[Federal Register: November 14, 2008 (Volume 73, Number 221)]
[Rules and Regulations]
[Page 67400-67406]
[DOCID:fr14no08-19]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2007-1161; FRL-8386-7]

Tetraconazole; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for residues of
tetraconazole in or on grape. Interregional Research Project Number 4
(IR-4) requested this tolerance under the Federal Food, Drug, and
Cosmetic Act (FFDCA).

DATES: This regulation is effective November 14, 2008. Objections and
requests for hearings must be received on or before January 13, 2009,
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-2007-1161. 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<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Susan Stanton, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number:<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>
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 Access Electronic Copies of this Document?

    In addition to accessing electronically available documents at
http://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at http://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of EPA's tolerance regulations
at 40 CFR part 180 through the Government Printing Office's e-CFR site
at http://www.gpoaccess.gov/ecfr.

C. Can I File an Objection or Hearing Request?

    Under section 408(g) of FFDCA, 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-2007-1161 in the subject line on the first
page of your submission. All requests must be in writing, and must be
mailed or delivered to the Hearing Clerk as required by 40 CFR part 178
on or before January 13, 2009.
    In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2007-1161, 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<PHONE_NUMBER>.

II. Petition for Tolerance

    In the Federal Register of January 23, 2008 (73 FR 3964) (FRL-8345-
7), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
7E7273) by Interregional Research Project Number 4 (IR-4), 500 College
Road East, Suite 201 W, Princeton, NJ 08540. The petition requested
that 40 CFR 180.557 be amended by establishing a tolerance for residues
of the fungicide tetraconazole, 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-
tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, in or on grape at 0.15
parts per million (ppm). That notice referenced a summary of the
petition prepared on behalf of IR-4 by Isagro, S.p.A, the registrant,
which is available to the public in the docket, at http://
www.regulations.gov. There were no comments received in response to the
notice of filing.
    Based upon review of the data supporting the petition, EPA has
revised the tolerance level for grape from 0.15 ppm to 0.20 ppm. The
reason for this change is 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 the petitioned-for
tolerance for residues of tetraconazole on grape at 0.20 ppm. EPA's
assessment of exposures and risks associated with establishing
tolerances 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 not a dermal
irritant or a dermal sensitizer. The liver and kidney are the primary
target organs of tetraconazole. In the subchronic, chronic and
reproduction rat studies, subchronic and carcinogenicity mouse studies,
and the chronic dog study, increases in liver weight, increases in
liver serum enzymes or gross and microscopic liver pathology were noted
at various doses, providing evidence of liver toxicity. There is no
evidence in the toxicity database that tetraconazole is an immuno- or
neurotoxicant.
    Tetraconazole is classified as ``likely to be carcinogenic to
humans'' by the oral route of exposure, based on the occurrence of
liver tumors in male and female mice. Cancer risk is assessed by EPA
using the linear low dose extrapolation approach with a potency factor
(Q1*) of 2.3 x 10-2 milligrams/kilograms/day (mg/
kg/day)-1.
    Oral rat and rabbit developmental toxicity studies showed no
increased susceptibility of fetuses to tetraconazole. Maternal toxicity
(decreased body weight gain and food consumption, increased water
intake and increased liver and kidney weights) and developmental
toxicity (increased incidence of small fetuses, supranumerary ribs and
hydroureter and hydronephrosis) occurred at the same dose level in the
rat study. No developmental toxicity was seen in the rabbit study,
whereas maternal toxicity (decreased body weight gain) was noted at the
highest dose tested. Similarly, there was no evidence of increased
susceptibility of offspring in the 2-generation rat reproduction study.
Parental toxicity (increased mortality in parental females) was
observed at a lower dose (4.9 mg/kg/day) than the dose (35.5 mg/kg/day)
resulting in pup effects (decreased litter weight and mean pup weight
in litters of all generations before weaning and increased relative
liver weight at weaning in both sexes of all litters).
    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 lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://
www.regulations.gov in the document Tetraconazole: Human-Health Risk
Assessment for New Use on Grapes and a Label Amendment for Pecans, page
34 in docket ID number EPA-HQ-OPP-2007-1161.

