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Tebufenozide; Pesticide Tolerance
Note: EPA no longer updates this information, but it may be useful as a reference or resource.
[Federal Register: April 7, 1999 (Volume 64, Number 66)]
[Rules and Regulations]
[Page 16850-16856]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr07ap99-12]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300828; FRL-6072-6]
RIN 2070-AB78
Tebufenozide; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
Tebufenozide, benzoic acid, 3,5-dimethyl-, 1-(1,1-dimethylethyl)-2-(4-
ethylbenzoyl) hydrazide in or on berry (crop group 13), cranberry, and
mint. The Interregional Research Project Number 4 (IR-4) requested
these tolerances under the Federal Food, Drug, and Cosmetic Act, as
amended by the Food Quality Protection Act of 1996.
DATES: This regulation is effective April 7, 1999. Objections and
requests for hearings must be received by EPA on or before June 7,
1999.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300828], 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-300828], 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 be submitted electronically by sending electronic mail (e-
mail) to: opp-docket@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 file
format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300828]. 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: Sidney Jackson, 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: Rm. 272, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, (703) 305-7610, e-mail:
jackson.sidney@epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of February 9, 1999
(64 FR 6351) (FRL-6058-3), EPA issued a notice pursuant to section 408
of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as
amended by the Food Quality Protection Act of 1996 (FQPA) (Pub. L. 104-
170) announcing the filing of pesticide petitions (PP) 8E5021, 8E4983,
and 8E5019 for tolerance by IR-4 . This notice included a summary of
the petition prepared by the Rohm and Haas Company, the registrant.
There were no comments received in response to the notice of filing.
The petition requested that 40 CFR 180.482 be amended by
establishing tolerances for residues of the insecticide tebufenozide,
benzoic acid, 3,5-dimethyl-, 1-(1,1-dimethylethyl)-2-(4-ethylbenzoyl)
hydrazide, in or on the berry crop group at 3.0 parts per million
(ppm), cranberry at 1.0 ppm, and mint at 10.0 ppm.
I. Background 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
tebufenozide and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for residues of
tebufenozide on the berry crop group at 3.0 ppm, cranberry at 1.0 ppm,
and mint at 10.0 ppm. 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 sensitivities
of major identifiable subgroups of consumers, including infants and
children. The nature of the toxic effects caused by tebufenozide are
discussed in this unit.
1. Acute toxicity. Results of a battery of toxicological studies
using technical grade product show tebufenozide has low acute toxicity.
Tebufenozide was practically non-toxic by ingestion of a single oral
dose in rats and mice (LD50 > 5,000 milligram/kilogram (mg/
kg)) and was practically non-toxic by dermal application lethal
dose(LD) LD50 > 5,000
[[Page 16851]]
mg/kg. Tebufenozide was not significantly toxic to rats after a 4-hr
inhalation exposure with a lethal concentration(LC) LC50
value of 4.5 mg/L (highest attainable concentration), is not considered
to be a primary eye irritant or a skin irritant and is not a dermal
sensitizer. An acute neurotoxicity study in rats did not produce any
neurotoxic or neuropathologic effects.
2. Genotoxicty. Tebufenozide technical was negative (non-
mutagenic) in an Ames assay with and without hepatic enzyme activation
and in a reverse mutation assay with E. coli. Tebufenozide technical
was negative in a hypoxanthine guanine phophoribosyl transferase
(HGPRT) gene mutation assay using Chinese hamster ovary (CHO) cells in
culture when tested with and without hepatic enzyme activation. In
isolated rat hepatocytes, tebufenozide technical did not induce
unscheduled DNA synthesis (UDS) or repair when tested up to the maximum
soluble concentration in culture medium. Tebufenozide did not produce
chromosome effects in vivo using rat bone marrow cells or in vitro
using Chinese hamster ovary cells (CHO). On the basis of the results
from this battery of tests, it is concluded that tebufenozide is not
mutagenic or genotoxic.
3. Reproductive and developmental toxicity-- i. Reproductive
toxicity. In a 1993 2-generation reproduction study in Sprague-Dawley
rats, the parental (systemic) no observable adverse effect levels
(NOAEL) was 0.8 and 0.9 mg/kg/day for males and females, respectively.
