[Federal Register Volume 64, Number 173 (Wednesday, September 8, 1999)]
[Notices]
[Pages 48829-48836]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-23198]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-888; FRL-6097-6]
Notice of Filing a Pesticide Petition to Establish a Tolerance
for Certain Pesticide Chemicals 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
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by docket control number PF-888, must be
received on or before October 8, 1999.
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'' section. To
ensure proper receipt by EPA, it is imperative that you identify docket
control number PF-888 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Linda Deluise, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 401 M St., SW., Washington, DC 20460; telephone
number: (703) 305-5428; and e-mail address: deluise.linda@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 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
[[Page 48830]]
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 in the ``FOR FURTHER INFORMATION CONTACT'' section.
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'' 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-888. 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-888 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, 401 M St., SW., 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 5.1/
6.1 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-888. 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 in the ``FOR FURTHER INFORMATION
CONTACT'' section.
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 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 petitions. Additional data
may be needed before EPA rules on the petitions.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: August 23, 1999.
James Jones,
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 48831]]
1. FMC Corporation
PP 9F6037, 4F4399, and 4F3012
EPA has received pesticide petitions (PP 9F6037, 4F4399, and
4F3012) from FMC Corporation, 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 part 180
by establishing a tolerance for residues of zeta-cypermethrin
(--cyano(3-phenoxyphenyl)methyl ()
cis, trans 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate)
in or on the raw agricultural commodity sugar beets, roots at 0.05
parts per million (ppm), sugar beets, tops at 0.20 ppm; sugarcane at
0.60 ppm; corn, grain (field, seed and pop) at 0.05 ppm; green onions
at 6.0 ppm; alfalfa seed at 0.5 ppm; alfalfa forage at 10.0 ppm; and
alfalfa hay at 30.0 ppm; and corn, sweet (K+CWHR) at 0.1 ppm; corn,
forage and corn, fodder at 30.0 ppm; poultry, meat at 0.05 ppm;
poultry, meat byproducts at 0.05 ppm; poultry, fat at 0.05 ppm; eggs at
0.05 ppm; meat of cattle, goats, hogs, horses, and sheep at 0.3 ppm;
fat of cattle, goats, hogs, horses, and sheep at 2.0 ppm; and milk, fat
at 1.0 ppm (reflecting 0.2 ppm in whole milk). 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 cypermethrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabelled cypermethrin in various crops all showing
similar results. The residue of concern is the parent compound only.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of cypermethrin in or on food with a
limit of detection that allows monitoring of food with residues at or
above the levels set in these tolerances (Gas Chromatography with
Electron Capture Detection (GC/ECD).
3. Magnitude of residues. Crop field trial residue data from
studies conducted at the maximum label rates for sugar beets,
sugarcane, corn (field, seed, pop and sweet), green and bulb onions,
and alfalfa, show that the proposed zeta-cypermethrin tolerances on
sugar beets, roots at 0.05 ppm; sugar beets, tops at 0.20 ppm;
sugarcane at 0.60 ppm; corn, grain (field, seed and pop) at 0.05 ppm;
green onions at 6.0 ppm; alfalfa seed at 0.5 ppm, alfalfa forage at
10.0 ppm, and alfalfa hay at 30.0 ppm; corn, sweet (K+CWHR) at 0.1 ppm,
and corn, forage and corn, fodder at 30.0 ppm will not be exceeded when
the zeta-cypermethrin products labeled for these uses are used as
directed.
B. Toxicological Profile
1. Acute toxicity. For the purposes of assessing acute dietary
risk, FMC has used the no observed adverse effect level (NOAEL) of 3.8
milligrams/kilograms/day (mg/kg/day) based on the NOAEL of 7.5 mg/kg/
day from the cypermethrin chronic feeding/oncogenicity study in rats
and a correction factor of two to account for the differences in the
percentage of the biologically active isomer. The lowest observed
adverse effect level (LOAEL) of 50.0 mg/kg/day was based on
neurological signs which were displayed during week one of the study.
This acute dietary endpoint is used to determine acute dietary risks to
all population subgroups.
2. Genotoxicity. The following genotoxicity tests were all
negative: in vivo chromosomal aberration in rat bone marrow cells; in
vitro cytogenic chromosome aberration; unscheduled DNA synthesis; CHO/
HGPTT mutagen assay; weakly mutagenic: gene mutation (Ames).
3. Reproductive and developmental toxicity. No evidence of
additional sensitivity to young rats was observed following prenatal or
postnatal exposure to zeta-cypermethrin.
i. A 2-generation reproductive toxicity study with zeta-
cypermethrin in rats demonstrated a NOAEL of 7.0 mg/kg/day and a LOAEL
of 27.0 mg/kg/day for parental/systemic toxicity based on body weight,
organ weight, and clinical signs. There were no adverse effects in
reproductive performance. The NOAEL for reproductive toxicity was
considered to be > 45.0 mg/kg/day, the highest dose tested.
ii. A developmental study with zeta-cypermethrin in rats
demonstrated a maternal NOAEL of 12.5 mg/kg/day and a LOAEL of 25 mg/
kg/day based on decreased maternal body weight gain, food consumption
and clinical signs. There were no signs of developmental toxicity at
35.0 mg/kg/day, the highest dose level tested.
iii. A developmental study with cypermethrin in rabbits
demonstrated a maternal NOAEL of 100 mg/kg/day and a LOAEL of 450 mg/
kg/day based on decreased body weight gain. There were no signs of
developmental toxicity at 700 mg/kg/day, the highest dose level tested.
4. Subchronic toxicity. Short- and intermediate-term toxicity. The
NOAEL of 3.8 mg/kg/day based on the NOAEL 7.5 mg/kg/day from the
cypermethrin chronic feeding/oncogenicity study in rats and a
correction factor of two to account for the biologically active isomer
would also be used for short- and intermediate-term MOE calculations
(as well as acute, discussed in (1) above). The LOAEL of 50.0 mg/kg/day
was based on neurological signs which were displayed during week one of
the study.
5. Chronic toxicity-- i. The reference dose (RfD) of 0.0125 mg/kg/
day for zeta-cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a
cypermethrin rat reproduction study and an uncertainty factor of 200
(used to account for the differences in the percentage of the
biologically active isomer). The endpoint effect of concern was based
on consistent decreased body weight gain in both sexes at the LOAEL of
7.5 mg/kg/day.
ii. Cypermethrin is classified as a Group C Chemical (possible
human carcinogen with limited evidence of carcinogenicity in animals)
based upon limited evidence for carcinogenicity in female mice;
assignment of a Q* has not been recommended.
6. Animal metabolism. The metabolism of cypermethrin in animals is
adequately understood. Cypermethrin has been shown to be rapidly
absorbed, distributed, and excreted in rats when administered orally.
