[Federal Register Volume 75, Number 86 (Wednesday, May 5, 2010)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-10406]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Tebuconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
tebuconazole in or on vegetable, fruiting, group 8. Bayer CropScience
requested these tolerances under the Federal Food, Drug, and Cosmetic
DATES: This regulation is effective May 5, 2010. Objections and
requests for hearings must be received on or before July 6, 2010, 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-2009-0611. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
FOR FURTHER INFORMATION CONTACT: Tracy Keigwin, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6605; e-mail address: keigwin.tracy @epa.gov.
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
B. How Can I Get Electronic Access to Other Related Information?
You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR cite at http://www.gpoaccess.gov/ecfr. To
access the harmonized test guidelines referenced in this document
electronically, please go to http://www.epa.gov/oppts and select ``Test
Methods and Guidelines.''
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-2009-0611 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 July 6, 2010.
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-2009-0611, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Petition for Tolerance
In the Federal Register of September 4, 2009 (74 FR 45848) (FRL-
8434-4), 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
9F7515) by Bayer CropScience, 2 T.W. Alexander Dr., P.O. Box 12014,
Research Triangle Park, NC 27709. The petition requested that 40 CFR
part 180 be amended by establishing tolerances for residues of the
fungicide tebuconazole in or on the raw agricultural commodity
vegetables, fruiting, group at 1.4 parts per million (ppm). That notice
referenced a summary of the petition prepared by Bayer CropScience, the
registrant, which is available to the public in the docket, 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
modified the proposed tolerance to 1.3 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
tolerances for residues of tebuconazole on vegetables, fruiting, group
8 at 1.3 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
Tebuconazole has low acute toxicity by the oral or dermal route of
exposure, and moderate toxicity by the inhalation route. It is not a
dermal sensitizer or a dermal irritant; however, it is slightly to
mildly irritating to the eye. The main target organs are the liver, the
adrenals, the hematopoetic system and the nervous system. Effects on
these target organs were seen in both rodent and non-rodent species. In
addition, ocular lesions are seen in dogs (including lenticular
degeneration and increased cataract formation) following subchronic or
Oral administration of tebuconazole caused developmental toxicity
in all species evaluated (rat, rabbit, and mouse), with the most
prominent effects seen in the developing nervous system. In the
available toxicity studies on tebuconazole, there was no
toxicologically significant evidence of endocrine disruptor effects.
Tebuconazole was classified as a Group C possible human carcinogen,
based on an increase in the incidence of hepatocellular adenomas,
carcinomas and combined adenomas/carcinomas in male and female mice.
Submitted mutagenicity studies did not demonstrate any evidence of
mutagenic potential for tebuconazole.
Specific information on the studies received and the nature of the
adverse effects caused by tebuconazole 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 entitled ``Tebuconazole: Human
Health Risk Assessment to support tolerances in/on Asparagus, Barley,
Beans, Beets, Brassica leafy greens, Bulb Vegetables, Coffee (import),
Commercial Ornamentals, Corn, Cotton, Cucurbits, Hops, Lychee, Mango,
Okra, Pome fruit, Soybean, Stone fruit, Sunflower, Tree Nut Crop Group,
Turf, Turnips and Wheat,'' pages 83-105 in docket ID number EPA-HQ-OPP-
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 tebuconazole used for
human risk assessment is shown in the Table of this unit.
Table--Summary of Toxicological Doses and Endpoints for Tebuconazole for Use in Human Risk Assessment
Point of Departure and
Exposure/Scenario Uncertainty/Safety RfD, PAD, LOC for Risk Study and Toxicological
Factors Assessment Effects
Acute dietary LOAEL = 8.8 milligram/ Acute RfD = 0.029 mg/kg/ Developmental
(General population including kilogram/day (mg/kg/ day Neurotoxicity Study -
infants and children, Females 13-50 day) aPAD = 0.029 mg/kg/day. Rat.
years of age). UF = 300............... LOAEL = 8.8 mg/kg/day
UFA = 10x.............. based on decreases in
UFH = 10x.............. body weights, absolute
FQPA (UFL) = 3x........ brain weights, brain
measurements and motor
activity in offspring.
Chronic dietary LOAEL = 8.8 mg/kg/day Chronic RfD = 0.029 mg/ Developmental
(All populations)................... UF = 300............... kg/day Neurotoxicity Study -
UFA = 10x.............. cPAD = 0.029 mg/kg/day. Rat.