The parental (systemic) lowest observable adverse effect level(LOAEL)
was 11.5 and 12.8 mg/kg/day for males and females, respectively, based
on decreased body weight, body weight gain, and food consumption in
males. An increased incidence and/or severity of splenic pigmentation
was also observed. The reproductive NOAEL was 11.5 and 12.8 mg/kg/day
for males and females, respectively. The reproductive LOAEL was 154.8
and 171.1 mg/kg/day for males and females, respectively, based on an
increase in the number of pregnant females with increased gestation
duration and dystocia. Effects in the offspring consisted of decreased
number of pups per litter on postnatal days 0 and/or 4.
In a 1995 2-generation reproduction study designed to evaluate
parental (systemic) toxicity in rats, the NOAEL was 1.6 and 1.8 mg/kg/
day in males and females, respectively. The LOAEL was 12.6 and 14.6 mg/
kg/day in males and females, respectively, based on histopathological
findings of congestion and extramedullary hematopoiesis in the spleen.
The offspring NOAEL was 12.6 and 14.6 mg/kg/day in males and females,
respectively. The offspring LOAEL was 126.0 and 143.2 mg/kg/day in
males and females, respectively, based on decreased body weight on
postnatal days 14 and 21.
ii. Developmental toxicity. In a prenatal developmental toxicity
study in Sprague-Dawley rats, there was no evidence of maternal or
developmental toxicity at the highest dose level of 1,000 mg/kg/day.
The maternal and developmental toxicity NOAEL was 1,000 mg/kg/day .
In a prenatal developmental toxicity study conducted in New Zealand
white rabbits, tebufenozide was administered in doses of 50, 250, or
1,000 mg/kg/day on gestation days 7-19. No evidence of maternal or
developmental toxicity was observed. The maternal and developmental
toxicity NOAEL was 1,000 mg/kg/day.
4. Subchronic toxicity. i. The NOAEL in a 90-day rat feeding study
was 200 ppm (13 mg/kg/day for males, 16 mg/kg/day for females). The
LOAEL was 2,000 ppm (133 mg/kg/day for males, 155 mg/kg/day for
females). Decreased body weights in males and females was observed at
the LOAEL of 2,000 ppm. As part of this study, the potential for
tebufenozide to produce subchronic neurotoxicity was investigated.
Tebufenozide did not produce neurotoxic or neuropathologic effects when
administered in the diets of rats for 3 months at concentrations up to
and including the limit dose of 20,000 ppm (NOAEL = 1,330 mg/kg/day for
males, 1,650 mg/kg/day for females).
ii. In a 90-day feeding study with mice, the NOAEL was 20 ppm (3.4
and 4.0 mg/kg/day for males and females, respectively). The LOAEL was
200 ppm (35.3 and 44.7 mg/kg/day for males and females, respectively).
Decreases in body weight gain were noted in male mice at the LOAEL of
200 ppm.
iii. A 90-day dog feeding study gave a NOAEL of 50 ppm (2.1 mg/kg/
day for males and females). The LOAEL was 500 ppm (20.1 and 21.4 mg/kg/
day for males and females, respectively). At the LOAEL, females
exhibited a decrease in rate of weight gain and males presented an
increased reticulocyte.
iv. A 10-week study was conducted in the dog to examine the
reversibility of the effects on hematological parameters that were
observed in other dietary studies with the dog. Tebufenozide was
administered for 6 weeks in the diet to 4 male dogs at concentrations
of either 0 or 1,500 ppm. After the sixth week, the dogs receiving
treated feed were switched to the control diet for 4 weeks.
Hematological parameters were measured in both groups prior to
treatment, at the end of the 6-week treatment, after 2 weeks of
recovery on the control diet and after 4 weeks of recovery on the
control diet. All hematological parameters in the treated/recovery
group were returned to control levels indicating that the effects of
tebufenozide on the hemopoietic system are reversible in the dog.
v. In a 21-day dermal toxicity study of tebufenozide, rats (6/sex/
dose) received repeated dermal administration of either the technical
96.1% product RH-75,992 at 1,000 mg/kg/day (Limit-Dose) or the
formulation (23.1% a.i.) product RH-755,992 2F at 0, 62.5, 250, or
1,000 mg/kg/day, 6 hours/day, 5 days/week for 21 days. The high dose
was administered as the ``neat'' compound, while the low and mid-dose
were prepared as dilutions with distilled water. While the untreated
group received no treatment, the solvent control group received a ``2F
Formulation Blank'' at a solvent volume equal to that received by the
formulation high-dose group.
