[Federal Register Volume 63, Number 189 (Wednesday, September 30, 1998)]
[Rules and Regulations]
[Pages 52160-52169]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-26002]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-300724; FRL-6033-4]
RIN 2070-AB78
Fluroxypyr; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for combined residues
of fluroxypyr 1-methylheptyl ester [1-methylheptyl ((4-amino-3,5-
dichloro-6-fluoro-2-pyridinyl)oxy)acetate] and its metabolite
fluroxypyr [((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic
acid] in or on the raw agricultural commodities (RAC) wheat, barley,
and oats as follows: 0.5 ppm (grain), 12 ppm (straw and forage), 20 ppm
(hay), and 0.6 ppm (aspirated grain fractions). Because residues of
fluroxypyr 1-methylheptyl ester and its metabolite fluroxypyr, free and
conjugated, may occur in animal feeds derived from wheat, barley, and
oats, the following meat and milk tolerances are also being
established: 0.1 ppm (meat, fat, milk, and meat byproducts except for
kidney) and 0.5 ppm (kidney). Dow AgroSciences LLC requested this
tolerance 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 September 30, 1998. [Objections and
requests for hearings must be received by EPA on or before November 30,
1998.
ADDRESSES: Written objections and hearing requests, identified by the
docket control number [OPP-300724, 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-300724, 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 electronic
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 or ASCII file format. All copies of
electronic objections and hearing requests must be identified by the
docket control number [OPP-300724]. No Confidential Business
Information (CBI) should be submitted through e-mail. Copies of
electronic objections and hearing requests on this rule may be filed
online at many Federal Depository Libraries.
FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller,
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) 305-6224, e-mail:
miller.joanne@epamail.epa.gov.
SUPPLEMENTARY INFORMATION: In the Federal Register of December 17, 1997
(62 FR 66083)(FRL-5759-1), 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 a pesticide petition (PP) 6F4772 for tolerance
by Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 46268.
This notice included a summary of the petition prepared by Dow
AgroSciences LLC, the registrant. There were no comments received in
response to the notice of filing.
In the Federal Register of August 14, 1998 (63 FR 43710)(FRL-6023-
3), 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 an amended pesticide petition (PP) 6F4772 for this tolerance
petition. The revised petition requested that 40 CFR part 180 be
amended by establishing a tolerance for combined residues of the
herbicide fluroxypyr 1-methylheptyl ester [1-methylheptyl ((4-amino-
3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetate] and its metabolite
fluroxypyr [((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic
acid] in or on the raw agricultural commodities wheat, barley, and oats
as follows: 0.5 ppm (grain), 12 ppm (straw and forage), 20 ppm (hay),
and 0.6 ppm (aspirated grain fractions). Because residues of fluroxypyr
1-methylheptyl ester and its metabolite fluroxypyr, free and
conjugated, may occur in animal feeds derived from wheat, barley, and
oats, the following meat and milk tolerances are also being
established: 0.1 ppm (meat, fat, milk, and meat byproducts except for
kidney) and 0.5 ppm (kidney).
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 ``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
[[Page 52161]]
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 adverse effect level'' or
``NOAEL'').
Once a study has been evaluated and the observed effects have been
determined to be threshold effects, EPA generally divides the NOAEL
from the study with the lowest NOAEL 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 NOAEL 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 NOAEL) 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/NOAEL 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 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
[[Page 52162]]
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 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, EPA has sufficient data to assess the hazards of
fluroxypyr and to make a determination on aggregate exposure,
consistent with section 408(b)(2), for tolerances for combined residues
of fluroxypyr 1-methylheptyl ester [1-methylheptyl ((4-amino-3,5-
dichloro-6-fluoro-2-pyridinyl)oxy)acetate] and its metabolite
fluroxypyr [((4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic
acid] in or on the raw agricultural commodities wheat, barley, and oats
as follows: 0.5 ppm (grain), 12 ppm (straw and forage), 20 ppm (hay),
and 0.6 ppm (aspirated grain fractions), and residues of fluroxypyr 1-
methylheptyl ester and its metabolite fluroxypyr, free and conjugated,
in meat, fat, milk, and meat byproducts except for kidney at 0.1 ppm
and kidney at 0.5 ppm. on at ppm. EPA's assessment of the dietary
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 fluroxypyr are
discussed below.
1. Several acute toxicology studies places the technical-grade
herbicide in Toxicity Category II.
2. A 90-day feeding study in Wistar rats (10/sex/group)
administered fluroxypyr (98.5% a.i.) in the diet at 0, 80, 750, 1,000
or 1,500 milligrams/kilogram/day (mg/kg/day) for 13 weeks. Significant
nephrotoxicity and deaths were observed at 1,000 and 1,500 mg/kg/day in
both sexes, and in males at 750 mg/kg/day. Death was due to renal
papillary necrosis. Also observed were signs of ill health, emaciation,
decreased food intake, increased kidney weight, histopathological
lesions and decreased renal function. Histological changes were
observed in the adrenals in both sexes at 1,000 and 1,500 mg/kg/day. In
males the NOAEL for this study is 80 mg/kg/day, and the LOEL is 750 mg/
kg/day based on kidney effects and death. In females the NOAEL is 750
mg/kg/day, with the LOEL at 1,000 mg/kg/day based on kidney effects and
death.
3. A 90-day feeding study in mice (12/sex/group) administered
fluroxypyr (99.3% active ingredient (a.i.)) in the diet at levels of 0,
200, 500, 2,500 or 10,000 ppm (males: 0, 26.7, 67.7, 330 or 1,342 mg/
kg/day; females: 0, 32.5, 81.7, 418, or 1,748 mg/kg/day) for 13 weeks.
Under the conditions of the study, no significant effects were observed
at any dose level. The NOAELs are therefore 1,342 and 1,748 mg/kg/day
in males and females, respectively, the highest dose level tested, and
above the 1,000 mg/kg limit dose. A LOEL could not be established.
