[Federal Register Volume 76, Number 167 (Monday, August 29, 2011)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-21947]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Tetraconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
tetraconazole in or on multiple commodities which are identified and
discussed later in this document. In addition, EPA is removing the
existing grape tolerance because grape is now covered under the newly
established tolerance for small fruit vine climbing, except fuzzy
kiwifruit, subgroup 13-07F. The Interregional Research Project Number 4
(IR-4) requested these tolerances under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective August 29, 2011. Objections and
requests for hearings must be received on or before October 28, 2011,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2010-0583. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
FOR FURTHER INFORMATION CONTACT: Sidney Jackson, Registration Divison,
Office of Pesticide Programs, Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(703) 305-7610; e-mail address: firstname.lastname@example.org.
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 those
engaged in the following activities:
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 to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
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://ecfr.gpoaccess.gov/cgi/t/text/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-2010-0583 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
October 28, 2011. Addresses for mail and hand delivery of objections
and hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket. Information not marked confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA without prior notice. Submit a copy of
your non-CBI objection or hearing request, identified by docket ID
number EPA-HQ-OPP-2010-0583, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Summary of Petitioned-For Tolerance
In the Federal Register of September 8, 2010 (75 FR 54629) (FRL-
8843-3) and December 15, 2010 (75 FR 78240) (FRL-8853-1), EPA issued
notices pursuant to section 408(d)(3) of FFDCA, 21 U.S.C. 346a(d)(3),
announcing the filing of pesticide petitions (PP) 0E7735 by
Interregional Research Project Number 4 (IR-4), IR-4 Project
Headquarters, 500 College Road East, Suite 201 W, Princeton, NJ 08450,
and (PP) 0F7737 by Isagro S.p.A., 430 Davis Drive, Suite 240,
Morrisville, NC 27560, respectively. The petitions requested that 40
CFR 180.557 be amended by establishing tolerances for residues of the
fungicide tetraconazole, 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-
tetrafluoroethoxyl)propyl]-1H-1,2,4-triazole, in or on small fruit vine
climbing, except fuzzy kiwifruit, subgroup 13-07F at 0.20 parts per
million (ppm); and low growing berry, subgroup 13-07G at 0.25 ppm
(0E7735), and corn, field, forage; corn field, grain; corn, field,
stover; corn pop, grain; and corn, pop, stover at 1.0, 0.01, 1.5, 0.01
and 1.5 ppm, respectively (0F7737). Each notice referenced a summary of
the petition prepared by Isagro, USA, the registrant, which is
available in the docket, http://www.regulations.gov. There were no
comments received in response to the notices of filing. Based upon
review of all available data supporting the petitions, EPA made the
1. Revised the tolerance expression in Sec. 180.557(a), and
corrected commodities name.
2. Revised proposed tolerance levels for corn, field, forage; corn,
field, stover; and corn, pop, stover.
3. EPA is also revising established tolerance levels for milk;
milk, fat; poultry, meat by-products, and fat, liver, and meat by-
products of cattle, goat, horse and sheep based on the proposed
tolerances and revisions to existing feed commodity tolerances.
4. EPA is removing the existing grape tolerance because grape is
covered under the newly established tolerance for small fruit vine
climbing, except fuzzy kiwifruit, subgroup 13-07F.
The reasons for these changes are explained 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 section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of 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 for tetraconazole including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with tetraconazole
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
Tetraconazole has low acute toxicity via the oral, dermal, and
inhalation routes. It is a slight eye irritant, but is not a dermal
irritant or a dermal sensitizer. The liver and kidney are the primary
target organs of tetraconazole in mice, rats and dogs. Toxicity in
these organs occurred following 28-day, 90-day, and 1- to 2-year oral
For chronic durations, the dog was the most sensitive species,
followed by the mouse, and then the rat. Chronic toxicity in the dog
included increased absolute and relative kidney weights and
histopathological changes in the male kidney (cortical tubular
hypertrophy) which were observed at the mid-dose. At the high dose,
liver effects were observed in both sexes. In the mouse, effects
included increased liver weights, hepatocellular vacuolization in both
sexes, and increased kidney weights in males. In rats, several effects
not related to liver and kidney toxicity were observed. These included
histopathological changes of the bone, pale and thickened incisors,
decreased absolute and relative adrenal and pituitary weights in males,
and decreased body weight (at terminal sacrifice) in females.