B. Toxicological Endpoints

    For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
dietary risks by comparing aggregate food and water exposure to the
pesticide to the acute population adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The aPAD and cPAD are calculated by
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
    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
greater than that 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 can be found at http://www.regulations.gov in the
document Tetraconazole: Human-Health Risk Assessment for New Use on
Grapes and a Label Amendment for Pecans, page 12 in docket ID number
EPA-HQ-OPP-2007-1161.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to tetraconazole, EPA considered exposure under the
petitioned-for tolerance as well as all existing tetraconazole
tolerances in 40 CFR 180.557. Additional metabolites of toxicological
concern (M14360-alcohol (free and conjugated), M14360-acid, M14360-DFA,
and M14360-hydroxydetriazolyl-O-malonyldiglucoside) that are not
included in the tolerance expression were included in the dietary
exposure assessments based on the ratio of metabolite to parent found
in metabolism studies. 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. EPA identified such effects
(increased incidence of small fetuses and supernumerary ribs) for the
population subgroup, females 13 years and older; however, no such
effects were identified for the general population, including infants
and children.
    In estimating acute dietary exposure, EPA used food consumption
information from the United States Department of Agriculture (USDA)
1994-1996 Nationwide Continuing Surveys of Food Intakes by Individuals
(CSFII). As to residue levels in food, EPA assumed tolerance-level
residues of tetraconazole and 100 percent crop treated (PCT) for all
existing and new 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. The assessment was refined through the incorporation of
empirical processing factors, average field trial residues, average
residues from the feeding studies and projected percent crop treated
(PPCT) estimates for the feed commodities. 100 PCT was assumed for all
food commodities.
    iii. Cancer. Tetraconazole is classified as ``likely to be
carcinogenic to humans'' by the oral route of exposure. Cancer risk
from tetraconazole exposure is assessed by EPA using the linear low
dose extrapolation approach with a potency factor (Q1*) of
2.3 x 10-2 (mg/kg/day)-1. EPA used the same food
residue estimates as discussed in Unit III.C.1.ii., chronic exposure.
    iv. Anticipated residue and PCT information. Section 408(b)(2)(E)
of FFDCA authorizes EPA to use available data and information on the
anticipated residue levels of pesticide residues in food and the actual
levels of pesticide residues that have been measured in food. If EPA
relies on such information,

