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/ 2002
/ August
/ Thursday, August 22, 2002
[Federal Register: August 22, 2002 (Volume 67, Number 163)]
[Rules and Regulations]
[Page 54351-54359]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22au02-10]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2002-0203; FRL-7194-3
Iprovalicarb; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes an import tolerance for residues
of iprovalicarb in or on grape at 2.0 parts per million (ppm). Tomen
Agro, Inc. and Bayer Corporation requested this tolerance under the
Federal Food, Drug, and Cosmetic Act, as amended by the Food Quality
Protection Act of 1996.
DATES: This regulation is effective August 22, 2002. Objections and
requests for hearings, identified by docket control number OPP-2002-
0203, must be received on or before October 21, 2002.
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-2002-0203 in
the subject line on the first page of your response.
FOR FURTHER INFORMATION CONTACT: By mail: Dennis McNeilly, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 308-6742; e-mail address:
mcneilly.dennis@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:
[[Page 54352]]
------------------------------------------------------------------------
Examples of Potentially
Categories NAICS 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 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. To access the OPPTS Harmonized Guidelines referenced
in this document, go directly to the guidelines at http://www.epa.gov/
opptsfrs/home/guidelin.htm.
2. In person. The Agency has established an official record for
this action under docket control number OPP-2002-0203. 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 September 22, 2000 (65 FR 57338) (FRL-
6737-8), 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 9E6020) by Tomen
Agro, Inc; and, Bayer Corporation, 100 First Street, Suite 1700, San
Francisco, CA 94105; and, 8400 Hawthorn Road, Kansas City, MO 64120,
respectively. This notice included a summary of the petition prepared
by Tomen Agro, Inc. and Bayer Corp., the registrant. Iprovalicarb is an
amino acid amide carbamate that belongs to a new class of chemicals
derived from natural amino acids. Iprovalicarb acts both as a contact
and systemic fungicide and is proposed for use in the European Union
for control of Oomycete fungi, such as downy mildew. Review of this
import tolerance was completed in cooperation with Canada's Pest
Management Regulatory Agency. There were no comments received in
response to the notice of filing.
The petition requested that 40 CFR part 180 be amended by
establishing import tolerances for residues of the fungicide
iprovalicarb, [2-methyl-1[[[(1S)-(4-methylphenyl) ethyl]
amino]carbonyl] propyl]carbamic acid methylethylester, in or on grape
and raisin at 2.0 ppm. An additional tolerance for the processed food,
raisins, is not necessary because any residue in raisin from this use
will be covered by the tolerance for grape.
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 an import tolerance for residues of iprovalicarb on
grape at 2.0 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 iprovalicarb are
discussed in the 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.
[[Page 54353]]
Table 1.--Subchronic, Chronic, and Other Toxicity
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Guideline No. Study Type Results
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity, mice NOAEL = 325.0 for males; 696.5 for females
mg/kg/day
LOAEL = 1,724.6 for males, 3,599.5 for
females mg/kg/day based on elevated water
intake and changes in hematological
parameters (erythrocyte count, MCV) in
males; increases in liver weights and
plasma cholesterol in females.
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity, rat NOAEL = 372.7 for males; 561.4 for females
mg/kg/day
LOAEL = 1,524.0 for males, 2,585.9 for
females mg/kg/day based on males: decrease
in plasma triglycerides and increase in
leukoyte counts, alkaline phosphatase
levels, pale livers and increased relative
liver weights; females: increased food
intake, decreased body weight gain and
food efficiency and increased plasma
cholesterol levels.
----------------------------------------------------------------------------------------------------------------
870.3150 90-Day oral toxicity, dog NOAEL = 9.1 mg/kg/day
LOAEL = 62.5 mg/kg/day based on increased
absolute and relative liver weight,
hepatocellular hypertrophy, increased
serum activity of activity of alkaline
phosphatase and decreased plasma protein
levels.
----------------------------------------------------------------------------------------------------------------
870.3700 Prenatal developmental in Maternal NOAEL = 1,000 mg/kg/day
rodents (rat) LOAEL = >1,000 mg/kg/day based on the
absence of treatment related toxicity in
the dams at the highest dose tested.
Developmental NOAEL = 1,000 mg/kg/day
LOAEL = >1,000 mg/kg/day based on the
absence of treatment related toxicity in
the fetuses at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.3700 Prenatal developmental in Maternal NOAEL = 1,000 mg/kg/day
nonrodents(rabbit) LOAEL = >1,000 mg/kg/day based on the
absence of treatment related toxicity in
the dams at the highest dose tested.
