Fenpyroximate; Time-Limited Pesticide Tolerance

[Federal Register: April 10, 2001 (Volume 66, Number 69)]
[Rules and Regulations]
[Page 18561-18569]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10ap01-21]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-301109; FRL-6773-2]
RIN 2070-AB78

Fenpyroximate; Time-Limited Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a time-limited tolerance for the
combined residues of fenpyroximate benzoic acid, 4-[[[(E)-(1,3-
dimethyl-5-phenoxy-1H-pyrazol-4-yl) methylene]amino] oxy]methyl]-, 1,1-
dimethylethyl ester] and its z-isomer benzoic acid, 4-[[[[(Z)-(1,3-
dimethyl-5-phenoxy-1H-pyrazol-4-yl) methylene]aminio]oxy]methyl]-,1,1-
dimethylethyl ester)] in or on wine grapes and hops. Nihon Nohyaku
requested this tolerance under the Federal Food, Drug, and Cosmetic
Act, as amended by the Food Quality Protection Act (FQPA) of 1996. The
tolerance will expire April 12, 2004.

DATES: This regulation is effective April 10, 2001. Objections and
requests for hearings, identified by docket control number OPP-301109,
must be received by EPA on or before June 11, 2001.

ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. To ensure proper receipt by EPA, your objections and
hearing requests must identify docket control number OPP-301109 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Melody Banks, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 305-5413; and e-mail address:
banks.melody@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
------------------------------------------------------------------------

This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person

[[Page 18562]]

listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'', ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/. A frequently updated electronic
version of 40 CFR part 180 is available at http://www.access.gpo.gov/
nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, a beta site currently
under development.
2. In person. The Agency has established an official record for
this action under docket control number OPP-301109. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.

II. Background and Statutory Findings

In the Federal Register of February 18, 1999 (64 FR 8090) (FRL-
6059-9), 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) (Public Law 104-170)
announcing the filing of a pesticide petition (PP) for tolerance by
Nihon Nohyaku, Nihon Noyaku Co., 2-5 Nihonsbashi 1-Chome, Chuoku, Tokyo
103, Japan. This notice included a summary of the petition prepared by
Nihon Nohyaku, the registrant.
The petition requested that 40 CFR part 180 be amended by
establishing a tolerance for residues of the insecticide, fenpyroximate
and its z-isomer, in or on wine grapes at 1.0 parts per million (ppm)
and hops at 10 ppm. The tolerance will expire April 12, 2004.
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).

III. 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 and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerance for residues of fenpyroximate and its z-
isomer on wine grapes at 1 ppm and hops at 10 ppm. EPA's assessment of
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 fenpyroximate are
discussed below following Table 1 as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effect level
(LOAEL) from the toxicity studies reviewed.
Fenpyroximate is toxicity category II for oral toxicity (the only
acute study conducted). Acute studies are not required for import
tolerances.
Subchronic and chronic studies in the rat resulted in decreased
body weight and weight gain (also observed in the mouse carcinogenicity
study). There were hematological effects and decreased plasma butyryl
cholinesterase and plasma acetylcholinesterase at higher doses. In the
subchronic and chronic dog studies there was a bradycardia which did
not appear to increase in severity with time. Also at this dose
diarrhea, decreased body weight, body weight gains and food consumption
were reported. At higher doses, there was also emesis. The high dose in
the subchronic study resulted in first and second degree heart block,
increased urea concentration, decreased glucose, and altered plasma
electrolyte levels among other signs of toxicity.
Male and female rats were given dietary levels of compound in feed
for a period of either 13 weeks or 104 weeks. Thirteen week doses
ranged from 20 ppm to 500 ppm (1.47 mg/kg/day to 36.91 mg/kg/day),
while 104 week doses ranged from 10 ppm to 150 ppm (0.4 mg/kg/day to
7.57 mg/kg/day). In the subchronic study, both sexes in the 100 and 500
ppm groups had impaired growth performance, reduced food intake, and
decreased body weights and body weight gains. Body weight gains for the
100 ppm groups were 85% of the control weight gains, and for the 500
ppm groups were 33-37% of the control gains. At 500 ppm in both sexes,
hematocrit, hemoglobin, and red blood cell counts were higher, and
white blood cell counts were lower than the control values. Total
plasma proteins were also lower. The 500 ppm females had alkaline
phosphatase activities that were 123% higher and plasma butyryl
cholinesterase and plasma acetylcholinesterase activities that were 72-
73% lower compared to the controls. Treatment-related effects noted in
the gross pathology of the 500 ppm groups were facial staining in both
sexes; encrustations of the muzzle and persistent hyaloid arteries in
males; and dorsal/ventral hair loss, skin encrustations, skin masses,
perineal staining, and skin exfoliation in females. The LOAEL was 6.57
mg/kg/day (100 ppm) for rats, based on decreased body weight gains in
both sexes. The NOAEL

