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Flufenacet and its metabolites (Bayer). March 29, 2000. Petition for pesticide tolerances. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2000/March/Day-29/p7742.htm
[Federal Register: March 29, 2000 (Volume 65, Number 61)]
[Notices]
[Page 16598-16602]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29mr00-66]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-925; FRL-6496-9]
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 a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket control number PF-925, must be
received on or before April 28, 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-925 in the subject line on the first page of your
response.
FOR FURTHER INFORMATION CONTACT: By mail: James Tompkins, Registration
Support Branch, Registration Division (7505W), Office of Pesticide
Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200
Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703)
305-5697; e-mail address: Tompkins.Jim@epamail.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
[[Page 16599]]
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-925. 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-925 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) 305-5697.
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 Wordperfect 6.1/
8.0 or ASCII file format. All comments in electronic form must be
identified by docket control number PF-925. 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 Cosmetic 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: March 21, 2000.
James Jones,
Director, Registration Division, Office of Pesticide Programs.
Summary of Petition
The petitioner summary of the pesticide petition is printed below
as required by section 408(d)(3) of the FFDCA. The summary of the
petition was prepared by the petitioner and represents the view of the
petitioners. EPA is publishing the petition summary verbatim without
editing it 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.
[[Page 16600]]
Bayer Corporation
0F6095
EPA has received a pesticide petition (0F6095) from Bayer
Corporation, 8400 Hawthorn Road, 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 180.527 by establishing a
tolerance for residues of flufenacet, N-(4-fluorophenyl)-N-(1-
methylethyl)-2-5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl oxyacetamide
and metabolites containing the 4-fluoro-N-methylethyl benzenamine
moiety in or on the raw agricultural commodities (RAC) wheat grain,
wheat forage, wheat hay, wheat bran, wheat germ, wheat straw, seed-
grass forage, seed-grass forage from re-growth, seed-grass hay from re-
growth, seed-grass straw, sweet corn kernel plus cob with husks removed
at 0.5, 9.0, 1.0, 1.0, 0.5, 0.5, 18.0, 0.1, 0.5, 0.5, 0.05 parts per
million (ppm), respectively. 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 nature of the residue in field corn, sweet
corn, wheat, seed-grasses, soybeans, rotational crops, and livestock is
adequately understood. The residues of concern for the tolerance
expression are flufenacet parent and its metabolites containing the 4-
fluoro-N-methylethyl benzenamine moiety. Based on the results of animal
metabolism studies it is unlikely that secondary residues would occur
in animal commodities from the use of flufenacet on field corn, sweet
corn, soybeans, wheat, and seed-grasses.
2. Analytical method. An adequate analytical method, gas
chromatography/mass spectrometry (GC/MS) with selected ion monitoring,
is available for enforcement purposes. Because of the long lead time
from establishing these tolerances to publication of the enforcement
methodology in the Pesticide Analytical Manual, Vol. II, the analytical
methodology is being made available in the interim to anyone interested
in pesticide enforcement when requested from: Calvin Furlow, Public
Information and Records Integrity Branch, Information Resources and
Services Division (7502C), Office of Pesticide Programs, Environmental
Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number: (703-305-5937).
3. Magnitude of residues. Time-limited tolerances exist for the
combined residues of flufenacet, N-(4-fluorophenyl)-N-(1-methylethyl)-
2-5-(trifluoromethyl)-1,3,4-thiadiazol-2-yloxyacetamide and metabolites
containing the 4-fluoro-N-methylethyl benzenamine moiety in or on field
corn grain at 0.05 ppm, field corn forage at 0.4 ppm, field corn stover
at 0.4 ppm, soybean seed at 0.1 ppm, alfalfa forage at 0.1 ppm, alfalfa
hay at 0.1 ppm, alfalfa seed at 0.1 ppm, clover forage at 0.1 ppm,
clover hay at 0.1 ppm, Crop Group 15 (cereal grains) at 0.1 ppm, Crop
Group 16 (forage, stover and hay of cereal grains) at 0.1 ppm, and
Group 17 (grass forage and grass hay) at 0.1 ppm.