Under conditions of this study, RH-75,992 Technical or RH-75,992 2F
demonstrated no systemic toxicity or dermal irritation at the highest
dose tested 1,000 mg/kg/ during the 21 day study.
Based on these results, the NOAEL for systemic toxicity and dermal
irritation in both sexes is 1,000 mg/kg/day, the highest dose tested. A
LOAEL for systemic toxicity and dermal irritation was not established.
5. Chronic toxicity/Carcinogenicity. i. A 1-year feeding study in
dogs resulted in decreased red blood cells, hematocrit, and hemoglobin
and increased Heinz bodies, reticulocytes, and platelets at the LOAEL
of 8.7 mg/kg/day. The NOAEL for systemic toxicity was 1.8 mg/kg/day.
ii. An 18-month mouse carcinogenicity study showed no signs of
carcinogenicity at dosage levels up to and including 1,000 ppm, the
highest dose tested.
iii. In a combined rat chronic/carcinogenicity study, the NOAEL for
chronic toxicity was 100 ppm (4.8 and 6.1 mg/kg/day for males and
females, respectively) and the LOAEL was 1,000 ppm (48 and 61 mg/kg/day
for males and females, respectively). No carcinogenicity was observed
at the dosage levels up to 2,000 ppm (97 mg/kg/day and 125 mg/kg/day
for males and females, respectively).
B. Toxicological Endpoints
1. Acute toxicity. Toxicity observed in oral toxicity studies were
not
[[Page 16852]]
attributable to a single dose (exposure). No neurological or systemic
toxicity was observed in rats given a single oral administration of
tebufenozide at 0, 500, 1,000 or 2,000 mg/kg. No maternal or
developmental toxicity was observed following oral administration of
tebufenozide at 1,000 mg/kg/day (Limit-Dose) during gestation to
pregnant rats or rabbits. The Agency concludes that this risk is
negligible. Therefore, no toxicological endpoint is required for acute
toxicity.
2. Short- and intermediate-term toxicity. Since there are no
registered residential uses, there were no dermal and inhalation
endpoints established for tebufenozide. No dermal or systemic toxicity
was seen in rats receiving 15 repeated dermal applications of the
technical (97.2%) product at 1,000 mg/kg/day (Limit-Dose) as well as a
formulated (23% a.i.) product at 0, 62.5, 250, or 1,000 mg/kg/day over
a 21-day period. The Agency noted that in spite of the hematological
effects seen in the dogs study, similar effects were not seen in rats
receiving the compound via the dermal route indicating poor dermal
absorption. Also, no developmental endpoints of concern were evident
due to the lack of developmental toxicity in either rat or rabbit
studies. The Agency concludes that this risk is negligible and no
toxicological endpoint is required for short- and intermediate-term
toxicity.
3. Chronic toxicity. EPA has established the Reference dose (RfD)
for tebufenozide at 0.018. This RfD is based on a chronic toxicity
study in dogs which found growth retardation, alterations in hematology
parameters, changes in organ weights, and histopathological lesions in
the bone, spleen and liver at 8.7 mg/kg/day.
4. Carcinogenicity. Tebufenozide has been classified as a Group E,
``no evidence of carcinogenicity for humans,'' chemical by the Agency's
RfD Committee.
5. Animal metabolism. The absorption, distribution, excretion and
metabolism of tebufenozide in rats was investigated. Tebufenozide is
partially absorbed, is rapidly excreted and does not accumulate in
tissues. Although tebufenozide is mainly excreted unchanged, a number
of polar metabolites were identified. These metabolites are products of
oxidation of the benzylic ethyl or methyl side chains of the molecule.
These metabolites were detected in plant and other animal (rat, goat,
hen) metabolism studies.
