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Cyfluthrin (Bayer). March 1, 2000. Petition for pesticide tolerances. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2000/March/Day-01/p4791.htm
[Federal Register: March 1, 2000 (Volume 65, Number 41)]
[Notices]
[Page 11052-11057]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr01mr00-61]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-916; FRL-6489-9]
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 pesticide
petitions 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-916, must be
received on or before March 31, 2000.
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-916 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: Tracy Keigwin, Registration
Support Branch, Registration Division (7505), Office of Pesticide
Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)
305-6605; e-mail address: keigwin.tracy@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'' 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-916. 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-916 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, Ariel Rios Bldg., 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
[[Page 11053]]
Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic
form must be identified by docket control number PF-916. 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 supports 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: February 17, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
The 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 petitioner and represents the view
of the petitioner. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summaries announce 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. Bayer Corporation
EPA has received a pesticide petition (PP5F4475) from Bayer
Corporation, 8400 Hawthorn Road, P.O. Box 4913, Kansas City, MO 64120-
0013 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 cyfluthrin, cyano (4-
fluoro-3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2- in or on the
raw agricultural commodity (RAC) cereal grains group; corn, starch;
corn, refined oil (wet milling); corn, flour; corn, refined oil (dry
milling); wheat, bran; corn, milled by-products; rice, hulls; wheat,
milled by-products at 2.0, 3.0, 12, 4.0, 15, 3.0, 4.0, 9.0, 3.0 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 cyfluthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabeled cyfluthrin in various crops all showing
similar results. The residue of concern is cyfluthrin.
2. Analytical method. Adequate analytical methodology (gas/liquid
chromatography with an electron capture detector (GLC/EC) is available
for enforcement purposes.
3. Magnitude of residues. Cyfluthrin is the active ingredient
(a.i.) in the registered end-use product Tempo 2E Grain, Bin and
Warehouse Insecticide , EPA FR 3125-ULO. Data to support the proposed
tolerances have been submitted to the Agency.
B. Toxicological Profile
1. Acute toxicity. There is a battery of acute toxicity studies for
cyfluthrin supporting an overall toxicity Category II for the active
ingredient.
2. Genotoxicty. Mutagenicity tests were conducted, including
several gene mutation assays (reverse mutation and recombination assays
in bacteria and a Chinese hamster ovary (CHO)/HGPRT assay); a
structural chromosome aberration assay (CHO/sister chromatid exchange
assay); and an unscheduled DNA synthesis (UDS) assay in rat
hepatocytes. All tests were negative for genotoxicity.
3. Reproductive and developmental toxicity. An oral developmental
toxicity study in rats with a maternal and fetal no observed adverse
effect level (NOAEL) of 10 milligrams/kilograms body weight/day (mg/kg
bwt/day) highest dose tested (HDT). An oral developmental toxicity
study in rabbits with a maternal NOAEL of 20 mg/kg bwt/day and a
maternal lowest effect level (LEL) of 60 mg/kg bwt/day, based on
decreased bwt gain and decreased food consumption during the dosing
period. A fetal NOAEL of 20 mg/kg bwt/day and a fetal LEL of 60 mg/kg
bwt/day were also observed in this study. The LEL was based on
increased resorptions and increased postimplantation loss. A 3-
generation reproduction study in rats with systemic toxicity NOAELs of
7.5 and 2.5 mg/kg bwt/day for parental animals and their offspring,
respectively. At highest dose levels (HDLs), the bwts of parental
animals and their offspring were reduced.
4. Subchronic toxicity. A subchronic toxicity feeding study using
rats demonstrated a NOAEL of 22.5 mg/kg bwt/day, the HDT. A 6-month
toxicity feeding study in dogs established a NOAEL of 5 mg/kg bwt/day.
The LEL
[[Page 11054]]
was 15 mg/kg bwt/day based on clinical signs and reduced thymus
weights.