EPA must require pursuant to section 408(f)(1) of FFDCA that data be
provided 5 years after the tolerance is established, modified, or left
in effect, demonstrating that the levels in food are not above the
levels anticipated. For the present action, EPA will issue such Data
Call-Ins as are required by section 408(b)(2)(E) of FFDCA and
authorized under section 408(f)(1) of FFDCA. Data will be required to
be submitted no later than 5 years from the date of issuance of these
tolerances.
    Section 408(b)(2)(F) of FFDCA states that the Agency may use data
on the actual percent of food treated for assessing chronic dietary
risk only if:
     Condition a: The data used are reliable and provide a
valid basis to show what percentage of the food derived from such crop
is likely to contain the pesticide residue.
     Condition b: The exposure estimate does not underestimate
exposure for any significant subpopulation group.
     Condition c: Data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area.
    In addition, the Agency must provide for periodic evaluation of any
estimates used. To provide for the periodic evaluation of the estimate
of PCT as required by section 408(b)(2)(F) of FFDCA, EPA may require
registrants to submit data on PCT.
    The Agency used projected percent crop treated (PPCT) information
as follows:
    In the chronic and cancer dietary assessments, EPA used PPCT for
the feed commodities derived from peanuts (77%), soybeans (27%) and
sugar beets (70%). Since tetraconazole was registered for use on these
crops recently (2007 and 2008), PCT estimates based on actual usage
data are not sufficient indicators of potential usage on these crops.
    EPA estimates PPCT for a new pesticide use by assuming that the PCT
during the pesticide's initial 5 years of use on a specific use site
will not exceed the average PCT of the market leader (i.e., the one
with the greatest PCT) on that site. Typically, EPA uses USDA/National
Agriculture Statistic Service (NASS) as the primary source for PCT
data. When a specific use site is not surveyed by USDA/NASS, EPA uses
other sources, including proprietary data, and calculates the PCT.
Comparisons are only made among pesticides of the same pesticide types
(i.e., the leading fungicide on the use site is selected for comparison
with the new fungicide). The PCTs included in the average may be for
the same pesticide, or for different pesticides, since the same, or
different pesticides, may dominate for each year selected. This PPCT,
based on the average PCT of the market leader, is appropriate for use
in chronic dietary risk assessment. The method of estimating a PPCT for
a new use of a registered pesticide or a new pesticide produces a high-
end estimate that is unlikely, in most cases, to be exceeded during the
initial 5 years of actual use. The predominant factors that bear on
whether the estimated PPCT could be exceeded are whether a new
pesticide use or new pesticide is more efficacious or controls a
broader spectrum of pests than the dominant pesticide; and/or whether
there are concerns with pest pressures as indicated in emergency
exemption requests or other readily available information; and/or other
factors based on analysis of additional information, such as the total
crop acreage and the geographical distribution of the crops and pests.
All information currently available for the predominant factors
mentioned above or relevant to the case in question have been
considered for this chemical, and EPA has determined that it is
unlikely that actual PCT for tetraconazole will exceed the PPCT 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's
drinking water models used in pesticide exposure assessment can be
found at http://www.epa.gov/oppefed1/models/water/index.htm.
    Based on the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of
tetraconazole for acute exposures are estimated to be 10.45 parts per
billion (ppb) for surface water and 0.40 ppb for ground water. For
chronic exposures for non-cancer assessments, EDWCs are estimated to be
4.68 ppb for surface water and 0.40 ppb for ground water. For chronic
exposures for cancer assessments, EDWCs 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 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 necessarily 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 efforts to determine which chemicals have a common mechanism of
toxicity and to evaluate the cumulative effects of such chemicals, see
EPA's website at http://www.epa.gov/pesticides/cumulative.
    Tetraconazole is a triazole-derived pesticide. This class of
compounds can form the common metabolite, 1,2,4-triazole (T), and
several triazole conjugates, including triazole alanine (TA) and
triazole acetic acid (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 was
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 safety factor
for the protection of infants and children. The assessment included
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 ID EPA-HQ-OPP-2005-0497). In March of 2008,
EPA updated the triazole risk assessment to include new uses of
fenbuconazole, ipconazole, metconazole, tebuconazole and uniconazole.
The updated risk assessment can be found at http://www.regulations.gov
in the document Dietary Exposure Assessments for the Common Triazole
Metabolites 1,2,4-Triazole, Triazolylalanine, Triazolylacetic Acid, and
Triazolylypyruvic Acid; Updated to Include New Uses of Fenbuconazole,
Ipconazole, Metconazole, Tebuconazole, and Uniconazole; and a Change in
Plant-back Restriction for Tetraconazole in docket ID number EPA-HQ-
OPP-2007-1199. When EPA updated the triazole risk assessment, it
considered triazole residues on grapes, because other triazole
fungicides are already registered for this use site. Triazole residues
on grapes from the use of tetraconazole are not expected to exceed
those from the use of other triazole fungicides on grapes; therefore,
establishing this tolerance for tetraconazole on grape will not
increase aggregate exposure to the triazole metabolites, and an updated
triazole risk assessment is unnecessary.

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. The pre- and postnatal
toxicology database for tetraconazole includes rat and rabbit
developmental toxicity studies and a 2-generation reproduction toxicity
study in rats. As discussed in section III.A, Toxicological Profile,
there was no evidence of increased susceptability to tetraconazole of
in utero rats or rabbits or offspring in these studies. In the rat
developmental toxicity study, maternal and developmental toxicity
occurred at the same dose, and in the rabbit study, no developmental
toxicity was seen at doses that resulted in maternal toxicity. In the
rat reproduction study, parental toxicity was observed at a lower dose
than that which resulted in pup effects.
    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:
    i. The toxicity database for tetraconazole is complete, except for
immunotoxicity testing. EPA began requiring functional immunotoxicity
testing of all food and non-food use pesticides on December 26, 2007.
Since this requirement went into effect well after the tolerance
petition was submitted, these studies are not yet available for
tetraconazole. In the absence of specific immunotoxicity studies, EPA
has evaluated the available tetraconazole toxicity data to determine
whether an additional database uncertainty factor is needed to account
for potential immunotoxicity. There was no evidence of adverse effects
on the organs of the immune system at the LOAEL in any study with
tetraconazole. In addition, tetraconazole does not belong to a class of
chemicals (e.g., the organotins, heavy metals, or halogenated aromatic
hydrocarbons) that would be expected to be immunotoxic. Based on these
considerations, EPA does not believe that conducting a special series
870.7800 immunotoxicity study will result in a point of departure less
than the NOAEL of 0.73 mg/kg/day used in calculating the cPAD for
tetraconazole; therefore, an additional database uncertainty factor is
not needed to account for potential immunotoxicity.
    ii. There is no indication that tetraconazole is a neurotoxic
chemical and there is no need for a developmental neurotoxicity study
or additional UFs to account for neurotoxicity.
    iii. There is no evidence that tetraconazole results in increased
susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the 2-generation reproduction
study.
    iv. There are no residual uncertainties identified in the exposure
databases. The acute dietary food exposure assessment assumed
tolerance-level residues and 100 PCT. The chronic and cancer dietary
food exposure assessments were refined using reliable PPCT information
and anticipated residue values calculated from valid field trial
results. EPA made conservative (protective) assumptions in the ground
and surface water modeling used to assess exposure to tetraconazole in
drinking water. Residential exposure to tetraconazole is not expected.
These assessments will not underestimate the

