[Federal Register: February 5, 2003 (Volume 68, Number 24)]
[Rules and Regulations]
[Page 5839-5847]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05fe03-23]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2002-0344; FRL-7289-7]
Cyprodinil; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for residues of
cyprodinil in or on the bushberry subgroup, caneberry subgroup,
juneberry, lingonberry, pistachio, salal and watercress. The
Interregional Research Project Number 4 (IR-4) requested these
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA) , as
amended by the Food Quality Protection Act of 1996 (FQPA).
DATES: This regulation is effective February 5, 2003. Objections and
requests for hearings, identified by docket ID number OPP-2002-0344,
must be received on or before April 7, 2003.
ADDRESSES: Written objections and hearing requests may besubmitted
electronically, by mail, or through hand delivery/courier. Follow the
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION.
FOR FURTHER INFORMATION CONTACT: Hoyt Jamerson, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW.,Washington, DC 20460-0001; telephone
number: (703) 308-9368; e-mail address: jamerson.hoyt@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
[sbull] Crop production (NAICS Code 111)
[sbull] Animal production (NAICS Code 112)
[sbull] Food manufacturing (NAICS Code 311)
[sbull] Pesticide manufacturing (NAICS Code 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be
[[Page 5840]]
affected by this action. Other types of entities not listed in this
unit could also be affected. The North American Industrial
Classification System (NAICS) codes have been provided to assist you
and others in determining whether this action might apply to certain
entities. If you have any questions regarding the applicability of this
action to a particular entity, consult the person listed under FOR
FURTHER INFORMATION CONTACT.
B. How Can I Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket identification (ID) number OPP-2002-0344. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under 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.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
II. Background and Statutory Findings
In the Federal Register of May 1, 2002 ( 67 FR 21671)(FRL-6833-4),
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a,
as amended by FQPA (Public Law 104-170), announcing the filing of
pesticide petitions (PP 2E6359, 2E6365, 2E6377 and 2E6393) by IR-4, 681
U.S. Highway 1 South, North Brunswick, NJ 08902-3390. That
notice included a summary of the petitions prepared by Syngenta Crop
Protection, Inc., the registrant. There were no comments received in
response to the notice of filing.
The petitions requested that 40 CFR 180.532 be amended by
establishing tolerances for residues of the fungicide cyprodinil, 4-
cyclopropyl- 6-methyl- N-phenyl-2-pyrimidinamine, in or on the
caneberry subgroup at 10.0 parts per million (ppm) (2E6393), watercress
at 20 ppm (2E6365), pistachio at 0.07 ppm (2E6377) and the bushberry
subgroup, lingonberry, juneberry, and salal, at 3.0 ppm (2E6359). IR-4
subsequently revised the petition to propose the following tolerances
for cyprodinil residues in or on the caneberry subgroup at 10.0 parts
per million (ppm), watercress at 20 ppm, pistachio at 0.10 ppm and the
bushberry subgroup, lingonberry, juneberry, and salal, at 3.0 ppm.
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) of the FFDCA defines ``safe'' to mean that``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of the FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical
residue....''
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 of the FFDCA 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) of the FFDCA, EPA has reviewed
the available scientific data and other relevant information in support
of this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2) of the FFDCA, for a tolerance for residues of cyprodinil on
the caneberry subgroup at 10.0 parts per million (ppm), watercress at
20 ppm, pistachio at 0.10 ppm and the bushberry subgroup, lingonberry,
juneberry, and salal, at 3.0 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 cyprodinil are
discussed in Table 1 of this unit as well as the no observed adverse
effect level (NOAEL) and the lowest observed adverse effectlevel
(LOAEL) from the toxicity studies reviewed.