B. Toxicological Profile
1. Acute toxicity--i. Technical grade flufenacet has a low to
moderate order of toxicity in rats by the oral route of exposure. The
acute oral LD50 was 1,617 milligrams/kilograms (mg/kg) for
males and 589 mg/kg for females.
ii. A dermal toxicity study on technical grade flufenacet revealed
low acute toxicity to rats. The dermal LD50 for both sexes
was > 2,000 mg/kg, the highest dose tested (HDT).
iii. An acute inhalation study on technical grade flufenacet showed
low toxicity in rats with a 4-hour liquid aerosol LC50 for
males and females of > 3,740 mg/m3 air, the highest
concentration tested.
iv. An eye irritation study on technical grade flufenacet in
rabbits showed minimal irritation to the conjunctiva completely
reversible within 7 days.
v. A dermal irritation study on technical grade flufenacet in
rabbits did not produced any irritation.
vi. Skin sensitization studies on technical grade flufenacet in
guinea pigs have produced equivocal results. A skin sensitization
potential was exhibited under the conditions of a maximization test,
whereby, there was no skin sensitization potential when tested by the
Buehler topical closed patch technique.
2. Genotoxicity. Flufenacet was negative for mutagenic/genotoxic
effects in a Gene mutation/in vitro assay in bacteria, a Gene mutation/
in vitro assay in Chinese hamster (CH) lung fibroblasts cells, a
Cytogenetics/in vitro assay in CH ovary cells, a Cytogenetics/in vivo
mouse micronucleus assay, and an in vitro unscheduled DNA synthesis
assay in primary rat hepatocytes.
3. Reproductive and developmental toxicity--i. A 2-generation rat
reproduction study with a parental systemic no observed adverse effect
level (NOAEL) of 20 ppm (1.4 mg/kg/day in males and 1.5 mg/kg/day in
females) and a reproductive NOAEL of 20 ppm (1.3 mg/kg/day) and a
parental systemic lowest observed adverse effect level (LOAEL) of 100
ppm (7.4 mg/kg/day in males and 8.2 mg/kg/day in females), based on
increased liver weight in F1 females and hepatocytomegaly in
F1 males, and a reproductive LOAEL of 100 ppm (6.9 mg/kg/
day) based on increased pup death in early lactation (including
cannibalism) for F1 litters and the same effects in both
F1 and F2 pups at the high dose level of 500 ppm
(37.2 mg/kg/day in males and 41.5 mg/kg/day in females), respectively.
ii. A rat developmental study with a maternal NOAEL of 25 mg/kg/day
and with a maternal LOAEL of 125 mg/kg/day based on decreased body
weight gain initially and a developmental NOAEL of 25 mg/kg/day and a
developmental LOAEL of 125 mg/kg/day based on decreased fetal body
weight, delayed development mainly delays in ossification in the skull,
vertebrae, sternebrae, and appendages, and an increase in the incidence
of extra ribs.
iii. A rabbit developmental study with a maternal NOAEL of 5 mg/kg/
day and a maternal LOAEL of 25 mg/kg/day based on histopathological
finds in the liver and a developmental NOAEL of 25 mg/kg/day and a
developmental LOAEL of 125 mg/kg/day based on increased skeletal
variations.
4. Subchronic toxicity--i. A 84-day rat feeding study with a NOAEL
less than 100 ppm (6.0 mg/kg/day) for males and a NOAEL of 100 ppm (7.2
mg/kg/day) for females and with a LOAEL of 100 ppm (6.8 mg/kg/day) for
males based on suppression of thyroxine (T4) level, and a LOAEL of 400
ppm (28.8 mg/kg/day) for females based on hematology, and clinical
chemistry findings.
ii. A 13-week mouse feeding study with a NOAEL of 100 ppm (18.2 mg/
kg/day for males and 24.5 mg/kg/day for females), and a LOAEL of 400
ppm (64.2 mg/kg/day for males and 91.3 mg/kg/day for females) based on
histopathology of the liver, spleen and thyroid.
iii. A 13-week dog dietary study with a NOAEL of 50 ppm (1.70 mg/
kg/day for males and 1.67 mg/kg/day for females), and a LOAEL of 200
ppm (6.90 mg/kg/day for males and 7.20 mg/kg/day for females), based on
evidence that the bio-transformation capacity of the liver has
[[Page 16601]]
been exceeded (as indicated by increase in LDH, liver weight, ALK and
hepatomegaly), globulin and spleen pigment in females, decreased T4 and
ALT values in both sexes, decreased albumin in males, and decreased
serum glucose in females.
iv. A 21-day rabbit dermal study with the dermal irritation NOAEL
of 1,000 mg/kg/day for males and females, and a systemic NOAEL of 20
mg/kg/day for males and 150 mg/kg/day for females, and a systemic LOAEL
of 150 mg/kg/day for males and 1,000 mg/kg/day for females based on
clinical chemistry data (decreased T4 and FT4 levels in both sexes) and
centrilobular hepatocytomegaly in females.
