[Federal Register Volume 71, Number 236 (Friday, December 8, 2006)]
[Rules and Regulations]
[Pages 71052-71058]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-20897]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2006-0654; FRL-8093-4]
Cyproconazole; Pesticide Tolerances for Emergency Exemptions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a time-limited tolerance for
residues of cyproconazole ((2RS,3RS)-2-(4-chlorophenyl)-3-cyclopropyl-
1-(1H -1,2,4- triazole-1-yl)butan-2-ol) in or on soybean seed. This
action is associated with EPA's granting of an emergency exemption
under section 18 of the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA) authorizing use of the pesticide on soybeans. This
regulation establishes a maximum permissible level for residues of
cyproconazole in this food commodity. The tolerance will expire and be
revoked on December 31, 2009.
DATES: This regulation is effective December 8, 2006. Objections and
requests for hearings must be received on or before February 6, 2007,
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-2006-0654. All documents in the
docket are listed on the regulations.gov website. 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 either 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 Room S-4400,
One Potomac Yard (South Building), 2777 South Crystal Drive Arlington,
VA 22202-3553. The hours of operation of this Docket Facility are from
8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays.
The Docket telephone number is (703) 305-5805.
FOR FURTHER INFORMATION CONTACT: Carmen Rodia, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 306-0327; fax: (703) 308-8041; e-mail address:
[email protected].
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's pilot e-CFR site at http://www.gpoaccess.gov/ecfr.
C. Can I File an Objection or Hearing Request?
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. 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-2006-0654 in the
subject line on the first page of your submission. All requests must be
in writing, and must be mailed or delivered to the Hearing Clerk on or
before February 6, 2007.
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 that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
number EPA-HQ-OPP-2006-0654, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP), Regulatory
Public Docket (7502P), Environmental Protection Agency, 1200
Pennsylvania Avenue, NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Room S-4400, One Potomac Yard (South
Building), 2777 South Crystal Drive, Arlington, VA 22202-3553.
Deliveries are only accepted during the Docket's normal hours of
operation (8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays). Special arrangements should
[[Page 71053]]
be made for deliveries of boxed information. The Docket telephone
number is (703) 305-5805.
II. Background and Statutory Findings
EPA, on its own initiative, in accordance with sections 408(e) and
408(l)(6) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(e) and 346a(l)(6), is establishing a tolerance for residues
of the fungicide cyproconazole, in or on soybean seed at 0.10 parts per
million (ppm). This tolerance will expire and be revoked on December
31, 2009. EPA will publish a document in the Federal Register to remove
the revoked tolerance from the Code of Federal Regulations (CFR).
Section 408(l)(6) of the FFDCA requires EPA to establish a time-
limited tolerance or exemption from the requirement for a tolerance for
pesticide chemical residues in food that will result from the use of a
pesticide under an emergency exemption granted by EPA under section 18
of FIFRA. Such tolerances can be established without providing notice
or period for public comment. EPA does not intend for its actions on
section 18 related tolerances to set binding precedents for the
application of the section 408 safety standard to other tolerances and
exemptions. Section 408(e) of the FFDCA allows EPA to establish a
tolerance or an exemption from the requirement of a tolerance on its
own initiative, i.e., without having received any petition from an
outside party.
Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(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. . .
.''
Section 18 of the FIFRA authorizes EPA to exempt any Federal or
State agency from any provision of FIFRA, if EPA determines that
``emergency conditions exist which require such exemption.'' EPA has
established regulations governing such emergency exemptions in 40 CFR
part 166.