6. Metabolite toxicology. Common metabolic pathways for
tebufenozide have been identified in both plants (grape, apple, rice
and sugar beet) and animals (rat, goat, hen). The metabolic pathway
common to both plants and animals involves oxidation of the alkyl
substituents (ethyl and methyl groups) of the aromatic rings primarily
at the benzylic positions. Extensive degradation and elimination of
polar metabolites occurs in animals such that residues are unlikely to
accumulate in humans or animals exposed to these residues through the
diet.
7. Endocrine disruption. The toxicology profile of tebufenozide
shows no evidence of physiological effects characteristic of the
disruption of the hormone estrogen. Based on structure-activity
information, tebufenozide is unlikely to exhibit estrogenic activity.
Tebufenozide was not active in a direct in vitro estrogen binding
assay. No indicators of estrogenic or other endocrine effects were
observed in mammalian chronic studies or in mammalian and avian
reproduction studies. Ecdysone has no known effects in vertebrates.
Overall, the weight of evidence provides no indication that
tebufenozide has endocrine activity in vertebrates.
C. Exposures and Risks
1. From food and feed uses. Tolerances have been established (40
CFR 180.482) for the residues of tebufenozide, in or on a variety of
raw agricultural commodities. Currently established tolerances for
residues of tebufenozide are listed under 40 CFR 180.482 and include
permanent tolerances for residues in/on pecans (0.01 ppm) and walnuts
(0.1 ppm), import tolerances for residues in/on apples (1.0 ppm) and
wine grapes (0.5 ppm), and time-limited tolerances on various plant and
animal commodities.
The metabolic fate of tebufenozide in animals is currently under
review by the Agency, therefore, in this risk assessment, only existing
and proposed uses of tebufenozide on raw agricultural commodities are
considered as no livestock feed items are derived from berry (crop
group 13), cranberry and mint. Risk assessments were conducted by EPA
to assess dietary exposures from tebufenozide as follows:
Section 408(b)(2)(F) states that the Agency may use data on the
actual percent of food treated (PCT) for assessing chronic dietary risk
only if the Agency can make the following findings: That 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 such pesticide
residue; that the exposure estimate does not underestimate exposure for
any significant subpopulation group; and if 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 percent of crop treated as required by the section 408(b)(2)(F), EPA
may require registrants to submit data on PCT.
The Agency used PCT information as follows:
To refine chronic dietary exposure and risk estimates obtained by
the use of the Dietary Exposure Evaluation Model (DEEM), which
incorporates data from the Continuing Survey of Food Intakes by
Individuals (CSFII) for a specified period.
The Agency believes that the three conditions, discussed in section
408 (b)(2)(F) in this unit concerning the Agency's responsibilities in
assessing chronic dietary risk findings, have been met. The PCT
estimates are derived from Federal and private market survey data,
which are reliable and have a valid basis. Typically, a range of
estimates are supplied and the upper end of this range is assumed for
the exposure assessment. By using this upper end estimate of the PCT,
the Agency is reasonably certain that the percentage of the food
treated is not likely to be underestimated. The 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 information on the regional consumption of food to
which tebufenozide may be applied in a particular area.
i. Acute exposure and risk. No endpoints were selected for acute
dietary exposure. 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 1-day or
single exposure. Toxicity observed in oral toxicity studies were not
attributable to a single dose (exposure). No neurological or systemic
toxicity was
[[Page 16853]]
observed in rats given a single oral administration of tebufenozide at
0, 500, 1,000 or 2,000 mg/kg. No maternal or developmental toxicity was
observed following oral administration of tebufenozide at 1,000 mg/kg/
day (Limit-Dose) during gestation to pregnant rats or rabbits. This
risk assessment is not required. The Agency considers acute exposure/
risk to be negligible.
ii. Chronic exposure and risk. The residue of concern for
tebufenozide in plant and animal commodities is the parent compound per
se. The RFD used for the chronic dietary analysis is 0.018 mg/kg/day.