exposure and risks posed by tetraconazole.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the aPAD and cPAD.
The aPAD and cPAD represent the highest safe exposures, taking into
account all appropriate SFs. EPA calculates the aPAD and cPAD by
dividing the POD by all applicable UFs. For linear cancer risks, EPA
calculates the probability of additional cancer cases 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 POD to ensure that the MOE called for
by the product of all applicable UFs is not exceeded.
    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% of the aPAD for females, 13 to 49
years old, the only population group for which an acute toxicity
endpoint of concern was identified.
    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 7.7% of the cPAD for
infants less than 1 year old, the population group receiving the
greatest exposure. There are no residential uses for tetraconazole.
    3. Short-/intermediate-term risk. Short- and intermediate term
aggregate exposures take into account short- and intermediate-term
residential exposure plus chronic exposure from food and water
(considered to be a background exposure level). Tetraconazole is not
registered for any use patterns that would result in residential
exposure. Therefore, the short- and intermediate-term aggregate risk is
the sum of the risk from exposure to tetraconazole through food and
water and will not be greater than the chronic aggregate risk.
    4. Aggregate cancer risk for U.S. population. Using the exposure
assumptions described in this unit for the cancer risk assessment, EPA
has concluded that exposure to tetraconazole from food and water will
result in a lifetime cancer risk of 3 x 10-6 for the U.S.
population. 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 3.16 x 10-7 and 3.16 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, 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. Since the calculated cancer risk for tetraconazole
falls within this range, estimated cancer risk is considered to be
negligible.
    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 (gas chromatography with electron
capture detection (GC/ECD)) is available to enforce the tolerance
expression. The method may be requested from: Chief, Analytical
Chemistry Branch, Environmental Science Center, 701 Mapes Rd., Ft.
Meade, MD 20755-5350; telephone number:<PHONE_NUMBER>; e-mail address:
<EMAIL_ADDRESS>
B. International Residue Limits

    There are no CODEX, Canadian or Mexican maximum residues levels
established for tetraconazole.

C. Revisions to Petitioned-For Tolerances

    Based upon review of the data supporting the petition, EPA has
revised the tolerance level for grape from 0.15 ppm to 0.20 ppm. EPA
revised the tolerance level based on analysis of the residue field
trial data using the Agency's Tolerance Spreadsheet in accordance with
the Agency's Guidance for Setting Pesticide Tolerances Based on Field
Trial Data. The recommended value differs from the value proposed by
IR-4, because only data from field plots harvested at the proposed pre-
harvest interval (PHI) were used in calculating the tolerance level.

V. Conclusion

    Therefore, a tolerance is established for residues of
tetraconazole, 1-[2-(2,4-dichlorophenyl)-3-(1,1,2,2-
tetrafluoroethoxy)propyl]-1H-1,2,4-triazole, in or on grape at 0.20
ppm.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, 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) (Public Law 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).

List of Subjects in 40 CFR Part 180

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

    Dated: October 31, 2008.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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

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

0
2. Section 180.557 is amended by alphabetically adding the following
commodity to the table in paragraph (a) to read as follows:

Sec.  180.557  Tetraconazole; tolerances for residues.

     (a) * * *

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Grape................................................               0.20
                                * * * * *
------------------------------------------------------------------------

* * * * *
[FR Doc. E8-26946 Filed 11-13-08; 8:45 am]

BILLING CODE 6560-50-S


exposure to pesticide handlers.  The estimates of exposure to pesticide
handlers are based upon surrogate study data available in the PHED (v.
1.1, 1998).   For pesticide handlers, it is HED standard practice to
present estimates of dermal exposure for “baseline” that is, for
workers wearing a single layer of work clothing consisting of a long
sleeved shirt, long pants, shoes plus socks and no protective gloves as
well as for “baseline” and the use of protective gloves or other PPE
as might be necessary.

