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Flumioxazin (Valent). April 18, 2001, Pesticide Tolerances for soybean seed and peanut nutmeat at 0.02 ppm. Final Rule. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2001/April/Day-18/p9597.htm
[Federal Register: April 18, 2001 (Volume 66, Number 75)]
[Rules and Regulations]
[Page 19870-19879]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18ap01-13]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-301116; FRL-6778-5]
RIN 2070-AB78
Flumioxazin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes a tolerances for residues of
flumioxazin in or on soybean seed and peanuts. Valent U.S.A.
Corporation requested this tolerance under the Federal Food, Drug, and
Cosmetic Act, as amended by the Food Quality Protection Act of 1996.
DATES: This regulation is effective April 18, 2001. Objections and
requests for hearings, identified by docket control number OPP-301116,
must be received by EPA on or before June 18, 2001.
ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please
[[Page 19871]]
follow the detailed instructions for each method as provided in Unit
VI.. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA,
your objections and hearing requests must identify docket control
number OPP-301116 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller,
Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave.,
NW.,Washington, DC 20460; telephone number: (703) 305-6224; and e-mail
address: miller.joanne@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:
------------------------------------------------------------------------
Examples of
Categories NAICS codes potentially
affected entities
------------------------------------------------------------------------
Industry 111 Crop production
112 Animal production
311 Food manufacturing
32532 Pesticide
manufacturing
------------------------------------------------------------------------
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Electronically.You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/. To access the OPPTS Harmonized
Guidelines referenced in this document, go directly to the guidelines
at http://www.epa.gov/opptsfrs/home/guidelin.htm. A frequently updated
electronic version of 40 CFR part 180 is available at http://
www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180._00.html, a
beta site currently under development.
2. In person. The Agency has established an official record for
this action under docket control number OPP-301116. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential Business Information (CBI). This official
record includes the documents that are physically located in the
docket, as well as the documents that are referenced in those
documents. The public version of the official record does not include
any information claimed as CBI. The public version of the official
record, which includes printed, paper versions of any electronic
comments submitted during an applicable comment period is available for
inspection in the Public Information and Records Integrity Branch
(PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy.,
Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The PIRIB telephone number is (703) 305-5805.
II. Background and Statutory Findings
In the Federal Register of February 14, 2001 (66 FR 10292) (FRL-
6765-8), EPA issued a notice pursuant to section 408 of the Federal
Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a as amended by the
Food Quality Protection Act of 1996 (FQPA) (Public Law 104-170)
announcing the filing of pesticide petitions (PP 7F4841 and OF6171) for
tolerances by Valent U.S.A. Corporation, 1333 North California,
Boulevard, Suite 600, Walnut Creek, CA 94596-8025. This notice included
a summary of the petition prepared by Valent U.S.A. Corporation, the
registrant. There were no comments received in response to the notice
of filing.
The petition requested that 40 CFR part 180 be amended by
establishing tolerances for residues of the herbicide flumioxazin, 2-
[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-6-yl]-
4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, in or on soybean seed
and peanuts at 0.01 part per million (ppm). Valent U.S.A. Corporation
subsequently amended the petition to request tolerances in or on
soybean seed and peanut nutmeat at 0.02 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) defines ``safe'' to mean that ``there is a reasonable
certainty that no harm will result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information.'' This
includes exposure through drinking water and in residential settings,
but does not include occupational exposure. Section 408(b)(2)(C)
requires EPA to give special consideration to exposure of infants and
children to the pesticide chemical residue in establishing a tolerance
and to ``ensure that there is a reasonable certainty that no harm will
result to infants and children from aggregate exposure to the pesticide
chemical residue * * *.''
EPA performs a number of analyses to determine the risks from
aggregate exposure to pesticide residues. For further discussion of the
regulatory requirements of section 408 and a complete description of
the risk assessment process, see the final rule on Bifenthrin Pesticide
Tolerances (62 FR 62961, November 26, 1997) (FRL--5754-7).
III. Aggregate Risk Assessment and Determination of Safety
Consistent with section 408(b)(2)(D), EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure, consistent with section
408(b)(2), for a tolerances for residues of flumioxazin on soybean seed
and peanut nutmeat at 0.02 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 flumioxazin are
discussed in the following Table 1 as well as the no observed adverse
effect level (NOAEL) and the lowest observed
[[Page 19872]]
adverse effect level (LOAEL) from the toxicity studies reviewed.