In performing chronic dietary exposure and risk analysis, the Agency
used the Dietary Exposure Evaluation Model (DEEM), which incorporates
data from the CSFII for the period, 1989 to 1992. Some refinement to
the dietary exposure estimates was made through the use of percent-of-
crop-treated data. The resulting Anticipated Residue Contributions
(ARC) for the U.S. population and various DEEM population subgroups can
be determined. Of these subgroups, the highest exposure is projected
for children ages 1-6 years, whose chronic intake is estimated as 73%
of the RfD. Percent RFD values for other subgroups include: U.S.
population for the 48 states (36), all infants less than 1 year old
(52) and children 7 to 12 years old (46). Generally, in the absence of
additional safety factors, the Agency is not concerned with exposures
less than 100% of the RfD. Thus, for all populations, the chronic human
health risk from exposure to tebufenozide in foods is below the
Agency's level of concern.
2. From drinking water. Available data suggest that tebufenozide
ranges from moderately persistent to persistent and is mobile; thus,
tebufenozide could potentially leach to ground water and runoff to
surface water under certain environmental conditions. There is no
Maximum contaminant Level (MCL) for residues of tebufenozide in
drinking water. No drinking water Health Advisories have been issued
for tebufenozide. There is no entry for tebufenozide in the
``Pesticides in Groundwater Database (EPA 734-12-92-001, September
1992). The Agency concludes that there is reasonable certainty that no
harmful exposure exist from drinking water.
Chronic exposure and risk. Monitoring data are not available to
assess the human exposure to tebufenozide via drinking water. In lieu
of these data, the Agency has calculated the Tier I estimated
concentrations in drinking water (DWECs) for tebufenozide using Generic
expected environmental concentration (GENEEC) (surface water) and
Screening concentration In Ground Water (SCI-GROW) (ground water) for
use in the human health risk assessment. According to Agency records,
the maximum application rate for tebufenozide is 0.25 lb a.i. x 5
applications per year on pecans. This application scenario was used to
calculate the DWECs for the human health risk assessment due to the
wide range of aerobic soil half-life of 6 (California Loam) and 729
(worst case soil with low microbial activity) days. For surface water,
the chronic (56-day) values are 13.3 parts per billion (ppb) and 16.5
ppb for the half-lives of 66 and 729 days, respectively. The ground
water screening concentrations are 0.16 ppb and 1.04 ppb for the half-
lives of 66 and 729 days, respectively. These values represent upper-
bound estimates of the concentrations that might be found in surface
and ground water due to the use of tebufenozide on pecans.
In performing this risk assessment, the Agency has calculated
drinking water levels of concern (DWLOCs) for each of the DEEM
population subgroups. Within each subgroup, the population with the
highest estimated exposure was used to determine the maximum
concentration of tebufenozide that can occur in drinking water without
causing an unacceptable human health risk. As a comparison value, the
Agency has used the 16.5 ppb value in this risk assessment, as this
represents a worst-case scenario. The DWLOCs for tebufenozide are above
the DWEC of 16.5 ppb for all population subgroups. Therefore, the
Agency believes that the human health risk from exposure to
tebufenozide through drinking water is not likely to exceed the
Agency's level of concern.
Because the Agency lacks sufficient water-related exposure data to
complete a comprehensive drinking water risk assessment for many
pesticides, EPA has commenced and nearly completed a process to
identify a reasonable yet conservative bounding figure for the
potential contribution of water-related exposure to the aggregate risk
posed by a pesticide. In developing the bounding figure, EPA estimated
residue levels in water for a number of specific pesticides using
various data sources. The Agency then applied the estimated residue
levels, in conjunction with appropriate toxicological endpoints (RfD's
or acute dietary no observed adverse effect levels (NOAEL's)) and
assumptions about body weight and consumption, to calculate, for each
pesticide, the increment of aggregate risk contributed by consumption
of contaminated water. While EPA has not yet pinpointed the appropriate
bounding figure for exposure from contaminated water, the ranges the
Agency is continuing to examine are all below the level that would
cause tebufenozide to exceed the RfD if the tolerance being considered
in this document were granted. The Agency has therefore concluded that
the potential exposures associated with tebufenozide in water, even at
the higher levels the Agency is considering as a conservative upper
bound, would not prevent the Agency from determining that there is a
reasonable certainty of no harm if the tolerance is granted.
3. From non-dietary exposure. Tebufenozide is not currently
registered for use on residential non-food sites. The Agency concludes
that there are no chronic, short- or intermediate-term non-dietary
exposure.
