Fenbuconazole; Time-Limited Pesticide Tolerance, 11572-11583 [05-4474]
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Federal Register / Vol. 70, No. 45 / Wednesday, March 9, 2005 / Rules and Regulations
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.446 is amended by
alphabetically adding commodities to
the table in paragraph (a) to read as
follows:
I
§ 180.446 Clofentezine; tolerances for
residues.
(a) * * *
Commodity
Parts per million
*
*
*
Grapes
*
*
*
*
*
*
*
*
1.0
Persimmons
*
*
*
0.05
*
*
*
EPA has established a
docket for this action under docket
identification (ID) number OPP–2004–
0410. All documents in the docket are
listed in the EDOCKET index athttps://
www.epa.gov/edocket. Although listed
in the index, some information is not
publicly available, i.e., 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
electronically in EDOCKET or in hard
copy at the Public Information and
Records Integrity Branch (PIRIB), Rm.
119, Crystal Mall #2, 1801 S. Bell St.,
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.
INFORMATION.
PART 180—[AMENDED]
*
*
*
40 CFR Part 180
J. R.
Tomerlin, Registration Division (0705C),
Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 305–0598; e-mail address:
tomerlin.bob@epa.gov.
[OPP–2004–0410; FRL–7699–2]
SUPPLEMENTARY INFORMATION:
Fenbuconazole; Time-Limited
Pesticide Tolerance
I. General Information
FOR FURTHER INFORMATION CONTACT:
[FR Doc. 05–4335 Filed 3–8–05; 8:45 am]
BILLING CODE 6560–50–S
ENVIRONMENTAL PROTECTION
AGENCY
A. Does this Action Apply to Me?
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
SUMMARY: This regulation establishes a
time-limited tolerance for the combined
residues of fenbuconazole [alpha-[2-(4chlorophenyl)-ethyl]-alpha-phenyl-3(1H-1,2,4-triazole)-1-propanenitrile] and
its metabolites cis- andtrans-5-(4chlorophenyl)-dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl)-2-3Hfuranone, expressed as fenbuconazole in
or on bananas (whole fruit); pecans; and
stone fruit crop group (except plums
and prunes). Dow AgroSciences, LLC
requested this tolerance under the
Federal Food, Drug, and Cosmetic Act
(FFDCA), as amended by the Food
Quality Protection Act of 1996 (FQPA).
The tolerance will expire on December
31, 2008.
DATES: This regulation is effective
March 9, 2005. Objections and requests
for hearings must be received on or
before May 9, 2005.
ADDRESSES: To submit a written
objection or hearing request follow the
detailed instructions as provided in
Unit VI. of theSUPPLEMENTARY
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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 underFOR FURTHER
INFORMATION CONTACT.
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B. How Can I Access Electronic Copies
of this Document and Other Related
Information?
In addition to using EDOCKET (http:/
/www.epa.gov/edocket/), you may
access this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr/. A
frequently updated electronic version of
40 CFR part 180 is available at E-CFR
Beta Site Two at https://
www.gpoaccess.gov/ecfr/. To access the
OPPTS Harmonized Guidelines
referenced in this document, go directly
to the guidelines athttps://www.epa.gpo/
opptsfrs/home/guidelin.htm/.
II. Background and Statutory Findings
In the Federal Register of November
17, 2004 (69 FR 67351) (FRL–7686–6),
EPA issued a notice pursuant to section
408(d)(3) of the FFDCA, 21 U.S.C.
346a(d)(3), announcing the filing of
pesticide petitions (PP 1F3989, 1F3995,
and 2F4154) by Dow AgroSciences,
LLC, 9330 Zionsville Road,
Indianapolis, IN 46268. The petitions
requested that 40 CFR 180.480 be
amended by establishing a tolerance for
combined residues of the fungicide
fenbuconazole [alpha-[2-(4chlorophenyl)-ethyl]-alpha-phenyl-3(1H-1,2,4-triazole)-1-propanenitrile] and
its metabolites cis- andtrans-5-(4chlorophenyl)-dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl)-2-3Hfuranone, in or on banana (whole fruit)
at 0.3 parts per million (ppm) (2F4154);
fruit, stone, group 12 (except plum,
prune) at 2.0 ppm (1F3989); pecan at 0.1
ppm (1F3995). This notice included a
summary of the petition prepared by
Dow AgroSciences, LLC, the registrant.
The tolerances will expire on
December 31, 2008.
Comments were received in response
to the notice of filing from one
individual. These comments are
addressed in Unit IV.C.
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
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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. . . .’’
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 the final
rule on Bifenthrin Pesticide Tolerances
(62 FR 62961, November 26, 1997)
(FRL–5754–7).
III. Aggregate Risk Assessment and
Determination of Safety
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 and to make a
determination on aggregate exposure,
consistent with section 408(b)(2) of the
FFDCA, for a tolerance for combined
residues of banana (whole fruit) at 0.3
parts per million (ppm); fruit, stone,
group 12 (except plum, prune) at 2.0
ppm; pecan at 0.1 ppm. EPA’s
assessment of exposures and risks
associated with establishing the
tolerance follows.
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A. Toxicological Profile
EPA has evaluated the available
toxicity data and considered its validity,
completeness, and reliability as well as
the relationship of the results of the
studies 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. The nature of the
toxic effects caused by fenbuconazole
are discussed in Table 1 of this unit as
well as the no observed adverse effect
level (NOAEL) and the lowest observed
adverse effect level (LOAEL) from the
toxicity studies reviewed.
TABLE 1.— SUBCHRONIC, CHRONIC, AND OTHER TOXICITY
Guideline No.
Study Type
Results
870.3100
90–Day oral toxicity rodents - rats
NOAEL = 1.3/1.5 mg/kg/day (M/F)
LOAEL = 5.1/6.3 mg/kg/day (M/F) based on liver histopathology
870.3100
90–Day oral toxicity rodents - mice
NOAEL = 3.8/5.7 mg/kg/day (M/F)
LOAEL = 11.1/17.6 mg/kg/day (M/F) based on liver histopathology
870.3150
90–Day oral toxicity in
nonrodents - dogs
NOAEL = 3.3/3.5 mg/kg/day (M/F)
LOAEL = 13.3/14.0 mg/kg/day (M/F) based on liver histopathology
870.3200
21/28–Day dermal toxicity - rats
NOAEL = 1,000 mg/kg/day (HDT)
LOAEL = > 1,000 mg/kg/day
870.3250
90–Day dermal toxicity
Not performed
870.3465
90–Day inhalation toxicity
Not performed
870.3700
Prenatal developmental in rodents rats
Maternal NOAEL = 30 mg/kg/day
Maternal LOAEL = 75 mg/kg/day based on decreased body weight and
body weight gain
Developmental NOAEL = 30 mg/kg/day
Developmental LOAEL = 75 mg/kg/day based on increased post-implantation loss and a decrease in the number of live fetuses/dam
870.3700
Prenatal developmental in nonrodents
- rabbits
Maternal NOAEL = 10 mg/kg/day
Maternal LOAEL = 30 mg/kg/day based on decreased food consumption
and increased incidence of clinical signs (soft/scant/no feces and red
discharge)
Developmental NOAEL = 30 mg/kg/day
Developmental LOAEL = 60 mg/kg/day based on increased early resorptions
870.3800
Reproduction and fertility effects - rats
Parental systemic NOAEL = 4 mg/kg/day
Parental systemic LOAEL = 40 mg/kg/day based on maternal death during
delivery, decreased body weight and food consumption, increased number of dams not delivering viable or delivering nonviable offspring, and
increased adrenal and thyroid/parathyroid weights
Reproductive NOAEL = 40 mg/kg/day (HDT)
Reproductive LOAEL = greater than 40 mg/kg/day
Offspring systemic NOAEL: 4 mg/kg/day
Offspring systemic LOAEL: 40 mg/kg/day based on decreased pup body
weight, increased number of stillborn pups, decreased number of total
offspring delivered and decreased viability indes
870.4100
Chronic toxicity - rodents
Requirements met by submission of studies according to OPPTS Harmonized Guideline 870.4300
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TABLE 1.— SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.4100
Chronic toxicity - dogs
NOAEL = 3.75/0.38 mg/kg/day (M/F)
LOAEL = 30/3.75 mg/kg/day (M/F) based on decreased body weight gain
Note: Dose-related adaptive liver changes were observed in high-dose
males and females
870.4200
Carcinogenicity - rats
Requirements met by submission of studies according to OPPTS Harmonized Guideline 870.4300
870.4200
Carcinogenicity - mice
NOAEL = 1.43 mg/kg/day (both M and F)
LOAEL = 28.6/92.9 mg/kg/day (M/F) based on decreased body weight, increased relative and absolute liver weight, and hepatocellular hypertrophy and vacuolization
Evidence of carcinogenicity
870.4300
Combined chronic toxicity/carcinogenicity rat
NOAEL = 3.0/4.0 mg/kg/day (M/F)
LOAEL = 30.6/43.1 mg/kg/day (M/F) based on decreased body weight
gain (F), hepatocellular enlargement and vacuolization (F), increased
thyroid weight (M and F), and histopathological lesions in the thyroid
gland (M)
Evidence of carcinogenicity
870.4300
Combined chronic toxicity/carcinogenicity rat
NOAEL = Not established
LOAEL = 30.4 mg/kg/day (M) based on decreased body weight gain, increased liver weight, and increased thyroid and parathyroid weights
Note: Only males were used in this study. Insufficient evidence of carcinogenicity
870.5100
Gene mutation - bacterial reverse mutation assay
No mutagenic activity in bacteria (Salmonella typhimurium) under conditions of this assay.
Note: Only TA1535, TA1537, TA98, and TA100 were tested. This study is
classified unacceptable.
870.5100
Gene mutation - bacterial reverse mutation assay
No mutagenic activity in bacteria (Salmonella typhimurium) under conditions of this assay.
Note: Only TA1535, TA1537, TA98, and TA100 were tested. This study is
classified unacceptable.
870.5300
Cytogenetics - in vitro
mammalian cell
gene mutation test
(CHO Cells)
No increase in mutant frequency at the HGPRT locus, in the presence or
absence of S9 activation.