Table 1.-- Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
Guideline No. Study type Results
----------------------------------------------------------------------------------------------------------------
870.1000 Acute Oral - rat LD50 >5,000 mg/kg (M and F); no clinical
signs
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870.1100 Acute Dermal - rat LD50 >2,000 mg/kg; no clinical signs
----------------------------------------------------------------------------------------------------------------
870.1200 Acute Inhalation - rat LC50 = 3.93 mg/L
----------------------------------------------------------------------------------------------------------------
870.2400 Primary Eye Irritation - No corneal irritation; mild irritation of
rabbit iris cleared by 24 hours; mild irritation
of conjunctival cleared by 48 hours
----------------------------------------------------------------------------------------------------------------
870.2500 Primary Skin Irritation - No erythema or edema
rabbit
----------------------------------------------------------------------------------------------------------------
870.2600 Dermal sensitization - Not a dermal sensitizer
guinea pig
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity - rat NOAEL = mg/kg/day: 69.7 (M), 71.5 (F)
LOAEL = mg/kg/day: 243.5 (M), 229.6 (F)
based on a decrease in MCV both sexes;
increase in platelets F only
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity - rat NOAEL = mg/kg/day: 65.0 (M), 72.9 (F)
LOAEL = mg/kg/day: 196.7 (M), 218.4 (F)
based on hematology changes
----------------------------------------------------------------------------------------------------------------
870.3150 90-Day capsule - dog NOAEL = mg/kg/day: 10 (M and F) LOAEL = mg/
kg/day: 100 (M and F) based on dose
dependent increase in total cholesterol,
phospholipid and alkaline phosphatase
----------------------------------------------------------------------------------------------------------------
870.3100 90-Day oral toxicity - NOAEL = mg/kg/day: 429 (M and F) LOAEL = mg/
mouse kg/day: 1429 (M and F) based on increased
liver weight in males
----------------------------------------------------------------------------------------------------------------
870.3100 4-Week oral toxicity - NOAEL = mg/kg/day: 151.5 (M), 164.5 (F)
mouse LOAEL = mg/kg/day: 419.9 (M), 481.6 (F)
based on increased absolute and/or
relative liver weights in M and F
----------------------------------------------------------------------------------------------------------------
870.3200 21-Day dermal toxicity - NOAEL = mg/kg/day: 1,000 (LIMIT DOSE) LOAEL
rat = mg/kg/day: £1,000 based on no
effects
----------------------------------------------------------------------------------------------------------------
870.3700a Prenatal developmental - Maternal NOAEL = 30 mg/kg/day (HDT) LOAEL =
rat (oral) >30 mg/kg/day (HDT) Developmental NOAEL =
3 mg/kg/day LOAEL = 10 mg/kg/day based on
cardiovascular effects (especially
ventricular septal defects)
----------------------------------------------------------------------------------------------------------------
870.3700a Prenatal developmental - Maternal NOAEL = 300 mg/kg/day (HDT) LOAEL
rat (dermal) = >300 mg/kg/day (HDT) Developmental NOAEL
= 30 mg/kg/day LOAEL = 100 mg/kg/day based
on cardiovascular effects (especially
ventricular septal defects)
----------------------------------------------------------------------------------------------------------------
870.3700b Prenatal developmental - Maternal NOAEL = 1,000 mg/kg/day LOAEL =
rabbit (oral) 3,000 mg/kg/day (HDT) based on decrease in
body weight and food consumption during
dosing Developmental NOAEL = 3000 mg/kg/
day (HDT) LOAEL = >3,000 mg/kg/day
----------------------------------------------------------------------------------------------------------------
870.3800 Reproduction and fertility Parental/Systemic NOAEL = mg/kg/day: males
effects - rat = 12.7, females = 15.1 LOAEL = mg/kg/day:
males = 18.9, females = 22.7 based on
increase in clinical signs (red substance
in vagina) and increased female mortality
as well as decreased body weight, body
