[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: [email protected]. 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: 
[email protected].

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:
    [email protected].

    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