UFH = 10x.............. LOAEL = 8.8 mg/kg/day
FQPA (UFL) = 3x........ based on decreases in
body weights, absolute
brain weights, brain
measurements and motor
activity in offspring.
Incidental oral short term/ LOAEL = 8.8 mg/kg/day Residential LOC for MOE Developmental
Intermediate term UF = 300............... = 300 Neurotoxicity Study -
(1 to 30 days/1-6 months)........... UFA = 10x.............. Rat.
UFH = 10x.............. LOAEL = 8.8 mg/kg/day
FQPA (UFL) = 3x........ based on decreases in
body weights, absolute
brain weights, brain
measurements and motor
activity in offspring.
Dermal short term/Intermediate term LOAEL = 8.8 mg/kg/day Residential LOC for MOE Developmental
(1 to 30 days/1 to 6 months)........ UF = 300............... = 300 Neurotoxicity Study -
UFA = 10x.............. Rat.
UFH = 10x.............. LOAEL = 8.8 mg/kg/day
UFL = 3x............... based on decreases in
DAF = 23.1%............ body weights, absolute
brain weights, brain
measurements and motor
activity in offspring.
Inhalation short term/Intermediate LOAEL = 8.8 mg/kg/day Residential LOC for MOE Developmental
term UF = 300............... = 300 Neurotoxicity Study -
(1 to 30 days/1 to 6 months)........ UFA = 10x.............. Rat.
UFH = 10x.............. LOAEL = 8.8 mg/kg/day
UFL = 3x............... based on decreases in
Inhalation and oral body weights, absolute
toxicity are assumed brain weights, brain
to be equivalent. measurements and motor
activity in offspring.
Cancer Classification: Group C-possible human carcinogen based on statistically
(Oral, dermal, inhalation).......... significant increase in the incidence of hepatocellular adenoma,
carcinoma, and combined adenoma/carcinomas in both sexes of NMRI mice.
Considering that there was no evidence of carcinogenicity in rats, there
was no evidence of genotoxicity for tebuconazole, and tumors were only
seen at a high and excessively toxic dose in mice, EPA concluded that the
chronic RfD would be protective of any potential carcinogenic effect. The
chronic RfD value is 0.029 mg/kg/day which is approximately 9,600 fold
lower than the dose that would induce liver tumors (279 mg/kg/day).
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. 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.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to tebuconazole, EPA considered exposure under the petitioned-
for tolerances as well as all existing tebuconazole tolerances in 40
CFR 180.474. EPA assessed dietary exposures from tebuconazole in food
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.
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, anticipated residues
for bananas, grapes, raisins, nectarines, peaches, peanut butter and
wheat were derived using the latest USDA Pesticide Data Program (PDP)
monitoring data. Anticipated residues for all other registered and
proposed food commodities were based on field trial data. For uses
associated with PP 9F7515, 100 percent crop treated (PCT) was assumed.
Dietary Exposure Evaluation Model (ver. 7.81) default processing
factors were assumed for processed commodities associated with petition
9F7515. For several other uses
EPA used PCT data as specified in Unit III.C.1.iv.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the same assumptions as stated in Unit III.C.1.i.
for acute exposure.
iii. Cancer. As explained in Unit III.B., the chronic risk
assessment is considered to be protective of any cancer effects;
therefore, a separate quantitative cancer dietary risk assessment was
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 PCT information as follows:
Grapes: 25%; grape, raisin: 25%; nectarine 25%; oats 2.5%; peach:
20%; and peanuts 45%.
In most cases, EPA uses available data from the USDA's National
Agricultural Statistics Service (NASS), proprietary market surveys, and
the National Pesticide Use Database for the chemical/crop combination
for the most recent 6 years. EPA uses an average PCT for chronic
dietary risk analysis. The average PCT figure for each existing use is
derived by combining available public and private market survey data
for that use, averaging across all observations, and rounding to the
nearest 5%, except for those situations in which the average PCT is
less than one. In those cases, 1% is used as the average PCT and 2.5%
is used as the maximum PCT. EPA uses a maximum PCT for acute dietary
risk analysis. The maximum PCT figure is the highest observed maximum
value reported within the recent 6 years of available public and
private market survey data for the existing use and rounded up to the
nearest multiple of 5%.
