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Tebuconazole - Pesticide Tolerance 12/98


[Federal Register: January 8, 1999 (Volume 64, Number 5)]
[Rules and Regulations]
[Page 1132-1138]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08ja99-17]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-300768; FRL 6050-5]
RIN 2070-AB78

Tebuconazole; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of
tebuconazole in or on grapes, grass forage, grass hay, grass seed
screenings, grass straw, milk, meat by-products of cattle, goats,
horses and sheep. Bayer Corporation requested these tolerances under
the Federal Food, Drug and Cosmetic Act (FFDCA), as amended by the Food
Quality Protection Act of 1996 (Pub. L. 104-170).
DATES: This regulation is effective January 8, 1999. Objections and
requests for hearings must be received by EPA on or before March 9,
1999.

ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300768], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled "Tolerance Petition Fees" and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300768], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 119, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
or ASCII file format. All copies of objections and hearing requests in
electronic form must be identified by the docket control number [OPP-
300768]. No Confidential Business Information (CBI) should be submitted
through e-mail. Electronic copies of objections and hearing requests on
this rule may be filed online at many Federal Depository Libraries.

FOR FURTHER INFORMATION CONTACT: By mail: Mary Waller, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA, (703) 308-9354; e-mail:
waller.mary@epamail.epa.gov.

SUPPLEMENTARY INFORMATION: In the Federal Register of February 2, 1997,
(62 FR 16590) (5F4577) and of March 5, 1997, (62 FR 10047) (6F4669),
EPA issued notices pursuant to section 408 of the Federal Food, Drug,
and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e) announcing the filing of
pesticide petitions (PP) for tolerances by Bayer Corporation, 8400
Hawthorne Road, Kansas City, MO, 64120-0013 (amended in a letter from
Bayer Corporation to EPA dated September 18, 1998). These notices
included summaries of the petitions prepared by Bayer Corporation, the
registrant. There were no comments received in response to the notice
of filing.
The petitions requested that 40 CFR 180.474 be amended by
establishing tolerances for residues of the fungicide, tebuconazole
(alpha-[2-(4-chlorophenyl)-ethyl]-alpha-(1,1-dimethylethyl)-1H-1,2,4-
triazole-1-ethanol) in or on grapes at 5 parts per million (ppm), grass
forage at 8 ppm, grass hay at 25 ppm, grass seed screenings at 55 ppm,
grass straw at 30 ppm, and by establishing tolerances for the combined
residues of tebuconazole and its 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-
1,2,4-triazole-1-yl-methyl)-pentane-3,5-diol metabolite (HWG 2061),
hereafter referred to in this document as tebuconazole, in milk at 0.1
ppm, and meat by-products of cattle, horses, goats and sheep at 0.2
ppm.

I. Risk Assessment and Statutory Findings

Section 408(b)(2)(A)(i) of the 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) 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)
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."

EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the Final Rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL-5754-7).

II. Aggregate Risk Assessment and Determination of Safety

Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of
tebuconazole and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for residues of
tebuconazole in or on grapes, grass forage, grass hay, grass seed
screenings, grass straw, milk, meat by-products of cattle, horses,
goats and sheep. EPA's assessment of the dietary exposures and risks
associated with establishing the tolerance 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

[[Page 1133]]

sensitivities of major identifiable subgroups of consumers, including
infants and children. The nature of the toxic effects caused by
tebuconazole is discussed below.

1. Acute toxicity. Tebuconazole exhibits moderate toxicity. The rat
acute oral LD50 = 3,933 milligram/kilogram (mg/kg) (category
III); the rabbit acute dermal LD50 > 5,000 mg/kg (category
IV); and the rat acute inhalation LC50 > 0.371 milligram/Liter
(mg/L) (category II). Technical tebuconazole was slightly irritating to
the eye (category III) and was not a skin irritant (category IV) in
rabbits. Tebuconazole was not a dermal sensitizer.

2. Subchronic toxicity--i. In a 90-day oral feeding study, rats
were administered technical tebuconazole at levels of 0, 100, 400, or
1,600 ppm (0, 8, 34.8, or 171.7 mg/kg/day for males or 0, 10.8, 46.5,
or 235.2 mg/kg/day for females). In males, the no observed adverse
effect level (NOAEL) was 34.8 mg/kg/day and the lowest observed adverse
effect level (LOAEL) was 171.7 mg/kg/day based on decreased body weight
and decreased body weight gain, adrenal vacuolation and spleen
hemosiderosis. In females, the NOAEL was 10.8 mg/kg/day and the LOAEL
of 46.5 mg/kg/day was based on adrenal vacuolation.

