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clomazone (Command) Pesticide Petition Filing 3/01

ENVIRONMENTAL PROTECTION AGENCY


[PF-1012; FRL-6775-4]



Notice of Filing a Pesticide Petition to Establish a Tolerance
for a Certain Pesticide Chemical in or on Food


AGENCY: Environmental Protection Agency (EPA).


ACTION: Notice.


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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.


DATES: Comments, identified by docket control number PF-1012, must be
received on or before April 27, 2001.


ADDRESSES: Comments may be submitted by mail, electronically, or in
person. Please follow the detailed instructions for each method as
provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure
proper receipt by EPA, it is imperative that you identify docket
control number PF-1012 in the subject line on the first page of your
response.


FOR FURTHER INFORMATION CONTACT: By mail: Dan Rosenblatt, Herbicide
Branch, Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460; telephone number: (703) 305-5697; e-
mail address: rosenblatt.dan@epa.gov.


SUPPLEMENTARY INFORMATION:


I. General Information


A. Does this Action Apply to Me?


    You may be affected by this action if you are an agricultural
producer, food manufacturer or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:


------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS codes         potentially
                                                      affected  entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  32532               Pesticide
                                                       manufacturing
------------------------------------------------------------------------


    This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.


B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?


    1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations'' ``Regulation and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to the Federal Register listings
at http://www.epa.gov/fedrgstr/.
    2. In person. The Agency has established an official record for
this action under docket control number PF-1012. The official record
consists of the documents specifically referenced in this action, any
public comments received during an applicable comment period, and other
information related to this action, including any information claimed
as confidential business information (CBI). This official record
includes the documents that are physically located in the docket, as
well as the documents that are referenced in those documents. The
public version of the official record does not include any information
claimed as CBI. The public version of the official record, which
includes printed, paper versions of any electronic comments submitted
during an applicable comment period, is available for inspection in the
Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.


C. How and to Whom Do I Submit Comments?


    You may submit comments through the mail, in person, or
electronically. To ensure proper receipt by EPA, it is imperative that
you identify docket control number PF-1012 in the subject line on the
first page of your response.
    1. By mail. Submit your comments to: Public Information and Records
Integrity Branch (PIRIB), Information Resources and Services Division
(7502C), Office of Pesticide Programs (OPP), Environmental Protection
Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.
    2. In person or by courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Information Resources
and Services Division (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921
Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
PIRIB telephone number is (703) 305-5805.
    3. Electronically. You may submit your comments electronically by
e-mail to: opp-docket@epa.gov, or you can submit a computer disk as
described above. Do not submit any information electronically that you
consider to be CBI. Avoid the use of special characters and any form of
encryption. Electronic submissions will be accepted in Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-1012. Electronic comments may
also be filed online at many Federal Depository Libraries.


D. How Should I Handle CBI That I Want to Submit to the Agency?


    Do not submit any information electronically that you consider to
be CBI. You may claim information that you submit to EPA in response to
this document as CBI by marking any part or all of that information as
CBI. Information so marked will not be disclosed except in accordance
with procedures set forth in 40 CFR part 2. In addition to one complete
version of the comment that includes any information claimed as CBI, a
copy of the comment that does not contain the information claimed as
CBI must be submitted for inclusion in the public version of the
official record. Information not marked confidential will be included
in the public version of the official record without prior notice. If
you have any questions about CBI or the procedures for claiming CBI,
please consult the person identified under FOR FURTHER INFORMATION
CONTACT.


E. What Should I Consider as I Prepare My Comments for EPA?


    You may find the following suggestions helpful for preparing your
comments:
    1. Explain your views as clearly as possible.
    2. Describe any assumptions that you used.
    3. Provide copies of any technical information and/or data you used
that support your views.
    4. If you estimate potential burden or costs, explain how you
arrived at the estimate that you provide.
    5. Provide specific examples to illustrate your concerns.
    6. Make sure to submit your comments by the deadline in this
notice.
    7. To ensure proper receipt by EPA, be sure to identify the docket
control number assigned to this action in the subject line on the first
page of your response. You may also provide the name, date, and Federal
Register citation.