Cypermethrin is metabolized by hydrolysis and oxidation.
7. Metabolite toxicology. The Agency has previously determined that
the metabolites of cypermethrin are not of toxicological concern and
need not be included in the tolerance expression.
8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of cypermethrin have been
conducted. However, no evidence of such effects were reported in the
standard battery of required toxicology studies which have been
completed and found acceptable. Based on these studies, there is no
evidence to suggest that cypermethrin has an adverse effect on the
endocrine system.
C. Aggregate Exposure
1. Dietary exposure-- i. Food. Permanent tolerances, in support of
registrations, currently exist for residues of zeta-cypermethrin on
cottonseed; pecans; lettuce, head; onions, bulb; and cabbage and
livestock commodities of cattle, goats, hogs, horses, and sheep (along
with the associated meat and milk tolerances). For the purposes of
[[Page 48832]]
assessing the potential dietary exposure for these existing and the
subject proposed tolerances, FMC has utilized available information on
anticipated residues, monitoring data and percent crop treated (PCT) as
follows:
ii. Acute exposure and risk. Acute dietary exposure 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. For the purposes of
assessing acute dietary risk for zeta-cypermethrin, FMC has used the
NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5 mg/kg/day from the
cypermethrin chronic feeding/oncogenicity study in rats and a
correction factor of two to account for the differences in the
percentage of the biologically active isomer. The LOAEL of 50.0 mg/kg/
day was based on neurological signs which were displayed during week
one of this study. This acute dietary endpoint is used to determine
acute dietary risks to all population subgroups. Available information
on anticipated residues, monitoring data and PCT was incorporated into
a Tier 3 analysis, using Monte Carlo modeling for commodities that may
be consumed in a single serving. These assessments show that the
margins of exposure (MOE) are significantly greater than the EPA
standard of 100 for all subpopulations. The 95th percentile of exposure
for the overall U. S. population was estimated to be 0.001934 mg/kg/day
(MOE of 1964); 99th percentile 0.003844 mg/kg/day (MOE of 988); and
99.9th percentile 0.012574 mg/kg/day (MOE of 302). The 95th percentile
of exposure for all infants < 1="" year="" old="" was="" estimated="" to="" be="" 0.002195="" mg/kg/day="" (moe="" of="" 1730);="" 99th="" percentile="" 0.004976="" mg/kg/day="" (moe="" of="" 763);="" and="" 99.9th="" percentile="" 0.016942="" mg/kg/day="" (moe="" of="" 224).="" the="" 95th="" percentile="" of="" exposure="" for="" nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.001090="" mg/kg/day="" (moe="" of="" 3484);="" 99th="" percentile="" 0.002516="" mg/kg/="" day="" (moe="" of="" 1510);="" and="" 99.9th="" percentile="" 0.004140="" mg/kg/day="" (moe="" of="" 917).="" the="" 95th="" percentile="" of="" exposure="" for="" non-nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.002288="" mg/kg/day="" (moe="" of="" 1660);="" 99th="" percentile="" 0.006164="" mg/kg/day="" (moe="" of="" 616);="" and="" 99.9th="" percentile="" 0.018741="" mg/kg/day="" (moe="" of="" 202).="" the="" 95th="" percentile="" of="" exposure="" for="" children="" 1="" to="" 6="" years="" old="" (the="" most="" highly="" exposed="" population="" subgroup)="" and="" children="" 7="" to="" 12="" years="" old="" was="" estimated="" to="" be,="" respectively,="" 0.002993="" mg/kg/day="" (moe="" of="" 1269)="" and="" 0.002286="" mg/kg/day="" (moe="" of="" 1662);="" 99th="" percentile="" 0.005234="" mg/kg/day="" (moe="" of="" 725)="" and="" 0.004178="" (moe="" of="" 909);="" and="" 99.9th="" percentile="" 0.034965="" mg/kg/day="" (moe="" of="" 108)="" and="" 0.014545="" (moe="" of="" 261).="" the="" 95th="" percentile="" of="" exposure="" for="" females="" (13+/nursing)="" was="" estimated="" to="" be="" 0.001448="" mg/kg/day="" (moe="" of="" 2623);="" 99th="" percentile="" 0.003594="" mg/kg/day="" (moe="" of="" 1057);="" and="" 99.9th="" percentile="" 0.011663="" mg/kg/day="" (moe="" of="" 325).="" therefore,="" fmc="" concludes="" that="" the="" acute="" dietary="" risk="" of="" zeta-cypermethrin,="" as="" estimated="" by="" the="" dietary="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" iii.="" chronic="" exposure="" and="" risk.="" the="" rfd="" of="" 0.0125="" mg/kg/day="" for="" zeta-cypermethrin="" is="" based="" on="" a="" noael="" of="" 2.5="" mg/kg/day="" from="" a="" cypermethrin="" rat="" reproduction="" study="" and="" an="" uncertainty="" factor="" of="" 200="" (used="" to="" account="" for="" the="" differences="" in="" the="" percentage="" of="" the="" biologically="" active="" isomer).="" the="" endpoint="" effect="" of="" concern="" was="" based="" on="" consistent="" decreased="" body="" weight="" gain="" in="" both="" sexes="" at="" the="" loael="" of="" 7.5="" mg/kg/day.="" a="" chronic="" dietary="" exposure/risk="" assessment="" has="" been="" performed="" for="" zeta-cypermethrin="" using="" the="" above="" rfd.="" available="" information="" on="" anticipated="" residues,="" monitoring="" data="" and="" pct="" was="" incorporated="" into="" the="" analysis="" to="" estimate="" the="" anticipated="" residue="" contribution="" (arc).="" the="" arc="" is="" generally="" considered="" a="" more="" realistic="" estimate="" than="" an="" estimate="" based="" on="" tolerance="" level="" residues.="" the="" arc="" is="" estimated="" to="" be="" 0.000379="" mg/kg="" body="" weight="" (bwt)/day="" and="" utilizes="" 3.0%="" of="" the="" rfd="" for="" the="" overall="" u.="" s.="" population.="" the="" arc="" for="" nursing="" infants=""><1 year)="" and="" non-nursing="" infants="">< 1="" year)="" is="" estimated="" to="" be="" 0.000104="" mg/kg="" bwt/day="" and="" 0.000509="" mg/kg="" bwt/day="" and="" utilizes="" 0.8%="" and="" 4.1%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" children="" 1-6="" years="" old="" (subgroup="" most="" highly="" exposed)="" and="" children="" 7-12="" years="" old="" is="" estimated="" to="" be="" 0.000904="" mg/kg="" bwt/day="" and="" 0.000544="" mg/kg="" bwt/day="" and="" utilizes="" 7.2%="" and="" 4.4%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" females="" (13+/="" nursing)="" is="" estimated="" to="" be="" 0.000365="" mg/kg="" bwt/day="" and="" utilizes="" 2.9%="" of="" the="" rfd.