cyfluthrin (Baythroid) Pesticide Petition Filing 10/98
[Federal Register: November 20, 1998 (Volume 63, Number 224)]
>From the Federal Register Online via GPO Access [wais.access.gpo.gov]
ENVIRONMENTAL PROTECTION AGENCY
Notice of Filing of Pesticide Petitions
AGENCY: Environmental Protection Agency (EPA).
SUMMARY: This notice announces the initial filing of pesticide
petitions proposing the establishment of regulations for residues of
certain pesticide chemicals in or on various food commodities.
DATES: Comments, identified by the docket control number PF-836, must
be received on or before December 21, 1998.
ADDRESSES: By mail submit written comments to: Public Information and
Records Integrity Branch, Information Resources and Services Division
(7502C), Office of Pesticides Programs, Environmental Protection
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically to: opp-
firstname.lastname@example.org. Follow the instructions under ``SUPPLEMENTARY
INFORMATION.'' No confidential business information should be submitted
Information submitted as a comment concerning this document may be
claimed confidential by marking any part or all of that information as
``Confidential Business Information'' (CBI). CBI should not be
submitted through e-mail. Information marked as CBI will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2. A copy of the comment that does not contain CBI must be submitted
for inclusion in the public record. Information not marked confidential
may be disclosed publicly by EPA without prior notice. All written
comments will be available for public inspection in Rm. 1132 at the
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays.
FOR FURTHER INFORMATION CONTACT: The product manager listed in the
Product Manager telephone number Address
Mark Dow PM-03................ Rm. 214, CM #2, 703- 1921 Jefferson
305-5533, e- Davis Hwy,
mail:dow.mark@epamail Arlington, VA
James Tompkins PM-25.......... Rm. 239, CM #2, 703- Do.
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as
follows proposing the establishment and/or amendment of regulations for
residues of certain pesticide chemicals in or on various food
commodities under section 408 of the Federal Food, Drug, and Comestic
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions
contain data or information regarding the elements set forth in section
408(d)(2); however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data supports granting of
the petition. Additional data may be needed before EPA rules on the
The official record for this notice of filing, as well as the
public version, has been established for this notice of filing under
docket control number [PF-836] (including comments and data submitted
electronically as described below). A public version of this record,
including printed, paper versions of electronic comments, which does
not include any information claimed as CBI, is available for inspection
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The official record is located at the address in
``ADDRESSES'' at the beginning of this document.
Electronic comments can be sent directly to EPA at:
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comments and data
will also be accepted on disks in Wordperfect 5.1 file format or ASCII
file format. All comments and data in electronic form must be
identified by the docket number (insert docket number) and appropriate
petition number. Electronic comments on notice may be filed online at
many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Food additives,
Feed additives, Pesticides and pests, Reporting and recordkeeping
Dated: October 27, 1998.
Director, Registration Division, Office of Pesticide Programs.
Summaries of Petitions
Petitioner summaries of the pesticide petitions are printed below
as required by section 408(d)(3) of the FFDCA. The summaries of the
petitions were prepared by the petitioners and represent the views of
the petitioners. EPA is publishing the petition summaries verbatim
without editing them in any way. The petition summary announces the
availability of a description of the analytical methods available to
EPA for the detection and measurement of the pesticide chemical
residues or an explanation of why no such method is needed.
1. Bayer Corporation
EPA has received a pesticide petition (PP 8F5023) from Bayer
Corporation, 8400 Hawthorn Road, Kansas City, MO 64120, proposing
pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance
for residues of cyfluthrin: [cyano[4-fluoro-3-phenoxyphenyl]-methyl-3-
[2,2-dichloroethenyl]-2,2-dimethyl-cyclopropanecarboxylate] in or on
the raw agricultural commodity soybean, bean at 0.03 parts per million
(ppm); soybean, forage at 8.0 ppm; soybean, hay at 4.0 ppm; field corn,
forage at 3.0 ppm; and field corn, fodder at 6.0 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 (gas/liquid
chromatography with an electron capture detector) is available for
3. Magnitude of residues. Cyfluthrin is the active ingredient in
the registered end-use product Baythroid 2 Emulsifiable Pyrethroid
Insecticide, EPA Reg. No. 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
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 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 milligram/kilogram 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 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
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 higher dose levels (HDLs), the body weights
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 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
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
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-- 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 1989 through 1992; and information on the percentages of crops
treated with cyfluthrin.