4. A 28-day feeding study in Beagle dogs administered Fluroxypyr
98.0% a.i. in the diet at levels of 0, 50, 150 or 450 mg/kg/day for 28
days. Dogs at 500 mg/kg/day exhibited ataxia and hind limb weakness as
well as decreases in body weight and food consumption and were
sacrificed on days 16/17 of the study. Histopathology showed moderate
acute tubular nephrosis and a slight to moderate acute gastroenteritis.
Some early signs of acute tubular nephrosis were also seen in both
sexes of dogs at 150 mg/kg/day. The NOAEL for the study was 50 mg/kg/
day, the LOEL was 150 mg/kg/day based on histopathological lesions in
the kidneys, decreased testes weights, and increased adrenal weights in
both sexes.
5. In a 21-day dermal study, fluroxypyr (98.5% a.i.) was
administered to New Zealand white rabbits (5/sex/group) at levels of 0,
100, 300, or 1,000 mg/kg/day for 3 weeks. Administration was 6 hr/day
to an area approx. 10 x 15 cm (10% of body surface area). No dermal or
systemic toxicity was observed at any dose level. The NOAEL for males
and females is therefore 1,000 mg/kg/day. A LOEL could not be
established.
6. In the combined chronic toxicity/carcinogenicity study in rats,
fluroxypyr 99.0% a.i. was administered to 50 Fischer 344 rats/sex/dose
via the diet at dose levels of 0, 100, 500, and 1,000, females only,
mg/kg/day for 24 months 10 rats/sex/dose for 12 months. There was no
apparent increase in the incidence of kidney tumors in either sex. With
the exception of an increased incidence of parafollicular cell
adenomas, single only, in males at 500 mg/kg/day, at the doses tested,
there was no apparent treatment-related increase in any tumor type in
either sex. The LOEL is 500 mg/kg/day, based on increased kidney weight
in both sexes, increased incidence of atrophy, adipose tissue
mesenteric tissues in males and an increase in the severity of chronic
progressive glomerulonephropathy in the kidney in both sexes. The NOAEL
is 100 mg/kg/day. Deaths occurred at 1,000 mg/kg/day in males within
the first 90 days on test 2 by day 28 and 3 more by day 56.
7. In the carcinogenicity study in mice, fluroxypyr 98.92% a.i. was
administered to 60 CD-1 mice/sex/dose via the diet at dose levels of 0,
100, 300, and 1,000 mg/kg/day for 18 months. There was no apparent
treatment-related increase in the incidence of any tumor type in either
sex. The LOEL is 1,000 mg/kg/day, based on decreased body weight/gain
in males and an increased incidence of kidney lesions in females. The
NOAEL is 300 mg/kg/day.
8. In a 1-year chronic feeding study, fluroxypyr 98.0% a.i. was
administered to Beagle dogs (4/sex/group) in the diet at 0, 20, 50 or
150 mg/kg/day for 12 months. No adverse effects were observed at any
dose level. No abnormalities in hematology, clinical chemistry or
urinalysis. No abnormal findings were made at necropsy, nor were there
any significant changes in food consumption or body weight. The NOAEL
for this study is 150 mg/kg/day, the highest dose level tested. The
LOEL could not be established.
[[Page 52163]]
9. In a developmental toxicity study, pregnant rats (six/dose
group) were administered fluroxypyr (99% a.i.) at oral dose levels of
0, 125, 250, or 500 mg/kg/day in 1% methyl cellulose on days 6 through
19 of gestation. Clinical signs such as salivation and brown facial
staining were observed at 250 and 500 mg/kg/day; a 10% increase in mean
kidney weight was observed at 500 mg/kg/day, along with renal pelvic
dilatation. No adverse effects were observed on food consumption, body
weight gain, live young, embryonic deaths, implants, corpora lutea,
pre- or post-implantation loss, litter weight or mean fetal weight. In
pups, reduced skeletal ossification was observed at the 500 mg/kg/day.
No other significant effects were observed on the conceptus. The
maternal NOAEL is 125 mg/kg/day, and the LOEL is 250 mg/kg/day based on
clinical signs. The developmental NOAEL is 250 mg/kg/day, the LOEL is
500 mg/kg/day based on reduced ossification.
10. In a developmental toxicity study in rats, fluroxypyr
methylheptyl ester 95.8% a.i. was administered to 28 naturally-mated
female Sprague-Dawley rats/group via gavage at dose levels of 0, 100,
300, and 600 mg/kg/day from days 6 through 15 of gestation. The
maternal NOAEL is 300 mg/kg/day, the LOEL is 600 mg/kg/day, based on
deaths and decreased body-weight gain and food consumption. The
developmental toxicity NOAEL is 300 mg/kg/day, and the LOEL is 600 mg/
kg/day, based on an increase in two ossification variations
incompletely ossified cervical vertebral transverse processes and
pubes.
11. In a developmental toxicity study in rabbits, fluroxypyr
methylheptyl ester 95.8% a.i. was administered to 20 naturally-
inseminated New Zealand female rabbits/group via gavage at dose levels
of 0, 100, 500, and 1,000 mg/kg/day from days 7 through 19 of
gestation. The maternal/developmental LOEL is 1,000 mg/kg/day, based on
an increased incidence of abortions. The maternal NOAEL is 500 mg/kg/
day.
12. In a prenatal developmental toxicity study in rabbits, pregnant
New Zealand White rabbits received oral (gavage) administration of
fluroxypyr at dose levels of 0, 25, 100, or 400 mg/kg/day during
gestation days 6 through 19. Due to a large number of maternal deaths
in the 400 mg/kg/day group, a dose level of 250 mg/kg/day was added to
the study, and the 400 mg/kg/day dose level was discontinued early. For
maternal toxicity, the NOAEL was 250 mg/kg/day and the LOEL was 400 mg/
kg/day based on maternal deaths. For developmental toxicity, the NOAEL
was 100 mg/kg/day and the LOEL was 250 mg/kg/day, based on increased
postimplantation loss.