="" generally="" speaking,="" the="" epa="" has="" no="" cause="" for="" concern="" if="" the="" total="" dietary="" exposure="" from="" residues="" for="" uses="" for="" which="" there="" are="" published="" and="" proposed="" tolerances="" is="" less="" than="" 100%="" of="" the="" rfd.="" therefore,="" fmc="" concludes="" that="" the="" chronic="" dietary="" risk="" of="" zeta-="" cypermethrin,="" as="" estimated="" by="" the="" dietary="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" iv.="" drinking="" water.="" laboratory="" and="" field="" data="" have="" demonstrated="" that="" cypermethrin="" is="" immobile="" in="" soil="" and="" will="" not="" leach="" into="" ground="" water.="" other="" data="" show="" that="" cypermethrin="" is="" virtually="" insoluble="" in="" water="" and="" extremely="" lipophilic.="" as="" a="" result,="" fmc="" concludes="" that="" residues="" reaching="" surface="" waters="" from="" field="" runoff="" will="" quickly="" adsorb="" to="" sediment="" particles="" and="" be="" partitioned="" from="" the="" water="" column.="" further,="" a="" screening="" evaluation="" of="" leaching="" potential="" of="" a="" typical="" pyrethroid="" was="" conducted="" using="" epa's="" pesticide="" root="" zone="" model="" (przm3).="" based="" on="" this="" screening="" assessment,="" the="" potential="" concentrations="" of="" a="" pyrethroid="" in="" ground="" water="" at="" depths="" of="" 1="" and="" 2="" meters="" are="" essentially="" zero=""><0.001 parts="" per="" billion).="" surface="" water="" concentrations="" for="" pyrethroids="" were="" estimated="" using="" przm3="" and="" exposure="" analysis="" modeling="" system="" (exams)="" using="" standard="" epa="" cotton="" runoff="" and="" mississippi="" pond="" scenarios.="" the="" maximum="" concentration="" predicted="" in="" the="" simulated="" pond="" was="" 0.052="" parts="" per="" billion.="" concentrations="" in="" actual="" drinking="" water="" would="" be="" much="" lower="" than="" the="" levels="" predicted="" in="" the="" hypothetical,="" small,="" stagnant="" farm="" pond="" model="" since="" drinking="" water="" derived="" from="" surface="" water="" would="" normally="" be="" treated="" before="" consumption.="" based="" on="" these="" analyses,="" the="" contribution="" of="" water="" to="" the="" dietary="" risk="" estimate="" is="" negligible.="" therefore,="" fmc="" concludes="" that="" together="" these="" data="" indicate="" that="" residues="" are="" not="" expected="" to="" occur="" in="" drinking="" water.="" 2.="" non-dietary="" exposure.="" zeta-cypermethrin="" is="" registered="" for="" agricultural="" crop="" applications="" only,="" therefore="" non-dietary="" exposure="" assessments="" are="" not="" warranted.="" d.="" cumulative="" effects="" in="" consideration="" of="" potential="" cumulative="" effects="" of="" cypermethrin="" and="" other="" substances="" that="" may="" have="" a="" common="" mechanism="" of="" toxicity,="" to="" our="" knowledge="" there="" are="" currently="" no="" available="" data="" or="" other="" reliable="" information="" indicating="" that="" any="" toxic="" effects="" produced="" by="" cypermethrin="" would="" be="" cumulative="" with="" those="" of="" other="" chemical="" compounds;="" thus="" only="" the="" potential="" risks="" of="" cypermethrin="" have="" been="" considered="" in="" this="" assessment="" of="" its="" aggregate="" exposure.="" fmc="" intends="" to="" submit="" information="" for="" the="" epa="" to="" consider="" concerning="" potential="" cumulative="" effects="" of="" cypermethrin="" consistent="" with="" the="" schedule="" established="" by="" epa="" in="" the="" federal="" register="" of="" august="" 4,="" 1997="" (62="" fr="" 42020)="" (frl-5734-6)="" and="" other="" epa="" publications="" pursuant="" to="" the="" food="" quality="" protection="" act.="" e.="" safety="" determination="" 1.="" u.s.="" population.="" based="" on="" a="" complete="" and="" reliable="" toxicology="" data="" base,="" the="" rfd="" for="" zeta-cypermethrin="" is="" 0.0125="" mg/kg/day,="" based="" on="" a="" noael="" of="" [[page="" 48833]]="" 2.5="" mg/kg/day="" and="" a="" loael="" of="" 7.5="" mg/kg/day="" from="" the="" cypermethrin="" rat="" reproduction="" study="" and="" an="" uncertainty="" factor="" of="" 200.="" available="" information="" on="" anticipated="" residues,="" monitoring="" data="" and="" pct="" was="" incorporated="" into="" an="" analysis="" to="" estimate="" the="" arc="" for="" 26="" population="" subgroups.="" the="" arc="" is="" generally="" considered="" a="" more="" realistic="" estimate="" than="" an="" estimate="" based="" on="" tolerance="" level="" residues.="" the="" arc="" is="" estimated="" to="" be="" 0.000379="" mg/kg="" body="" weight="" (bwt)/day="" and="" utilizes="" 3.0%="" of="" the="" rfd="" for="" the="" overall="" u.="" s.="" population.="" the="" arc="" for="" nursing="" infants=""><1 year)="" and="" non-nursing="" infants=""><1 year)="" is="" estimated="" to="" be="" 0.000104="" mg/kg="" bwt/day="" and="" 0.000509="" mg/kg="" bwt/day="" and="" utilizes="" 0.8%="" and="" 4.1%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" children="" 1-6="" years="" old="" (subgroup="" most="" highly="" exposed)="" and="" children="" 7-12="" years="" old="" are="" estimated="" to="" be="" 0.000904="" mg/kg="" bwt/day="" and="" 0.000544="" mg/kg="" bwt/day="" and="" utilizes="" 7.2%="" and="" 4.4%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" females="" (13+/nursing)="" is="" estimated="" to="" be="" 0.000365="" mg/kg="" bwt/day="" and="" utilizes="" 2.9%="" of="" the="" rfd.="" generally="" speaking,="" the="" epa="" has="" no="" cause="" for="" concern="" if="" the="" total="" dietary="" exposure="" from="" residues="" for="" uses="" for="" which="" there="" are="" published="" and="" proposed="" tolerances="" is="" less="" than="" 100%="" of="" the="" rfd.="" therefore,="" fmc="" concludes="" that="" the="" chronic="" dietary="" risk="" of="" zeta-="" cypermethrin,="" as="" estimated="" by="" the="" aggregate="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" the="" 95th="" percentile="" of="" exposure="" for="" the="" overall="" u.="" s.="" population="" was="" estimated="" to="" be="" 0.001934="" mg/kg/day="" (moe="" of="" 1964);="" 99th="" percentile="" 0.003844="" mg/kg/day="" (moe="" of="" 988);="" and="" 99.9th="" percentile="" 0.012574="" mg/kg/="" day="" (moe="" of="" 302).="" the="" 95th="" percentile="" of="" exposure="" for="" all="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.002195="" mg/kg/day="" (moe="" of="" 1730);="" 99th="" percentile="" 0.004976="" mg/kg/day="" (moe="" of="" 763);="" and="" 99.9th="" percentile="" 0.016942="" mg/kg/day="" (moe="" of="" 224).