III. Emergency Exemption for Cyproconazole on Soybeans and FFDCA
Tolerances
Australasian soybean rust (SBR) is a plant disease caused by two
fungal species, Phakopsora pachyrhizi and P. meibomiae, and is spread
primarily by windborne spores that can be transported over long
distances. SBR models suggest that most of the soybean acreage in the
U.S. could be compromised by an SBR epidemic. In accordance with the
2002 Agricultural Bioterrorism Protection Act, SBR was identified by
USDA as a select biological agent with the potential to pose a severe
threat to the soybean industry and livestock production, in general. As
such, USDA has invested in extensive readiness and outreach activities
among soybean producers. The states of Minnesota and South Dakota
petitioned EPA to allow under FIFRA section 18, the use of
cyproconazole on soybeans for control of Australasian soybean rust in
Minnesota and South Dakota. After having reviewed the submission, EPA
concurs that emergency conditions exist for these States.
As part of its assessment of this emergency exemption, EPA assessed
the potential risks presented by residues of cyproconazole in or on
soybeans. In doing so, EPA considered the safety standard in section
408(b)(2) of the FFDCA, and EPA decided that the necessary tolerance
under section 408(l)(6) of the FFDCA would be consistent with the
safety standard and with FIFRA section 18. Consistent with the need to
move quickly on the emergency exemption in order to address an urgent
non-routine situation and to ensure that the resulting food is lawful,
EPA is issuing this tolerance without notice and opportunity for public
comment as provided in section 408(l)(6) of the FFDCA. Although this
tolerance expires and is revoked on December 31, 2009, under section
408(l)(5) of the FFDCA, residues of the pesticide not in excess of the
amounts specified in the tolerance remaining in or on soybean seed
after that date will not be unlawful, provided the pesticide is applied
in a manner that was lawful under FIFRA, and the residues do not exceed
a level that was authorized by this tolerance at the time of that
application. EPA will take action to revoke this tolerance earlier if
any experience with, scientific data on, or other relevant information
on this pesticide indicate that the residues are not safe.
Because this tolerance is being approved under emergency
conditions, EPA has not made any decisions about whether cyproconazole
meets EPA's registration requirements for use on soybeans or whether a
permanent tolerance for this use would be appropriate. Under these
circumstances, EPA does not believe that this tolerance serves as a
basis for registration of cyproconazole by a State for special local
needs under FIFRA section 24(c). Nor does this tolerance serve as the
basis for growers in any State other than those in which State lead
agencies have obtained an exemption to use this pesticide on this crop
under section 18 of FIFRA without following all provisions of EPA's
regulations implementing FIFRA section 18 as identified in 40 CFR part
166. For additional information regarding the emergency exemption for
cyproconazole, contact the Agency's Registration Division at the
address provided under FOR FURTHER INFORMATION CONTACT.
IV. Aggregate Risk Assessment and Determination of Safety
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 of the FFDCA and a complete
description of the risk assessment process, see http://www.epa.gov/fedrgstr/EPA-PEST/1997/November/Day-26/p30948.htm.
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. EPA has sufficient data to assess the hazards of
cyproconazole and to make a determination on aggregate exposure,
consistent with section 408(b)(2) of the FFDCA, for a time-limited
tolerance for residues of cyproconazole in or on soybean seed at 0.10
ppm. EPA's assessment of the dietary exposures and risks associated
with establishing the tolerance follows.
A. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological endpoint. However, the
lowest dose at which adverse effects of concern are identified (the
LOAEL) is sometimes used for risk assessment if no NOAEL was achieved
in the toxicology study selected. An uncertainty factor (UF) is applied
to reflect uncertainties inherent
[[Page 71054]]
in the extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10x to account for
interspecies differences and 10x for intra species differences.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA SF.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the level of concern (LOC). For example, when 100 is the
appropriate UF (10x to account for interspecies differences and 10x for
intraspecies differences), the LOC is 100. To estimate risk, a ratio of
the NOAEL to exposures (margin of exposure (MOE) = NOAEL/exposure) is
calculated and compared to the LOC.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as 1 x 10-6 or one in a million).