5. Chronic toxicity. A 12-month chronic feeding study in dogs
established a NOAEL of 4 mg/kg bwt/day. The LEL for this study is
established at 16 mg/kg bwt/day, based on slight ataxia, increased
vomiting, diarrhea, and decreased body weight. A 24-month chronic
feeding/carcinogenicity study in rats demonstrated a NOAEL of 2.5 mg/kg
bwt/day and LEL of 6.2 mg/kg bwt/day, based on decreased body weights
in males, decreased food consumption in males, and inflammatory foci in
the kidneys in females. A 24-month carcinogenicity study in mice was
conducted. Under the conditions of the study there were no carcinogenic
effects observed. A 24-month chronic feeding/carcinogenicity study in
rats was conducted. There were no carcinogenic effects observed under
the conditions of the study.
6. Animal metabolism. A metabolism study in rats showed that
cyfluthrin is rapidly absorbed and excreted, mostly as conjugated
metabolites in the urine, within 48 hours. An enterohepatic circulation
was observed.
7. Metabolite toxicology. No toxicology data have been required for
cyfluthrin metabolites. The residue of concern is cyfluthrin.
8. Endocrine disruption. There is no evidence of endocrine effects
in any of the studies conducted with cyfluthrin, thus, there is no
indication at this time that cyfluthrin causes endocrine effects.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Dietary exposure was estimated using
Novigen's Dietary Exposure Evaluation Model (DEEM ) software; results
from field trial and processing studies; consumption data from the
Department of Agricultural (USDA) Continuing Surveys of Food Intake by
Individuals (CSFIIs), conducted from 1994 through 1996; and information
on the percentages of crops treated with cyfluthrin. Cyfluthrin is
currently registered for use in alfalfa, carrots, citrus, cotton, sweet
corn, sorghum, sunflower, sugarcane, potatoes, peppers, radishes, and
tomatoes. In addition, it has an import tolerance for hops. Various
formulations are registered for use in food handling establishments and
in combination with another active ingredient, for use in field corn,
pop corn, and sweet corn. Chronic dietary exposure estimates with the
current label uses plus the proposed uses on stored grain, field and
pop corn, soybeans, hops, peas and lentils, lettuce, head and stem
brassica, and mustard greens for the overall U.S. population were 5% of
the population adjusted dose (PAD) (0.008 mg/kg bwt/day). For the most
highly exposed population subgroup, children 1 to 6 years of age, the
exposure was estimated to be 15% of the PAD. Acute dietary exposure
estimates with the current label uses plus the proposed uses on stored
grain, field and pop corn, soybeans, hops, peas and lentils, lettuce,
head and stem brassica, and mustard greens for the overall U.S.
population were 11% of the aPAD (0.07 mg/kg bwt/day). For the most
highly exposed population subgroup, children 1 to 6 years of age, the
exposure was estimated to be 18% of the aPAD.
ii. Drinking water. Cyfluthrin is immobile in soil, therefore, will
not leach into ground water. Additionally, due the insolubility and
lipophilic nature of cyfluthrin, any residues in surface water will
rapidly and tightly bind to soil particles and remain with sediment,
therefore, not contributing to potential dietary exposure from drinking
water. 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 2 meters are essentially zero (0.001
parts per billion (ppb)). 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 52 parts per trillion (ppt). Concentration in actual drinking water
would be much lower. Based on these analyses, the contribution of water
to the dietary risk estimate is negligible.
2. Non-dietary exposure. Non-occupational exposure to cyfluthrin
may occur as a result of inhalation or contact from indoor residential,
indoor commercial, and outdoor residential uses. Pursuant to the
requirements of Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) as amended by the Food Quality Protection Act (FQPA) of 1996
non-dietary and aggregate risk analyses for cyfluthrin were conducted.
