Document ID: EPA-HQ-OPP-2007-0506-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-01-23T05:00Z

<COMPANY FEDERAL REGISTER DOCUMENT SUBMISSION TEMPLATE  (1/1/2006)>

<EPA Registration Division contact: [insert name and telephone number
with area code]>

 

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please insert “NA-Remove” and maintain the outline.  The comment
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<TEMPLATE:>

<Bayer CropScience>

<[Insert petition number]>

<	EPA has received a pesticide petition ([insert petition number]) from
Bayer CropScience, 2 T.W. Alexander Drive, P.O. Box 12014, Research
Triangle Park, NC  27709 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.>

<(Options (pick one)>

<	1. by establishing a tolerance for residues of>

<	2. to establish an exemption from the requirement of a tolerance for>

<	  SEQ CHAPTER \h \r 1 Cyfluthrin; cyano
(4-fluoro-3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimethyl-cy
clopropanecarboxylate in or on the raw agricultural commodity alfalfa,
forage at 5.0 parts per million (ppm), and alfalfa, hay at 15.0 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 FDDCA; 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.>    SEQ CHAPTER \h \r 1 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.   SEQ CHAPTER \h \r 1 Adequate analytical
methodology using GC/EC detection is available for enforcement purposes.
>

<	3. Magnitude of residues.  A total of 12 field trials were conducted
to measure the magnitude of cyfluthrin
[cyano(4-fluoro-3-phenoxyphenyl)methyl-3-(2,2-dichloroethenyl)-2,2-dimet
hylcyclopropanecarboxylate residues in/on alfalfa following two foliar
spray applications of BAYTHROID 2E (emulsifiable concentrate formulation
containing 2.0 lb ai/gal) to alfalfa at a target rate of 0.044 lb
ai/A/application (0.043 to 0.047 lb ai/A/application) prior to each of
four cuttings. The interval between applications was 5 to 9 days.  No
adjuvants were added to the spray mixture. All applications were made
using ground-based equipment. In each of the field trials, duplicate
composite samples of both alfalfa forage and hay were collected at each
of four cuttings at commercial maturity at a pre-harvest interval (PHI)
of 5 to 8 days after the application just preceding cutting
(applications 2, 4, 6, and 8). Single composite samples of both alfalfa
forage and hay were collected at the first cutting from the control
plots when the forage and hay were at commercial maturity, 5 to 8 days
following the last treatment to the corresponding treated plot. 

The residue of cyfluthrin was quantitated in alfalfa forage and hay by
gas chromatography/mass spectrometry (GC/MS) using a stable isotopically
labeled internal standard. The limit of quantitation (LOQ) for
cyfluthrin residue was 0.01 ppm for both alfalfa forage and hay. 

The HAFT cyfluthrin residue was 5.65 ppm in/on alfalfa forage (37% dry
matter) for all cuttings at commercial maturity at a PHI of 6 days
(target PHI is 7 days). The maximum cyfluthrin residue was 5.88 ppm
in/on alfalfa forage (37% dry matter) for all cuttings at commercial
maturity at a PHI of 6 days. However, if residues were adjusted to 35%
dry matter, the HAFT and maximum cyfluthrin residue found in another
sample with 21% dry matter would have been 7.52 ppm and 7.68 ppm,
respectively. The HAFT cyfluthrin residue was 15.27 ppm in/on alfalfa
hay (74% dry matter) for all cuttings at commercial maturity at a PHI of
7 days (target PHI is 7 days). The maximum cyfluthrin residue was 16.49
ppm in/on alfalfa hay (74% dry matter) for all cuttings at commercial
maturity at a PHI of 7 days. However, if harvest had occurred at 89% dry
matter, the HAFT and maximum cyfluthrin residue would have been 18.37
ppm and 19.84 ppm, respectively.

 

<B. Toxicological Profile>

<	1. Acute toxicity.    SEQ CHAPTER \h \r 1 There is a full battery of
acute toxicity studies for cyfluthrin supporting an overall toxicity
Category II for the active ingredient.>

<	2. Genotoxicty.   SEQ CHAPTER \h \r 1 Based on the results of a
complete genotoxicity database, there is no evidence of mutagenicity
activity in a battery of studies, 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 assay in rat hepatocytes. All tests were negative for
genotoxicity.  >

<	3. Reproductive and developmental toxicity.   SEQ CHAPTER \h \r 1 A
developmental toxicity study in rats with beta-cyfluthrin indicated a
maternal NOAEL of 3 mg/kg bw/day based on reduced body weight gain and
food consumption at 10 mg/kg bw/day.  The developmental NOAEL was 10
mg/kg bw/day, based on reduced fetal body weights and increased skeletal
variations at the maternally toxic dose of 40 mg/kg bw/day.   An oral
developmental toxicity study in rabbits with cyfluthrin indicated a
maternal NOAEL of 20 mg/kg bw/day and a maternal LOAEL of 60 mg/kg
bw/day, based on decreased body weight gain and decreased food
consumption during the dosing period. A fetal NOAEL of greater than 180
mg/kg bw/day was also observed in this study.   A two-generation 
reproduction study in rats indicated parental and offspring NOAELs of
3.0 mg/kg bw/day, based on reductions in body weight and food
consumption in the parents and course tremors and decreased mean litter
weights in the offspring at 9.0 mg/kg bw/day.  The NOAELs were confirmed
in a supplemental two-generation study. >