ii. In a 90-day oral feeding study, Beagle dogs were administered
technical tebuconazole at levels of 0, 200, 1,000, or 5,000 ppm (0, 74,
368, or 1,749 mg/kg/day for males or 0, 73, 352, or 1,725 mg/kg/day for
females). In females, the NOAEL was 73 mg/kg/day and the LOAEL was 352
mg/kg/day based on decreased body weight and decreased body weight
gain, decreased food consumption and increased liver N-demethylase
activity. At the highest dose tested (HDT), lens opacity was seen in
all males and in one female and cataracts were seen in three females.

iii. In a 21-day dermal toxicity study, rabbits were exposed
dermally to technical tebuconazole 5 days a week at doses of 0, 50,
250, or 1,000 mg/kg/day. No significant systemic effects were seen. The
systemic NOAEL > 1,000 mg/kg/day.
iv. In a 21-day inhalation toxicity study, rats were exposed to
technical tebuconazole (15 exposures - 6 hours/day for 3 weeks) at
airborne concentrations of 0, 0.0012, 0.0106, or 0.1558 mg/L/day. The
NOAEL was 0.0106 mg/L/day and the LOAEL was 0.1558 mg/L/day based on
piloerection and induction of liver N-demethylase.

3. Chronic toxicity--i. In a 2-year combined chronic feeding/
carcinogenicity study, rats were administered technical tebuconazole at
levels of 0, 100, 300, or 1,000 ppm (0, 5.3, 15.9, or 55 mg/kg/day for
males or 0, 7.4, 22.8, or 86.3 mg/kg/day for females). In males, the
NOAEL was 5.3 mg/kg/day and the LOAEL was 15.9 mg/kg/day based on C-
cell hyperplasia in the thyroid gland. In females, the NOAEL was 7.4
mg/kg/day and the LOAEL was 22.8 mg/kg/day based on body weight
depression, decreased hemoglobin, hematocrit, mean corpuscular volume
and mean corpuscular hemoglobin concentration and increased liver
microsomal enzymes. No evidence of carcinogenicity was found at the
levels tested.

ii. In a 1-year chronic feeding study, Beagle dogs were
administered technical tebuconazole at levels of 0, 40, 200, or 1,000
(weeks 1-39) and 2,000 ppm (weeks 40-52) (0, 1, 5 or 25/50 mg/kg/day
for males and females). The NOAEL was 1 mg/kg/day and the LOAEL was 5
mg/kg/day based on ocular lesions (lenticular and corneal opacity) and
hepatic toxicity (changes in the appearance of the liver and increased
siderosis).

iii. In a 1-year chronic feeding study, Beagle dogs were
administered technical tebuconazole at levels of 0, 100, or 150 ppm (0,
3.0, or 4.4 mg/kg/day for males or 0, 3.0 or 4.5 mg/kg/day for
females). The NOAEL was 3.0 mg/kg/day and the LOAEL was 4.4 mg/kg/day
based on adrenal affects in both sexes. In males there was hypertrophy
of adrenal zona fasciculata cells amounting to 4/4 at 150 ppm and to 0/
4 at 100 ppm and in controls. Other adrenal findings in males included
fatty changes in the zona glomerulosa (3/4) and lipid hyperplasia in
the cortex (2/4) at 150 ppm vs. (1/4) for both effects at 100 ppm and
control dogs. In females there was hypertrophy of zona fasciculata
cells of the adrenal amounting to 4/4 at 150 ppm and to 0/4 at 100 ppm
and 1/4 in controls. Fatty changes in the zona glomerulosa of the
female adrenal amounted to 2/4 at 150 ppm and to 1/4 at 100 ppm and in
controls.

4. Carcinogenicity. In a 91-week carcinogenicity study, mice were
administered technical tebuconazole at levels of 0, 500, or 1,500 ppm
(0, 84.9, or 279 mg/kg/day for males or 0, 103.1, or 365.5 mg/kg/day
for females). Neoplastic histopathology consisted of statistically
significant increased incidences of hepatocellular neoplasms; adenomas
(35.4%) and carcinomas (20.8%) at 1,500 ppm in males and carcinomas
(26.1%) at 1,500 ppm in females. Statistically significant decreased
body weights and increased food consumption were reported that were
consistent with decreased food efficiency at 500 and 1,500 ppm in males
and at 1,500 ppm in females. Clinical chemistry values (dose-dependent
increases in plasma GOT, GPT and Alkaline Phosphatase) for both sexes
were consistent with hepatotoxic effects at both 500 and 1,500 ppm.
Relative liver weight increases reached statistical significance at
both 500 and 1,500 ppm in males and at 1,500 ppm in females. Non-
neoplastic histopathology included dose-dependent increases in hepatic
pancinar fine fatty vacuolation, statistically significant at 500 and
1,500 ppm in males and at 1,500 ppm in females. Other histopathology
included significant oval cell proliferation in both sexes and dose-
dependent ovarian atrophy that was statistically significant at 500 and
1,500 ppm. The Maximum Tolerated Dose (MTD) was achieved at or around
500 ppm.