The analyses include evaluation of potential non-dietary acute
application and post-application exposures. Non-occupational, non-
dietary exposure was assessed based on the assumption that a flea
infestation control scenario represents a ``worst case'' scenario. For
the flea control infestation scenario indoor fogger, and professional
residential turf same day treatments were included for cyfluthrin.
Deterministic (point values) were used to present a worse case upper-
bound estimate of non-dietary exposure. The non-dietary exposure
estimates were expressed as systemic absorbed doses for a summation of
inhalation, dermal, and incidental ingestion exposures. These worst
case non-dietary exposures were aggregated with chronic dietary
exposures to evaluate potential health risks that might be associated
with cyfluthrin products. The chronic dietary exposures were expressed
as an oral absorbed dose to combine with the non-dietary systemic
absorbed doses for comparison to a systemic absorbed dose NOAEL.
Results for each potential exposed subpopulation (of adults, children
1-6 years, and infants 1 year) were compared to the systemic absorbed
dose NOAEL for cyfluthrin to provide estimates of margins of exposure
(MOE). The large MOEs for cyfluthrin clearly demonstrate a substantial
degree of safety. The total non-dietary MOEs are 3,800, 2,700, and
2,500 for adults, children (1-6 years), and infants (1 year),
respectively. The aggregate MOE for adults is approximately 3,700 and
the MOEs for infants and children exceed 2,400. The non-dietary methods
used in the analyses can be characterized as highly conservative. This
is due to the conservatism inherent in the calculation procedures and
input assumptions. An example of this is the conservatism inherent in
the jazzercise methodology's over-representation of residential post-
application exposures. It is important to acknowledge that these MOEs
are likely to significantly underestimate actual MOEs due to a variety
of conservative assumptions and biases inherent in the derivatization
of exposure by this method. Therefore, it can be concluded that large
MOEs associated with potential non-dietary and aggregate exposures to
cyfluthrin will result in little or no health risks to exposed persons.
The aggregate risk analysis demonstrates compliance with the health-
based requirements of the FQPA of 1996 for the current label uses. The
additional use of cyfluthrin on field corn and soybean crops will have
no impact on the analysis for non-dietary exposure.
D. Cumulative Effects
Bayer will submit information for EPA to consider concerning
potential cumulative effects of cyfluthrin consistent with the schedule
established by EPA at 62 FR 42020 (August 4, 1997) (FRL-5734-6) and
other EPA publications pursuant to the FQPA.
[[Page 11055]]
E. Safety Determination
1. U.S. population. Based on the exposure assessments described
above and on the completeness and reliability of the toxicity data, it
can be concluded that total aggregate exposure to cyfluthrin from all
label uses will utilize less than 20% of the RfD for chronic dietary
exposures and that MOE in excess of 1,000 exist for aggregate exposure
to cyfluthrin for non-cupational exposure. EPA generally has no
concerns for exposures below 100% of the RfD, because the RfD
represents the level at or below which daily aggregate exposure over a
lifetime will not pose appreciable risks to human health. MOE of 100 or
more (300 for infants and children) also indicate an adequate degree of
safety. Thus, it can be concluded that there is a reasonable certainty
that no harm will result from aggregate exposure to cyfluthrin
residues.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of cyfluthrin, the data
from developmental studies in both rat and rabbit and a 2-generation
reproduction study in the rat can be considered. The developmental
toxicity studies evaluate any potential adverse effects on the
developing animal resulting from pesticide exposure of the mother
during prenatal development. The reproduction study evaluates any
effects from exposure to the pesticide on the reproductive capability
of mating animals through 2-generations, as well as any observed
systemic toxicity. The toxicology data which support these uses of
cyfluthrin include: A rat oral developmental toxicity study in which
maternal and fetal NOAELs of 10 mg/kg bwt/day HGT were observed. An
oral developmental toxicity study in which rabbits had a maternal NOAEL
of 20 mg/kg bwt/day and a maternal LEL of 60 mg/kg bwt/day, based on
decreased bodyweight gain and decreased food consumption during the
dosing period. A fetal NOAEL of 20 mg/kg bwt/day and a fetal LEL of 60
mg/kg bwt/day were also observed in this study. The LEL was based on
increased resorptions and increased postimplantation loss. An oral
developmental toxicity study performed with beta-cyfluthrin, the
resolved isomer mixture of cyfluthrin, has been submitted to the Agency
and is currently under review. A developmental toxicity study in rats
exposed via inhalation to liquid aerosols of cyfluthrin revealed
developmental toxicity, but only in the presence of maternal toxicity.