<	4. Subchronic toxicity.    SEQ CHAPTER \h \r 1  In a 90-day feeding
study in rats with beta-cyfluthrin the resulting NOAEL was 9.5 mg/kg
bw/day, based on decreased body weight gain, gait abnormalities, skin
lesions and mortality seen at 37.5 mg/kg bw/day.   A six-month toxicity
feeding study in dogs established a NOAEL of 5 mg/kg bw/day for
cyfluthrin.  The LOAEL was 15 mg/kg bw/day based on clinical signs of
neurotoxicity and gastrointestinal disturbances.

Two subchronic inhalation studies were conducted with cyfluthrin.  In
the first study cyfluthrin was administered via inhalation for five days
per week for 4 weeks.  The resulting NOAEL was 0.44 mg/m3, based on
treatment-related behavioral effects, body weight decreases and clinical
chemistry changes at 6.0 mg/m3.  In the second study cyfluthrin was
administered via inhalation for 13 weeks.  The resulting NOAEL was 0.09
mg/m3, based treatment-related behavioral effects in females and
increased urinary protein in males at 0.71 mg/m3. >

<	5. Neurotoxicity.    SEQ CHAPTER \h \r 1 An acute neurotoxicity study
in rats was conducted using beta-cyfluthrin.  The NOAEL for this study
is 2 mg/kg, based on clinical signs, changes in FOB parameters and
decreases in motor activity noted at 10 mg/kg.  In a subchronic
neurotoxicity study with beta-cyfluthrin the resulting NOAEL was
8 mg/kg, based on clinical signs, changes in FOB parameters, and
slightly decreased body weight gain and food consumption at 27
mg/kg/day.  In a developmental neurotoxicity study with beta-cyfluthrin
the resulting maternal and offspring NOAEL was 11.0 mg/kg body
weight/day based on decreased body weight and a change in startle
response in PND 22 male pups.  The database for cyfluthrin is complete
and there is no indication of pre- or post-natal susceptibility.  There
is no indication of delayed neurotoxicity as a result of exposure to
cyfluthrin.  >

<	6. Chronic toxicity.    SEQ CHAPTER \h \r 1 A 12-month chronic feeding
study in dogs established a no-observed adverse effect level (NOAEL) of
2.4 mg/kg bw/day (males) and 3.6 mg/kg bw/day (females). The lowest
effect level (LOAEL) for this study is established at 11 mg/kg bw/day,
clinical signs, gait abnormalities and abnormal postural reactions in
males and females.  A 24-month chronic feeding/ carcinogenicity study in
rats demonstrated a NOAEL of 2.6 mg/kg bw/day and LOAEL of 11.6 mg/kg
bw/day, based on decreased body weights.  A 24-month carcinogenicity
study in mice was conducted.  The NOAEL was 31.9 (males) and 140.6
(females) mg/kg/bw/day.  The LOAEL was 114.8 mg/kg bw/day (males) based
on ear skin lesions and reduced body weight gains, and 309.7 mg/kg
bw/day (females) based on clinical signs, macroscopic and microscopic
pathology findings and reduced body weights, body weight gains, and food
consumption. Under the conditions of these studies, there was no
evidence of carcinogenic potential.  >

<	7. Animal metabolism.    SEQ CHAPTER \h \r 1 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.  >

<	8. Metabolite toxicology.   SEQ CHAPTER \h \r 1 The residue of concern
is cyfluthrin.  No toxicology data have been required for cyfluthrin
metabolites. Available data indicate that the metabolites are much less
toxic than the parent and are not of concern. >

<	9. Endocrine disruption.   SEQ CHAPTER \h \r 1 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.     SEQ CHAPTER \h \r 1 The insecticide
cyfluthrin has uses on food crops in agriculture and also non-dietary
uses for homeowners.  Aggregate exposure for cyfluthrin should consider
dietary exposure, both food and drinking water and non-dietary exposure
both applicator and post application exposure.  For the dietary exposure
an acute Population Adjusted Dose (aPAD) of 0.02 mg/kg bw/day was
selected using an uncertainty factor of 100 based on the acute
neurotoxicity study.  A chronic Population Adjusted Dose (cPAD) of 0.024
mg/kg bw/day was based on the chronic toxicity test in dogs with an
uncertainty factor of 100.>

