[Federal Register Volume 63, Number 69 (Friday, April 10, 1998)]
[Rules and Regulations]
[Pages 17699-17706]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9679]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300643; FRL-5785-1]
RIN 2070-AB78
Cyprodinil; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
cyprodinil, 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine in or on
the folowing commodities: almond hulls at 0.05 ppm; almond nutmeats at
0.02 ppm; apple pomace, wet at 0.15 ppm; grapes at 2.0 ppm; pome fruit
at 0.1 ppm; raisins at 3.0 ppm and stone fruit at 2.0 ppm. Novartis
Crop Protection, Inc. requested these tolerances under the Federal
Food, Drug and Cosmetic Act (FFDCA), as amended by the Food Quality
Protection Act of 1996 (Pub. L. 104-170).
DATES: This regulation is effective April 10, 1998. Objections and
requests for hearings must be received by EPA on or before June 9,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number, [OPP-300643], must be submitted to: Hearing
Clerk (1900), Environmental Protection Agency, Rm. M3708, 401 M St.,
SW., Washington, DC 20460. Fees accompanying objections and hearing
requests shall be labeled ``Tolerance Petition Fees'' and forwarded to:
EPA Headquarters Accounting Operations Branch, OPP (Tolerance Fees),
P.O. Box 360277M, Pittsburgh, PA 15251. A copy of any objections and
hearing requests filed with the Hearing Clerk identified by the docket
control number, [OPP-300643], must also be submitted to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460. In person,
bring a copy of objections and hearing requests to Rm. 119, CM #2, 1921
Jefferson Davis Hwy., Arlington, VA.
A copy of objections and hearing requests filed with the Hearing
Clerk may also be submitted electronically by sending electronic mail
(e-mail) to: opp-docket@epamail.epa.gov. Copies of objections and
hearing requests must be submitted as an ASCII file avoiding the use of
special characters and any form of encryption. Copies of objections and
hearing requests will also be accepted on disks in WordPerfect 5.1/6.1
file format or ASCII file format. All copies of objections and hearing
requests in electronic form must be identified by the docket control
number [OPP-300643]. No Confidential Business Information (CBI) should
be submitted through e-mail. Electronic copies of objections and
hearing requests on this rule may be filed online at many Federal
Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Mary L. Waller, Acting
Product Manager (PM) 21, Registration Division 7505C, Office of
Pesticide Programs, Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location, telephone number, and e-mail
address: Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA,
(703) 308-9354, e-mail: waller.mary@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of April 2, 1997 (64
FR 15690)(FRL-5593-9) EPA issued a notice pursuant to section 408 of
the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(e)
announcing the filing of pesticide petitions (PP 6F4656 and 6H5746) for
tolerances by Novartis Crop Protection, Inc. Greensboro, NC 27419
(formerly Ciba Crop Protection). This notice included a summary of the
petitions prepared by Novartis Crop Protection, Inc., the registrant.
There were no comments received in response to the notice of filing.
The petitions requested that 40 CFR part 180 be amended by
establishing tolerances for residues of the fungicide cyprodinil, 4-
cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine in or on the following
commodities: almond hulls at 0.05 ppm; almond nutmeats at 0.02 ppm;
apple pomace, wet at 0.15 ppm; grapes at 2.0 ppm; pome fruit at 0.1
ppm; raisins at 3.0 ppm and stone fruit at 2.0 ppm.
Note that the scientific assessments relevant to establishing these
tolerances for cyprodinil were conducted jointly between EPA and the
Pest Management Regulatory Agency (PMRA) of Canada as a pilot project
under the North American Free Trade Agreement (NAFTA) and the Canadian
United States Trade Agreement (CUSTA). Cyprodinil qualified as the
first candidate for such a pilot program due to its classification as a
reduced risk pesticide.
I. Risk Assessment and Statutory Findings
New 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
[[Page 17700]]
``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. First, EPA determines the
toxicity of pesticides based primarily on toxicological studies using
laboratory animals. These studies address many adverse health effects,
including (but not limited to) reproductive effects, developmental
toxicity, toxicity to the nervous system, and carcinogenicity. Second,
EPA examines exposure to the pesticide through the diet (e.g., food and
drinking water) and through exposures that occur as a result of
pesticide use in residential settings.
A. Toxicity
1. Threshold and non-threshold effects. For many animal studies, a
dose response relationship can be determined, which provides a dose
that causes adverse effects (threshold effects) and doses causing no
observed effects (the ``no-observed effect level'' or ``NOEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOEL from
the study with the lowest NOEL by an uncertainty factor (usually 100 or
more) to determine the Reference Dose (RfD). The RfD is a level at or
below which daily aggregate exposure over a lifetime will not pose
appreciable risks to human health. An uncertainty factor (sometimes
called a ``safety factor'') of 100 is commonly used since it is assumed
that people may be up to 10 times more sensitive to pesticides than the
test animals, and that one person or subgroup of the population (such
as infants and children) could be up to 10 times more sensitive to a
pesticide than another. In addition, EPA assesses the potential risks
to infants and children based on the weight of the evidence of the
toxicology studies and determines whether an additional uncertainty
factor is warranted. Thus, an aggregate daily exposure to a pesticide
residue at or below the RfD (expressed as 100 percent or less of the
RfD) is generally considered acceptable by EPA. EPA generally uses the
RfD to evaluate the chronic risks posed by pesticide exposure. For
shorter term risks, EPA calculates a margin of exposure (MOE) by
dividing the estimated human exposure into the NOEL from the
appropriate animal study. Commonly, EPA finds MOEs lower than 100 to be
unacceptable. This hundredfold MOE is based on the same rationale as
the hundredfold uncertainty factor.
Lifetime feeding studies in two species of laboratory animals are
conducted to screen pesticides for cancer effects. When evidence of
increased cancer is noted in these studies, the Agency conducts a
weight of the evidence review of all relevant toxicological data
including short-term and mutagenicity studies and structure activity
relationship. Once a pesticide has been classified as a potential human
carcinogen, different types of risk assessments (e.g., linear low dose
extrapolations or MOE calculation based on the appropriate NOEL) will
be carried out based on the nature of the carcinogenic response and the
Agency's knowledge of its mode of action.