weight gain and food consumption
Reproductive NOAEL = mg/kg/day: males =
18.9 (HDT), females = 22.7 (HDT) LOAEL =
mg/kg/day: males = >18.9 (HDT), females =
>22.7 (HDT) Offspring NOAEL = mg/kg/day:
males = 6.3, females = 7.6 LOAEL = mg/kg/
day: males = 12.7, females = 15.1 based on
a decrease in the number of liveborn and a
decrease in pup body weight
----------------------------------------------------------------------------------------------------------------
870.4100 12-Month capsule - dog NOAEL = 100 mg/kg/day (M and F) LOAEL =
1,000 mg/kg/day (M and F), (LIMIT DOSE)
based on the following for males and
females: increased absolute and relative
liver weights; 300% increase in alkaline
phosphatase values
----------------------------------------------------------------------------------------------------------------
870.4200 Carcinogenicity - mouse NOAEL = mg/kg/day: males = 754.1, females =
859.1 (LIMIT DOSE) LOAEL = no systemic
effects at LIMIT DOSE in males or females
No evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
[[Page 19873]]
870.4300 Combined chronic NOAEL = mg/kg/day: males = 1.8, females =
carcinogenicity - rat 2.2 LOAEL = mg/kg/day: males = 18.0,
females = 21.8 based on increased chronic
nephropathy in males and decreased
hematological parameters in females (Hgb,
MCV, MCH and MCHC)
No evidence of carcinogenicity
----------------------------------------------------------------------------------------------------------------
870.5100 Gene mutation in S. Neither cytotoxic nor mutagenic up to 2,000
typhimurium and E. coli µg/plate. There were reproducible
increases in revertant colonies of S.
typhimurium strains TA1538 and TA98 in S9
activated phases of the preliminary
cytotoxicity and both mutation assays.
Results considered to be equivocal.
----------------------------------------------------------------------------------------------------------------
870.5375 Gene mutation in chinese Precipitation at 3200 µM.
hamster ovary cells Cytotoxicity at 500 µM. Positive
+S9 3100 µM and negative
at 30-500 µM -S9. Aberrations were
chromatid breaks and exchanges.
----------------------------------------------------------------------------------------------------------------
870.5395 In vivo rat bone marrow Negative in male (up to 5,000 mg/kg) and
female rats (up to 4,400 mg/kg) when
tested orally.
----------------------------------------------------------------------------------------------------------------
870.5550 UDS assay Negative up to 5,000 mg/kg.
----------------------------------------------------------------------------------------------------------------
870.7485 Metabolism and Gastrointestinal tract absorption >90% at 1
pharmacokinetics - rat mg/kg and up to 50% at 100 mg/kg. At least
(oral) 97% recovery in feces and urine 7 days
after dosing. Highest levels of residues
(36-49 ppb) in blood cells at low dose and
2800-3000 ppg at high dose (RBC levels >
plasma). In addition to untransformed
parent, 7 metabolites identified in urine
and feces (38-46% for low dose and about
71% at high dose).
----------------------------------------------------------------------------------------------------------------
870.7600 Dermal penetration - rat Males dosed with suspension of 50 WDG
formulation in water at 0.02, 0.20 or 1.0
mg/rat (0.002, 0.020 or 0.100 cm2. At 0.02
mg/rat, absorption ranged from 0.48% at
0.5 hours to 5.46% at 24 hours. At 0.2 mg/
rat, absorption ranged from 0.007% at 0.5
hours to 0.74% at 24 hours. At 1.0 mg/rat,
absorption ranged from 0.004% at 0.5 hours
to 10.47% at 24 hours.
----------------------------------------------------------------------------------------------------------------
870.7600 Dermal penetration - rat Females dosed with 200 or 800 mg/kg b.w.
Dermal absorption for 200 and 800 mg/kg
was 3.9 and 8.0% by 48 hours after
initiation of treatment for 6 hours. Blood
levels at 6-24 hours after dermal dosing
with 200 mg/kg were similar to those
obtained at 2-6 hours after oral dosing
with 1 mg/kg. Blood levels at 6-24 hours
after dermal dosing with 800 mg/kg were
similar to those obtained at 2-6 hours
after oral dosing with 30 mg/kg.