13. In a 2-generation reproduction study, fluroxypyr 99.0% a.i. was
administered to 30 Sprague-Dawley rats/sex/dose via the diet at dose
levels of 0, 100, 500, and 750 mg/kg/day males and 0, 100, 500, and
1,000 mg/kg/day females during the pre-mating period of 10 weeks
(F1 generation) 12 weeks (F2 generation). There
was one litter (F1) in the first generation and two litters
(F2A and F2B) in the second generation. The NOAEL
for maternal/paternal toxicity is 500/100 mg/kg/day, and the LOEL is
1,000/500 mg/kg/day, based on death in females and increased kidney
weight with corresponding gross and microscopic findings papillary
atrophy, edema, necrosis, hyperplasia of the pelvic epithelium,
degeneration/regeneration of the tubular epithelium, tubulo-
interstitial nephritis, and dilatation of the tubules in both sexes.
The reproductive NOAEL is 1,000/750 mg/kg/day, the highest dose tested.
The neonatal NOAEL is 500 mg/kg/day, and the LOEL is 1,000 mg/kg/day,
based on decreased pup body weight/body-weight gain and slightly lower
survival.
14. In a Salmonella typhimurium reverse gene mutation assay,
fluroxypyr was not mutagenic up to a cytotoxic dose (10,000 g/
plate +S9). In a Salmonella typhimurium/Escherichia coli reverse gene
mutation assay with fluroxypyr methylheptyl ester, independent trials
were negative up to insoluble doses with or without S9 activation
( 2,500 g/plate).
15. In a Chinese hamster ovary (CHO) cell Hypoxanthine guanine
phosphoribosyl transferase (HGPRT) forward gene mutation assay),
fluroxypyr was negative up a cytotoxic concentration (2,000 g/
mL +/-S9). In a Chinese hamster ovary (CHO) cell HGPRT forward gene
mutation assay with fluroxypyr methylheptyl ester, independent trials
were negative up to cytotoxic concentrations without S9 activation
( 30 g/mL -S9). In the presence of S9 activation,
the test was also negative over the entire dose range investigated
(100-1,200 g/mL) in two trials.
16. An in vitro chromosome aberration assay in CHO cells with
fluroxypyr was negative for damage to structural chromosomes up to
doses causing moderate cytotoxicity (500 and 1,000 g/mL +/-
S9). There was, however, marginal and nondose-related evidence of
polyploidy under nonactivated and S9-activated conditions. Also, in an
in vitro unscheduled DNA synthesis (UDS) assay in human embryonic lung
fibroblasts, cell line no. 2002 was negative up to nonactivated and S9-
activated doses causing precipitation and moderate cytotoxicity. For
fluroxypyr methylheptyl ester, in an in vitro chromosome aberration
assay with rat lymphocytes, independent trials were negative up to
cytotoxic concentrations ( 270 g/mL +/-S9). Also,
in an in vivo bone marrow micronucleus assay, negative results were
obtained in CD-1 (ICR) male and female mice receiving single oral
gavage administrations of 225-900 mg/kg. Lethality and other clinical
signs of toxicity were noted at 900 mg/kg. There was, however, no
evidence of bone marrow cytotoxicity at any dose.
17. In a metabolism study, fluroxypyr 14C-methylheptyl
ester 95.8% a.i. unlabeled; radiochemical purity 99%; labeled on the
methylheptanol portion of the molecule or 14C-
methylheptanol 98.9% unlabeled; radiochemical purity 97.5% was
administered to 5 plasma/3 balance male Fischer 344 rats/group in
single oral equimolar doses of 50 mg fluroxypyr methylheptyl ester/kg
body weight or 17.7 mg methylheptanol/kg body weight. The total
recovery of the administered dose was 105% and 104%, with the principal
route of excretion being expired 14CO2, which
contained approxiamately () 61% and 63% of the radioactivity
for the fluroxypyr and methylheptanol balance groups, respectively. The
urine contained 30% and 27% and the feces contained 5% and
7% of the administered dose for the fluroxypyr and Methylheptanol
groups, respectively. At 48 hours post dose, 7% of the
administered dose was recovered in the blood, carcass, and skin of both
groups. The overall rates and routes of elimination were comparable
between the groups. Each was extensively absorbed and rapidly
eliminated. Approximately 52% and 54% of the administered fluroxypyr
and Methylheptanol, respectively, was absorbed and expired as
14CO2 within 12 hours post dose, and an
additional 18% of the administered dose was excreted in the urine
within 12 hours post dose. Based on the percentage of the dose in the
expired 14CO2, urine, and tissues,
90% of the dose was absorbed by the rats in each case. Once absorbed,
both were extensively metabolized (20-22 metabolites) and rapidly
expired as 14CO2 and eliminated in the urine with
a half-life of 6 hours. Fluroxypyr displayed a slower absorption rate
than Methylheptanol, but once absorbed, the pharmacokinetic parameters
were similar. Peak plasma concentrations of 14C-
radioactivity were attained by 7 and 10 hours post dose, and the half-
lives for the elimination
[[Page 52164]]
phase were 18.2 and 17.4 hours for fluroxypyr and
Methylheptanol, respectively. It was stated that the percentage of
radioactivity recovered in the tissues and carcass 7%
suggests 14C-incorporation into the carbon pool that may
account for the longer half life in plasma as compared to the urinary
half-life of 6 hours. Average area under the curve values were 140
g equivalent hours/gram (eq hr/g) and 163 g eq hr/g
for the fluroxypyr and Methylheptanol groups, respectively. Clearance
values were comparable for these groups also 2.1 and 1.8 mL/min kg.
These pharmacokinetic parameters indicate no difference in kinetics of
Methylheptanol, based on whether it is labeled alone or as part of the
fluroxypyr molecule. Urine profiles were similar and indicated
extensive metabolism (20-22 metabolites). Unchanged fluroxypyr was not
detected in any of the samples, and the author stated that this ``is
consistent with the majority of the dose metabolized to
CO2.'' The data indicate that the fluroxypyr bond is readily
hydrolyzed and that the methylheptyl ester portion of fluroxypyr is
bioequivalent to Methylheptanol.
