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Flumetsulam (DowElanco). September 17, 1997. Pesticide Tolerance Petition. Federal Register.


http://www.epa.gov/fedrgstr/EPA-PEST/1997/September/Day-17/p24693.htm


[Federal Register: September 17, 1997 (Volume 62, Number 180)]
[Notices]
[Page 48842-48848]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17se97-67]

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ENVIRONMENTAL PROTECTION AGENCY

[PF-753; FRL-5735-5]


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-753, must
be received on or before October 17, 1997.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch (7506C), 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 by following
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

[[Page 48843]]

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
------------------------------------------------------------------------
Joanne Miller (PM 23).........  Rm. 237, CM #2, 703-    1921 Jefferson
                                 305-6224, e-            Davis Hwy,
                                 mail:miller.joanne@ep   Arlington, VA
                                 amail.epa.gov.
Cynthia Giles-Parker (PM 22)..  Rm. 229, CM #2, 703-    Do.
                                 305-7740, e-mail:
                                 giles-
                                 parker.cynthia@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-753] (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 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number [PF-753] 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: September 5,1997

James Jones,

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.

1. DowElanco

PP 7F4851

    EPA has received a pesticide petition (PP 7F4851) from DowElanco,
9330 Zionsville Road, Indianapolis, IN 46268-1054, 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 flumethsulam in or on the raw agricultural commodity dry
beans at 0.05 ppm. The proposed analytical method involves
homogenization, filtration, partition and cleanup with analysis by high
performance liquid chromatography using UV 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 in plants is adequately
understood. No metabolites of significance were detected in plant
metabolism studies.
    2. Analytical method. There is a practical analytical method for
detecting and measuring levels of flumetsulam in or on food with a
limit of quantitation (LOQ) of 0.010 ppm, and a limit of detection of
0.005 ppm that allows monitoring of food with residues at or above the
levels set in these tolerances. EPA has provided information on this
method to FDA. The method is availabe to anyone who is interested in
pesticide residue enforcement.
    3. Magnitude of residues. No detectable residues of flumetsulam
were found in any of the drybean samples obtained from multiple sites
and multiple varieties and analyzed using a method with a limit of
detection of 0.005 ppm.

B. Toxicological Profile

    1. Acute toxicity. Flumetsulam has low acute toxicity. The rat oral
LD50 is >5,000 mg/kg or greater for males and females. The
rabbit dermal LD50 is >2,000 mg/kg and the rat inhalation
LC50 is >1.2mg/L air (the highest attainable concentration).
In addition, flumetsulam is not a skin sensitizer in guinea pigs, is
not a dermal irritant and is not an ocular irritant. Therefore based on
the available acute toxicity data, flumetsulam does not pose any acute
dietary risks.
    2. Genotoxicty. Flumetsulam is not genotoxic. The following studies
have been conducted and all were negative for genotoxic responses: a
dominant lethal assay, an In vivo rat cytogenic study, an In vitro
Salmonella and Saccharomyces assay, an in vivo mouse host-mediated
assay, and an unscheduled DNA synthesis assay in rats.
    3. Reproductive and developmental toxicity. In a 2-generation
reproduction study in rats, there was no compound-related reproductive
toxicity. The No-Observed-Effect Level (NOEL) was greater than 1,000
mg/kg/day. Developmental toxicity was studied using rats and rabbits.
The developmental study in rats resulted in a developmental NOEL
greater than 1.000 mg/kg/day (highest dose tested) and a maternal NOEL
of 500 mg/kg/day. A study in rabbits resulted in a

[[Page 48844]]