----------------------------------------------------------------------------------------------------------------
Special Study - Rat Pregnant females were administered 400 mg/
Developmental: Critical kg by gavage on gestation day 11 or 12 or
Time for Defects 13 or 14 or 15. Day 12 administration
showed: largest incidence of embryonic
death, lowest fetal body weights and
greatest incidence of ventricular spetal
defects.
----------------------------------------------------------------------------------------------------------------
B. Toxicological Endpoints
The dose at which no adverse effects are observed (the NOAEL) from
the toxicology study identified as appropriate for use in risk
assessment is used to estimate the toxicological level of concern
(LOC). However, the lowest dose at which adverse effects of concern are
identified (the LOAEL) is sometimes used for risk assessment if no
NOAEL was achieved in the toxicology study selected. An uncertainty
factor (UF) is applied to reflect uncertainties inherent in the
extrapolation from laboratory animal data to humans and in the
variations in sensitivity among members of the human population as well
as other unknowns. An UF of 100 is routinely used, 10x to account for
interspecies differences and 10x for intra species differences.
For dietary risk assessment (other than cancer) the Agency uses the
UF to calculate an acute or chronic reference dose (acute RfD or
chronic RfD) where the RfD is equal to the NOAEL divided by the
appropriate UF (RfD = NOAEL/UF). Where an additional safety factor is
retained due to concerns unique to the FQPA, this additional factor is
applied to the RfD by dividing the RfD by such additional factor. The
acute or chronic Population Adjusted Dose (aPAD or cPAD) is a
modification of the RfD to accommodate this type of FQPA Safety Factor.
For non-dietary risk assessments (other than cancer) the UF is used
to determine the LOC. For example, when 100 is the appropriate UF (10x
to account for interspecies differences and 10x for intraspecies
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and
compared to the LOC.
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 (MOE cancer = point of
departure/exposures) is calculated. A summary of the toxicological
endpoints for flumioxazin used for human risk assessment is shown in
the following Table 2:
[[Page 19874]]
Table 2.--Summary of Toxicological Dose and Endpoints for Flumioxazin for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
FQPA SF* and level of
Exposure scenario Dose used in risk concern for risk Study and toxicological
assessment, UF assessment effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary Females 13-50 NOAEL = 3 mg/kg/day FQPA SF = 10 aPAD = Oral developmental and
Acute RfD = 0.03 mg/kg/ acute RfD FQPA SF = supplemental prenatal
day 0.003 mg/kg/day studies in the rat
LOAEL = 10 mg/kg/day
based on
cardiovascular effects
(especially
ventricular septal
defects in fetuses)
----------------------------------------------------------------------------------------------------------------
Acute Dietary General Population An endpoint attributable to a single dose (exposure) was not identified
from the available studies, including the developmental toxicity studies
in rats and rabbits.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary all populations NOAEL = 2 mg/kg/day UF FQPA SF = 10 cPAD = 2-Year Chronic/
= 100 Chronic RfD = chronic RfD FQPA SF = Carcinogenicity Study
0.02 mg/kg/day 0.002 mg/kg/day in the rat LOAEL = 18
mg/kg/day based on
increased chronic
nephropathy in males
and decreased
hematological
parameters in females
(Hgb, MCV, MCH and
MCHC)
----------------------------------------------------------------------------------------------------------------
Incidental Oral (short and NOAEL = 65 mg/kg/day Target MOE = 1,000 90-Day Toxicity Studies
intermediate term) (Residential) in the rat LOAEL =
196.7 mg/kg/day based
on hematology changes
(decrease in MCV and
increase in female
platelets)
----------------------------------------------------------------------------------------------------------------
Dermal (all durations) NOAEL = 30 mg/kg/day Target MOE = 1,000 Dermal Developmental
(Residential) Study in the rat LOAEL
= 100 mg/kg/day based
on cardiovascular
effects (especially
ventricular septal
defects in fetuses)
----------------------------------------------------------------------------------------------------------------
Short-term Inhalation NOAEL = 3 mg/kg/day Target MOE = 1,000 Oral Developmental
(Residential) Study in the rat LOAEL
= 10 mg/kg/day based
on cardiovascular
effects (especially
ventricular septal
defects in fetuses)
----------------------------------------------------------------------------------------------------------------
Intermediate- and Long-term NOAEL = 2 mg/kg/day Target MOE = 1,000 2-Year Chronic/
Inhalation (Residential) Carcinogenicity Study
in the rat LOAEL = 18
mg/kg/day based on
increased chronic
nephropathy in males
and decreased
hematological
parameters in females
(Hgb, MCV, MCH and
MCHC)
----------------------------------------------------------------------------------------------------------------
Cancer (oral, dermal, inhalation) Not likely to be a carcinogen for humans based on the lack of
carcinogenicity in a 2-year rat study, an 18-month mouse study and a
battery of mutagenic studies.
