4, 1993). Because this final
rule has been exempted from review under Executive Order 12866, this
final rule is not subject to Executive Order 13211, entitled Actions
Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001), or Executive Order
13045, entitled Protection of Children from Environmental Health Risks
and Safety Risks (62 FR 19885, April 23, 1997). This final rule does
not contain any information collections subject to OMB approval under
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it
require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance
exemption in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999), and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000), do not apply to this final rule. In addition,
rule does not impose any enforceable duty or contain any unfunded
mandate as described under Title II of the Unfunded Mandates Reform Act
of 1995 (UMRA) (Public Law 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
X. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: June 14, 2010.
Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.1297 is added to subpart D to read as follows:
Sec. 180.1297 Homobrassinolide; exemption from the requirement of a
An exemption from the requirement of a tolerance is established for
the residues of homobrassinolide in or on all food commodities when
applied/used as a plant growth regulator in accordance with good
[FR Doc. 2010-16771 Filed 7-8-10; 8:45 am]
BILLING CODE 6560-50-S