B. Toxicological Endpoints
1. Acute toxicity. In a prenatal developmental toxicity study,
pregnant New Zealand White rabbits received oral (gavage)
administration of fluroxypyr (unspecified purity) in 0.5%
carboxymethylcellulose (5 mL/kg) at dose levels of 0, 25, 100, or 400
mg/kg/day during gestation days 6 through 19. Due to a large number of
maternal deaths in the 400 mg/kg/day group, a dose level of 250 mg/kg/
day was added to the study, and the 400 mg/kg/day dose levels was
discontinued early. For maternal toxicity, the NOAEL was 250 mg/kg/day
and the LOEL was 400 mg/kg/day based on maternal deaths. For
developmental toxicity, the NOAEL was 100 mg/kg/day and the LOEL was
250 mg/kg/day, based on increased postimplantation loss. The
postimplantation loss is presumed to occur after a single exposure
(dose). Appropriate endpoints attributable to a single exposure (dose)
for this population were not seen in oral toxicity studies including
maternal toxicity in the developmental toxicity studies in rats and
rabbits.
EPA determined that the 10X factor to protect infants and children
(as required by FQPA) should be reduced to 3X. This conclusion was
based on the fact that the developmental toxicity study in rats showed
no increased sensitivity in fetuses as compared to maternal animals
following in utero exposures, the 2-generation reproduction toxicity
study in rats showed no increased sensitivity in pups when compared to
adults, and the toxicology data base is complete (i.e., no data gaps).
However, EPA determined that an uncertainty factor of 300 is required
because, in the prenatal developmental toxicity study in rabbits, there
is an indication of additional susceptibility following prenatal
exposure to fluroxypyr since the developmental NOAEL was less than the
maternal NOAEL. The confidence in these data, however, were minimized
by the fact that the value is only slightly above the historical
control, and because no statistical significance was indicated.
Additionally, susceptibility to the offspring was not observed in any
of the other prenatal developmental toxicity studies examined, and
there is always the possibility that maternal toxicity may have been
present (as kidney pathology) but that the relevant endpoint was not
examined.
For acute dietary risk assessment, a Margin of Exposure (MOE) of
300 is required. This includes the conventional 100X for inter- and
intra-species variation, and 3X for FQPA. This risk assessment is
required for females 13+ only, since the endpoint is based on an in
utero effect. The available data, which include developmental studies
in rats and rabbits, a 3-month feeding rat study and a 28-day mouse
feeding study, did not demonstrate toxicity which can be observed
following one exposure only.
2. Short - and intermediate - term toxicity. i. Dermal absorption.
A dermal absorption study was not available for review. Therefore an
absorption factor of 100% will be assumed.
ii. Short-term toxicity. Although a 21-day dermal toxicity study
with fluroxypyr methylheptyl ester (98.5%) in New Zealand White rabbits
with a NOAEL of > 1,000 mg/kg/day is available, the developmental NOAEL
from an oral study with fluroxypyr in the same species (rabbits) was
selected for this risk assessment because of the concern for
developmental effects seen in the oral study with the acid which was
not studied with the ester, and because developmental effects are not
evaluated in the dermal toxicity study (i.e., the consequence of these
effects can not be ascertained for the dermal route of exposure. Since
an oral dose was identified, a dermal absorption rate of 100% should be
used for dermal risk assessments, to convert to oral equivalents.
Therefore, a developmental NOAEL of 100 mg/kg/day based on increased
postimplantation loss at 250 mg/kg/day (LOEL) was used for risk
assessment.
iii. Intermediate-term toxicity. For the reasons discussed above
with short-term toxicity, a developmental NOAEL of 100 mg/kg/day based
on increased postimplantation loss at 250 mg/kg/day (LOEL) was used for
risk assessment.
3. Chronic toxicity. EPA has established the RfD for fluroxypyr at
0.5 mg/kg/day. This RfD is based on histopathological lesions in the
kidneys, decreased testes weights, and increased adrenal weights in
both sexes observed in a 4-week range-finding feeding study in the dog
with a NOAEL of 50 mg/kg/day. An uncertainty factor of 100 was used in
calculating the RfD to account for both inter- and intra-species
variations.
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, fluroxypyr was
classified as a ``not likely'' human carcinogen by the EPA's Hazard
Identification Assessment Review Committee (document dated December 1,
1997) according to EPA Proposed Guidelines for Carcinogen Risk
Assessment (document dated April 10, 1996).
B. Exposures and Risks
1. From food and feed uses. No previous tolerances have been
established for the combined residues of fluroxypyr 1-methylheptyl
ester and its metabolite fluroxypyr. Risk assessments were conducted by
EPA to assess dietary exposures and risks from fluroxypyr 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 1 day or single exposure. The acute dietary (food only) risk
assessment used the theoretical maximum residue contribution (TMRC). By
using TMRC in conducting this chronic dietary risk assessment, EPA has
made very conservative assumptions: 100% of wheat, oats, and barley
RACs having fluroxypyr tolerances will contain fluroxypyr residues and
those residues will be at the level of the established tolerance. This
results in an overestimate of human dietary exposure. Thus, in making a
safety determination for this tolerance, EPA is taking into account
this conservative exposure assessment. The exposure estimate for
females (13+ years old) results in a dietary (food only) MOE of 50,000.
This should be viewed as a conservative risk estimate; refinement using
anticipated residue values and percent crop-treated data in conjunction
with Monte Carlo analysis would result
[[Page 52165]]
in a lower acute dietary exposure estimate.
ii. Chronic exposure and risk. In conducting this chronic dietary
risk assessment, EPA has made very conservative assumptions -- 100% of
wheat, barley, oats and all other commodities having fluroxypyr 1-
methylheptyl ester tolerances will contain fluroxypyr 1-methylheptyl
ester residues and those residues would be at the level of the
tolerance -- which result in an overestimation of human dietary
exposure. Thus, in making a safety determination for this tolerance,
EPA is taking into account this conservative exposure assessment.