="" the="" 95th="" percentile="" of="" exposure="" for="" nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.001090="" mg/kg/day="" (moe="" of="" 3484);="" 99th="" percentile="" 0.002516="" mg/kg/day="" (moe="" of="" 1510);="" and="" 99.9th="" percentile="" 0.004140="" mg/kg/day="" (moe="" of="" 917).="" the="" 95th="" percentile="" of="" exposure="" for="" non-nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.002288="" mg/kg/day="" (moe="" of="" 1660);="" 99th="" percentile="" 0.006164="" mg/kg/day="" (moe="" of="" 616);="" and="" 99.9th="" percentile="" 0.018741="" mg/kg/day="" (moe="" of="" 202).="" the="" 95th="" percentile="" of="" exposure="" for="" children="" 1="" to="" 6="" years="" old="" (the="" most="" highly="" exposed="" population="" subgroup)="" and="" children="" 7="" to="" 12="" years="" old="" was="" estimated="" to="" be,="" respectively,="" 0.002993="" mg/kg/day="" (moe="" of="" 1269)="" and="" 0.002286="" mg/kg/day="" (moe="" of="" 1662);="" 99th="" percentile="" 0.005234="" mg/kg/day="" (moe="" of="" 725)="" and="" 0.004178="" (moe="" of="" 909);="" and="" 99.9th="" percentile="" 0.034965="" mg/kg/day="" (moe="" of="" 108)="" and="" 0.014545="" (moe="" of="" 261).="" the="" 95th="" percentile="" of="" exposure="" for="" females="" (13+/nursing)="" was="" estimated="" to="" be="" 0.001448="" mg/="" kg/day="" (moe="" of="" 2623);="" 99th="" percentile="" 0.003594="" mg/kg/day="" (moe="" of="" 1057);="" and="" 99.9th="" percentile="" 0.011663="" mg/kg/day="" (moe="" of="" 325).="" therefore,="" fmc="" concludes="" that="" there="" is="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" acute="" exposure="" to="" zeta-cypermethrin.="" 2.="" infants="" and="" children--="" i.="" general.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" zeta-="" cypermethrin,="" fmc="" considered="" data="" from="" developmental="" toxicity="" studies="" in="" the="" rat="" and="" rabbit,="" and="" a="" 2-generation="" reproductive="" study="" in="" the="" rat.="" the="" data="" demonstrated="" no="" indication="" of="" increased="" sensitivity="" of="" rats="" to="" zeta-cypermethrin="" or="" rabbits="" to="" cypermethrin="" in="" utero="" and/or="" postnatal="" exposure="" to="" zeta-cypermethrin="" or="" cypermethrin.="" the="" developmental="" toxicity="" studies="" are="" designed="" to="" evaluate="" adverse="" effects="" on="" the="" developing="" organism="" resulting="" from="" pesticide="" exposure="" during="" prenatal="" development="" to="" one="" or="" both="" parents.="" 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="" may="" apply="" an="" additional="" margin="" of="" safety="" for="" infants="" and="" children="" in="" the="" case="" of="" threshold="" effects="" to="" account="" for="" prenatal="" and="" postnatal="" toxicity="" and="" the="" completeness="" of="" the="" data="" base.="" ii.="" developmental="" toxicity="" studies.="" in="" the="" prenatal="" developmental="" toxicity="" studies="" in="" rats="" and="" rabbits,="" there="" was="" no="" evidence="" of="" developmental="" toxicity="" at="" the="" highest="" doses="" tested="" (35.0="" mg/kg/day="" in="" rats="" and="" 700="" mg/kg/day="" in="" rabbits).="" decreased="" body="" weight="" gain="" was="" observed="" at="" the="" maternal="" loael="" in="" each="" study;="" the="" maternal="" noael="" was="" established="" at="" 12.5="" mg/kg/day="" in="" rats="" and="" 100="" mg/kg/day="" in="" rabbits.="" iii.="" reproductive="" toxicity="" study.="" in="" the="" 2-generation="" reproduction="" study="" in="" rats,="" offspring="" toxicity="" (body="" weight)="" and="" parental="" toxicity="" (body="" weight,="" organ="" weight,="" and="" clinical="" signs)="" was="" observed="" at="" 27.0="" mg/kg/day="" and="" greater.="" the="" parental="" systemic="" noael="" was="" 7.0="" mg/kg/day="" and="" the="" parental="" systemic="" loael="" was="" 27.0="" mg/kg/day.="" there="" were="" no="" developmental="" (pup)="" or="" reproductive="" effects="" up="" to="" 45.0="" mg/kg/day,="" highest="" dose="" tested.="" iv.="" prenatal="" and="" postnatal="" sensitivity.="" there="" was="" no="" evidence="" of="" developmental="" toxicity="" in="" the="" studies="" at="" the="" highest="" doses="" tested="" in="" the="" rat="" (35.0="" mg/kg/day)="" or="" in="" the="" rabbit="" (700="" mg/kg/day).="" therefore,="" there="" is="" no="" evidence="" of="" a="" special="" dietary="" risk="" (either="" acute="" or="" chronic)="" for="" infants="" and="" children="" which="" would="" require="" an="" additional="" safety="" factor.="" v.="" postnatal.="" based="" on="" the="" absence="" of="" pup="" toxicity="" up="" to="" dose="" levels="" which="" produced="" toxicity="" in="" the="" parental="" animals,="" there="" is="" no="" evidence="" of="" special="" postnatal="" sensitivity="" to="" infants="" and="" children="" in="" the="" rat="" reproduction="" study.="" vi.="" conclusion.="" based="" on="" the="" above,="" fmc="" concludes="" that="" reliable="" data="" support="" use="" of="" the="" standard="" 100-fold="" uncertainty="" factor,="" and="" that="" an="" additional="" uncertainty="" factor="" is="" not="" needed="" to="" protect="" the="" safety="" of="" infants="" and="" children.="" as="" stated="" above,="" aggregate="" exposure="" assessments="" utilized="" significantly="" less="" than="" 1%="" of="" the="" rfd="" for="" either="" the="" entire="" u.="" s.="" population="" or="" any="" of="" the="" 26="" population="" subgroups="" including="" infants="" and="" children.="" therefore,="" it="" may="" be="" concluded="" that="" there="" is="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" cypermethrin="" residues.="" f.="" international="" tolerances="" there="" are="" no="" codex,="" canadian,="" or="" mexican="" residue="" limits="" for="" residues="" of="" zeta-cypermethrin="" in="" or="" on="" sugar="" beets,="" sugarcane,="" corn="" (field,="" seed,="" pop="" and="" sweet),="" green="" and="" bulb="" onions,="" and="" alfalfa.="" 2.="" fmc="" corporation="" pp="" 9f6040="" epa="" has="" received="" a="" pesticide="" petition="" (pp="" 9f6040)="" from="" fmc="" corporation,="" 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="" part="" 180="" by="" establishing="" a="" tolerance="" for="" residues="" of="" zeta-cypermethrin="">--
cyano(3-phenoxyphenyl)methyl () cis, trans 3-(2,2-
dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate) in or on the raw
agricultural commodity rice, grain at 1.2 ppm; rice, straw at 2.0 ppm;
and rice, hulls at 16.0 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.