Under certain specific circumstances, MOE calculations will be used for
the carcinogenic risk assessment. In this non-linear approach, a
``point of departure'' is identified below which carcinogenic effects
are not expected. The point of departure is typically a NOAEL based on
an endpoint related to cancer effects though it may be a different
value derived from the dose response curve. To estimate risk, a ratio
of the point of departure to exposure (MOEcancer = point of
departure/exposures) is calculated. A summary of the toxicological
endpoints for cyproconazole used for human risk assessment is shown in
the following Table:
Summary of Toxicological Dose and Endpoints for Cyproconazole for Use in Human Risk Assessment
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FQPA SF* and Level of
Exposure/Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
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Acute Dietary (U.S. general Not applicable None An endpoint of concern
population including infants and (effect) attributable
children) to a single exposure
(dose) for the U.S.
General Population was
not identified in the
oral toxicity studies
reviewed.
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Acute Dietary (Females 13-49 years of LOAEL = 2.0 mg/kg/day FQPA SF = 1x Developmental toxicity
age) UF = 300............... aPAD = acute........... Chinchilla rabbits;
Acute RfD = 2.0 mg/kg/ RfD / FQPA SF = 0.01 mg/ LOAEL = 2.0 mg/kg/day
day/300 = 0.01 mg/kg/ kg/day. based on hydrocephalus
day. internus observed in
one fetus at each
treatment level.
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Chronic Dietary (All populations) NOAEL = 1.0 mg/kg/day FQPA SF = 1x Chronic oral toxicity -
UF = 100............... cPAD = chronic......... dog;
Chronic RfD = 1.0 mg/kg/ RfD/FQPA SF = 0.01 mg/ LOAEL = 3.2 mg/kg/day
day/100 = 0.01 mg/kg/ kg/day. based on liver effects
day. (P450 induction in
females and
histopathology,
laminar eosinophilic
intrahepatocytic
bodies in males).
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Short-Term Incidental Oral (1 to 30 NOAEL = 1.5 mg/kg/day Residential LOC for MOE 90-day oral toxicity -
days) = 100 rat;
Intermediate-Term Incidental Oral (1 Occupational LOC for LOAEL = 27.3 mg/kg/day
to 6 months). MOE = 100. based on decreased
body weight gain in
males and increased
liver weight in
females.
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Short-Term Dermal (1 to 30 days) NOAEL = 2.0 mg/kg/day Residential LOC for MOE Developmental toxicity
Intermediate-Term Dermal (1 to 6 (dermal absorption = 300 Chinchilla rabbits;
months). rate = 11%) Occupational LOC for LOAEL = 2.0 mg/kg/day
MOE = 300. based on hydrocephalus
internus observed in
one fetus at each
treatment level.
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Long-Term Dermal (>6 months) NOAEL = 1.0 mg/kg/day Residential LOC for MOE Chronic oral toxicity -
(dermal absorption = 100 dog;
rate = 11%) Occupational LOC for LOAEL = 3.2 mg/kg/day
MOE = 100. based on liver effects
(P450 induction in
females and
histopathology,
laminar eosinophilic
intrahepatocytic
bodies in males).
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Short-Term Inhalation (1 to 30 days) NOAEL = 2.0 mg/kg/day Residential LOC for MOE Developmental toxicity
Intermediate-Term Inhalation (1 to 6 (inhalation-absorption = 300 Chinchilla rabbits;
months). rate = 100% oral Occupational LOC for LOAEL = 2.0 mg/kg/day
equivalent) MOE = 300. based on hydrocephalus
internus observed in
one fetus at each
treatment level.
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Long-Term Inhalation (>6 months) NOAEL = 1.0 mg/kg/day Residential LOC for MOE Chronic oral toxicity -
(inhalation-absorption = 100 dog;
rate = 100% oral Occupational LOC for LOAEL = 3.2 mg/kg/day
equivalent) MOE = 100. based on liver effects
(P450 induction in
females and
histopathology,
laminar eosinophilic
intrahepatocytic
bodies in males).