Centrilobular hepatocyte hypertrophy was observed in the high-dose
groups for both sexes in this study.
Oral rat and rabbit prenatal developmental studies showed no
increased quantitative susceptibility of the fetus to tetraconazole
exposure in utero. In the developmental toxicity study in rats, the
maternal toxicity was manifested as decreased body weight gain, food
consumption, increased water intake, increased liver and kidney
weights. There were developmental effects in rats which suggested
qualitative susceptibility. They consisted of increased incidences of
supernumerary ribs, and increased incidences of hydroureter and
hydronephrosis, which exceeded the high end value of the historical
control range. No developmental toxicity was seen in the rabbit study.
The sole maternal effect in this rabbit study was decreased body weight
gain which occurred at the highest dose tested.
A 2-generation rat reproduction study also revealed no increased
quantitative susceptibility in offspring. Parental toxicity resulted in
increased mortality in females of the P and F1 generations
at the mid dose. This increase in mortality had a higher incidence at
the highest dose tested. Effects in parental animals that survived the
duration of the study were consistent with other studies in the
database including decreased body-weight gain and food consumption
during pre-mating, increased relative liver and kidney weights, and
hepatocellular hypertrophy in males and females at the lowest-observed
adverse-effect levels (LOAELs).
There were signs of neurotoxicity in the acute neurotoxicity study.
no evidence of neurotoxicity in any of the other studies in the
toxicity database for tetraconazole. In the absence of specific
immunotoxicity studies, EPA has evaluated the available tetraconazole
toxicity database to determine whether an additional database
uncertainty factor (UFDB) is needed to account for potential
immunotoxicity. No evidence of immunotoxicity was found.
There were no systemic effects observed in the 21-day dermal
toxicity study up to the highest dose used. In the 28-day inhalation
study in rats, toxicity was observed at the lowest concentration/dose.
At the highest concentration tested, there were treatment-related
increases in absolute lung weights in both sexes. There were also
treatment-related increases in absolute and relative liver weights in
males. In the kidney, there were treatment-related increases in
absolute and relative kidney and adrenal gland weights in females. In
females there was a treatment-related statistically-significant
increase in circulating globulins at the mid and high concentrations.
Finally in the kidney, at the highest concentration tested, there was a
50% increase in the incidence of tubular hyaline droplets with features
characteristic of [alpha]-2 microglobulin. This was observed only in
males, and this effect is not considered relevant to humans.
Tetraconazole did not show evidence of mutagenicity in in vitro or
in vivo studies. Carcinogenicity studies with tetraconazole resulted in
an increased incidence of combined benign and malignant liver tumors in
mice of both sexes. In contrast to mice, no tumors were noted in male
or female rats after long-term dietary administration of tetraconazole.
The Agency classified tetraconazole as ``likely to be carcinogenic to
humans'' by the oral route based on the occurrence of liver tumors in
male and female mice.
Specific information on the studies received and the nature of the
adverse effects caused by tetraconazole as well as the no-observed-
adverse-effect level (NOAEL) and the LOAEL from the toxicity studies
can be found at http://www.regulations.gov in document ``Tetraconazole:
Human-Health Risk Assessment for Proposed Uses of Small Fruit Vine
Climbing Subgroup 13-07F, Low-Growing Berry Subgroup 13-07G, and Field
Corn and Popcorn'' dated April 14, 2011 at pages 38-47 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 tetraconazole used for
human risk assessment is shown in the following Table.
Table--Summary of Toxicological Doses and Endpoints for Tetraconazole for Use in Dietary and Non-Occupational
Human Health Risk Assessment
Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological
factors assessment effects
Acute dietary (Females 13-50 years of NOAEL = 22.5 milligrams/ Acute RfD = 0.225 mg/kg/ Developmental toxicity
age). kilograms/day (mg/kg/ day. study in rats
day). aPAD = 0.225 mg/kg/day. Developmental LOAEL =
UFA = 10x.............. 100 mg/kg/day based on
UFH = 10x.............. increased incidence of
FQPA SF = 1x........... small fetuses,
and hydroureter and
Acute dietary (General population NOAEL = 50 mg/kg/day... Acute RfD = 0.5 mg/kg/ Acute neurotoxicity
including infants and children). UFA = 10x.............. day. (rat) LOAEL = 200 mg/
UFH = 10x.............. aPAD = 0.5 mg/kg/day... kg/day based on
FQPA SF = 1x........... decreased motor
activity on day 0 in
both sexes, and
clinical signs in
and/or red or yellow
material on various
Chronic dietary (All populations).... NOAEL= 0.73 mg/kg/day.. Chronic RfD = 0.0073 mg/ Chronic oral toxicity
UFA = 10x.............. kg/day. (dog) Developmental
UFH = 10x.............. cPAD = 0.0073 mg/kg/day LOAEL = 100 mg/kg/day
FQPA SF = 1x........... based on absolute and
changes in the male
Cancer (Oral, dermal, inhalation).... Classification: ``Likely to be Carcinogenic to Humans'' and report cancer
slope factor (Q1*) of 2.3 x 10-2 mg/kg/day derived from the male mouse
liver benign and/or malignant combined tumor rates.
