[Federal Register Volume 78, Number 128 (Wednesday, July 3, 2013)]
[Rules and Regulations]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-15867]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Fenbuconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
fenbuconazole in or on pepper. Dow AgroSciences LLC requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective July 3, 2013. Objections and
requests for hearings must be received on or before September 3, 2013,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2012-0520, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory
Public Docket (OPP Docket) in the Environmental Protection Agency
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal
holidays. The telephone number for the Public Reading Room is (202)
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information
about the docket available at http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Erin Malone, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 347-0253; email address: email@example.com.
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.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
B. How can I get electronic access to other related information?
You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2012-0520 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
September 3, 2013. Addresses for mail and hand delivery of objections
and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing (excluding any Confidential Business Information (CBI)) for
inclusion in the public docket. Information not marked confidential
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without
prior notice. Submit the non-CBI copy of your objection or hearing
request, identified by docket ID number EPA-HQ-OPP-2012-0520, by one of
the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider to be CBI or other
information whose disclosure is restricted by statute.
Mail: OPP Docket, Environmental Protection Agency Docket
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC
Hand Delivery: To make special arrangements for hand
delivery or delivery of boxed information, please follow the
instructions at http://www.epa.gov/dockets/contacts.htm.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at http://www.epa.gov/dockets.
II. Summary of Petitioned-For Tolerance
In the Federal Register of September 28, 2012 (77 FR 59578) (FRL-
9364-6), EPA issued a document pursuant to FFDCA section 408(d)(3), 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
2F8034) by Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis,
Indiana 46268. The petition requested that 40 CFR 180.480 be amended by
modifying the tolerance for residues of the fungicide fenbuconazole,
propanenitrile, and its metabolites RH-9129, cis-5-(4-chlorophenyl)-
dihydro-3-phenyl-3-(1H-1,2,4-triazole-1-ylmethyl)-2-3 H-furanone, and
triazole-1-ylmethyl)-2-3 H-furanone, in or on pepper from 0.4 parts per
million (ppm) to 1.0 ppm. That document referenced a summary of the
petition prepared by Dow AgroSciences LLC, the registrant, which is
available in the docket, http://www.regulations.gov. A comment was
received on the notice of filing. EPA's response to this comment is
discussed in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of 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 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 FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical residue. . .
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), 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 for fenbuconazole including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with fenbuconazole
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 main target organ of fenbuconazole is the liver.
Increased liver weight, hepatocellular hypertrophy, and clinical
chemistry changes were observed in the rat, dog,
and mouse following subchronic and chronic exposure. In the rat (but
not the dog or mouse), effects on the thyroid were also observed. A
mechanistic study demonstrated that these findings are secondary to
changes in liver metabolic enzyme activities, which result in
alterations to levels of circulating thyroid hormone due to increased
clearance via increased liver metabolism and, eventually, thyroid
hyperplasia. The rat is significantly more sensitive to these effects
than other species. Clear NOAELs and LOAELs were established for these
findings, and the endpoints selected for human health risk assessment
are protective of the thyroid effects. The endpoints are also
protective of potential thyroid perturbation to offspring, as the
developmental NOAELs were significantly higher than the NOAELs for
thyroid and liver effects in adults (e.g., chronic dietary endpoint
based on rat chronic/carcinogenicity NOAEL of 3 mg/kg/day vs. rat
developmental NOAEL of 30 mg/kg/day), and no increased quantitative
susceptibility was observed for thyroid and liver effects among the
offspring relative to the parental animals. Kidney and adrenal weights
were increased in dogs after chronic exposure. Although acute and
subchronic neurotoxicity have not been submitted, EPA concluded that
these studies are not required, taking into consideration the lack of
observed neurotoxic effects in the available studies for fenbuconazole
as well as many other triazole fungicides. There was no evidence of
increased quantitative or qualitative susceptibility to in utero or
post-natal exposure to fenbuconazole. Since the previous assessment,
new rabbit developmental toxicity and rat metabolism studies were
submitted; the findings of these studies are consistent with the data
EPA assessed previously and do not affect the overall characterization
of hazard or selection of doses and endpoints for risk assessment.