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 tebufenozide 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,
tebufenozide 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 tebufenozide 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. Since no acute toxicity endpoints were identified
for tebufenozide, the Agency concludes that acute aggregate risk from
the use of the pesticide will not pose an unacceptable risk to human
health.
2. Chronic risk. In aggregating risks, the Agency has considered
only dietary exposure. Due to lack of endpoints and/or relevant use
registrations, assessment
[[Page 16854]]
of exposure via non-dietary routes (e.g., dermal, inhalation, non-
dietary oral) are not required. Using the Anticipated Residue
Contribution exposure assumptions described in this unit, EPA has
concluded that aggregate exposure to tebufenozide from food will
utilize 36% of the RFD for the U.S. population. The major identifiable
subgroup with the highest aggregate exposure is children (1-6 years
old) at 73% of the RFD and is 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.
Since the dietary risk for tebufenozide is below the Agency's level
of concern and the estimated concentrations of tebufenozide in drinking
water are below EPA's drinking water level of concern, the Agency
believes that establishment of the requested tolerances for
tebufenozide will not pose an unacceptable aggregate health risk to
infants, children, or adults.
3. Short- and intermediate-term risk. In aggregating risks, the
Agency has considered only dietary exposure. Due to lack of endpoints
and/or residential use registrations, the agency concludes that short-
and intermediate-term risk via non-dietary routes (e.g., dermal,
inhalation, non-dietary oral) will not pose an unacceptable risk to
human health.
4. Aggregate cancer risk for U.S. population. Tebufenozide is
classified as a Group E chemical (no evidence of carcinogenicity in
humans). The Agency concludes that the aggregate cancer risk for the U.
S. population is not impacted by the establishment of these proposed
tolerances.
5. Determination of safety. EPA concludes that there is a
reasonable certainty that no harm will result from aggregate exposure
to tebufenozide 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 tebufenozide EPA considered data from
developmental toxicity studies in the rat and rabbit 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 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 and the
completeness of the database unless EPA determines that a different
margin of safety will be safe for infants and children. Margins of
safety are incorporated into EPA risk assessments either directly
through use of a margin of exposure (MOE) analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. EPA believes that reliable data support
using the standard uncertainty factor (usually 100 for combined inter-
and intra-species 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. Developmental toxicity studies. Developmental toxicity studies
showed no increased sensitivity in fetuses as compared to maternal
animals following in utero exposures in rats and rabbits. See
discussion under Unit II.A. of this preamble.
iii. Reproductive toxicity study. Multi-generation reproduction
toxicity studies in rats showed no increased sensitivity in pups as
compared to adults and offsprings. See discussion under Unit II.A. of
this premble.
iv. Pre- and post-natal sensitivity. The Agency determined that
available data provide no indication of increased sensitivity of rats
or rabbits to in utero and/or postnatal exposure to tebufenozide.
v. Conclusion. The Agency believes that reliable data support using
the standard hundredfold safety factor for assessing sensitivity to
residues of tebufenozide and that an additional tenfold margin of
safety for infants and children is not warranted. There is a complete
toxicity database for tebufenozide and exposure data are complete or
estimated based on data that reasonably account for potential
exposures.
2. Acute risk. No acute toxicity endpoints for tebufenozide have
been identified and this risk assessment is not required.
3. Chronic risk. Using the exposure assumptions described in this
unit, EPA has concluded that aggregate exposure to tebufenozide from
food only will utilize 52% and 73% of the RfD for all infants (<1 yr
old) and children (1-6 yr old), respectively. 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. EPA does not
expect the aggregate exposure from tebufenozide in food, drinking water
and from non-dietary exposure to exceed the Agency level of concern.
4. Short- or intermediate-term risk. Since no short- or
intermediate-term toxicological endpoints were identified by the Agency
for tebufenozide and there are no registered uses that would result in
residential exposure, the Agency concludes that this risk criterion is
negligible and the subject tolerances adequately protect the safety of
infants and children.
5. 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 tebufenozide
residues.