The HED HIARC has met to discuss the adequacy of the toxicological
database relative to myclobutanil (HED DOC NO 013740, “MYCLOBUTANIL -
Second Report of the Hazard Identification Assessment Review
Committee,” M. Copley, 9/2/99).  Subsequently, the RAB1 toxicologists
re-evaluated the myclobutanil toxicology database and concluded that the
28-day dermal toxicity study previously used for short-term dermal risk
assessment was not appropriate.  A two-generation reproduction study in
rats was selected.  With regards to the assessment herein, the
short-term duration (1-30 days) and the intermediate-term duration (1-6
months) dermal and inhalation toxicological endpoints are identified
from a 2-generation reproduction toxicity study in the rat.  The NOAEL
is 10.0 mg ai/kg bw/day based on atrophy of the testes and prostate as
well as an increase in the number of stillborn pups and a decrease in
pup weight gain during lactation.  The HIARC identified a 50% dermal
absorption factor for use in assessing dermal exposures.  The RAB 1
toxicology team cited the same study for the inhalation endpoint, noting
the same effects and NOAEL.  Inhalation absorption is assumed to be
100%.  The intermediate-term dermal and inhalation NOAELs are the same
as those noted for short-term duration exposures and are cited from the
same 2-generation rat reproduction study.  See Table 9.1 for a summary
of exposures and risks to occupational pesticide handlers.  See the
Attachment A for a summary of the toxicological endpoints used for risk
assessment.

Table 9.1 Summary of Exposure & Risk for Occupational Handlers Applying
Myclobutanil

Unit Exposure1

mg ai/lb handled	Applic. Rate2

lb ai/unit	Units Treated3	Avg. Daily Exposure4

mg ai/kg bw/day	MOE5

Mixer/Loader Using WP in Water Soluble Packaging (in support of aerial
operations)

Dermal:

SLNoGlove     0.021 LC

SLWithGlove  0.0098 LC

Inhal.              0.00024 LC	0.25	350	Dermal:

SLNoGlove    0.013

SLWithGlove 0.00613

Inhal.              0.0003	No Glove

752

With Glove

1,555

Applicator - Groundboom Open-Cab

Dermal:

SLNoGlove     0.014 HC

SLWithGlove  0.014 MC

Inhal.               0.00074 HC	0.125	200	Dermal:

SLNoGlove    0.0025

SLWithGlove 0.0025

Inhal.          0.000264	No Glove

3,617

With Glove

3,617

Applicator - Airblast Open-Cab

Dermal:

SLNoGlove     0.36 HC

SLWithGlove  0.24 HC

Inhal.              0.0045 HC	0.25	40	Dermal:

SLNoGlove    0.0257

SLWithGlove 0.017

Inhal.           0.000643	No Glove

380

With Glove

567

Aerial Applicator

Dermal:

SLNoGlove      0.0050 MC

Inhal.            0.000068 MC	0.25	350	Dermal:

SLNoGlove  0.00313

Inhal.          0.000085	No Glove

3,110

1.  Unit Exposures are taken from “PHED SURROGATE EXPOSURE GUIDE”,
Estimates of Worker Exposure from The Pesticide Handler Exposure
Database Version 1.1, August 1998.   Inhal. = Inhalation.  Units = mg
a.i./pound of active ingredient handled.  Data Confidence: LC = Low
Confidence, MC = Medium Confidence, HC = High Confidence.

2.  Applic. Rate. = Taken from the  IR 4 submission Sections B

3.  Units Treated are taken from “Standard Values for Daily Acres
Treated in Agriculture”; SOP  No. 9.1.   Science Advisory Council for
Exposure;  Revised 5 July 2000;

4.  Average Daily Dose (ADD) = Unit Exposure * Applic. Rate * Units
Treated * absorption factor (50% dermal) ( Body Weight 70 kg.

5.  NOAEL = No Observable Adverse Effect Level (10 mg a.i./kg bw/day for
short-term and intermediate-term dermal and  inhalation)

6.  MOE = Margin of Exposure = (NOAEL = 10 mg ai/kg bw/day)  ( ADD.
The ADD = dermal exposure + inhalation exposure.

 A MOE of 100 is adequate to protect occupational pesticide handlers
from exposures to myclobutanil.  All MOEs are > 100 therefore the
proposed uses do not exceed ARIA’s level of concern.