The fluroxypyr 1-methylheptyl ester tolerances result in a TMRC
that is equivalent to the following percentages of the RfD:
------------------------------------------------------------------------
U.S. Population (48 States)................................ 0.41%
U.S. Population - Fall Season.............................. 0.43%
U.S. Population - Winter Season........................... 0.43%
Northeast Region........................................... 0.43%
North Central Region....................................... 0.43%
Western Region............................................. 0.44%
Hispanics.................................................. 0.48%
Non-Hispanic Whites........................................ 0.42%
Non-Hispanic Others........................................ 0.43%
Nursing Infants (< 1="" year="" old).............................="" 0.39%="" non-nursing="" infants="">< 1="" year="" old).........................="" 1.55%="" children="" (1-6="" years="" old)...................................="" 1.06%="" children="" (7-12="" years="" old)..................................="" 0.69%="" males="" (13-19="" years="" old)....................................="" 0.46%="" ------------------------------------------------------------------------="" the="" subgroups="" listed="" above="" are:="" (1)="" the="" u.s.="" population="" (48="" states);="" (2)="" those="" for="" infants="" and="" children;="" and,="" (3)="" the="" other="" subgroups="" for="" which="" the="" percentage="" of="" the="" rfd="" occupied="" is="" greater="" than="" that="" occupied="" by="" the="" subgroup="" u.s.="" population="" (48="" states).="" 2.="" from="" drinking="" water.="" in="" terrestrial="" and="" aquatic="" environments,="" fluroxypyr="" 1-methylheptyl="" ester="" is="" rapidly="" hydrolyzed="" to="" fluroxypyr.="" fluroxypyr="" is="" further="" degraded="" (although="" less="" rapidly)="" by="" microbes="" to="" 4-amino-3,5-dichloro-6-fluoro-pyridin-2-ol="" (``pyridinol'')="" and="" 4-amino-="" 3,5-dichloro-6-fluoro-2-methoxypyridine="" (``methoxypyridine'').="" in="" aerobic="" environments,="" fluroxypyr,="" pyridinol,="" and="" methoxypyridine="" are="" ultimately="" degraded="" to="" carbon="" dioxide.="" there="" are="" no="" established="" maximum="" contaminant="" levels="" for="" residues="" of="" fluroxypyr="" 1-methylheptyl="" ester="" in="" drinking="" water.="" no="" health="" advisory="" levels="" for="" fluroxypyr="" 1-methylheptyl="" ester="" in="" drinking="" water="" have="" been="" established.="" the="" assessment="" used="" sci-grow2="" for="" groundwater="" assessment="" and="" generic="" expected="" environmental="" concentration="" (geneec)="" version="" 1.2="" for="" acute="" and="" chronic="" surface="" water="" assessments.="" estimated="" environmental="" concentrations="" (eec's)="" in="" surface="" water="" reflecting="" 0.25="" lb="" acid="" equivalents/a/yr="" applied="" by="" air="" were="" 11.2="">g/L for
acute and 3.9 g/L for chronic. EEC's for groundwater were
0.025 g/L parts per billion (ppb) for acute and chronic. The
computer generated EECs represent conservative estimates and should be
used only for screening.
i. Acute exposure and risk. EPA has calculated drinking water
levels of concern (DWLOCs) for acute exposure to fluroxypyr in drinking
water for the only relevant population subgroup, females (13+ years
old): 9,930 g/L.
To calculate the DWLOCs for acute exposure relative to an acute
toxicity endpoint, the acute dietary food exposure (from the Dietary
Exposure Evaluation System (DRES) analysis) was subtracted from the
ratio of the acute NOAEL (used for acute dietary assessments) to the
acceptable MOE for aggregate exposure to obtain the acceptable acute
exposure to fluroxypyr in drinking water. DWLOCs were then calculated
using default body weights and drinking water consumption figures.
Estimated maximum concentrations of fluroxypyr in surface and
ground water are 11.2 ppb and 0.025 ppb, respectively and the DWLOC is
9,930 g/L. The estimated maximum concentrations of fluroxypyr
in surface and ground water are less than EPA's level of concern for
fluroxypyr in drinking water as a contribution to acute aggregate
exposure.
Therefore, taking into account present uses and uses proposed in
this action, EPA concludes with reasonable certainty that residues of
fluroxypyr in drinking water (when considered along with other sources
of exposure for which EPA has reliable data) would not result in
unacceptable levels of aggregate human health risk at this time.
ii. Chronic exposure and risk. The ``Interim Guidance for
Conducting Drinking Water Exposure and Risk Assessments'' issued on
November 24, 1997 was followed for this assessment. Thus, the GENEEC
model and the SCI-GROW model were run to produce estimates of
fluroxypyr concentrations in surface and ground water, respectively.
The primary use of these models is to provide a coarse screen for
sorting out pesticides for which EPA has a high degree of confidence
that the true levels of the pesticide in drinking water will be less
than the human health DWLOCs. A DWLOC is the concentration of a
pesticide in drinking water which would be acceptable as an upper limit
in light of total aggregate exposure to that chemical from food, water,
and non-occupational (residential) sources. The DWLOC for chronic
exposure is the concentration in drinking water as a part of the
aggregate chronic exposure that occupies no more than 100% of the RfD.
The Agency's default body weights and water consumption values used to
calculate DWLOCs are as follows: 70 kg/2L (adult male), 60 kg/2L (adult
female), and 10 kg/1L (child).
For chronic (non-cancer) exposure to fluroxypyr in surface and
ground water, the drinking water levels of concern are 17,400
g/L for the U.S. population, 14,900 g/L for females
(13+ years old), and 4,950 g/L for children (1-6 years old).