----------------------------------------------------------------------------------------------------------------
*The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
to the FQPA.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. No previous tolerances
have been established for the residues of flumioxazin. Risk assessments
were conducted by EPA to assess dietary exposures from flumioxazin 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)
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 acute
exposure assessments: For this acute analysis the assumption was made
that 100% of the crops with flumioxazin tolerances are treated with
flumioxazin. In addition, the assumption was made that all commodities
contain tolerance level residues when consumed, with the exception of
those with default processing factors. Default processing factors were
used for peanuts-butter (1.89x) and for soybeans-sprouted seeds
(0.33x). As the exposure and risk estimates were low, no further
refinements were made to this analysis.
ii. Chronic exposure. In conducting this chronic dietary risk
assessment the DEEM analysis evaluated the individual food consumption
as reported by respondents in the USDA 1989-1992 nationwide CSFII and
accumulated exposure to the chemical for each commodity. The following
assumptions were made for the chronic exposure assessments: For this
chronic analysis the assumption was made that 100% of the crops with
flumioxazin tolerances are treated with flumioxazin. In addition, the
assumption was made that all commodities contain tolerance level
residues when consumed, with the exception of those with default
processing factors. Default processing factors were used for peanuts-
butter (1.89x) and for soybeans-sprouted seeds (0.33x). As the exposure
and risk estimates were low, no further refinements were made to this
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 flumioxazin 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 flumioxazin.
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
Screening Concentrations in Ground
[[Page 19875]]
Water (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.
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 %RfD or %PAD. 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 flumioxazin they are further
discussed in the aggregate risk sections below.
The hydrolysis study for flumioxazin indicates that flumioxazin
forms the metabolite 482-HA, which can further hydrolyze to metabolites
APF and THPA. The rates of the two hydrolytic reactions are very pH
dependent, but the parent is not very stable at any likely
environmental pH. Additional data indicated that THPA and APF are
likely to be very mobile. Although THPA can comprise a major portion of
the total residue in water, it does not possess the phenyl ring and is
thus considered significantly less toxic than parent, APF, and 482-HA,
thus THPA needs not be included in the residue of concern for drinking
water. Therefore, parent flumioxazin and the metabolites 482-HA and APF
are the residues of concern in drinking water.
Based on the GENEEC and SCI-GROW models the estimated environmental
concentrations (EECs) of flumioxazin and its metabolites of concern in
water for acute exposures are estimated to be 2.4 parts per billion
(ppb) for surface water and 6.3 ppb for ground water. The EECs for
chronic exposures are estimated to be 0.67 ppb for surface water and
6.3 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).
Flumioxazin is not registered for use on any sites that would
result in residential exposure.
4. Cumulative exposure to substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
consider ``available information'' concerning the cumulative effects of
a particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.''
EPA does not have, at this time, available data to determine
whether flumioxazin 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,
flumioxazin 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 flumioxazin has a common mechanism of toxicity
with other substances. For information regarding EPA's efforts to
determine which chemicals have a common mechanism of toxicity and to
evaluate the cumulative effects of such chemicals, see the final rule
for Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997).
D. Safety Factor for Infants and Children
1. In general. FFDCA section 408 provides that EPA shall apply an
additional tenfold margin of safety for infants and children in the
case of threshold effects to account for prenatal and postnatal
toxicity and the completeness of the data base on toxicity and exposure
unless EPA determines that a different margin of safety will be safe
for infants and children. Margins of safety are incorporated into EPA
risk assessments either directly through use of a margin of exposure
(MOE) analysis or through using uncertainty (safety) factors in
calculating a dose level that poses no appreciable risk to humans.