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. PAD = population-
adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to tetraconazole, EPA considered exposure under the
petitioned-for tolerances as well as all existing tetraconazole
tolerances in 40 CFR 180.557. EPA assessed dietary exposures from
tetraconazole 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 tetraconazole. In estimating acute dietary exposure, EPA used food
consumption information from the United States Department of
Agriculture (USDA) 1994-1996 and 1998 Nationwide Continuing Surveys of
Food Intake by Individuals (CSFII). As to residue levels in food, EPA
assumed tolerance level residues and 100 percent crop treated (PCT) for
all existing and proposed uses.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA 1994-1996
and 1998 CSFII. As to residue levels in food, the chronic analysis
(food and water) was refined through the incorporation of empirical
processing factors, average field trial residues, average residues from
the feeding studies, and PCT estimates for sugar beet, peanut, field
corn and soybean.
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 non-linear 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 determine 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 tetraconazole should be classified as ``Likely to be
Carcinogenic to Humans'' and a linear approach has been used to
quantify cancer risk. The cancer analysis (food and water) was refined
through the incorporation of empirical processing factors, average
field trial residues, average residues from the feeding studies, and
projected PCT estimates for sugar beet, field corn, peanut, and
iv. Percent crop treated (PCT) information. 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 uses as follows: sugarbeet--70%; and
In most cases, EPA uses available data from the 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 1. 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
data for the existing use and rounded up to the nearest multiple of 5%.
The Agency estimated the PCT for as follows: field corn--9% and
soybean at 5%.
EPA estimates of the PCT for proposed new uses of tetraconazole
represent the upper bound of use expected during the pesticide's
initial 5 years of registration. Because soybean has not been
registered for 5 years, the Agency has treated it as a new use for
analyzing PCT. The PCT for new uses for use in the chronic dietary
assessment is calculated as the average PCT of the market leader or
leaders (i.e., the pesticides with the greatest PCT) on that site over
the three most recent years of available data. Comparisons are only
made among pesticides of the same pesticide type (e.g., the market
leader for fungicides on the use site is selected for comparison with a
new fungicide). The market leader included in the estimation may not be
the same for each year since different pesticides may dominate at
To evaluate whether the PCT estimate for tetraconazole could be
exceeded, EPA considered whether there may be unusually high pest
pressure, as indicated in emergency exemption requests for
tetraconazole; the pest spectrum of the new pesticide in comparison
with the market leaders and whether the market leaders are well
established for that use; and whether pest resistance issues with past
market leaders provide tetraconazole with significant market potential.
Given currently available information, EPA concludes that it is
unlikely that actual PCT for tetraconazole will exceed the estimated
PCT for new uses during the next 5 years.
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
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 reliable information on the regional consumption of
food to which tetraconazole may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for tetraconazole in drinking water.
These simulation models take into account data on the physical,
chemical, and fate/transport characteristics of tetraconazole. 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 (PRZM ver. 3.12.2) and
Exposure Analysis Modeling System (EXAMS ver. 2.98.04.06) and Screening
Concentration in Ground Water (SCI-GROW) models, ver. 2.3, the
estimated drinking water concentrations (EDWCs) of tetraconazole for
acute exposures are estimated to be 10.45 parts per billion (ppb) for
surface water and 0.40 ppb for ground water. Chronic exposures for non-
cancer assessments are estimated to be 4.68 ppb for surface water and
0.40 ppb for ground water. Chronic exposures for cancer assessments are
estimated to be 3.29 ppb for surface water and 0.40 ppb for ground
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 10.45 ppb was used to
assess the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 4.68 ppb was used to
assess the contribution to drinking water. For cancer dietary risk
assessment, the water concentration of value 3.29 ppb was used to
assess the contribution to 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). Tetraconazole 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.''