870.5385
Cytogenetics - mammalian bone marrow
chromosomal aberration test (rats)
No increase in number of cells with aberrations or in aberrations per cell.
870.5550
Other effects - unscheduled DNA synthesis in mammalian
cells in culture (rats)
No evidence (or a dose related positive response) that unscheduled DNA
synthesis was induced.
870.7485
Metabolism and pharmacokinetics - rat
The mean recovery of radioactivity 4 days after exposure was 82.6–93.0%
following single or repeated oral doses and 88.2–99.2% following single
i.v. doses, indicating rapid absorption, distribution, and elimination.
Rapid elimination and low tissue levels indicate low bioaccumulation of
the parent and metabolites.
Elimination occurred primarily by biliary excretion because recovery of radioactivity was mostly in the feces: 75.6–83.7% following oral exposure
and 77.2–91.4% following i.v. exposure. In urine, radioactivity recovery
was 5.5-12.6% for all dose scenarios. Peak radioactivity in the blood occurred 3 hours following a single low dose and 3–6 hours after a single
high dose, indicating biphasic elimination.
Only 8.5–14.8% and 0.0–2.7% of the parent compound was recovered in
the feces and urine, respectively, indicating extensive metabolism. A
number of major metabolites were identified; however, 50% and 20% of
metabolites in the feces and urine, respectively, were not identified.
Sex-related differences include a greater number of sulfate metabolites
in female excreta compared to males, and a greater number of ketoacid
metabolites in male urine compared to females.
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11575
TABLE 1.— SUBCHRONIC, CHRONIC, AND OTHER TOXICITY—Continued
Guideline No.
Study Type
Results
870.7485
Metabolism and pharmacokinetics - rat
The mean recovery of radioactivity 3–4 days after exposure was 90.4–
104.5% following single or repeated oral doses, indicating rapid absorption, distribution, and elimination. Bioaccumulation of the parent compound and metabolites is low. There were no major sex- or dose-related
differences in absorption, distribution, or elimination.
Elimination occurred primarily by biliary excretion: Recovery of the administered dose occurred mainly in the bile (79.1–87.1%) 3 days after exposure and mostly in the feces (78.7–94.4%) 4 days after exposure. In
contrast, radioactivity recovery in the urine was 3.2–11.5% at 3 and 4
days after exposure.
Extensive metabolism occurred; numerous metabolites were found in the
feces and urine. There is a dose-related difference in metabolism. A
higher amount of parent compound was found in the feces following the
single high dose compared to the single or repeated low dose(s), which
suggests that saturation may be occurring at the high dose.
870.7600
Dermal penetration rat
The highest dermal absorption was found in animals having the longest
exposure dose.
Mean % of the dose absorbed (sum of urine, feces, carcass, and skin)
after 10 hours of exposure:
Dose (mg/kg)
Percent Dermal Absorption
0.125
4.25
1.25
2.08
125
0.45
B. 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 level
of concern (LOC). 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
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
intraspecies 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 Safety
Factor (SF).
For non-dietary risk assessments
(other than cancer) the UF is used to
determine the 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 as1 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 fenbuconazole used for human risk
assessment is shown in Table 2 of this
unit:
TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR FENBUCONAOZLE FOR USE IN HUMAN RISK
ASSESSMENT
Dose Used in Risk Assessment, UF
Exposure Scenario
Acute dietary (females 13–
49 years of age)
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NOAEL = 30 mg/kg/day
UF = 100a
Acute RfD = 0.3 mg/kg
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Special FQPA SF* and
Level of Concern for Risk
Assessment
Special FQPA SF = 1
aPAD = acute RfD ÷
FQPA SF = 0.3 mg/
kg
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Study and Toxicological Effects
Developmental rat study
Developmental LOAEL = 75 mg/kg/day
based on increased resorptions and
decreased live fetuses per dam
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TABLE 2.—SUMMARY OF TOXICOLOGICAL DOSE AND ENDPOINTS FOR FENBUCONAOZLE FOR USE IN HUMAN RISK
ASSESSMENT—Continued
Dose Used in Risk Assessment, UF
Exposure Scenario
Special FQPA SF* and
Level of Concern for Risk
Assessment
Study and Toxicological Effects
Acute dietary (general population including infants
and children)
None
None
Not selected
No appropriate dose and endpoint could
be identified for these population
groups.
Chronic dietary (all populations)
NOAEL = 3 mg/kg/day
UF = 100a
Chronic RfD = 0.03 mg/
kg/day
Special FQPA SF = 1
cPAD = chronic RfD ÷
FQPA SF = 0.03 mg/
kg/day
Combined chronic toxicity/carcinogenicity
- rat
LOAEL = 30.6/43.1 (M/F) mg/kg/day
based on decreased body weight gain,
increased
thyroid
weight,
and
histopathological lesions in the liver
and thyroid gland
Incidental oral (all durations)
None
None
Not selected
No registered uses would result in residential exposure
Short-term (1 to 30 days)
and intermediate-term (1
to 6 months)
Dermal
None
None
Not selected
No dermal or systemic toxicity was seen
in a 21–day dermal toxicity study; poor
absorption was seen in the dermal absorption study
Long-term dermal (several
months to lifetime)
Oral study NOAEL = 3
mg/kg/day
(dermal absorption rate
= 4.25%)
Residential LOC for
MOE = Not applicable
Occupational LOC for
MOE = 100a
Combined chronic toxicity/carcinogenicity
- rat
LOAEL = 30.6/43.1 (M/F) mg/kg/day
based on decreased body weight gain,
increased
thyroid
weight,
and
histopathological lesions in the liver
and thyroid gland
Inhalation (all durations)
None
None
Not selected
Low toxicity and use pattern does not indicate a need for risk assessment via
inhalation.
Cancer (oral, dermal, inhalation)
Classification: Under the 1986 cancer classification scheme, fenbuconazole was classified as a
Group C - Possible Human Carcinogen, with a low dose extrapolation model applied to the animal data for the quantification of human risk (Q1*). This was based on increased incidence of
hepatocellular adenomas and carcinomas in male and female mice and of thyroid follicular adenomas and combined adenomas/carcinomas in male rats. Based on mechanistic data, quantification of risk was derived using combined hepatocellular adenomas/carcinomas in female
mice. The upper bound estimate of unit risk, Q1* (mg/kg/day)-1 is 3.59 x 10-3 in human equivalents.
*Database uncertainty factor reduced to 1X.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. Tolerances have been
established (40 CFR 180.480) for the
combined residues of fenbuconazole, in
or on a variety of raw agricultural
commodities. Risk assessments were
conducted by EPA to assess dietary
exposures from fenbuconazole in food
as follows:
i. Acute exposure. Acute dietary risk
assessments are performed for a fooduse pesticide if a toxicological study has
indicated the possibility of an effect of
concern occurring as a result of a 1 day
or single exposure. The Dietary
Exposure Evaluation Model (DEEMTM)
analysis evaluated the individual food
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consumption as reported by
respondents in the U.S. Department of
Agriculture (USDA) 1994–1996 and
1998 Nationwide Continuing Surveys of
Food Intake by Individuals (CSFII) and
accumulated exposure to the chemical
for each commodity. The following
assumptions were made for the acute
exposure assessments: Tolerance level
residues were used for all food
commodities, 100% of all commodities
were assumed to be treated, and default
processing factors were used for
processed commodities.
ii. Chronic exposure. In conducting
this chronic dietary risk assessment, the
DEEMTM analysis evaluated the food
consumption as reported by
respondents in the USDA 1994–1996
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and 1998 CSFII and accumulated
exposure to the chemical for each
commodity. The following assumptions
were made for the chronic exposure
assessments: The chronic analysis is
slightly refined in that it incorporates
estimates of average percent crop treated
(PCT), although it does use tolerance
value residues for most commodities
and default processing factors.
Anticipated residues from USDA
Pesticide Data Program monitoring data
were used only for banana in the
chronic dietary exposure analysis and
risk assessment.
iii. Cancer. Chronic cancer risk for the
overall U.S. population was estimated
by multiplying the chronic exposure
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estimate by the carcinogenic potential
(Q*) of 0.0359 (mg/kg/day)-1.
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
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. As required by
section 408(b)(2)(E) of the FFDCA, EPA
will issue a Data Call-In for information
relating to anticipated residues 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 percent crop treated
(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 as
follows:
A routine chronic dietary exposure
analysis for the fungicide fenbuconazole
and itscis and trans metabolites was
based on 10% of apricot crop treated,
25% of blueberry crop treated, 25% of
cherry crop treated, 30% of grapefruit
crop treated, 15% of nectarine crop
treated, 15% of peach crop treated, and
10% of pecan crop treated.
The Agency believes that the three
conditions previously discussed have
been met. With respect to Condition 1,
EPA finds that the PCT information for
fenbuconazole is reliable and has a valid
basis. Time-limited tolerances have
existed for all crop commodities
included in the risk assessment, and the
Agency obtained estimates of
fenbuconazole use from recognized
pesticide use data bases. As to
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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
fenbuconazole may be applied in a
particular area.
2. Dietary exposure from drinking
water. The Agency lacks sufficient
monitoring exposure data to complete a
comprehensive dietary exposure
analysis and risk assessment for
fenbuconazole in drinking water.
Because the Agency does not have
comprehensive monitoring data,
drinking water concentration estimates
are made by reliance on simulation or
modeling taking into account data on
the physical characteristics of
fenbuconazole.
The Agency uses the Generic
Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/
Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide
concentrations in surface water and SCIGROW, which predicts pesticide
concentrations in ground water. In
general, EPA will use GENEEC (a Tier
1 model) before using PRZM/EXAMS (a
Tier 2 model) for a screening-level
assessment for surface water. The
GENEEC model is a subset of the PRZM/
EXAMS model that uses a specific highend runoff scenario for pesticides.
GENEEC incorporates a farm pond
scenario, while PRZM/EXAMS
incorporate an index reservoir
environment in place of the previous
pond scenario. The PRZM/EXAMS
model includes a percent crop area
factor as an adjustment to account for
the maximum percent crop coverage
within a watershed or drainage basin.