Fenbuconazole is classified as a ``Group C,'' or possible human
carcinogen, based on an increased incidence of liver tumors in male and
female mice. A cancer potency factor has been used to quantify
potential cancer risk associated with fenbuconazole uses.
Specific information on the studies received and the nature of the
adverse effects caused by fenbuconazole as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document ``Fenbuconazole: Human Health Risk
Assessment for an Increased Tolerance for Residues in Peppers and a
Label Amendment for the Enable 2F Product'' at page 14 in docket ID
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). Uncertainty/safety factors are used in conjunction with
the POD to calculate a safe exposure level--generally referred to as a
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe
margin of exposure (MOE). For non-threshold risks, the Agency assumes
that any amount of exposure will lead to some degree of risk. Thus, the
Agency estimates risk in terms of the probability of an occurrence of
the adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm. A summary of the toxicological
endpoints for fenbuconazole used for human risk assessment is shown in
Table 1 of this unit.
A summary of the toxicological endpoints for fenbuconazole used for
human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Fenbuconazole for Use in Human Health Risk Assessment
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
Acute dietary (Females 13-49 NOAEL = 30 mg/kg/day Acute RfD = 0.3 mg/ Developmental rat study
years of age). UFA = 10x........... kg/day. LOAEL = 75 mg/kg/day based on
UFH = 10x........... aPAD = 0.3mg/kg/day increased resorptions,
FQPA SF = 1x........ postimplantation loss and
decreased live fetuses per dam.
Acute dietary (General population None................ None............... Not selected
including infants and children). No appropriate single dose and
endpoint could be identified for
these population groups.
Chronic dietary (All populations) NOAEL = 3 mg/kg/day. Chronic RfD = 0.03 Combined chronic toxicity/
UFA = 10x........... mg/kg/day. carcinogenicity--Rat
UFH = 10x........... cPAD = 0.03 mg/kg/ LOAEL = 30.6/43.1 (M/F) mg/kg/day
FQPA SF = 1x........ day. based on decreased body weight
gain, increased thyroid weight,
and hispathological lesions in
the liver and thyroid gland.
Cancer (Oral, dermal, inhalation) 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
classification was based on a statistically significant increase in combined
hepatocellular adenomas and/or carcinomas by pair-wise comparison with
concurrent controls, and significantly increasing trend in both the
incidences of adenomas, and combined adenomas/carcinomas, in female mice.
The upper bound estimate of unit risk, Q1* (mg/kg/day)-1 is 3.59 x -3 in
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. mg/kg/day =
milligrams/kilogram/day. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute,
c = chronic). RfD = reference dose. UF = uncertainty factor. UFA = extrapolation from animal to human
(interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies).
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to fenbuconazole, EPA considered exposure under the
petitioned-for tolerances as well as all existing fenbuconazole
tolerances in 40 CFR 180.480. For the acute, chronic, and cancer
dietary exposure assessments, EPA used food consumption information
from the United States Department of Agriculture's (USDA) National
Health and Nutrition Examination Survey/What We Eat In America (NHANES/
WWEIA) collected from 2003-2008. In addition, EPA assessed dietary
exposures from fenbuconazole in food as follows:
i. Acute exposure. Quantitative acute dietary exposure and 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.
Such effects were identified for fenbuconazole only for females age
13-49. As to residue levels in food, EPA used tolerance-level residues
and assumed 100% crop treated for all commodities in the acute dietary
ii. Chronic exposure. As to residue levels in food, EPA used a
combination of tolerance-level residues and, for many foods, average
residue levels from crop field trials. One-hundred percent crop treated
was assumed for all commodities in the chronic dietary exposure
iii. Cancer. EPA determines whether quantitative cancer exposure
and risk assessments are appropriate for a food-use pesticide based on
the weight of the evidence from cancer studies and other relevant data.
If quantitative cancer risk assessment is appropriate, cancer risk may
be quantified using a linear or nonlinear approach. If sufficient
information on the carcinogenic mode of action is available, a
threshold or nonlinear approach is used and a cancer RfD is calculated
based on an earlier noncancer key event. If carcinogenic mode of action
data are not available, or if the mode of action data determines a
mutagenic mode of action, a default linear cancer slope factor approach
is utilized. Based on the data summarized in Unit III.A., EPA has
concluded that fenbuconazole should be classified as ``Possibly
Carcinogenic to Humans'' and a linear approach has been used to
quantify cancer risk.