Tetraconazole is a member of the triazole-containing class of
pesticides. Although conazoles act similarly in plants (fungi) by
inhibiting ergosterol biosynthesis, there is not necessarily a
relationship between their pesticidal activity and their mechanism of
toxicity in mammals. Structural similarities do not constitute a common
mechanism of toxicity. Evidence is needed to establish that the
chemicals operate by the same, or essentially the same, sequence of
major biochemical events (EPA, 2002). In conazoles, however, a variable
pattern of toxicological responses is found; some are hepatotoxic and
hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some
induce developmental, reproductive, and neurological effects in
rodents. Furthermore, the conazoles produce a diverse range of
biochemical events including altered cholesterol levels, stress
responses, and altered DNA methylation. It is not clearly understood
whether these biochemical events are directly connected to their
toxicological outcomes. Thus, there is currently no evidence to
indicate that conazoles share common mechanisms of toxicity and EPA is
not following a cumulative risk approach based on a common mechanism of
toxicity for the conazoles. For information regarding EPA's procedures
for cumulating effects from substances found to have a common mechanism
of toxicity, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
Triazole-derived pesticides can form the common metabolite T and
two triazole conjugates (TA and TAA). To support existing tolerances
and to establish new tolerances for triazole-derivative pesticides,
including tetraconazole, EPA conducted a human-health risk assessment
for exposure to T, TA, and TAA 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). In addition, the Agency retained the additional 10X
FQPA SF for the protection of infants and children. 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-2005-0497, and an update to assess the addition of the commodities
included in this action may be found in docket ID EPA-HQ-OPP-2010-0583
in the document titled ``Common Triazole Metabolites, Updated Aggregate
Human-Health Risk Assessment to address tolerance petitions for
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. There are no residual
uncertainties for pre- and post-natal toxicity. There is no evidence of
increased quantitative susceptibility of rat or rabbit fetuses to in
utero exposure to tetraconazole. There is evidence of increased
qualitative susceptibility to fetuses in the rat prenatal developmental
toxicity (increased incidences of supernumary ribs, and hydroureter and
hydronephrosis). The level of concern is low however because:
i. The fetal effects were seen at the same dose as the maternal
ii. A clear NOAEL was established.
iii. The developmental NOAEL from the study in rats is being used
as the POD for the acute dietary endpoint (females 13-49 years of age).
iv. There were no developmental effects in the rabbit study. There
is also no evidence of increased quantitative or qualitative
susceptibility to offspring in the 2-generation reproduction study.
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
findings: The toxicity database for tetraconazole is complete. The EPA
has recently received an immunotoxicity study for tetraconazole.
Preliminary review of the study shows no evidence of immunotoxicity and
does not impact the selection of endpoints. EPA believes the existing
data are sufficient for endpoint selection for exposure/risk assessment
scenarios and for evaluation of the requirements under the FQPA, and an
additional safety factor does not need to be applied.
i. There were effects indicative of neurotoxicity (motor activity
effects) in the acute neurotoxicity study in rats. However, the level
of concern is low for the following reasons:
A clear NOAEL was established which is being used in
Comparison of the LOAELs from the acute neurotoxicity and
chronic dog studies reveal a ~70-fold difference between the effects
from the two studies, with the chronic effects being the more sensitive
of the two.
Neither of the more severe endpoints indicative of
neurotoxicity (changes in brain weight or histopathological changes in
the brain or nerve processes) were observed in the acute neurotoxicity
study. Additionally, the EPA has recently received a subchronic
neurotoxicity study for tetraconazole. A preliminary review of this
study shows no signs of neurotoxicity. Furthermore, neurotoxicity was
not seen in any other study in the toxicity database for tetraconazole.
Therefore, there is no need for a developmental neurotoxicity study or
additional UFs to account for neurotoxicity.
ii. There is no evidence that tetraconazole results in increased
quantitative susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the 2-generation reproduction
study. There is evidence of increased qualitative susceptibility to
fetuses in the rat prenatal developmental toxicity (increased
incidences of supernumary ribs, and hydroureter and hydronephrosis).