The developmental NOAEL was 0.46 mg/m3 on the basis of
reduced placental and fetal weights, and delayed ossification. The
NOAEL for overt maternal toxicity was 0.46 mg/m3, the LDT.
In a rat 3-generation reproduction study, systemic toxicity NOAELs of
7.5 and 2.5 mg/kg bwt/day for parental animals and their offspring,
respectively, were observed. At HDL, the bwts of parental animals and
their offspring were reduced. Another multiple-generation reproduction
study in rats has been submitted to the Agency and is currently under
review. To assess acute dietary exposure and determine a MOE for the
overall U.S. population and certain subgroups, the Agency has used the
rabbit developmental toxicity study which had a maternal NOAEL of 20
mg/kg bwt/day. Because the toxicological endpoint is one of
developmental toxicity, the population group of concern for this
analysis was women aged 13 and above. This subgroup most closely
approximates women of child-bearing age. The MOE is calculated as the
ratio of the NOAEL to the exposure. The Agency calculated the MOE to be
over 600. Generally, MOE's greater than 100 for data derived from
animal studies are regarded as showing no appreciable risk. FFDCA
section 408 provides that EPA may apply an additional safety factor for
infants and children. The additional safety factor may be used when
prenatal and postnatal threshold effects were observed in studies or to
account for incompleteness of the toxicity data base. The results of
the 3-generation study in rats provided evidence suggesting that, with
respect to effects of cyfluthrin on body weight, pups were more
sensitive than adult rats. Thus, the Agency determined that an
additional 3-fold uncertainty factor (UF) should be used in risk
assessments to ensure adequate protection of infants and children.
Generally, EPA considers MOEs of at least 100 to indicate an adequate
degree of safety. With an additional 3x uncertainty factor, this would
be 300 for infants and children.
F. International Tolerances
There is a Codex maximum residue level (MRLs) for maize of 0.05
ppm. There is a Codex MRL for sweet corn of 0.02 ppm.
2. Bayer Corporation. EPA has received a pesticide petition
(PP0F6084) from Bayer Corporation, 8400 Hawthorn Road, P.O. Box 4913,
Kansas City, MO 64120-0013 proposing, pursuant to section 408(d) of the
FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a
tolerance for residues of cyfluthrin, cyano (4-fluoro-3-
phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2- in or on the RAC,
mustard greens, greens; lettuce, head; lettuce, leaf; head and stem
brassica subgroup (5A) at 7.0, 2.0, 3.0, 2.0 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.
A. Residue Chemistry
1. Plant metabolism. The metabolism of cyfluthrin in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabeled cyfluthrin in various crops all showing
similar results. The residue of concern is cyfluthrin.
2. Analytical method. Adequate analytical methodology GLC/EC
detector is available for enforcement purposes.
3. Magnitude of residues. Cyfluthrin is the active ingredient in
the registered end-use product Baythroid 2 Emulsifiable Pyrethroid
Insecticide, EPA FR 3125-351. Data to support the proposed tolerances
have been submitted to the Agency.
B. Toxicological Profile
1. Acute toxicity. There is a battery of acute toxicity studies for
cyfluthrin supporting an overall toxicity Category II for the active
ingredient.