[[Page 48834]]
A. Residue Chemistry
1. Plant metabolism. The metabolism of cypermethrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabelled cypermethrin in various crops all showing
similar results. The residue of concern is the parent compound only.
2. Analytical method. There is a practical analytical method for
detecting and measuring levels of cypermethrin in or on food with a
limit of detection that allows monitoring of food with residues at or
above the levels set in these tolerances (Gas Chromatography with
Electron Capture Detection (GC/ECD).
3. Magnitude of residues. Crop field trial residue data from
studies conducted at the maximum label rates for rice grain show that
the proposed zeta-cypermethrin tolerances on rice, grain at 1.2 ppm,
rice, straw at 2.0 ppm and rice, hulls at 16.0 ppm will not be exceeded
when the zeta-cypermethrin products labeled for these uses are used as
directed.
B. Toxicological Profile
1. Acute toxicity. For the purposes of assessing acute dietary
risk, FMC has used the NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5
mg/kg/day from the cypermethrin chronic feeding/oncogenicity study in
rats and a correction factor of two to account for the differences in
the percentage of the biologically active isomer. The LOAEL) of 50.0
mg/kg/day was based on neurological signs which were displayed during
week one of the study. This acute dietary endpoint is used to determine
acute dietary risks to all population subgroups.
2. Genotoxicity. The following genotoxicity tests were all
negative: in vivo chromosomal aberration in rat bone marrow cells; in
vitro cytogenic chromosome aberration; unscheduled DNA synthesis; CHO/
HGPTT mutagen assay; weakly mutagenic: gene mutation (Ames).
3. Reproductive and developmental toxicity. No evidence of
additional sensitivity to young rats was observed following prenatal or
postnatal exposure to zeta-cypermethrin.
i. A 2-generation reproductive toxicity study with zeta-
cypermethrin in rats demonstrated a NOAEL of 7.0 mg/kg/day and a LOAEL
of 27.0 mg/kg/day for parental/systemic toxicity based on body weight,
organ weight, and clinical signs. There were no adverse effects in
reproductive performance. The NOAEL for reproductive toxicity was
considered to be > 45.0 mg/kg/day, the highest dose tested.
ii. A developmental study with zeta-cypermethrin in rats
demonstrated a maternal NOAEL of 12.5 mg/kg/day and a LOAEL of 25 mg/
kg/day based on decreased maternal body weight gain, food consumption
and clinical signs. There were no signs of developmental toxicity at
35.0 mg/kg/day, the highest dose level tested.
iii. A developmental study with cypermethrin in rabbits
demonstrated a maternal NOAEL of 100 mg/kg/day and a LOAEL of 450 mg/
kg/day based on decreased body weight gain. There were no signs of
developmental toxicity at 700 mg/kg/day, the highest dose level tested.
4. Subchronic toxicity. Short- and intermediate-term toxicity. The
NOAEL of 3.8 mg/kg/day based on the NOAEL 7.5 mg/kg/day from the
cypermethrin chronic feeding/oncogenicity study in rats and a
correction factor of two to account for the biologically active isomer
would also be used for short- and intermediate-term MOE calculations
(as well as acute, discussed in (1) above). The LOAEL of 50.0 mg/kg/day
was based on neurological signs which were displayed during week one of
the study.
5. Chronic toxicity-- i. The RfD of 0.0125 mg/kg/day for zeta-
cypermethrin is based on a NOAEL of 2.5 mg/kg/day from a cypermethrin
rat reproduction study and an uncertainty factor of 200 (used to
account for the differences in the percentage of the biologically
active isomer). The endpoint effect of concern was based on consistent
decreased body weight gain in both sexes at the LOAEL of 7.5 mg/kg/day.
ii. Cypermethrin is classified as a Group C Chemical (possible
human carcinogen with limited evidence of carcinogenicity in animals)
based upon limited evidence for carcinogenicity in female mice;
assignment of a Q* has not been recommended.
6. Animal metabolism. The metabolism of cypermethrin in animals is
adequately understood. Cypermethrin has been shown to be rapidly
absorbed, distributed, and excreted in rats when administered orally.
Cypermethrin is metabolized by hydrolysis and oxidation.
7. Metabolite toxicology. The Agency has previously determined that
the metabolites of cypermethrin are not of toxicological concern and
need not be included in the tolerance expression.
8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of cypermethrin have been
conducted. However, no evidence of such effects were reported in the
standard battery of required toxicology studies which have been
completed and found acceptable. Based on these studies, there is no
evidence to suggest that cypermethrin has an adverse effect on the
endocrine system.