2. Differences in toxic effect due to exposure duration. The
toxicological effects of a pesticide can vary with different exposure
durations. EPA considers the entire toxicity data base, and based on
the effects seen for different durations and routes of exposure,
determines which risk assessments should be done to assure that the
public is adequately protected from any pesticide exposure scenario.
Both short and long durations of exposure are always considered.
Typically, risk assessments include ``acute,'' ``short-term,''
``intermediate term,'' and ``chronic'' risks. These assessments are
defined by the Agency as follows.
Acute risk, by the Agency's definition, results from 1-day
consumption of food and water, and reflects toxicity which could be
expressed following a single oral exposure to the pesticide residues.
High end exposure to food and water residues are typically assumed.
Short-term risk results from exposure to the pesticide for a period
of 1-7 days, and therefore overlaps with the acute risk assessment.
Historically, this risk assessment was intended to address primarily
dermal and inhalation exposure which could result, for example, from
residential pesticide applications. However, since enaction of FQPA,
this assessment has been expanded to include both dietary and non-
dietary sources of exposure, and will typically consider exposure from
food, water, and residential uses when reliable data are available. In
this assessment, risks from average food and water exposure, and high-
end residential exposure, are aggregated. High-end exposures from all
three sources are not typically added because of the very low
probability of this occurring in most cases, and because the other
conservative assumptions built into the assessment assure adequate
protection of public health. However, for cases in which high-end
exposure can reasonably be expected from multiple sources (e.g.
frequent and widespread homeowner use in a specific geographical area),
multiple high-end risks will be aggregated and presented as part of the
comprehensive risk assessment/characterization. Since the toxicological
endpoint considered in this assessment reflects exposure over a period
of at least 7 days, an additional degree of conservatism is built into
the assessment; i.e., the risk assessment nominally covers 1-7 days
exposure, and the toxicological endpoint/NOEL is selected to be
adequate for at least 7 days of exposure. (Toxicity results at lower
levels when the dosing duration is increased.)
Intermediate-term risk results from exposure for 7 days to several
months. This assessment is handled in a manner similar to the short-
term risk assessment.
Chronic risk assessment describes risk which could result from
several months to a lifetime of exposure. For this assessment, risks
are aggregated considering average exposure from all sources for
representative population subgroups including infants and children.
B. Aggregate Exposure
In examining aggregate exposure, FFDCA section 408 requires that
EPA take into account available and reliable information concerning
exposure from the pesticide residue in the food in question, residues
in other foods for which there are tolerances, residues in groundwater
or surface water that is consumed as drinking water, and other non-
occupational exposures through pesticide use in gardens, lawns, or
buildings (residential and other indoor uses). Dietary exposure to
residues of a pesticide in a food commodity are estimated by
multiplying the average daily consumption of the food forms of that
commodity by the tolerance level or the anticipated pesticide residue
level. The Theoretical Maximum Residue
[[Page 17701]]
Contribution (TMRC) is an estimate of the level of residues consumed
daily if each food item contained pesticide residues equal to the
tolerance. In evaluating food exposures, EPA takes into account varying
consumption patterns of major identifiable subgroups of consumers,
including infants and children. The TMRC is a ``worst case'' estimate
since it is based on the assumptions that food contains pesticide
residues at the tolerance level and that 100% of the crop is treated by
pesticides that have established tolerances. If the TMRC exceeds the
RfD or poses a lifetime cancer risk that is greater than approximately
one in a million, EPA attempts to derive a more accurate exposure
estimate for the pesticide by evaluating additional types of
information (anticipated residue data and/or percent of crop treated
data) which show, generally, that pesticide residues in most foods when
they are eaten are well below established tolerances.
Percent of crop treated estimates are derived from federal and
private market survey data. Typically, a range of estimates are
supplied and the upper end of this range is assumed for the exposure
assessment. By using this upper end estimate of percent of crop
treated, the Agency is reasonably certain that exposure is not
understated for any significant subpopulation group. Further, regional
consumption information is taken into account through EPA's computer-
based model for evaluating the exposure of significant subpopulations
including several regional groups, to pesticide residues. For this
pesticide, the most highly exposed population subgroup, non-nursing
infants, was not regionally based.
II. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. Reviews of the submitted data were conducted under a joint
review between Pest Management Regulatory Agency (PMRA), Canada and the
EPA. EPA has sufficient data to assess the hazards of cyprodinil and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for tolerances for residues of cyprodinil in or on these
commodities: almond hulls at 0.05 ppm; almond nutmeats at 0.02 ppm;
apple pomace, wet at 0.15 ppm; grapes at 2.0 ppm; pome fruit at 0.1
ppm; raisins at 3.0 ppm and stone fruit at 2.0 ppm.
EPA's assessment of the dietary exposures and risks associated with
establishing these tolerances 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 below.
1. Acute toxicity. The acute toxicity data of cyprodinil show that
this chemical is not acutely toxic by the oral, inhalation and dermal
routes of exposure. Technical cyprodinil, however, is a dermal
sensitizer.
2. Subchronic toxicity. i. In a range-finding subchronic toxicity
study, cyprodinil was administered in the diet to rats at 0, 100, 600,
3,000 or 15,,000 ppm (males - 0, 10.3, 64.8, 316 or 1460 milligrams/
kilogram/day (mg/kg/day); females - 0, 10.1, 62.2, 299 or 1390 mg/kg/
day) for 28 days. In this study, the LOEL is 3,000 ppm (316 and 299 mg/
kg/day for males and females respectively) based on lower bodyweight
gains, microcytosis, increased cholesterol and phospholipid levels and
hepatocyte hypertrophy. The NOEL is 600 ppm (64.8 and 62.2 mg/kg/day
for males and females respectively).
ii. In a subchronic toxicity study, cyprodinil was administered to
rats by gavage at dose levels of 0, 10, 100, or 1,000 mg/kg/day for 28
days. In this study, the LOEL is 100 milligrams/kilogram body weight/
day (mg/kg bwt/day) for rats, based on increased liver weights and
abnormalities in liver morphology. The NOEL is 10 mg/kg bwt/day.