None of these models include
consideration of the impact processing
(mixing, dilution, or treatment) of raw
water for distribution as drinking water
would likely have on the removal of
pesticides from the source water. The
primary use of these models by the
Agency at this stage is to provide a
coarse screen for sorting out pesticides
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for which it is highly unlikely that
drinking water concentrations would
ever exceed human health levels of
concern.
Since the models used are considered
to be screening tools in the risk
assessment process, the Agency does
not use estimated environmental
concentrations (EECs) from these
models to quantify drinking water
exposure and risk as a %RfD or %PAD.
Instead drinking water levels of
comparisons (DWLOCs) are calculated
and used as a point of comparison
against the model estimates of a
pesticide’s concentration in water.
DWLOCs are theoretical upper limits on
a pesticide’s concentration in drinking
water in light of total aggregate exposure
to a pesticide in food, and from
residential uses. Since DWLOCs address
total aggregate exposure to
fenbuconaozle, they are further
discussed in the aggregate risk sections
in Unit III.E.
Based on the PRZM/EXAMS and SCIGROW models, the estimated EECs of
fenbuconazole for acute exposures are
estimated to be 14.1 parts per billion
(ppb) for surface water and 0.005 ppb
for ground water. The EECs for chronic
exposures are estimated to be 7.3 ppb
(peak annual) and 5.9 ppb (30–year
average) for surface water and 0.005 ppb
for ground water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, non-dietary exposure
(e.g., for lawn and garden pest control,
indoor pest control, termiticides, and
flea and tick control on pets).
Fenbuconazole is not registered for
use on any sites that would result in
residential exposure.
4. Cumulative exposure to 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.’’
Unlike other pesticides for which EPA
has followed a cumulative risk approach
based on a common mechanism of
toxicity, fenbuconazole does not appear
to produce a toxic metabolite produced
by other substances. For the purposes of
this tolerance action, therefore, EPA has
not assumed that fenbuconazole has 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
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the cumulative effects of such
chemicals, see the final rule for
Bifenthrin Pesticide Tolerances (62 FR
62961, November 26, 1997) (FRL–5754–
7).
However, the Agency does have
concern about potential toxicity to 1,2,4triazole and two conjugates,
triazolylalanine and triazolyl acetic
acid, metabolites common to most of the
triazole fungicides. To support the
extension of existing parent triazolederivative fungicide tolerances, EPA
conducted an interim human health
assessment for aggregate exposure to
1,2,4-triazole. The exposure and risk
estimates presented in this assessment
are overestimates of actual likely
exposures and therefore, should be
considered to be highly conservative.
Based on this assessment, EPA
concluded that for all exposure
durations and population subgroups,
aggregate exposures to 1,2,4-triazole are
not expected to exceed its level of
concern. This assessment should be
considered interim due to the ongoing
series of studies being conducted by the
U.S. Triazole Task Force (USTTF).
Those studies are designed to provide
the Agency with more complete
toxicological and residue information
for free triazole and are expected to be
submitted to the Agency in late 2004
and early 2005. Upon completion of
review of these data, EPA will prepare
a more sophisticated assessment based
on the revised toxicological and
exposure data bases.
i. Toxicology. The toxicological data
base for 1,2,4-triazole is incomplete.
Preliminary summary data presented by
the USTTF to EPA indicate that the
most conservative endpoint currently
available for use in a risk assessment for
1,2,4-triazole is a LOAEL of 15 mg/kg/
day, based on body weight decreases in
male rats in the reproductive toxicity
study (currently underway). This
endpoint, with an uncertainty factor of
1,000 was used for both acute and
chronic dietary risk, resulting in an RfD
of 0.015 mg/kg/day. The uncertainty
factor of 1,000 includes an additional
10X safety factor for the protection of
infants and children. The resulting PAD
is 0.015 mg/kg/day.
ii. Dietary exposure. The USTTF
conducted an acute dietary exposure
assessment based on the highest
triazole-derivative fungicide tolerance
level combined with worst-case
molecular weight and plant/livestock
metabolic conversion factors. This
approach provides a conservative
estimate of all sources for 1,2,4-triazole
except the in vivo conversion of parent
compounds to free-triazole following
dietary exposure. The degree of animal
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in vivo conversion is dependent on the
identity of the parent fungicide. In rats,
this conversion ranges from 0% to 77%,
thein vivo conversion for fenbuconaozle
is 2.5%. For purposes of this interim
assessment, EPA used the dietary
exposure estimates provided by the
USTTF adjusted based on the highest
rate of conversion observed for any of
the parent triazole-derivative fungicides
to account for this metabolic
conversion. The assessment includes
residue estimates for all food
commodities with either existing or
pending triazole-derivative fungicide
registrations. The resulting acute dietary
exposure estimates are extremely
conservative and range from 0.0032 mg/
kg/day for males 20+ years old to 0.014
mg/kg/day for children 1 to 6 years old.
Estimated risks range from 22% to 93%
of the PAD. In order to estimate chronic
exposures via food, EPA used the 70th
percentile of exposures from the acute
assessment. The 70th percentile is a
common statistic used to estimate
central tendency from a distribution and
its use to estimate chronic exposures is
appropriate. Estimated risks range from
10% to 47% of the PAD. It is
emphasized that the use of both highest
tolerance level residues and the highest
in vivo conversion factor results in
dietary risk estimates that far exceed the
likely actual risk.
iii. Non-dietary exposure. Triazolederivative fungicides are registered for
use on turf, resulting in the potential for
residues of free triazole in grass and/or
soil. Thus dermal and incidental oral
exposures to children may occur. It is
believed that residues of free triazole
occur within the plant matrices and are
not available as surface residues.
Therefore, direct dermal exposure to
1,2,4-triazole due to contact with plants
is not likely to occur. However, dermal
exposure to parent fungicide and
subsequent in vivo conversion to 1,2,4triazole may occur. In order to account
for this indirect exposure to free
triazole, EPA used a conversion factor of
10%, which is the highest rate of in
vivo conversion observed in rats for any
of the triazole-derivative fungicides
with registrations on turf. Incidental
oral exposure may occur by direct and
indirect routes. To assess direct
exposure, EPA used a conversion factor
of 17%, which is the highest rate of
conversion to free triazole observed in
any of the plant metabolism studies. As
with indirect dermal exposure, EPA
used a conversion factor of 10% in its
assessment of indirect oral exposure.
Based on residential exposure values
estimated for propiconazole (0.0005 mg/
kg/day via the dermal route and 0.03
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mg/kg/day via the oral route) and the
conversion factors described above,
combined direct and indirect dermal
exposures are estimated to be less than
0.0001 mg/kg/day and combined oral
exposures are estimated to be less than
0.0019 mg/kg/day. The overall
residential exposure is likely to be less
than 0.0020 mg/kg/day. Relative to the
15 mg/kg/day point of departure, this
gives an MOE of approximately 7,500
for children. Based on the current set of
uncertainty factors, the target MOE is
1,000, indicating that the risk associated
with residential exposure to 1,2,4triazole for children is below EPA’s
level of concern. The adult dermal
exposure estimate is slightly less than
that of children. Incidental oral
exposure is not expected to occur with
adults.
iv. Drinking water. Modeled estimates
of 1,2,4-triazole residues in surface
water and ground water, as reported by
the USTTF, and the DWLOC approach
were used to address exposure to free
triazole in drinking water. EECs of free
triazole in ground water were obtained
from the SCI-GROW model and range
from 0.0 to 0.026 ppb, with the higher
concentrations associated with uses on
turf. Surface water EECs were obtained
using the FIRST model. Acute surface
water EECs ranged from 0.29 to 4.64 ppb
for agricultural uses and up to 32.1 ppb
from use on golf course turf. EPA notes
that ground water monitoring studies in
New Jersey and California showed
maximum residues of 16.7 and 0.46
ppb, respectively, which exceed the
SCI-GROW estimates significantly.
Contrariwise, preliminary monitoring
data from USDA’s Pesticide Data
Program for 2004 show no detectable
residues of 1,2,4-triazole in any drinking
water samples, either treated or
untreated (maximum LOD = 0.73 ppb, n
= 40 each).
v. Aggregate exposure. In estimating
aggregate exposure, EPA combined
potential dietary and non-dietary
sources of 1,2,4-triazole. To account for
the drinking water component of dietary
exposure, EPA used the DWLOC
approach, as noted above. The DWLOC
represents a maximum concentration of
a chemical in drinking water at or below
which aggregate exposure will not
exceed EPA’s level of concern. In
considering non-dietary exposure, EPA
used the residential exposure estimate
for children and applied it to all
population subgroups. As previously
noted, this estimate is considered to be
highly conservative for children. Since
adults are not expected to have nondietary oral exposure to 1,2,4-triazole
and that pathway makes up the majority
of the residential exposure estimate for
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children, application of that exposure
estimate to adults is considered to be
extremely conservative. Residential
exposure is expected to occur for shortterm and/or intermediate-term
durations, and therefore is not a
component in the acute or chronic
aggregate exposure assessment. In order
to assess aggregate short-term and
intermediate-term exposure, EPA
combined the residential exposure
estimate and the background level of
exposure to free triazole via food. Less
than 1% of lawns in the U.S. are
expected to be treated with triazole
fungicides, so the likelihood of cooccurring dietary and residential
exposures is very low.
With the exception of the acute
DWLOCs for infants and children 1–6
years, all DWLOCs are greater than the
largest EEC (surface water estimate from
use on turf), indicating that aggregate
exposures are not likely to exceed EPA’s
level of concern. Although the acute
DWLOCs for infants and children 1–6
years indicate that aggregate exposure
may exceed the aPAD of 0.015 mg/kg/
day, EPA does not believe this to be the
case due to the extremely conservative
nature of the overall assessment
(highest-tolerance level residues, 100%
crop treated, 77% in vivo conversion
factor). Furthermore, the drinking water
monitoring data from the Pesticide Data
Program found no detectable residues of
either free triazole or parent triazolederivative fungicide in its preliminary
2004 dataset, indicating that neither
parent compounds nor 1,2,4-triazole are
likely to occur in drinking water. For all
exposure durations and population
subgroups, EPA does not expect
aggregate exposures to 1,2,4-triazole to
exceed its level of concern.
The Agency is planning to conduct a
more sophisticated human health
assessment in early 2005 following
submission and review of the ongoing
toxicology and residue chemistry
studies for 1,2,4-triazole.