[[Page 18563]]

was 1.3 mg/kg/day (20 ppm). In the chronic study, similar toxicity was
observed in males and females in the 75 or 150 ppm groups. Toxicity
included depressed growth rates that were 86% and 78% of controls in
males and females, respectively, at 150 ppm in the carcinogenicity
phase after 104 weeks. Low growth rates were accompanied by less than a
10% decrease in mean food consumption and a 12-14% reduction in food
efficiency at the 150 ppm level when compared with controls. The LOAEL
for systemic toxicity was 75 ppm (3.08 and 3.79 mg/kg/day in males and
females, respectively), and the NOAEL was 25 ppm (0.97 mg/kg/day for
males and 1.16 mg/kg/day for females) based on decreased body weight
gain. Under the conditions of this study, there was no evidence of
carcinogenic potential. Dosing was considered adequate based on dose-
related decreases in body weight gain and feed consumption in both
sexes relative to the controls.
In the mouse carcinogenicity study, doses ranged from 25 to 800 ppm
(approximately 2.4 - 73.0 mg/kg/day) for up to 18 months. Toxicity was
similar to that observed in the rat studies and included dose-related
decreases at 100 ppm and above in mean body weight, weight gain (9, 37,
and 52% (male); 18, 44, and 60% (female) for increasing doses) and in
mean feed consumption. Based on decreased body weights and food
consumption observed at 100 ppm and higher dose levels, the chronic
LOAEL was established at 100 ppm (9.5 mg/kg/day for male mice and 10
mg/kg/day for females). The NOAEL was 25 ppm (2.4 mg/kg/day for male
mice and 2.5 mg/kg/day for females). Under the conditions of this
study, there was no evidence of carcinogenic potential. Dosing was
considered adequate based on dose-related decreases in body weight gain
and feed consumption in both sexes relative to the controls.
Dogs were given fenpyroximate in capsules for either 13 weeks with
doses ranging from 2 to 50 mg/kg/day or for 52 weeks with doses ranging
from 0.5 to 15 mg/kg/day. In the subchronic study, two high dose
females were sacrificed in extremis during weeks 4 or 5 after a period
of treatment-related inappetence and body weight loss. Both sexes at
all treatment levels exhibited slight bradycardia (slow heart rate) and
a dose-related increase in diarrhea. Emaciation and torpor were
observed in the 2 mg/kg/day females and in both sexes from the 50 mg/
kg/day groups. Emesis was observed in both sexes at 10 mg/kg/day and
above. The 50 mg/kg/day male and in all treated female groups had
reduced body weights and body weight gains (7% (male); 6, 14 and 24%
(female)). Food consumption was also decreased in all female groups. In
males, glucose levels and total white blood cell counts were lower at
10 mg/kg/day and above. Prothombin time values were prolonged and urea
concentrations were higher in the 50 mg/kg/day females. Absolute and
relative adrenal gland weights and relative liver weights were
increased in the 50 mg/kg/day males and females. In the 50 mg/kg/day
females, there was depleted hepatocytic glycogen and fine vacuolation
of the cell cytoplasm in the renal medullary rays. One or both of the
50 mg/kg/day females sacrificed in extremis exhibited first and second
degree heart block, increased urea concentration, low glucose
concentration, disturbances in plasma electrolyte levels, depleted
hepatocytic glycogen, and fine vacuolation of the cell cytoplasm in the
renal medullary rays. The LOAEL was 2 mg/kg/day based on slight
bradycardia and an increased incidence of diarrhea in both sexes. In
females only, there were reduced food consumption, body weight, body
weight gain, emaciation, and torpor. No NOAEL was established.
In the chronic dog study, similar signs of toxicity were observed.
Male beagles in the 5.0 or 15.0 mg/kg/day treatment groups had diarrhea