Developmental NOAEL = 1,000 mg/kg/day
LOAEL = >1,000 mg/kg/day based on the
absence of treatment related toxicity in
the fetuses at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and fertility Parental/Systemic NOAEL = 214.9 mg/kg/day
effects, rat LOAEL = 2,509 mg/kg/day based on increased
relative liver weights in both sexes and
bile duct proliferation in F0 and F1
parental males.
Reproductive NOAEL = 214.9 mg/kg/day
LOAEL = 2,509 mg/kg/day based on decreased
mean litter weight at day 28 (F1 and F2),
reduced body weight development in F1 and
F2 pups.
Offspring NOAEL = 214.9 mg/kg/day
LOAEL = 2,509 mg/kg/day based on reduced
body weight development during lactation
and increased relative liver weights of
the pups.
----------------------------------------------------------------------------------------------------------------
870.4100 Chronic toxicity, dog NOAEL = 2.62 mg/kg/day
LOAEL = 24.69 mg/kg/day based on
biochemical and morphological liver
effects, e.g., swelling, distinct
lobulation and discoloration, increases in
absolute and relative liver weights, and
activities of ALT and ALP, hepatocellular
hypertrophy and periportal fatty change.
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity, mice NOAEL = 58.5 mg/kg/day
LOAEL = 283.4 mg/kg/day based on increased
blood urea nitrogen concentration,
decreased kidney weights and
histopathological changes in the kidneys.
No evidence of carcinogenicity.
----------------------------------------------------------------------------------------------------------------
870.4300 Combined chronic toxicity/ NOAEL = 26.0 mg/kg/day
Carcinogenicity, rats LOAEL = 262.5 mg/kg/day based on
histopathological changes in the liver
(bile duct hyperplasia). Evidence of
carcinogenicity, consisting of treatment-
related rare and uncommon tumors in
multiple organs/tissues in male and female
rats.
----------------------------------------------------------------------------------------------------------------
870.5100 Gene mutation Negative with and without S9 activation up
to 5,000 micrograms/plate in bacterial
reverse mutation test (S. typhimurium).
----------------------------------------------------------------------------------------------------------------
870.5300 In vitro mammalian cell Negative with and without S9 activation up
gene mutation to 125 micrograms/mL (with S9) and 150
micrograms/mL (without S9) in in vitro
mammalian cell forward mutation test
(Chinese hamster lung fibroblasts).
----------------------------------------------------------------------------------------------------------------
870.5375 In vitro mammalian Negative with and without S9 activation up
chromosomal aberration to 150 micrograms/ml in in vitro mammalian
tests cell assay (Chinese hamster ovary cells).
870.5385 Mammalian chromosomal Negative at 2,000 mg/kg in in vivo bone
aberration marrow micronucleus assay (mice).
----------------------------------------------------------------------------------------------------------------
[[Page 54354]]
870.5550 Unscheduled DNA synthesis Negative up to 500 micrograms/ml in in
vitro mammalian cell assay (rat primary
hepatocytes).
----------------------------------------------------------------------------------------------------------------
870.6200 Acute neurotoxicity NOAEL = 2,000 mg/kg/day
screening battery, rat LOAEL = >2,000 mg/kg/day based on no
effects at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.6200 Subchronic neurotoxicity Systemic. NOAEL = 86.0 mg/kg/day
screening battery LOAEL = 342.0 mg/kg/day based on decreased
body weight and increased food
consumption.
Neurotoxicity. NOAEL = 1,434 mg/kg/day for
males and 2,314 mg/kg/day for females
LOAEL = >1,434 mg/kg/day for males and
>2314 mg/kg/day for females based on no
effects at the highest dose tested.
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and pharmaco- Up to 99% excreted via urine and feces
kinetics within 72 hours. Material metabolized
extensively; small percentage passed
through rat unchanged. Twelve metabolites
identified. Proposed biotransformation
pathway via oxidation of methyl group on
aromatic ring, leading to carboxylic acid
metabolite via hydroxymethyl-derivative.
----------------------------------------------------------------------------------------------------------------
Special studies 28-Day Dietary - Dog: NOAEL was 3.0 mg/kg/
day for males and 3.4 mg/kg/day for
females. The LOAEL was 31.5 mg/kg/day for
males and 35.0 mg/kg/day for females based
on hepatocellular hypertrophy, vacuolated
hepatocytes and elevated serum alkaline
phosphatase activity.
28-Day Dietary + 28-Day Recovery - Dog: The
microsomal enzyme induction LOAEL was 2.93-
3.01 mg/kg/day (the highest dose tested).
The NOAEL was 0.77 mg/kg/day.