D. 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 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
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analysis or through using uncertainty
(safety) factors in calculating a dose
level that poses no appreciable risk to
humans.
2. Prenatal and postnatal sensitivity.
There are no data gaps for the
assessment of the effects of
fenbuconazole following in utero and/or
postnatal exposure; a developmental
neurotoxicity study is not required.
There is no indication of quantitative or
qualitative increased susceptibility of
rats or rabbits to in utero and/or
postnatal exposure to fenbuconazole.
3. Conclusion. There is a complete
toxicity data base for fenbuconazole and
exposure data are complete or are
estimated based on data that reasonably
accounts for potential exposures. The
FQPA Safety Factor (SF) could be
removed (i.e., reduced to 1X) in
assessing the risk posed by
fenbuconazole for several reasons:
(i) There are no data gaps for the
assessment of the effects of
fenbuconazole following in utero and/or
postnatal exposure; a developmental
neurotoxicity study is not required.
(ii) There is no indication of
quantitative or qualitative increased
susceptibility of rats or rabbits to in
utero and/or postnatal exposure to
fenbuconazole.
(iii) The dietary food exposure
assessment utilizes conservative
assumptions (tolerance level residues)
with respect to residues in food.
Although some %CT information was
used for the chronic dietary food
exposure assessment, 100% CT was
assumed for the acute assessment.
Together, these assumptions result in
high-end estimates of dietary exposure
and risk.
(iv) The dietary drinking water
assessment (Tier 1 estimates) utilizes
values generated by model and
associated modeling parameters which
are designed to provide conservative,
health protective, high-end estimates of
water concentrations;
(v) At this time, there are no
registered residential uses for
fenbuconazole; therefore, this type of
exposure to infants and children is not
expected.
E. Aggregate Risks and Determination of
Safety
To estimate total aggregate exposure
to a pesticide from food, drinking water,
and residential uses, the Agency
calculates DWLOCs which are used as a
point of comparison against the model
estimates of a pesticide’s concentration
in water (EECs). DWLOC values are not
regulatory standards for drinking water.
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DWLOCs are theoretical upper limits on
a pesticide’s concentration in drinking
water in light of total aggregate exposure
to a pesticide in food and residential
uses. In calculating a DWLOC, the
Agency determines how much of the
acceptable exposure (i.e., the PAD) is
available for exposure through drinking
water (e.g., allowable chronic water
exposure (mg/kg/day) = cPAD - (average
food + residential exposure). This
allowable exposure through drinking
water is used to calculate a DWLOC.
A DWLOC will vary depending on the
toxic endpoint, drinking water
consumption, and body weights. Default
body weights and consumption values
as used by the USEPA Office of Water
are used to calculate DWLOCs: 2 Liter
(L)/70 kg (adult male), 2L/60 kg (adult
female), and 1L/10 kg (child). Default
body weights and drinking water
consumption values vary on an
individual basis. This variation will be
taken into account in more refined
screening-level and quantitative
drinking water exposure assessments.
Different populations will have different
DWLOCs. Generally, a DWLOC is
calculated for each type of risk
assessment used: Acute, short-term,
intermediate-term, chronic, and cancer.
When EECs for surface water and
ground water are less than the
calculated DWLOCs, EPA concludes
with reasonable certainty that exposures
to the pesticide in drinking water (when
considered along with other sources of
exposure for which EPA has reliable
data) would not result in unacceptable
levels of aggregate human health risk at
this time. Because EPA considers the
aggregate risk resulting from multiple
exposure pathways associated with a
pesticide’s uses, levels of comparison in
drinking water may vary as those uses
change. If new uses are added in the
future, EPA will reassess the potential
impacts of residues of the pesticide in
drinking water as a part of the aggregate
risk assessment process.
1. Acute risk. Using the exposure
assumptions discussed in this unit for
acute exposure, the acute dietary
exposure from food to fenbuconazole
will occupy 0.9% of the aPAD for
females 13 years and older, the only
population subgroup for which an acute
endpoint was identified. After
calculating DWLOCs and comparing
them to the EECs for surface water and
ground water, EPA does not expect the
aggregate exposure to exceed 100% of
the aPAD, as shown in Table 3 of this
unit:
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TABLE 3.—AGGREGATE RISK ASSESSMENT FOR ACUTE EXPOSURE TO FENBUCONAZOLE
aPAD (mg/
kg)
Population Subgroup
Females 13 - 49 years old
% aPAD
(Food)
0.3
2. Chronic risk. Using the exposure
assumptions described in this unit for
chronic exposure, EPA has concluded
that exposure to fenbuconazole from
food will utilize 0.3% of the cPAD for
the U.S. population, 1.3% of the cPAD
Surface
Water EEC
(ppb)
0.9
for all infants, and 1.0% of the cPAD for
children 1 to 2 years old. There are no
residential uses for fenbuconazole that
result in chronic residential exposure to
fenbuconazole. After calculating
DWLOCs and comparing them to the
14.1
Ground
Water EEC
(ppb)
Acute
DWLOC
(ppb)
0.005
8,900
EECs for surface water and ground
water, EPA does not expect the
aggregate exposure to exceed 100% of
the cPAD, as shown in Table 4 of this
unit:
TABLE 4.— AGGREGATE RISK ASSESSMENT FOR CHRONIC (NON-CANCER) EXPOSURE TO FENBUCONAZOLE
cPAD mg/kg/
day
Population Subgroup
%cPAD
(Food)
Surface
Water EEC
(ppb)
Ground
Water EEC
(ppb)
Chronic
DWLOC
(ppb)
U.S. population
0.03
0.3
7.3
0.005
1,000
All infants
0.03
1.3
7.3
0.005
300
Children 1 - 2 years old
0.03
1.0
7.3
0.005
300
3. Short-term risk. Short-term
aggregate exposure takes into account
residential exposure plus chronic
exposure to food and water (considered
to be a background exposure level).
Fenbuconazole 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 water, which do not exceed
the Agency’s level of concern.
4. Intermediate-term risk.
Intermediate-term aggregate exposure
takes into account residential exposure
plus chronic exposure to food and water
(considered to be a background
exposure level).
Fenbuconazole 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 water, which do not exceed
the Agency’s level of concern.
5. Aggregate cancer risk for U.S.
population. Based on the chronic
dietary (food) exposure and using
default body weights and water
consumption figures, DWLOC for cancer
risk were calculated. To calculate the
DWLOC, the chronic dietary food
exposure for the overall U.S. population
was subtracted from the exposure
required to achieve a one in one million
cancer risk (1 x 10-6). Under FFDCA
section 408, pesticides posing a
negligible cancer risk can qualify as
meeting section 408’s reasonable
certainty of no harm safety standard.
EPA has traditionally interpreted a
negligible cancer risk as a cancer risk in
the range of a one in one million risk.
Risks as high as three in one million
have been regarded as in the range of
one in one million. A value of 1 x 10-6
was used in calculating the DWLOC for
fenbuconazole as a conservative, firsttier cancer risk assessment. The
exposure required to achieve negligible
risk is calculatedas 1 x 10-6 ÷ Q1*
0.00359 (mg/kg/day)-1. For cancer risk
exposure, based on an adult body
weight of 70 kg and 2L consumption of
water per day, the estimated cancer
DWLOC is 6.3 ppb for the U.S.
population. EFED’s 30–year average EEC
of 5.9 ppb is lower than the cancer
DWLOCs for the U.S. population.
Therefore, the Agency concludes with
reasonable certainty that, the aggregate
cancer risk for fenbuconazole does not
exceed the negligible risk standard (i.e.,
will not result in a cancer risk of greater
than the range of 1 x 10-6). The process
is illustrated in Table 5.
TABLE 5.—AGGREGATE RISK ASSESSMENT FOR CHRONIC (CANCER) EXPOSURE TO FENBUCONAZOLE
Negligible Exposure mg/
kg/day
U.S. population
6. Determination of safety. Based on
these risk assessments, EPA concludes
that there is a reasonable certainty that
no harm will result to the general
population, and to infants and children
from aggregate exposure to
fenbuconazole residues.
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%PAD (Food)
0.000279
Population Subgroup
0.3
IV. Other Considerations
A. Analytical Enforcement Methodology
An adequate analytical method for
fenbuconazole in or on plants was
submitted for inclusion in the Pesticide
Analytical Manual Vol. 2 (PAM II).
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Surface
Water EEC
(ppb)
5.9
Chronic
Ground
Water EEC
(ppb)
0.005
Chronic
DWLOC
(ppb)
6.3
B. International Residue Limits
There are Codex maximum residues
levels (MRLs) expressed as
fenbuconazole (fat-soluble) in milk,
cattle meat, liver, kidney, and fat, all at
0.05 ppm (limit of quantitation, LOQ).
Since the MRLs levels are based on
different residue definitions and LOQs
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than that of U.S. registrations,
international harmonization is not
feasible.
C. Response to Comments
A commenter raised several
objections to the extension of timelimited tolerances for fenbuconzaole: (1)
Complete data should be in before any
approval is given by EPA; further, the
Agency should not rely on limited
evidence; (2) a 4–hour toxicity test is
not a fair amount of time to test
anything; (3) testing conducted on
animals has absolutely no validity and
is cruel to the test animals; and (4) the
DEEMTM software is not suitable for
evaluating risk.
These points will be addressed in
turn.
1. Missing data/limited evidence. The
commenter’s mention of limited
evidence appears to be a reference to the
cancer potential for febuconazole. The
carcinogenicity testing performed on
fenbuconazole is complete and meets
Agency scientific standards; however,
the results of these tests are limited in
that fenbuconazole does not appear to
be a strong carcinogen. This evidence
was taken into account in EPA’s risk
assessment and in making the safety
determination. To the extent the
commenter is concerned with the fact
that there is limited information
regarding 1,2,4-triazole, EPA would note
that it more than compensated for the
data limitations with regard to that
chemical by making extremely
conservative (i.e., health-protective)
assumptions in assessing its risk.
2. 4–Hour toxicity test. The Agency
does not agree that the toxicity of
pesticides can be judged by some
undefined 4–hour toxicity test. Testing
requirements for pesticides have been
developed over many years following
extensive review by the FIFRA Science
Advisory Panel and many other
scientific experts and groups, as well as
exhaustive notice and comment
rulemaking procedures. This comment
is frivolous.