The Agency used projected percent crop treated (PPCT) information
for tebuconazole on apples, apricots, cherries (preharvest), sweetcorn,
hops, plums, and turnips. The PPCT for each crop is as follows: Apples,
acute assessment 44%, chronic assessment 41%; apricots: acute
assessment 56%, chronic assessment 43%; cherries, preharvest: acute
assessment 42%, chronic assessment 37%; corn, sweet: acute assessment
22%, chronic assessment 14%; hops: acute assessment 64%, chronic
assessment 64%; plum: acute assessment 26%, chronic assessment 24%;
turnip: acute assessment 68%, chronic assessment 44%. EPA estimates
PPCT for a new pesticide use by assuming that its actual PCT during the
initial 5 years of use on a specific use site will not exceed the
recent PCT of the market leader (i.e., the one with the greatest PCT)
on that site. An average market leader PCT, based on three recent
surveys of pesticide usage, if available, is used for chronic risk
assessment, while the maximum PCT from the same three recent surveys,
if available, is used for acute risk assessment. The average and
maximum market leader PCTs may each be based on one or two surveys if
three are not available. 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 market leader
PCTs used to determine the average and the maximum may be each for the
same pesticide or for different pesticides since the same or different
pesticides may dominate for each year. Typically, EPA uses USDA/NASS as
the source for raw PCT data because it is publicly available. When a
specific use site is not surveyed by USDA/NASS, EPA uses other sources
including proprietary data.
An estimated PPCT, based on the average PCT of the market leaders,
is appropriate for use in chronic dietary risk assessment, and an
estimated PPCT, based on the maximum PCT of the market leaders, is
appropriate for use in acute dietary risk assessment. This method of
estimating PPCTs for a new use of a registered pesticide or a new
pesticide produces high-end estimates that are unlikely, in most cases,
to be exceeded during the initial 5 years of actual use. Predominant
factors that bear on whether the PPCTs could be exceeded may include
PCTs of similar chemistries, pests controlled by alternatives, pest
prevalence in the market and other factors. All relevant information
currently available for predominant factors have been considered for
tebuconazole on cherries, resulting in adjustments to the initial
estimates for three crops to account for lack of confidence in
projections based on less than three observations, old data and/or data
based on expert opinion.
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 tebuconazole 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 tebuconazole in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of tebuconazole. Further information regarding EPA
drinking water models used in pesticide exposure assessment can be
found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI
GROW) models, the estimated drinking water concentrations (EDWCs) of
tebuconazole for acute exposures are estimated to be 47.23 micrograms/
Liter ([mu]g/L) for surface water and 0.447 [mu]g/L for ground water.
The EDWCs for chronic, noncancer are estimated to be 16.97 [mu]g/L for
surface water and 0.447 [mu]g/L for ground water. The EDWCs for
chronic, cancer exposures are estimated to be 12.14 for surface water
and 0.447 [mu]g/L for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For the acute dietary risk
assessment, the water concentration value of 47.23 [mu]g/L was used to
assess the contribution to drinking water. For the chronic dietary risk
assessment (which is protective of any possible cancer effects), the
water concentration value of 16.97 [mu]g/L 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).
Tebuconazole has currently registered uses that could result in
residential exposures. Short term dermal and inhalation exposures are
possible for residential adult handlers mixing, loading, and applying
tebuconazole products outdoors to ornamental plants. Short- and
intermediate-term dermal postapplication exposures to adults and
children are also possible during golfing and/or playing on treated
wood structures. Children may also be exposed via the incidental oral
route when playing on treated wood structures. Long-term exposure is
not expected. As a result, risk assessments have been completed for
residential handler scenarios as well as residential post-application
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.''
Tebuconazole is a member of the triazoles (and more specifically,
triazole-derivative fungicides). Although triazoles 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. In triazole-derivative
fungicides, however, a variable pattern of toxicological responses is
found: Some are hepatotoxic and hepatocarcinogenic in mice; some induce
thyroid tumors in rats; and some induce developmental, reproductive,
and neurological effects in rodents. Furthermore, the triazoles 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 triazole-derivative fungicides share common
mechanisms of toxicity and EPA is not following a cumulative risk
approach based on a common mechanism of toxicity for the triazole-
derivative fungicides. For information regarding EPA's procedures for
cumulating effects from substances found to have a common mechanism of
toxicity, see EPA's website at http://www.epa.gov/pesticides/cumulative.