5. Developmental toxicity--i. In a developmental toxicity study,
pregnant female rats were gavaged with technical tebuconazole at levels
of 0, 30, 60, or 120 mg/kg/day between days 6 and 15 of gestation. The
maternal NOAEL was 30 mg/kg/day and the maternal LOAEL was 60 mg/kg/day
based on increased absolute and relative liver weights. The
developmental NOAEL was 30 mg/kg/day and the developmental LOAEL was 60
mg/kg/day based on delayed ossification of thoracic, cervical and
sacral vertebrae, sternum and limbs plus an increase in supernumerary
ribs.

ii. In a developmental toxicity study, pregnant female rabbits
were gavaged with technical tebuconazole at levels of 0, 10, 30, or 100
mg/kg/day between days 6 and 18 of gestation. The maternal NOAEL was 30
mg/kg/day and the maternal LOAEL was 100 mg/kg/day based on minimal
depression of body weight gains and food consumption. The developmental
NOAEL was 30 mg/kg/day and the developmental LOAEL was 100 mg/kg/day
based on increased postimplantation losses, malformations in 8 fetuses
out of 5 litters (including peromelia in 5 fetuses/4 litters;
palatoschisis in 1 fetus/1 litter), hydrocephalus and delayed
ossification.

iii. In a developmental toxicity study, pregnant female mice were
gavaged with technical tebuconazole at levels of 0, 10, 30, or 100 mg/
kg/day between days 6 and 15 of gestation (part 1 of study) or at
levels of 0, 10, 20, 30, or 100 mg/kg/day between days 6 and 15 of
gestation (part 2 of study). The maternal NOAEL was 10 mg/kg/day and
the maternal LOAEL was 20 mg/kg/day. Maternal toxicity (hepatocellular
vacuolation and elevations in AST, ALP and alkaline phosphatase)
occurred at

[[Page 1134]]

all dose levels but was minimal at 10 mg/kg/day. Reduction in mean
corpuscular volume in parallel with reduced hematocrit occurred at
doses greater than or equal to 20 mg/kg/day. The liver was the target
organ. The developomental NOAEL was 10 mg/kg/day and the developmental
LOAEL was 30 mg/kg/day based on an increase in the number of runts.
iv. In a developmental toxicity study, pregnant female mice were
administered dermal doses of technical tebuconazole applied at levels
of 0, 100, 300, or 1,000 mg/kg/day between days 6 and 15 of gestation.
Equivocal maternal toxicity was observed 1,000 mg/kg/day. The maternal
NOAEL was approx. 1,000 mg/kg/day. The developmental NOAEL was
1,000 mg/kg/day.

v. In a 2-generation reproduction study, rats were fed technical
tebuconazole at levels of 0, 100, 300, or 1,000 ppm, (0, 5, 15, or 50
mg/kg/day, males and females). The parental maternal NOAEL was 15 mg/
kg/day and the parental LOAEL was 50 mg/kg/day based on depressed body
weights, increased spleen hemosiderosis and decreased liver and kidney
weights. The reproductive NOAEL was 15 mg/kg/day and the reproductive
LOAEL of 50 mg/kg/day based on decreased pup body weights from birth
through 3 - 4 weeks.

6. Mutagenicity. An Ames test with Salmonella sp., a mouse
micronucleus assay, a sister chromatid exchange assay with Chinese
hamster ovary cells, and an unscheduled DNA synthesis assay with rat
hepatocytes provided no evidence of mutagenicity.
7. Dermal penetration. Radio-labeled technical tebuconazole in
ethanol was applied dermally to rats in doses of 0.604, 5.85, 52.4, or
547 micrograms per square centimeter (μg/cm**2). The
percent of dose absorbed after 24 hours amounted to 27.77, 27.06,
23.01, and 6.38% of the applied dose, respectively. The amount which
remained on the application site after soap and water wash increased
with the dose and amounted at 24 hours to 24.7, 24.4, 32.02, and 53.11%
of the above applied doses, respectively. The percent of the dose
absorbed after 8 hours was 49.9% at the dose of 0.604 μg/cm**2.
The ethanol used as a solvent may have led to an
overestimate of absorption.