Cyfluthrin is currently registered for use in alfalfa, carrots,
citrus, cotton, peppers, radishes, sorghum, sunflower, sugarcane, sweet
corn, 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. For potential cyfluthrin
use on soybeans and field corn the impact on the exposure assessment
Chronic dietary exposure estimates with the current label uses for
the overall U.S. population were 0.9% of the reference dose (RfD)
(0.008 mg/kg/ bwt/day). When soybeans, field corn and potatoes were
included the chronic dietary exposure estimates for the overall U.S.
population were 0.8% of the RfD. For the most highly exposed population
subgroups, non-nursing infants (<1 year) and children 1 to 6 years of
age, the exposure was estimated to be 1.9% of the RfD and 1.8% of the
RfD respectively for current label uses and 1.7% of the RfD and 1.7% of
the RfD respectively for label uses plus potatoes, soybeans, field
corn. The apparent drop in the percentage of the RfD when these uses
are added may be explained by the lower limit of detection of the field
trial data for these crops as opposed to the food handling data.
Acute dietary exposures were estimated for the overall U.S.
population, females 13 years and older, children, ages 1-6, and 7-12
years, infants, non-nursing and nursing. The exposure was compared to
the NOAEL of 20 mg/kg/ bwt/day to estimate the margin of exposures
For the all the population subgroups studies the 95th and 99.9th
percentile of exposure the MOEs were calculated to be over 18,000 and
5,000 respectively for all current label uses and 9,900 and 3,800
respectively for all label uses plus potatoes, field corn and soybeans.
For women aged 13 years and older the 95th, and 99.9th percentile
of acute exposure the MOEs were calculated as 66,746 and 18,390
respectively for all current label uses and 33,704 and 11,516
respectively for label uses plus potatoes, field corn, and soybeans.
Lastly, for the potentially highest exposed population subgroups,
non-nursing infants (<1 year) and children ages 1-6 years, the 95th,
and 99.9th percentile of acute exposure to the MOEs were calculated at
53,356; 18,346 and 5,179; 6,319 respectively for all current label uses
and 19,624; 9,964 and 3802; 3943 respectively for label uses plus
potatoes, field corn, and soybeans.
2. Drinking water. Cyfluthrin is immobile in soil, therefore, will
not leach into groundwater. 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
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.
3. 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 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 jassercise 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) and other EPA
publications pursuant to the FQPA.
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 plus soybeans and field corn will utilize less than 2% of
the RfD for chronic dietary exposures and that MOE 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
i. A rat oral developmental toxicity study in which maternal and
fetal NOAELs of 10 mg/kg/bwt/day HDT were observed.
ii. 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 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 postimplantation loss.
iii. 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.
iv. 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 lowest dose tested (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 higher dose levels, 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, 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 pre- and post-natal threshold effects were observed in
studies or to account for incompleteness of the toxicity database.
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, the EPA considers MOE of at least 100 to indicate an
adequate degree of safety. With an additional 3x UF, this would be 300
for infants and children. Using the exposure assessments described
above and based on the described toxicity data aggregate exposure to
infants and children indicate a margin of exposure in excess of 3,800.
Thus, it can be concluded that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to
The available data indicate that there is reasonable certainty of
no harm from the aggregate exposure from all currently registered uses
of cyfluthrin plus potatoes, field corn and soybeans.
G. International Tolerances
There are no Codex maximum residue levels (MRLs) currently
established for residues of cyfluthrin on soybean commodities. There is
a Codex MRLs for maize of 0.05 ppm.
[FR Doc. 98-31066 Filed 11-19-98; 8:45 am]
BILLING CODE 6560-50-F