iii. In a subchronic toxicity study, cyprodinil was administered in
the diet to rats at dose levels of 0 or 12,000 ppm (0 or 810 mg/kg/day,
respectively, for males; 0 or 803 mg/kg/day, respectively, for
females), and to rats at dose levels of 50, 300, or 2,000 ppm (3.14,
19.0, or 134 mg/kg/day, respectively, for males; 3.24, 19.3, or 137 mg/
kg/day for females) for 90 days. In this study, the LOEL is 300 ppm (19
mg/kg bwt/day) for rats, based on increased chronic tubular kidney
lesions in males. The NOEL is 50 ppm (3.14 mg/kg/day).
iv. A 3-month range-finding study was carried out in mice where
animals were fed diets containing 0, 500, 2,000 or 6,000 ppm (actual
doses: males - 0, 73.3, 257 or 849 mg/kg/day; females - 0, 103, 349 or
1,121 mg/kg/day) of cyprodinil. In this study, the LOEL is 2,000 ppm
based on histopathological changes in the liver. The NOEL is 500 ppm
(males - 73.3; females - 103 mg/kg/day).
v. A 3-month study was carried out in Beagle dogs where animals
were fed diets containing 0, 200, 1,500, 7,000 or 20,000 ppm (actual
doses: males - 0, 6.07, 45.87, 210.33 or 559.66 mg/kg/day; females - 0,
6.79, 52.75, 231.93 or 580.95 mg/kg/day) of cyprodinil. In this study,
the LOEL is 20,000 ppm (males - 560, females - 581 mg/kg/day) based on
lower bodyweight gains and decreased food consumption in both sexes.
The NOEL is 7,000 ppm (males - 210, females - 232 mg/kg/day).
vi. Groups of rats received repeated dermal applications of
cyprodinil at doses of 0, 5, 25, 125 or 1,000 mg/kg/day, 6 hours/day, 5
days /week over a 28-day period. Hunched posture was observed in
females at 125 mg/kg/day. In this study, the LOEL is 25 mg/kg/day for
female rats and 1,000 mg/kg/day for male rats, based on alterations in
clinical signs (piloerection). The NOEL is 5 mg/kg/day for females and
125 mg/kg/day for males.
3. Chronic toxicity. i. A 24-month chronic toxicity/carcinogenicity
study was carried out in rats where animals (50 rats/sex/dose -
carcinogenicity portion, plus 20/sex/dose laboratory investigations)
were fed diets containing 0, 5, 75, 1,000 or 2,000 ppm cyprodinil
(actual doses: males - 0, 0.177, 2.7, 35.6 or 73.6 mg/kg/day; females -
0, 0.204, 3.22, 41.2 or 87.1 mg/kg/day). An additional 10/sex/dose were
fed test diets for 12 months (interim sacrifice). In this study the
LOEL is 1,000 ppm (35.6 mg/kg/day) based on the degenerative liver
lesions (spongiosis hepatis) in males. The NOEL for chronic toxicity is
set at 75 ppm (2.7 mg/kg/day).
ii. In a chronic toxicity study, cyprodinil was administered to
five Beagle dogs/sex/dose in the diet at dose levels of 25, 50, or 100
ppm for females (0.7, 1.6, or 3.1 mg/kg/day, respectively) and 50, 100,
or 200 ppm for males (1.8, 3.0, or 5.7 mg/kg/day, respectively) for 52
weeks. An additional 1-year study was carried out in Beagle dogs where
animals (4/sex/dose) were fed diets containing 0, 25, 250, 2,500 or
15,000 ppm (actual doses: males - 0, 0.72, 6.87, 65.63 or 449.25;
females - 0, 0.76, 6.80, 67.99 or 446.37 mg/kg/day) cyprodinil. In this
study, the LOEL is 15,000 ppm (males - 449.25, females 446.37 mg/kg/
day) based on lower bodyweight gains and decreased food consumption and
food efficiency. The NOEL is 2,500 ppm (males - 65.63, females - 67.99
mg/kg/day).
[[Page 17702]]
4. Carcinogenicity. i. For the discussion of the rat study, see
Unit II.A.3.i. of this preamble. This study was tested to adequate
levels based on signs of toxicity in males at 2,000 ppm and females at
5,000 ppm. There was no indication of carcinogenic potential at any
dose level.
ii. An 18-month carcinogenicity study was carried out in mice where
animals (50 mice/sex/dose - carcinogenicity portion, plus 10/sex/dose -
hematology) were fed diets containing 0, 10, 150, 2,000 or 5,000 ppm
(actual doses: males - 0, 1.15, 16.1, 212.4 or 630; females - 0, 1.08,
14.7, 196.3 or 558.1 mg/kg/day) of cyprodinil. In this study the LOEL
is 2,000 ppm (males - 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. The NOEL is 150 ppm (males - 16.1 mg/kg/day). This
study was tested to adequate levels based on signs of toxicity in males
at 2,000 ppm and females at 5,000 ppm. There was no indication of
carcinogenic potential at any dose level.
5. Developmental toxicity. i. In a developmental toxicity study,
cyprodinil was administered in 3% aqueous corn starch suspension by
oral gavage to 20-23 female rats per dose of 0, 20, 200 or 1,000 mg/kg/
day or gestation days 6-15. The LOEL for maternal toxicity is 1,000 mg/
kg/day based on lower bodyweight/bodyweight gain and reduced food
consumption. The NOEL for maternal toxicity was 200 mg/kg/day. The LOEL
for developmental toxicity is 1,000 mg/kg/day based on lower mean fetal
weights and an increased incidence of delayed ossification. The NOEL
for developmental toxicity is 200 mg/kg/day.
ii. In a developmental toxicity study, cyprodinil was administered
in 3% aqueous corn starch suspension to 19 inseminated female rabbits,
dosed by gavage at dose levels of 0, 5, 30, 150, or 400 mg/kg/day from
days 7 through 19 of gestation. In this study, the maternal LOEL is 400
mg/kg/day, based on decreased body weight gain. The maternal NOEL is
150 mg/kg/day. The fetal developmental LOEL is 400 mg/kg/day based on a
slight increase of litters showing extra (13th) ribs. The fetal
developmental NOEL is 150 mg/kg/day.