8. Neurotoxicity. No acute or subchronic neurotoxicity studies are
available for tebuconazole. In a battery of subchronic and chronic
studies, there were no indications of treatment-related effects on the
central or peripheral nervous system of experimental animals. In the
prenatal developmental toxicity studies, however, several effects on
the fetal nervous system were noted. These effects included alterations
in the development of the fetal nervous system in mice (increased
malformations of the brain and spinal column, and exencephaly), in rats
(anophthalmia), and in rabbits (neural tubule defects characterized as
meningocoele and spina bifida, and hydrocephalus).

9. General metabolism. Rats were gavaged with 1 or 20 mg/kg radio-
labeled technical tebuconazole. 98.1 % of the oral dose was absorbed.
Within 72 hours of dosing, over 87% of the dose was excreted in urine
and feces. At sacrifice (72 hours post dosing), total residue (-GI
tract) amounted to 0.63% of the dose. A total of 10 compounds were
identified in the excreta. A large fraction of the identified
metabolites corresponded to successive oxidations steps of a methyl
group of the test material. At 20 mg/kg, changes in detoxication
patterns may be occurring.

B. Toxicological Endpoints

1. Acute toxicity. EPA selected the NOAEL of 10 mg/kg/day from a
developmental toxicity study in mice based on an increased incidence of
runts observed at the LOAEL of 30 mg/kg/day. The population subgroups
of concern are females (13+ years), infants, and children. An
Uncertainty Factor of 100 was used to account for inter-species
extrapolation and intra-species variability. On this basis, the acute
Reference dose (RfD) for tebuconazole was calculated to be 0.10 mg/kg/
day. EPA determined that a 10 x FQPA safety factor is applicable to the
subpopulations females (13+ years), as well as infants and children
because the effects seen were developmental, the severity of observed
effects and the effects are presumed to occur following "acute"
exposures. A dose and toxicity endpoint were not identified for the
general population.

2. Short - and intermediate - term toxicity. No short -
intermediate - or long-term dermal toxicity endpoints were identified.
For short - intermediate - and long-term inhalation toxicity, the NOAEL
of 0.0106 mg/L/day from the 21-day rat inhalation toxicity study was
selected for risk assessment. The LOAEL of 0.1558 mg/L/day was based on
induction of liver microsomal enzymes and piloerection.

3. Chronic toxicity. EPA established the RfD for tebuconazole at
0.03 mg/kg/day. The RfD is based on a 1-year feeding study in dogs in
which the NOAEL was 3.0 mg/kg/day and the LOAEL was 4.4 mg/kg/day based
on histopathological changes in the adrenal gland. An Uncertainty
Factor of 100 was used to account for inter-species extrapolation and
intra-species variability.

4. Carcinogenicity. EPA concluded that tebuconazole should be
classified as a Group C - possible human carcinogen and determined that
the RfD approach be used to estimate human risk. A statistically
significant increase in the incidence of hepatocellular adenomas,
carcinomas and combined adenoma/carcinomas was observed in male mice at
the highest dose tested; a statistically significant increase in the
incidence of hepatocellular carcinomas and combined adenomas/carcinomas
was observed in female mice at the highest dose tested; and
tebuconazole was determined to be structurally related to at least six
other triazole fungicides that also produce hepatocellular tumors in
male and/or female mice.

C. Exposures and Risks

1. From food and feed uses. Tolerances are established under 40
CFR Sec. 180.474(a) for residues of the fungicide tebuconazole in or on
bananas at 0.05 ppm, barley forage, hay and straw at 0.10, barley grain
at 0.05 ppm, cherries at 4.0 ppm, oat forage, hay and straw at 0.10
ppm, oat grain at 0.05 ppm, peaches (includes nectarines) at 1.0 ppm,
peanuts at 0.1 ppm, peanut hulls at 4.0 ppm, wheat forage, hay, and
straw at 0.10 ppm, and wheat grain at 0.05 ppm. Time-limited tolerances
for section 18 emergency exemptions are established under 40 CFR
Sec. 180.474(b)(1) for residues of the fungicide tebuconazole in or on
barley grain at 2.0 ppm, barley hay and straw at 20 ppm; pistachios at
1.0 ppm, wheat hay at 15 ppm, and wheat straw at 2.0 ppm. Time-limited
tolerances for section 18 emergency exemptions are established under 40
CFR Sec. 180.474(b)(2) for residues of the fungicide tebuconazole in or
on milk at 0.1 ppm; cattle, goats, hogs, horses, poultry, and sheep
meat byproducts at 0.2 ppm. Risk assessments were conducted by EPA to
assess dietary exposures from tebuconazole as follows.

