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Cyfluthrin (IR-4). April 15, 1998. Pesticide Tolerance Petition. Federal Register
http://www.epa.gov/fedrgstr/EPA-PEST/1998/April/Day-15/p9395.htm
[Federal Register: April 15, 1998 (Volume 63, Number 72)]
[Notices]
[Page 18411-18420]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15ap98-90]
[[Page 18411]]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-801; FRL-5781-9]
Notice of Filing of Pesticide Petitions
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 the docket control number PF-801, must
be received on or before May 15, 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. 119FF, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION.'' No confidential
business information should be submitted through e-mail.
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
table below:
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Office location/
Product Manager telephone number Address
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Sidney Jackson (PM 5)......... Rm. 268, CM #2, 703- 1921 Jefferson
305-7610, e- Davis Hwy,
mail:jackson.sidney@e Arlington, VA
pamail.epa.gov.
Bipin Gandhi (PM 5)........... Rm. 4W53, CS #2, 703- Do.
308-8380, e-mail:
gandhi.bipin@epamail.
epa.gov.
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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 support granting of the
petition. Additional data may be needed before EPA rules on the
petition.
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-801] (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:
opp-docket@epamail.epa.gov
Electronic comments must be submitted as an ASCII file avoiding the
use of special characters and any form of encryption. Comment 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 FRL-5781-9 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
requirements.
Dated: April 1, 1998
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.
1. Interregional Research Project
PP 2E4101
EPA has received a pesticide petition (PP 2E4101) from the
Interregional Research Project Number 4 (IR-4), 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 the insecticide cyfluthrin, [cyano[4-fluoro-3-
phenoxyphenyl]-methyl-3-[2,2- dicloroethenyl]-2,2-
dimethylcyclopropanecarboxylate] in or on the raw agricultural
commodity dried hops at 20.0 parts per million (ppm) and to remove the
established tolerance for fresh hops at 4.0 ppm. EPA has determined
that the petition contains data or information regarding the elements
set forth in section 408(d)(2) of the Federal Food Drug and Cosmetic
Act (FFDCA); however, EPA has not fully evaluated the sufficiency of
the submitted data at this time or whether the data supports granting
of the proposed tolerance. Additional data may be needed before EPA
rules on the petition. This notice includes a summary of the petition
prepared by Bayer Corporations (Bayer), the registrant.
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.
[[Page 18412]]
2. Analytical method. Adequate analytical methodology (gas liquid
chromatography with an electron capture detector) is available for
enforcement purposes. The methodology was successfully validated by
EPA's Beltsville laboratory in support of tolerances on cottonseed. The
enforcement methodology has been submitted to the Food and Drug
Administration for publication in the Pesticide Analytical Manual Vol.
II (PAM II). Because of the long lead time for publication of the
method in PAM II, the analytical methodology is being made available in
the interim to anyone interested in pesticide enforcement when
requested from Calvin Furlow, Public Response and Program Resource
Branch, Field Operations Division (7502C), Office of Pesticide
Programs, U.S. Environmental Protection Agency, 401 M St., SW.,
Washington, DC 20460. Office location and telephone number: Rm. 119FF,
CM #2, 1921 Jefferson-Davis Hwy., Arlington, VA 22202, (703) 305-5232.
The established tolerances for residues of cyfluthrin in/on eggs,
milks, fat, meat and meat by-products of cattle, goats, hogs, horses,
sheep and poultry are adequate to cover secondary residues resulting
from the proposed use as delineated in 40 CFR 180.6(a)(2).
3. Magnitude of residues. Import tolerances for cyfluthrin are
presently established on fresh hops at 4.0 ppm and on dried hops at
20.0 ppm. IR-4 has conducted field trials in Washington, Oregon and
Idaho in order to support expansion of the tolerances to include the
domestic production of hops in the United States.
The residue data submitted to the EPA by IR-4 consist of three
trials, one each in Washington, Oregon and Idaho. In each trial, hops
were planted in three plots, two treated and one untreated. Cyfluthrin
(Baythroid 2) was applied by foliar (ground) application at a rate of
0.05 pounds(lb) active ingredient(ai)/acre(A) to one plot and 0.1 lb
ai/A to another. Five separate applications were made with an interval
of 7-days between the last application and harvest.