C. Aggregate Exposure
1. Dietary exposure-- i. Food. Permanent tolerances, in support of
registrations, currently exist for residues of zeta-cypermethrin on
cottonseed; pecans; lettuce, head; onions, bulb; and cabbage and
livestock commodities of cattle, goats, hogs, horses, and sheep (and
their associated meat and milk tolerances). For the purposes of
assessing the potential dietary exposure for these existing and the
subject proposed tolerances, FMC has utilized available information on
anticipated residues, monitoring data and PCT as follows:
ii. Acute exposure and risk. Acute dietary exposure 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. For the purposes of
assessing acute dietary risk for zeta-cypermethrin, FMC has used the
NOAEL of 3.8 mg/kg/day based on the NOAEL of 7.5 mg/kg/day from the
cypermethrin chronic feeding/oncogenicity study in rats and a
correction factor of two to account for the differences in the
percentage of the biologically active isomer. The LOAEL of 50.0 mg/kg/
day was based on neurological signs which were displayed during week
one of this study. This acute dietary endpoint is used to determine
acute dietary risks to all population subgroups. Available information
on anticipated residues, monitoring data and PCT was incorporated into
a Tier 3 analysis, using Monte Carlo modeling for commodities that may
be consumed in a single serving. These assessments show that the
margins of exposure (MOE) are significantly greater than the EPA
standard of 100 for all subpopulations. The 95th percentile of exposure
for the overall U. S. population was estimated to be 0.001049 mg/kg/day
(MOE of 3622); 99th percentile 0.003166 mg/kg/day (MOE of 1200); and
99.9th percentile 0.012313 mg/kg/day (MOE of 308). The 95th percentile
of exposure for all infants < 1="" year="" old="" was="" estimated="" to="" be="" 0.000610="" mg/kg/day="" (moe="" of="" 6229);="" 99th="" percentile="" 0.001955="" mg/kg/day="" (moe="" of="" 1943);="" and="" 99.9th="" percentile="" 0.019362="" mg/kg/day="" (moe="" of="" 196).="" the="" 95th="" percentile="" of="" exposure="" for="" nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.000283="" mg/kg/day="" (moe="" of="" 13418);="" 99th="" percentile="" 0.001141="" mg/="" kg/day="" [[page="" 48835]]="" (moe="" of="" 3330);="" and="" 99.9th="" percentile="" 0.002424="" mg/kg/day="" (moe="" of="" 1567).="" the="" 95th="" percentile="" of="" exposure="" for="" non-nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.000657="" mg/kg/day="" (moe="" of="" 5784);="" 99th="" percentile="" 0.007700="" mg/kg/day="" (moe="" of="" 493);="" and="" 99.9th="" percentile="" 0.019395="" mg/kg/="" day="" (moe="" of="" 195).="" the="" 95th="" percentile="" of="" exposure="" for="" children="" 1="" to="" 6="" years="" old="" (the="" most="" highly="" exposed="" population="" subgroup)="" and="" children="" 7="" to="" 12="" years="" old="" was="" estimated="" to="" be,="" respectively,="" 0.001184="" mg/kg/day="" (moe="" of="" 3208)="" and="" 0.001177="" mg/kg/day="" (moe="" of="" 3227);="" 99th="" percentile="" 0.003894="" mg/kg/day="" (moe="" of="" 975)="" and="" 0.003337="" (moe="" of="" 1138);="" and="" 99.9th="" percentile="" 0.034204="" mg/kg/day="" (moe="" of="" 111)="" and="" 0.013940="" (moe="" of="" 272).="" the="" 95th="" percentile="" of="" exposure="" for="" females="" (13+/nursing)="" was="" estimated="" to="" be="" 0.001070="" mg/kg/day="" (moe="" of="" 3549);="" 99th="" percentile="" 0.003318="" mg/kg/="" day="" (moe="" of="" 1145);="" and="" 99.9th="" percentile="" 0.011127="" mg/kg/day="" (moe="" of="" 341).="" therefore,="" fmc="" concludes="" that="" the="" acute="" dietary="" risk="" of="" zeta-="" cypermethrin,="" as="" estimated="" by="" the="" dietary="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" iii.="" chronic="" exposure="" and="" risk.="" the="" rfd="" of="" 0.0125="" mg/kg/day="" for="" zeta-cypermethrin="" is="" based="" on="" a="" noael="" of="" 2.5="" mg/kg/day="" from="" a="" cypermethrin="" rat="" reproduction="" study="" and="" an="" uncertainty="" factor="" of="" 200="" (used="" to="" account="" for="" the="" differences="" in="" the="" percentage="" of="" the="" biologically="" active="" isomer).="" the="" endpoint="" effect="" of="" concern="" was="" based="" on="" consistent="" decreased="" body="" weight="" gain="" in="" both="" sexes="" at="" the="" loael="" of="" 7.5="" mg/kg/day.="" a="" chronic="" dietary="" exposure/risk="" assessment="" has="" been="" performed="" for="" zeta-cypermethrin="" using="" the="" above="" rfd.="" available="" information="" on="" anticipated="" residues,="" monitoring="" data="" and="" pct="" was="" incorporated="" into="" the="" analysis="" to="" estimate="" the="" arc.="" the="" arc="" is="" generally="" considered="" a="" more="" realistic="" estimate="" than="" an="" estimate="" based="" on="" tolerance="" level="" residues.="" the="" arc="" is="" estimated="" to="" be="" 0.000158="" mg/kg="" body="" weight="" (bwt)/day="" and="" utilizes="" 1.3%="" of="" the="" rfd="" for="" the="" overall="" u.="" s.="" population.="" the="" arc="" for="" non-nursing="" infants=""><1 year)="" and="" nursing="" infants=""><1 year)="" is="" estimated="" to="" be="" 0.000212="" mg/kg/day="" and="" 0.000032="" mg/kg/day="" and="" utilizes="" 1.7%="" and="" 0.3%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" children="" 1-6="" years="" old="" (subgroup="" most="" highly="" exposed)="" and="" children="" 7-12="" years="" old="" is="" estimated="" to="" be="" 0.000268="" mg/kg="" bwt/day="" and="" 0.000168="" mg/kg="" bwt/day="" and="" utilizes="" 2.1%="" and="" 1.3%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" females="" (13+/nursing)="" is="" estimated="" to="" be="" 0.000170="" mg/kg="" bwt/day="" and="" utilizes="" 1.4%="" of="" the="" rfd.="" generally="" speaking,="" the="" epa="" has="" no="" cause="" for="" concern="" if="" the="" total="" dietary="" exposure="" from="" residues="" for="" uses="" for="" which="" there="" are="" published="" and="" proposed="" tolerances="" is="" less="" than="" 100%="" of="" the="" rfd.="" therefore,="" fmc="" concludes="" that="" the="" chronic="" dietary="" risk="" of="" zeta-cypermethrin,="" as="" estimated="" by="" the="" dietary="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" vi.