9.2	Post-Application Exposure to Agricultural Workers

It is possible for agricultural workers to have post-application
exposures to pesticide residues during the course of typical
agricultural activities.  HED in conjunction with the Agricultural
Re-entry Task Force (ARTF) has identified a number of post-application
agricultural activities that may occur and which may result in
post-application exposures to pesticide residues.  HED has also
identified Transfer Coefficients (TC) (cm²/hr) relative to the various
activities which express the amount of foliar contact over time, during
each of the activities identified.

 For the proposed new crop use sites, the highest TC for fruiting
vegetables and artichoke is 1,000 cm2/hr for hand harvesting.  The
highest TC for root vegetables and for greens is 2,500 cm2/hr for hand
harvesting.  Tropical fruit are not named specifically in the database.
However, ARIA assumes there would not be significant difference from the
highest TCs for hand harvesting citrus or pome or stone fruit (which is
3,000 cm2/hr).  Therefore, as a “screening” level assessment, ARIA
herein uses a TC of 3,000 cm²/hr.

The TCs used in this assessment are from an interim TC Standard
Operating Procedure (SOP) developed by HED’s ExpoSAC using proprietary
data from the ARTF database (SOP # 3.1).  It is the intention of HED’s
ExpoSAC that this SOP will be periodically updated to incorporate
additional information about agricultural practices in crops and new
data on transfer coefficients.  Much of this information will originate
from exposure studies currently being conducted by the ARTF, from
further analysis of studies already submitted to the Agency, and from
studies in the published scientific literature.

Lacking compound specific dislodgeable foliar residue (DFR) data, HED
assumes 20 % of the application rate is available as DFR on day zero
after application.  This is adapted from the ExpoSAC SOP No. 003 (7 May
1998 - Revised 7 August 2000).

The following convention may be used to estimate post-application
exposure.

Average Daily Dose (ADD) (mg a.i./kg bw/day) = DFR µg/cm2 * TC cm2/hr *
hr/day * 0.001 mg/µg * 1/70 kg bw

 and where:

Surrogate Dislodgeable Foliar Residue (DFR) = application rate * 20%
available as dislodgeable residue * (1-D)t * 4.54 x 108 µg/lb * 2.47 x
10-8 A/cm2 .

0.25 lb a.i./A * 0.20 * (1-0)0 * 4.54 x 108 µg/lb *  2.47 x10-8 A/cm²
= 0.56 µg/cm2 , therefore,

0.56 µg/cm2 * 3,000 cm2/hr * 8 hr/day * 0.001 mg/µg * 0.50 (% dermal
absorption) ( 70 kg bw = 0.096 mg/kg bw/day.

MOE = NOAEL ( ADD then 10.0 mg/kg bw/day ( 0.096 mg/kg bw/day =  104.

A MOE of 100 is adequate to protect agricultural workers from
post-application exposures.  Since the estimated MOEs are > 100, the
proposed uses do not exceed ARIA’s level of concern.

9.3	Restricted Entry Interval

Myclobutanil is classified in Acute Toxicity Category I for primary eye
irritation and in Acute Toxicity Category IV for acute dermal toxicity,
acute inhalation toxicity and primary skin irritation.  It is a dermal
sensitizer.  The labels list a 24-hour REI.

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hour REI is established for any product containing an active ingredient
that is in toxicity category I (most acutely toxic category) because of
dermal toxicity or skin or eye irritation.”

The 24-hour REI listed on the product labels should be confirmed or
corrected as may be necessary.

10.0	Data Needs and Label Requirements

10.1	Toxicology

None.

10.2	Residue Chemistry

A revised Section F is required for the residues of myclobutanil on
papaya, sapote, canistel, mamey sapote, mango, sapodilla, and star apple
at 3.0 ppm.

A revised Section F is required for the residues of myclobutanil on
fruiting vegetables (except cucurbits), crop group 8, except tomato at
4.0 ppm.

A revised Section F is required for the residues of myclobutanil on okra
at 4.0 ppm.

A revised Section F is required for the residues of myclobutanil on
leafy greens, crop subgroup 4A, except spinach at 9.0 ppm.

A revised Section F is required for the residues of myclobutanil on
cilantro at 9.0 ppm.