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Cancer (oral, dermal, inhalation) Cyproconazole has been classified as a Group B2, probable human
carcinogen; Q1* is 1.58 x 10-1 (mg/kg/day)-1 in human equivalents, based
on male mouse liver adenoma and/or carcinoma combined tumor rates.
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* The reference to the FQPA SF refers to any additional SF retained due to concerns unique to the FQPA.
[[Page 71055]]
UF = uncertainty factor; FQPA SF = Special FQPA safety factor; NOAEL = no observed adverse effect level; LOAEL =
lowest observed adverse effect level; PAD = population adjusted dose (a = acute, c = chronic); RfD = reference
dose; MOE = margin of exposure; and LOC = level of concern.
B. Exposure Assessment
1. Dietary exposure from food and feed uses. A tolerance has been
established (40 CFR 180.485) for residues of cyproconazole in or on the
imported agricultural commodity coffee, bean, green. There are no U.S.
registrations for cyproconazole on raw agricultural commodities at this
time. Risk assessments were conducted by EPA to assess dietary
exposures from cyproconazole in food as follows:
i. Acute exposure. Acute dietary risk assessments are performed for
a food use pesticide if a toxicological study has indicated the
possibility of an effect of concern occurring as a result of a one day
or single exposure. The Dietary Exposure Evaluation Model software with
the Food Commodity Intake Database (DEEM-FCID\TM\) analysis evaluated
the individual food consumption as reported by respondents in the USDA
1994-1996 and 1998 nationwide Continuing Surveys of Food Intake by
Individuals (CSFII) and accumulated exposure to the chemical for each
commodity. The acute dietary exposure analysis for cyproconazole is
based on Tier 1 assumptions of tolerance-level residues and 100% crop
treated (CT).
ii. Chronic exposure. In conducting the chronic dietary risk
assessment, the DEEM-FCID\TM\ analysis evaluated the individual food
consumption as reported by respondents in the USDA 1994-1996 and 1998
nationwide CSFII and accumulated exposure to the chemical for each
commodity. The chronic dietary exposure analysis for cyproconazole is
refined in that it incorporates estimates of anticipated residues (AR)
for all commodities, 10% CT for soybeans and empirical processing
factors (a Tier 3 analysis).
iii. Cancer. The Q1* for cyproconazole is 1.58 x 10-1
milligrams/kilograms/day (mg/kg/day) in human equivalents, based on
liver tumor data in male mice. The 10% CT (i.e., 7.4 million acres)
resulted in an acceptable calculated dietary cancer risk of 1.1 x
10-6, which is equivalent to the Agency's LOC (generally 1 x
10-6).
iv. Anticipated residue and percent crop treated (PCT) information.
Section 408(b)(2)(E) of the FFDCA authorizes EPA to use available data
and information on the anticipated residue levels of pesticide residues
in food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must, pursuant
to section 408(f)(1), require that data be provided 5 years after the
tolerance is established, modified or left in effect, demonstrating
that the levels in food are not above the levels anticipated. Following
the initial data submission, EPA is authorized to require similar data
on a time frame it deems appropriate. For the present action, EPA will
issue such Data Call-Ins for information relating to anticipated
residues as are required by FFDCA section 408(b)(2)(E) and authorized
under FFDCA section 408(f)(1). Such Data Call-Ins will be required to
be submitted no later than 5 years from the date of issuance of this
tolerance.
Section 408(b)(2)(F) of the FFDCA states that the Agency may use
data on the actual percent of food treated for assessing chronic
dietary risk only if the Agency can make the following findings:
Condition 1, that the data used are reliable and provide a valid basis
to show what percentage of the food derived from such crop is likely to
contain such pesticide residue; Condition 2, that the exposure estimate
does not underestimate exposure for any significant subpopulation
group; and Condition 3, if data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F) of the FFDCA, EPA may require registrants to
submit data on PCT.