[[Page 5841]]
Table 1.--Subchronic, Chronic, and Other Toxicity
------------------------------------------------------------------------
Guideline No. Study Type Results
------------------------------------------------------------------------
870.3100 90-Day oral NOAEL = 73.3/103
toxicity mouse (male/female (m/
f)) milligram/
kilogram/day (mg/
kg/day)
LOAEL = 257/349 (m/
f) mg/kg/day
based on
histopathological
changes in the
liver (m/f)
------------------------------------------------------------------------
870.3100 90-Day oral NOAEL = 3.14 (mg/
toxicity rat kg/day)
LOAEL = 19 mg/kg/
day based on
increasedtubular
kidney lesions in
males
------------------------------------------------------------------------
870.3150 90-Day oral- NOAEL = 210/232 (m/
toxicity - dog f) mg/kg/day
LOAEL = 560/581 mg/
kg/day based on
lowerbody-weight
gains and
decreased food
consumption
inboth sexes
------------------------------------------------------------------------
870.3200 Carcinogenicity - NOAEL = 16.1 mg/kg/
mice day
LOAEL = 212.4 mg/
kg/day based on a
dose-related
increase in the
incidence of
focal and
multifocal
hyperplasia of
the exocrine
pancreas in males
No evidence of
carcinogenicity
------------------------------------------------------------------------
870.3700 Prenatal Maternal NOAEL =
developmental - 200 mg/kg/day
rat LOAEL = 1,000 mg/
kg/day based on
lower body-weight/
body-weight gain
and reduced food
consumption
Developmental
NOAEL = 200 mg/kg/
day
LOAEL = 1,000 mg/
kg/day based on
lowermean fetal
weights and
increased
incidence of
delayedossificati
on
------------------------------------------------------------------------
870.3700 Prenatal Maternal NOAEL =
developmental - 150 mg/kg/day
rabbit LOAEL = 400 mg/kg/
day based on
decreasedbody-
weight gain
Developmental
NOAEL = 150 mg/kg/
day
LOAEL = 400 mg/kg/
day based on
slight increase
of litters
showing extra
(13th) ribs
------------------------------------------------------------------------
870.3800 Reproduction and Parental/Systemic
fertility effects NOAEL = 81 mg/kg/
- rat day
LOAEL = 326 mg/kg/
day based on
lowerbody-weights
in the F0 females
during the pre-
matingperiod.
Reproductive/
Developmental
NOAEL = 81mg/kg/
day
LOAEL = 326 mg/kg/
day based on
decreasedpup
weights (F1 and
F2)
------------------------------------------------------------------------
870.4100 Chronic toxicity NOAEL = 65.63/
dogs 67.99 (m/f) mg/kg/
day
LOAEL = 449.25/
446.3 (m/f) mg/kg/
day based on
lower body-weight
gains and
decreased food
consumption and
food efficiency
------------------------------------------------------------------------
870.4300 Chronic toxicity/ NOAEL = 2.7 mg/kg/
Carcinogenicity(f day
eeding) - rat LOAEL = 35.6 mg/kg/
day based on
degenerative
liver lesions
(spongiosis
hepatis) in males
No evidence of
carcinogenicity
------------------------------------------------------------------------
870.5265 and 870.5100 Gene Mutation In a reverse gene
mutation assay
withSalmonella
typhimurium/
Escherichia coli,
cyprodinil was
negative up to
concentrations
(>=1,250 [mu]g/
plate +/-S9) that
produced
reproducible
cytotoxicity for
the majority of
strains. Compound
insolubility was
reported at >=313
[mu]g/plate.
------------------------------------------------------------------------
870.5300 Gene Mutation In a Chinese
hamster V79 cell
HGPRT forward
gene mutation
assay, cyprodinil
was negative up
to cytotoxic
concentrations
(>=96.0 [mu]g/mL
with S9) (>=24
[mu]g/mL without
S9).
------------------------------------------------------------------------
870.5375 Cytogenetics/In In an in vitro
vitro Chromosomal assay for
Aberration chromosome
aberrations in
Chinese hamster
ovary (CHO)
cells, cyprodinil
gave negative
results up
tocytotoxic
concentrations
(>=50 [mu]g/mL
without S9, 18-
or 42-hour cell
harvest or >=25
[mu]g/mL with S9,
18-hour cell
harvest) or to
the highest sub-
cytotoxic
concentration (50
[mu]g/mL with S9,
42-hour cell
harvest).
------------------------------------------------------------------------
[[Page 5842]]
870.5395 Cytogenetics/In In an in vivo bone
vivo bone marrow marrow
micronucleus micronucleus
assay, cyprodinil
was negative when
administered
orally (gavage)
at 5,000 mg/
kg(HDT) to both
sexes of Tif:MAGF
mice. No signs of
overt toxicity or
clear evidence of
cytotoxicity for
the target organ
were noted at any
dose or sacrifice
time.