="" drinking="" water.="" laboratory="" and="" field="" data="" have="" demonstrated="" that="" cypermethrin="" is="" immobile="" in="" soil="" and="" will="" not="" leach="" into="" ground="" water.="" other="" data="" show="" that="" cypermethrin="" is="" virtually="" insoluble="" in="" water="" and="" extremely="" lipophilic.="" as="" a="" result,="" fmc="" concludes="" that="" residues="" reaching="" surface="" waters="" from="" field="" runoff="" will="" quickly="" adsorb="" to="" sediment="" particles="" and="" be="" partitioned="" from="" the="" water="" column.="" further,="" a="" screening="" evaluation="" of="" leaching="" potential="" of="" a="" typical="" pyrethroid="" was="" conducted="" using="" epa's="" pesticide="" root="" zone="" model="" (przm3).="" based="" on="" this="" screening="" assessment,="" the="" potential="" concentrations="" of="" a="" pyrethroid="" in="" ground="" water="" at="" depths="" of="" 1="" and="" 2="" meters="" are="" essentially="" zero=""><0.001 parts="" per="" billion).="" surface="" water="" concentrations="" for="" pyrethroids="" were="" estimated="" using="" przm3="" and="" exposure="" analysis="" modeling="" system="" (exams)="" using="" standard="" epa="" cotton="" runoff="" and="" mississippi="" pond="" scenarios.="" the="" maximum="" concentration="" predicted="" in="" the="" simulated="" pond="" was="" 0.052="" ppb.="" concentrations="" in="" actual="" drinking="" water="" would="" be="" much="" lower="" than="" the="" levels="" predicted="" in="" the="" hypothetical,="" small,="" stagnant="" farm="" pond="" model="" since="" drinking="" water="" derived="" from="" surface="" water="" would="" normally="" be="" treated="" before="" consumption.="" based="" on="" these="" analyses,="" the="" contribution="" of="" water="" to="" the="" dietary="" risk="" estimate="" is="" negligible.="" therefore,="" fmc="" concludes="" that="" together="" these="" data="" indicate="" that="" residues="" are="" not="" expected="" to="" occur="" in="" drinking="" water.="" 2.="" non-dietary="" exposure.="" zeta-cypermethrin="" is="" registered="" for="" agricultural="" crop="" applications="" only,="" therefore="" non-dietary="" exposure="" assessments="" are="" not="" warranted.="" d.="" cumulative="" effects="" in="" consideration="" of="" potential="" cumulative="" effects="" of="" cypermethrin="" and="" other="" substances="" that="" may="" have="" a="" common="" mechanism="" of="" toxicity,="" to="" our="" knowledge="" there="" are="" currently="" no="" available="" data="" or="" other="" reliable="" information="" indicating="" that="" any="" toxic="" effects="" produced="" by="" cypermethrin="" would="" be="" cumulative="" with="" those="" of="" other="" chemical="" compounds;="" thus="" only="" the="" potential="" risks="" of="" cypermethrin="" have="" been="" considered="" in="" this="" assessment="" of="" its="" aggregate="" exposure.="" fmc="" intends="" to="" submit="" information="" for="" the="" epa="" to="" consider="" concerning="" potential="" cumulative="" effects="" of="" cypermethrin="" consistent="" with="" the="" schedule="" established="" by="" epa="" in="" federal="" register="" august="" 4,="" 1997="" (62="" fr="" 42020)="" and="" other="" epa="" publications="" pursuant="" to="" the="" food="" quality="" protection="" act.="" e.="" safety="" determination="" 1.="" u.s.="" population.="" based="" on="" a="" complete="" and="" reliable="" toxicology="" data="" base,="" the="" rfd="" for="" zeta-cypermethrin="" is="" 0.0125="" mg/kg/day,="" based="" on="" a="" noael="" of="" 2.5="" mg/kg/day="" and="" a="" loael="" of="" 7.5="" mg/kg/day="" from="" the="" cypermethrin="" rat="" reproduction="" study="" and="" an="" uncertainty="" factor="" of="" 200.="" available="" information="" on="" anticipated="" residues,="" monitoring="" data="" and="" pct="" was="" incorporated="" into="" an="" analysis="" to="" estimate="" the="" arc="" for="" 26="" population="" subgroups.="" the="" arc="" is="" generally="" considered="" a="" more="" realistic="" estimate="" than="" an="" estimate="" based="" on="" tolerance="" level="" residues.="" the="" arc="" is="" estimated="" to="" be="" 0.000158="" mg/kg="" body="" weight="" (bwt)/day="" and="" utilizes="" 1.3%="" of="" the="" rfd="" for="" the="" overall="" u.="" s.="" population.="" the="" arc="" for="" non-nursing="" infants=""><1 year)="" and="" nursing="" infants=""><1 year)="" is="" estimated="" to="" be="" 0.000212="" mg/kg/day="" and="" 0.000032="" mg/kg/day="" and="" utilizes="" 1.7%="" and="" 0.3%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" children="" 1-6="" years="" old="" (subgroup="" most="" highly="" exposed)="" and="" children="" 7-12="" years="" old="" is="" estimated="" to="" be="" 0.000268="" mg/kg="" bwt/day="" and="" 0.000168="" mg/kg="" bwt/day="" and="" utilizes="" 2.1%="" and="" 1.3%="" of="" the="" rfd,="" respectively.="" the="" arc="" for="" females="" (13+/nursing)="" is="" estimated="" to="" be="" 0.000170="" mg/kg="" bwt/day="" and="" utilizes="" 1.4%="" of="" the="" rfd.="" generally="" speaking,="" the="" epa="" has="" no="" cause="" for="" concern="" if="" the="" total="" dietary="" exposure="" from="" residues="" for="" uses="" for="" which="" there="" are="" published="" and="" proposed="" tolerances="" is="" less="" than="" 100%="" of="" the="" rfd.="" therefore,="" fmc="" concludes="" that="" the="" chronic="" dietary="" risk="" of="" zeta-cypermethrin,="" as="" estimated="" by="" the="" aggregate="" risk="" assessment,="" does="" not="" appear="" to="" be="" of="" concern.="" the="" 95th="" percentile="" of="" exposure="" for="" the="" overall="" u.="" s.="" population="" was="" estimated="" to="" be="" 0.001049="" mg/kg/day="" (moe="" of="" 3622);="" 99th="" percentile="" 0.003166="" mg/kg/day="" (moe="" of="" 1200);="" and="" 99.9th="" percentile="" 0.012313="" mg/kg/="" day="" (moe="" of="" 308).="" the="" 95th="" percentile="" of="" exposure="" for="" all="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.000610="" mg/kg/day="" (moe="" of="" 6229);="" 99th="" percentile="" 0.001955="" mg/kg/day="" (moe="" of="" 1943);="" and="" 99.9th="" percentile="" 0.019362="" mg/kg/day="" (moe="" of="" 196).="" the="" 95th="" percentile="" of="" exposure="" for="" nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.000283="" mg/kg/day="" (moe="" of="" 13418);="" 99th="" percentile="" 0.001141="" mg/kg/day="" (moe="" of="" 3330);="" and="" 99.9th="" percentile="" 0.002424="" mg/kg/day="" (moe="" of="" 1567).="" the="" 95th="" percentile="" of="" [[page="" 48836]]="" exposure="" for="" non-nursing="" infants="">< 1="" year="" old="" was="" estimated="" to="" be="" 0.000657="" mg/kg/day="" (moe="" of="" 5784);="" 99th="" percentile="" 0.007700="" mg/kg/day="" (moe="" of="" 493);="" and="" 99.9th="" percentile="" 0.019395="" mg/kg/day="" (moe="" of="" 195).="" the="" 95th="" percentile="" of="" exposure="" for="" children="" 1="" to="" 6="" years="" old="" (the="" most="" highly="" exposed="" population="" subgroup)="" and="" children="" 7="" to="" 12="" years="" old="" was="" estimated="" to="" be,="" respectively,="" 0.001184="" mg/kg/day="" (moe="" of="" 3208)="" and="" 0.001177="" mg/kg/day="" (moe="" of="" 3227);="" 99th="" percentile="" 0.003894="" mg/kg/day="" (moe="" of="" 975)="" and="" 0.003337="" (moe="" of="" 1138);="" and="" 99.9th="" percentile="" 0.034204="" mg/kg/day="" (moe="" of="" 111)="" and="" 0.013940="" (moe="" of="" 272).="" the="" 95th="" percentile="" of="" exposure="" for="" females="" (13+/nursing)="" was="" estimated="" to="" be="" 0.001070="" mg/="" kg/day="" (moe="" of="" 3549);="" 99th="" percentile="" 0.003318="" mg/kg/day="" (moe="" of="" 1145);="" and="" 99.9th="" percentile="" 0.011127="" mg/kg/day="" (moe="" of="" 341).="" therefore,="" fmc="" concludes="" that="" there="" is="" reasonable="" certainty="" that="" no="" harm="" will="" result="" from="" acute="" exposure="" to="" zeta-cypermethrin.="" 2.="" infants="" and="" children--="" i.="" general.="" in="" assessing="" the="" potential="" for="" additional="" sensitivity="" of="" infants="" and="" children="" to="" residues="" of="" zeta-="" cypermethrin,="" fmc="" considered="" data="" from="" developmental="" toxicity="" studies="" in="" the="" rat="" and="" rabbit,="" and="" a="" 2-generation="" reproductive="" study="" in="" the="" rat.="" the="" data="" demonstrated="" no="" indication="" of="" increased="" sensitivity="" of="" rats="" to="" zeta-cypermethrin="" or="" rabbits="" to="" cypermethrin="" in="" utero="" and/or="" postnatal="" exposure="" to="" zeta-cypermethrin="" or="" cypermethrin.="" the="" developmental="" toxicity="" studies="" are="" designed="" to="" evaluate="" adverse="" effects="" on="" the="" developing="" organism="" resulting="" from="" pesticide="" exposure="" during="" prenatal="" development="" to="" one="" or="" both="" parents.="" 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="" may="" apply="" an="" additional="" margin="" of="" safety="" for="" infants="" and="" children="" in="" the="" case="" of="" threshold="" effects="" to="" account="" for="" prenatal="" and="" postnatal="" toxicity="" and="" the="" completeness="" of="" the="" data="" base.="" ii.="" developmental="" toxicity="" studies.="" in="" the="" prenatal="" developmental="" toxicity="" studies="" in="" rats="" and="" rabbits,="" there="" was="" no="" evidence="" of="" developmental="" toxicity="" at="" the="" highest="" doses="" tested="" (35.0="" mg/kg/day="" in="" rats="" and="" 700="" mg/kg/day="" in="" rabbits).="" decreased="" body="" weight="" gain="" was="" observed="" at="" the="" maternal="" loael="" in="" each="" study;="" the="" maternal="" noael="" was="" established="" at="" 12.5="" mg/kg/day="" in="" rats="" and="" 100="" mg/kg/day="" in="" rabbits.="" iii.="" reproductive="" toxicity="" study.="" in="" the="" 2-generation="" reproduction="" study="" in="" rats,="" offspring="" toxicity="" (body="" weight)="" and="" parental="" toxicity="" (body="" weight,="" organ="" weight,="" and="" clinical="" signs)="" was="" observed="" at="" 27.0="" mg/kg/day="" and="" greater.="" the="" parental="" systemic="" noael="" was="" 7.0="" mg/kg/day="" and="" the="" parental="" systemic="" loael="" was="" 27.0="" mg/kg/day.="" there="" were="" no="" developmental="" (pup)="" or="" reproductive="" effects="" up="" to="" 45.0="" mg/kg/day,="" highest="" dose="" tested.="" iv.="" prenatal="" and="" postnatal="" sensitivity.="" there="" was="" no="" evidence="" of="" developmental="" toxicity="" in="" the="" studies="" at="" the="" highest="" doses="" tested="" in="" the="" rat="" (35.0="" mg/kg/day)="" or="" in="" the="" rabbit="" (700="" mg/kg/day).="" therefore,="" there="" is="" no="" evidence="" of="" a="" special="" dietary="" risk="" (either="" acute="" or="" chronic)="" for="" infants="" and="" children="" which="" would="" require="" an="" additional="" safety="" factor.="" v.="" postnatal.="" based="" on="" the="" absence="" of="" pup="" toxicity="" up="" to="" dose="" levels="" which="" produced="" toxicity="" in="" the="" parental="" animals,="" there="" is="" no="" evidence="" of="" special="" postnatal="" sensitivity="" to="" infants="" and="" children="" in="" the="" rat="" reproduction="" study.="" vi.="" conclusion.="" based="" on="" the="" above,="" fmc="" concludes="" that="" reliable="" data="" support="" use="" of="" the="" standard="" 100-fold="" uncertainty="" factor,="" and="" that="" an="" additional="" uncertainty="" factor="" is="" not="" needed="" to="" protect="" the="" safety="" of="" infants="" and="" children.="" as="" stated="" above,="" aggregate="" exposure="" assessments="" utilized="" significantly="" less="" than="" 1%="" of="" the="" rfd="" for="" either="" the="" entire="" u.="" s.="" population="" or="" any="" of="" the="" 26="" population="" subgroups="" including="" infants="" and="" children.="" therefore,="" it="" may="" be="" concluded="" that="" there="" is="" reasonable="" certainty="" that="" no="" harm="" will="" result="" to="" infants="" and="" children="" from="" aggregate="" exposure="" to="" cypermethrin="" residues.="" f.="" international="" tolerances="" there="" are="" no="" codex,="" canadian,="" or="" mexican="" residue="" limits="" for="" residues="" of="" zeta-cypermethrin="" in="" or="" on="" rice="" grain,="" straw="" or="" hulls.="" [fr="" doc.="" 99-23198="" filed="" 9-7-99;="" 8:45="" am]="" billing="" code="" 6560-50-f="">