To calculate the DWLOC for chronic (non-cancer) exposure relative to a
chronic toxicity endpoint, the chronic dietary food exposure (from
DRES) was subtracted from the RfD to obtain the acceptable chronic
(non-cancer) exposure to fluroxypyr in drinking water. DWLOCs were then
calculated using default body weights and drinking consumption figures.
Estimated average concentrations of fluroxypyr in surface and
ground water are 3.9 ppb and 0.025 ppb, respectively. The DWLOCs are
17,400 g/L for the U.S. population, 14,900 g/L for
females (13+ years old), and 4,950 g/L for children (1-6 years
old). The estimated average concentrations of fluroxypyr in surface and
ground water are less than EPA's level of concern for fluroxypyr in
drinking water as a contribution to chronic aggregate exposure.
3. From non-dietary exposure. There are no registered or proposed
residential uses for fluroxypyr 1-methylheptyl ester or its metabolite
fluroxypyr.
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
[[Page 52166]]
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 fluroxypyr 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,
fluroxypyr 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 fluroxypyr has a common mechanism of toxicity
with other substances.
C. Aggregate Risks and Determination of Safety for U.S. Population
1. Acute risk. For the population subgroup of concern, females 13+
years old, the calculated MOE value (food) is 50,000. The Agency
acknowledges the potential for exposure to fluroxypyr 1-methylheptyl
ester in drinking water, but does not expect that exposure would result
in an aggregate MOE (food plus water) that would exceed the Agency's
level of concern for acute dietary exposure.
2. Chronic risk. Using the TMRC exposure assumptions described Unit
II.B.1. of this preamble, EPA has concluded that aggregate exposure to
fluroxypyr from food will utilize 0.41% of the RfD for the U.S.
population. The major identifiable subgroup with the highest aggregate
exposure is 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 fluroxypyr in drinking water and from non-dietary, non-occupational
exposure, EPA does not expect the aggregate exposure to exceed 100% of
the RfD.
3. Short- and intermediate-term risk. Short- and intermediate-term
aggregate exposure takes into account chronic dietary food and water
(considered to be a background exposure level) plus indoor and outdoor
residential exposure. There are no proposed residential uses for
fluroxypyr. Therefore, the short and intermediate aggregate risks are
adequately addressed by the chronic aggregate dietary risk assessment.
4. Aggregate cancer risk for U.S. population. Fluroxypyr has been
classified as a ``not likely'' carcinogenic chemical by the Agency
5. Conclusion. EPA concludes that there is a reasonable certainty
that no harm will result from aggregate exposure to fluroxypyr
residues.
D. Aggregate Risks and Determination of Safety for Infants and Children
1. Safety factor for infants and children-- a. In general. In
assessing the potential for additional sensitivity of infants and
children to residues of fluroxypyr, EPA considered data from
developmental toxicity studies in the rat and rabbit and a 2-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 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 margin of exposure analysis or through using
uncertainty (safety) factors in calculating a dose level that poses no
appreciable risk to humans. In either case, EPA generally defines the
level of appreciable risk as exposure that is greater than 1/100 of the
no observed effect level in the animal study appropriate to the
particular risk assessment. This hundredfold uncertainty (safety)
factor/margin of exposure (safety) is designed to account for inter-
species extrapolation and intra-species variability. EPA believes that
reliable data support using the hundredfold margin/factor, rather than
the thousandfold margin/factor, when EPA has a complete data base under
existing guidelines, and when the severity of the effect in infants or
children, the potency or unusual toxic properties of a compound, or the
quality of the exposure data do not raise concerns regarding the
adequacy of the standard margin/factor.
In the case of fluroxypyr, EPA determined that the 10X factor to
protect infants and children (as required by FQPA) should be reduced to
3X. This conclusion was based on the fact that the developmental
toxicity study in rats showed no increased sensitivity in fetuses as
compared to maternal animals following in utero exposures, the 2-
generation reproduction toxicity study in rats showed no increased
sensitivity in pups when compared to adults, and the toxicology data
base is complete (i.e., no data gaps). However, EPA determined that an
uncertainty factor of 300 is required because, in the prenatal
developmental toxicity study in rabbits, there is an indication of
additional susceptibility following prenatal exposure to fluroxypyr
since the developmental NOAEL was less than the maternal NOAEL. The
confidence in these data, however, were minimized by the fact that the
value is only slightly above the historical control, and because no
statistical significance was indicated. Additionally, susceptibility to
the offspring was not observed in any of the other prenatal
developmental toxicity studies examined, and there is always the
possibility that maternal toxicity may have been present (as kidney
pathology) but that the relevant endpoint was not examined.
b. Developmental toxicity studies. In the developmental study in
rats, the maternal (systemic) NOAEL was 125 mg/kg/day, based on
clinical signs at the LOEL of 250 mg/kg/day. The developmental (fetal)
NOAEL was 250 mg/kg/day, based on reduced ossification at the LOEL of
500 mg/kg/day.
In the developmental toxicity study in rabbits, the maternal
(systemic) NOAEL was 250 mg/kg/day, based on maternal
[[Page 52167]]
deaths at the LOEL of 400 mg/kg/day. The developmental (pup) NOAEL was
125 mg/kg/day, based on increased postimplantation loss at the LOEL of
250 mg/kg/day.
c. Reproductive toxicity study. In the 2-generation reproductive
toxicity study in rats, the maternal (systemic) NOAEL was 100 mg/kg/
day, based on increased kidney weights and kidney histopathology at the
LOEL of 500 mg/kg/day. The developmental (pup) NOAEL was 500 mg/kg/day,
based on decreased body weight at the LOEL of 1,000 mg/kg/day. The
reproductive NOAEL was 1,000 mg/kg/day Highest Dose Tested.
d. Pre- and post-natal sensitivity. The toxicological data base for
evaluating pre- and post-natal toxicity for fluroxypyr is complete with
respect to current data requirements. Based on the results of the
rabbit developmental toxicity study for fluroxypyr there does appear to
be an extra sensitivity for pre-natal effects.
e. Conclusion. Based on the above, EPA concludes that reliable
data support use of a 300-fold margin of exposure/uncertainty factor,
rather than the standard thousandfold margin/factor, to protect infants
and children.