2. Prenatal and postnatal sensitivity. The data for flumioxazin
indicate that there is both quantitative and qualitative evidence of
increased susceptibility to flumioxazin from prenatal or postnatal
exposures. Quantitative susceptibility is observed when the young
respond more than the adults at a given dose, and qualitative
susceptibility is observed when there is a unique biological target,
such as the developing brain, that predisposes the individual.
The quantitative and qualitative evidence of increased
susceptibility is observed with the rat fetuses to in utero exposure to
flumioxazin in the oral and dermal developmental studies. In both
studies, there was an increased incidence in fetal cardiovascular
anomalies (especially ventricular septal defects). In the oral study,
no maternal effects were seen at the highest dose tested (HDT) (30
milligrams/kilograms (mg/kg/day)); whereas, the effects in the fetuses
were observed at 10 mg/kg/day. In the dermal study, no maternal effects
were noted at the HDT (300 mg/kg/day); whereas, the effects in the
fetuses were observed at 100 mg/kg/day. Regarding the 2-generation rat
reproduction study, parental effects (red substance in vagina and
increased mortality in females as well as decreases in male and female
body weights, body weight gains, and food consumption) were noted at
18.9 mg/kg/day in males HDT and 22.7 mg/kg/day in females HDT. Based on
the results of the study, no apparent reproduction effects were
attributed to test article administration. The effects observed
regarding the offspring were a decrease in both the number of liveborn
and pup body weights at 12.7 mg/kg/day for males and 15.1 mg/kg/day for
females. Therefore, it was considered that there was both a
quantitative and qualitative increase in susceptibility.
3. Conclusion. There is a complete toxicity data base for
flumioxazin and exposure data are complete or are estimated based on
data that reasonably accounts for potential exposures. The FQPA safety
factor (as required by the Food Quality Protection Act of August 3,
1996) has been retained at 10x for all population subgroups for all
exposure durations (acute and chronic) in assessing the risk posed by
this chemical. The reasons for retaining the 10x safety factor are as
follows. First, there is evidence of increased susceptibility of the
rat fetuses to in utero exposure to flumioxazin by the
[[Page 19876]]
oral and dermal route in the prenatal developmental toxicity studies in
rats. In addition, there is evidence of increased susceptibility of
young animals exposed to flumioxazin in the 2-generation reproduction
toxicity study in rats. Finally, there is concern for the severity of
the effects observed in fetuses and young animals when compared to
those observed in the maternal and parental animals (dose- and
treatment-related increase in the incidence of cardiovascular
abnormalities, particularly ventricular septal defect, in the
developmental studies; and decreases in the number of live born pups
and pup body weights in the absence of parental toxicity in the
reproduction study).
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 Office of Water are used to calculate
DWLOCs: 2L/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, OPP concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which OPP has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because OPP 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, OPP will reassess the potential impacts
of residues of the pesticide in 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 to the subgroup of concern, the acute dietary
exposure from food to flumioxazin will occupy 0.72% of the aPAD for
females 13 years and older. In addition, there is potential for acute
dietary exposure to flumioxazin 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 the following Table 3:
Table 3.--Aggregate Risk Assessment for Acute Exposure to Flumioxazin
----------------------------------------------------------------------------------------------------------------
Surface Ground
Population subgroup aPAD (mg/ % aPAD water EEC water EEC Acute DWLOC
kg) (food) (ppb) (ppb) (ppb)
----------------------------------------------------------------------------------------------------------------
Females (13+ years) 0.003 0.72 2.4 6.3 90
----------------------------------------------------------------------------------------------------------------
2. Chronic risk. Using the exposure assumptions described inthis
unit for chronic exposure, EPA has concluded that exposure to
flumioxazin from food will utilize 0.5% of the cPAD for the U.S.
population, 2.3% of the cPAD for all infants (< 1 year) and 1.2% of the
cPAD for children (1-6 years). There are no residential uses for
flumioxazin that result in chronic residential exposure to flumioxazin.
