Document ID: EPA-HQ-OPP-2010-0583-0004
Agency: epa
Document Type: Rule
Title: Pesticide Tolerances: Tetraconazole
Posted Date: 2011-08-29T04:00Z

[Federal Register Volume 76, Number 167 (Monday, August 29, 2011)]
[Rules and Regulations]
[Pages 53641-53648]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-21947]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2010-0583; FRL-8885-1]

Tetraconazole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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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) 
305-5805.

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: jackson.sidney@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to 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 
INFORMATION CONTACT.

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.

[[Page 53642]]

     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 
following modifications:
    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 
follows.

A. Toxicological Profile

    EPA has evaluated the available toxicity data and considered its 
validity, completeness, and reliability, as well as the relationship of 
the results of the studies to human risk. EPA has also considered 
available information concerning the variability of the sensitivities 
of major identifiable subgroups of consumers, including infants and 
children.
    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 
exposures.
    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. 
There is

[[Page 53643]]

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 
number EPA-HQ-OPP-2010-0583-0004.

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
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                                        Point of departure and
          Exposure/scenario               uncertainty/safety     RfD, PAD, LOC for risk  Study and toxicological
                                               factors                 assessment                effects
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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,
                                                                                          supernumerary ribs,
                                                                                          and hydroureter and
                                                                                          hydronephrosis.
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
                                                                                          females including
                                                                                          hunched posture,
                                                                                          decreased defecation,
                                                                                          and/or red or yellow
                                                                                          material on various
                                                                                          body surfaces.
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
                                                                                          relative kidney
                                                                                          weights and
                                                                                          histopathological
                                                                                          changes in the male
                                                                                          kidney.
                                      --------------------------------------------------------------------------
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
  concern.

[[Page 53644]]

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 
soybean.
    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 
peanut--77%.
    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 
different times.
    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.

[[Page 53645]]

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 
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 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 
residential exposure.
    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 
Tetraconazole''.

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 
factor.
    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 
effects.
    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:

[[Page 53646]]

     A clear NOAEL was established which is being used in 
endpoint selection.
     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 
maternal effects.
     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 
age).
     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

[[Page 53647]]

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 
established tolerances.
    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: 
residuemethods@epa.gov.

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.

V. Conclusion

    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-
tetrafluoroethoxy)propyl]-1H-1,2,4-triazole).

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 
note).

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 
U.S.C. 804(2).

[[Page 53648]]

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: August 18, 2011.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority: 21 U.S.C. 321(q), 346a and 371.

0
2. Section 180.557 is amended by:
0
i. Revising the introductory text in paragraph (a);
0
ii. Removing the commodity ``Grape'' from the table in paragraph (a);
0
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
0
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 
follows:

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-
dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl]-1H-1,2,4-
triazole), in or on the following commodities.

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
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........................................................        0.03
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
 13-07F.....................................................
 
                                * * * * *
------------------------------------------------------------------------

* * * * *
[FR Doc. 2011-21947 Filed 8-26-11; 8:45 am]
BILLING CODE 6560-50-P