developmental NOEL equal to or greater than 700 mg/kg/day (highest dose
tested) with a maternal NOEL of 100 mg/kg/day and a maternal LOEL
(lowest observed effect level) of 500 mg/kg/day evidenced by decreased
body weight gain. Based on all of the data for flumetsulam, there is no
evidence of developmental toxicity at dose levels that do not result in
maternal toxicity.
    4. Subchronic toxicity . In a 13-week oral feeding study in mice at
5,000 mg/kg/day, slight effects on the liver, kidney, and cecum
appeared to represent adaptive responses to treatment and have
questionable toxicological significance. The NOEL was 1,000 mg/kg/day
(limit dose). In a 13-week oral feeding study in dogs, the lowest-
observed-effect level (LOEL) for both male and female dogs was 500 mg/
kg/day. A NOEL was not established for males or females. In a 13-week
dietary study in rats, the NOEL was 250 mg/kg/day and the LOEL was
1,000 mg/kg/day.
    5. Chronic toxicity. In a 1-year dietary study in dogs, the NOEL
was 100 mg/kg/day and the LOEL was 500 mg/kg/day. The animals were
administered feed containing 0, 20, 100, and 500 mg/kg/day. Reduced
body weights and inflammatory and atrophic changes in the kidneys
occurred in the 500 mg/kg/day dose groups. In a combined feeding
carcinogenicity/chronic study in mice there were no treatment-related
effects and there was no evidence of a carcinogenic response. Systemic
NOEL was greater than or equal to 1,000 mg/kg/day (limit dose); a LOEL
was not established. In a combined feeding carcinogenicity/chronic
study in rats, renal pathological alterations were seen in males. No
treatment-related effects were seen in females at the highest dose
(1,000 mg/kg/day) which is the limit dose. There was no carcinogenic
response. The NOELs were 500 mg/kg/day in males and 1,000mg/kg/day in
females. The LOEL was 1,000 mg/kg/day in males; a LOEL was not
established in females. Based on the chronic toxicity data, EPA has
established the RfD for flumetsulam at 1.0 milligram (mg)/kilogram
(kg)/day. The RfD for flumetsulam is based on the 1-year chronic study
in dogs with a NOEL of 100 mg/kg/day and an uncertainty (or safety)
factor of 100. Thus, it would not be necessary to require the
application of an additional uncertainty factor above the 100-fold
factor already applied to the NOEL.
    6. Animal metabolism. Disposition and metabolism of flumetsulam
were tested in male and female rats and male mice at an oral dose of 5
and 1,000 mg/kg for rats and 1,000 mg/kg for mice Flumetsulam was
rapidly excreted. The majority of a radioactive dose was excreted in 48
hours of all dose groups. The principle route for elimination was the
urine and to a lessor extent by fecal elimination. Detectable levels of
residual radioactivity were observed in the carcass and stomach at 72
hours post-dose. HPLC and TLC analysis of urine and fecal extracts
showed no apparent metabolism of flumetsulam.
    7. Metabolite toxicology. There are no flumetsulam metabolites of
toxicological significance.
    8. Endocrine effects. There is no evidence to suggest that
flumetsulam has an effectt on any endocrine system.

C. Aggregate Exposure

    1. Food. For purposes of assessing the potential dietary exposure
under these tolerances, exposure is estimated based on the Theoretical
Maximum Residue Contribution (TMRC) from the existing and pending
tolerances for flumetsulam on food crops. The TMRC is obtained by
multiplying the tolerance level residues by the consumption data which
estimates the amount of those food products eaten by various population
subgroups. Exposure of humans to residues could also result if such
residues are transferred to meat, milk, poultry or eggs. The following
assumptions were used in conducting this exposure assessment: 100% of
the crops were treated, the RAC residues would be at the level of the
tolerance, certain processed food residues would be at anticipated
(average) levels based on processing studies and all current and
pending tolerances were included. This results in an overestimate of
human exposure and a conservative assessment of risk. Based on a NOEL
of 100 mg/kg/day in a 1-year chronic feeding study in the dog and a
hundredfold safety factor the reference dose (RfK) would be 1.0 mg/kg/
day. The TMRC for the general population would be 4.1 X 10-5
mg/kg/day or 0.0041% of the RfD. For non-nursing infants, the TMRC wold
be 1.37 X 10-5 mg/kg/day or 0.014% of the RfD.
    2. Drinking water. Another potential source of dietary exposure to
residues of pesticides are residues in drinking water. There is no
established Maximum Concentration Level for residues of flumetsulam in
drinking water. Although there has been limited detections at ppb
levels in some of the specially designed studies under highly
vulnerable test conditions and at elevated non-labeled application
rates, no ongoing monitoring studies, have reported residues of
flumetsulam in ground or surface waters.
    Based on the physical and chemical characteristics of flumetsulam,
such as water solubility and its stability under hydrolysis and
photolysis, it has potential for downward movement through the soil
profile. Degradation based on over 20 laboratory studies indicated a
half-life range of 2 weeks to 4 months with 80% less than 2 months.
Degradation is driven primarily by microbial processes. However based
on the low application rate and detection in groundwater samples only
under extremely vulnerable soil conditions at elevated non-labeled
application rates with detections in single digit ppb levels,
flumetsulam is not anticipated to be a groundwater contaminant.
    In summary, these data on potential water exposure indicate
insignificant additional dietary intake of flumetsulam and any exposure
is more than compensated for in the conservative dietary risk
evaluation. Therefore, it is concluded that there is a reasonable
certainty of no harm even at potential upper limit exposures to
flumetsulam from drinking water.
    3. Non-dietary exposure. There are no non-dietary uses for
flumetsulam registered under the Federal Insecticide, Fungicide and
Rodenticide Act. Potential exposures for children is therefore limited
to dietary exposure.