The level of concern is low however because:
The fetal effects were seen at the same dose as the
A clear NOAEL was established.
The developmental NOAEL from the study in rats is being
used as the POD for the acute dietary endpoint (females 13-49 years of
There were no developmental effects in the rabbit study.
There is also no evidence of increased quantitative or qualitative
susceptibility to offspring in the 2-generation reproduction study.
iii. There are no residual uncertainties identified for pre- and
post-natal toxicity in the exposure databases. Tolerance-level
residues, 100% crop treated, and modeled water estimates were
incorporated into the acute dietary exposure analysis. Therefore, the
acute analysis is highly conservative. The chronic and cancer dietary
exposure analyses utilized empirical processing factors, average field
trial residues, average residues from the feeding studies, percent crop
treated estimates, and modeled drinking water estimates. A critical
commodity analysis for the chronic/cancer runs indicated that more than
half of the exposure was derived from water. The models upon which the
water estimates were based incorporate conservative (protective)
assumptions with actual concentrations likely to be significantly
lower. As a result, it can be concluded that the chronic/cancer risk
estimates provided in this document do not underestimate the risks
posed by tetraconazole.
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. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food and water
to tetraconazole will occupy 1.8% of the aPAD for children 1-2 years
old, the population group receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
tetraconazole from food and water will utilize 5% of the cPAD for all
infants < 1 year old, the population group receiving the greatest
exposure. There are no residential uses for tetraconazole.
3. Short-term risk and intermediate-term risks. Short-term and
intermediate-term aggregate risk takes into account short-term and
intermediate-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
A short-term and intermediate-term adverse effect was identified;
however, tetraconazole is not registered for any use patterns that
would result in short-term or intermediate-term residential exposure.
Short-term and intermediate-term risk is assessed based on short-term
and intermediate-term residential exposure plus chronic dietary
exposure. Because there is no short-term and intermediate-term
residential exposure and chronic dietary exposure has already been
assessed under the appropriately protective cPAD (which is at least as
protective as the POD used to assess short-term and intermediate-term
risk), no further assessment of short-term and intermediate-term risk
is necessary, and EPA relies on the chronic dietary risk assessment for
evaluating short-term and intermediate-term risk for tetraconazole.
4. Aggregate cancer risk for U.S. population. Using the exposure
assumptions described in Unit III.C.1.iii., EPA has concluded the
cancer risk from food and water for all existing and proposed
tetraconazole uses will result in a lifetime cancer risk of 3 x
10-6. A critical commodity analysis for the cancer/chronic
risk assessment indicated that water was the major contributor to the
estimated cancer risk (63% of total exposure). The drinking water
estimate incorporated into the cancer dietary assessment was based on
models which make conservative (protective) assumptions to derive a
concentration in ground and surface water. Actual concentrations are
likely to be significantly lower. EPA generally considers cancer risks
in the range of 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 log 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 above 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.
5. 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 tetraconazole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology is available to enforce the
tolerance expression currently established for tetraconazole plant and
livestock tolerances. As part of the corn petition, Isagro submitted
adequate method validation and independent laboratory validation (ILV)
data which indicate that the QuEChERS multi-residue method L 00.00-115
is capable of quantifying tetraconazole residues in or on a variety of
fruit, cereal grain, root, oilseed, and livestock commodities (note
that mean recoveries in or on wheat straw were 50-70%). Based on these
data and since the extraction
solvent employed in the QuEChERS method is similar to the extraction
solvent employed in the radiovalidated enforcement methods, the Agency
concludes that the QuEChERS method is adequate for enforcement of
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; e-mail 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 U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
There are no Canadian or Codex maximum residue limits (MRLs)
established for tetraconazole.
C. Revisions to Petitioned-For Tolerances
After completing review of the current tetraconazole database and
utilizing the Agency's tolerance spreadsheet (see Guidance for Setting
Tolerances Based on Field Trial Data SOP (August 2009 version)), EPA
revised, added or deleted tolerances, or otherwise modified the
tolerance levels proposed in the notices of filing. EPA is removing the
existing grape tolerance because grape is covered under the newly
established tolerance for small fruit vine climbing, except fuzzy
kiwifruit, subgroup 13-07F. The Agency corrected listings of certain
commodity names and replaced them with the preferred commodity terms.