3. Animal testing. This commenter’s
objections to animal testing have been
addressed in prior rulemaking
documents. See 69 FR 63083, October
29, 2004.
4. DEEMTM software. The commenter
provides no basis for claiming that the
DEEMTM is unsuitable for risk
assessment. For this reason alone, the
comment is insignificant. EPA would
note, however, that the DEEMTM
software has been thoroughly tested by
the Agency and has been reviewed by
an independent body of technical
experts, the FIFRA Scientific Advisory
Panel, and found to be suitable for
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evaluating risks to pesticide residues on
food. The results of that review may be
found athttps://www.epa.gov/scipoly/
sap/2000/ february/
partialfinalreport06292000.pdf.
D. Conditions
Time-limited tolerances were
originally proposed for fenbuconazole
because of several conditions of
registration, namely the submission of
the following items. Five additional
studies had to be submitted: (1) Fish life
cycle, (2) growth and reproduction of
aquatic plants, (3) droplet size
spectrum, (4) drift field evaluation, and
(5) 49–month storage stability study.
Several corrections to the labels were
required. Mitigation measures to
address chronic non-target organism
toxicity concerns had to be identified
and submitted. Production of the Indar
75 WSP product could not exceed
38,000 lb (28,500 lb active ingredient)
for each year of conditional registration
and information on its production had
to be submitted for the first federal fiscal
year during which fenbuconazole was
registered for use on stone fruits and
pecans. Production information had to
be submitted for the Enable 2F product
(EPA Registration Number 62719–416)
for the first federal fiscal year during
which this product was registered for
use on pecans. The company has
subsequently submitted studies,
information, and corrected labels, and
participated in task forces, intended to
satisfy all these condition-of-registration
requirements. All such submissions that
have been reviewed have been found to
satisfy the appropriate registration
condition. However, the establishment
of permanent tolerances for
fenbuconazole depends upon the
resolution of recent questions the
Agency has raised regarding the toxicity
of 1,2,4-triazole, triazolylalanine, and
triazolyl acetic acid, metabolites
common to the triazole class of
fungicides. New data to address the
Agency’s questions about these
compounds is being generated and will
be reviewed by the Agency. However,
the Agency has decided to extend the
time-limited tolerances until such data
are reviewed and the questions about
1,2,4-triazole, triazolylalanine, and
triazolyl acetic acid have been resolved.
V. Conclusion
Therefore, the tolerance is established
for the combined residues of
fenbuconazole, [alpha-[2-(4chlorophenyl)-ethyl]-alpha-phenyl-3(1H-1,2,4-triazole)-1-propanenitrile] and
its metabolites cis- andtrans-5-(4chlorophenyl)-dihydro-3-phenyl-3-(1H1,2,4-triazole-1-ylmethyl)-2-3H-
PO 00000
Frm 00047
Fmt 4700
Sfmt 4700
11581
furanone, in or on banana (whole fruit)
at 0.3 ppm; fruit, stone, group 12 (except
plum, prune) at 2.0 ppm; pecan at 0.1
ppm.
VI. 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), 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–2004–0410 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 May 9, 2005.
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 (1900L),
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Federal Register / Vol. 70, No. 45 / Wednesday, March 9, 2005 / Rules and Regulations
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 Suite 350, 1099 14th St., NW.,
Washington, DC 20005. 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 (202) 564–6255.
2. Copies for the Docket. In addition
to filing an objection or hearing request
with the Hearing Clerk as described in
Unit VI.A., you should also send a copy
of your request to the PIRIB for its
inclusion in the official record that is
described in ADDRESSES. Mail your
copies, identified by docket ID number
OPP–2004–0410, 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
ADDRESSES. You may also send an
electronic copy of your request via email to: opp-docket@epa.gov. 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).
VII. Statutory and Executive Order
Reviews
This final rule establishes a tolerance
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,
VerDate jul<14>2003
17:19 Mar 08, 2005
Jkt 205001
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 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,
entitledFederalism (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
PO 00000
Frm 00048
Fmt 4700
Sfmt 4700
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.
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 in 40 CFR Part 180
Environmental protection,
Administrative practice and procedure,
Agricultural commodities, Pesticides
and pests, Reporting and recordkeeping
requirements.
E:\FR\FM\09MRR1.SGM
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Federal Register / Vol. 70, No. 45 / Wednesday, March 9, 2005 / Rules and Regulations
Dated:February 18, 2005
Betty Shackleford,
Acting Director, Registration Division, Office
of Pesticide Programs.
Therefore, 40 CFR chapter I is
amended as follows:
I
PART 180—AMENDED
1. The authority citation for part 180
continues to read as follows:
I
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.480 is amended by
revising the table in paragraph (a)(1) to
read as follows:
I
§ 180.480 Fenbuconaozle; tolerances for
residues.
(a) General. * * *
Banana (whole
fruit) ...............
Fruit, stone,
group 12, except plums
and prunes ....
Pecans ..............
*
*
*
Expiration/
revocation
date
Parts per
million
Commodity
0.3
2.0
0.1
*
12/31/08
12/31/08
12/31/08
*
FR Doc. 05–4474 Filed 3–8–05; 8:45 am
BILLING CODE 6560–50–S
A. Background
The Department of Health and Human
Services issued a direct final rule on
January 3, 2005 amending its
acquisition regulation (HHSAR) and
comments were due by February 2,
2005. Comments were received
requesting (1) that contracts covered by
the Service Contract Act not be
excluded from the authority to write
service contracts for a period of up to 10
years, (2) that the assignment of order
numbers be up to seventeen digits,
rather than requiring that all orders be
comprised of seventeen digits, and (3)
the redesignation of paragraphs
pertaining to numbering acquisitions.
The direct final rule, which became a
final rule on March 4, 2005, is being
corrected to reflect these comments.
List of Subjects in 48 CFR, Parts 304,
317, and 352.
Government procurement.
Dated: March 3, 2005.
Ed Sontag,
Assistant Secretary for Administration and
Management.
Accordingly, 48 CFR chapter 3, parts
304, 317, and 352 are corrected as
follows:
I 1. The authority citation for 48 CFR
chapter 3, parts 304, 317, and 352
continues to read as follows:
I
Authority: 5 U.S.C. 301; 40 U.S.C. 486(c).
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
PART 304—ADMINISTRATIVE
MATTERS
Office of the Secretary
304.7001 Numbering Acquisitions.
[Amended]
48 CFR Chapter 3
I
2. Redesignate paragraph 304.7001(d)
as paragraph 304.7001(e).
I 3. Redesignate paragraph 304.7001(c)
as paragraph 304.7001(d).
I 4. Revise paragraph (a) introductory
text and add paragraph (c) of Section
304.7001 to read as follows:
Acquisition Regulation
Department of Health and
Human Services (HHS).
ACTION: Final rule; correction.
AGENCY:
The Department of Health and
Human Services is correcting a direct
final rule that appeared in the Federal
Register on January 3, 2005 amending
its acquisition regulation (HHSAR).
Significant adverse comments were not
received and the direct final rule
became effective on March 4, 2005. The
final rule is being corrected to address
non-adverse comments received in
response to the direct final rule.
DATE: Effective Date: Effective on March
9, 2005.
FOR FURTHER INFORMATION CONTACT:
Tracey Mock, Office of Acquisition
Management and Policy, telephone
(202) 205–4430, e-mail: Tracey.Mock@
hhs.gov.
SUMMARY:
304.7001
SUPPLEMENTARY INFORMATION:
a. Acquisitions which require
numbering. The following acquisitions
shall be numbered in accordance with
the system prescribed in paragraphs (b),
(c), and (d) of this section:
b. * * *
c. Numbering system for orders. Order
numbers will be assigned to contracts
with orders. The order number shall be
up to a seventeen digit number
consisting of the following:
(1) The three digit identification code
of the Department (HHS);
(2) A one digit numeric identification
code of the servicing agency:
O Office of the Secretary
P Program Support Center
M Centers for Medicare & Medicaid
Services
VerDate jul<14>2003
17:19 Mar 08, 2005
Jkt 205001
PO 00000
Numbering acquisitions.
Frm 00049
Fmt 4700
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11583
F Food and Drug Administration
D Centers for Disease Control and
Prevention
I Indian Health Service
S Substance Abuse and Mental Health
Administration
N National Institutes of Health
H Health Resources and Services
Administration
A Agency for Health Care Research
and Quality;
(3) The three digit numeric
identification code assigned by the
Office of Acquisition Management and
Policy (OAMP) to the contracting office
within the servicing agency;
(4) An alphanumeric tracking number,
up to ten characters, the content of
which is determined by the contracting
office within the servicing agency.
*
*
*
*
*
PART 317—SPECIAL CONTRACTING
METHODS
I
5. Correct section to read as follows:
317.204
Contracts
The total of the basic and option
periods shall not exceed 10 years in the
case of services and the total of the basic
and option quantities shall not exceed
the requirement for 5 years in the case
of supplies. These limitations do not
apply to information technology
contracts. However, statutes applicable
to various classes of contracts may place
additional restrictions on the length of
contracts.
PART 352—SOLICITATION
PROVISIONS AND CONTRACT
CLAUSES
352.224–70
[Amended]
6. In 352.224–70 amend paragraph (g)
by removing ‘‘The provisions of
paragraph (e) of this clause shall not
apply when the information is subject to
conflicting or overlapping provisions in
other Federal, State, or local laws’’ and
adding ‘‘The provisions of paragraph (d)
of this clause shall not apply when the
information is subject to conflicting or
overlapping provisions in other Federal,
State, or local laws’’ in its place.