The Agency used PCT information for cyproconazole as follows: As
stated in Unit IV.B.1. acute and chronic dietary exposure and risk
analyses were conducted to determine the exposure and risk estimates
resulting from the use of cyproconazole in soybeans to control
Australasian soybean rust. The acute analysis is based on Tier 1
assumptions of tolerance-level residues and 100% CT. The chronic
analysis is refined in that it incorporates estimates of AR for all
commodities, 10% CT for soybeans and empirical processing factors (a
Tier 3 analysis).
The Agency believes that the three conditions previously discussed
have been met. With respect to Condition 1, EPA finds that the PCT
information described in Unit IV.B.1. and in the preceding paragraph
for cyproconazole used on soybeans is reliable and has a valid basis.
As to Conditions 2 and 3, regional consumption information and
consumption information for significant subpopulations is taken into
account through EPA's computer-based model for evaluating the exposure
of significant subpopulations including several regional groups. Use of
this consumption information in EPA's risk assessment process ensures
that EPA's exposure estimate does not understate exposure for any
significant subpopulation group and allows the Agency to be reasonably
certain that no regional population is exposed to residue levels higher
than those estimated by the Agency. Other than the data available
through national food consumption surveys, EPA does not have available
information on the regional consumption of food to which cyproconazole
may be applied in a particular area.
2.--i. Dietary exposure from drinking water. The Agency used the
Pesticide Root Zone Model and Exposure Analysis Modeling System (PRZM/
EXAMS) to calculate estimated drinking water concentrations (EDWCs) for
the use of cyproconazole in soybeans, using the standard Mississippi
soybean scenario. Thus, the estimated exposure concentrations for water
are based on the proposed highest use rate. The Agency used the Generic
Expected Environmental Concentration model to calculate estimated
environmental concentrations (EECs) for the use of cyproconazole in
turf. Ground water concentrations were estimated with the Screening
Concentration in Groundwater (SCI-GROW) model.
ii. Ground water and surface water EDWCs. A Tier 2 drinking water
assessment was conducted for the proposed use of cyproconazole in
soybeans using the proposed maximum application rate of 0.026 lbs.
a.i./acre with 2 applications per year and a 7-day Retreatment interval
(RTI). The Preharvest interval (PHI) will be 30 days. The linked PRZM
and EXAMS models predicted a peak EDWC of 0.79 parts per billion (ppb)
for aerial applications. The PRZM/EXAMS model predicted chronic EDWCs
of 0.21 ppb (1-in-10 Year Annual Average) for aerial applications and
0.12 ppb (30-year Annual Average) for ground applications. The SCI-GROW
model estimated the concentration of cyproconazole in shallow ground
water sources to be 0.027 ppb.
[[Page 71056]]
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets). Cyproconazole is not
registered for use on any sites that would result in residential
exposure.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
Cyproconazole is a member of the triazole-containing class of
pesticides. Although conazoles act similarly in plants (fungi) by
inhibiting ergosterol biosynthesis, there is not necessarily a
relationship between their pesticidal activity and their mechanism of
toxicity in mammals. Structural similarities do not constitute a common
mechanism of toxicity. Evidence is needed to establish that the
chemicals operate by the same, or essentially the same, sequence of
major biochemical events (EPA, 2002). In conazoles, however, a variable
pattern of toxicological responses is found. Some are hepatotoxic and
hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some
induce developmental, reproductive, and neurological effects in
rodents. Furthermore, the conazoles produce a diverse range of
biochemical events including altered cholesterol levels, stress
responses, and altered DNA methylation. It is not clearly understood
whether these biochemical events are directly connected to their
toxicological outcomes. Thus, there is currently no evidence to
indicate that conazoles share common mechanisms of toxicity and EPA is
not following a cumulative risk approach based on a common mechanism of
toxicity for the conazoles. For information regarding EPA's procedures
for cumulating effects form substances found to have a common mechanism
of toxicity see EPA's website at http://www.epa.gov/pesticides/cumulative.