2. Acute risk. The acute dietary MOE (food) was calculated to be
6,666 for infants (< 1="" year="" old),="" 10,000="" for="" children="" (1-6="" years="" old),="" and="" 50,000="" females="" 13+="" years="" old="" (accounts="" for="" both="" maternal="" and="" fetal="" exposure).="" these="" moe="" calculations="" were="" based="" on="" the="" developmental="" noael="" in="" rabbits="" of="" 100="" mg/kg/day.="" this="" risk="" assessment="" assumed="" 100%="" crop-="" treated="" with="" tolerance="" level="" residues="" on="" all="" treated="" crops="" consumed,="" resulting="" in="" a="" significant="" over="" estimation="" of="" dietary="" exposure.="" the="" large="" acute="" dietary="" moe="" calculated="" for="" females="" 13+="" years="" old="" and="" the="" infants="">< 1="" year="" old="" subgroup="" (lowest="" moe)="" provides="" assurance="" that="" there="" is="" a="" reasonable="" certainty="" of="" no="" harm="" for="" females="" 13+="" years="" old,="" infants,="" and="" children.="" epa="" acknowledges="" the="" potential="" for="" exposure="" to="" fluroxypyr="" 1-="" methylheptyl="" ester="" in="" drinking="" water,="" but="" does="" not="" expect="" that="" exposure="" would="" result="" in="" aggregate="" moes="" (food="" plus="" water)="" that="" would="" exceed="" the="" agency's="" level="" of="" concern="" for="" acute="" dietary="" exposure.="" 3.="" chronic="" risk.="" using="" the="" conservative="" exposure="" assumptions="" described="" above,="" epa="" has="" concluded="" that="" aggregate="" exposure="" to="" fluroxypyr="" from="" food="" will="" utilize="" from="" 0.39%="" of="" the="" rfd="" for="" nursing="" infants="">< 1="" year="" old)="" up="" to="" 1.55%="" of="" the="" rfd="" for="" non-nursing="" infants="">< 1="" year="" 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="" fluroxypyr="" in="" drinking="" water.="" 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="" fluroxypyr="" residues.="" 4.="" short-="" or="" intermediate-term="" risk.="" short-="" and="" intermediate-term="" aggregate="" exposure="" takes="" into="" account="" chronic="" dietary="" food="" and="" water="" (considered="" to="" be="" a="" background="" exposure="" level)="" plus="" indoor="" and="" outdoor="" residential="" uses.="" there="" are="" no="" proposed="" residential="" uses="" for="" fluroxypyr.="" therefore,="" the="" short="" and="" intermediate="" aggregate="" risks="" are="" adequately="" addressed="" by="" the="" chronic="" aggregate="" dietary="" risk="" assessment.="" iii.="" other="" considerations="" a.="" metabolism="" in="" plants="" and="" animals="" the="" nature="" of="" the="" residue="" in="" plants="" and="" animals="" is="" adequately="" understood.="" the="" residues="" of="" concern="" in="" plants="" and="" animals="" are="" fluroxypyr="" 1-methylheptyl="" ester="" and="" its="" metabolite="" fluroxypyr,="" free="" and="" conjugated,="" all="" expressed="" as="" fluroxypyr="" .="" b.="" analytical="" enforcement="" methodology="" adequate="" enforcement="" methodology="" is="" available="" for="" plants="" (gas="" chromatography/mass="" spectrometry="" (gc/ms)="" and="" capillary="" gas="" chromatography/ms)="" to="" enforce="" the="" tolerance="" expression.="" the="" petitioner="" validated="" the="" limit="" of="" quantitation="" at="" 0.01="" ppm="" for="" cereal="" grains="" and="" 0.05="" ppm="" for="" forage,="" straw,="" and="" hay="" of="" cereal="" grains.="" adequate="" enforcement="" methodology="" is="" available="" for="" livestock="" (gas="" chromatography/electron="" capture="" detection="" (gc/ecd)="" and="" capillary="" gas="" chromatography="" with="" mass="" selective="" detection)="" to="" enforce="" the="" tolerance="" expression.="" the="" petitioner="" validated="" the="" limit="" of="" quantitation="" of="" method="" grm="" 96.03="" at="" 0.01="" ppm="" for="" all="" animal="" substrates.="" c.="" magnitude="" of="" residues="" residues="" of="" fluroxypyr="" 1-methylheptyl="" ester="" and="" fluroxypyr="" are="" not="" expected="" to="" exceed="" the="" established="" tolerance="" levels="" in="" rac's="" and="" processed="" commodities="" of="" wheat,="" barley,="" oats,="" and="" animal="" commodities="" as="" a="" result="" of="" this="" use.="" d.="" international="" residue="" limits="" there="" are="" no="" codex,="" canadian,="" or="" mexican="" tolerances="" for="" residues="" of="" fluoroxypyr="" 1-methylheptyl="" ester="" on="" wheat,="" barley,="" or="" oats.="" e.="" rotational="" crop="" restrictions="" a="" confined="" rotational="" crop="" study="" was="" conducted="" in="" which="" fluroxypyr="" was="" applied="" at="" the="" rate="" of="" 8.8="" oz="" acid="" equivalent/acre="" (ae/a).="" residues="" in="" crops="" planted="" 120="" days="" after="" soil="" treatment="" were="" 0.01="" to="" 0.08="" ppm;="" however,="" based="" on="" this="" study="" and="" the="" use="" rates,="" residues="" of="" fluroxypyr="" 1-methylheptyl="" ester="" and="" fluroxypyr="" are="" not="" expected="" to="" occur="" in="" rotational="" crops="" at="" levels=""> 0.01 ppm at the 120-day plant-back
interval. The end-use product label will contain a statement limiting
the planting of rotational crops for at least 120 days after
application.
