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Fluroxypyr - Pesticide Petition Filing 12/97

ENVIRONMENTAL PROTECTION AGENCY
[PF-782; FRL-5759-1]
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-782, must
be received on or before January 16, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7502C), Information Resources and Services
Division, Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 1132, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
docket@epamail.epa.gov. Follow the instructions under "SUPPLEMENTARY
INFORMATION." No confidential business information should be submitted
through e-mail.
    Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
"Confidential Business Information" (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment 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. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the
table below:

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                                   Office location/
        Product Manager            telephone number          Address
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Joanne Miller (PM 23).........  Rm. 237, CM #2, 703-    1921 Jefferson
                                 305-6224, e-mail:       Davis Hwy,
                                 miller.joanne@epamail   Arlington, VA
                                 .epa.gov.
James Tompkins (PM 25)........  Rm. 239, CM #2, 703-    Do.
                                 305-5697, e-mail:
                                 tompkins.james@epamai
                                 l.epa.gov.
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SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
petition.
    The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-782] (including comments and data submitted
electronically as described below). 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 official record is located at the address in
"ADDRESSES" at the beginning of this document.
    Electronic comments can 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. Comment and data
will also be accepted on disks in Wordperfect 5.1/6.1 or ASCII file
format. All comments and data in electronic form must be identified by
the docket control number [PF-782] and appropriate petition number.
Electronic comments on this notice may be filed online at many Federal
Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
requirements.

    Dated: December 3, 1997.

Peter Caulkins,

Acting Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summary announces the
availability of a description of the analytical methods available to
EPA for the detection and measurement of the pesticide chemical
residues or an explanation of why no such method is needed.

[[Page 66084]]

1. DowElanco

PP 6F4772

    EPA has received a pesticide petition (PP 6F4772) from DowElanco,
9330 Zionsville Road, Indianapolis, IN 46268, proposing pursuant to
section 408(d) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C.
346a(d), to amend 40 CFR part 180 by establishing a tolerance for
residues of fluroxypyr methylheptyl ester (MHE) and its only
significant metabolite fluroxypyr, free and conjugated, all expressed
as fluroxypyr in or on the raw agricultural commodities wheat, barley,
and oats as follows: 0.5 parts per million (ppm) (grain), 10 ppm (straw
and forage), 20 ppm (hay), and 0.5 ppm (aspirated grain fractions,
wheat). Because residues of fluroxypyr MHE or fluroxypyr, free or
conjugated, may occur in animal feeds derived from wheat, barley, and
oats, the following meat and milk tolerances are also being proposed:
0.1 ppm (meat, fat, milk, and meat byproducts except for kidney) and
0.5 ppm (kidney). The proposed analytical method is based on gas
chomatography (GC) with mass spectral (MS) detection. EPA has
determined that the petition contains data or information regarding the
elements set forth in section 408(d)(2) of the FFDCA; however, EPA has
not fully evaluated the sufficiency of the submitted data at this time
or whether the data supports granting of the petition. Additional data
may be needed before EPA rules on the petition.

A. Residue Chemistry

    1. Plant metabolism. The metabolism of fluroxypyr MHE in plants
(wheat) and animals (goats and poultry) is adequately understood for
the purposes of this tolerance. A rotational crop study showed no
carryover of significant fluroxypyr MHE related residues in
representative test crops except for cereal grains for which tolerances
are being proposed.
    2. Analytical method. There is a practical method (GC with MS
detection) for measuring levels of fluroxypyr MHE in or on food with a
limit of detection that allows monitoring of food with residues at or
above the levels set for the proposed tolerances. Fluroxypyr has been
tested through the FDAs Multiresidue Methodology, Protocols C, D. and
E. The results have been published in the FDA Pesticide Analytical
Manual, Volume I.
    3. Magnitude of residues. Magnitude of residue studies were
conducted for wheat, barley, and oats. Residues of fluroxypyr MHE did
not concentrate in process fractions in samples treated at a 7.5 X
application rate.