Section 408(b)(2)(E) authorizes EPA to use available data and
information on the anticipated residue levels of pesticide residues in
food and the actual levels of pesticide chemicals that have been
measured in food. If EPA relies on such information, EPA must require
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. Following the initial data
submission, EPA is authorized to require similar data on a time frame
it deems appropriate. As required by

[[Page 1135]]

section 408(b)(2)(E), EPA will issue a data call-in for information
relating to anticipated residues to be submitted no later than 5 years
from the date of issuance of this tolerance.

i. Acute exposure and risk. Acute dietary 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 one day or single exposure. The acute dietary (food only) risk
assessment used a highly refined Monte Carlo analysis based on the
following assumptions: percent crop treated data were used for all
commodities; maximum residue levels from crop field trials for single
serving commodities such as bananas and peaches were utilized; average
residue levels from crop field trials were used for blended commodities
such as fruit juices, grains and oils; anticipated residue levels for
ruminant commodities were calculated using a livestock diet constructed
from anticipated residue levels for livestock feed items. Application
of the 10 x safety factor to the Acute RfD of 0.10 mg/kg/day results in
an acceptable acute dietary risk of 10% or less of the Acute RfD for
the following subpopulations of concern: 8.5% for children (1 to 6
years); 7.4% for non-nursing infants (<1 year); 7% for all infants (<1
year); 6.7% for nursing infants (<1 year); and 3.3% for children (7 to
12 years) and females (13+ years). Application of the 10 x safety
factor to the Acute RfD results in an acceptable acute dietary exposure
of 10% or less of the Acute RfD.

ii. Chronic exposure and risk. The chronic dietary (food only) risk
assessment used the RfD of 0.03 mg/kg/day. EPA used the Dietary
Exposure Evaluation Model (DEEM) which utilized data from the USDA
1989-91 Continuing Survey of Food Intake by Individuals (CSFII). The
risk assessment is very conservative and uses the Theoretical Maximum
Residue Concentration (TMRC) which assumes that 100% of all treated
food and/or feed commodities having tebuconazole tolerances will
contain tebuconazole residues at the tolerance level. EPA generally has
no concern for exposures below 100% of the chronic RfD (when the FQPA
factor has been removed) because this RfD represents the level at or
below which daily aggregate dietary exposure over a lifetime will not
pose appreciable risks to human health. The Agency has estimated that
chronic dietary exposure to tebuconazole from food only will utilize
12% of the chronic RfD for the population subgroup, U.S. Population,
and the maximum percent of the chronic RfD (41%) is utilized by
children (1-6 years).

2. From drinking water. There are no monitoring data for residues
of tebuconazole in ground water. No health advisory levels or Maximum
Contaminant Levels for residues of tebuconazole in drinking water have
been established. Tebuconazole is persistent and relatively immobile in
water.

The Agency used the Screening Concentration in Ground Water (SCI-
GROW) screening model to determine the Estimated Environmental
Concentration (EEC) of 0.3 μg/L of tebuconazole in ground water
for both chronic and acute analysis. SCI-GROW is an empirical model
based upon actual ground water monitoring data collected from the
registration of a number of pesticides that serve as benchmarks for the
model. SCI-GROW provides realistic estimates of pesticide
concentrations in shallow, highly vulnerable ground water sites (i.e.,
sites with sand soils and depth to ground water of 10 to 20 feet). EPA
compares drinking water levels of concern (DWLOC) directly with the
SCI-GROW model values.
The Agency used the Generic Estimated Environmental Concentration
(GENEEC) screening model to determine the surface water acute EEC of 14
μg/L (peak) and the surface water chronic EEC of 10 μg/
L (avg 56-day concentration). GENEEC is used to estimate pesticide
concentrations in surface water for up to 56 days after a single runoff
event. GENEEC provides an upper-bound concentration value and can
substantially overestimate (by a ≤3-fold factor) true
pesticide concentrations in drinking water. EPA applies a factor of 3
to GENEEC model values when determining whether or not a level of
concern has been exceeded. If the GENEEC model value is ≤3
times the DWLOC, the pesticide is considered to have passed the screen
and no further assessment is needed.

i. Acute exposure and risk. The acute DWLOC is 200 μg/L for
females (13+ years old) and 14 μg/L for infants/children. The
EEC's for acute analysis of water are 0.3 μg/L (ground water)
and 14 μg/L (surface water). EPA does not expect the acute
aggregate exposure to exceed 10% of the acute RfD. Therefore, EPA
concludes with reasonable certainty that no harm will result to the
subpopulations of concern, females (13+ years old), or infants and
children from aggregate exposure to residues of tebuconazole.

ii. Chronic exposure and risk. The chronic DWLOC is 910 μg/
L for the U.S. population, 720 μg/L for females (13+ years,
nursing), and 190 μg/L for infants/children. The EEC's for
chronic analysis of water are 0.3 μg/L (ground water) and 10
μg/L (surface water). EPA does not expect the chronic aggregate
exposure to exceed 100% of the chronic RfD. Therefore, EPA concludes
with reasonable certainty that no harm will result from chronic (non-
cancer) aggregate exposure to tebuconazole residues.