Liver foci test for tumor initiating
effects - Rats (males only): Negative for
tumor initiating potential in rat liver.
28-Day Dietary Rat: NOAEL = 579.3 mg/kg/day
for males and 195.8 mg/kg/day for females.
LOAEL=1,934.4 mg/kg/day for males and
572.8 mg/kg/day for females based on
increases in alkaline phosphatase,
cholesterol and relative liver weights in
males; increases in cholesterol and
triglycerides as well as absolute and
relative liver weights in females.
----------------------------------------------------------------------------------------------------------------
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 intra species differences. No
special uncertainty factors were appropriate or used in the dietary
risk assessment.
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. In this case because this is an import tolerance
only, there is only dietary risk.
The linear default risk methodology (Q1*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q1*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q1* is calculated and used to estimate risk which
represents a probability of occurrence of additional cancer cases
(e.g., risk is expressed as 1 x 10-6 or one in a
million). Under certain specific circumstances, MOE calculations will
be used for the carcinogenic risk assessment. In this non-linear
approach, a ``point of departure'' is identified below which
carcinogenic effects are not expected. The point of departure is
typically a NOAEL based on an endpoint related to cancer effects though
it may be a different value derived from the dose response curve. To
estimate risk, a ratio of the point of departure to exposure
(MOEcancer = point of departure/exposures) is calculated. A
summary of the toxicological endpoints for iprovalicarb used for human
risk assessment is shown in the following Table 2:
[[Page 54355]]
Table 2.--Summary of Toxicological Dose and Endpoints for iprovalicarb for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF\1\ and Level of
Exposure Scenario Dose Used in Risk Concern for Risk Study and Toxicological
Assessment, UF Assessment Effects
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations NOAEL= 2.6 mg/kg/day FQPA SF = 1X 1-Year Dog Study
UF = 100 Chronic RfD = cPAD = chronic RfD/FQPA LOAEL = 24.69 mg/kg/day
0.026 mg/kg/day. SF = 0.026 mg/kg/day. based on liver
effects: swelling,
enlargement, distinct
lobulation and
discoloration,
increased absolute and
relative liver
weights, and
accompanying
hepatocellular
hypertrophy and fatty
change, and elevated
serum liver enzyme
activities.
----------------------------------------------------------------------------------------------------------------
Cancer (oral) Q1* = 4.5 X 104 (mg/kg/ ..................... Combined chronic
day)-1 toxicity/
carcinogenicity, two-
year rat study Q1*
based on the combined
follicular cell
adenomas and
carcinomas in the
thyroid gland of
female rats.
----------------------------------------------------------------------------------------------------------------
\1\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns
unique to the FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. This is the first feed
and/or food use for iprovalicarb in the United States. This activity
reflects the establishment of a U.S. import tolerance on grape without
a U.S. registration and therefore the only exposure that occurs is
dietary. Risk assessments were conducted by EPA to assess dietary
exposures from iprovalicarb in food as follows:
i. Acute 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 one day
or single exposure. Iprovalicarb is of low acute oral toxicity in rats
with no adverse effects observed at doses well above the limit test
dose (>5,000 mg/kg). In addition, rat and rabbit teratology studies and
an acute neurotoxicity rat study, presented no effects indicative of
early toxicity. Also, in sub-chronic feeding and reproduction toxicity
studies, there were no treatment-related effects that could be
attributable to a single dose. It is for these reasons that an acute
analysis was not conducted, i. e., due to the lack of any appropriate
toxicological end-point. Accordingly, an acute risk analysis was not
appropriate and was not conducted.
ii. Chronic exposure.In conducting this chronic dietary risk
assessment the Dietary Exposure Evaluation Model (DEEM)
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 nationwide Continuing Surveys of Food
Intake by Individuals (CSFII) and accumulated exposure to the chemical
for each commodity. The following assumptions were made for the chronic
exposure assessments: A DEEM chronic dietary exposure
analysis was performed using tolerance residue levels and 100% crop
treated. Data from a grape processing study indicated that iprovalicarb
residues did not concentrate in grape processed commodities; therefore,
the DEEM concentration factors for grape (i.e.: juice, juice-
concentrate, raisin) were set at 1, indicating no concentration of
residues. The DEEM analysis included wine, sherry and raisin.