more frequently (especially during the first 3-4 months of the study).
Males in the 15.0 mg/kg/day treatment group were an average 12%
lighter, consumed 10% less food than the controls, and had heartbeat
rates 30% slower £24 hours after dosing compared to the
controls at study termination. Female beagles in the 5.0 or 15.0 mg/kg/
day treatment groups had diarrhea more frequently than control animals.
The LOAEL was 15.0 mg/kg/day for both male and female beagles, based on
diarrhea, bradycardia, decreased cholesterol, body weight gain and food
consumption in males and vomiting, diarrhea, excessive salivation and
decreased cholesterol in females. The NOAEL was 5.0 mg/kg/day.
In a 2-generation reproduction study, fenpyroximate was
administered continuously in the diet at approximate doses ranging from
0.83 to 8.60 mg/kg/day for females and from 0.67 to 9.92 mg/kg/day for
males (with some variation depending on generation) (dietary
concentrations ranging 10 to 100 ppm) for 2 successive generations (1-
litter/generation). No treatment-related effects were observed in the
10 or 30 ppm treatment groups. The systemic NOAEL was 1.99 and 2.44 mg/
kg/day (30 ppm) for males and females, respectively. The systemic LOAEL
was 6.59 and 8.60 mg/kg/day (100 ppm) for males and females,
respectively, based on decreased body weights of both sexes during the
premating period. The mean premating body weights were slightly
depressed at 30 ppm, in the P1 males and females (5-6%) and
significantly depressed in F1 males (14% compared to
controls; p <0.01); body weight gains for the F1 males were
also significantly lower (p <0.01). Food consumption at 30 ppm for
P1 and F1 males was also slightly depressed. The
mean weights of the 100 ppm P1 females were significantly
reduced during gestation, and weight gain was 12% lower than in
controls at gestation day 20 (p <0.05); by the end of lactation the
weights were similar to control. The mean body weights of the
F1 females were also lower than controls during gestation
(6-9%), but recovered to control levels by the end of lactation. For
reproductive effects, the NOAEL was 2.44 mg/kg/day (30 ppm). The
reproductive LOAEL was 8.60 mg/kg/day (100 ppm) based on decreased
lactational weight gain in both generations of pups. Mean pup weights
were similar in all groups at day 0 of lactation, but the weight gains
in both generations were decreased at 100 ppm; mean weights at day 25
were 24% and 15% lower than control (p <0.01) in F1 and
F2 pups, respectively.
In a developmental toxicity study, rats were dosed by gavage at
dose levels of 0, 1.0, 5.0, or 25 mg/kg/day from days 6 through 15 of
gestation. The maternal NOAEL was 5 mg/kg/day and the LOAEL was 25 mg/
kg/day based on marginal maternal toxicity (decreased body weight gain
and decreased food consumption). This included a marginal depression in
maternal body weight and food at 25 mg/kg/day. It is apparent that
animals could have tolerated higher dose levels of the test material.
However, since developmental toxicity was observed as noted below, the
lack of overt maternal toxicity does not affect acceptability of the
study. The high dose as a LOAEL was also supported by the range-finding
study. The developmental NOAEL was 5.0 mg/kg/day. The developmental
LOAEL was 25 mg/kg/day based on increase in the fetal incidence of
additional thoracic ribs. Additional historical control data (and an
additional evaluation of the study data on this effect - combined
bilateral and unilateral incidence by fetus/litter) is requested for
increased number of thoracic ribs in order to determine whether this is
in fact a treatment-related effect.
In a developmental toxicity study, rabbits were dosed by gavage at
dose levels of 0, 1.0, 2.5, or 5.0 mg/kg/day from days 6 through 19 of
gestation. Both the maternal LOAEL and the NOAEL were greater than 5.0
mg/kg/