In its assessment of dietary cancer risk, EPA used the same residue
levels as described for the chronic assessment. EPA also assumed 100%
crop treated, except for the percent crop treated estimates described
in Unit III.C.1.iv., below.
iv. Anticipated residue and percent crop treated (PCT) information.
Section 408(b)(2)(E) of 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 residues that have been
measured in food. If EPA relies on such information, EPA must require
pursuant to FFDCA section 408(f)(1) 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. For the present action, EPA will issue such Data Call-Ins
as are required by FFDCA section 408(b)(2)(E) and authorized under
FFDCA section 408(f)(1). Data will be required to be submitted no later
than 5 years from the date of issuance of these tolerances.
Section 408(b)(2)(F) of FFDCA states that the Agency may use data
on the actual percent of food treated for assessing chronic dietary
risk only if:
Condition a: 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 the pesticide residue.
Condition b: The exposure estimate does not underestimate
exposure for any significant subpopulation group.
Condition c: Data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area.
In addition, the Agency must provide for periodic evaluation of any
estimates used. To provide for the periodic evaluation of the estimate
of PCT as required by FFDCA section 408(b)(2)(F), EPA may require
registrants to submit data on PCT.
The Agency estimated the PCT for existing uses as follows for the
cancer assessment: Almonds: 5%; apples: 5%; apricots: 5%; blueberries:
55%; cherries: 15%; grapefruit: 40%; nectarines: 5%; oranges: 5%;
peaches: 15%; pecans: 10%; plums/prunes: 1%; sugar beets: 1%; tangelos:
10%; tangerines: 1%.
In most cases, EPA uses available data from United States
Department of Agriculture/National Agricultural Statistics Service
(USDA/NASS), proprietary market surveys and the National Pesticide Use
Database for the chemical/crop combination for the most recent 6-7
years. EPA uses an average PCT for chronic dietary risk analysis. The
average PCT figure for each existing use is derived by combining
available public and private market survey data for that use, averaging
across all observations, and rounding to the nearest 5%, except for
those situations in which the average PCT is less than one. In those
cases, 1% is used as the average PCT and 2.5% is used as the maximum
PCT. EPA uses a maximum PCT for acute dietary risk analysis. The
maximum PCT figure is the highest observed maximum value reported
within the recent 6 years of available public and private market survey
for the existing use and rounded up to the nearest multiple of 5%.
The Agency believes that the three conditions discussed in Unit
III.C.1.iv. have been met. With respect to Condition a, PCT estimates
are derived from Federal and private market survey data, which are
reliable and have a valid basis. The Agency is reasonably certain that
the percentage of the food treated is not likely to be an
underestimation. As to Conditions b and c, regional consumption
information and consumption information for significant subpopulations
are 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 reliable information on the
regional consumption of food to which fenbuconazole may be applied in a
2. Dietary exposure from drinking water. The Agency used screening-
level water exposure models in the dietary exposure analysis and risk
assessment for fenbuconazole in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of fenbuconazole. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of
fenbuconazole for acute exposures are estimated to be 24.1 parts per
billion (ppb) for surface water and 0.031 ppb for ground water, for
chronic exposures for non-cancer assessments are estimated to be 16.5
ppb for surface water and 0.031 ppb for ground water, and for chronic
exposures for cancer assessments are estimated to be 11.7 ppb for
surface water and 0.031 ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 24.1 ppb was used to
assess the contribution from drinking water. For chronic dietary risk
assessment, the water concentration of value 16.5 ppb was used to
assess the contribution from drinking water. For cancer dietary risk
assessment, the water concentration of value 11.7 ppb was used to
assess the contribution from drinking 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 any specific use patterns that would result in
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of 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.''
