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Flonicamid (ISK Biosciences). July 7, 2004. Pesticide tolerance petition. Federal Register.
http://www.epa.gov/fedrgstr/EPA-PEST/2004/July/Day-07/p15206.htm
[Federal Register: July 7, 2004 (Volume 69, Number 129)]
[Notices]
[Page 40916-40920]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr07jy04-90]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0132; FRL-7362-5]
Flonicamid; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical 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 ID number OPP-2004-0132, must be
received on or before August 6, 2004.
ADDRESSES: Comments may be submitted electronically, by mail, or
through hand delivery/courier. Follow the detailed instructions as
provided in Unit I. of the SUPPLEMENTARY INFORMATION.
FOR FURTHER INFORMATION CONTACT: Ann Sibold, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6502; e-mail address: sibold.ann@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
You may be potentially affected by this action if you [grow
brassica crops or mustard greens or consume them] Potentially affected
entities may include, but are not limited to:
• Crop production (NAICS code 111)
• Other vegetable (except potato) Farming (NAICS 111219)
• Farming (NAICS code 112 )
• Food manufacturing (NAICS 311)
• Fruit and vegetable preserving and specialty food
manufacturing (NAICS code 3114)
• Pesticide manufacturing (NAICS code 32532)
• Entomological; services, agrecultural; insect control for
crops (NAICS code 115112)
• Agricultural production or harvesting crews (NAICS code 115115)
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 this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
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 Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2004-0132. The official public docket
consists of the documents specifically referenced in this action, any
public comments received, and other information related to this action.
Although, a part of the official docket, the public docket does not
include Confidential Business Information (CBI) or other information
whose disclosure is restricted by statute. The official public docket
is the collection of materials that is available for public viewing at
the Public Information and Records Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA. This
docket facility is open from 8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays. The docket telephone number is (703)
305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although, not all docket materials may be
available electronically, you may still
[[Page 40917]]
access any of the publicly available docket materials through the
docket facility identified in Unit I.B.1. Once in the system, select
``search,'' then key in the appropriate docket ID number.
Certain types of information will not be placed in the EPA
Dockets. Information claimed as CBI and other information whose
disclosure is restricted by statute, which is not included in the
official public docket, will not be available for public viewing in
EPA's electronic public docket. EPA's policy is that copyrighted
material will not be placed in EPA's electronic public docket but will
be available only in printed, paper form in the official public docket.
To the extent feasible, publicly available docket materials will be
made available in EPA's electronic public docket. When a document is
selected from the index list in EPA Dockets, the system will identify
whether the document is available for viewing in EPA's electronic
public docket. Although, not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.
EPA intends to work towards providing electronic access to all of the
publicly available docket materials through EPA's electronic public
docket.
For public commenters, it is important to note that EPA's policy
is that public comments, whether submitted electronically or in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also, include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/
edocket/, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2004-0132. The system is an ``anonymous access'' system, which
means EPA will not know your identity, e-mail address, or other contact
information unless you provide it in the body of your comment.
ii. E-mail. Comments may be sent by e-mail to opp-docket@epa.gov,
Attention: Docket ID number OPP-2004-0132. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID number OPP-2004-0132.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
#2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket
ID number OPP-2004-0132. Such deliveries are only accepted during the
docket's normal hours of operation as identified in Unit I.B.1.
D. How Should I Submit CBI to the Agency?
Do not submit information that you consider to be CBI
electronically through EPA's electronic public docket or by e-mail. You
may claim information that you submit to EPA as CBI by marking any part
or all of that information as CBI (if you submit CBI on disk or CD ROM,
mark the outside of the disk or CD ROM as CBI and then identify
electronically within the disk or CD ROM the specific information that
is 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 docket and EPA's electronic public docket. If you submit
the copy that does not contain CBI on disk or CD ROM, mark the outside
of the disk or CD ROM clearly that it does not contain CBI. Information
not marked as CBI will be included in the public docket and EPA's
electronic public docket without prior
[[Page 40918]]
notice. If you have any questions about CBI or the procedures for
claiming CBI, please consult the person listed 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
ID 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 FFDCA 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.
List of Subjects
Environmental protection, Agricultural commodities, Feed
additives, Food additives, Pesticides and pests, Reporting and
recordkeeping requirements.
Dated: June 21, 2004.
Lois Rossi,
Director, Registration Division, Office of PesticidePrograms.Summary of Petition
The petitioner's summary of the pesticide petition is printed
below as required by FFDCA section 408(d)(3). The summary of the
petition was prepared by ISK Biosciences Corporation, and represents
the view of the petitioner. 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.
ISK Biosciences Corporation
PP 4F6832P
EPA has received a pesticide petition PP 4F6832 from ISK
Biosciences Corporation, 7470 Auburn Road, Suite A, Concord, Ohio,
44077, 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 part 180,
by establishing tolerances for the combined residues of the insecticide
flonicamid (N-(cyanomethyl)-4-trifluoromethyl)-3-pridinecarboxamide
(CA) or N-cyanomethyl-4- trifluoromethylnicotinamide (IUPAC) and its
metabolites, TFNA [4-trifluoromethylnicotinic acid, TFNA-AM (4-
trifluoromethylnicotinamide) and TFNG N-(4-trifluoromethylnicotinoyl)-
glycine) in or on the raw agricultural commodities: Brassica, head and
stem, subgroup 5-A, at 1.5 parts per million (ppm), and mustard greens
at 11 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 support granting of the petition.
Additional data may be needed before EPA rules on the petition.A. Residue Chemistry
1. Plant metabolism. Wheat, potato and peach metabolism studies
were conducted using 14C-pyridyl-flonicamid. The metabolic
profile was similar for all three matrices. The major metabolites for
the various crops were: TFNA in peach, TFNA and TFNG in potato and TFNG in wheat. The metabolism of flonicamid in plants shows the main pathway of metabolism involves hydrolysis of -CN and CONH2
functional groups in the molecule. The metabolism of flonicamid in
plants is well understood.
2. Analytical method. Analytical methodology has been developed to
determine the residues of flonicamid and its three major plant
metabolites, TFNA, TFNG, and TFNA-AM in various crops. The residue
analytical method for the majority of crops includes an initial
extraction with acetonitrile (ACN)/deionized (DI) water, followed by a
liquid-liquid partition with ethyl acetate. The residue method for
wheat straw is similar, except that a C18 solid phase
extraction (SPE) is added prior to the liquid-liquid partition. The
final sample solution is quantitated using a liquid chromatograph (LC)
equipped with a reverse phase column and a triple quadruple mass
spectrometer (MS/MS).
3. Magnitude of residues. Residue data were collected on mustard
greens and the Brassica leafy vegetables, head and stem subgroup during
field trials. Maximum total residues for head and stem Brassica (total
of 12 field trials) ranged from 0.590 ppm (broccoli) to 1.281 ppm
(cabbage). Maximum total residues for mustard greens (total of 6 field
trials) ranged from 2.115 ppm to 10.113 ppm.B. Toxicological Profile
1. Acute toxicity. A battery of acute toxicity studies was
conducted which placed flonicamid technical in Toxicity Category III
for oral LD50, Category IV for dermal LD50,
inhalation LC50, dermal irritation, and eye irritation.
Flonicamid technical is not a dermal sensitizer. In an acute
neurotoxicity study, the no observed adverse effect levels (NOAELs) for
neurotoxicity were 600 milligrams/kilogram (mg/kg) in males and 1,000
mg/kg in female highest doses tested (HDT). The systemic NOAELs were
600 mg/kg in males and 300 mg/kg in females.
2. Genotoxicty. Flonicamid technical did not cause mutations in the
bacterial reverse mutation or mouse lymphoma tests with or without
metabolic activation, chromosome damage in the mouse micronucleus or
cytogenetics tests with and without metabolic activation, an increase
in DNA damage in the comet assay or in an in vivo rat unscheduled DNA
synthesis (UDS) study. Based on the weight of evidence, it is
concluded, that flonicamid technical is not genotoxic.
3. Reproductive and developmental toxicity A developmental toxicity
study in rats resulted in the maternal and developmental no observed
effect levels (NOELs) of 100 mg/kg/day. The maternal lowest observed
effect level (LOEL) was 500 mg/kg/day based on the treatment-related
effects observed on the liver and kidney of the dams in the highest
dose group. The developmental LOEL was 500 mg/kg/day based on the
increases in placental weights and incidences of fetal skeletal
variations seen only at maternally toxic doses of 500 mg/kg/day.
In the rabbit developmental toxicity study, the maternal and
developmental NOELs were 7.5 mg/kg/day and 25 mg/kg/day HDT,
respectively. The maternal LOEL was 25 mg/kg/day based on
[[Page 40919]]
decreased body weights and food consumption. No adverse effects on the
fetuses were observed at the highest dose.
In the multigeneration rat reproduction study, the NOAEL was 300
ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day,
respectively, for males and females) and their offspring. The effects
at the highest dose of 1,800 ppm included the following: Increased
kidney weights and gross and histopathological alterations in the
kidney. Findings noted in the top dose females included delayed vaginal
opening and increased liver, kidney and spleen weights in the F1
generation and reduced ovary and adrenal weights in the parental
generation and decreased uterine weights in the F1 female weanlings.
There was an increase in the follicle stimulating hormone (FSH) and
luteinizing hormone (LH) levels in F1 females tested for these
endpoints. These findings did not affect the reproductive performance
or survival of offspring in the study.4. Subchronic toxicity. The no observed adverse effect level
(NOAEL) for flonicamid technical in the rat 28-day dermal toxicity
study was 1,000 mg/kg/day, which was the highest dose tested.
In a 90-day rat feeding study the NOAEL was established at 200 ppm
(12.11 mg/kg/day) for males and 1,000 ppm (72.3 mg/kg/day) for females.
The NOAELs were based on effects on hematology, triglycerides, and
pathology in the liver and kidney.
In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day
in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm (153.9
mg/kg/day in males and 191.5 mg/kg/day in females) based on hematology
effects and changes in glucose, creatinine, bilirubin, sodium, chloride
and potassium levels, increased liver and spleen weights and
histopathology findings in the bone marrow, spleen and kidney.
In a subchronic toxicity study in dogs with capsule
administration, the NOAEL was 20 mg/kg/day based on findings of severe
toxicity at a dose exceeding the maximum tolerated dose; symptoms
included collapse, prostration and convulsions leading to early
sacrifice at the LOAEL of 50 mg/kg/day.
In a subchronic neurotoxicity study in rats, the NOAEL for dietary
administration was 1,000 ppm (67 mg/kg/day in males and 81 mg/kg/ day
in females) for systemic toxicity based on body weight and food
consumption effects. The NOAEL for neurotoxicity was 10,000 ppm (625
and 722 mg/kg/day in males and females, respectively highest dose tested.5. Chronic toxicity. In the chronic dog study with administration
via using capsules, the NOEL was 8 mg/kg/day. The LOAEL was 20 mg/kg/
day based on reduced body weights in females and effects on the
circulating red blood cells.
In a rat 24-month combined chronic and oncogenicity study,
flonicamid technical was not carcinogenic in rats. The NOAEL was 200
ppm (7.32 mg/kg/day) for males and 1,000 ppm (44.1 mg/kg/day) for
females. The LOAEL was 1,000 ppm for males and 5,000 ppm for females
based on histopathology in the kidney, hematology effects, hepatic
effects including changes in biochemical parameters, increased organ
weights, and histopathological changes. Atrophy of striated muscle
fibers, cataract and retinal atrophy observed in the high dose females
were considered to be due to acceleration of spontaneous age-related
lesions.