However, the triazole-derivative fungicides can form the common
metabolites 1,2,4-triazole and conjugated triazole metabolites. To
support existing tolerances and to establish new tolerances for
triazole-derivative fungicides, including tebuconazole, EPA conducted a
human health risk assessment for exposure to 1,2,4-triazole,
triazolylalanine, and triazolylacetic acid resulting from the use of
all current and pending uses of any triazole-derivative 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 the Food Quality Protection Act (FQPA) Safety Factor (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 ID number EPA-HQ-OPP-2005-0497.
In connection with the pending new uses of tebuconazole (and other
triazole-derivative fungicides), the Agency has revised the triazole
dietary assessment to include the new uses of tebuconazole and has
determined that aggregate risk (food, water and residential) remains
below the Agency's level of concern. This revised assessment can be
found at http://www.regulations.gov in docket ID EPA-HQ-OPP-2009-0061.
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 FQPA 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 toxicity database for
tebuconazole is complete, and includes prenatal developmental toxicity
studies in three species (mouse, rat, and rabbit), a reproductive
toxicity study in rats, acute and subchronic neurotoxicity studies in
rats, and a developmental neurotoxicity study in rats. The data from
prenatal developmental toxicity studies in mice and a developmental
neurotoxicity study in rats indicated an increased quantitative and
qualitative susceptibility following in utero exposure to tebuconazole.
The NOAELs/LOAELs for developmental toxicity in these studies were
found at dose levels less than those that induce maternal toxicity or
in the presence of slight maternal toxicity. There was no indication of
increased quantitative susceptibility in the rat and rabbit
developmental toxicity studies, the NOAELs for developmental toxicity
were comparable to or higher than the NOAELs for maternal toxicity. In
all three species, however, there was indication of increased
qualitative susceptibility. For most studies, minimal maternal toxicity
was seen at the LOAEL (consisting of increases in hematological
findings in mice, increased liver weights in rabbits and rats, and
decreased body weight gain/food consumption in rats) and did not
increase substantially in severity at higher doses; however, there was
more concern for the developmental effects at each LOAEL which included
increases in runts, increased fetal loss, and malformations in mice,
increased skeletal variations in rats, and increased fetal loss and
frank malformations in rabbits. Additionally, more severe developmental
effects (including frank malformations) were seen at higher doses in
mice, rats and rabbits. In the developmental neurotoxicity study,
maternal toxicity was seen only at the high dose (decreased body
weights, body weight gains, and food consumption, prolonged gestation
with mortality, and increased number of dead fetuses), while offspring
toxicity (including decreases in body weight, brain weight, brain
measurements and functional activities) was seen at all doses.
Available data indicated greater sensitivity of the developing
organism to exposure to tebuconazole, as demonstrated by increases in
qualitative sensitivity in prenatal developmental toxicity studies in
rats, mice, and rabbits, and by increases in both qualitative and
quantitative sensitivity in the developmental neurotoxicity study in
rats with tebuconazole. However, the degree of concern is low because
the toxic endpoints in the prenatal developmental toxicity studies were
well characterized with clear NOAELs established and the most sensitive
endpoint from the developmental neurotoxicity study is used for overall
risk assessments. Therefore, there are no residual uncertainties for
prenatal and/or postnatal susceptibility.
There is a concern with regard to the DNT study because of the
failure to achieve a NOAEL in that study. This concern is addressed by
the retention of FQPA SF in the form of UFL of 3x. Reduction
of the FQPA safety factor from 10x to 3x is based on a Benchmark Dose
(BMD) analysis of the datasets relevant to the adverse offspring
effects (decreased body weight, decreases in absolute brain weights,
changes in brain morphometric parameters, and decreases in motor
activity) seen at the LOAEL in the DNT study. All of the BMDLs (the
lower limit of a one-sided 95% confidence interval on the BMD) modeled
successfully on statistically significant effects are 1-2x lower than
the LOAEL. The results indicate that the extrapolated NOAEL is not
likely to be 10x lower than the LOAEL and that the use of the FQPA SF
of 3x would not underestimate risk. Using a 3x FQPA SF in the risk
assessment (8.8 mg/kg/day / 3x = 2.9 mg/kg/day) is further supported by
the NOAELs established in other studies in the tebuconazole toxicity
database [i.e., 3 and 2.9 mg/kg/day, from a developmental toxicity
study in mice and a chronic toxicity study in dogs, respectively
(respective LOAELs 10 and 4.5 mg/kg/day)].