I
[FR Doc. 05–4605 Filed 3–8–05; 8:45 am]
BILLING CODE 4151–17–P
E:\FR\FM\09MRR1.SGM
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]]>Agencies
[Federal Register Volume 70, Number 45 (Wednesday, March 9, 2005)]
[Rules and Regulations]
[Pages 11572-11583]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-4474]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2004-0410; FRL-7699-2]
Fenbuconazole; Time-Limited Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes a time-limited tolerance for the
combined residues of fenbuconazole [alpha-[2-(4-chlorophenyl)-ethyl]-
alpha-phenyl-3-(1H-1,2,4-triazole)-1-propanenitrile] and its
metabolites cis- andtrans-5-(4-chlorophenyl)-dihydro-3-phenyl-3-(1H-
1,2,4-triazole-1-ylmethyl)-2-3H-furanone, expressed as fenbuconazole in
or on bananas (whole fruit); pecans; and stone fruit crop group (except
plums and prunes). Dow AgroSciences, LLC requested this tolerance under
the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the
Food Quality Protection Act of 1996 (FQPA). The tolerance will expire
on December 31, 2008.
DATES: This regulation is effective March 9, 2005. Objections and
requests for hearings must be received on or before May 9, 2005.
ADDRESSES: To submit a written objection or hearing request follow the
detailed instructions as provided in Unit VI. of theSUPPLEMENTARY
INFORMATION. EPA has established a docket for this action under docket
identification (ID) number OPP-2004-0410. All documents in the docket
are listed in the EDOCKET index athttps://www.epa.gov/edocket. Although
listed in the index, some information is not publicly available, i.e.,
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 electronically
in EDOCKET or in hard copy at the Public Information and Records
Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 1801 S.
Bell St., 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.
FOR FURTHER INFORMATION CONTACT: J. R. Tomerlin, Registration Division
(0705C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-0598; e-mail address: tomerlin.bob@epa.gov.
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 underFOR FURTHER INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document and Other
Related Information?
In addition to using EDOCKET (https://www.epa.gov/edocket/), you may
access this Federal Register document electronically through the EPA
Internet under the ``Federal Register'' listings at https://www.epa.gov/
fedrgstr/. A frequently updated electronic version of 40 CFR part 180
is available at E-CFR Beta Site Two at https://www.gpoaccess.gov/ecfr/.
To access the OPPTS Harmonized Guidelines referenced in this document,
go directly to the guidelines athttps://www.epa.gpo/opptsfrs/home/
guidelin.htm/.
II. Background and Statutory Findings
In the Federal Register of November 17, 2004 (69 FR 67351) (FRL-
7686-6), EPA issued a notice pursuant to section 408(d)(3) of the
FFDCA, 21 U.S.C. 346a(d)(3), announcing the filing of pesticide
petitions (PP 1F3989, 1F3995, and 2F4154) by Dow AgroSciences, LLC,
9330 Zionsville Road, Indianapolis, IN 46268. The petitions requested
that 40 CFR 180.480 be amended by establishing a tolerance for combined
residues of the fungicide fenbuconazole [alpha-[2-(4-chlorophenyl)-
ethyl]-alpha-phenyl-3-(1H-1,2,4-triazole)-1-propanenitrile] and its
metabolites cis- andtrans-5-(4-chlorophenyl)-dihydro-3-phenyl-3-(1H-
1,2,4-triazole-1-ylmethyl)-2-3H-furanone, in or on banana (whole fruit)
at 0.3 parts per million (ppm) (2F4154); fruit, stone, group 12 (except
plum, prune) at 2.0 ppm (1F3989); pecan at 0.1 ppm (1F3995). This
notice included a summary of the petition prepared by Dow AgroSciences,
LLC, the registrant.
The tolerances will expire on December 31, 2008.
Comments were received in response to the notice of filing from one
individual. These comments are addressed in Unit IV.C.
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
[[Page 11573]]
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. . . .''
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 the final rule on
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).
III. Aggregate Risk Assessment and Determination of Safety
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 and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of the FFDCA, for a tolerance for combined residues of banana
(whole fruit) at 0.3 parts per million (ppm); fruit, stone, group 12
(except plum, prune) at 2.0 ppm; pecan at 0.1 ppm. EPA's assessment of
exposures and risks associated with establishing the tolerance follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies 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. The nature of the toxic effects caused by fenbuconazole are
discussed in Table 1 of this unit as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.
Table 1.-- Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
Guideline No. Study Type Results
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity NOAEL = 1.3/1.5 mg/kg/day (M/F)
rodents - rats LOAEL = 5.1/6.3 mg/kg/day (M/F) based on
liver histopathology
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity NOAEL = 3.8/5.7 mg/kg/day (M/F)
rodents - mice LOAEL = 11.1/17.6 mg/kg/day (M/F) based on
liver histopathology
----------------------------------------------------------------------------------------------------------------
870.3150 90-Day oral toxicity in NOAEL = 3.3/3.5 mg/kg/day (M/F)
nonrodents - dogs LOAEL = 13.3/14.0 mg/kg/day (M/F) based on
liver histopathology
----------------------------------------------------------------------------------------------------------------
870.3200 21/28-Day dermal toxicity - NOAEL = 1,000 mg/kg/day (HDT)
rats LOAEL = > 1,000 mg/kg/day
----------------------------------------------------------------------------------------------------------------
870.3250 90-Day dermal toxicity Not performed
----------------------------------------------------------------------------------------------------------------
870.3465 90-Day inhalation toxicity Not performed
----------------------------------------------------------------------------------------------------------------
870.3700 Prenatal developmental in Maternal NOAEL = 30 mg/kg/day
rodents - rats Maternal LOAEL = 75 mg/kg/day based on
decreased body weight and body weight gain
Developmental NOAEL = 30 mg/kg/day
Developmental LOAEL = 75 mg/kg/day based on
increased post-implantation loss and a
decrease in the number of live fetuses/dam
----------------------------------------------------------------------------------------------------------------
870.3700 Prenatal developmental in Maternal NOAEL = 10 mg/kg/day
nonrodents - rabbits Maternal LOAEL = 30 mg/kg/day based on
decreased food consumption and increased
incidence of clinical signs (soft/scant/no
feces and red discharge)
Developmental NOAEL = 30 mg/kg/day
Developmental LOAEL = 60 mg/kg/day based on
increased early resorptions
----------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and fertility Parental systemic NOAEL = 4 mg/kg/day
effects - rats Parental systemic LOAEL = 40 mg/kg/day
based on maternal death during delivery,
decreased body weight and food
consumption, increased number of dams not
delivering viable or delivering nonviable
offspring, and increased adrenal and
thyroid/parathyroid weights
Reproductive NOAEL = 40 mg/kg/day (HDT)
Reproductive LOAEL = greater than 40 mg/kg/
day
Offspring systemic NOAEL: 4 mg/kg/day
Offspring systemic LOAEL: 40 mg/kg/day
based on decreased pup body weight,
increased number of stillborn pups,
decreased number of total offspring
delivered and decreased viability indes
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity - rodents Requirements met by submission of studies
according to OPPTS Harmonized Guideline
870.4300
----------------------------------------------------------------------------------------------------------------
[[Page 11574]]
870.4100 Chronic toxicity - dogs NOAEL = 3.75/0.38 mg/kg/day (M/F)
LOAEL = 30/3.75 mg/kg/day (M/F) based on
decreased body weight gain
Note: Dose-related adaptive liver changes
were observed in high-dose males and
females
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity - rats Requirements met by submission of studies
according to OPPTS Harmonized Guideline
870.4300
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity - mice NOAEL = 1.43 mg/kg/day (both M and F)
LOAEL = 28.6/92.9 mg/kg/day (M/F) based on
decreased body weight, increased relative
and absolute liver weight, and
hepatocellular hypertrophy and
vacuolization
Evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.4300 Combined chronic toxicity/ NOAEL = 3.0/4.0 mg/kg/day (M/F)
carcinogenicity - rat LOAEL = 30.6/43.1 mg/kg/day (M/F) based on
decreased body weight gain (F),
hepatocellular enlargement and
vacuolization (F), increased thyroid
weight (M and F), and histopathological
lesions in the thyroid gland (M)
Evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.4300 Combined chronic toxicity/ NOAEL = Not established
carcinogenicity - rat LOAEL = 30.4 mg/kg/day (M) based on
decreased body weight gain, increased
liver weight, and increased thyroid and
parathyroid weights
Note: Only males were used in this study.
Insufficient evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.5100 Gene mutation - bacterial No mutagenic activity in bacteria
reverse mutation assay (Salmonella typhimurium) under conditions
of this assay.
Note: Only TA1535, TA1537, TA98, and TA100
were tested. This study is classified
unacceptable.
----------------------------------------------------------------------------------------------------------------
870.5100 Gene mutation - bacterial No mutagenic activity in bacteria
reverse mutation assay (Salmonella typhimurium) under conditions
of this assay.
Note: Only TA1535, TA1537, TA98, and TA100
were tested. This study is classified
unacceptable.
----------------------------------------------------------------------------------------------------------------
870.5300 Cytogenetics - in vitro No increase in mutant frequency at the
mammalian cell gene HGPRT locus, in the presence or absence of
mutation test (CHO Cells) S9 activation.
----------------------------------------------------------------------------------------------------------------
870.5385 Cytogenetics - mammalian No increase in number of cells with
bone marrow chromosomal aberrations or in aberrations per cell.
aberration test (rats)
----------------------------------------------------------------------------------------------------------------
870.5550 Other effects - No evidence (or a dose related positive
unscheduled DNA synthesis response) that unscheduled DNA synthesis
in mammalian cells in was induced.
culture (rats)
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and The mean recovery of radioactivity 4 days
pharmacokinetics - rat after exposure was 82.6-93.0% following
single or repeated oral doses and 88.2-
99.2% following single i.v. doses,
indicating rapid absorption, distribution,
and elimination. Rapid elimination and low
tissue levels indicate low bioaccumulation
of the parent and metabolites.
Elimination occurred primarily by biliary
excretion because recovery of
radioactivity was mostly in the feces:
75.6-83.7% following oral exposure and
77.2-91.4% following i.v. exposure. In
urine, radioactivity recovery was 5.5-
12.6% for all dose scenarios. Peak
radioactivity in the blood occurred 3
hours following a single low dose and 3-6
hours after a single high dose, indicating
biphasic elimination.
Only 8.5-14.8% and 0.0-2.7% of the parent
compound was recovered in the feces and
urine, respectively, indicating extensive
metabolism. A number of major metabolites
were identified; however, 50% and 20% of
metabolites in the feces and urine,
respectively, were not identified. Sex-
related differences include a greater
number of sulfate metabolites in female
excreta compared to males, and a greater
number of ketoacid metabolites in male
urine compared to females.