6. Reproductive toxicity. A two-generation reproduction study was
carried out in rats, with one litter per generation. Animals (30 rats/
sex/dose) received cyprodinil in the diet at doses of 0, 10, 100, 1,000
or 4,000 ppm (actual intake males - 0, 0.7, 6.7, 68 or 273; females -
0, 0.8, 8.2, 81 or 326 mg/kg/day) for a 10 week pre-mating period. In
this study, the LOEL for maternal systemic toxicity is 4,000 (about 326
mg/kg/day) based on lower body weights in the F0 females
during the pre-mating period. The NOEL for maternal systemic toxicity
is 1,000 ppm (about 81 mg/kg/day). The LOEL for reproductive/
developmental toxicity is 4,000 ppm (about 326 mg/kg/day) based on
decreased pup weights (F1 and F2). The NOEL for
reproductive toxicity is 1,000 ppm (about 81 mg/kg/day).
7. Neurotoxicity. Neurotoxicity studies were not required for this
chemical.
8. Mutagenicity. Mutagenicity studies with cyprodinil included gene
mutation assays in bacterial and mammalian cells, a mouse micronucleus
assay and in vivo unscheduled DNA synthesis (UDS) assays. The results
were negative for mutagenicity in all studies.
9. Metabolism. In a metabolism study, single oral doses (0.5 or 100
mg/kg bwt) of phenyl or pyrimidyl-radiolabelled cyprodinil were
administered to rats, with one low-dose group receiving unlabeled
cyprodinil 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. A biphasic first order kinetics was
observed for radioactivity depletion, with a duration of 0.3-1.2 hours
for the first phase, and 27-65 hours for the second phase. 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. Tissue residues declined rapidly, with
the highest concentrations ( 1.8 ppm) found in kidneys,
liver, lungs, spleen, thyroid, whole blood, and carcass. The urine,
fecal, and bile metabolite patterns were complex, with 8 and 9 defined
metabolite fractions, respectively. Unchanged parent compound was
detected in feces extract only. Excretion, distribution and metabolite
profiles were essentially independent of dose level, pretreatment, and
type of label, although there were some sex-dependent qualitative
differences in two urinary metabolite fractions.
Excreta (Group D1 and D2) and bile (Group G1) from radiolabelled
cyprodinil-treated rats were used to characterize, isolate and identify
metabolites of cyprodinil. 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 almost completely metabolized by hydroxylation of the phenyl ring (
position 4) or pyrimidine ring (position 5), followed by conjugation.
An alternative pathway involved oxidation of the phenyl ring followed
by glucuronic acid conjugation. A quantitative sex difference was
observed with respect to sulfonation of the 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 general circulation,
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
1. Acute toxicity. No effects that could be attributed to a single
exposure (dose) were observed in oral toxicity studies including the
developmental toxicity studies in rats and rabbits. Therefore, a dose
and endpoint were not identified for acute dietary risk assessment.
2. Short- and intermediate-term toxicity. The dose of 25 mg/kg/day
was selected as the toxicological endpoint for short- and intermediate-
term risk calculations based on the repeated dose study in rats
resulting in hunched postures in female rats at 125 mg/kg/day.
3. Chronic toxicity. EPA has established the RfD for cyprodinil at
0.03 mg/kg/day. This RfD is based on a chronic rat study with a NOEL of
2.7 mg/kg/day and an Uncertainty Factor of 100. Effects seen at the
LOEL, 35.6 mg/kg/day, were histopathological alternations in the liver
(spongiosis hepatis) in males.
4. Carcinogenicity. Based on the lack of evidence of
carcinogenicity in mice and rats at doses that were judged to be
adequate to assess the carcinogenic potential, cyprodinil was
classified as ``not likely'' human carcinogen according to EPA Proposed
Guidelines for Carcinogen Risk Assessment (April 10, 1996).
C. Exposures and Risks
1. From food and feed uses. Currently, there are no established
tolerances (40 CFR part 180) for the residue of cyprodinil, in or on
any raw agricultural commodities. Risk assessments were conducted by
EPA to assess dietary
[[Page 17703]]
exposures and risks from cyprodinil as follows:
i. Acute exposure and risk. Acute dietary risk assessments are
performed for a food-use pesticide if a toxicological study has
indicated the possibility of an effect of concern occurring as a result
of a one day or single exposure. No effects that could be attributed to
a single exposure (dose) were observed in oral toxicity studies
including the developmental toxicity studies in rats and rabbits.
Therefore, a dose and endpoint were not identified for acute dietary
risk assessment.