------------------------------------------------------------------------
870.5550 Unscheduled DNA In an Unscheduled
Synthesis DNA
Synthesis(UDS)
assay in primary
rat hepatocytes,
cyprodinil was
negative up to a
cytotoxic
concentration
(80[mu]g/mL).
------------------------------------------------------------------------
870.7485 Metabolism and Single oral doses
pharmacokinetics (0.5 or 100 mg/kg
bw) of phenyl or
pyrimidyl-
radiolabelled
cyprodinil
(purity >=98%)
were administered
toTif:RAIf(SPF)
rats, with one
low-dose group
receiving
unlabelled
cyprodinil
(purity >=99%)
for 2 weeks prior
to treatment with
radiolabelled
compound.
Absorption was
very rapid
(tcmax= 0.3
hours) with rapid
clearance (tcmax/
2=1.2 hours). A
minimum of 75% of
the administered
dose was
absorbed.
Excretion was
rapid and almost
complete, with
urine as the
principle route
of excretion (48-
68%), and >90%of
the administered
dose detected in
the urine and
feces within 48
hours. Excretion,
distribution and
metabolite
profiles were
essentially
independent of
dose level,
pretreatment, and
type of label,
although there
were some
quantitative
differences sex-
dependent
qualitative
differences in
two urinary
metabolite
fractions.
------------------------------------------------------------------------
870.7485 Metabolism and Excreta (Group D1
pharmacokinetics and D2) and bile
(Group G1) from
radiolabelled
cyprodinil-
treated
Tif:RAIf(SPF)
rats were used to
characterize,
isolateand
identify
cyprodinil
metabolites.
Eleven
metabolites were
isolated from
urine, feces and
bile, and the
metabolic
pathways in the
rat were
proposed. All
urinary and
biliary
metabolites (with
the exception of
7U) were
conjugated with
glucuronic acid
or sulfonated,
and excreted.
Cyprodinil was
almostcompletely
metabolized by
hydroxylation of
the phenyl ring
(position 4) or
pyrimidine ring
(position 5),
followed by
conjugation. An
alternative
pathwayinvolved
oxidation of the
phenyl ring
followed by
glucuronic acid
conjugation. A
quantitative sex
difference was
observed with
respect to
sulfonation ofthe
major metabolite
that formed 6U.
The monosulfate
metabolite (1U)
was predominant
in females,
whereas equal
amounts of mono-
and disulfate
(6U) conjugates
were noted in
males. Most of
the significant
metabolites in
feces were
exocons of
biliary
metabolites (2U,
3U, 1G). These
were assumed to
be deconjugated
in the
intestines,
partially
reabsorbed into
the
generalcirculatio
n, conjugated
again, and
eliminated
renally. The
major metabolic
pathways of
cyprodinil were
not significantly
influenced by the
dose, treatment
regimen, or sex
of the animal.
------------------------------------------------------------------------
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 (SF)
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 SF.
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
[[Page 5843]]
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.
The linear default risk methodology (Q*) is the primary method
currently used by the Agency to quantify carcinogenic risk. The Q*
approach assumes that any amount of exposure will lead to some degree
of cancer risk. A Q* 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 cyprodinil used for human risk assessment is shown in
Table 2 of this unit:
Table 2.--Summary of Toxicological Dose and Endpoints for cyprodinil for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Dose Used in Risk FQPA SF and Endpoint Study and Toxicological
Exposure Scenario Assessment, UF for Risk Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary females 13-50years of Developmental NOAEL = FQPA SF = 1X Developmental Toxicity
age 150 mg/kg/day aPAD = acute RfD / FQPA rabbit
UF = 100............... SF = 1.5 mg/kg/day. Developmental LOAEL =
Acute RfD = 1.5 mg/kg/ 400 mg/kg/day based on
day. slight increase of
litters showing extra
ribs (13th).
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations NOAEL= 2.7 FQPA SF = 1X 2-Year Chronic Toxicity/
UF = 100............... cPAD = chronic RfD / Carcinogenicity- rat
Chronic RfD = 0.03 mg/ FQPA SF = 0.03 mg/kg/ LOAEL = 35.6 mg/kg/day
kg/day. day. based on degenerative
liver lesions
(spongiosis hepatis)
in males.