II. What Action is the Agency Taking?


    EPA has received a pesticide petition as follows proposing the
establishment and/or amendment of regulations for residues of a certain
pesticide chemical 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 this petition contains 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 support granting
of the petition. Additional data may be needed before EPA rules on the
petition.


List of Subjects


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



    Dated: March 14, 2001.


James Jones,


Director, Registration Division, Office of Pesticide Programs.


Summary of Petition


    The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioners. EPA is publishing the petition summary verbatim without
editing it 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.


FMC Corporation, Agricultural Products Group


PP 9F06056


    EPA has received a pesticide petition (9F06056) from FMC
Corporation, Agricultural Products Group, 1735 Market Street,
Philadelphia, PA, 19103 proposing, pursuant to section 408(d) of the
Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to
amend 40 CFR 180.425 by establishing a tolerance for residues of
clomazone, 2-(2-chloroprene)methyl-4,4- diethel-3-isoxazolidinone in or
on the raw agricultural commodity sugarcane, cane at 0.05 parts per
million (ppm). 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 clomazone in plants is
adequately understood. The metabolism of clomazone has been studied in
both monocotyledonous and dicotyledonous plant species, such as corn
and soybeans. The residue of significance is the parent compound,
clomazone. This picture is consistent with plant metabolism studies in
other species (cotton, sweet potatoes and tobacco), all of which have
shown a similar metabolic pathway with the residue of significance
being clomazone.
    2.  Analytical method. There is a practical analytical method for
detecting and measuring levels of clomazone in or on sugarcane (cane)
and its processed parts (molasses, refined sugar) with a limit of
detection that allows monitoring of food for residues at or above the
levels proposed in this tolerance. Sugarcane and processed parts
samples are analyzed using an analytical method consisting of an acid
reflux, a C18 solid phase extraction (SPE), a Florisil SPE
clean-up followed by gas chromatography (GC)-mass selective detection
(MSD). The method limit of quantitation (LOQ) is 0.05 ppm. The method
limit of detection (LOD) is 0.01 ppm.
    3. Magnitude of residues. FMC conducted a residue study (consisting
of 10 trials) to determine the magnitude of the residue of clomazone
in/on sugarcane (cane) after Command 3ME was applied once as a
postemergence broadcast spray to either plant cane or ratoon cane, but
preemergence to weeds, at 1.25 lb. ai/A. The residues found in the
treated cane samples ranged from non-detectable (ND) to just above LOD
at 0.02 ppm. A second study, applied in the same fashion as described
above, was conducted using an exaggerated rate of 2.5 lb. ai/A (2X the
intended use rate). Sugarcane (cane) was processed into two fractions,
molasses and refined sugar, using simulated commercial practices.
Analysis of the processed parts (molasses, refined sugar) yielded no
clomazone residues (ND, 0.01 ppm) and no concentration factor. Since no
detectable residues were found in molasses, the only identified
sugarcane byproduct feedstuff (for beef and dairy cattle), animal
feeding studies in cows are not needed.


B. Toxicological Profile


    1. Acute toxicity. The following mammalian toxicity studies have
been conducted with clomazone technical (unless noted otherwise) to
support registrations and/or tolerances of clomazone:
    i. A rat acute oral study with an LD50 of 2,077 mg/kg
(male) and 1,369 mg/kg (female).
    ii. A rabbit acute dermal LD50 of > 2,000 mg/kg.
    iii. A rat acute inhalation LC50 of 6.25 mg/L/4 hr
(male), 4.23 mg/L/hr (female) and 4.85 mg/L/4 hr (combined sexes).
    iv. A primary eye irritation study in the rabbit which showed
practically no irritation.
    v. A primary dermal irritation study in the rabbit which showed
minimal irritation.
    vi. A primary dermal sensitization study in the guinea pig which
showed no sensitization.
    vii. Acute delayed neurotoxicity - clomazone, and its known
metabolites, 3 are not structurally related to known neurotoxic
substances.
    2. Genotoxicity. The following genotoxicity tests were all
negative: Ames Assay; CHO/HGPRT Mutation Assay; and Structural
Chromosomal Aberration. The Unscheduled DNA Synthesis genotoxicity was
negative with activation; weakly positive without activation.
    3. Reproductive and developmental toxicity. A two-generation
reproduction study was conducted in the rat with a parental systemic
NOAEL of 1,000 ppm (50 mg/kg/day) based on decreased body weight and
food consumption at 2,000 ppm; and a progeny systemic NOAEL of 1,000
ppm (50 mg/kg/day) based on decreased pup body weight at 2,000 ppm. The
reproductive performance NOAEL was >4,000 ppm which was the highest
dose tested. There was an unexplained decrease in the fertility index
during mating of the F1b generation at 4,000 ppm which was not observed
in the F1a litter or repeated in the F2 generation. Additionally, there
was one F2a pup at 1,000 ppm which had non-functional hindlimbs and one
F2b pup at 4,000 ppm which had extended hindlimbs with no flexion at
the ankle. These limb abnormalities were not considered treatment-
related for the following reasons: (i) There was no dose response
observed, (ii) the findings were not statistically significant, (iii)
the findings were not repeated at the 1,000 ppm dose level in the F2b
litter or found in the F1a or F1b litters; and (iv) these findings or
related hindlimb abnormalities were not observed in developmental
studies at gavage dose levels up to 100 mg/kg/day in the rat or 240 mg/
kg/day in the rabbit.
    A developmental toxicity study in rats given gavage doses of 100,
300 and 600 mg/kg/day and with maternal and fetal NOAELs of 100 mg/kg/
day. The maternal NOAEL is based on decreased locomotion, genital
staining and runny eyes and the developmental NOAEL is based on
increased incidence of delayed ossification at 300 mg/kg/day. This
study was negative for teratogenicity at all doses tested.
    A developmental toxictiy study in rabbits given gavage doses of 30,
240 and 700 mg/kg/day with maternal and
fetal NOAELs of 240 mg/kg/day. The maternal NOAEL is based on a
decrease in body weight and the developmental NOAEL is based on an
increase in the number of fetal resorptions at 700 mg/kg/day. This
study was negative for teratogenicity at all doses tested.
    In all cases, the reproductive and developmental NOAELs were equal
to the parental NOAELs, thus indicating that clomazone does not pose
any increased risk to infants or children.
    4. Subchronic toxicity. In a 90-day feeding subchronic study in
mice the NOAEL was 20 ppm (2.9 mg/kg/day) based on liver cytomegaly at
20 ppm.
    5. Chronic toxicity. A 12-month feeding study in the dog with a
NOAEL of 500 ppm (14.0 mg/kg/day for males; 14.9 mg/kg/day for females)
based on increased blood cholesterol and liver weights at 2,500 ppm.
    A 24-month chronic feeding/oncogenicity study in the rat with a
NOAEL of 100 ppm (4.3 mg/kg/day for males; 5.5 mg/kg/day for females)
based on increased liver weights and increased liver cytomegaly at 500
ppm. There were no oncogenic effects observed under the conditions of
the study. A 24-month chronic feeding/oncogenicity study in the mouse
with a NOAEL of 100 ppm (15 mg/kg/day) based on an increase in the
white blood cell count. There were no oncogenic effects observed under
the conditions of the study.
    Using the Guidelines for Carcinogen Risk Assessment, it is proposed
that clomazone be classified as Group E for carcinogenicity (no
evidence of carcinogenicity) based on the results of carcinogenicity
studies in two species. In 24-Month Feeding/ Oncogenicity studies in
rats and mice at dosages up to 2,000 ppm, there was no evidence of
caricnogenicity. The NOAEL in the 24-Month Feeding/oncogenicity study
in the rat was 100 ppm (4.3 mg/kg/day for males and 5.5 mg/kg/day for
females). The NOAEL in the 24-Month Feeding/Oncogenicity study in mice
was 100 ppm (15 mg/kg/day). The studies were negative for carcinogenic
effects at all dosage levels tested.
    The Reference Dose (RfD) for clomazone has been established at
0.043 mg/kg/day. The RfD for clomazone is based on the 24-Month
Feeding/Carcinogenicity Study in the Rat with a NOAEL of 4.3 mg/kg/day
and an uncertainty factor of 100.
    6. Animal metabolism. The metabolism of clomazone in animals is
adequately understood. Clomazone degrades rapidly and extensively in
rats, goats and poultry to a variety of metabolites which were readily
excreted from the body via excreta.
    7. Metabolite toxicology. No clomazone related metabolite residues
have been identified as being of toxicological concern. The residue of
significance is parent. Clomazone, has been thoroughly investigated in
a full battery of studies including acute, genetic, reproduction,
developmental and oncogenic tests. These studies have demonstrated that
clomazone has low acute toxicity, an overall absence of genotoxicity
and does not cause reproductive toxicity, developmental toxicity or
carcinogenicity.
    8. Endocrine disruption. No specific tests have been conducted with
clomazone to determine whether the herbicide may have an effect in
humans that is similar to an effect produced by a naturally occurring
estrogen or other endocrine effects. It should be noted, however, that
the chemistry of clomazone is unrelated to that of any compound
previously identified as having estrogen or other endocrine effects.
Additionally, a standard battery of required studies has been
completed. These studies include an evaluation of the potential effects
on reproduction and development, and an evaluation of the pathology of
the endocrine organs following repeated or long-term exposure. No
endocrine effects were noted in any of these studies with clomazone.


C. Aggregate Exposure


    1. Dietary exposure--Food. i. For purposes of assessing the
potential dietary exposure, EPA has estimated aggregate exposure based
on the Theoretical Maximum Residue Contribution (TMRC) from the
established tolerances for clomazone. The TMRC is a worst case estimate
of dietary exposure since it is assumed that 100% of all crops for
which tolerances are established are treated and that pesticide
residues are present at the tolerance levels. Dietary exposure to
residues of clomazone in or on food will be limited to residues on
cabbage (0.1 ppm), cottonseed (0.05 ppm), cucumber (0.1 ppm), succulent
peas (0.05 ppm), peppers (0.05 ppm), pumpkins (0.1 ppm), soybeans (0.05
ppm), winter squash (0.1 ppm), summer squash (0.1 ppm), sweet potato
(0.05 ppm), snap beans (0.05 ppm) rice (0.05 ppm) and sugar (from cane)
(0.05 ppm). Various feedstuffs from cotton and soybeans are fed to
animals, thus exposure of humans to residues might result if such
residues carry through to meat, milk, poultry or eggs. No tolerances
are proposed for meat, milk, poultry or eggs since no detectable
residues from clomazone have been found in animal feed items in the
past or were found in any sugarcane processed animal feed products.
Although the RAC bagasse was once a feed item, EPA has concluded that
it is now mainly used for fuel. Accordingly molasses is the only
sugarcane feed contributing fraction. As noted above, in conducting
this exposure assessment, EPA has made very conservative assumptions,
i.e., 100% of crops treated will contain clomazone residues and those
residues would be at the level of the tolerance. It is FMCs opinion
that these assumptions result in an overestimate of human exposure.
    ii. Drinking water. It is unlikely that there will be exposure to
residues of clomazone through drinking water supplies. A field mobility
study was conducted at a loamy sand location. Clomazone was found only
in the top 0-1 ft. soil samples during the 61 day study period. No
clomazone residue (0.02 ppm) was detected in the deeper soil levels (1-
2, 2-3 and 3-4 ft.). Mathematical modeling (PESTANS) was also applied
to the loamy sand site. PESTANS showed very limited potential for
movement of clomazone. That is, clomazone did not move lower than the
top seven inches of soil over the first 30 days with 10 inches of
precipitation and 100% recharge. Predictions were also obtained for
other soil types including sand, sandy loam, silt loam and clay loam.
These outputs yielded a similar conclusion, that clomazone has low
potential for downward movement with its highest mobility being sand.
The field leaching study and PESTANS modeling results were further
confirmed by field dissipation studies conducted in silt loam (IL and
AR), sandy loam (NJ), sandy clay loam (NC), silty clay loam (IA) and
silt loam (LA) soils. Results of these studies demonstrated that
clomazone tended to remain in the top soil layer (0-6 ), with residues
in the 6-12 layer being at or below method sensitivity (0.10 ppm) and
generally declining to non-detectable. An aquatic field dissipation
study was conducted at locations in AR and TX, having silty clay loam
and loam soils characteristics respectively. Soil samples were taken
over a period of 12 months following the herbicide application.
Detectable residues of clomazone were found only in the 0-6 horizon.
Should movement into surface water occur, potential for clomazone
residues to be detected in drinking water supplies at significant
levels is minimal. Results from an aquatic field dissipation study
(static water situation) demonstrated half-lives of 12-13 days,
indicating even shorter durations are likely under flowing water
situations. Accordingly, there is no
reasonable expectation that there would be an additional incremental
aggregate dietary contribution of clomazone through groundwater or
surface water.
    2. Non-dietary exposure. Clomazone is only registered for use on
food crops. Since the proposed use on sugarcane is consistent with
existing registrations, there will be no non-dietary, non-occupational
exposure.