ii. Chronic exposure and risk. Chronic dietary (food only) exposure
estimates were calculated by using the proposed tolerance levels for
all pome fruit, stone fruit, almond and grape commodities. The required
tolerances result in a Theoretical Maximum Residue Contribution (TMRC)
that is equivalent to the following percent of the RfD: (only values
greater than those for the U.S. population are listed below)
------------------------------------------------------------------------
Percent of
Subgroups RFD
------------------------------------------------------------------------
U.S. population (48 states)................................ 5.8
Non-Hispanic White......................................... 6.2
Nursing Infants (< 1="" year="" old).............................="" 14.0="" non-nursing="" infants="">< 1="" year="" old).........................="" 27.0="" females="" (13+="" years,="" nursing)...............................="" 6.5="" children="" (1-6="" years="" old)...................................="" 15.0="" children="" (7-12="" years="" old)..................................="" 7.5="" ------------------------------------------------------------------------="" epa="" does="" not="" consider="" the="" chronic="" dietary="" risk="" to="" exceed="" the="" level="" of="" concern.="" 2.="" from="" drinking="" water--i.="" acute="" exposure="" and="" risk.="" no="" acute="" endpoint="" was="" identified,="" therefore="" no="" drinking="" water="" risk="" assessment="" is="" presented.="" ii.="" chronic="" exposure="" and="" risk.="" the="" drinking="" water="" levels="" of="" concern="" (dwloc)="" are="" 990="" parts="" per="" billion="" (ppb)="" for="" u.s.="" population="" and="" 200="" ppb="" for="" non-nursing="" infants.="" the="" estimated="" maximum="" concentration="" in="" surface="" water="" is="" 16="" ppb.="" the="" estimated="" average="" concentration="" in="" surface="" water="" is="" expected="" to="" be="" less="" than="" 16="" ppb.="" chronic="" concentrations="" in="" groundwater="" are="" not="" expected="" to="" be="" higher="" than="" the="" acute="" concentrations.="" the="" maximum="" estimated="" concentrations="" of="" cyprodinil="" in="" surface="" water="" are="" less="" than="" opp's="" levels="" of="" concern="" for="" cyprodinil="" in="" drinking="" water="" as="" a="" contribution="" to="" acute="" aggregate="" exposure.="" also,="" the="" estimated="" average="" concentrations="" in="" groundwater="" are="" less="" than="" opp's="" levels="" of="" concern="" for="" cyprodinil="" in="" drinking="" water="" as="" a="" contributor="" to="" chronic="" aggregate="" exposure.="" therefore,="" taking="" into="" account="" the="" proposed="" uses="" in="" this="" action,="" epa="" concludes="" with="" reasonable="" certainty="" that="" residues="" of="" cyprodinil="" 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.="" epa="" bases="" this="" determination="" on="" a="" comparison="" of="" estimated="" concentrations="" of="" cyprodinil="" in="" surface="" water="" and="" groundwaters="" to="" back-="" calculated="" ``levels="" of="" concern''="" for="" cyprodinil="" in="" drinking="" water.="" these="" levels="" of="" concern="" in="" drinking="" water="" were="" determined="" after="" epa="" has="" considered="" all="" other="" non-occupational="" exposures="" for="" which="" it="" has="" reliable="" data,="" including="" all="" uses="" considered="" in="" this="" action.="" the="" estimates="" of="" cyprodinil="" in="" surface="" water="" are="" derived="" from="" water="" quality="" models="" that="" use="" conservative="" assumptions="" (health-protective)="" regarding="" the="" pesticide="" transport="" from="" the="" point="" of="" application="" to="" surface="" and="" ground="" water.="" 3.="" from="" non-dietary="" exposure.="" cyprodinil="" is="" not="" currently="" registered="" for="" use="" on="" residential="" non-food="" sites.="" therefore="" residential="" risk="" assessments="" are="" not="" required.="" 4.="" cumulative="" exposure="" to="" substances="" with="" common="" mechanism="" of="" toxicity.="" section="" 408(b)(2)(d)(v)="" requires="" that,="" when="" considering="" whether="" to="" establish,="" modify,="" or="" revoke="" a="" tolerance,="" the="" agency="" consider="" ``available="" information''="" concerning="" the="" cumulative="" effects="" of="" a="" particular="" pesticide's="" residues="" and="" ``other="" substances="" that="" have="" a="" common="" mechanism="" of="" toxicity.''="" the="" agency="" believes="" that="" ``available="" information''="" in="" this="" context="" might="" include="" not="" only="" toxicity,="" chemistry,="" and="" exposure="" data,="" but="" also="" scientific="" policies="" and="" methodologies="" for="" understanding="" common="" mechanisms="" of="" toxicity="" and="" conducting="" cumulative="" risk="" assessments.="" for="" most="" pesticides,="" although="" the="" agency="" has="" some="" information="" in="" its="" files="" that="" may="" turn="" out="" to="" be="" helpful="" in="" eventually="" determining="" whether="" a="" pesticide="" shares="" a="" common="" mechanism="" of="" toxicity="" with="" any="" other="" substances,="" epa="" does="" not="" at="" this="" time="" have="" the="" methodologies="" to="" resolve="" the="" complex="" scientific="" issues="" concerning="" common="" mechanism="" of="" toxicity="" in="" a="" meaningful="" way.="" epa="" has="" begun="" a="" pilot="" process="" to="" study="" this="" issue="" further="" through="" the="" examination="" of="" particular="" classes="" of="" pesticides.="" the="" agency="" hopes="" that="" the="" results="" of="" this="" pilot="" process="" will="" increase="" the="" agency's="" scientific="" understanding="" of="" this="" question="" such="" that="" epa="" will="" be="" able="" to="" develop="" and="" apply="" scientific="" principles="" for="" better="" determining="" which="" chemicals="" have="" a="" common="" mechanism="" of="" toxicity="" and="" evaluating="" the="" cumulative="" effects="" of="" such="" chemicals.="" the="" agency="" anticipates,="" however,="" that="" even="" as="" its="" understanding="" of="" the="" science="" of="" common="" mechanisms="" increases,="" decisions="" on="" specific="" classes="" of="" chemicals="" will="" be="" heavily="" dependent="" on="" chemical="" specific="" data,="" much="" of="" which="" may="" not="" be="" presently="" available.="" although="" at="" present="" the="" agency="" does="" not="" know="" how="" to="" apply="" the="" information="" in="" its="" files="" concerning="" common="" mechanism="" issues="" to="" most="" risk="" assessments,="" there="" are="" pesticides="" as="" to="" which="" the="" common="" mechanism="" issues="" can="" be="" resolved.="" these="" pesticides="" include="" pesticides="" that="" are="" toxicologically="" dissimilar="" to="" existing="" chemical="" substances="" (in="" which="" case="" the="" agency="" can="" conclude="" that="" it="" is="" unlikely="" that="" a="" pesticide="" shares="" a="" common="" mechanism="" of="" activity="" with="" other="" substances)="" and="" pesticides="" that="" produce="" a="" common="" toxic="" metabolite="" (in="" which="" case="" common="" mechanism="" of="" activity="" will="" be="" assumed).="" 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.