cyfluthrin (Baythroid) Pesticide Tolerance Petition Filing 3/97
ENVIRONMENTAL PROTECTION AGENCY
Bayer Corporation; Pesticide Tolerance Petition Filing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice of filing.
SUMMARY: This notice announces the filing of a pesticide petition proposing
regulations establishing tolerances for residues of the pyrethroid cyfluthrin
in or on the raw agricultural commodities (RACs) group citrus, fruits and to
establish a maximum residue limit for cyfluthrin on citrus oil and dried pulp.
This notice includes a summary of the petition that was prepared by Bayer
DATES: Comments, identified by the docket control number [PF-717], must be
received on or before April 14, 1997.
ADDRESSES: By mail, submit written comments to Public Response and Program
Resources Branch, Field Operations Division (7506C), Office of Pesticide
Programs, Environmental Protection Agency, 401 M St. SW., Washington, DC
20460. In person, bring comments to Rm. 1132, CM #2. 1921 Jefferson Davis
Highway, Arlington, VA 22202.
Comments and data may also be submitted electronically be sending electronic
mail (e-mail) to: email@example.com. 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 in ASCII file format. All comments and data in electronic
form must be identified by docket control number [PF-717]. Electronic comments
on this notice may be filed online at many Federal Depository Libraries.
Additional information on electronic submissions can be found below this
Information submitted as a comments 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: By mail: George T. LaRocca, Product Manager
(PM) 13, Registration Division (7505C), Office of Pesticide Programs,
Environmental Protection Agency, 401 M St., SW., Washington, DC 20460. Office
location, telephone number, and e-mail address: Rm. 200, CM #2, 1921 Jefferson
Davis Highway, Arlington, VA 22202. (703) 305-6100;
SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions (PP) 4F4313
and 4H5687 from Bayer Corporation, 8400 Hawthorn Road, Kansas City, MO 64120.
The petition proposes, pursuant to section 408(d) of the Federal Food Drug and
Cosmetic Act, 21 U.S.C. section 346a, to amend 40 CFR 180.436 to establish
tolerances for residues of the insecticide cyfluthrin, [cyano[4-fluoro-3-
dimethylcyclopropanecarboxylate] in or on the raw agricultural commodities
group citrus, fruits at 0.2 part per million (ppm) and the processed
commodities citrus, oil and citrus, dried pulp at 0.3 part per million (ppm).
The proposed analytical method is gas chromatography equipped with electron
As required by section 408(d) of the FFDCA, as recently amended by the Food
Quality Protection Act, Bayer Corporation included in the petition a summary
of the petition and authorization for the summary to be published in the
Federal Register in a notice of receipt of the petition. The summary
represents the views of Bayer Corporation; EPA is in the process of evaluating
the petition. As required by section 408(d)(3) EPA is including the summary as
a part of this notice of filing. EPA may have made minor edits to the summary
for the purpose of clarity.
I. Petition Summary
A. Residue Chemistry
1. Use pattern. Baythroid 2 will be used on citrus only in California and
Arizona, to control citrus thrips. A dosage of 6.4 fluid ounces of Baythroid 2
(0.1 lb active ingredient per acre) will be applied by ground equipment only,
in sufficient water for complete coverage of foliage in dilute or concentrate
sprays, but not less than 25 gallons per acre. A single application may be
made per season.
2. 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.
3. Analytical methodology. Adequate analytical methodology (Gas liquid
chromatography with an electron capture detector) is available for enforcement
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).
4. Magnitude of the residue. On December 20, 1993, Bayer Corp. filed a
petition (PP 4F4313) for a tolerance for residues of cyfluthrin on the raw
agricultural commodity, citrus and proposed food/feed additive regulation
(4H5687) for citrus oil, citrus dried pulp, and citrus molasses under section
409 of FFDCA. A request was filed May 2, 1996, to withdraw the feed additive
petition for citrus molasses, submitted in response to EPA's determination
that citrus molasses is no longer considered a significant feed item. See
EPA's final 860 Series Residue Chemistry Guidelines (860.1000) published as
public drafts on August 25, 1995 (60 FR 44343) (formerly Table II of
Subdivision O, Residue Chemistry, of the Pesticide Assessment Guidelines).
The food/feed additive petition for citrus oil and citrus dried pulp has been
revised to propose these tolerances at 0.3 ppm under section 408 instead
section 409 in accordance the Food Quality Protection Act.
The proposed section 408 tolerance for cyfluthrin on citrus is 0.2 ppm. The
highest average residue found in crop field trials for cyfluthrin on citrus
fruits was 0.06 ppm. A processing study showed that in producing citrus oil
and dried pulp residues concentrated 530 (a concentration factor of 5.3 x ).
Thus with this information it is likely that cyfluthrin residues of 0.32 ppm
(0.06 x 5.3) could occur in citrus oil and dried pulp.