3. From non-dietary exposure. Tebuconazole is currently registered
for use on the following residential non-food sites: the formulation of
wood-based composite products, wood products for in-ground contact,
plastics, exterior paints, glues and adhesives. Exposure via incidental
ingestion (by children) and inhalation are not a concern for these
products which are used outdoors. No paints or other end-use products
containing tebuconazole are available for interior use. Thus, no risk
is expected for residential nonfood sites.

4. Cumulative exposure to substances with common mechanism of
toxicity. Section 408(b)(2)(D)(v) 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."

EPA does not have, at this time, available data to determine
whether tebuconazole has a common mechanism of toxicity with other
substances or how to include this pesticide in a cumulative risk
assessment. Unlike other pesticides for which EPA has followed a
cumulative risk approach based on a common mechanism of toxicity,
tebuconazole does not appear to produce a toxic metabolite produced by
other substances. For the purposes of this tolerance action, therefore,
EPA has not assumed that tebuconazole has a common mechanism of
toxicity with other substances. 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 the Final Rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).

D. Aggregate Risks and Determination of Safety for U.S. Population

1. Acute risk. Application of the 10x safety factor for enhanced
susceptibility of infants and children to the Acute RfD of 0.1 mg/kg/
day results in an acceptable acute dietary exposure of 10% or less of
the Acute RfD for the subpopulations of concern, females (13+ years),
infants and children. The acute

[[Page 1136]]

DWLOC for females (13+ years) is 200 μg/L and for infants/
children is 14 μg/L. These values are higher than the SCI-GROW
EEC value of 0.3 μg/L for ground water and the GENEEC acute EEC
of 14 μg/L for surface water (peak value) when divided by
three. Therefore, EPA concludes with reasonable certainty that the
potential risks from aggregate acute exposure (food & water) would not
exceed the Agency's level of concern.

2. Chronic risk. Using the TMRC exposure assumptions described
above, EPA has concluded that aggregate exposure to tebuconazole from
food will utilize 12% of the RfD for the U.S. population. The major
identifiable subgroup with the highest aggregate exposure is children
1-6 years old, as discussed below. EPA generally has no concern for
exposures below 100% of the RfD because the RfD represents the level at
or below which daily aggregate dietary exposure over a lifetime will
not pose appreciable risks to human health. Despite the potential for
exposure to tebuconazole in drinking water and from non-dietary, non-
occupational exposure, EPA does not expect the aggregate exposure to
exceed 100% of the RfD. EPA concludes that there is reasonable
certainty that no harm will result from aggregate exposure to
tebuconazole residues.

3. Aggregate cancer risk for U.S. population. EPA classified
tebuconazole as a Group C - possible human carcinogen and determined
that the RfD approach be used to estimate the carcinogenic risk to
humans. Risk concerns for carcinogenicity due to long-term consumption
of tebuconazole residues are adequately addressed by the aggregate
chronic exposure analysis using the chronic RfD. Therefore, EPA
concludes that there is reasonable certainty that no harm will result
from aggregate exposure to tebuconazole residues.

4. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
from aggregate exposure to tebuconazole residues.

E. Aggregate Risks and Determination of Safety for Infants and Children

1. Safety factor for infants and children--i. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of tebuconazole, EPA considered data from
developmental toxicity studies in mice, rats, rabbits and a 2-
generation reproduction study in the rat. The developmental toxicity
studies are designed to evaluate adverse effects on the developing
organism resulting from maternal pesticide exposure during gestation.
Reproduction studies provide information relating to effects from
exposure to the pesticide on the reproductive capability of mating
animals and data on systemic toxicity.

FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for pre-and post-natal toxicity ecies
variability) and not the additional tenfold MOE/uncertainty factor when
EPA has a complete data base under existing guidelines and when the
severity of the effect in infants or children or the potency or unusual
toxic properties of a compound do not raise concerns regarding the
adequacy of the standard MOE/safety factor.

ii. Pre- and post-natal sensitivity. Pre-natal developmental
toxicity studies indicated several effects on the fetal nervous system.
These effects included alterations in the development of the fetal
nervous system in mice (increased malformations of the brain and spinal
column, and exencephaly), in rats (anophthalmia), and in rabbits
(neural tubule defects characterized as meningocoele and spina bifida,
and hydrocephalus). On the basis of comparable developmental and
maternal NOAEL's and LOAEL's, EPA determined that there was no
indication of increased sensitivity of the offspring of mice, rats, or
rabbits to pre-natal or post-matal exposure to tebuconazole. However,
EPA does note that there is increased sensitivity in the pups based on
the more severe developmental effects observed at the developmental
LOAEL's and at higher doses as compared to the maternal effects
observed at the maternal LOAEL's and at higher doses. EPA also notes
that tebuconazole is structurally related to several other triazole
fungicides which have demonstrated a developmental LOAEL below the
maternal LOAEL in rats and/or rabbits.

iii. Conclusion. EPA determined that based on the observed fetal
nervous system effects and the fact that data on several other
structurally related triazole fungicides indicate neurotoxic effects, a
developmental neurotoxicity study will be required. Otherwise, there is
a complete toxicity database for tebuconazole and exposure data is
complete or is estimated based on data that reasonably accounts for
potential exposures. EPA determined that the 10x safety factor be
retained because of the increased sensitivity of pups as demonstrated
by the severity of the observed developmental effects, evidence of
alterations in the development of the fetal nervous system, the
structural relationship of tebuconazole to several other triazole
fungicides which have been shown to cause developmental effects, and
the fact that a developmental neurotoxicity study will be required.

2. Acute risk. EPA determined that the 10x factor to account for
enhanced sensitivity of infants and children be retained . Application
of the 10x safety factor to the Acute RfD of 0.10 mg/kg/day results in
an acceptable acute dietary risk of 10% or less of the Acute RfD for
the following subpopulations of concern: 8.5% for children (1 to 6
years); 7.4% for non-nursing infants (<1 year); 7% for all infants (<1
year); 6.7% for nursing infants (<1 year); and 3.3% for children (7 to
12 years) and females (13+ years). EPA concludes with reasonable
certainty that the potential risks from aggregate acute exposure (food
& water) would not exceed the Agency's level of concern.

3. Chronic risk. Using the exposure assumptions described above,
EPA has concluded that the highest aggregate exposure to tebuconazole
from food will utilize 41% of the RfD for children (1-6 years). EPA
generally has no concern for exposures below 100% of the RfD because
the RfD represents the level at or below which daily aggregate dietary
exposure over a lifetime will not pose appreciable risks to human
health. Despite the potential for exposure to tebuconazole in drinking
water and from non-dietary, non-occupational exposure, EPA does not
expect the aggregate exposure to exceed 100% of the RfD.

4. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to infants and children from aggregate exposure to tebuconazole
residues.

III. Other Considerations

A. Metabolism In Plants and Animals

The nature of the residue in plants and animals is adequately
understood. The residue of concern in plants is tebuconazole. The
residues of concern in animals are the parent compound, tebuconazole,
and its 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazole-1-yl-
methyl)-pentane-3,5-diol metabolite. Tolerances on animal commodities
milk at 0.1 ppm, and meat by-products of cattle, horses, goats and
sheep at 0.2 ppm are required in conjunction with this use.

B. Analytical Enforcement Methodology

Adequate enforcement methodology (gas chromatography) is available
to enforce the tolerance expression. The method may be requested from:
Calvin

[[Page 1137]]

Furlow, PIRIB, IRSD (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460.
Office location and telephone number: Rm 101FF, Crystal Mall #2, 1921
Jefferson Davis Hwy., Arlington, VA 22202, (703-305-5229).

C. Magnitude of Residues

EPA has concluded that residue data submitted in support of the
tolerances for grapes at 5 ppm, grass forage at 8 ppm, grass hay at 25
ppm, grass seed screenings at 55 ppm, grass straw at 30 ppm, milk at
0.1 ppm, and meat by-products of cattle, horses, goats and sheep at 0.2
ppm indicate that the tolerances requested by the petitioner are
adequate.

D. International Residue Limits

There are no established Codex, Canadian, or Mexican MRLs
established for tebuconazole. A Codex MRL is proposed for residues of
tebuconazole in or on grapes at 2.0 ppm. There are no proposed MRLs for

tebuconazole in or on grapes in Canada and Mexico. Tolerance
compatibility problems do not exist with respect to Mexico or Canada,
but do exist with respect to the Codex MRL. The submitted residue data
support a U.S. tolerance level of 5.0 ppm for tebuconazole in/on
grapes, and it is not possible to harmonize the proposed tolerance for
residues of tebuconazole in or on grapes with Codex. The higher
residues in the U.S. may be due to different agricultural practices
and/or climatic conditions.