="" d.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" u.s.="" population="" 1.="" acute="" risk.="" there="" was="" no="" acute="" dietary="" endpoint="" identified,="" since="" cyprodinil="" does="" not="" pose="" acute="" dietary="" risk.="" 2.="" chronic="" risk.="" using="" the="" theoretical="" maximum="" residue="" contribution="" (tmrc)="" exposure="" assumptions="" described="" above,="" epa="" has="" concluded="" that="" aggregate="" exposure="" to="" cyprodinil="" from="" food="" will="" utilize="" 5.8%="" of="" the="" rfd="" for="" the="" u.s.="" population.="" the="" major="" identifiable="" subgroup="" with="" the="" highest="" aggregate="" exposure="" is="" non-nursing="" infants="">< 1="" year="" old)="" discussed="" below.="" epa="" generally="" has="" no="" concern="" for="" exposures="" below="" 100%="" of="" the="" rfd="" because="" the="" rfd="" represents="" the="" level="" at="" or="" below="" which="" daily="" aggregate="" dietary="" exposure="" over="" a="" lifetime="" will="" not="" pose="" appreciable="" risks="" to="" human="" health.="" despite="" the="" potential="" for="" exposure="" to="" cyprodinil="" in="" drinking="" water="" and="" from="" non-dietary,="" non-occupational="" exposure,="" epa="" does="" not="" expect="" the="" aggregate="" exposure="" to="" exceed="" 100%="" of="" the="" rfd.="" epa="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" [[page="" 17704]]="" aggregate="" exposure="" to="" cyprodinil="" residues.="" e.="" aggregate="" risks="" and="" determination="" of="" safety="" for="" infants="" and="" children="" 1.="" safety="" factor="" for="" infants="" and="" children--="" i.="" in="" general.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" cyprodinil,="" epa="" considered="" data="" from="" developmental="" toxicity="" studies="" in="" the="" rat="" and="" rabbit="" and="" a="" two-="" generation="" reproduction="" study="" in="" the="" rat.="" the="" developmental="" toxicity="" studies="" are="" designed="" to="" evaluate="" adverse="" effects="" on="" the="" developing="" organism="" resulting="" from="" maternal="" pesticide="" exposure="" during="" gestation.="" reproduction="" studies="" provide="" information="" relating="" to="" effects="" from="" exposure="" to="" the="" pesticide="" on="" the="" reproductive="" capability="" of="" mating="" animals="" and="" data="" on="" systemic="" toxicity.="" ffdca="" section="" 408="" provides="" that="" epa="" shall="" apply="" an="" additional="" tenfold="" margin="" of="" safety="" for="" infants="" and="" children="" in="" the="" case="" of="" threshold="" effects="" to="" account="" for="" pre-and="" post-natal="" toxicity="" and="" the="" completeness="" of="" the="" database="" unless="" epa="" determines="" that="" a="" different="" margin="" of="" safety="" will="" be="" safe="" for="" infants="" and="" children.="" margins="" of="" safety="" are="" incorporated="" into="" epa="" risk="" assessments="" either="" directly="" through="" use="" of="" a="" moe="" analysis="" or="" through="" using="" uncertainty="" (safety)="" factors="" in="" calculating="" a="" dose="" level="" that="" poses="" no="" appreciable="" risk="" to="" humans.="" epa="" believes="" that="" reliable="" data="" support="" using="" the="" standard="" uncertainty="" factor="" (usually="" 100="" for="" combined="" inter-="" and="" intra-species="" variability))="" and="" not="" the="" additional="" tenfold="" moe/uncertainty="" factor="" when="" epa="" has="" a="" complete="" data="" base="" under="" existing="" guidelines="" and="" when="" the="" severity="" of="" the="" effect="" in="" infants="" or="" children="" or="" the="" potency="" or="" unusual="" toxic="" properties="" of="" a="" compound="" do="" not="" raise="" concerns="" regarding="" the="" adequacy="" of="" the="" standard="" moe/safety="" factor.="" ii.="" developmental="" toxicity="" studies.="" in="" a="" prenatal="" developmental="" toxicity="" study,="" rats="" received="" oral="" administration="" of="" cyprodinil="" in="" 3.0%="" aqueous="" corn="" starch="" suspension="" at="" dose="" levels="" of="" 0,="" 20,="" 200="" or="" 1,000="" mg/kg/day="" during="" gestation="" days="" 6="" through="" 15.="" for="" maternal="" toxicity,="" the="" noel="" was="" 200="" mg/kg/day,="" and="" the="" loel="" was="" 1,000="" mg/kg/day="" based="" on="" decreased="" body="" weight,="" decreased="" body="" weight="" gain,="" and="" decreased="" food="" consumption.="" for="" developmental="" toxicity,="" the="" noel="" was="" 200="" mg/kg/day,="" and="" the="" loel="" was="" 1,000="" mg/kg/day="" based="" on="" increased="" incidence="" of="" skeletal="" variations="" (primarily="" absent="" or="" reduced="" ossification="" of="" the="" metacarpals)="" and="" on="" decreased="" mean="" fetal="" weight.="" in="" a="" prenatal="" developmental="" toxicity="" study,="" new="" zealand="" white="" rabbits="" (19/group)="" received="" oral="" administration="" of="" cyprodinil="" in="" 3.0%="" corn="" starch="" suspension="" (4="" ml/kg)="" at="" dose="" levels="" of="" 0,="" 5,="" 30,="" 150="" or="" 400="" mg/kg/day="" during="" gestation="" days="" 7="" through="" 19.="" for="" maternal="" toxicity,="" the="" noel="" was="" 150="" mg/kg/day="" and="" the="" loel="" was="" 400="" mg/kg/day="" based="" on="" decreased="" body="" weight="" gain="" during="" the="" treatment="" period.="" for="" developmental="" toxicity,="" the="" noel="" was="" 150="" mg/kg/day="" and="" the="" loel="" was="" 400="" mg/kg/day,="" based="" on="" an="" increased="" incidence="" of="" 13th="" rib.="" iii.="" reproductive="" toxicity="" study.="" in="" a="" two-generation="" reproduction="" study,="" rats="" (30/sex/group)="" were="" fed="" diets="" containing="" cyprodinil="" at="" does="" levels="" of="" 0,="" 10,="" 100,="" 1,000="" or="" 4,000="" ppm="" (0.7,="" 6.7,="" 68="" or="" 273="" mg/kg/day="" in="" males="" and="" 0.8,="" 8.2,="" 81="" or="" 326="" mg/kg/day="" in="" females)="" for="" parental="" systemic="" toxicity,="" the="" noel="" was="" 1,000="" ppm="" (81="" mg/kg/day)="" and="" the="" loel="" was="" 4,000="" ppm="" (326="" mg/kg/day)="" based="" on="" decreased="" parental="" female="" premating="" body="" weight="" gain.="" in="" addition,="" significant="" increases="" in="" liver="" and="" kidney="" weight="" at="" 4,000="" ppm="" were="" judged="" to="" be="" non-adverse="" due="" to="" lack="" of="" corroborative="" histopathological="" lesions.="" however,="" in="" light="" of="" the="" fact="" that="" the="" chronic="" study="" demonstrates="" liver="" toxicity,="" the="" epa="" believes="" that="" these="" organ="" weight="" changes="" should="" be="" considered="" as="" supportive="" evidence="" of="" toxicity="" at="" the="" loel="" of="" 4,000="" ppm.="" organ="" weight="" changes="" at="" 1,000="" ppm="" were="" not="" considered="" sufficient="" in="" magnitude="" to="" allow="" revision="" of="" the="" noel="" and="" loel="" for="" parental="" systemic="" toxicity.="" for="" offspring="" toxicity,="" the="" noel="" was="" 1,000="" ppm="" (81="" mg/kg/day)="" and="" the="" loel="" was="" 4,000="" ppm="" (326="" mg/kg/day),="" based="" on="" decreased="">1 and
F2 pup body weight during lactation and continuing into
adulthood for F1 rats.