----------------------------------------------------------------------------------------------------------------
[[Page 11575]]
870.7485 Metabolism and The mean recovery of radioactivity 3-4 days
pharmacokinetics - rat after exposure was 90.4-104.5% following
single or repeated oral doses, indicating
rapid absorption, distribution, and
elimination. Bioaccumulation of the parent
compound and metabolites is low. There
were no major sex- or dose-related
differences in absorption, distribution,
or elimination.
Elimination occurred primarily by biliary
excretion: Recovery of the administered
dose occurred mainly in the bile (79.1-
87.1%) 3 days after exposure and mostly in
the feces (78.7-94.4%) 4 days after
exposure. In contrast, radioactivity
recovery in the urine was 3.2-11.5% at 3
and 4 days after exposure.
Extensive metabolism occurred; numerous
metabolites were found in the feces and
urine. There is a dose-related difference
in metabolism. A higher amount of parent
compound was found in the feces following
the single high dose compared to the
single or repeated low dose(s), which
suggests that saturation may be occurring
at the high dose.
----------------------------------------------------------------------------------------------------------------
870.7600 Dermal penetration - rat The highest dermal absorption was found in
animals having the longest exposure dose.
Mean % of the dose absorbed (sum of urine,
feces, carcass, and skin) after 10 hours
of exposure:
Dose (mg/kg) Percent Dermal Absorption
0.125 4.25
1.25 2.08
125 0.45
----------------------------------------------------------------------------------------------------------------
B. 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 level of concern
(LOC). 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 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 intraspecies 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 Safety Factor
(SF).
For non-dietary risk assessments (other than cancer) the UF is used
to determine the 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 as1 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 fenbuconazole used for human risk assessment is shown in
Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for Fenbuconaozle for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Special FQPA SF* and
Exposure Scenario Dose Used in Risk Level of Concern for Study and Toxicological
Assessment, UF Risk Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (females 13-49 years of NOAEL = 30 mg/kg/day Special FQPA SF = 1 Developmental rat study
age) UF = 100a.............. aPAD = acute RfD / Developmental LOAEL =
Acute RfD = 0.3 mg/kg.. FQPA SF = 0.3 mg/kg 75 mg/kg/day based on
increased resorptions
and decreased live
fetuses per dam
----------------------------------------------------------------------------------------------------------------
[[Page 11576]]
Acute dietary (general population None None Not selected
including infants and children) No appropriate dose and
endpoint could be
identified for these
population groups.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (all populations) NOAEL = 3 mg/kg/day Special FQPA SF = 1 Combined chronic
UF = 100a.............. cPAD = chronic RfD / toxicity/
Chronic RfD = 0.03 mg/ FQPA SF = 0.03 mg/kg/ carcinogenicity - rat
kg/day. day. LOAEL = 30.6/43.1 (M/F)
mg/kg/day based on
decreased body weight
gain, increased
thyroid weight, and
histopathological
lesions in the liver
and thyroid gland
----------------------------------------------------------------------------------------------------------------
Incidental oral (all durations) None None Not selected
No registered uses
would result in
residential exposure
-----------------------------------------------------------------------------------------
Short-term (1 to 30 days) and None None Not selected
intermediate-term (1 to 6 months) No dermal or systemic
Dermal............................... toxicity was seen in a
21-day dermal toxicity
study; poor absorption
was seen in the dermal
absorption study
-----------------------------------------------------------------------------------------
Long-term dermal (several months to Oral study NOAEL = 3 mg/ Residential LOC for MOE Combined chronic
lifetime) kg/day = Not applicable toxicity/
(dermal absorption rate Occupational LOC for carcinogenicity - rat
= 4.25%). MOE = 100\a\. LOAEL = 30.6/43.1 (M/F)
mg/kg/day based on
decreased body weight
gain, increased
thyroid weight, and
histopathological
lesions in the liver
and thyroid gland
-----------------------------------------------------------------------------------------
Inhalation (all durations) None None Not selected
Low toxicity and use
pattern does not
indicate a need for
risk assessment via
inhalation.
-----------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) Classification: Under the 1986 cancer classification scheme,
fenbuconazole was classified as a Group C - Possible Human Carcinogen,
with a low dose extrapolation model applied to the animal data for the
quantification of human risk (Q1*). This was based on increased
incidence of hepatocellular adenomas and carcinomas in male and female
mice and of thyroid follicular adenomas and combined adenomas/carcinomas
in male rats. Based on mechanistic data, quantification of risk was
derived using combined hepatocellular adenomas/carcinomas in female
mice. The upper bound estimate of unit risk, Q1* (mg/kg/day)-\1\ is 3.59
x 10-\3\ in human equivalents.
----------------------------------------------------------------------------------------------------------------
*Database uncertainty factor reduced to 1X.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.480) for the combined residues of
fenbuconazole, in or on a variety of raw agricultural commodities. Risk
assessments were conducted by EPA to assess dietary exposures from
fenbuconazole 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 1 day or
single exposure. The Dietary Exposure Evaluation Model (DEEM\TM\)
analysis evaluated the individual food consumption as reported by
respondents in the U.S. Department of Agriculture (USDA) 1994-1996 and
1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII) and accumulated exposure to the chemical for each commodity.
The following assumptions were made for the acute exposure assessments:
Tolerance level residues were used for all food commodities, 100% of
all commodities were assumed to be treated, and default processing
factors were used for processed commodities.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment, the DEEM\TM\ analysis evaluated the food consumption as
reported by respondents in the USDA 1994-1996 and 1998 CSFII and
accumulated exposure to the chemical for each commodity. The following
assumptions were made for the chronic exposure assessments: The chronic
analysis is slightly refined in that it incorporates estimates of
average percent crop treated (PCT), although it does use tolerance
value residues for most commodities and default processing factors.
Anticipated residues from USDA Pesticide Data Program monitoring data
were used only for banana in the chronic dietary exposure analysis and
risk assessment.
iii. Cancer. Chronic cancer risk for the overall U.S. population
was estimated by multiplying the chronic exposure
[[Page 11577]]
estimate by the carcinogenic potential (Q*) of 0.0359 (mg/kg/
day)-\1\.
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
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. As required by section 408(b)(2)(E) of the
FFDCA, EPA will issue a Data Call-In for information relating to
anticipated residues 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 percent crop
treated (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 as follows:
A routine chronic dietary exposure analysis for the fungicide
fenbuconazole and itscis and trans metabolites was based on 10% of
apricot crop treated, 25% of blueberry crop treated, 25% of cherry crop
treated, 30% of grapefruit crop treated, 15% of nectarine crop treated,
15% of peach crop treated, and 10% of pecan crop treated.
The Agency believes that the three conditions previously discussed
have been met. With respect to Condition 1, EPA finds that the PCT
information for fenbuconazole is reliable and has a valid basis. Time-
limited tolerances have existed for all crop commodities included in
the risk assessment, and the Agency obtained estimates of fenbuconazole
use from recognized pesticide use data bases. 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 fenbuconazole
may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for fenbuconazole in drinking
water. Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of fenbuconazole.
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW, which predicts pesticide concentrations in ground water. In
general, EPA will use GENEEC (a Tier 1 model) before using PRZM/EXAMS
(a Tier 2 model) for a screening-level assessment for surface water.
The GENEEC model is a subset of the PRZM/EXAMS model that uses a
specific high-end runoff scenario for pesticides. GENEEC incorporates a
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir
environment in place of the previous pond scenario. The PRZM/EXAMS
model includes a percent crop area factor as an adjustment to account
for the maximum percent crop coverage within a watershed or drainage
basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a coarse screen for sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a %RfD or %PAD. Instead drinking
water levels of comparisons (DWLOCs) are calculated and used as a point
of comparison against the model estimates of a pesticide's
concentration in water. DWLOCs are theoretical upper limits on a
pesticide's concentration in drinking water in light of total aggregate
exposure to a pesticide in food, and from residential uses. Since
DWLOCs address total aggregate exposure to fenbuconaozle, they are
further discussed in the aggregate risk sections in Unit III.E.
Based on the PRZM/EXAMS and SCI-GROW models, the estimated EECs of
fenbuconazole for acute exposures are estimated to be 14.1 parts per
billion (ppb) for surface water and 0.005 ppb for ground water. The
EECs for chronic exposures are estimated to be 7.3 ppb (peak annual)
and 5.9 ppb (30-year average) for surface water and 0.005 ppb for
ground water.
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).
Fenbuconazole is not registered for use on any sites that would
result in residential exposure.
4. Cumulative exposure to 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.''
Unlike other pesticides for which EPA has followed a cumulative
risk approach based on a common mechanism of toxicity, fenbuconazole
does not appear to produce a toxic metabolite produced by other
substances. For the purposes of this tolerance action, therefore, EPA
has not assumed that fenbuconazole has 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
[[Page 11578]]
the cumulative effects of such chemicals, see the final rule for
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).
However, the Agency does have concern about potential toxicity to
1,2,4-triazole and two conjugates, triazolylalanine and triazolyl
acetic acid, metabolites common to most of the triazole fungicides. To
support the extension of existing parent triazole-derivative fungicide
tolerances, EPA conducted an interim human health assessment for
aggregate exposure to 1,2,4-triazole. The exposure and risk estimates
presented in this assessment are overestimates of actual likely
exposures and therefore, should be considered to be highly
conservative. Based on this assessment, EPA concluded that for all
exposure durations and population subgroups, aggregate exposures to
1,2,4-triazole are not expected to exceed its level of concern. This
assessment should be considered interim due to the ongoing series of
studies being conducted by the U.S. Triazole Task Force (USTTF). Those
studies are designed to provide the Agency with more complete
toxicological and residue information for free triazole and are
expected to be submitted to the Agency in late 2004 and early 2005.