IV. Conclusion
Therefore, the tolerances is are established for combined residues
of fluroxypyr 1-methylheptyl ester and its metabolite fluroxypyr in
wheat, barley, and oats as follows: 0.5 ppm (grain), 12 ppm (straw and
forage), 20 ppm (hay), and 0.6 ppm (aspirated grain fractions), and
residues of fluroxypyr 1-methylheptyl ester and its metabolite
fluroxypyr, free and conjugated, in meat, fat, milk, and meat
byproducts except for kidney at 0.1 ppm and kidney at 0.5 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 November 30, 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
[[Page 52168]]
accompanied by the fee or a request for a waiver as specified 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 Record and Electronic Submissions
EPA has established a record for this rulemaking under docket
control number [OPP-300724 (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 1132 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
A. Certain Acts and Executive Orders
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 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 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.
B. Executive Order 12875
Under Executive Order 12875, entitled Enhancing the
Intergovernmental Partnership (58 FR 58093, October 28, 1993), EPA may
not issue a regulation that is not required by statute and that creates
a mandate upon a State, local, or tribal government, unless the Federal
government provides the funds necessary to pay the direct compliance
costs incurred by those governments. If the mandate is unfunded, EPA
must provide to OMB a description of the extent of EPA's prior
consultation with representatives of affected State, local, and tribal
governments, the nature of their concerns, copies of any written
communications from the governments, and a statement supporting the
need to issue the regulation. In addition, Executive Order 12875
requires EPA to develop an effective process permitting elected
officials and other representatives of State, local, and tribal
governments ``to provide meaningful and timely input in the development
of regulatory proposals containing significant unfunded mandates.''
Today's rule does not create an unfunded Federal mandate on State,
local, or tribal governments. The rule does not impose any enforceable
duties on these entities. Accordingly, the requirements of section 1(a)
of Executive Order 12875 do not apply to this rule.
C. Executive Order 13084
Under Executive Order 13084, entitled Consultation and Coordination
with Indian Tribal Governments (63 FR 27655, May 19,1998), EPA may not
issue a regulation that is not required by statute, that significantly
or uniquely affects the communities of Indian tribal governments, and
that imposes substantial direct compliance costs on those communities,
unless the Federal government provides the funds necessary to pay the
direct compliance costs incurred by the tribal governments. If the
mandate is unfunded, EPA must provide to OMB, in a separately
identified section of the preamble to the rule, a description of the
extent of EPA's prior consultation with representatives of affected
tribal governments, a summary of the nature of their concerns, and a
statement supporting the need to issue the regulation. In addition,
Executive Order 13084 requires EPA to develop an effective process
permitting elected officials and other representatives of Indian tribal
governments ``to provide
[[Page 52169]]
meaningful and timely input in the development of regulatory policies
on matters that significantly or uniquely affect their communities.''
Today's rule does not significantly or uniquely affect the
communities of Indian tribal governments. This action does not involve
or impose any requirements that affect Indian tribes. Accordingly, the
requirements of section 3(b) of Executive Order 13084 do 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 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: September 23, 1998.
Marcia E. Mulkey,
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 revising Sec. 180.535 to read as follows:
Sec. 180.535 Fluroxypyr 1-methylheptyl ester; tolerances for residues.
(a) General . Tolerances are established for combined residues of
fluroxypyr 1-methylheptyl ester [1-methylheptyl ((4-amino-3,5-dichloro-
6-fluoro-2-pyridinyl)oxy)acetate] and its metabolite fluroxypyr [((4-
amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy)acetic acid] in or on the
following raw agricultural commodities.
------------------------------------------------------------------------
Parts
Commodity per
million
------------------------------------------------------------------------
Aspirated grain fractions...................................... 0.6
Barley, grain.................................................. 0.5
Barley, forage................................................. 12.0
Barley, hay.................................................... 20.0
Barley, straw.................................................. 12.0
Cattle, fat.................................................... 0.1
Cattle, kidney................................................. 0.5
Cattle, meat................................................... 0.1
Cattle, meat byproducts........................................ 0.1
Goats, fat..................................................... 0.1
Goats, kidney.................................................. 0.5
Goats, meat.................................................... 0.1
Goats, meat byproducts......................................... 0.1
Hogs, fat...................................................... 0.1
Hogs, kidney................................................... 0.5
Hogs, meat..................................................... 0.1
Hogs, meat byproducts.......................................... 0.1
Horses, fat.................................................... 0.1
Horses, kidney................................................. 0.5
Horses, meat................................................... 0.1
Horses, meat byproducts........................................ 0.1
Milk........................................................... 0.1
Oats, forage................................................... 12.0
Oats, grain.................................................... 0.5
Oats, hay...................................................... 20.0
Oats, straw.................................................... 12.0
Sheep, fat..................................................... 0.1
Sheep, kidney.................................................. 0.5
Sheep, meat.................................................... 0.1
Sheep, meat byproducts......................................... 0.1
Wheat, forage.................................................. 12.0
Wheat, grain................................................... 0.5
Wheat, hay..................................................... 20.0
Wheat, straw................................................... 12.0
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. Time-limited tolerances are
established for the combined residues of fluroxypyr 1-methylheptyl
ester and its metabolite fluroxypyr, in connection with use of the
pesticide under section 18 emergency exemptions granted by EPA. The
tolerances will expire and are revoked on the dates specified in the
following table.
------------------------------------------------------------------------
Parts Expiration/
Commodity per Revocation
million Date
------------------------------------------------------------------------
Corn, field, forage............................... 2.0 12/1/99
Corn, field, grain................................ 0.05 12/1/99
Corn, field, stover............................... 2.5 12/1/99
Corn, sweet, forage............................... 2.0 12/1/99
Corn, sweet, K + CWHR............................. 0.05 12/1/99
Corn, sweet, stover............................... 2.5 12/1/99
------------------------------------------------------------------------
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 98-26002 Filed 9-29-98; 8:45 am]
BILLING CODE 6560-50-F