iv. Pre- and post-natal sensitivity. The pre- and post-natal
toxicology database is complete with respect to current toxicological
data requirements. Based on the developmental and reproductive toxicity
studies discussed above, there does not appear to be an extra
sensitivity to pre- and post- natal effects.
v. Conclusion. EPA concludes that reliable data support use of the
hundredfold uncertainty factor and that an additional tenfold factor is
not needed to ensure the safety of infants and children from dietary
exposure.
2. Chronic risk. Using the conservative exposure assumptions
described above, EPA has concluded that aggregate exposure to
cyprodinil from food will utilize 14% of the RfD for nursing infants (< 1="" year="" old),="" 27%="" of="" the="" rfd="" for="" non-nursing="" infants="">< 1="" year="" old),="" 15%="" of="" the="" rfd="" for="" children="" 1="" to="" 6="" years="" old="" and="" 7.5%="" of="" the="" rfd="" for="" children="" 7="" to="" 12="" years="" old.="" epa="" generally="" has="" no="" concern="" for="" exposures="" below="" 100%="" of="" the="" rfd="" because="" the="" rfd="" represents="" the="" level="" at="" or="" below="" which="" daily="" aggregate="" dietary="" exposure="" over="" a="" lifetime="" will="" not="" pose="" appreciable="" risks="" to="" human="" health.="" despite="" the="" potential="" for="" exposure="" to="" cyprodinil="" in="" drinking="" water="" and="" from="" non-dietary,="" non-occupational="" exposure,="" epa="" does="" not="" expect="" the="" aggregate="" exposure="" to="" exceed="" 100%="" of="" the="" rfd.="" epa="" concludes="" that="" there="" is="" a="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" cyprodinil="" residues.="" iii.="" other="" considerations="" a.="" metabolism="" in="" plants="" and="" animals="" 1.="" nature="" of="" residue="" --="" plants.="" the="" nature="" of="" the="" residue="" in="" plants="" is="" understood.="" acceptable="" metabolism="" studies="" using="">14C-
labeled cyprodinil have been performed in stone fruit (peaches), pome
fruit (apples), wheat, tomatoes, and potatoes. Cyprodinil is
metabolized primarily by hydroxylation followed by sugar conjugation.
Cleavage of the amino bridge, opening of the pyrimidine ring, opening
of the cyclopropyl ring and formation of thiolactic acid conjugates are
also minor pathways. Incorporation into starch was also observed in
potato tubers and wheat grain.
EPA has determined that there are no cyprodinil metabolites of
toxicological or regulatory concern in plants.
2. Nature of residue-- animals-- i. Ruminants. The nature of the
residue in ruminants is understood. An acceptable metabolism study
using 14C phenyl-labeled cyprodinil has been performed in
goats. Based on the structures characterized, the metabolism of
cyprodinil proceeded predominantly via hydroxylation followed by
conjugation with sulfuric and glucuronic acid. A breakdown of the
pyrimidine ring was seen only in the liver and resulted in metabolite
L1. Cleavage of the amino bridge between the phenyl and the pyrimidine
ring was only a minor reaction as indicated by the small amounts of CGA
249287 found in the liver and kidneys of goats dosed with
14C-pyrimidine cyprodinil.
For compounds with multiple rings, it is generally required that
acceptable metabolism studies be performed with each ring labeled.
However, as the acceptable metabolism study using 14C-
phenyl-labeled cyprodinil indicated that ring cleavage is a minor
pathway and the available data from a supplementary ruminant metabolism
study using 14C-pyrimidine-labeled cyprodinil support this
conclusion, further ruminant
[[Page 17705]]
metabolism studies for cyprodinil will not be required.
EPA has determined that there are no cyprodinil metabolites of
toxicological or regulatory concern in animals based on the dietary
burden associated with the proposed uses.
ii. Poultry. There are no poultry feed items associated with the
proposed uses. Therefore data on the nature of the residue in poultry
is not required for this petition.
B. Analytical Enforcement Methodology
An adequate enforcement methodology, AG-631B, is available to
enforce the tolerance on stone fruits, pome fruits, almond hulls,
almond nutmeats and grapes. Quantitation is by high performance liquid
chromatography with column switching. Information about the analytical
method is available to the public from: Calvin Furlow, Information
Resources and Services Division, Public Information and Records
Integrity Branch, 7502C, Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460, office
location and telephone number: Room 101FF, CM #2, 1921 Jefferson Davis
Highway, Arlington, VA 22202 (703-305-5229).
Because no tolerances for animal commodities are required, no
analytical methods for animal commodities were required.
C. Magnitude of Residues
The residues of cyprodinil resulting from the proposed uses will
not exceed almond hulls at 0.05 ppm; almond nutmeats at 0.02 ppm; apple
pomace, wet at 0.15 ppm; grapes at 2.0 ppm; pome fruit at 0.1 ppm;
raisins at 3.0 ppm and stone fruit at 2.0 ppm. .