Upon completion of review of these data, EPA will prepare a more
sophisticated assessment based on the revised toxicological and
exposure data bases.
i. Toxicology. The toxicological data base for 1,2,4-triazole is
incomplete. Preliminary summary data presented by the USTTF to EPA
indicate that the most conservative endpoint currently available for
use in a risk assessment for 1,2,4-triazole is a LOAEL of 15 mg/kg/day,
based on body weight decreases in male rats in the reproductive
toxicity study (currently underway). This endpoint, with an uncertainty
factor of 1,000 was used for both acute and chronic dietary risk,
resulting in an RfD of 0.015 mg/kg/day. The uncertainty factor of 1,000
includes an additional 10X safety factor for the protection of infants
and children. The resulting PAD is 0.015 mg/kg/day.
ii. Dietary exposure. The USTTF conducted an acute dietary exposure
assessment based on the highest triazole-derivative fungicide tolerance
level combined with worst-case molecular weight and plant/livestock
metabolic conversion factors. This approach provides a conservative
estimate of all sources for 1,2,4-triazole except the in vivo
conversion of parent compounds to free-triazole following dietary
exposure. The degree of animal in vivo conversion is dependent on the
identity of the parent fungicide. In rats, this conversion ranges from
0% to 77%, thein vivo conversion for fenbuconaozle is 2.5%. For
purposes of this interim assessment, EPA used the dietary exposure
estimates provided by the USTTF adjusted based on the highest rate of
conversion observed for any of the parent triazole-derivative
fungicides to account for this metabolic conversion. The assessment
includes residue estimates for all food commodities with either
existing or pending triazole-derivative fungicide registrations. The
resulting acute dietary exposure estimates are extremely conservative
and range from 0.0032 mg/kg/day for males 20+ years old to 0.014 mg/kg/
day for children 1 to 6 years old. Estimated risks range from 22% to
93% of the PAD. In order to estimate chronic exposures via food, EPA
used the 70th percentile of exposures from the acute assessment. The
70th percentile is a common statistic used to estimate central tendency
from a distribution and its use to estimate chronic exposures is
appropriate. Estimated risks range from 10% to 47% of the PAD. It is
emphasized that the use of both highest tolerance level residues and
the highest in vivo conversion factor results in dietary risk estimates
that far exceed the likely actual risk.
iii. Non-dietary exposure. Triazole-derivative fungicides are
registered for use on turf, resulting in the potential for residues of
free triazole in grass and/or soil. Thus dermal and incidental oral
exposures to children may occur. It is believed that residues of free
triazole occur within the plant matrices and are not available as
surface residues. Therefore, direct dermal exposure to 1,2,4-triazole
due to contact with plants is not likely to occur. However, dermal
exposure to parent fungicide and subsequent in vivo conversion to
1,2,4-triazole may occur. In order to account for this indirect
exposure to free triazole, EPA used a conversion factor of 10%, which
is the highest rate of in vivo conversion observed in rats for any of
the triazole-derivative fungicides with registrations on turf.
Incidental oral exposure may occur by direct and indirect routes. To
assess direct exposure, EPA used a conversion factor of 17%, which is
the highest rate of conversion to free triazole observed in any of the
plant metabolism studies. As with indirect dermal exposure, EPA used a
conversion factor of 10% in its assessment of indirect oral exposure.
Based on residential exposure values estimated for propiconazole
(0.0005 mg/kg/day via the dermal route and 0.03 mg/kg/day via the oral
route) and the conversion factors described above, combined direct and
indirect dermal exposures are estimated to be less than 0.0001 mg/kg/
day and combined oral exposures are estimated to be less than 0.0019
mg/kg/day. The overall residential exposure is likely to be less than
0.0020 mg/kg/day. Relative to the 15 mg/kg/day point of departure, this
gives an MOE of approximately 7,500 for children. Based on the current
set of uncertainty factors, the target MOE is 1,000, indicating that
the risk associated with residential exposure to 1,2,4-triazole for
children is below EPA's level of concern. The adult dermal exposure
estimate is slightly less than that of children. Incidental oral
exposure is not expected to occur with adults.
iv. Drinking water. Modeled estimates of 1,2,4-triazole residues in
surface water and ground water, as reported by the USTTF, and the DWLOC
approach were used to address exposure to free triazole in drinking
water. EECs of free triazole in ground water were obtained from the
SCI-GROW model and range from 0.0 to 0.026 ppb, with the higher
concentrations associated with uses on turf. Surface water EECs were
obtained using the FIRST model. Acute surface water EECs ranged from
0.29 to 4.64 ppb for agricultural uses and up to 32.1 ppb from use on
golf course turf. EPA notes that ground water monitoring studies in New
Jersey and California showed maximum residues of 16.7 and 0.46 ppb,
respectively, which exceed the SCI-GROW estimates significantly.
Contrariwise, preliminary monitoring data from USDA's Pesticide Data
Program for 2004 show no detectable residues of 1,2,4-triazole in any
drinking water samples, either treated or untreated (maximum LOD = 0.73
ppb, n = 40 each).
v. Aggregate exposure. In estimating aggregate exposure, EPA
combined potential dietary and non-dietary sources of 1,2,4-triazole.
To account for the drinking water component of dietary exposure, EPA
used the DWLOC approach, as noted above. The DWLOC represents a maximum
concentration of a chemical in drinking water at or below which
aggregate exposure will not exceed EPA's level of concern. In
considering non-dietary exposure, EPA used the residential exposure
estimate for children and applied it to all population subgroups. As
previously noted, this estimate is considered to be highly conservative
for children. Since adults are not expected to have non-dietary oral
exposure to 1,2,4-triazole and that pathway makes up the majority of
the residential exposure estimate for
[[Page 11579]]
children, application of that exposure estimate to adults is considered
to be extremely conservative. Residential exposure is expected to occur
for short-term and/or intermediate-term durations, and therefore is not
a component in the acute or chronic aggregate exposure assessment. In
order to assess aggregate short-term and intermediate-term exposure,
EPA combined the residential exposure estimate and the background level
of exposure to free triazole via food. Less than 1% of lawns in the
U.S. are expected to be treated with triazole fungicides, so the
likelihood of co-occurring dietary and residential exposures is very
low.
With the exception of the acute DWLOCs for infants and children 1-6
years, all DWLOCs are greater than the largest EEC (surface water
estimate from use on turf), indicating that aggregate exposures are not
likely to exceed EPA's level of concern. Although the acute DWLOCs for
infants and children 1-6 years indicate that aggregate exposure may
exceed the aPAD of 0.015 mg/kg/day, EPA does not believe this to be the
case due to the extremely conservative nature of the overall assessment
(highest-tolerance level residues, 100% crop treated, 77% in vivo
conversion factor). Furthermore, the drinking water monitoring data
from the Pesticide Data Program found no detectable residues of either
free triazole or parent triazole-derivative fungicide in its
preliminary 2004 dataset, indicating that neither parent compounds nor
1,2,4-triazole are likely to occur in drinking water. For all exposure
durations and population subgroups, EPA does not expect aggregate
exposures to 1,2,4-triazole to exceed its level of concern.
The Agency is planning to conduct a more sophisticated human health
assessment in early 2005 following submission and review of the ongoing
toxicology and residue chemistry studies for 1,2,4-triazole.
D. 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 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. Prenatal and postnatal sensitivity. There are no data gaps for
the assessment of the effects of fenbuconazole following in utero and/
or postnatal exposure; a developmental neurotoxicity study is not
required. There is no indication of quantitative or qualitative
increased susceptibility of rats or rabbits to in utero and/or
postnatal exposure to fenbuconazole.
3. Conclusion. There is a complete toxicity data base for
fenbuconazole and exposure data are complete or are estimated based on
data that reasonably accounts for potential exposures. The FQPA Safety
Factor (SF) could be removed (i.e., reduced to 1X) in assessing the
risk posed by fenbuconazole for several reasons:
(i) There are no data gaps for the assessment of the effects of
fenbuconazole following in utero and/or postnatal exposure; a
developmental neurotoxicity study is not required.
(ii) There is no indication of quantitative or qualitative
increased susceptibility of rats or rabbits to in utero and/or
postnatal exposure to fenbuconazole.
(iii) The dietary food exposure assessment utilizes conservative
assumptions (tolerance level residues) with respect to residues in
food. Although some %CT information was used for the chronic dietary
food exposure assessment, 100% CT was assumed for the acute assessment.
Together, these assumptions result in high-end estimates of dietary
exposure and risk.
(iv) The dietary drinking water assessment (Tier 1 estimates)
utilizes values generated by model and associated modeling parameters
which are designed to provide conservative, health protective, high-end
estimates of water concentrations;
(v) At this time, there are no registered residential uses for
fenbuconazole; therefore, this type of exposure to infants and children
is not expected.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against the model estimates of
a pesticide's concentration in water (EECs). DWLOC values are not
regulatory standards for drinking water. DWLOCs are theoretical upper
limits on a pesticide's concentration in drinking water in light of
total aggregate exposure to a pesticide in food and residential uses.
In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is available for exposure through
drinking water (e.g., allowable chronic water exposure (mg/kg/day) =
cPAD - (average food + residential exposure). This allowable exposure
through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA Office of Water are used to calculate
DWLOCs: 2 Liter (L)/70 kg (adult male), 2L/60 kg (adult female), and
1L/10 kg (child). Default body weights and drinking water consumption
values vary on an individual basis. This variation will be taken into
account in more refined screening-level and quantitative drinking water
exposure assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
Acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and ground water are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, EPA will reassess the potential impacts
of residues of the pesticide in drinking water as a part of the
aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
fenbuconazole will occupy 0.9% of the aPAD for females 13 years and
older, the only population subgroup for which an acute endpoint was
identified. After calculating DWLOCs and comparing them to the EECs for
surface water and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the aPAD, as shown in Table 3 of this unit:
[[Page 11580]]
Table 3.--Aggregate Risk Assessment for Acute Exposure to Fenbuconazole
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC
kg) (Food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
Females 13 - 49 years old 0.3 0.9 14.1 0.005 8,900
----------------------------------------------------------------------------------------------------------------
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
fenbuconazole from food will utilize 0.3% of the cPAD for the U.S.
population, 1.3% of the cPAD for all infants, and 1.0% of the cPAD for
children 1 to 2 years old. There are no residential uses for
fenbuconazole that result in chronic residential exposure to
fenbuconazole. After calculating DWLOCs and comparing them to the EECs
for surface water and ground water, EPA does not expect the aggregate
exposure to exceed 100% of the cPAD, as shown in Table 4 of this unit:
