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Chlorfenapyr (American Cyanamid). August 26, 1999. Petition for Pesticide Tolerances for residues in or on imported citrus at 0.5 ppm. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/1999/August/Day-26/p22190.htm
[Federal Register: August 26, 1999 (Volume 64, Number 165)]
[Notices]
[Page 46677-46680]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26au99-61]
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ENVIRONMENTAL PROTECTION AGENCY
[PF-880; FRL-6090-1]
Notice of Filing; Pesticide Petition
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
chlorfenapyr in or on various food commodities.
DATES: Comments, identified by the docket control number PF-880, must
be received on or before September 27, 1999.
ADDRESSES: By mail submit written comments to: Information and Records
Integrity Branch, Public Information and Services Division (7502C),
Office of Pesticides 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.
Comments and data may also be submitted electronically by following
the instructions under ``SUPPLEMENTARY INFORMATION (CBI).'' No
confidential business information (CBI) 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
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: Ann Sibold, Insecticide Branch,
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. 212, Crystal
Mall #2, 1921 Jefferson Davis Highway, Arlington, VA 22202, (703) 305-
6502; e-mail: sibold.ann@epa.gov.
SUPPLEMENTARY INFORMATION: EPA has received a pesticide petition as
follows proposing the establishment and/or amendment of regulations for
residues of chlorfenapyr 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 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.
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-880] (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@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 control number (PF-880) and appropriate
petition number. Electronic comments on this proposed rule may be filed
online at many Federal Depository Libraries.
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: August 19, 1999.
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 views of the
petitioner. EPA is publishing the petition summary verbatim without
editing it in any way. The petition summary announces the
[[Page 46678]]
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.
American Cyanamid
PP 6E4683
EPA has received a pesticide petition (6E4683) from American
Cyanamid, P.O. Box 400, Princeton, NJ 08543-0400 proposing, pursuant to
section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR 180 by
establishing a tolerance for residues of chlorfenapyr [4-bromo-2-(4-
chlorophenyl)-1-(ethoxymethyl)-5-(trifluoromethyl)-1-pyrrole-3-
carbonitrile] in or on the raw agricultural commodity (RAC) imported
citrus at 0.5 ppm. As citrus processed commodities fed to food animals
may be transferred to milk and edible tissues, tolerances are also
proposed for the following ruminant food items, milk at 0.01 parts per
million (ppm); milk fat at 0.15 ppm; meat at 0.01 ppm; and meat
byproducts (including fat) at 0.10 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 nature of the residues of chlorfenapyr in
plants is adequately understood and the residue of concern in citrus
consists of the parent molecule. Expressed on a whole basis, the parent
compound accounted for 56-75% of the total radioactive residue (TRR)
98% of which was associated with the external rinse and peel.
2. Analytical method. The gas chromatography (GC) analytical method
M2284, which is proposed as the enforcement method for the residues of
chlorfenapyr in citrus, has a limit of detection (LOD) of 0.01 ppm
(0.025 ppm for juice), and a limit of quantitation (LOQ) of 0.05 ppm.
3. Magnitude of residues. Extensive citrus field trials have been
conducted over multiple growing seasons in all major citrus growing
regions of the United States, Argentina, and Brazil. The results of
these studies indicate that at application rates of 1.05 lbs active
ingredient acre (ai/A), the maximum expected chlorfenapyr residues are
0.4 ppm in oranges, 0.38 ppm in lemons, and 0.27 ppm in grapefruit
samples harvested at a minimum of 7 days following the last
application. These field trial data are adequate to support the
proposed tolerance of 0.5 ppm in/on citrus. The results of processing
studies indicate that chlorfenapyr residues do not concentrate in
molasses and juice. The actual concentration factors in dried pulp
(2.4x), and citrus oil (70x) are well below the maximum theoretical
concentration factors for these commodities. Although citrus oil is not
considered to be a ready-to-eat item and is not expected to contribute
to the dietary exposure, a tolerance at 35 ppm (0.5 ppm x 70) is
proposed for enforcement purposes.
B. Toxicological Profile
1. Acute toxicity. Based on EPA's toxicity category criteria, the
acute toxicity category for chlorfenapyr technical is Category II or
moderately toxic (signal word WARNING), and the acute toxicity category
for the 2SC formulation is Category III or slightly toxic (signal word
CAUTION). Males appear to be more sensitive to the effects of
chlorfenapyr than females. The acute toxicity profile indicates that
absorption by the oral route appears to be greater than by the dermal
route. The following are the results from the acute toxicity tests
conducted on the technical material.
i. Rat oral LD<INF>50</INF> 441/1,152 milligrams/kilograms/body
weight (mg/kg/bwt) male/female -- Toxicity Category II.
ii. Rabbit dermal LD<INF>50</INF>: > 2,000 mg/kg/bwt male/female --
Toxicity Category III.
iii. Acute inhalation. LC<INF>50</INF> 0.83/ > 2.7 milligrams per
liter (mg/L) male/female -- Toxicity Category III.
iv. Eye irritation. Moderately irritating -- Toxicity Category III.
v. Dermal irritation. Non-irritating -- Toxicity Category IV.
vi. Dermal sensitization. Non-sensitizer -- Non Sensitizer.
vii. Acute neurotoxicity. No observed adverse effect level (NOAEL)
45 mg/kg bwt. Not an acute neurotoxicant.
2. Genotoxicty. Chlorfenapyr technical (94.5% a.i.) was examined in
a battery of in vitro, and in vivo tests to assess its genotoxicity and
its potential for carcinogenicity. These tests are summarized below.
i. Microbial/microsome mutagenicity assay. Non-mutagenic.
ii. Mammalian Cell Chinese hampster ovary/hypoxanthine guanine
phophoribosyl transferase (CHO/HGPRT) Mutagenicity Assay. Non-
mutagenic.
iii. In vivo micronucleus assay. Non-genotoxic.
iv. In vitro--chromosome aberration assay in CHO. Non-clastogenic.
v. In vitro--chromosome aberration assay in CHLC. Non-clastogenic.
vi. Unscheduled DNA synthesis (UDS) assay. Non-genotoxic.
3. Reproductive and developmental toxicity. Chlorfenapyr is neither
a reproductive or developmental toxicant and is not a teratogenic agent
in the Sprague-Dawley rat, or the New Zealand white rabbit. This is
demonstrated by the results of the following studies:
i. Rat oral teratology. NOAEL for maternal toxicity 25 mg/kg bwt/
day, and NOAEL for fetal/development toxicity 225 mg/kg/bwt/day.
ii. Rabbit oral teratology. NOAEL for maternal toxicity 5 mg/kg/
bwt/day and NOAEL for fetal/development toxicity 30 mg/kg/bwt/day.
iii. Rat 2-generation reproduction. NOAEL for parental toxicity/
growth and offspring development 60 ppm (5 mg/kg/bwt/day). NOAEL for
reproductive performance 600 ppm (44 mg/kg/bwt/day).
4. Subchronic toxicity. The following are the results of the
subchronic toxicity tests that have been conducted with chlorfenapyr:
i. 28-Day rabbit dermal. NOAEL 100 mg/kg/bwt/day.
ii. 28-Day rat feeding. NOAEL > 600 ppm (< 71.6 mg/kg/bwt/day).
iii. 28-Day mouse feeding. NOAEL > 160 ppm (< 32 mg/kg/bwt/day).
iv. 13-Week rat dietary. NOAEL 150 ppm (11.7 mg/kg/bwt/day).
v. 13-Week mouse dietary. NOAEL 40 ppm (8.2 mg/kg/bwt/day).
vi. 13-Week dog dietary. NOAEL 120 ppm (4.2 mg/kg/bwt/day).
5. Chronic toxicity. Chlorfenapyr is not oncogenic in either
Sprague Dawley rats or CD-1 mice and is not likely to be carcinogenic
in humans. The following are the results of the chronic toxicity tests
that have been conducted with chlorfenapyr:
i. 1-Year neurotoxicity in rats. NOAEL 60 ppm (2.6/3.4 mg/kg/bwt/
day male/female).
ii. 1-Year dog dietary. NOAEL 120 ppm (4.0/4.5 mg/kg/bwt/day male/
female).
iii. 24-Month rat dietary. NOAEL for chronic effects 60 ppm (2.9/
3.6 mg/kg/bwt/day male/female) and NOAEL for oncogenic effects 600 ppm
(31/37 mg/kg/bwt/day male/female).
iv. 18-Month mouse dietary. NOAEL for chronic effects 20 ppm (2.8/
3.7 mg/kg/bwt/day male/female) and NOAEL for oncogenic effects 240 ppm
(34.5/44.5 mg/kg/bwt/day male/female).
6. Animal metabolism. A metabolism study was conducted in Sprague
Dawley rats at approximately 20 and 200 mg/kg/bwt using radiolabeled
chlorfenapyr. Approximately 65% of the administered
[[Page 46679]]
dose was eliminated during the first 24 hours (62% in feces and 3% in
urine) and by 48 hours following dosing, approximately 85% of the dose
had been excreted (80% in feces and 5% in urine). The absorbed
chlorfenapyr-related residues were distributed throughout the body and
detected in tissues and organs of all treatment groups. The principal
route of elimination was via feces, mainly as unchanged parent plus
minor N-dealkylated, debrominated and hydroxylated oxidation products.
The metabolic pathway of chlorfenapyr in the laying hen and the
lactating goat was also similar to that in laboratory rats.
7. Metabolite toxicology. The parent molecule is the only moiety of
toxicological significance which needs regulation in plant and animal
commodities.
8. Endocrine disruption. Collective organ weights and
histopathological findings from the 2-generation rat reproduction
study, as well as from the subchronic and chronic toxicity studies in
two or more animal species, demonstrate no apparent estrogenic effects
or effects on the endocrine system. There is no information available
which suggests that chlorfenapyr would be associated with endocrine
effects.
C. Aggregate Exposure
1. Food. For purposes of assessing the potential dietary exposure,
a Theoretical Maximum Residue Contribution (TMRC) has been calculated
from the tolerance of chlorfenapyr in/on citrus at 0.5 ppm. This
exposure assessment is based on very conservative assumptions, namely
100% of all citrus is treated with chlorfenapyr and that the residues
of chlorfenapyr in citrus are at the tolerance level. Although there
are no other established United States permanent tolerances for
chlorfenapyr, a petition for a permanent tolerance at 0.5 ppm in
cottonseed is pending at the Agency. Therefore, the dietary exposures
to residues of chlorfenapyr in or on food will be limited to residues
in cottonseed, citrus and food and feed items derived from them. As
dried citrus pulp is a dairy and beef cattle feed item, a cold feeding
study with dairy cattle was conducted. Since this study demonstrated
that measurable residues of chlorfenapyr may occur in milk, meat, and
meat byproducts, appropriate residue tolerances for these items are
proposed. The contribution of the citrus tolerances alone to the daily
consumption uses only 0.23% of the reference dose (RfD) for the overall
U.S. population. The combined contributions of the citrus and the
pending cottonseed tolerances to the daily consumption uses less than
1% (actual 0.85%) of the RfD for the overall U.S. population and less
than 3% (actual 2.23%) and less than 1% (actual 0.89%) of the RfD for
children aged 1-6 and for non-nursing infants, respectively.
2. Drinking water. This proposed tolerance is for imported citrus.
Since there are no currently registered uses of chlorfenapyr in the
United States, potential exposure from drinking water is not relevant
to this petition.
3. Non-dietary exposure. This petition is for a tolerance on
imported citrus. As there are no registered uses of chlorfenapyr in the
United States at present, the potential for non-dietary exposure is not
pertinent to this petition.
D. Cumulative Effects
The pyrrole insecticides represent a new class of chemistry with a
unique mechanism of action. The parent molecule, AC 303,630 is a pro-
insecticide which is converted to the active form, CL 303,268, via
rapid metabolism by mixed function oxidases (MFOs). The active form
uncouples oxidative phosphorylation in the insect mitochondria by
disrupting the proton gradient across the mitochondrial membrane. The
production of adenosine triphosphate (ATP) is inhibited resulting in
the cessation of all cellular functions. Because of this unique
mechanism of action, it is highly unlikely that toxic effects produced
by chlorfenapyr would be cumulative with those of any other pesticide
chemical.
In mammals, there is a lower titer of MFOs, and chlorfenapyr is
metabolized by different pathways (including dehalogenation, oxidation
and ring hydroxylation) to other polar metabolites without any
significant accumulation of the potent uncoupler, CL 303,268. In the
rat, approximately 85% of the administered dose is excreted in the
feces within 48 hours, thereby reducing the levels of AC 303,630 and CL
303,268 that are capable of reaching the mitochondria. This
differential metabolism of AC 303,630 to CL 303,268 in insects versus
to other polar metabolites in mammals is responsible for the selective
insect toxicity of the pyrroles.
E. Safety Determination
1. U.S. population. The RfD of 0.03 mg/kg/bwt/day for the residues
of chlorfenapyr in citrus is calculated by applying a 100-fold safety
factor to the overall NOAEL of 3 mg/kg/bwt/day. This NOAEL is based on
the results of the chronic feeding studies in the rat and mouse and the
2-generation reproduction study in the rat. The theoretical maximum
residue contribution (TMRC) for the proposed tolerances in citrus
alone, (0.0000692 mg/kg/bwt/day), will utilize only 0.23% of the RfD
for the general U.S. population and the combined TMRC for the proposed
chlorfenapyr tolerances in cottonseed, citrus, milk, and meat
(0.0002558 mg/kg/bwt/day) will utilize approximately 0.85% of the RfD
for the general U.S. population.
2. Infants and children. The TMRC in milk consumed by a non-nursing
infant (> 1-year of age) is 0.0002435 mg/kg/bwt/day. The combined
tolerances will use less than 1% (actual 0.89%) of the RfD for non-
nursing infants. The TMRC in milk consumed by a child (1-6 years of
age) is 0.0003886 mg/kg/bwt/day. The combined TMRC for the proposed
chlorfenapyr tolerances in cottonseed, citrus meat and milk consumed by
a child 1-6 years of age is 0.0006708 mg/kg/bwt/day, which is less than
3% (actual 2.23%) of the RfD. Therefore, the results of the toxicology
and metabolism studies support both the safety of chlorfenapyr to
humans based on the intended use as an insecticide-miticide on citrus
and cottonseed and the granting of the requested tolerances in
cottonseed, citrus, milk, milk fat solids, meat, and meat by-products.
Based on the conservative assumptions used in proposing the above
tolerances and the absence of other non-dietary routes of exposure to
chlorfenapyr, and since the calculated exposures are well below 100% of
the reference dose, there is a reasonable certainty that no harm will
result from aggregate exposure to residues of chlorfenapyr, including
all anticipated dietary exposure and all other non-occupational
exposures. The use of a 100-fold safety factor ensures an acceptable
margin of safety for both the overall U.S. population as well as
infants and children. As the toxicology database (reproduction/
developmental and teratology studies) is complete, valid and reliable,
no additional safety factor is needed.
The 100-fold margin of safety is adequate to assure a reasonable
certainty of no harm to infants and children from the proposed use. As
stated earlier, the NOAEL is based on the effects observed in the rat
and mouse chronic oncogenicity studies, (reduced bwt gains, increased
globulin and cholesterol values and increased liver weights in the rat
and reduced bwt gains and vacuolation of white matter of the mouse
brain), the 1-year neurotoxicity study in the rat, (reduced bwt gains
and vacuolar myelinopathy of
[[Page 46680]]
the brain and spinal cord that is completely reversible following
termination of treatment and is not associated with any damage to
neuronal cell bodies or axons; vacuolation of the white matter is a
consequence of edema (water) formation between the myelin layers which
result from the unrestricted movement of ions across the cell
membranes) and the 2-generation rat reproduction study, (reduced bwt
gains for parental animals and reduced pup body weights for the F1 and
F2 litters; however no behavioral changes were observed in either F1 or
F2 offsprings in the 2-generation reproduction study). Moreover, as the
NOAELs for fetal/developmental toxicity are significantly higher than
those for maternal toxicity, the results indicate that chlorfenapyr is
neither a developmental toxicant nor a teratogenic agent in either the
Sprague-Dawley rat or New Zealand White rabbit. Thus, there is no
reliable information to indicate that there would be a variability in
the sensitivities of infants and children and adults to the effects of
exposure to chlorfenapyr.
F. International Tolerances
Section 408(b)(4) of the amended FFDCA requires EPA to determine
whether a maximum residue level has been established for the pesticide
chemical by the Codex Alimentarius Commission. There is neither a Codex
proposal, nor Canadian, or Mexican tolerances/limits for residues of
chlorfenapyr in/on citrus. Therefore, a compatibility issue is not
relevant to the proposed tolerance.
[FR Doc. 99-22190 Filed 8-25-99; 8:45 am]
BILLING CODE 6560-50-F