2. Genotoxicity. Mutagenicity tests were conducted, including
several gene mutation assays (reverse mutation and recombination assays
in bacteria and a CHO/HGPRT assay; a structural chromosome aberration
assay (CHO/sister chromatid exchange assay); and an UDS assay in rat
hepatocytes. All tests were negative for genotoxicity.
3. Reproductive and developmental toxicity. An oral developmental
toxicity study in rats with a maternal and fetal NOAEL of 10 mg/kg bwt/
day HDT. An oral developmental toxicity study in rabbits with a
maternal NOAEL of 20 mg/kg bwt/day and a maternal LEL of 60 mg/kg bwt/
day, based on decreased body weight gain and decreased food consumption
during the dosing period. A fetal NOAEL of 20 mg/kg bwt/day and a fetal
LEL of 60 mg/kg bwt/day were also observed in this study. The LEL was
based on increased resorptions and increased post-implantation loss. A
3-generation reproduction study in rats with systemic toxicity NOAELs
of 7.5 and 2.5 mg/kg bwt/day for parental animals and their offspring,
respectively. At HDLs, the body weights of parental animals and their
offspring were reduced.
[[Page 11056]]
4. Subchronic toxicity. A subchronic toxicity feeding study using
rats demonstrated a NOAEL of 22.5 mg/kg bwt/day, the HDT. A 6-month
toxicity feeding study in dogs established a NOAEL of 5 mg/kg bwt/day.
The LEL was 15 mg/kg bwt/day based on clinical signs and reduced thymus
weights.
5. Chronic toxicity. A 12-month chronic feeding study in dogs
established a NOAEL of 4 mg/kg bwt/day. The LEL for this study is
established at 16 mg/kg bwt/day, based on slight ataxia, increased
vomiting, diarrhea and decreased body weight. A 24-month chronic
feeding/carcinogenicity study in rats demonstrated a NOAEL of 2.5 mg/kg
bwt/day and LEL of 6.2 mg/kg bwt/day, based on decreased body weights
in males, decreased food consumption in males, and inflammatory foci in
the kidneys in females. A 24-month carcinogenicity study in mice was
conducted. Under the conditions of the study there were no carcinogenic
effects observed. A 24-month chronic feeding/carcinogenicity study in
rats was conducted. There were no carcinogenic effects observed under
the conditions of the study.
6. Animal metabolism. A metabolism study in rats showed that
cyfluthrin is rapidly absorbed and excreted, mostly as conjugated
metabolites in the urine, within 48 hours. An enterohepatic circulation
was observed.
7. Metabolite toxicology. No toxicology data have been required for
cyfluthrin metabolites. The residue of concern is cyfluthrin.
8. Endocrine disruption. There is no evidence of endocrine effects
in any of the studies conducted with cyfluthrin, thus, there is no
indication at this time that cyfluthrin causes endocrine effects.
C. Aggregate Exposure
1. Dietary exposure--i. Food. Dietary exposure was estimated using
Novigen's Dietary Exposure Evaluation Model (DEEM ) software; results
from field trial and processing studies; consumption data from the USDA
Continuing Surveys of Food Intake by Individuals (CSFIIs), conducted
from 1994 through 1996; and information on the percentages of crops
treated with cyfluthrin. Cyfluthrin is currently registered for use in
alfalfa, carrots, citrus, cotton, sweet corn, sorghum, sunflower,
sugarcane, potatoes, peppers, radishes, and tomatoes. In addition, it
has an import tolerance for hops. Various formulations are registered
for use in food handling establishments and in combination with another
active ingredient, for use in field corn, pop corn, and sweet corn.
Chronic dietary exposure estimates with the current label uses plus the
proposed uses on stored grain, field and pop corn, soybeans, hops, peas
and lentils, lettuce, head and stem brassica, and mustard greens for
the overall U.S. population were 5% of the PAD (0.008 mg/kg bwt/day).