5. Chronic toxicity--i. A 1-year dog chronic feeding study with a
NOAEL was 40 ppm (1.29 mg/kg/day in males and 1.14 mg/kg/day in
females), and a LOAEL of 800 ppm (27.75 mg/kg/day in males and 26.82
mg/kg/day in females) based on increased alkaline phosphatase, kidney,
and liver weight in both sexes, increased cholesterol in males,
decreased T2, T4 and ALT values in both sexes, and increased incidences
of microscopic lesions in the brain, eye, kidney, spinal cord, sciatic
nerve, and liver.
ii. A rat chronic feeding/carcinogenicity study with a NOAEL less
than 25 ppm (1.2 mg/kg/day in males and 1.5 mg/kg/day in females), and
a LOAEL of 25 ppm (1.2 mg/kg/day in males and 1.5 mg/kg/day in females)
based on methemoglobinemia, and multi-organ effects in blood, kidney,
spleen, heart, and uterus. Under experimental conditions the treatment
did not alter the spontaneous tumor profile.
iii. In a mouse carcinogenicity study the NOAEL was less than 50
ppm (7.4 mg/kg/day) for males and the NOAEL was 50 ppm (9.4 mg/kg/day)
for females. The LOAEL was 50 ppm (7.4 mg/kg/day) for males and the
LOAEL was 200 ppm (38.4 mg/kg/day) for females based on cataract
incidence and severity. There was no evidence of carcinogenicity for
flufenacet in this study.
6. Animal metabolism. A rat metabolism study showed that radio-
labeled flufenacet was rapidly absorbed and metabolized by both sexes.
Urine was the major route of excretion at all dose levels and smaller
amounts were excreted via the feces.
7. Metabolite toxicology. A 55-day dog study with subcutaneous
administration of thiadone flufenacet metabolite supports the
hypothesis that limitations in glutathione interdependent pathways and
antioxidant stress result in metabolic lesions in the brain and heart
following flufenacet exposure.
8. Endocrine disruption. EPA is required to develop a screening
program to determine whether certain substances (including all
pesticides and inerts) may have an effect in humans that is similar to
an effect produced by a naturally occurring estrogen, or such other
effect. The Agency is currently working with interested stakeholders,
including other government agencies, public interest groups, industry
and research scientists in developing a screening and testing program
and a priority setting scheme to implement this program. Congress has
allowed 3 years from the passage of FQPA (August 3, 1999) to implement
this program. At that time, EPA may require further testing of this
active ingredient and end use products for endocrine disrupter effects.
Based on the toxicological findings for flufenacet relating to
endocrine disruption effects, flufenacet should be considered as a
candidate for evaluation as an endocrine disrupter when the criteria
are established.
9. Other studies--i. An acute rat neurotoxicity study with a NOAEL
less than 75 mg/kg/day and a LOAEL of 75 mg/kg/day based on decreased
motor activity in males.
ii. A rat subchronic neurotoxicity study with a NOAEL of 120 ppm
(7.3 mg/kg/day in males and 8.4 mg/kg/day in females), and a LOAEL of
600 ppm (38.1 mg/kg/day in males and 42.6 mg/kg/day in females) based
on microscopic lesions in the cerebellum/medulla and spinal cords.
C. Aggregate Exposure
1. Dietary exposure--i. Food. 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. In evaluating food
exposures, varying consumption patterns of major identifiable subgroups
of consumers, including infants and children is taken into account. A
refined dietary risk assessment was performed and adjustments were made
to account for market share and processing factors. The residues in the
diet (food only) are calculated to be 0.000078 mg/kg bwt day or 1.9% of
the RfD for the general U.S. population and 0.000174 mg/kg bwt day or
4.4% of the RfD for non-nursing infants (> 1-year)
ii. Drinking water. Residues of flufenacet in drinking water may
comprise up to 0.0039 mg/kg bwt day (0.0040-0.000078 mg/kg bwt day) for
the U.S. population and 0.0038 mg/kg bwt day (0.00400-0.000174 mg/kg
bwt day) for children 1-6 years old.