Residues of cyfluthrin were detected in all treated samples from
each trial and no interferences were detected in samples from control
plots. The residue data are consistent for each trial. Cyfluthrin
applied at 0.05 lb ai/A was detected from 0.44 to 0.78 ppm on fresh
hops and from 1.83 to 2.36 ppm on dried hops. At 0.10 lb ai/A, residues
were detected at 1.10 to 2.70 ppm on fresh hops and 3.76 to 7.57 ppm on
dried hops.
B. Toxicological Profile
The data base for cyfluthrin is essentially complete. Data lacking
but desirable are an acute neurotoxicity study in rats and a 90-day
neurotoxicity study in rats. Although these data are lacking, Bayer
believes the available toxicity data are sufficient to support the
proposed tolerance and these missing data will not significantly change
its risk assessment. Bayer has committed to submit the acute
neurotoxicity study and the 90-day neurotoxicity study.
1. Acute toxicity. Results of acute toxicity tests show an acute
oral lethal dose (LD<INF>50</INF>) grater than or equal to 16.2
milligram (mg)/ kilogram (kg), a dermal (LD<INF>50</INF>) >5,000 mg/kg,
inhalation lethal concentration (LC<INF>50</INF> greater than or equal
to 0.468 mg/liter(L), primary eye irritation and primary dermal
irritation show toxicity categories III and IV, respectively. Dermal
sensitization tests conducted show that cyfluthrin is not a dermal
sensitizer.
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 effect
level (NOEL) of 10 mg/kg/day (highest dose tested). An oral
developmental toxicity study in rabbits with a maternal NOEL of 20 mg/
kg/day and a maternal lowest effect level (LEL) of 60 mg/kg/day, based
on decreased body weight gain and decreased food consumption during the
dosing period. A fetal NOEL of 20 mg/kg/day and a fetal LEL of 60 mg/
kg/day were also observed in this study. The LEL was based on increased
resorptions and increased postimplantation loss.
A developmental toxicity study in rats by the inhalation route of
administration with a maternal NOEL of 0.0011 mg/l and a LEL of 0.0047
mg/l, based on reduced mobility, dyspnea, piloerection, ungroomed coats
and eye irritation. The fetal NOEL is 0.00059 mg/l and the fetal LEL is
0.0011 mg/l, based on sternal anomalies and increased incidence of
runts. A second developmental toxicity study in rats by the inhalation
route of administration has been submitted to the Agency. A 3-
generation reproduction study in rats with a systemic NOEL of 2.5 mg/
kg/day and a systemic LEL of 7.5 mg/kg/day due to decreased parent and
pup body weights. The reproductive NOEL and LEL are 7.5 mg/kg/day and
22.5 mg/kg/day respectively.
4. Subchronic toxicity. In a 28-day oral toxicity study in rats,
cyfluthrin demonstrated a NOEL of 20 mg/kg/day. The lowest-observed-
effect level (LOEL) was 80 (40) mg/kg/day in both sexes based on
clinical signs of nerve toxicity, decreases in body weight gain, and
changes in liver and adrenal weights. The high dose was 80 mg/kg/day
during the first and third weeks and 40 mg/kg/day during the second and
fourth weeks.
In a six month dog feeding study established a NOEL at 5 mg/kg/day
for male and females. The LOEL for this study was 15 mg/kg/day for both
sexes, based on neurological effects (hindlimb abnormalities) and
gastrointestinal disturbances.
A 21-day repeated dose dermal toxicity study, male and female rats
were treated with cyfluthrin by dermal occlusion at target doses of 0,
100, 340, or 1,000 mg/kg/day for 6 hours/day (average actual dose
levels were 0, 113, 376 or 1,077 mg/kg/day). No mortality was observed,
and there were no treatment-related effects on body weight,
ophthalmology, organ weights, clinical biochemistry, or hematology. The
LOEL for dermal effects was 376 mg/kg/day for male and female Sprague-
Dawley rats based on gross and histological skin lesions. The NOEL for
dermal effects was 113 mg/kg/day. The LOEL for systemic effects was
1,077 mg/kg/day based on decreased food consumption, red nasal
discharge and urine staining. The NOEL for systemic effects was 376 mg/
kg/day.