For the most highly exposed population subgroup, children 1 to 6 years
of age, the exposure was estimated to be 15% of the PAD. Acute dietary
exposure estimates with the current label uses plus the proposed uses
on stored grain, field and pop corn, soybeans, hops, peas and lentils,
lettuce, head and stem brassica, and mustard greens for the overall
U.S. population were 11% of the aPAD (0.07 mg/kg bwt/day). For the most
highly exposed population subgroup, children 1 to 6 years of age, the
exposure was estimated to be 18% of the aPAD.
ii. Drinking water. Cyfluthrin is immobile in soil, therefore, will
not leach into ground water. Additionally, due the insolubility and
lipophilic nature of cyfluthrin, any residues in surface water will
rapidly and tightly bind to soil particles and remain with sediment,
therefore, not contributing to potential dietary exposure from drinking
water. 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 2 meters are essentially zero (0.001
ppb). 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 52 ppt. Concentration in actual
drinking water would be much lower. Based on these analyses, the
contribution of water to the dietary risk estimate is negligible.
2. Non-dietary exposure. Non-occupational exposure to cyfluthrin
may occur as a result of inhalation or contact from indoor residential,
indoor commercial, and outdoor residential uses. Pursuant to the
requirements of FIFRA as amended by the FQPA of 1996 non-dietary and
aggregate risk analyses for cyfluthrin were conducted. The analyses
include evaluation of potential non-dietary acute application and post-
application exposures. Non-occupational, non-dietary exposure was
assessed based on the assumption that a flea infestation control
scenario represents a ``worst case'' scenario. For the flea control
infestation scenario indoor fogger, and professional residential turf
same day treatments were included for cyfluthrin. Deterministic (point
values) were used to present a worse case upper-bound estimate of non-
dietary exposure. The non-dietary exposure estimates were expressed as
systemic absorbed doses for a summation of inhalation, dermal, and
incidental ingestion exposures. These worst case non-dietary exposures
were aggregated with chronic dietary exposures to evaluate potential
health risks that might be associated with cyfluthrin products. The
chronic dietary exposures were expressed as an oral absorbed dose to
combine with the non-dietary systemic absorbed doses for comparison to
a systemic absorbed dose NOAEL. Results for each potential exposed
subpopulation (of adults, children 1-6 years, and infants 1 year) were
compared to the systemic absorbed dose NOAEL for cyfluthrin to provide
estimates of MOE. The large MOEs for cyfluthrin clearly demonstrate a
substantial degree of safety. The total non-dietary MOEs are 3,800,
2,700, and 2,500 for adults, children (1-6 years), and infants ( 1
year), respectively. The aggregate MOE for adults is approximately
3,700 and the MOEs for infants and children exceed 2,400. The non-
dietary methods used in the analyses can be characterized as highly
conservative. This is due to the conservatism inherent in the
calculation procedures and input assumptions. An example of this is the
conservatism inherent in the jazzercise methodology's over-
representation of residential post-application exposures. It is
important to acknowledge that these MOEs are likely to significantly
underestimate actual MOEs due to a variety of conservative assumptions
and biases inherent in the derivatization of exposure by this method.
Therefore, it can be concluded that large MOEs associated with
potential non-dietary and aggregate exposures to cyfluthrin will result
in little or no health risks to exposed persons. The aggregate risk
analysis demonstrates compliance with the health-based requirements of
the FQPA of 1996 for the current label uses. The additional use of
cyfluthrin on field corn and soybean crops will have no impact on the
analysis for non-dietary exposure.
D. Cumulative Effects
Bayer will submit information for EPA to consider concerning
potential cumulative effects of cyfluthrin consistent with the schedule
established by EPA at 62 FR 42020 (August 4, 1997) (FRL-5734-6) and
other EPA publications pursuant to the FQPA.