[[Page 18564]]

day, the highest dose level tested. The developmental LOAEL and the
NOAEL were also greater than 5.0 mg/kg/day. The Hazard Identification
Assessment Review Committee (HIARC) considered the occurrence of folded
retina in the high dose fetuses to be questionable. There was, however,
a borderline maternal body weight effect at the 5.0 mg/kg/day dose in
the range-finding study.
Fenpyroximate is not considered to be a mutagen with the currently
available data base. The overall quality of the toxicology data base is
good with the exception of the two developmental toxicity studies. EPA
is requiring that the developmental toxicity studies in rats and
rabbits with fenpyroximate be repeated at doses which are adequate to
characterize developmental susceptibility. Confidence in the hazard and
dose response is also good with the exception noted above. Although
there are no data gaps, the two developmental toxicity studies must be
repeated, and the additional historical control data must be submitted
as requested for the existing rat developmental study.

B. Toxicological Endpoints

The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10x to account for
interspecies differences and 10x for intraspecies differences.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10x
to account for interspecies differences and 10x for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC, as shown in the following Table 1:

Table 1.-- Summary of Toxicological Dose and Endpoints for Fenpyroximate for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Exposure Scenario Dose (mg/kg/day) Endpoint Study
----------------------------------------------------------------------------------------------------------------
Acute dietary females - 13 to 50 NOAEL = 5 UF = 100 FQPA LOAEL = 25 mg/kg/day is Developmental rat
SF = 10 based on increase in
the fetal incidence of
additional thoracic
ribs.

Acute RfD = 0.05 mg/kg/
day

Acute PAD = 0.005 mg/kg/
day
----------------------------------------------------------------------------------------------------------------
Chronic (non-cancer) dietary NOAEL= 0.97 mg/kg/day LOAEL = 75 ppm (3.08 Two year rat feeding
UF = 100 FQPA SF = 1 and 3.79 mg/kg/day in study
males and females),
based on decreased
body weights,
accompanied by reduced
food efficiency and a
slight decrease in
mean food consumption.

Chronic RfD = 0.01 mg/
kg/day

Chronic PAD = 0.01 mg/
kg/day
----------------------------------------------------------------------------------------------------------------
Chronic (cancer) Dietary ``Not likely'' to be carcinogenic to humans via relevant routes of
exposure
----------------------------------------------------------------------------------------------------------------
Short-, Intermediate, and Long-Term NOAEL = NA NA NA
(Dermal)
----------------------------------------------------------------------------------------------------------------
Short-, intermediate, and long-term NOAEL = NA NA NA
(Inhalation)
----------------------------------------------------------------------------------------------------------------
NA = Not applicable. This request is for an import tolerance; therefore, applicator exposure risk assessments
are not required.

EPA has conducted a risk assessment for the acaricide fenpyroximate
benzoic acid, 4-[[[[(E)-(1,3-dimethyl1-5-phenoxy-1H-pyrazol-4-yl)
methylene]amino]oxy]methyl]-, 1,1-dimethylethylethyl ester] and its z-
isomer in support of the establishment of time-limited tolerances on
imported wine grapes and hops. EPA has evaluated toxicology and residue
data for fenpyroximate submitted by Nihon Nohyaku.
Fenpyroximate is registered for use on grapes in Germany, France,
Portugal, and Italy and on hops in Germany. The

[[Page 18565]]

maximum application rate for fenpyroximate is 130 grams active
ingredient hectare (g/a.i./ha) (0.12 lb. a.i./acre) for grapes and 263
g a.i./ha (0.23 lb. a.i./acre) for hops. The preharvest interval (PHI)
is 21 days for hops and 14 days for grapes.
The proposed use is limited to imported wine grapes and hops only.
Therefore, no water or occupational or residential exposure assessments
are required.