In addition, there is potential for chronic dietary exposure to
flumioxazin 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 the
following Table 4:
Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to flumioxazin
----------------------------------------------------------------------------------------------------------------
Surface Ground
U.S population subgroup cPAD mg/kg/ % cPAD water EEC water EEC Chronic
day (food) (ppb) (ppb) DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. Population 0.002 0.5 0.67 6.3 70
----------------------------------------------------------------------------------------------------------------
Infants (< 1 year) 0.002 2.3 0.67 6.3 20
----------------------------------------------------------------------------------------------------------------
Females (13+ years) 0.002 0.4 0.67 6.3 60
----------------------------------------------------------------------------------------------------------------
Males (13 - 19 years) 0.002 0.6 0.67 6.3 70
----------------------------------------------------------------------------------------------------------------
3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level).
Flumioxazin 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.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account residential exposure
[[Page 19877]]
plus chronic exposure to food and water (considered to be a background
exposure level).
Flumioxazin 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. 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 flumioxazin residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (gas chromatography) is available
to enforce the tolerance expression. The method may be requested from:
Calvin Furlow, PIRIB, IRSD (7502C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW,
Washington, DC 20460; telephone number: (703) 305-5229; e-mail address:
furlow.calvin@epa.gov.
B. International Residue Limits
There are no Codex, Canadian or Mexican maximum residue limits
established on soybeans or peanuts.
V. Conclusion
Therefore, the tolerances are is established for residues of
flumioxazin, 2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-
benzoxazin-6-yl]-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, in or
on soybean seed and peanuts at 0.02 ppm.
VI. Objections and Hearing Requests
Under section 408(g) of the FFDCA, as amended by the FQPA, any
person may file an objection to any aspect of this regulation and may
also request a hearing on those objections. The EPA procedural
regulations which govern the submission of objections and requests for
hearings appear in 40 CFR part 178. Although the procedures in those
regulations require some modification to reflect the amendments made to
the FFDCA by the FQPA of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) provides essentially
the same process for persons to ``object'' to a regulation for an
exemption from the requirement of a tolerance issued by EPA under new
section 408(d), as was provided in the old FFDCA sections 408 and 409.
However, the period for filing objections is now 60 days, rather than
30 days.
A. What Do I Need to Do to File an Objection or Request a Hearing?
You must file your objection or request a hearing on this
regulation in accordance with the instructions provided in this unit
and in 40 CFR part 178. To ensure proper receipt by EPA, you must
identify docket control number OPP-301116 in the subject line on the
first page of your submission. All requests must be in writing, and
must be mailed or delivered to the Hearing Clerk on or before June 18,
2001.
1. Filing the request. Your objection must specify the specific
provisions in the regulation that you object to, and the grounds for
the objections (40 CFR 178.25). If a hearing is requested, the
objections must include a statement of the factual issues(s) on which a
hearing is requested, the requestor's contentions on such issues, and a
summary of any evidence relied upon by the objector (40 CFR 178.27).
Information submitted in connection with an objection or hearing
request may be claimed confidential by marking any part or all of that
information as CBI. Information so marked will not be disclosed except
in accordance with procedures set forth in 40 CFR part 2. A copy of the
information that does not contain CBI must be submitted for inclusion
in the public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice.
Mail your written request to: Office of the Hearing Clerk (1900),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460. You may also deliver your request to the Office
of the Hearing Clerk in Rm. C400, Waterside Mall, 401 M St., SW.,
Washington, DC 20460. The Office of the Hearing Clerk is open from 8
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
telephone number for the Office of the Hearing Clerk is (202) 260-4865.
2. Tolerance fee payment. If you file an objection or request a
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must
mail the fee to: EPA Headquarters Accounting Operations Branch, Office
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please
identify the fee submission by labeling it ``Tolerance Petition Fees.''
EPA is authorized to waive any fee requirement ``when in the
judgement of the Administrator such a waiver or refund is equitable and
not contrary to the purpose of this subsection.'' For additional
information regarding the waiver of these fees, you may contact James
Tompkins by phone at (703) 305-5697, by e-mail at tompkins.jim@epa.gov,
or by mailing a request for information to Mr. Tompkins at Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
If you would like to request a waiver of the tolerance objection
fees, you must mail your request for such a waiver to: James Hollins,
Information Resources and Services Division (7502C), Office of
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460.