B. Toxicological Profile

    1. Acute toxicity. Fluroxypyr MHE has low acute toxicity. The rat
oral LD-50 is > 5000 mg/kg, the rabbit dermal LD-50
is > 2000 mg/kg, and the rat inhalation LC-50 is > 1.0 mg/l
(1,000 mg/cubic meter), the maximum attainable concentration. In
addition, fluroxypyr MHE is not a skin sensitizer in guinea pigs, has
no dermal irritation in rabbits, and shows mild ocular irritation in
rabbits. The end use formulation of fluroxypyr MHE has a similar low
acute toxicity profile.
    2. Genotoxicity. Short term assays for genotoxicity consisting of a
bacterial reverse mutation assay (Ames test), an in vitro assay for
cytogenetic damage using the Chinese hamster ovary cells, an in
vitrochromosomal aberration assay using rat lymphocytes, and an in vivo
cytogenetic assay in the mouse bone marrow (micronucleus test) have
been conducted with fluroxypyr MHE. DowElanco believes that these
studies show a lack of genotoxicity. In addition, short term assays for
genotoxicity consisting of an Ames metabolic activation test, point
mutations at the HGPRT-Locus of Chinese hamster ovary cells, in vivo
and in vitro chromosomal aberrations in the Chinese hamster ovary
cells, unscheduled DNA synthesis in human embryonic cells, and an assay
in mouse lymphoma cells have been conducted with fluroxypyr. DowElanco
believes that the weight of evidence also indicates a lack of
genotoxicity.
    3. Reproductive and developmental toxicity. Developmental studies
in rats and rabbits were conducted with both fluroxypyr MHE and
fluroxypyr. Studies with fluroxypyr MHE showed maternal and fetal no
observed effect levels (NOELs) of 300 milligram/kilogram (mg/kg/day)
(rat) and 500 mg/kg/day (rabbit). Studies with fluroxypyr showed no
observed adverse effect levels (NOAELs) in the rat of 250 mg/kg/day for
maternal effects and 500 mg/kg/day for fetal effects and a NOEL in the
rabbit of 250 mg/kg/day for both maternal and fetal effects. DowElanco
believes that these studies show that fluroxypyr and fluroxypyr MHE are
not teratogenic nor will they interfere with in utero development. Two
multi-generation reproduction studies were conducted with fluroxypyr in
rats. The first in Wistar rats showed no effect on fertility or
reproductive performance and had a NOAEL of 500 mg/kg/day (highest dose
tested). The second study in Sprague-Dawley rats showed a parental NOEL
for systemic effects of 100 mg/kg/day in male rats and 500 mg/kg/day in
female rats. The NOEL for reproductive effects was 750 mg/kg/day for
males and 1,000 mg/kg/day for females (highest dose tested). The NOEL
for neonatal effects was 500 mg/kg/day.
    4. Subchronic toxicity. Fluroxypyr MHE showed a NOEL of 1,000 mg/
kg/day in a 90-day rat dietary study and a 21-day rabbit dermal study.
Ninety day feeding studies with fluroxypyr showed NOELs of 80 mg/kg/day
(Wistar rats), 700 mg/kg/day (Fischer 344 rats), 1342 mg/kg/day (male
mice), and 1,748 mg/kg/day (female mice). In a 4-week dietary, range
finding study with fluroxypyr in dogs the NOEL was > 50 mg/kg/day.
    5. Chronic toxicity. Based on chronic testing with fluroxypyr in
the mouse, dog, and rat (two studies), a reference dose (RfD) of 0.8
mg/kg/day is proposed for fluroxypyr and fluroxypyr MHE. The RfD has
incorporated a 100-fold safety factor to the NOEL found in the rat
chronic test. NOELs found in the chronic dietary studies are as
follows: 150 mg/kg/day (dog), 300 mg/kg/day (mouse), 80 mg/kg/day
(Wistar rats), 100 mg/kg/day (male Fischer 344 rats), and 500 mg/kg/day
(female Fischer 344 rats).
    6. Animal metabolism. Both fluroxypyr and fluroxypyr MHE have been
evaluated in rat metabolism studies. In summary, these studies show
that fluroxypyr MHE is rapidly hydrolyzed and the fate of the
hydrolysis products, fluroxypyr and 1-methylheptanol, are independent
of whether they were given as the ester or the acid. Fluroxypyr, per
se, was extensively absorbed and rapidly excreted principally unchanged
in the urine. 1-Methylheptanol also was rapidly absorbed and rapidly
eliminated. Repeated administration of fluroxypyr MHE was not
associated with accumulation in tissues. Also, the metabolism and
pharmacokinetics of methylheptanol are comparable to that of the
methylheptyl portion of fluroxypyr MHE.
    7. Metabolite toxicology. Administration of fluroxypyr, as the acid
or methylheptyl ester, in a variety of toxicological studies has
produced similar effects. The principal response to sufficiently high
dosages, whether administered over the short-term or, in some cases,
over a lifetime, was nephrosis. Fluroxypyr is an organic acid that is
actively excreted into the urine by the kidney. Thus, the target organ
and dose response relationship for fluroxypyr toxicity are entirely
consistent with the data on the toxicokinetics of fluroxypyr.
Metabolism studies have shown that fluroxypyr MHE is rapidly and
completely hydrolyzed to fluroxypyr acid and methylheptanol.