3. Conclusion. The Agency has determined that reliable data show
that it would be safe for infants and children to reduce the FQPA SF to
3x for all potential exposure scenarios. That decision is based on the
i. The toxicity database for tebuconazole is complete with the
exception of an immunotoxicity study requirement under the new 40 CFR
part 158 guidelines for toxicity data. The available guideline studies
do not suggest that tebuconazole directly targets the immune system. A
peer-reviewed developmental neurotoxicity/immunotoxicity literature
study (Moser et al., 2001) found in high dose groups (60 mg/kg/day)
increased spleen weights and alterations in splenic lymphocyte
subpopulations. At the same dose there were no effects seen in the T-
cell dependent antibody response to SRBC (sheep red blood cells) and
natural killer (NK) cell activity indicating that tebuconazole did not
alter the functional immune response in rats. Based on guideline and
open literature, the overall weight of evidence suggests that
tebuconazole does not directly target the immune system. The Agency
does not believe that conducting a functional immunotoxicity study will
result in a lower POD than currently used for overall risk assessment;
therefore, a database uncertainty factor (UFDB) is not needed to
account for the lack of the study.
ii.Although there is qualitative evidence of increased
susceptibility in the prenatal developmental studies in rats, the risk
assessment team did not identify any residual uncertainties after
establishing toxicity endpoints and traditional UFs to be used in the
risk assessment of tebuconazole. The degree of concern for residual
uncertainties for prenatal and/or postnatal toxicity is low.
iii.The FQPA SF is retained as a UFL. Reduction of the
UFL from 10 to 3x is based on a BMD analyses of the datasets
relevant to the adverse offspring effects (decreased body weight and
brain weight) seen at the LOAEL in the DNT study. All of the BMDLs
modeled successfully on statistically significant effects are 1-2x
lower than the LOAEL. The results indicate that an extrapolated NOAEL
is not likely to be 10x lower than the LOAEL and that use of an
UFL of 3x would not underestimate risk. Using an
UFL of 3x in risk assessment (8.8 mg/kg/day / 3x = 2.9 mg/
kg/day) is further supported by other studies in the tebuconazole
toxicity database [with the lowest NOAELs being 3 and 2.9 mg/kg/day,
from a developmental toxicity study in mice and a chronic toxicity
study in dogs, respectively (respective LOAELs 10 and 4.5 mg/kg/day)].
iv.There are no residual uncertainties identified in the exposure
databases. Although the acute and chronic food exposure assessments are
refined, EPA believes that the assessments are based on reliable data
and will not underestimate exposure/risk. The drinking water estimates
were derived from conservative screening models. The residential
exposure assessment utilizes reasonable high-end variables set out in
EPA's Occupational/Residential Exposure SOPs (Standard Operating
Procedures). The aggregate assessment is based upon reasonable worst-
case residential assumptions, and is also not likely to underestimate
exposure/risk to any subpopulation, including those comprised of
infants and children.
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 tebuconazole will occupy 56% of the aPAD for the population group
(children 3-5 years old) receiving the greatest exposure.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
tebuconazole from food and water will utilize 4.9% of the cPAD for the
U.S. population and 7.5% of the cPAD for the most highly exposed
population group (children 1-2 years old).
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). Tebuconazole
is currently registered for uses that could result in short-term
residential exposure and the Agency has determined that it is
appropriate to aggregate chronic exposure through food and water with
short-term residential exposures to tebuconazole.
Using the exposure assumptions described in this unit for short
term exposures, EPA has concluded that the short-term aggregate MOE
from dietary exposure (food + drinking water) and non-occupational/
residential handler exposure for adults using a hose-end sprayer on
ornamentals is 390. The short-term aggregate MOE from dietary exposure
and exposure from golfing is 1,700. The short-term aggregate MOE to
children from dietary exposure and exposure from wood surfaces treated
at the above ground use rate is 520. The short-term aggregate MOE to
children from dietary exposure and exposure to wood surfaces treated at
the below ground use rate is 230. The combined and aggregate MOEs for
wood treated for below ground uses exceed the Agency's LOC, and
indicate a potential risk of concern. However, the combined MOE for
wood treated for above-ground uses does not exceed the LOC, and
therefore is not of concern. Exposure to above-ground wood is expected
to more closely represent actual exposures to children. Frequency of
exposures to above-ground wood should greatly exceed any exposures to
below-ground wood, and exposures to below ground wood would be minimal,
or negligible. It is unrealistic to expect a full duration of exposure
to below ground wood. Therefore, this assessment should be
characterized as a conservative screening-level assessment.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). Tebuconazole is currently registered for uses that could result
in intermediate-term residential exposure and the Agency has determined
that it is appropriate to aggregate chronic exposure through food and
water with intermediate-term residential exposures to tebuconazole.