[[Page 11057]]
E. Safety Determination
1. U.S. population. Based on the exposure assessments described
above and on the completeness and reliability of the toxicity data, it
can be concluded that total aggregate exposure to cyfluthrin from all
label uses will utilize less than 20% of the RfD for chronic dietary
exposures and that MOEs in excess of 1,000 exist for aggregate exposure
to cyfluthrin for non-occupational exposure. EPA generally has no
concerns for exposures below 100% of the RfD, because the RfD
represents the level at or below which daily aggregate exposure over a
lifetime will not pose appreciable risks to human health. MOE of 100 or
more (300 for infants and children) also indicate an adequate degree of
safety. Thus, it can be concluded that there is a reasonable certainty
that no harm will result from aggregate exposure to cyfluthrin
residues.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of cyfluthrin, the data
from developmental studies in both rat and rabbit and a 2-generation
reproduction study in the rat can be considered. The developmental
toxicity studies evaluate any potential adverse effects on the
developing animal resulting from pesticide exposure of the mother
during prenatal development. The reproduction study evaluates any
effects from exposure to the pesticide on the reproductive capability
of mating animals through 2-generations, as well as any observed
systemic toxicity. The toxicology data which support these uses of
cyfluthrin include: A rat oral developmental toxicity study in which
maternal and fetal NOAELs of 10 mg/kg bwt/day HDT were observed. An
oral developmental toxicity study in which rabbits had a maternal NOAEL
of 20 mg/kg bwt/day and a maternal LEL of 60 mg/kg bwt/day, based on
decreased bwt gain and decreased food consumption during the dosing
period. A fetal NOAEL of 20 mg/kg bwt/day and a fetal LEL of 60 mg/kg
bwt/day were also observed in this study. The LEL was based on
increased resorptions and increased postimplantation loss. An oral
developmental toxicity study performed with beta-cyfluthrin, the
resolved isomer mixture of cyfluthrin, has been submitted to the Agency
and is currently under review. A developmental toxicity study in rats
exposed via inhalation to liquid aerosols of cyfluthrin revealed
developmental toxicity, but only in the presence of maternal toxicity.
The developmental NOAEL was 0.46 mg/m3 on the basis of
reduced placental and fetal weights, and delayed ossification. The
NOAEL for overt maternal toxicity was 0.46 mg/m3, the LDT.
In a rat 3-generation reproduction study, systemic toxicity NOAELs of
7.5 and 2.5 mg/kg bwt/day for parental animals and their offspring,
respectively, were observed. At HDL, the body weights of parental
animals and their offspring were reduced. Another multiple-generation
reproduction study in rats has been submitted to the Agency and is
currently under review. To assess acute dietary exposure and determine
a MOE for the overall U.S. population and certain subgroups, the Agency
has used the rabbit developmental toxicity study which had a maternal
NOAEL of 20 mg/kg bwt/day. Because the toxicological endpoint is one of
developmental toxicity, the population group of concern for this
analysis was women aged 13 and above. This subgroup most closely
approximates women of child-bearing age. The MOE is calculated as the
ratio of the NOAEL to the exposure. The Agency calculated the MOE to be
over 600. Generally, MOEs greater than 100 for data derived from animal
studies are regarded as showing no appreciable risk. FFDCA section 408
provides that EPA may apply an additional safety factor for infants and
children. The additional safety factor may be used when prenatal and
postnatal threshold effects were observed in studies or to account for
incompleteness of the toxicity data base. The results of the 3-
generation study in rats provided evidence suggesting that, with
respect to effects of cyfluthrin on body weight, pups were more
sensitive than adult rats. Thus, the Agency determined that an
additional 3-fold uncertainty factor (UF) should be used in risk
assessments to ensure adequate protection of infants and children.
Generally, EPA considers MOEs of at least 100 to indicate an adequate
degree of safety. With an additional 3x UF, this would be 300 for
infants and children.
F. International Tolerances
There are currently no Codex maximum residue levels for mustard
greens, lettuce or head and stem brassicas.
[FR Doc. 00-4791 Filed 2-29-00; 8:45 am]
BILLING CODE 6560-50-F