D. Cumulative Effects


    Clomazone is an isoxazolidinone herbicide. No other registered
chemical exists in this class of chemistry. Therefore, given clomazone
s unique chemistry low acute toxicity, the absence of genotoxic,
oncogenic, developmental or reproductive effects, and low exposure
potential (see Sections A and C), the expression of cumulative human
health effects with clomazone and other natural or synthetic pesticides
is not anticipated.


E. Safety Determination


    1. U.S. population. Using the conservative exposure assumptions
described above, based on the completeness and reliability of the
toxicology data, it is concluded that aggregate exposure due to
existing registered uses, and pending uses, of clomazone will utilize
less than 1% of the RfD for the U.S. population. Additionally, an
analysis concluded that aggregate exposure to clomazone adding
sugarcane at a 0.05 ppm tolerance level will utilize 0.04 percent 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. It is concluded that there
is a reasonable certainty that no harm will result from aggregate
exposure to residues of clomazone, including all anticipated dietary
exposure.
    2. Infants and children. Based on the current toxicological data
requirements, the database relative to pre- and post-natal effects for
children is complete (See Section B.3). Further, for clomazone, the
NOAEL in the two year feeding study which was used to calculate the RfD
(0.043 mg/kg/day) is already lower than the NOAELs from the
reproductive and developmental studies by a factor of more than 10-
fold. Therefore, it can be concluded that no additional uncertainty
factors are warranted and that the RfD at 0.043 mg/kg/day is
appropriate for assessing aggregate risk to infants, children as well
as adults.
    Using the conservative exposure assumptions described above, FMC
has concluded that the percent of the RfD that will be utilized by
aggregate exposure to residues of clomazone in/on sugarcane for non-
nursing infants (1 year old), the population subgroup most sensitive,
is 0.114 and the percent of the RfD that will be utilized by the
children (1-6 years old) population subgroup is 0.086. The percent of
the RfD utilized for infants and children for sugarcane plus all other
current and pending (i.e., rice, tanier, cassava and arracacha)
clomazone tolerances is 0.872 and 0.510 respectively.
    Based on the above information, FMC has concluded that there is a
reasonable certainty that no harm will result to infants, children or
adults from dietary food consumption exposure to clomazone residues
from either sugarcane sourced foods alone or sugarcane sourced foods
plus all other clomazone treated human dietary food sources.


F. International Tolerances


    There are Codex residue limits for residues of clomazone in or on
oilseed rape, potatoes, tobacco, soybeans, rice, cottonseed, sugarcane
and peas.
[FR Doc. 01-7644 Filed 3-27-01; 8:45 am]
BILLING CODE 6560-S