III. Other Considerations
A. Metabolism In Plants and Animals
The metabolism of tebufenozide in plants (grapes, apples, rice and
sugar beets) is adequately understood for the purpose of these
tolerances. The metabolism of tebufenozide in all crops was similar and
involves oxidation of the alkyl substituents of the aromatic rings
primarily at the benzylic positions. The extent of metabolism and
degree of oxidation are a function of time from application to harvest.
In all crops, parent compound comprised the majority of the total
dosage. None of the metabolites were in excess of 10% of the total
dosage.
Since there are no animal feed items associated with the berry crop
group, cranberry and mint tops (leaves and stems), a discussion of the
qualitative nature of the residue in animals is not germane to this
action.
B. Analytical Enforcement Methodology
High performance liquid chromatographic (HPLC) analytical methods
using ultraviolet (UV) detection have been validated for blueberries,
raspberries, cranberries, and mint foliage. The methods involve
extraction by blending with solvents, purification of the extracts by
liquid-liquid partitions and final purification of the residues using
solid phase extraction column chromatography. The limits of
quantitation is 0.005 ppm for blueberries, 0.01 ppm for mint foliage,
[[Page 16855]]
and raspberries, 0.02 ppm for mint oil, and 0.05 ppm for cranberries.
C. Magnitude of Residues
Field residue trials were conducted with a 70WP formulation in
geographically representative regions of the United States. A total of
eight field residue trials were conducted in blueberries. The average
blueberry residue value from all trials was 0.81 ppm.
A total of six field residue trials were conducted in cranberries.
The average cranberry residue value from all trials was 0.30 ppm.
A total of five field residue trials were conducted in mint. The
average mint foliage residue value from all trials was 7.11 ppm. Mint
oil was prepared from foliage from two residue trials. The average oil
residue was 0.23 ppm. Since residues do not concentrate in oil, a
tolerance is not needed.
A total of five field residue trials were conducted in raspberries.
The average raspberry residue value from all trials was 0.62 ppm.
D. International Residue Limits
There are currently no CODEX, Canadian or Mexican maximum residue
levels (MRLs) established for tebufenozide in blueberries, cranberries
or mint, therefore no harmonization issues are required for this
action.
IV. Conclusion
Therefore, the tolerance is established for residues of
tebufenozide in the berry crop group at 3.0 ppm, cranberry at 1.0 ppm,
and mint at 10.0 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 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 June 7, 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 under the ``ADDRESSES'' section (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
regulation. 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(i). EPA is authorized to waive any fee requirement
``when in the judgement of the Administrator such a waiver or refund is
equitable and not contrary to the purpose of this subsection.'' For
additional information regarding tolerance objection fee waivers,
contact James Tompkins, 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: Rm. 239, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, (703) 305-5697, tompkins.jim@epa.gov. Requests for
waiver of tolerance objection fees should be sent to James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460.
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 regulation under docket
control number [OPP-300828] (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.
Objections and hearing requests may be sent by e-mail directly to
EPA at:
opp-docket@epa.gov.
E-mailed objections and hearing requests must be submitted as an
ASCII file avoiding the use of special characters and any form of
encryption. The official record for this regulation, as well as the
public version, as described in this unit 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 record which
will also include all comments submitted directly in writing. The
official 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 a tolerance under section 408(d) of the
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). 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
[[Page 16856]]
Order 12898, entitled Federal Actions to 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
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. Nevertheless, the Agency 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 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 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: March 24, 1999.
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. 180.482, by revising the introductory text to paragraph
(a) and by adding alphabetically the following entries to the table in
paragraph (a).
Sec. 180.482 Tebufenozide; tolerances for residues.
(a) General. Tolerances are established for residues of the
insecticide tebufenozide, benzoic acid, 3,5-dimethyl-1-(1,1-
dimethylethyl)-2-(4-ethylbenzoyl)hydrazide, in or on the following raw
agricultural commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
* * * * *
Berry (crop group 13)...................................... 3.0
Cranberry.................................................. 1.0
* * * * *
Peppermint, tops........................................... 10.0
Spearmint, tops........................................... 10.0
------------------------------------------------------------------------
* * * * *
[FR Doc. 99-8341 Filed 4-6-99; 8:45 am]
BILLING CODE 6560-50-F