The drinking water levels of concern (DWLOCs) for chronic exposure
to flufenacet in drinking water calculated for the U.S. population was
136 parts per billion (ppb) assuming that an adult weighs 70 kg and
consumes a maximum of 2 liters of water per day. For children (1-6
years old), the DWLOC was 37.7 ppb assuming that a child weighs 10 kg
and consumes a maximum of 1 liter of water per day.
The drinking water estimated concentration (DWECs) for ground water
(parent flufenacet and degradate thiadone) calculated from the
monitoring data is 0.03 ppb for chronic concentrations which does not
exceed DWLOC of 37.7 ppb for children (1-6 years old). The DWEC for
surface water based on the computer models PRZM 2.3 and EXAMS 2.97.5
was calculated to be 14.2 ppb for chronic concentration (parent
flufenacet and degradate thiadone) which does not exceed the DWLOC of
37.7 ppb for children (1-6 years old).
2. Non-dietary exposure. There are no non-food uses of flufenacet
currently registered under the Federal Insecticide, Fungicide, and
Rodenticide Act, as amended. No non-dietary exposures are expected for
the general population.
D. Cumulative Effects
Flufenacet is structurally a thiadiazole. EPA is not aware of any
other pesticides with this structure. For flufenacet, EPA has not yet
conducted a detailed review of common mechanisms to determine whether
it is appropriate, or how to include this chemical in a cumulative risk
assessment. After EPA develops a methodology to address common
mechanism of toxicity issues to risk assessments, the Agency will
develop a process (either as part of the periodic review of pesticides
or otherwise) to reexamine these tolerance decisions. Unlike other
pesticides for which EPA has followed a cumulative risk approach based
on a common mechanism of toxicity, flufenacet does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of these tolerance actions, therefore, EPA has not assumed
that flufenacet has a common mechanism of toxicity with other
substances.
E. Safety Determination
1. U.S. population. As presented previously, the exposure of the
U.S. general population to flufenacet is low, and the risks, based on
comparisons to the RfD, are minimal. The margins of safety from the use
of flufenacet are within EPA's acceptable limits. Bayer
[[Page 16602]]
Corporation concludes that there is a reasonable certainty that no harm
will result to the U.S. population from aggregate exposure to
flufenacet residues.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of flufenacet, EPA
considered data from developmental toxicity studies in the rat and
rabbit and a 2-generation reproduction study in the rat. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from pesticide exposure during
prenatal development to one or both parents. Reproduction studies
provide information relating to effects from exposure to the pesticide
on the reproductive capability of mating animals and data on systemic
toxicity. FFDCA section 408 provides that EPA shall apply an additional
tenfold margin of safety for infants and children in the case of
threshold effects to account for prenatal and postnatal toxicity and
the completeness of the data base unless EPA determines that a
different margin of safety will be safe for infants and children.
Although there is no indication of increased sensitivity to young rats
or rabbits following prenatal and/or postnatal exposure to flufenacet
in the standard developmental and reproductive toxicity studies, an
additional developmental neurotoxicity study, which is not normally
required, is needed to access the susceptibility of the offspring in
function/neurological development. Therefore, EPA has required that a
developmental neurotoxicity study be conducted with flufenacet and a
threefold safety factor for children and infants will be used in the
aggregate dietary acute and chronic risk assessment. Although there is
no indication of additional sensitivity to young rats or rabbits
following prenatal and/or postnatal exposure to flufenacet in the
developmental and reproductive toxicity studies; the Agency concluded
that the FQPA safety factor should not be removed but instead reduced
because: (i) There was no assessment of susceptibility of the offspring
in functional/neurological developmental and reproductive studies; (ii)
there is evidence of neurotoxicity in mice, rats, and dogs; (iii) there
is concern for thyroid hormone disruption.
F. International Tolerances
Maximum residue levels are established or proposed for countries of
the European Communities in the following commodities: cereals at 0.5
ppm, corn at 0.5 ppm, potato at 0.1 ppm, sunflower at 0.05 ppm, soybean
at 0.05 ppm, animal meat at 0.05 ppm, animal edible offal's at 0.05
ppm, animal fat at 0.05 ppm, milk at 0.01 ppm, and eggs at 0.05 ppm.
[FR Doc. 00-7742 Filed 3-28-00; 8:45 am]
BILLING CODE 6560-50-F