Cyproconazole is a triazole-derived pesticide. This class of
compounds can form the common metabolite 1,2,4-triazole and two
triazole conjugates (triazole alanine and triazole acetic acid). To
support existing tolerances and to establish new tolerances for
triazole-derivative pesticides, including cyproconazole, EPA conducted
a human health risk assessment for exposure to 1,2,4-triazole, triazole
alanine and triazole acetic acid resulting from the use of all current
and pending uses of any triazole-derived fungicide. The risk assessment
is a highly conservative, screening-level evaluation in terms of
hazards associated with the common metabolites (e.g., use of maximum
combination of uncertainty factors) and potential dietary and non-
dietary exposures (i.e, high end estimates of both dietary and non-
dietary exposures). In addition, the Agency retained the additional 10x
FQPA safety factor for the protection of infants and children. The
assessment includes evaluations of risks for various population
subgroups, including those comprised of infants and children.
The Agency's complete risk assessment is found in the propiconazole
reregistration docket at http://www.regulations.gov, Docket ID number
EPA-HQ-OPP-2005-0497-0013.
C. Safety Factor for Infants and Children
1. In general. Section 408 of the FFDCA 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/or
postnatal toxicity and the completeness of the data base on toxicity
and exposure unless EPA determines that a different margin of safety
will be safe for infants and children. Margins of safety are
incorporated into EPA risk assessments either directly through use of a
MOE analysis or through using uncertainty (safety) factors in
calculating a dose level that poses no appreciable risk to humans.
2. Developmental toxicity studies. There is no evidence of
increased susceptibility in either the developmental study in rats or
in the 2-generation reproduction study in rats. The concern is low for
the increased susceptibility in the New Zealand rabbit study since
clear NOAELs/LOAELs were established for maternal and developmental
toxicities. Similarly, the concern is low for the increased
susceptibility in the Chinchilla rabbit study since the incidences of
hydrocephaly were low, there was no dose response, the hydrocephaly was
not seen at the same doses in the New Zealand White strain of rabbit
and this endpoint of concern is used with a 3x FQPA safety factor for
risk assessment.
A 3x safety factor (as opposed to a 10x) for the lack of a NOAEL in
this critical study is adequate because the magnitude of the response
was low (low incidences without dose response) and the effect of
concern was seen in an unusual strain (Chinchilla) of rabbits and not
in the New Zealand strain commonly used in developmental toxicity
studies. The Agency evaluated the quality of the hazard and exposure
data for cyproconazole and determined that the FQPA safety factor can
be reduced to 1x. Therefore, there is no residual uncertainty for
prenatal and/or postnatal exposure to cyproconazole.
3. Reproductive toxicity study. There was no evidence of
reproductive toxicity in the 2-generation reproduction study in rats.
In this study, cyproconazole was administered to rats at dose levels of
0, 0.4, 1.7 and 10.6 mg/kg/day. The parental systemic NOAEL is 1.7 mg/
kg/day and LOAEL of 10.6 mg/kg/day, based on liver effects. The
reproductive toxicity NOAEL is 10.6 mg/kg/day. Although gestation
length was slightly increased and litter size decreased, these changes
were not considered to be treatment-related.
4. Prenatal and postnatal sensitivity. Please refer to the
explanation provided above in Unit IV.C.2. for a detailed discussion
regarding ``prenatal and/or postnatal sensitivity.''
5. Conclusion. The Agency evaluated the quality of the hazard and
exposure data and determined that, based on the hazard and exposure
data, the special FQPA SF is reduced to 1x. In terms of hazard, there
are low concerns and no residual uncertainties with regard to prenatal
and/or postnatal toxicity.
D. Aggregate Risks and Determination of Safety
EPA conducted human health risk assessments for acute, chronic and
cancer dietary exposures (food + drinking water only) for existing and
proposed uses. Because there are no uses of cyproconazole that are
expected to result in residential exposures, this aggregate risk
assessment takes into consideration dietary food + drinking water
exposure only; therefore, the acute and chronic aggregate estimates
would be the same as the dietary exposure results.