Fenbuconazole is a member of the triazole-containing class of
pesticides. Although conazoles act similarly in fungi by inhibiting
ergosterol biosynthesis, there is not necessarily a relationship
between their pesticidal activity and their mechanism of toxicity in
mammals. Structural similarities do not constitute a common mechanism
of toxicity. Evidence is needed to establish that the chemicals operate
by the same, or essentially the same, sequence of major biochemical
events. In conazoles, however, a variable pattern of toxicological
responses is found: Some conazoles are hepatotoxic and
hepatocarcinogenic in mice, some induce thyroid tumors in rats, and
some induce developmental, reproductive, and neurological effects in
rodents. Furthermore, the conazoles produce a diverse range of
biochemical events including altered cholesterol levels, stress
responses, and altered DNA methylation. It is not clearly understood
whether these biochemical events are directly connected to their
toxicological outcomes. Thus, there is currently no evidence to
indicate that conazoles share common mechanisms of toxicity and EPA is
not following a cumulative risk approach based on a common mechanism of
toxicity for the conazoles. For information regarding EPA's procedures
for cumulating effects from substances found to have a common mechanism
of toxicity, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
Fenbuconazole is a triazole-derived pesticide. This class of
compounds can form the common metabolite 1,2,4-triazole as well as the
common triazole conjugates (triazolylalanine, triazolylacetic acid, and
triazolylpyrivic acid). To support existing tolerances and to establish
new tolerances for triazole-derivative pesticides, including
fenbuconazole, EPA conducted human health risk assessments for exposure
to 1,2,4-triazole and the common triazole conjugates resulting from the
use of all current and pending uses of any triazole-derived fungicide.
The risk assessment is a highly conservative, screening-level
evaluation in terms of hazards associated with common metabolites
(e.g., use of a maximum combination of uncertainty factors) and
potential dietary and non-dietary exposures (i.e., high end estimates
of both dietary and non-dietary exposures). The assessment includes
evaluations of risks for various subgroups, including those comprised
of infants and children. The Agency's complete risk assessment is found
in the propiconazole reregistration docket at http://www.regulations.gov, docket identification (ID) number EPA-HQ-OPP-2005-
Aggregate risk from exposure to the common triazole metabolites
were recently estimated by the Agency (1 May 2013) and found to be not
of concern. An updated dietary exposure and risk analysis for the
common triazole metabolites 1,2,4-triazole (T), triazolylalanine (TA),
triazolylacetic acid (TAA), and triazolylpyruvic acid (TP), reflecting
the revised tolerance for residues of fenbuconazole in/on pepper was
completed on May 21, 2013. Given that the updated dietary risk estimate
increased by less than 1% relative to the previous assessment, new
aggregate risk estimates were not made, and aggregate risk estimates
for the common triazole metabolites remain below the Agency's level of
concern. These documents may be found on http://www.regulations.gov by
searching for the following titles and docket numbers: ``Common
Triazole Metabolites: Updated Aggregate Human Health Risk Assessment to
Address The New Section 3 Registrations For Use of Prothioconazole on
Bushberry Crop Subgroup 13-07B, Low Growing Berry, Except Strawberry,
Crop Subgroup 13-07H, and Cucurbit Vegetables Crop Group 9; Use of
Flutriafol on Coffee; and Ipconazole on Crop Group 6'' (located in
docket ID number EPA-HQ-OPP-2012-0876) and ``Common Triazole
Metabolites: Updated Dietary (Food + Water) Exposure and Risk
Assessment to Address the Revised
Tolerance for Residues of Fenbuconazole in Peppers'' (docket ID number
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA Safety
Factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
2. Prenatal and postnatal sensitivity. In the rat and rabbit
developmental toxicity studies and the 2-generation study in rats, all
effects in the pups occurred in the presence of maternal toxicity,
including changes in body weight and body weight gains in rats and
decreased food consumption and clinical signs in rabbits. Developmental
effects included increased post-implantation loss and decreased live
fetuses per dam in the rat developmental study; increased early
resorptions in the rabbit developmental study; and decreased mean pup
body weight, increased number of stillborn pups, decreased number of
total offspring delivered, and decreased viability index of pups in the
two generation study in rats. No increased qualitative or quantitative
susceptibility was observed in any of the studies. In the rat
developmental toxicity study, although a decrease in the number of live
fetuses per litter was observed at the LOAEL, this effect was due
largely to reduced implantation sites, which may reflect maternal
toxicity. Additionally, the increases in postimplantation loss and
early resorptions were marginal at the LOAEL. Therefore, the findings
in this study were not considered indicative of increased offspring
susceptibility. In the rabbit developmental study, developmental
effects were observed at a higher dose than maternal effects. In the
rat reproduction study, effects on pup viability were observed at a
dose that resulted in maternal mortality during delivery. There was no
evidence of neurotoxicity in any of the studies available in the
toxicology database. Therefore, a developmental neurotoxicity study is
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1x. That decision is based on the following
i. The toxicity database is complete, except for an immunotoxicity
study; however, due to the lack of any evidence of immunotoxicity based
upon the available studies, EPA does not believe that an immunotoxicity
study will result in a lower point-of-departure than those being relied
upon for the present risk assessments. Therefore, an uncertainty factor
is not required to account for the lack of this study.