In addition, the Agency revised existing tolerance levels for
tetraconazole residues in or on certain livestock commodities and
established the following tolerances: Cattle, fat at 0.15 ppm; cattle,
liver at 1.5 ppm; cattle, meat by-products, except liver at 0.15 ppm;
goat, fat at 0.15 ppm; goat, liver at 1.50 ppm; goat, meat by-product,
except liver at 0.15 ppm; horse, fat at 0.15 ppm; horse, liver at 1.50
ppm; horse, meat by-products, except liver at 0.15 ppm; milk at 0.03
ppm; milk, fat at 0.75 ppm; poultry, meat by-products at 0.05 ppm;
sheep, fat at 0.15 ppm; sheep, liver at 1.50 ppm; and sheep, meat by-
products, except liver at 0.15 ppm. Using resources defined above in
this section, the Agency revised tolerance levels for livestock
commodities because of increased livestock dietary exposure as a result
of newly established corn tolerances and to take into account all
tetraconazole residues in animal feed commodities.
Finally, the Agency is modifying the tolerance expression for
tetraconazole to clarify that, as provided in FFDCA section 408(a)(3),
the tolerance covers metabolites and degradates of tetraconazole not
specifically mentioned; and that compliance with the specified
tolerance levels is to be determined by measuring only the specific
compounds mentioned in the tolerance expression.
Therefore, tolerances are established for residues of
tetraconazole, including its metabolites and degradates, in or on the
commodities listed in the Table below under Sec. 180.557. Compliance
with the following tolerance levels is to be determined by measuring
only tetraconazole (1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under section 408(d) of
FFDCA in response to petitions submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Pub. L. 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: August 18, 2011.
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. Section 180.557 is amended by:
i. Revising the introductory text in paragraph (a);
ii. Removing the commodity ``Grape'' from the table in paragraph (a);
iii. Revising the tolerance level for these commodities: ``Cattle,
fat'' ``Cattle, liver'' ``Cattle, meat byproducts, except liver''
``Goat, fat'' ``Goat, liver'' ``Goat, meat byproducts, except liver''
``Horse, fat'' ``Horse, liver'' ``Horse, meat byproducts, except
liver'' ``Milk'' ``Milk, fat'' ``Poultry, meat byproducts'' ``Sheep,
fat'' ``Sheep, liver'' and ``Sheep, meat byproducts, except liver'' in
the table in paragraph (a); and
iv. Alphabetically adding the following commodities: ``Corn, field,
forage'' ``Corn, field, grain'' ``Corn, field, stover'' ``Corn, pop,
grain'' ``Corn, pop stover'' ``Low growing berry subgroup 13-07G,
except cranberry;'' and ``Small fruit vine climbing, except fuzzy
kiwifruit, subgroup 13-07F'' to the table in paragraph (a) to read as
Sec. 180.557 Tetraconazole; Tolerances for residues.
(a) General. Tolerances are established for residues of
tetraconazole, including its metabolites and degradates, in or on the
commodities listed below. Compliance with the following tolerance
levels is to be determined by measuring only tetraconazole (1-[2-(2,4-
triazole), in or on the following commodities.
* * * * *
Cattle, fat................................................. 0.15
Cattle, liver............................................... 1.50
* * * * *
Cattle, meat byproducts, except liver....................... 0.15
Corn, field, forage......................................... 1.1
Corn, field, grain.......................................... 0.01
Corn, field, stover......................................... 1.7
Corn, pop, grain............................................ 0.01
Corn, pop, stover........................................... 1.7
Goat, fat................................................... 0.15
Goat, liver................................................. 1.50
* * * * *
Goat, meat byproducts, except liver......................... 0.15
Horse, fat.................................................. 0.15
Horse, liver................................................ 1.50
* * * * *
Horse, meat byproducts, except liver........................ 0.15
Low growing berry subgroup 13-07G, except cranberry......... 0.25
Milk, fat................................................... 0.75
* * * * *
Poultry, meat byproducts.................................... 0.05
* * * * *
Sheep, fat.................................................. 0.15
Sheep, liver................................................ 1.50
* * * * *
Sheep, meat byproducts, except liver........................ 0.15
Small fruit vine climbing, except fuzzy kiwifruit, subgroup 0.20
* * * * *
* * * * *
[FR Doc. 2011-21947 Filed 8-26-11; 8:45 am]
BILLING CODE 6560-50-P