EPA does not expect the chronic risk to exceed 100% of the cPAD, as
shown in the following Table 3:
Table 3.--Chronic (Non-Cancer) Exposure to Iprovalicarb
----------------------------------------------------------------------------------------------------------------
Dietary exposure %cPAD
Population Subgroup (mg/kg/day) cPAD (mg/kg/day) (Food)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.000688 0.026 2.6
----------------------------------------------------------------------------------------------------------------
All infants (<1 year old) 0.001282 0.026 4.9
----------------------------------------------------------------------------------------------------------------
Children (1-6 years old) 0.002443 0.026 9.3
----------------------------------------------------------------------------------------------------------------
Children (7-12 years old) 0.000668 0.026 2.6
----------------------------------------------------------------------------------------------------------------
iii. Cancer. In accordance with the EPA Draft Guidelines for
Carcinogen Risk Assessment (July, 1999) the Agency has classified
iprovalicarb into the category ``Likely to be carcinogenic to humans''
based on the following weight-of-the-evidence considerations:
Iprovalicarb induced rare and infrequently occurring tumors in
Wistar rats. At the high dose, males developed malignant osteosarcomas
and females also developed benign transitional cell papillomas of the
urinary bladder. At the mid and high doses, females also developed
malignant mixed Mullerian tumors of the uterus and follicular cell
adenomas and carcinomas in the thyroid gland. Although the incidences
of these tumors were low, they are rare or uncommon in Wistar rats.
Most of these tumors were induced above the limit dose (1,000 mg/kg/
day) which was adequate and not excessively toxic. In mice, no
treatment-related increase in tumors was observed in animals treated
above the limit dose which was adequate and not excessively toxic.
Iprovalicarb is not mutagenic. Although mechanistic studies
suggested that iprovalicarb may not be a tumor initiator, these studies
were inadequate to establish the definitive mode of action for tumor
induction in rats.
The Agency is using a linear low-dose extrapolation
(Q1*) approach for estimating the human cancer risk based
[[Page 54356]]
on the most potent tumor in rats. This approach is supported by the
lack of confirmation of the mode of action of iprovalicarb. The most
potent Q1* for iprovalicarb was determined to be 4.5 x
10-4 (mg/kg/day)-1 based on combined follicular
cell adenomas and carcinomas in the thyroid gland of the female rat.
Percent crop treated and/or anticipated residues were not used.
2. Dietary exposure from drinking water. Residues in drinking water
are not expected to result as a consequence of establishing an import
tolerance for iprovalicarb residues in or on grape. Iprovalicarb is not
registered for use in the United States. Therefore, exposures through
drinking water is unlikely.
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).
Iprovalicarb 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 iprovalicarb 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,
iprovalicarb 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 iprovalicarb 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. 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 database 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.
2. Prenatal and postnatal sensitivity. There is no evidence for
increased susceptibility of fetuses to in utero exposure of
iprovalicarb in either the rat developmental or rabbit developmental
studies. In both studies, the NOAEL for both maternal and developmental
toxicity was the highest dose tested.
Based on the results in the 2-generation reproduction study in
rats, a qualitative increased susceptibility of the neonates (as
compared with adults) was demonstrated for iprovalicarb. The parental
systemic NOAELs were based on decreased body weights and liver weights
as well as bile duct proliferation; for females, the parental systemic
NOAELs were based on increased relative liver weights. Reproductive
LOAELs were not attained (greater than higest dose tested (HDT), limit
dose). In offspring, the NOAELs were based on decreased mean litter
weight on day 28, reduced body weight during lactation, and increased
pup relative liver weights as well as reduced lactation index in
F1. There was considered to be an increase in sensitivity of
the neonates (as compared with adults) because of the lower lactation
index (decreased pup survival) and decreased pup body weight. Although
there is evidence of qualitative susceptibility in the 2-generation
reproduction study, the Agency concludes that there is a low level of
concern (and no residual uncertainty) because: (1) The increased
susceptibility (decrease in pup survival) was seen only at the highest
dose tested (2,074 mg/kg/day) which is twice the limit dose; (2) the
decrease in pup survival was seen only in one generation
(F1, not replicated in F2); (3) there are clearly
defined NOAELs/LOAELs for parental and offspring toxicity; and (4) the
effects seen in the offspring occurred at a much higher dose (192 mg/
kg/day) than that used to establish the chronic RFD (NOAEL of 2.6 mg/
kg/day).
3. Conclusion. There is a complete toxicity database for an import
tolerance for iprovalicarb and exposure data are complete or are
estimated based on data that reasonably accounts for potential dietary
exposures. The Agency concludes that there are reliable data that
indicate there are no (residual) concerns for pre- and/or postnatal
toxicity following exposure to iprovalicarb and therefore, no
additional safety factor (1X) is necessary to protect the safety of
infants and children.