ii. There is no evidence of neurotoxicity in the available
database, and a developmental neurotoxicity study is not required.
iii. There is no evidence that fenbuconazole results in increased
susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the 2-generation reproduction
iv. There are no residual uncertainties identified in the exposure
databases. The acute dietary exposure assessment is a screening-level
assessment, utilizing tolerance-level residues and assuming 100% crop
treated. The chronic dietary exposure assessment is slightly refined,
utilizing some tolerance-level residues and some average residue levels
from crop field trials and assuming 100% crop treated. The cancer
dietary exposure assessment is also slightly refined, utilizing the
same residue estimates as for the chronic assessment and some percent
crop treated estimates. EPA made conservative (protective) assumptions
in the ground water and surface water modeling used to assess exposure
to fenbuconazole in drinking water. There are no registered residential
uses for fenbuconazole. These assessments will not underestimate the
exposure and risks posed by fenbuconazole.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA
calculates the lifetime probability of acquiring cancer given the
estimated aggregate exposure. Short-, intermediate-, and chronic-term
risks are evaluated by comparing the estimated aggregate food, water,
and residential exposure to the appropriate PODs to ensure that an
adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. The only population subgroup that is relevant for an
acute assessment is females of child-bearing age (i.e., females 13-49
years old). The acute risk estimate that results from this analysis is
2.9% of the acute population adjusted dose (aPAD) at the 95th
percentile of exposure. This risk estimate is considerably lower than
EPA's level of concern (100% of the aPAD).
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
fenbuconazole from food and water will utilize 6.7% of the cPAD for
children 1-2 years old, the population group receiving the greatest
exposure. There are no residential uses for fenbuconazole.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). For
fenbuconazole, there are no residential uses and therefore a short-term
aggregate risk assessment was not needed.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). There are no residential uses for fenbuconazole at this time,
therefore an intermediate-term risk assessment was not needed.
5. Aggregate cancer risk for U.S. population. Fenbuconazole is
classified as a Group C (possible human) carcinogen under the Agency's
1986 Cancer Guidelines, based on increased incidences of liver tumors
in male and female mice and thyroid tumors in male rats. Using the
conservative exposure assumptions described in this unit for cancer
risk from chronic exposure and an upper bound estimate of unit risk
(Q1*) of 3.59 x 10-3 (mg/kg/day)-1,
EPA has derived a cancer risk estimate of 2.2 x 10-6 from
dietary exposure to fenbuconazole.
EPA generally considers cancer risks (expressed as the probability
of an increased cancer case) in the range of 1 in 1 million (or 1 x
10-6) or less to be negligible. The precision which can be
assumed for cancer risk estimates is best described by rounding to the
nearest integral order of magnitude on the logarithmic scale; for
example, risks falling between 3 x 10-7 and 3 x
10-6 are expressed as risks in the range of 10-6.
Considering the precision with
which cancer hazard can be estimated, the conservativeness of low-dose
linear extrapolation, and the rounding procedure described in this
unit, cancer risk should generally not be assumed to exceed the
benchmark level of concern of the range of 10-6 until the
calculated risk exceeds approximately 3 x 10-6. This is
particularly the case where some conservatism is maintained in the
exposure assessment. Although the fenbuconazole exposure risk
assessment is somewhat refined, it retains significant conservatism in
that the analysis relies on field trial data and assumes 100% crop
treated for many commodities. Accordingly, EPA has concluded the
aggregate cancer risk for all existing fenbuconazole uses and the uses
associated with the tolerances established in this action fall within
the range of 1 x 10-6 and are thus negligible.