Since the POD, relevant exposure scenarios and exposure assumptions
used for intermediate-term aggregate risk assessments are the same as
those used for short-term aggregate risk assessments, the short-term
aggregate risk assessments represent and are protective of both short-
and intermediate-term exposure durations.
5. Aggregate cancer risk for U.S. population. As discussed in this
unit, the chronic risk assessment is considered to be protective of any
cancer effects; therefore, because the chronic risk assessment
indicates exposure is lower than the cPAD, tebuconazole does not pose a
cancer risk of concern.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children from aggregate
exposure to tebuconazole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate gas chromatography/nitrogen phosphorus detector (GC/NPD)
and liquid chromatography/mass spectrometry (LC/MS/MS) methods are
available for both collecting and enforcing tolerances for tebuconazole
and its metabolites in plant commodities, livestock matrices and
processing studies. The methods have been adequately validated by an
independent laboratory in conjunction with a previous petition. The
method may be requested from: Chief, Analytical Chemistry Branch,
Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350;
telephone number: (410) 305-2905; email address:
B. International Residue Limits
Codex and Canada have established maximum residue limits (MRLs) for
tebuconazole in/on a variety of plant and livestock commodities. The
tolerance expression for tebuconazole is harmonized between the United
States, Codex, and Canada. There are currently no established Codex,
Canadian, or Mexican MRLs for tebuconazole on fruiting vegetables.
However, there are CODEX MRLs for chili pepper at 5 ppm and sweet
pepper and tomato at 0.5 ppm. The Codex MRLs are based on European
field trials, where the single application rate is approximately
equivalent to the U.S. single application rate but the pre-harvest
interval (PHI) is 3 days in the European Union as opposed to a PHI of 0
days in the United States. Given these different use practices,
international harmonization is not possible at this time.
C. Revisions to Petitioned-For Tolerances
Based upon review of the data supporting the petition, EPA
determined that the proposed tolerances for vegetable, fruiting, group
8, should be reduced to 1.3 ppm from 1.4 ppm. EPA revised these
tolerance levels 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 Standard Operating Procedure (SOP).''
Therefore, tolerances are established for residues of the fungicide
tebuconazole, including its metabolites and degradates, in or on
vegetable, fruiting, group 8 at 1.3 ppm Compliance with the tolerance
levels specified in Unit IV.C. is to be determined by measuring only
dimethylethyl)-1H-1,2,4-triazole-1-ethanol), in or on vegetable,
fruiting, group 8.
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
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
Dated: April 20, 2010.
G. Jeffrey Herndon,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. Section 180.474 is amended by revising the introductory text of
paragraphs (a)(1), (a)(2), and (c) and alphabetically add the commodity
``vegetable, fruiting, group 8'' to the table in paragraph (a)(1) to
read as follows:
Sec. 180.474 Tebuconazole; tolerances for residues.
(a) General. (1) Tolerances are established for residues of the
fungicide tebuconazole, including its metabolites and degradates, in or
on the commodities in the following table. Compliance with the
tolerance levels specified in the following table is to be determined
by measuring only tebuconazole (alpha-[2-(4-chlorophenyl)ethyl]-alpha-
(1,1-dimethylethyl)-1H-1,2,4-triazole-1-ethanol), in or on the
Commodity Parts per million
* * * * *
Vegetable, fruiting, group 8................... 1.3
* * * * *
(2) Tolerances are established for residues of the fungicide
tebuconazole, including its metabolites and degradates, in or on the
commodities in the following table. Compliance with the tolerance
levels specified in the following table is to be determined by
measuring only the sum of tebuconazole (alpha-[2-(4-
ethanol) and its diol metabolite (1-(4-chlorophenyl)-4,4-dimethyl-3-(1H
-1,2,4-triazole-1-yl-methyl)-pentane-3,5-diol), calculated as the
stoichiometric equivalent of tebuconzole, in or on the commodity.
* * * * *
(c) Tolerances with Regional Registrations. Tolerances are
established for residues of the fungicide tebuconazole, including its
metabolites and degradates, in or on the commodities in the following
table. Compliance with the tolerance levels specified below is to be
determined by measuring only tebuconazole, alpha-[2-(4-
ethanol, in or on the commodity.
* * * * *
[FR Doc. 2010-10406 Filed 5-4-10; 8:45 am]
BILLING CODE 6560-50-S