E. Aggregate Risks and Determination of Safety
1. Acute risk. Iprovalicarb is of low acute oral toxicity in rats
with no adverse effects observed at doses well above the limit test
dose (>5,000 mg/kg). In addition, rat and rabbit teratology studies and
an acute neurotoxicity rat study, presented no effects indicative of
early toxicity. Also, in sub-chronic feeding and reproduction toxicity
studies, there were no treatment-related effects that could be
attributable to a single dose. It is for these reasons that
iprovalicarb is not expected to pose an acute risk.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
iprovalicarb from food will utilize 2.6% of the cPAD for the U.S.
population, 4.9% of the cPAD for All infants (<1 year old), 9.3% of the
cPAD for children 1-6 years old and 2.6% of the cPAD for children 7-12
years old. There are no residential uses for iprovalicarb.
In addition, there is not any potential for chronic dietary
exposure to iprovalicarb in drinking water because the only use is an
import tolerance. There are no U.S. registered products or uses at this
time. EPA does not expect the aggregate exposure to exceed 100% of the
cPAD, as shown in the following Table 4:
Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to iprovalicarb
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup cPAD (mg/kg/ %cPAD Water EEC Water EEC Chronic
day) (Food) (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.026 2.6 N/A N/A N/A
----------------------------------------------------------------------------------------------------------------
[[Page 54357]]
All infants (<1 year old) 0.026 4.9 N/A N/A N/A
----------------------------------------------------------------------------------------------------------------
Children (1-6 years old) 0.026 9.3 N/A N/A N/A
----------------------------------------------------------------------------------------------------------------
Children (7-12 years old) 0.026 2.6 N/A N/A N/A
----------------------------------------------------------------------------------------------------------------
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
Iprovalicarb is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern. Residues in water, both surface and ground water, are
expected to be zero because there are no U.S. uses, only this import
tolerance for grape.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
Iprovalicarb is not registered for use on any sites that would
result in residential exposure. Therefore, the aggregate risk is the
sum of the risk from food and water, which do not exceed the Agency's
level of concern. Residues in water, both surface and ground water, are
expected to be zero because there are no U.S. uses, only this import
tolerance for grape.
5. Aggregate cancer risk for U.S. population. The lifetime risk of
developing cancer from iprovalicarb exposure is determined for the U.S.
population (total) only. The estimated exposure to iprovalicarb is
0.000688 mg/kg/day. Applying the Q1* of 4.5 x
10-4 (mg/kg/day)-1 to the exposure value results
in a cancer risk estimate of 3.1 x 10-7. This risk is
negligible.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, and to infants and children from aggregate
exposure to iprovalicarb residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
The enforcement analytical residue analytical method is an liquid
chromotography/mass spectrometry method. The limit of quantitation is
0.05 ppm in grape, wine, juice and raisin. Recovery and sensitivity of
the method is considered adequate (95-114%).
Adequate enforcement methodology (example--gas chromatography) is
available to enforce the tolerance expression. The method may be
requested from: Paul Golden, USEPA (7503C), Office of Pesticide
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW,
Washington, DC 20460; telephone number: (410) 305-2960; e-mail address:
www.epa.gov/oppbead1/methods/ (RAM Mailbox).
B. International Residue Limits
No maximum residue levels have yet been established by the CODEX
Alimentarius Commission for iprovalicarb in/on grape or raisin.
V. Conclusion
Therefore, tolerances are established for residues of iprovalicarb,
[2-methyl-1[[[(1S)-(4-methylphenyl)ethyl] amino]carbonyl]
propyl]carbamic acid methylethylester, in or on grape at 2.0 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-2002-0203 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 October
21, 2002.
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
[[Page 54358]]
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-2002-0203, 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). Because this rule has been
exempted from review under Executive Order 12866 due to its lack of
significance, this rule is not subject to Executive Order 13211,
Actions Concerning Regulations That Significantly Affect Energy Supply,
Distribution, or Use (66 FR 28355, May 22, 2001). 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) (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 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. 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
[[Page 54359]]
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 record
keeping requirements.
Dated:August 15, 2002.
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), 346(a) and 374.
2. Section 180.581 is added to read as follows:
Sec. 180.581 Iprovalicarb; tolerances for residues.
(a) General. Tolerances are established for residues of
iprovalicarb, [2-methyl-1[[[(1S)-(4-methylphenyl) ethyl]
amino]carbonyl] propyl]carbamic acid methylethylester, in or on the
following commodities.
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
Grape\1\ 2.0
------------------------------------------------------------------------
\1\ No U.S. registration as of July 31, 2002.
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 02-21293 Filed 8-21-02; 8:45 am]
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