E. Rotational Crop Restrictions

Rotational crop restrictions are not required as rotation to other
crops in conjunction with the production of grapes and grass grown for
seed is not considered significant.

IV. Conclusion

Therefore, the tolerances are established for residues of
tebuconazole in or on grapes at 5 ppm, grass forage at 8 ppm, grass hay
at 25 ppm, grass seed screenings at 55 ppm, grass straw at 30 ppm, and
tolerances are established for the combined residues of tebuconazole,
and its 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazole-1-yl-
methyl)-pentane-3,5-diol metabolite in milk at 0.1 ppm, and meat by-
products of cattle, horses, goats and sheep at 0.2 ppm.

V. Objections and Hearing Requests

The new FFDCA section 408(g) provides essentially the same process
for persons to "object" to a tolerance regulation issued by EPA under
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.

Any person may, by March 9, 1999, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33. If a hearing is requested, the objections must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the requestor (40 CFR 178.27). A request for a hearing
will be granted if the Administrator determines that the material
submitted shows the following: There is genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary; and resolution of the
factual issues in the manner sought by the requestor would be adequate
to justify the action requested (40 CFR 178.32). Information submitted
in connection with an objection or hearing request may be claimed
confidential by marking any part or all of that information as CBI.
Information so marked will not be disclosed except in accordance with
procedures set forth in 40 CFR part 2. A copy of the information that
does not contain CBI must be submitted for inclusion in the public
record. Information not marked confidential may be disclosed publicly
by EPA without prior notice.

VI. Public Record and Electronic Submissions

EPA has established a record for this rulemaking under docket
control number [OPP-300768] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA.
Electronic comments may be sent directly to EPA at:
opp-docket@epamail.epa.gov.

Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in "ADDRESSES" at the beginning of this document.

VII. Regulatory Assessment Requirements

A. Certain Acts and Executive Orders

This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). 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., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior consultation as specified by Executive Order
12875, entitled Enhancing the Intergovernmental Partnership (58 FR
58093, October 28, 1993), or special considerations as required by
Executive Order 12898, entitled Federal Actions to

[[Page 1138]]

Address Environmental Justice in Minority Populations and Low-Income
Populations (59 FR 7629, February 16, 1994), or require OMB review in
accordance with Executive Order 13045, entitled Protection of Children
from Environmental Health Risks and Safety Risks (62 FR 19885, April
23, 1997).

In addition, since tolerances and exemptions that are established
on the basis of a petition under FFDCA section 408(d), such as the
tolerances 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. Nevertheless, the Agency has
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.

B. Executive Order 12875

Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local, or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments "to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates."
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.

C. Executive Order 13084

Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide to OMB, in a separately
identified section of the preamble to the rule, a description of the
extent of EPA's prior consultation with representatives of affected
tribal governments, a summary of the nature of their concerns, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 13084 requires EPA to develop an effective process
permitting elected officials and other representatives of Indian tribal
governments "to provide meaningful and timely input in the development
of regulatory policies on matters that significantly or uniquely affect
their communities."

Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do not apply to
this rule.

VIII. Submission to Congress and the Comptroller General

The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
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 the rule in the Federal Register. This 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: December 21, 1998.

James Jones,
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:

PART 180 -- [AMENDED]

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

Authority: 21 U.S.C. 346a and 371.

2. In Sec. 180.474, in paragraph (a), by designating the text after
the heading as paragraph (a)(1) and alphabetically adding the following
commodities to the table and by adding a new paragraph (a)(2) to read
as follows:

Sec. 180.474 Tebuconazole; tolerances for residues.

(a)(1) * * *

------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
* * * * *

Grapes.................................... 5.0

Grass, forage............................. 8.0

Grass, hay................................ 25.0

Grass, seed screenings.................... 55.0

Grass, straw.............................. 30.0

* * * * *
------------------------------------------------------------------------

(a)(2) Tolerances are established for the combined residues of the
fungicide, tebuconazole and its 1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-
1,2,4-triazole-1-yl-methyl)-pentane-3,5-diol metabolite.

------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Cattle, mbyp.............................. 0.2

Goats, mbyp............................... 0.2

Horses, mbyp.............................. 0.2

Milk...................................... 0.1

Sheep, mbyp............................... 0.2
------------------------------------------------------------------------

* * * * *
[FR Doc. 99-319 Filed 1-7-99; 8:45 am]
BILLING CODE 6560-50-F