5. Chronic toxicity. A 12-month chronic feeding study in dogs with
a NOEL of 4 mg/kg/day. The LEL for this study is established at 16 mg/
kg/day, based on slight ataxia, increased vomiting, diarrhea and
decreased body weight.
A 24-month chronic feeding/carcinogenicity study in rats showed a
NOEL of 2.5 mg/kg/day and LEL of 6.2 mg/kg/day, based on decreased body
weights in males, decreased food consumption in males, and inflammatory
foci in the kidneys in females.
6. Carcinogenicity. A 24-month carcinogenicity study in mice was
conducted. There were no carcinogenic effects observed under the
conditions of the study.
A 24-month chronic feeding/carcinogenicity study in rats was
conducted. There were no carcinogenic effects observed under the
conditions of the study.
[[Page 18413]]
Cyfluthrin has been classified as a Group E chemical (evidence of
non-carcinogenicity for humans) by the Agency. The classification was
based on a lack of convincing evidence of carcinogenicity in adequate
studies with two animal species, rat and mouse.
7. 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.
8. Ednocrine effects. No special studies investigating potential
estrogenic or endocrine effects of cyfluthrin have been conducted.
However, the standard battery of required studies has been completed.
These studies include an evaluation of the potential effects on
reproduction and development, and an evaluation of the pathology of the
endocrine organs following repeated or long-term exposure. According to
Bayer no endocrine effects were noted in any of the studies.
C. Aggregate Exposure
1. Dietary exposure. In examining aggregate exposure, FFDCA section
408 requires that EPA take into account available and reliable
information concerning exposure from the pesticide residue in the food
in question, residues in other foods for which there are tolerances,
residues in ground water or surface water that is consumed as drinking
water, and other non-occupational exposures through pesticide use in
gardens, lawns, or buildings (residential and other indoor uses).
Dietary exposure to residues of a pesticide in a food commodity are
estimated by multiplying the average daily consumption of the food
forms of that commodity by the tolerance level or the anticipated
pesticide residue level. The Theoretical Maximum Residue Contribution
(TMRC) is an estimate of the level of residues consumed daily if each
food item contained pesticide residues equal to the tolerance. In
evaluating food exposures, EPA takes into account varying consumption
patterns of major identifiable subgroups of consumers, including
infants and children. The TMRC is a ``worst case'' estimate since it is
based on the assumptions that food contains pesticide residues at the
tolerance level and that 100% of the crop is treated by pesticides that
have established tolerances. If the TMRC exceeds the Reference Dose
(RfD) or poses a lifetime cancer risk that is greater than
approximately one in a million, EPA attempts to derive a more accurate
exposure estimate for the pesticide by evaluating additional types of
information (anticipated residue data and/or percent of crop treated
data) which show, generally, that pesticide residues in most foods when
they are eaten are well below established tolerances.
2. Food. Under a petition to establish tolerances for cyfluthrin in
or on citrus (PP 4F4313 and FAP 4H5687, the EPA has recently performed
a chronic dietary exposure/risk assessment for cyfluthrin using a RfD
of 0.025 mg/kg body weight(bwt)/day, based on a NOEL of 50 ppm (2.5 mg/
kg bwt/day) and an uncertainty factor of 100. The NOEL was determined
in a 2-year rat feeding study. The endpoint effects of concern were
decreased body weights in males and inflammation of the kidneys in
females at the LEL of 6.2 mg/kg/day. This dietary exposure/risk
assessment estimated the current dietary exposure for the U.S.
population resulting from established tolerances, including the current
4 ppm tolerance on fresh hops, is 0.002907 mg/kg/bwt day. This
represents 11.6% of the RfD. The exposure to children (1-6 years old),
the subgroup population exposed to the highest risk was 0.00662 mg/kg/
bwt/day or 26.4% of the RfD. The current action will increase the
exposure to 0.003266 mg/kg/bwt day or 13% of the RfD for the U.S.
population and 0.006622 mg/kg/bwt day or 26.4% or the RfD for children
(1-6 years old). Generally speaking, 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 the RfD. Therefore,
Bayer concludes that the chronic dietary risk of cyfluthrin, as
estimated by the dietary risk assessment, does not appear to be of
concern.