10.3	Occupational/Residential Exposure

ARIA suggests that the RD confirm or correct, as may be necessary, the
24-hour REI listed on the product label.

References	DP Num: 336660, M. Dow, 3/8/07

PP#s: 7E4861, 7E4877, 3E6562, 8E4939, 6E7138, & 7E4866, DP Num: 341689
MRID: 45596301, 45880301, 45883401, 45908101, 45908201, 45910601, &
46990901-03, W. Cutchin, 9/26/07

DP Num: 319227, MRID: 40489302 & 44952901, T. Dole, 2/8/06

PP#s: 7E4861, 7E4877, 3E6562, 8E4939, 6E7138, & 7E4866, DP Number:
341690, W. Cutchin, 10/2/07

HED Doc. No. 013740, M. Copley, 9/2/99

		HED Doc. No. 013734, 9/13/99

		DP Num: 330235, J. Tyler, 7/12/06

		DP Num: 336254, J. Wolf, 9/26/07

Attachment A

Toxicity Tables

Table A.1  Acute Toxicity of Myclobutanil

Guideline

 No.

Study Type

MRID #(S)

Results

Toxicity Category

81-1

Acute Oral

00141662

LD50 = 1.6 g/kg (M)

LD50 = 2.29 g/kg (F)

III

81-2

Acute Dermal

00141663

LD50> 5000 mg/kg

IV

81-3

Acute Inhalation

40357101

LC50 > 5.1 m/L

IV

81-4

Primary Eye  Irritation

00141663

Severe eye irritant

I

81-5

Primary Skin Irritation

00141663

Non-irritating to skin

IV

81-6

Dermal Sensitization

40357102

Positive sensitizer

Table A.2  Summary of Toxicological Doses and Endpoints for Myclobutanil

EXPOSURE

SCENARIO	DOSE

(mg/kg/day)	ENDPOINT	STUDY

Acute Dietary

females 13-50 years of age	NOAEL=60

UF = 100	LOAEL = 200 mg/kg/day based on increased resorptions, decreased
litter size and a decrease in the viability index.	Developmental
Toxicity - rabbit

	Acute RfD = 0.60

Acute Dietary

general population including infants and children	none

	Acute RfD = none

Chronic Dietary	NOAEL =2.49 mg/kg/day

UF = 100	LOAEL = 10 mg/kg/day based on decreased testicular weights and
increased testicular atrophy.	Chronic Toxicity/ Carcinogenicity - rat

	Chronic RfD = 0.025 mg/kg/day

Short-Term

(Dermal)	oral NOAEL=10 mg/kg/day1	LOAEL = 50 mg/kg/day based on atrophy
of the testes and prostate as well as an increase in the number of
stillborn pups and a decrease in pup weight gain during lactation.	2
Generation Reproduction Toxicity - rat

Intermediate-Term

(Dermal)	oral NOAEL=10 mg/kg/day1	LOAEL = 50 mg/kg/day based on atrophy
of the testes and prostate as well as an increase in the number of
stillborn pups and a decrease in pup weight gain during lactation.	2
Generation Reproduction Toxicity - rat

Long-Term (Dermal)	oral NOAEL =2.49 mg/kg/day1	LOAEL = 10 mg/kg/day
based on decreased testicular weights and increased testicular atrophy.
Chronic Toxicity/ Carcinogenicity - rat

Short Term

(Inhalation)	oral NOAEL=10 mg/kg/day2	LOAEL = 50 mg/kg/day based on
atrophy of the testes and prostate as well as an increase in the number
of stillborn pups and a decrease in pup weight gain during lactation.	2
Generation Reproduction Toxicity - rat

 Intermediate Term

(Inhalation)	oral NOAEL=10 mg/kg/day2	LOAEL = 50 mg/kg/day based on
atrophy of the testes and prostate as well as an increase in the number
of stillborn pups and a decrease in pup weight gain during lactation.	2
Generation Reproduction Toxicity - rat

Long Term

(Inhalation)	oral NOAEL =2.49 mg/kg/day2	LOAEL = 10 mg/kg/day based on
decreased testicular weights and increased testicular atrophy.	Chronic
Toxicity/ Carcinogenicity - rat

1 Use the appropriate dermal absorption factor (50%) since the NOAEL is
from an oral study.

2 Use the appropriate absorption factor (100%) since the NOAEL is from
an oral study.

Attachment B

Review of Human Research

No MRID - PHED Surrogate Exposure Guide

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