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) Classification: ``not likely to be carcinogenic tohumans''
----------------------------------------------------------------------------------------------------------------
* The reference to the FQPA SF refers to any additional SF retained due to concerns unique tothe FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.352) for the residues of cyprodinil, in or on a
variety of raw agricultural commodities. Risk assessments were
conducted by EPA to assess dietary exposures from cyprodinil 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. The Dietary Exposure Evaluation Model (DEEM[reg])
analysis evaluated the individual food consumption as reported by
respondents in the USDA insert 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 acute exposure assessments: 100% crop treated (PCT) and tolerance-
level residues for cyprodinil on all treated crops. This assessment was
a Tier I analysis. However, the only acute endpoint identified was for
the population subgroup females 13-50 years old based on a slight
increase of litters showing extra ribs (13th). No effects that could be
attributed to a single exposure were observed (no end point was chosen)
for any other population subgroup, including the general U.S.
population; therefore, an acute dietary assessment for the general U.S.
population or other subgroups was not conducted.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the Dietary Exposure Evaluation Model (DEEM[reg]) 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: 100% crop treated (PCT) and tolerance-level residues for
cyprodinil on all treated crops. This assessment was a Tier I analysis.
2. Dietary exposure from drinking water. The Agency lacks
sufficient monitoring exposure data to complete a comprehensive dietary
exposure analysis and risk assessment for cyprodinil in drinking water.
Because the Agency does not have comprehensive monitoring data,
drinking water concentration estimates are made by reliance on
simulation or modeling taking into account data on the physical
characteristics of cyprodinil.
The Agency uses the Generic Estimated Environmental Concentration
(GENEEC) or the Pesticide Root Zone/Exposure Analysis Modeling System
(PRZM/EXAMS) to estimate pesticide concentrations in surface water and
SCI-GROW, which predicts pesticide concentrations in groundwater. In
general, EPA will use GENEEC (a tier 1 model) before using PRZM/EXAMS
(a tier 2 model) for a screening-level assessment for surface water.
The GENEEC model is a subset of the PRZM/EXAMS model that uses a
specific high-end runoff scenario for pesticides. GENEEC incorporates a
farm pond scenario, while PRZM/EXAMS incorporate an index reservoir
environment in place of the previous pond scenario. The PRZM/EXAMS
model includes a percent crop area factor as an adjustment to account
for the maximum percent crop coverage within a watershed or drainage
basin.
None of these models include consideration of the impact processing
(mixing, dilution, or treatment) of raw water for distribution as
drinking water would likely have on the removal of pesticides from the
source water. The primary use of these models by the Agency at this
stage is to provide a coarse screen for sorting out pesticides for
which it is highly unlikely that drinking water concentrations would
ever exceed human health levels of concern.
[[Page 5844]]
Since the models used are considered to be screening tools in the
risk assessment process, the Agency does not use estimated
environmental concentrations (EECs) from these models to quantify
drinking water exposure and risk as a percent of reference dose or
percent of population adjusted dose. Instead, drinking water levels of
comparison (DWLOCs) are calculated and used as a point of comparison
against the model estimates of a pesticide's concentration in water.
DWLOCs are theoretical upper limits on a pesticide's concentration in
drinking water in light of total aggregate exposure to a pesticide in
food, and from residential uses. Since DWLOCs address total aggregate
exposure to cyprodinil they are further discussed in the aggregate risk
sections below.
Based on the PRZM/EXAMS and SCI-GROW models the estimated
environmental concentrations (EECs) of cyprodinil for acute exposures
are estimated to be 32 parts per billion (ppb) for surface water and
0.04 ppb for ground water. The EECs for chronic exposures are estimated
to be 6 ppb for surface water and 0.04 ppb for ground water.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
Cyprodinil 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) of the FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether cyprodinil 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,
cyprodinil 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 cyprodinil 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. Section 408 of the FFDCA 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 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 of
increased susceptibility of rat or rabbit fetuses followingin utero
exposure in the developmental studies with cyprodinil. There is no
evidence of increased susceptibility of young rats in the reproduction
study with cyprodinil.
3. Conclusion. With the exception of missing 21/28-day dermal-
toxicity and 28-day inhalation-toxicity studies in rats, there is a
complete toxicity data base for cyprodinil and exposure data are
complete or are estimated based on data that reasonably accounts for
potential exposures. Since there are no residential uses for cyprodinil
the only exposure route to infants and children is the oral route, for
which the toxicity and exposure data base is complete. Therefore dermal
and inhalation-toxicity studies, are not needed to assess risk to
infants and children and EPA determined that the 10X safety factor to
protect infants and children should be reduced to 1X.