D. International Residue Limits
There are no Codex or Mexican residue limits established for
cyprodinil. As part of the joint review, Canada will be setting
equivalent tolerances for pome fruits and stone fruits and equivalent
import tolerances for almonds and grapes. Therefore no compatibility
problems exist for the proposed tolerances.
E. Rotational Crop Restrictions
Stone fruit, pome fruit, almonds and grapes are not rotated,
therefore rotational crop restrictions do not apply to this petition.
IV. Conclusion
Therefore, the following tolerances are established for residues of
cyprodinil: almond hulls at 0.05 ppm; almond nutmeats at 0.02 ppm;
apple pomace, wet at 0.15 ppm; grapes at 2.0 ppm; pome fruit at 0.1
ppm; raisins at 3.0 ppm and stone fruit at 2.0 ppm.
V. Objections and Hearing Requests
The new FFDCA section 408(g) provides essentially the same process
for persons to ``object'' to a tolerance regulation issued by EPA under
new section 408(e) and (l)(6) as was provided in the old section 408
and in section 409. However, the period for filing objections is 60
days, rather than 30 days. EPA currently has procedural regulations
which govern the submission of objections and hearing requests. These
regulations will require some modification to reflect the new law.
However, until those modifications can be made, EPA will continue to
use those procedural regulations with appropriate adjustments to
reflect the new law.
Any person may, by June 9, 1998, file written objections to any
aspect of this regulation and may also request a hearing on those
objections. Objections and hearing requests must be filed with the
Hearing Clerk, at the address given above (40 CFR 178.20). A copy of
the objections and/or hearing requests filed with the Hearing Clerk
should be submitted to the OPP docket for this rulemaking. The
objections submitted must specify the provisions of the regulation
deemed objectionable and the grounds for the objections (40 CFR
178.25). Each objection must be accompanied by the fee prescribed by 40
CFR 180.33(i). If a hearing is requested, the objections must include a
statement of the factual issues on which a hearing is requested, the
requestor's contentions on such issues, and a summary of any evidence
relied upon by the requestor (40 CFR 178.27). A request for a hearing
will be granted if the Administrator determines that the material
submitted shows the following: There is genuine and substantial issue
of fact; there is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary; and resolution of the
factual issues in the manner sought by the requestor would be adequate
to justify the action requested (40 CFR 178.32). Information submitted
in connection with an objection or hearing request may be claimed
confidential by marking any part or all of that information as
Confidential Business Information (CBI). Information so marked will not
be disclosed except in accordance with procedures set forth in 40 CFR
part 2. A copy of the information that does not contain CBI must be
submitted for inclusion in the public record. Information not marked
confidential may be disclosed publicly by EPA without prior notice.
VI. Public Docket
EPA has established a record for this rulemaking under docket
control number [OPP-300643] (including any comments and data submitted
electronically). A public version of this record, including printed,
paper versions of electronic comments, which does not include any
information claimed as CBI, is available for inspection from 8:30 a.m.
to 4 p.m., Monday through Friday, excluding legal holidays. The public
record is located in Room 119 of the Public Information and Records
Integrity Branch, Information Resources and Services Division (7502C),
Office of Pesticide Programs, Environmental Protection Agency, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments may be sent directly to EPA at:
opp-docket@epamail.epa.gov.
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption.
The official record for this rulemaking, as well as the public
version, as described above will be kept in paper form. Accordingly,
EPA will transfer any copies of objections and hearing requests
received electronically into printed, paper form as they are received
and will place the paper copies in the official rulemaking record which
will also include all comments submitted directly in writing. The
official rulemaking record is the paper record maintained at the
Virginia address in ``ADDRESSES'' at the beginning of this document.
VII. Regulatory Assessment Requirements
This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). This final rule does not contain
any information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose any enforceable
duty or contain any unfunded mandate as described under Title II of the
Unfunded Mandates Reform Act of 1995 (UMRA) (Pub. L. 104-4). Nor does
it require any prior
[[Page 17706]]
consultation as specified by Executive Order 12875, entitled Enhancing
the Intergovernmental Partnership (58 FR 58093, October 28, 1993), or
special considerations as required by Executive Order 12898, entitled
Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994),
or require OMB review in accordance with Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997).
In addition, since these tolerances and exemptions that are
established on the basis of a petition under FFDCA section 408(d), such
as the tolerances set in this final rule, do not require the issuance
of a proposed rule, the requirements of the Regulatory Flexibility Act
(RFA) (5 U.S.C. 601 et seq.) do not apply. Nevertheless, the Agency has
previously assessed whether establishing tolerances, exemptions from
tolerances, raising tolerance levels or expanding exemptions might
adversely impact small entities and concluded, as a generic matter,
that there is no adverse economic impact. The factual basis for the
Agency's generic certification for tolerance actions published on May
4, 1981 (46 FR 24950) and was provided to the Chief Counsel for
Advocacy of the Small Business Administration.
VIII. Submission to Congress and the General Accounting Office
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by
the Small Business Regulatory Enforcement Fairness Act of 1996,
generally provides that before a rule may take effect, the agency
promulgating the rule must submit a rule report, which includes a copy
of the rule, to each House of the Congress and to the Comptroller
General of the United States. EPA will submit a report containing this
rule and other required information to the U.S. Senate, the U.S. House
of Representatives, and the Comptroller General of the United States
prior to publication of the rule in the Federal Register. This rule is
not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 6, 1998.
Stephen L. Johnson,
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. 346a and 371.
2. By adding Sec. 180.532 to subpart C to read as follows:
Sec. 180.532 Cyprodinil, tolerances for residues.
(a) General . Tolerances are established for residues of the
fungicide cyprodinil, 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine
in or on the following food commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Almond hulls............................................... 0.05
Almond nutmeats............................................ 0.02
Apple pomace, wet.......................................... 0.15
Grapes..................................................... 2.0
Pome fruit................................................. 0.1
Raisins.................................................... 3.0
Stone fruit................................................ 2.0
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 98-9679 Filed 4-9-98; 8:45 am]
BILLING CODE 6560-50-F