C. Exposure Assessment

1. Dietary exposure from food and feed uses. Tolerances are being
established (40 CFR 180.566) for the residues of fenpyroximate, in or
on Wine grapes and hops. Risk assessments were conducted by EPA to
assess dietary exposures from fenpyroximate in food as follows.
i. Dietary exposure and risk analysis. A dietary exposure analysis
using the Dietary Exposure Evaluation Model (DEEM) was completed (Memo,
J. Rowell, D271394, January 11, 2001) for acute and chronic (non-
cancer). The DEEM analysis evaluated the individual food consumption as
reported by respondents in the USDA 1989-91 Continuing Surveys for Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. The following assumptions were made: tolerance
level residues were used and 100% Crop Treated (CT) was assumed for all
commodities. Default DEEM concentration factors were used for all
processed food forms.
The acute dietary exposure analysis estimates the distribution of
single-day exposures for the U.S. population and certain subgroups.
Each analysis assumes uniform distribution of fenpyroximate for the
commodities on which fenpyroximate is used.
The Tier 1 acute analysis was performed for females 13-50 years old
using tolerance levels and assuming 100% CT information for all
commodities. EPA retained the 10x safety factor for the females 13-50
years old in acute dietary risk assessments only, therefore the acute
RfDs for these subgroups have been adjusted to reflect the aPAD. The
aPAD for females 13-50 years old is 0.005 (0.05 mg/kg/day ÷ 10 =
0.005 mg/kg/day). For acute dietary risk, EPA's level of concern is
>100% aPAD. Dietary exposures and associated acute risk for females 13-
50 are shown in the following Table 2:

Table 2.--Summary of Results of Acute DEEM Analysis for Fenpyroximate at the 95th Percentile
----------------------------------------------------------------------------------------------------------------
Subgroups Exposure (mg/kg/day) % aPAD
----------------------------------------------------------------------------------------------------------------
Females (13+ years old/pregnant/not nursing) 0.000000 0
----------------------------------------------------------------------------------------------------------------
Females (13+ years old/nursing) 0.000098 2
----------------------------------------------------------------------------------------------------------------
Females (13-19 years old/not pregnant/not nursing) 0.000000 0
----------------------------------------------------------------------------------------------------------------
Females (20+ years old/not pregnant/not nursing) 0.000208 4
----------------------------------------------------------------------------------------------------------------
Females (13-50 years old) 0.000160 3
----------------------------------------------------------------------------------------------------------------

The results of the acute analysis indicate that at the 95th
percentile the acute dietary risk associated with the proposed uses of
fenpyroximate is below EPA's level of concern.
ii. Chronic Exposure. In conducting this chronic dietary risk
assessment the DEEM analysis evaluated the individual food consumption
as reported by respondents in the USDA 1989-1991 nationwide CSFII and
accumulated exposure to the chemical for each commodity. The following
assumptions were made for the chronic exposure assessments: Tolerance
level residues were used and 100% CT was assumed for all commodities.
Default DEEM concentration factors were used for all processed food
forms.
The chronic dietary exposure analysis used mean consumption (3-day
average) data. The Tier 1 chronic analysis was performed using
tolerance levels and assuming 100% CT information for all commodities.
For chronic risk assessments, the 10x safety factor was removed
(reduced to 1x), therefore the chronic RfD and cPAD are equivalent. The
cPAD for the U.S. population and all subgroups is 0.01. For chronic
dietary risk, EPA's level of concern is >100% cPAD. Dietary exposures
for the U.S. population and other subgroups are presented in Table 3.
The other subgroups included in Table 3 represent the highest dietary
exposures for their respective subgroups (i.e., children, infants, and
male subgroups).

Table 3.--Summary of Results from Chronic DEEM Analysis of Fenpyroximate
----------------------------------------------------------------------------------------------------------------
Subgroups Exposure (mg/kg/day) % cPAD
----------------------------------------------------------------------------------------------------------------
U.S. population (48 states) 0.000099 1
----------------------------------------------------------------------------------------------------------------
All infants (>1 yr old) no exposure -
----------------------------------------------------------------------------------------------------------------
Children 1-6 yrs. old 0.000002 0
----------------------------------------------------------------------------------------------------------------
Females 13+ years old (nursing) 0.000166 2
----------------------------------------------------------------------------------------------------------------
Males 20+ yrs old 0.000138 1
----------------------------------------------------------------------------------------------------------------

The results of the chronic analysis indicate that the chronic
dietary risk associated with the proposed uses of fenpyroximate is
below EPA's level of concern for the U.S. population and all subgroups.
iii. Cancer dietary risk. Fenpyroximate was classified as ``not
likely'' to be carcinogenic to humans via relevant routes of exposure
using the proposed new guidelines (RfD document dated February 19,
1997).