3. Drinking water. Cyfluthrin is immobile in soil, therefore, will
not leach into ground water. Additionally, due to 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, Bayer does not anticipate dietary exposures to cyfluthrin
from drinking water.
4. 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. Reliable data to
determine aggregate exposures from these sources are currently not
available. However, determinations of worst case exposure from
inhalation in indoor settings (continuous exposure at saturation vapor
concentration) indicated that adequate margins of safety existed even
under these conditions. Since this evaluation greatly overestimated
exposure, the contribution to aggregate exposure from inhalation in
normal uses would be expected to be negligible. Estimations of outdoor
residential exposure have been required for cyfluthrin in a data call-
in issued in 1995. These data are being generated by the Outdoor
Residential Exposure Task Force (ORETF). However, available data show
that the acute dermal toxicity of cyfluthrin is very low, with the
LD<INF>50</INF> being greater than 5,000 mg/kg, the highest dose
tested. Sub-acute (21-day) dermal toxicity data showed only localized
(skin) effects at higher level exposures (1,000 mg/kg/day and 340 mg/
kg/day). Other than skin effects at these high exposure levels, no
effects were observed at any exposure levels, the highest level tested
being 1,000 mg/kg/day. The use rate for cyfluthrin on residential turf
is 1 g (1,000 mg) active ingredient per 1,000 square feet which would
indicate that potential exposures would be well below levels tested. In
addition, the localized skin effects seen at the prolonged higher
exposures in animal tests have not been reported for non-occupational
exposures to cyfluthrin in currently accepted uses, indicating that
exposures are below the threshold of any observable effects. Indoor
uses are limited to areas with little or no contact, so exposures would
be expected to be even less. Thus, the dermal route of exposure does
not appear to be significant and the contribution to aggregate exposure
from dermal contact would be expected to be negligible.
D. Cumulative Effects
In consideration of potential cumulative effects of cyfluthrin and
other substances that have a common mechanism of toxicity, Bayer
concludes that there are currently no available data or other reliable
information indicating that any toxic effects produced by cyfluthrin
would be cumulative with those of other chemical compounds; thus only
the potential risks of cyfluthrin have been considered in this
assessment of its aggregate exposure.
E. Safety Determination
1. U.S. population. Using the conservative exposure assumptions
described above and based on the completeness and reliability of the
toxicity data it can be concluded that total aggregate exposure to
cyfluthrin from all current uses as well as the proposed tolerance will
utilize little more than 13% of the RfD for the U.S. population. EPA
generally has no concerns for exposures below 100% of
[[Page 18414]]
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. 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.
FFDCA section 408 provides that EPA may apply an additional safety
factor for infants and children in the case of threshold effects to
account for pre- and post- natal effects and the completeness of the
toxicity database. Based on current toxicological data requirements,
the toxicology database for cyfluthrin relative to pre- and post-natal
effects is complete. The NOELs observed in the developmental and
reproduction study are equivalent or higher than the NOEL from the 2-
year rat feeding study, used with a 100 fold uncertainty factor to
establish the reference dose. Therefore, Bayer believes that an
additional uncertainty factor is not warranted and that the RfD at
0.025 mg/kg/day is appropriate for assessing aggregate risk to infants
and children.
Using the conservative exposure assumptions described above,
cyfluthrin residues resulting from established tolerances, including a
tolerance of 20 ppm on dry hops, would utilize 26.4% of the RfD for
children (1-6 years old), the subgroup population exposed to the
highest risk. Generally, EPA has no cause for concern if the exposure
is less than 100% of the RfD. Therefore, based on the completeness and
the reliability of the toxicity data and the conservative exposure
assessment, Bayer concludes that there is a reasonable certainty that
no harm will result to infants and children from aggregate exposure to
the residues of cyfluthrin, including all anticipated dietary exposure
and all other non-occupational exposures.
F. International Tolerances
A Codex maximum residue levels (MRLs) or 20 ppm has been
established for residues of cyfluthrin on dried hops.
[FR Doc. 98-9395 Filed 4-14-98; 8:45 am]
BILLING CODE 6560-50-F