 the registered uses of cyfluthrin are well within acceptable limits for
all sectors of the population.  Potential dietary exposures from food
were estimated using the DEEM™ software system (Exponent, Inc.) and
the 1994-96 and 1998 USDA consumption data. For the chronic analysis,
mean residue values were calculated from the appropriate field trial
studies conducted for cyfluthrin and submitted as part of the cyfluthrin
petitions.  For the acute analysis, the entire distribution of field
trial residue values was used for non-blended and partially blended
commodities and the mean value used for blended commodities.  Processing
factors were obtained from GLP processing studies for the appropriate
commodities.  Percent crop treated values were based on EPA’s dietary
risk assessments (15-Aug-02) and on Bayer CropScience projections for
crops added since then.  For alfalfa 100 % crop treated was assumed.
Using these data and assumptions for the acute analysis the most highly
exposed sub-population was All Infants at 89 % (0.0178 mg/kg bw/day for
food incl. drinking water) of the acute PAD with the US Population at 45
% (0.009 mg/kg bw/day for food incl. drinking water) of the acute PAD. 
For the chronic analysis, the most highly exposed sub-population was
Children 1-2 utilizing 19.4 % (0.0047 mg/kg bw/day for food incl.
drinking water) of the chronic PAD.  The US Population utilized 5.6 %
(0.0013 mg/kg bw/day for food incl. drinking water) of the chronic PAD.
 Actual exposures are likely to be much less because of the many
conservative assumptions incorporated in this analysis.  >

<	ii. Drinking Water.  The estimated drinking water concentration was
taken form   SEQ CHAPTER \h \r 1 US EPA’s calculation of the drinking
water estimated environmental concentrations (EEC) for cyfluthrin
published in the Federal Register (FR Vol 70, no. 176, 13-Sep-05). These
EECs were directly incorporated into the calculation of the dietary
exposure. >

<	2. Non-dietary exposure.    SEQ CHAPTER \h \r 1 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 Food Quality
Protection Act 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
no-observed-effect-level (NOEL).  Results for each potential exposed
subpopulation (of adults, children 1-6 years, and infants <1 year) were
compared to the systemic absorbed dose NOEL 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 3800, 2700, and 2500 for adults, children (1-6
years), and infants (<1 year), respectively.  The non-dietary methods
used in the analyses can be characterized as highly conservative 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.  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. 
>

<D. Cumulative Effects>

<	  SEQ CHAPTER \h \r 1 Cyfluthrin is a member of the pyrethroid class
of pesticides. EPA is not currently following a cumulative risk approach
based on a common mechanism of toxicity for the pyrethroids while
research on this subject is still ongoing (FR Vol. 70, No. 176,
13-Sep-05).  >

<E. Safety Determination>

<	1. U.S. population.    SEQ CHAPTER \h \r 1 Using the assumptions and
data described above, based on the completeness and reliability of the
toxicity data, it is concluded that chronic dietary exposure to the
registered and proposed uses of cyfluthrin will utilize at most 5.6 % of
the chronic PAD for the US Population.  The acute dietary exposure to
cyfluthrin will utilize at most 45 % of the acute PAD.  The actual
exposure both acute and chronic is likely to be much less as more
realistic data and models are developed.  EPA generally has no concern
for exposures below 100% of the PAD because the PAD represents the level
at or below which daily aggregate exposure over a lifetime will not pose
appreciable risk to human health.   Potential exposure from drinking
water was included in the calculations.  Large margins of safety exist
for the non-dietary and aggregate exposure.  Therefore, there is a
reasonable certainty that no harm will occur to the US Population from
aggregate exposure (food, drinking water and non-dietary) to residues of
cyfluthrin.  >

<	2. Infants and children.    SEQ CHAPTER \h \r 1 The relevant toxicity
studies as discussed in the toxicology section above show no extra
sensitivity of infants and children to cyfluthrin, therefore the FQPA
safety factor can be removed. Using the assumptions and data described
in the exposure section above, the percent of the chronic PAD that will
be used for exposure to residues of cyfluthrin in food for Children 1-2
(the most highly exposed sub-population) is 19.4 %.  Infants utilize 5.5
% of the chronic PAD.  For the acute assessment children 1-2 utilize 84
% of the acute PAD and Infants utilize 89 % of the acute PAD.  As in
the adult situation, drinking water exposure was included in the
calculation of the PAD.  As with adults, large margins of safety exist
for the non-dietary and aggregate exposure for infants and children. 
Therefore, there is a reasonable certainty that no harm will occur to
infants and children from aggregate exposure to residues of cyfluthrin. 
>

<F. International Tolerances>

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 for apples at 0.5 ppm, cattle milk at 0.01 ppm, cotton seed at 0.05
ppm, maize at 0.05 ppm, peppers, sweet at 0.2 ppm, rape seed at 0.05 ppm
and tomatoes at 0.5 ppm.  There is no existing international tolerance
for the proposed new use.  >