[[Page 18566]]

Therefore, no cancer dietary exposure analysis was performed.
2. Dietary exposure from drinking water. The use on wine grapes and
hops is an import use only. At present there is one registered use for
fenpyroximate in the U.S. for ornamental greenhouse use. No run-off to
surface water or drainage to ground water is expected.
Therefore, a drinking water exposure assessment is not necessary.
If domestic uses are added in the future, OPP will reassess the
potential impacts of fenpyroximate on drinking water as a part of the
aggregate risk assessment process.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Fenpyroximate is not registered for use on any sites that would
result in residential exposure.
4. Cumulative exposure to substances with a 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 fenpyroximate 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,
fenpyroximate 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 fenpyroximate 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. Safety Factor for Infants and Children

1. Safety factor for infants and children--i. In general. 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 prenatal and postnatal toxicity and the completeness of the
data base on toxicity and exposure 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.
ii. Prenatal and postnatal sensitivity. Although there are no
toxicity data gaps according to EPA's Subdivision F Guideline
requirements for an import tolerance, EPA is requiring that the
developmental toxicity studies in rats and rabbits be repeated at doses
which are adequate to characterize developmental susceptibility. EPA is
retaining the 10x FQPA safety factor due to uncertainties in evaluating
potential susceptablilty following in utero exposure as a result of
inadequate developmental toxicity studies in both species (rat and
rabbit). This should be applied only to females 13 to 50 for the
determination of acute dietary risk because the potential effects occur
only during in utero exposure and are not postnatal effects.
The FQPA safety factor is reduced to 1x for chronic dietary risk
assessment because the developmental toxicity studies (for which we
have uncertainty) are not relevant to chronic risk assessments (in
utero exposure is not chronic) for the following reasons: (1) The NOAEL
used in deriving the RfD was based on decreased body weight gain in
rats in the rat chronic toxicity/carcinogenicity study; (2) the
developmental effects on which the FQPA factor is based were seen in
pregnant animals; and (3) the developmental effects are considered to
be ``acute'' effects. There was no evidence of increased susceptibility
in the multigeneration reproduction study, a longer study.
EPA concluded that the doses selected in the developmental toxicity
studies with rats and rabbits should have been higher since the highest
doses produced only marginal maternal toxicity, or were supported by
marginal toxicity in range finding studies. Additionally, there is some
question as to the significance (due to maternal toxicity or to direct
fetal effects) of fetal variations in both species (rats- increased
thoracic ribs, rabbits-questionable increase in retinal folding).
Therefore, EPA could not dismiss the possibility of increased
susceptibility in both species.
EPA further concluded that the data from the 2-generation
reproduction study in rats provided no indication of quantitative or
qualitative increased susceptibility since maternal toxicity and
reproductive toxicity occurred at the same dose.
A developmental neurotoxicity study was not recommended because
neurotoxic compounds of similar structure were not identified and there
was no evidence of neurotoxicity in the current toxicity data base.
iii. Conclusion. The toxicological data base for fenpyroximate is
adequate to support a time-limited import tolerance. Fenpyroximate
exposure data are complete or are estimated based on data that
reasonably accounts for potential exposures. EPA is retaining the 10x
FQPA safety factor due to uncertainties in evaluating potential
susceptablilty following in utero exposure as a result of inadequate
developmental toxicity studies in both species (rat and rabbit). This
should be applied only to females 13 to 50 for the determination of
acute dietary risk because the potential effects occur only during in
utero exposure and are not postnatal effects.
2. Acute risk. The Aggregate acute risk is the same as the acute
risk set forth in Unit III.C.1.i. The other registered use does not
contribute to aggregate acute risk.
3. Chronic risk. The chronic acute risk is the same as the chronic
risk set forth in Unit III.C.1.i. The other registered use does not
contribute to chronic acute risk.
4. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to fenpyroximate residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

Adequate enforcement methodology (example: gas chromotography) is
available to enforce the tolerance expression. The method may be
requested from: Calvin Furlow, PIRIB, IRSD (7502C), Office of Pesticide
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703) 305-5229; e-mail address:
furlow.calvin@epa.gov.

B. International Residue Limits

There is neither a Codex proposal, nor Canadian or Mexican limits
for residues of fenpyroximate in wine grapes and hops. Therefore, a
compatibility issue is not relevant to the proposed tolerances.