1. Acute risk. Using the exposure assumptions discussed in this
unit, the acute dietary exposure from food to cyproconazole will occupy
1.3% of the aPAD for females 13-49 years old. Given existing and
proposed uses, the Agency has no risk concern for exposure to
cyproconazole through food and/or drinking water. EPA does not expect
the aggregate exposure to exceed 100% of the aPAD.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
cyproconazole from
[[Page 71057]]
food will utilize 1% of the cPAD for all infants less than a year old.
There are no residential uses for cyproconazole that will result in
chronic residential exposure to cyproconazole. Given existing and
proposed uses, the Agency has no risk concern for exposure to
cyproconazole through food and/or drinking water. EPA does not expect
the aggregate exposure to exceed 100% of the cPAD.
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and drinking
water (considered to be a background exposure level). Cyproconazole is
not registered for use on any sites that would result in residential
exposure. Therefore, the aggregate risk is the sum of the risk from
food and drinking water, which were previously addressed.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account non-dietary, non-occupational exposure plus chronic
exposure to food and drinking water (considered to be a background
exposure level). Cyproconazole is not registered for use on any sites
that would result in residential exposure. Therefore, the aggregate
risk is the sum of the risk from food and drinking water, which were
previously addressed.
5. Aggregate cancer risk for U.S. population. When relying on the
exposure assumptions described in this notice, EPA calculated an
acceptable cancer risk of 1.1 x 10-6, which is equivalent to
the Agency's LOC (generally 1.0 x 10-6).
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the U.S. general population and to infants and children from
aggregate exposure to cyproconazole residues.
V. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (example--gas chromatography) is
available to enforce the tolerance expression. The method may be
requested from: Chief, Analytical Chemistry Branch, Environmental
Science Center, 701 Mapes Road, Ft. Meade, MD 20755-5350; telephone
number: (410) 305-2905; e-mail address: [email protected].
B. International Residue Limits
No CODEX, Canadian or Mexican MRLs or tolerances have been
established for cyproconazole on soybeans. Therefore, international
harmonization is not an issue at this time.
C. Conditions
EPA has concluded that the toxicological, residue chemistry,
dietary exposure and occupational/residential exposure assessments are
adequate to support a time-limited tolerance of 0.10 ppm for residues
of cyproconazole per se in/on soybean, seed.
VI. Conclusion
Therefore, the tolerance is established for residues of
cyproconazole per se, in or on soybean, seed at 0.10 ppm.
VII. Statutory and Executive Order Reviews
This final rule establishes a time-limited tolerance under section
408 of the FFDCA. 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 FIFRA
section 18 exemption under section 408 of the FFDCA, such as the
tolerance in this final rule, do not require the issuance of a proposed
rule, the requirements of the Regulatory Flexibility Act (RFA) (5
U.S.C. 601 et seq.) do not apply. 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.
[[Page 71058]]
VIII. 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 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: November 24, 2006.
Donald R. Stubbs,
Acting Director, Registration Division, 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), 346a and 371.
0
2. Section 180.485 is amended by adding text and table to paragraph (b)
to read as follows:
Sec. 180.485 Cyproconazole; tolerances for residues.
* * * * *
(b) Section 18 emergency exemptions. A time-limited tolerance is
established for residues of the fungicide cyproconazole per se
((2RS,3RS)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H -1,2,4- triazole-1-
yl)butan-2-ol) in or on soybean seed in connection with the use of the
pesticide under section 18 emergency exemptions granted by EPA. The
tolerance will expire and be revoked on the date specified in the
following table.
------------------------------------------------------------------------
Expiration/revocation
Commodity Parts per million date
------------------------------------------------------------------------
Soybean, seed 0.10 12/31/09
------------------------------------------------------------------------
[FR Doc. E6-20897 Filed 12-7-06; 8:45 am]
BILLING CODE 6560-50-S