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 Corp. believes there is
sufficient toxicity data to support the proposed tolerance and these missing
data will not significantly change the risk assessment. In a letter dated
November 2, 1995, Bayer Corp. has committed to submit the acute neurotoxicity
study by December 1996 and the 90-day neurotoxicity study by May 1997.
The toxicology data cited in support of the tolerance include: 1. Chronic
effects. A 12-month chronic feeding study in dogs with a no-observed effect
level (NOEL) of 4 mg/kg/day. The lowest effect level (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 with 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
2. Acute toxicity. For the purposes of assessing acute dietary risk, the
Agency has used an oral developmental toxicity study in rabbits with a
maternal NOEL of 20 mg/kg/day and a maternal 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.
3. 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.
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.
4. Other. 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.
C. Aggregate Exposure
A chronic dietary exposure/risk assessment was performed for cyfluthrin using
a Reference Dose (RfD) of 0.025 mg/kg 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. For purposes of this dietary exposure/risk assessment tolerance
level residues were used and percent crop treated assumption made for some of
the commodities. The current estimated dietary exposure for the overall U.S.
population resulting from established tolerances 0.009420 mg/kg/ bwt/day or
37.6 percent of the RfD. The current estimated dietary exposure for the
subgroup population exposed to the highest risk, non- nursing infants less
than 1 year old, 0.025266 mg/kg bwt/day or 101 percent of the RfD. Although
the estimate of dietary exposure for the subgroup, non-nursing infants less
than 1 year old, is slightly higher than the Agency's level of concern, i.e.,
greater than 100 percent of the RfD, Bayer Corp. believes that actual exposure
and risk would be lower. The basis for this is that the risk reflects a higher
than actual dietary exposure because it assumes that 100 percent of most
commodities for which cyfluthrin tolerances exist have cyfluthrin residues and
that all will bear residue levels as high as the tolerances. In reality, all
these commodities will not have residues of this pesticide and actual levels
will be lower than tolerance levels. To assess the dietary exposure from the
establishment of the proposed citrus tolerances, the incremental increase in
dietary exposure was taken from the dietary exposure analysis conducted by the
Agency. These estimates are based on the assumption that 100 percent of the
citrus crop in the U.S. would be treated with cyfluthrin. In reality, this use
of cyfluthrin will be limited to California and Arizona only for the control
of citrus thrips. For the prior six years, cyfluthrin has been utilized in the
California's Central Valley under the provisions of a FIFRA section 18
Emergency Exemption. In 1995, approximately 77,000 out of 170,000 acres (46
percent) of the citrus grown in Central Valley was treated with cyfluthrin.
Assuming that a similar proportion of acreage, that is 46 percent, would be
treated throughout California and Arizona, the total estimated acreage treated
with cyfluthrin would be 94,000 acres. This represents only 9.4 percent of the
1,026,000 fruit bearing acres of citrus grown in the U.S. Therefore, a 10
percent treated crop adjustment to the dietary exposure can be considered
Adding this incremental exposure to the current estimated dietary exposure
results in a total dietary exposure for the U.S. population of 0.0094934 mg/kg
bwt/day representing 38 percent of RfD. The highest exposure group, non-
nursing infants will increase only very slightly, to 0.253653 mg/kg bwt/day
representing 101.4 percent of the RfD. As described above, although this still
slightly exceeds the RfD, actual exposure is expected to be much less.
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.
Other potential sources of exposure to residues of pesticides are residues in
drinking water and exposure from non-occupational sources. Based on available
studies used in previous EPA assessments, Bayer Corp. does not anticipate
exposures to cyfluthrin in drinking water. Non-occupational exposure to
cyfluthrin may occur as a result of inhalation or contact from indoor
residential, indoor commercial, and outdoor residential uses. The Agency does
not currently have reliable data to determine aggregate exposures from these
sources. However, determinations of worst case exposure from inhalation in
indoor settings (continuous exposure at saturation vapor concentration) should
indicate that adequate margins of safety exist even under these conditions.
Since this evaluation greatly overestimates 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 LD50
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 1000 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.
In consideration of potential cumulative effects of cyfluthrin and other
substances that have a common mechanism of toxicity, 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.
D. Safety Determinations
1. U.S. population in general. 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 and maximum residue levels for
the use of cyfluthrin on citrus will utilize little more than 38 percent of
the RfD for the U.S. population. EPA generally has no concerns for exposures
below 100 percent 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. Thus, it can be concluded that there is a reasonable
certainty that no harm will result from aggregate exposure to cyfluthrin
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 two generations, as well as any observed
The toxicology data cited in support of the tolerance include: An oral
developmental toxicity study in rats with a maternal and fetal 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 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 and is currently under review.