The FQPA 10X safety factor is removed because:
[sbull] i. There are currently no registered or proposed
residential(non-occupational) uses of cyprodinil.
[sbull] ii. There was no evidence (qualitative or quantitative) of
increased susceptibility in the developmental rat or rabbit study
following in utero exposure or in the two-generation reproduction study
following pre- or post-natal exposure.
[sbull] iii. There was also no evidence of a neurodevelopmental
effect in the rat or rabbit developmental toxicity studies or in the
rat two-generation reproductive-toxicity study.
[sbull] iv. There are no data deficiencies for pre- and/or post-
natal exposure and hence there are no residual uncertainties.
[sbull] v. Food and drinking water exposure assessments will
notunderestimate the potential exposure for all populations, including
infants and children.
E. Aggregate Risks and Determination of Safety
To estimate total aggregate exposure to a pesticide from food,
drinking water, and residential uses, the Agency calculates DWLOCs
which are used as a point of comparison against the model estimates of
a pesticide's concentration in water (EECs). DWLOC values are not
regulatory standards for drinking water. DWLOCs are theoretical upper
limits on a pesticide's concentration in drinking water in light of
total aggregate exposure to a pesticide in food and residential uses.
In calculating a DWLOC, the Agency determines how much of the
acceptable exposure (i.e., the PAD) is available for exposure through
drinking water [e.g., allowable chronic water exposure (mg/kg/day) =
cPAD - (average food + residential exposure)]. This allowable exposure
through drinking water is used to calculate a DWLOC.
A DWLOC will vary depending on the toxic endpoint, drinking water
consumption, and body weights. Default body weights and consumption
values as used by the USEPA are used to calculate DWLOCs: 2 liter (L)/
70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg (child).
Default body weights and drinking water consumption values vary on an
individual basis. This variation will be taken into account in more
refined screening-level and quantitative drinking water exposure
assessments. Different populations will have different DWLOCs.
Generally, a DWLOC is calculated for each type of risk assessment used:
Acute, short-term, intermediate-term, chronic, and cancer.
When EECs for surface water and groundwater are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA considers the aggregate risk resulting from
multiple exposure pathways associated with a pesticide's uses, levels
of comparison in drinking water may vary as those uses change. If new
uses are added in the future, EPA will reassess the potential impacts
of residues of the pesticide in
[[Page 5845]]
drinking water as a part of the aggregate risk assessment process.
1. Acute risk. Using the exposure assumptions discussed in this
unit for acute exposure, the acute dietary exposure from food to
cyprodinil will occupy <1% of the aPAD for the subpopulation females
13-50 years old, the only population for whom an effect attributable to
an acute exposure could be observed. In addition, there is potential
for acute dietary exposure to cyprodinil in drinking water. After
calculating DWLOCs and comparing them to the EECs for surface and
ground water, EPA does not expect the aggregate exposure to exceed 100%
of the aPAD, as shown in Table 3 of this unit:
Table 3.--Aggregate Risk Assessment for Acute Exposure to cyprodinil
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup aPAD (mg/ % aPAD Water EEC Water EEC Acute DWLOC
kg) (Food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
Females 13-50 years old 1.5 <1.0 32 0.04 44,000
----------------------------------------------------------------------------------------------------------------
2. Chronic risk.Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
cyprodinil from food will utilize 7.4% of the cPAD for the U.S.
population, 24% of the cPAD for all infants (< 1 year old) and 22% of
the cPAD for children 1-6 years old. There are no residential uses for
cyprodinil that result in chronic residential exposure to cyprodinil.
Based the use pattern, chronic residential exposure to residues of
cyprodinil is not expected. In addition, there is potential for chronic
dietary exposure to cyprodinil in drinking water. After calculating
DWLOCs and comparing them to the EECs for surface and ground water, EPA
does not expect the aggregate exposure to exceed 100% of the cPAD, as
shown in Table 4 of this unit:
Table 4.-- Aggregate Risk Assessment for Chronic (Non- Cancer) Exposure to cyprodinil
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population Subgroup cPAD mg/kg/ % cPAD Water EEC Water EEC Chronic
day (Food) (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.03 7.4 6 0.04 970
----------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.03 24 6 0.04 230
----------------------------------------------------------------------------------------------------------------
Children 1-6 years old 0.03 22 6 0.04 230
----------------------------------------------------------------------------------------------------------------
Children 7-12 years old 0.03 9.1 6 0.04 270
----------------------------------------------------------------------------------------------------------------
Females 13-50years old 0.03 5.3 6 0.04 1,000
----------------------------------------------------------------------------------------------------------------
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure take into account residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level).