[[Page 18567]]

C. Conditions

The petitioner is required to perform storage stability studies in
grape juice and grapes. As Chile is a major source of wine, additional
grape residue data from this country and a translation of the Chilean
label are required. Additional information on uses of fenpyroximate in
Mexico and a translation of the Mexician label are required. The
specificity of Method DFG S 19 should be demonstrated by performing an
interference study with all pesticides for which tolerances are
established on grapes and hops. Alternatively, a very specific
confirmatory method (e.g., uses of MS detection) should be submitted.
The two developmental toxicity studies must be repeated and historical
control data submitted for the existing rat developmental study.

V. Conclusion

Therefore, a tolerance with an expiration of 3 years after date of
publication in the Federal Register is established for residues of
fenpyroximate, benzoic acid, 4-[[[(E)-)1,3-dimethyl-5-phenoxy-1H-
pyrazol-4-yl) methylene]amino]oxy]methyl-, 1,1-dimethylethyl ester],
and its z-isomer in or on wine grapes at 1.0 ppm and hops at 10 ppm.

VI. Objections and Hearing Requests

Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to ``object'' to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-301109 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before June 11,
2001.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
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.
Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW.,
Washington, DC 20460. The Office of the Hearing Clerk is open from 8
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
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 the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460.
3. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-301109, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-docket@epa.gov. Please use an ASCII file
format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
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(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).

VII. Regulatory Assessment Requirements

This final rule establishes a tolerance 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

[[Page 18568]]

enforceable duty or contain any unfunded mandate as described under
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law
104-4). Nor does it require any special considerations under Executive
Order 12898, entitled Federal Actions to Address Environmental Justice
in Minority Populations and Low-Income Populations (59 FR 7629,
February 16, 1994); or OMB review or any Agency action under Executive
Order 13045, entitled Protection of Children from Environmental Health
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does
not involve any technical standards that would require Agency
consideration of voluntary consensus standards pursuant to section
12(d) of the National Technology Transfer and Advancement Act of 1995
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under FFDCA section 408(d), such as the exemption 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. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive Order to include regulations
that have ``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). For these same reasons, the Agency has
determined that this rule does not have any ``tribal implications'' as
described in Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000). Executive Order 13175, requires EPA to develop an accountable
process to ensure ``meaningful and timely input by tribal officials in
the development of regulatory policies that have tribal implications.''
``Policies that have tribal implications'' is defined in the Executive
Order to include regulations that have ``substantial direct effects on
one or more Indian tribes, on the relationship between the Federal
government and the Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes.''
This rule will not have substantial direct effects on tribal
governments, on the relationship between the Federal government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal government and Indian tribes, as specified in
Executive Order 13175. Thus, Executive Order 13175 does 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 this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

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

Dated: March 27, 2001.

Joseph J. Merenda,

Acting Director, 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. 321(q), (346a) and 371.

2. Section 180.566 is added to read as follows:

Sec. 180.566 Fenpyroximate; tolerances for residues.

(a) General. This regulation establishes a time-limited tolerance
for the combined residues of fenpyroximate benzoic acid, 4-[[[(E)-(1,3-
dimethyl-5-phenoxy-1H-pyrazol-4-yl) methylene] amino] oxy]methyl]-,
1,1-dimethylethyl ester] and its z-isomer benzoic acid, 4-[[[[(Z)-(1,3-
dimethyl-5-phenoxy-1H-pyrazol-4-yl) methylene]aminio] oxy]methyl]-,
1,1-dimethylethyl ester)] in or on wine grapes and hops. These
tolerances will expire and are revoked on the dates specified in the
following table.

----------------------------------------------------------------------------------------------------------------
Parts per
Commodity million Expiration/Revocation Date
----------------------------------------------------------------------------------------------------------------
Hops\1\.................................. 10 April 12, 2004.
Wine grapes\1\........................... 1.0 April 12, 2004.
----------------------------------------------------------------------------------------------------------------
\1\There are no U.S. registrations on Hops and Wine grapes.

[[Page 18569]]

(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 01-8806 Filed 4-9-01; 8:45 am]
BILLING CODE 6560-50-S

Fenpyroximate; Time-Limited Pesticide Tolerance

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