[[Page 66085]]

    8. Carcinogenicity. Using the Guidelines for Carcinogen Risk
Assessment published September 24, 1986 (51 FR 33992), it is proposed
that fluroxypyr and fluroxypyr MHE be classified as Group E for
carcinogenicity (no evidence of carcinogenicity) based on the results
of carcinogenicity studies in two species. DowElanco believes that
there was no evidence of carcinogenicity in an 18-month mouse feeding
study and a 24-month rat feeding study at all dosages tested. The NOELs
shown in the mouse and rat oncogenicity studies were 1,000 and 320 mg/
kg/day, respectively. A maximum tolerated dose was achieved at the top
dosage level tested in both of these studies based on excessive renal
toxicity. Thus, the doses tested are adequate for identifying a cancer
risk. Accordingly, DowElanco believes that a cancer risk assessment is
not needed.
    9. Endocrine effects. There is no evidence to suggest that
fluroxypyr and fluroxypyr HME have an effect on any endocrine system.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. An over estimation of dietary
exposure from use of fluroxypyr MHE on wheat, barley, oats is
determined by basing the TMRC on the conservative assumptions that all
cereal grain commodities will have tolerance level residues of
fluroxypyr and that 100% of the wheat, barley, and oat crops grown in
the U.S. are treated with fluroxypyr MHE. The TMRC is obtained by
multiplying the tolerance residue levels by the consumption data which
estimates the amount of crops and related foodstuffs consumed by
various population subgroups. There are no other established U.S.
tolerances or exemption from tolerances for fluroxypyr MHE and no other
registered uses for fluroxypyr MHE on food or feed crops in the United
States. The use of a tolerance level and 100% of crop treated clearly
results in an overestimate of human exposure and a safety determination
for the use of fluroxypyr MHE on wheat, barley, and oats that is based
on a conservative exposure assessment.
    ii. Drinking water. Another potential source of dietary exposure
are residues in drinking water. Based on the available environmental
studies conducted with fluroxypyr MHE and fluroxypyr wherein the
properties of these materials show little persistence in the soil
environment, there is no anticipated exposure to residues of fluroxypyr
MHE and fluroxypyr in drinking water. In addition, there is no
established Maximum Concentration Level for residues of fluroxypyr MHE
and fluroxypyr in drinking water.
    2. Non-dietary exposure. There are no other uses currently
registered for fluroxypyr MHE and fluroxypyr. The proposed use on
wheat, barley, and oats involves application of fluroxypyr MHE to crops
grown in an agriculture environment. Thus, the potential for non-
occupational exposure to the general population is not expected to be
significant.

D. Cumulative Effects

    The potential for cumulative effects of fluroxypyr MHE and
fluroxypyr and other substances that have a common mechanism of
toxicity is also considered. There is no reliable information to
indicate that toxic effects produced by fluroxypyr MHE and fluroxypyr
would be cumulative with those of any other pesticide chemical. Thus,
it is appropriate to consider only the potential risks of fluroxypyr
MHE and fluroxypyr in an aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. Using the conservative exposure assumptions and
the proposed RfD, the dietary exposure to fluroxypyr MHE use on wheat,
barley, and oats will utilize 0.2% of the RfD for the U.S. population.
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. Since there are no anticipated residues in drinking water
or from other non-occupational sources and no reliable information
exists on cumulative effects due to common mechanism of toxicity, the
aggregate exposure to fluroxypyr MHE is adequately represented by the
dietary route. Thus, DowElanco believes that there is reasonable
certainty that no harm will result from aggregate exposure to
fluroxypyr MHE residues on wheat, barley, and oats.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of fluroxypyr MHE, data
from developmental toxicity studies in rats and rabbits and a 2-
generation reproduction study in the rat are considered. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from pesticide exposure during
prenatal development. Reproduction studies provide information relating
to effects from exposure to the pesticide on the reproductive
capability and potential systemic toxicity of mating animals and on
various parameters associated with the well-being of pups.
    FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post-natal toxicity and the completeness of the
database. Based on the current toxicological data requirements, the
database for fluroxypyr MHE relative to pre- and post-natal effects for
children is complete. Further, for fluroxypyr MHE, the NOEL in the
chronic feeding studies which was used to calculate the RfD (0.8 mg/kg/
day) is already lower than the NOELs from the developmental studies in
rats and rabbits by a factor of more than three.
    Concerning the reproduction studies in rats, the pup effects shown
at the highest dose tested (1,000 mg/kg/day) were attributed to
maternal toxicity. Therefore, DowElanco concludes that an additional
uncertainty factor is not needed and that the RfD at 0.8 mg/kg/day is
appropriate for assessing risk to infants and children.
    As noted above for the general U.S. population, aggregate exposure
for infants and children will result from the dietary (i.e. not
drinking water or non-occupational) route of exposure. In addition,
there is no reliable information that shows cumulative effects based on
a common mechanism of toxicity for infants and children. Using the
conservative exposure assumptions previously described, the percent RfD
utilized by the aggregate dietary exposure to residues of fluroxypyr
MHE on wheat, barley, and oats is 0.6% for children 1 to 6 years old,
the most sensitive population subgroup. Thus, based on the completeness
and reliability of the toxicity data and the conservative exposure
assessment, DowElanco believes that there is a reasonable certainty
that no harm will result to infants and children from aggregate
exposure to fluroxypyr MHE residues on wheat, barley, and oats.

F. International Tolerances

    There are no Codex maximum residue levels established for residues
of fluroxypyr MHE and fluroxypyr on any food or feed crop. (J. Miller)

[FR Doc. 97-32936 Filed 12-16-97; 8:45 am]
BILLING CODE 6560-50-F