D. Cumulative Effects

    The potential for cumulative effects of flumetsulam and other
substances that have a common mechanism of toxicity was considered. The
mammalian toxicity of flumetsulam is well defined. However, no reliable
information exists to indicate that toxic effects produced by
flumetsulam would be cumulative with those of any other chemical
compound. Additionally, flumetsulam does not appear to produce a toxic
metabolite produced by other substances. Therefore, consideration of a
common mechanism of toxicity with other compounds is not appropriate at
this time. Thus only the potential exposures to flumetsulam were
considered in the aggregate exposure assessment.

E. Safety Determination

    1. U.S. population. Based on a NOEL of 100 mg/kg/bwt/day from a
one-year dog feeding study with a reduced weight and inflammatory and
atrophic kidney effect, and using an uncertainty factor of 100 to
account for the interspecies extrapolation and intraspecies
variability, a Reference Dose (RfD) of 1.0 mg/kg bwt/day was used for
this assessment of chronic risk. As indicated, there is no endpoint of
concern identified with acute and short-or intermediate-term exposures.
The existing and proposed tolerances

[[Page 48845]]

would utilize 0.000041 mg/kg bwt/day or less than 0.01% of the RfD for
the U.S. population. And, as indicated previously, whatever upper limit
might be used for drinking water exposure, the exposure estimate for
flumetsulam would not exceed the RfD. Generally, exposures below 100
percent of the RfD are of no concern because the RfD represents the
level at or below which daily aggregate dietary exposure over a
lifetime will not pose appreciable risk to human health. Thus, there is
a reasonable certainty that no harm will result from aggregate exposure
to flumetsulam residues.
    2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of flumetsulam, data
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat were considered. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism during prenatal development resulting from
pesticide exposure to one or both parents. Reproduction studies provide
(1) information relating to effects from exposure to the pesticide on
the reproductive capability of mating animals and (2) data on systemic
toxicity.
    As indicated previously, reproductive and developmental toxicity
was studied using rats and rabbits. The data base is complete and based
on all of the data for flumetsulam, there is no evidence of
reproductive or developmental toxicity at dose levels that do not
result in maternal toxicity.
    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 relative to pre- and post-natal effects for children is
complete. These data suggest minimal concern for developmental or
reproductive toxicity and do not indicate any increased pre- or post-
natal sensitivity. Therefore, an additional uncertainty factor is not
necessary to protect the safety of infants and children and that the
RfD at 1.0 mg/kg/day is appropriate for assessing aggregate risk to
infants and children.
    The percent of the RfD that will be utilized by the aggregate
exposure from all tolerances to flumetsulamill be less than 0.1% for
non-nursing infants and for children (1-6 years of age). Therefore,
based on the completeness and reliability of the toxicity data and the
conservative exposure assessment, it is concluded that there is a
reasonable certainty that no harm will result to infants and children
from aggregate exposure to flumetsulam residues.

F. International Tolerances

    There are no Codex maximum residue levels established for
flumetsulam. (Joanne Miller)


[FR Doc. 97-24693 Filed 9-16-97; 8:45 am]
BILLING CODE 6560-50-F