Cyprodinil 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.
5. Aggregate cancer risk for U.S. population. Cyprodinil has been
classified as ``not likely to be carcinogenic in humans'' based on the
results of a carcinogenicity study in mice and the combined chronic
toxicity and carcinogenicity study in rats. Therefore, cyprodinil is
not expected to pose a cancer risk to humans.
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 cyprodinil residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
The results of Multiresidue Method testing of cyprodinil and its
metabolite CGA-232449 have been forwarded to the Food and Drug
Administration (FDA). Cyprodinil was tested according to the FDA
Multiresidue protocols (Protocols C, D, and E), and acceptable
recoveries were obtained for cyprodinil fortified in apples at 0.50 ppm
using Protocol D. The petitioner is proposing the Method AG-631A as a
tolerance enforcement method for residues of cyprodinil in/on the
subject crops. This method, entitled ``Analytical Method for the
Determination of Residues of CGA-219417 in Crops by High Performance
Liquid Chromatography With Column Switching,'' is a reissue of Methods
AG-631 and REM 141.01. The method includes confirmatory procedures
using gas chromatography/nitrogen/phosphorus detector (GC/NPD). The
method has successfully undergone radiovalidation using 14C-
labeled tomato samples and independent laboratory validation. In
addition, the method has been the subject of acceptable Agency petition
method validations on stone fruits and almond nutmeat and hulls.
B. International Residue Limits
There are no Mexican, Canadian or Codex maximum residue limits
established for cyprodinil in/on caneberries, bushberries, pistachios
and watercress, and thus no compatibility issues to be reconciled.
C. Conditions
The Agency is requiring as conditions for registration the
following:An acceptable 21/28-day dermal-toxicity study in rats (GLN
870.3200). A 28-day inhalation-toxicity study in rats (GLN 870.3465)
V. Conclusion
Therefore, the tolerance is established for residues of cyprodinil
on the caneberry subgroup at 10.0 ppm, watercress at 20 ppm, pistachio
at 0.10 ppm and the bushberry subgroup, lingonberry, juneberry, and
salal, at 3.0 ppm.
[[Page 5846]]
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, EPA will continue to use those procedures, with
appropriate adjustments, until the necessary modifications can be made.
The new section 408(g) of the FFDCA 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)
of FFDCA, as was provided in the old sections 408 and 409 of the FFDCA.
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 ID number -OPP-2002-0344 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 April 7,
2003.
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 (1900C),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001. You may also deliver your request to the
Office of the Hearing Clerk in Rm.104, Crystal Mall 2, 1921
Jefferson Davis Hwy., Arlington, VA. 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
(703) 603-0061.
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-
0001.
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 20460-0001.
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.1. Mail your
copies, identified by docket ID number OPP-2002-0344, 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-
0001. In person or by courier, bring a copy to the location of the
PIRIB described in Unit I.B.1. 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. Statutory and Executive Order Reviews
This final rule establishes a tolerance under section 408(d) of the
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). 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
[[Page 5847]]
tolerances and exemptions that are established on the basis of a
petition under section 408(d) of the FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. 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 section 408(n)(4) of the FFDCA. 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: January 24, 2003.
Peter Caulkins,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346(a) and 371.
2. Section 180.532 is amended by adding alphabetically the
following commodities to the table in paragraph (a)(1) to read as
follows:
Sec. 180.532 Cyprodinil; tolerances forresidues.
(a) * * *
(1) * * *
------------------------------------------------------------------------
Commodity Parts per million
------------------------------------------------------------------------
* * * * *
Bushberry subgroup 13B............................... 3.0
Caneberry subgroup 13A............................... 10
* * * * *
Juneberry............................................ 3.0
Lingonberry.......................................... 3.0
Pistachio............................................ 0.10
* * * * *
Salal................................................ 3.0
Watercress........................................... 20
------------------------------------------------------------------------
* * * * *
[FR Doc. 03-2771 Filed 2-4-03; 8:45 am]
BILLING CODE 6560-50-S