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 or to infants and children from aggregate
exposure to fenbuconazole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (GC/NPD method, TR 34-940-47 and
TR34-90-47R) is available to enforce the tolerance expression.
The method may be requested from: Chief, Analytical Chemistry
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD
20755-5350; telephone number: (410) 305-2905; email address:
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nations
Food and Agriculture Organization/World Health Organization food
standards program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has established an MRL for fenbuconazole in or on pepper
at 0.6 ppm. This MRL is different than the tolerance established for
fenbuconazole in the United States. The Codex MRL for pepper was most
likely established before the Enable[supreg] 2F formulation was
proposed for use on peppers and includes only residues of the parent
compound. This new formulation has higher residues values ranging up to
0.7 ppm, and the U.S. tolerance includes the two lactone metabolites.
Harmonization with the 0.6 ppm tolerance is not feasible given the
proposed new use pattern/formulation and the observed residue levels.
C. Response to Comments
EPA received a comment to the notice of filing which said that
residue levels of fenbuconazole should not be raised. The Agency
understands the commenter's concerns and recognizes that some
individuals believe that pesticides should be banned on agricultural
corps. However, the existing legal framework provided by section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA) states that tolerances
may be set when persons seeking such tolerances or exemptions have
demonstrated that the pesticide meets the safety standard imposed by
that statute. This citizen's comment appears to be directed at the
underlying statute and not EPA's implementation of it; the citizen has
made no contention that EPA has acted in violation of the statutory
Therefore, tolerances are modified to establish residues of
fenbuconazole in or on pepper at 1.0 ppm. Consistent with the petition
and EPA's policy for clarifying its tolerance expressions, EPA is
revising the tolerance expression for fenbuconazole to clarify that the
tolerance includes metabolites and degradates of fenbuconazole and that
compliance with the tolerance levels specified in the table is to be
determined by measuring only the sum of fenbuconazole, alpha-[2-(4-
propanenitrile, and its metabolites RH-;9129, cis-5-(4-chlorophenyl)-
dihydro-3-phenyl-3-(1H-1,2,4-triazole-1-ylmethyl)-2-3 H-furanone, and
triazole-1-ylmethyl)-2-3 H-furanone, calculated as the stoichiometric
equivalent of fenbuconazole,
VI. Statutory and Executive Order Reviews
This final rule establishes a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled ``Regulatory Planning and
Review'' (58 FR 51735, October 4, 1993). Because this final rule has
been exempted from review under Executive Order 12866, this final rule
is not subject to Executive Order 13211, entitled ``Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any
special considerations under Executive Order 12898, entitled ``Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations'' (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under FFDCA section 408(d), 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.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
as described under Title II of the Unfunded Mandates Reform Act of 1995
(UMRA) (2 U.S.C. 1501 et seq.).
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) (15 U.S.C. 272 note).
VII. Congressional Review Act
Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
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
the rule in the Federal Register. This action 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
Dated: June 21, 2013.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.480 revise paragraph (a) introductory text and revise
the entry ``Pepper'' in the table in paragraph (a) to read as follows:
Sec. 180.480 Fenbuconazole; tolerances for residues.
(a) Tolerances are established for residues of the fungicide
fenbuconazole, including its metabolites and degradates, in or on the
commodities in the table below. Compliance with the tolerance levels
specified below is to be determined by measuring only the sum of
1,2,4-triazole)-1-propanenitrile, and its metabolites RH-9129, cis-5-
H-furanone, and RH-9130, trans-5-(4-chlorophenyl)-dihydro-3-phenyl-3-
(1H-1,2,4-triazole-1-ylmethyl)-2-3 H-furanone, calculated as the
stoichiometric equivalent of fenbuconazole, in or on the following
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[FR Doc. 2013-15867 Filed 7-2-13; 8:45 am]
BILLING CODE 6560-50-P