3. Copies for the Docket. In addition to filing an objection or
hearing request with the Hearing Clerk as described in Unit VI.A., you
should also send a copy of your request to the PIRIB for its inclusion
in the official record that is described in Unit I.B.2. Mail your
copies, identified by docket control number OPP-301116, to: Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-docket@epa.gov. Please use an ASCII file
format and avoid the use of special characters and any form of
encryption. Copies of electronic objections and hearing requests will
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format.
Do not include any CBI in your electronic copy. You may also submit an
electronic copy of your request at many Federal Depository Libraries.
B. When Will the Agency Grant a Request for a Hearing?
A request for a hearing will be granted if the Administrator
determines that the material submitted shows the following: There is a
genuine and substantial issue of fact; there is a reasonable
possibility that available evidence identified by the requestor would,
if established resolve one or more of such issues in favor of the
requestor, taking into account uncontested claims or facts to the
contrary; and resolution of the factual issues(s) in the manner sought
by the requestor would be adequate to justify the action requested (40
CFR 178.32).
VII. Regulatory Assessment Requirements
This final rule establishes a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and
[[Page 19878]]
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) (Public Law 104-4). Nor
does it require any special considerations under Executive Order 12898,
entitled Federal Actions to Address Environmental Justice in Minority
Populations and Low-Income Populations (59 FR 7629, February 16, 1994);
or OMB review or any Agency action under Executive Order 13045,
entitled Protection of Children from Environmental Health Risks and
Safety Risks (62 FR 19885, April 23, 1997). This action does not
involve any technical standards that would require Agency consideration
of voluntary consensus standards pursuant to section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (NTTAA),
Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since
tolerances and exemptions that are established on the basis of a
petition under FFDCA section 408(d), such as the exemption in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. In addition, the Agency has determined that this
action will not have a substantial direct effect on States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government, as specified in Executive Order 13132, entitled Federalism
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to
develop an accountable process to ensure ``meaningful and timely input
by State and local officials in the development of regulatory policies
that have federalism implications.'' ``Policies that have federalism
implications'' is defined in the Executive Order to include regulations
that have``substantial direct effects on the States, on the
relationship between the national government and the States, or on the
distribution of power and responsibilities among the various levels of
government.'' This final rule directly regulates growers, food
processors, food handlers and food retailers, not States. This action
does not alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of FFDCA section 408(n)(4). For these same reasons, the Agency has
determined that this rule does not have any ``tribal implications'' as
described in Executive Order 13175, entitled Consultation and
Coordination with Indian Tribal Governments (65 FR 67249, November 6,
2000). Executive Order 13175, requires EPA to develop an accountable
process to ensure ``meaningful and timely input by tribal officials in
the development of regulatory policies that have tribal implications.''
``Policies that have tribal implications'' is defined in the Executive
Order to include regulations that have ``substantial direct effects on
one or more Indian tribes, on the relationship between the Federal
government and the Indian tribes, or on the distribution of power and
responsibilities between the Federal government and Indian tribes.''
This rule will not have substantial direct effects on tribal
governments, on the relationship between the Federal government and
Indian tribes, or on the distribution of power and responsibilities
between the Federal government and Indian tribes, as specified in
Executive Order 13175. Thus, Executive Order 13175 does not apply to
this rule.
VIII. Submission to Congress and the Comptroller General
The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this rule and other
required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of this final rule in the Federal Register. This final
rule is not a ``major rule'' as defined by 5 U.S.C. 804(2).
List of Subjects in 40 CFR Part 180
Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: April 7, 2001.
Joseph J. Merenda,
Acting Director, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180-- [AMENDED]
1. The authority citation for part 180 continues to read as
follows:
Authority: 21 U.S.C. 321(q), 346(a) and 371.
2. Section 180.568 is added to read as follows:
Sec. 180.568 Flumioxazin; tolerances for residues.
(a) General. Tolerances are established for residues of
flumioxazin, 2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-
benzoxazin-6-yl]-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione, in or
on the following raw agricultural commodities:
------------------------------------------------------------------------
Parts
Commodity per
million
------------------------------------------------------------------------
Peanuts 0.02
Soybean seed 0.02
------------------------------------------------------------------------
[[Page 19879]]
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 01-9597 Filed 4-17-01; 8:45 am]
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