A three-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
The Agency used the rabbit developmental toxicity study with a maternal NOEL
of 20 mg/kg/day to assess acute dietary exposure and determine a margin of
exposure (MOE) for the overall U.S. population and certain subgroups. Since
this toxicological endpoint pertains to developmental toxicity the population
group of concern for this analysis was women aged 13 and above, the subgroup
which most closely approximates women of child-bearing age. The MOE is
calculated as the ration of the NOEL to the exposure. For this analysis 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
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 no-effect-
levels 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, 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
Using the conservative exposure assumptions described above, EPA has
previously concluded that the residues from use of cyfluthrin on citrus will
contribute the highest incremental increase to the aggregate exposure to the
population subgroup children 1 to 6 years old, accounting for 3.9 percent of
the RfD and giving a total dietary exposure from all uses of 95.9 percent of
the RfD for this subgroup. However, this assessment was based on an assumption
of 100 percent crop treated. When adjusted for a 10 percent crop treatment (as
described in section B. above) the incremental exposure is negligible,
increasing form the current 0.022985 mg/kg bwt /day (91.9 percent of the RfD)
to 0.231522 mg /kg bwt/day or 92.6 percent of the RfD. For nursing infants
current exposure is 0.005692 mg/kg bwt/day or 22.8 percent of the RfD. The use
on citrus would increase exposure to 0.0057377 mg/kg bwt/day representing 22.9
percent of the RfD. For children 7 to 12, current exposure is 0.015237 mg/kg
bwt/ day, 60.9 percent of the RfD. The use on citrus would increase this to
0.153416 mg/kg bwt /day, or 61.4 percent of the RfD. For non-nursing infants,
the current is exposure is calculated to be 0.025267 mg/kg bwt /day, 101
percent of the RfD. The use on citrus would increase this slightly to
0.0253653 or 101.4 percent. Both the current and the resulting calculated
exposure from adding the estimated exposure from citrus exposure are slightly
higher than the Agency's level of concern. However, the Agency has previously
assessed this risk in the evaluation of PP 2F4137 and believed the actual
exposure and risk would be much lower. The basis for this was the fact that
this calculated exposure assumes, with the exception of citrus, that 100
percent of the commodities for which cyfluthrin tolerance exists have residues
and that the residues all bear residues as high as the tolerance levels. In
reality, it is known that not all commodities will have cyfluthrin residues
and actual levels will be lower than the tolerance values. In addition, the
food commodity that contributes most to this slight exceedence is milk, at
88.2 percent of the RfD; 71.2 percent from milk fat and 17 percent from whole
milk and milk sugars. However, metabolism data indicate that essentially all
of the cyfluthrin will concentrate in milk fat and there would be negligible
amounts in other components. Thus the 17 percent contribution from non-milk
fat portions of milk is an overestimation of actual exposure, which would be
below the RfD.
Generally, EPA has no cause for concern if the total aggregate exposure is
less than the RfD, therefore it may be concluded that there is a reasonable
certainty of no harm will result to infants and children.
The available data indicate that there is reasonable certainty of no harm from
the incremental exposure resulting from the potential residues of cyfluthrin
from the use of Baythroid 2, EPA Reg. No. 3125- 351, on citrus. Thus in
accordance with the provisions of the FFDCA as amended August 3, 1996,
regulations to establish the tolerance and maximum residue levels to support
this use can be effected.
F. International Tolerances
There are no Codex maximum residue levels (MRLs) established for residues
ofcyfluthrin on citrus fruits or any resulting processed products.
II. Public Record
Interested persons are invited to submit comments on this notice of filing.
Comments must bear a notation indicating the docket control number, [PF-717].
All written comments filed in response to this petition will be available in
the Public Response and Program Resources Branch, at the address given above
from 8:30 a.m. to 4 p.m., Monday through Friday, except legal holidays.
A record has been established for this notice under docket control number [PF-
717] 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 public record is located in Rm. 1132 of the
Public Response and Program Resources Branch, Field Operations Division
(7506C), Office of Pesticide Programs, Environmental Protection Agency,
Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA.
Electronic comments can be sent directly to EPA at: firstname.lastname@example.org
Electronic comments must be submitted as ASCII file avoiding the use of
special characters and any form of encryption.
The official record for this notice, as well as the public version, as
described above will be kept in paper form. Accordingly, EPA will transfer all
comments received electronically into printed, paper form as they are received
and will place the paper copies in the official record which will also include
all comments submitted directly in writing. The official record is the paper
record maintained at the address in "ADDRESSES" at the beginning of this
Authority: 21 U.S.C. 346a.
List of Subjects
Environmental Protection, Administrative practice and procedure, Agricultural
commodities, Pesticides and pests, Reporting and recordkeeping requirements.
Dated: March 7, 1997.
Stephen L. Johnson,
Director, Registration Division, Office of Pesticide Programs.
[FR Doc. 97-6516 Filed 3-13-97; 8:45 am]