In the 18-month mouse study, effects were observed in the lung,
liver, spleen and bone marrow at 250 ppm or higher. Findings included
centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis
and pigment deposition in the spleen and decreased cellularity
(hypocellularity) in the bone marrow. There were statistically
significant increases in the incidence of alveolar/bronchiolar adenomas
in both sexes of treated groups with hyperplasia/hypertrophy of
epithelial cells in terminal bronchioles. There was a statistically
significant increase in the incidence of alveolar/bronchiolar
carcinomas in males at 750 ppm and 2,250 ppm and in females at 2,250
ppm only. These effects in the lungs of mice were not life threatening
as most of effects were observed at the terminal sacrifice and there
was no effect of treatment on mortality in the study. A no observed
adverse effect level (NOAEL) could not be determined from the dose
levels administered. Mechanism-of-action studies have indicated that
the lung effects are unique to the mouse and are not likely to
translate to other species including the rat. A second 18-month mouse
study was conducted in CD-1 mice at dose levels ranging from 10 to 250
ppm to establish a NOAEL for hyperplasia/hypertrophy of epithelial
cells in terminal bronchioles and for the incidence of alveolar/
bronchiolar adenomas and carcinomas in both sexes. There was a
statistically significant increase in the incidence of alveolar/
bronchiolar adenomas in males at 250 ppm. In females, there was no
statistically significant increase in the incidence of pulmonary
neoplastic lesions at any dose level. The incidence of hyperplasia/
hypertrophy of epithelial cells lining the terminal bronchioles of the
lungs was statistically increased at 250 ppm in both sexes. There were
no treatment-related increases in neoplastic or non-neoplastic lesions
at dose levels of 80 ppm or lower in either sex. The NOAEL was 80 ppm,
equivalent to 10.0 and 11.8 mg/kg body weight/day for males and
females, respectively. This study confirmed a threshold for these
effects at 80 ppm, which had been indicated in studies on the
mechanism. Mechanism-of-action studies have indicated that the lung
effects are unique to the mouse and are not likely to translate to
other species including the rat. Flonicamid technical was not
carcinogenic in the rat.6. Animal metabolism. Rat, goat and poultry metabolism studies were
conducted using 14C-pyridyl-flonicamid. The majority of the
dose was rapidly excreted. Flonicamid was a major component of rat
urine 48 hours after dosing. TFNA-AM was the major metabolite found in
rats (urine), goats (milk and tissues) and in laying hens (tissues and
eggs). TFNG was found between 8%-24% of the total radioactive residue
(TRR) in the livers of rats sacrificed at intervals between 0.5-6 hours
after dosing. The liver samples at these time intervals had
14C-residues of 2.3%-4.6% of the dose. TFNA was not a major
component in animal tissues. The metabolism of flonicamid in animals
shows the main pathway of metabolism involves hydrolysis of -CN and -
CONH2 functional groups in the molecule, identical to plant
metabolism. The main metabolic reactions were hydrolysis of cyano to
the amide function and ring hydroxylation. In rats flonicamid was
further metabolized by several routes, including nitrile hydrolysis,
amide hydrolysis, N-oxidation, and hydroxylation of the pyridine ring,
leading to multiple metabolites. The metabolism of flonicamid in
animals is well understood.
7. Metabolite toxicology. The main metabolites of flonicamid were
examined in acute oral toxicity studies in rats and bacterial reverse
mutation tests. All the metabolites were less toxic than flonicamid and
not mutagenic.
8. Endocrine disruption. No special studies investigating potential
estrogenic or other endocrine effects of flonicamid have been
conducted. Some suggestions of possible endocrine effects were reported
at the highest dose tested (1,800 ppm) in the multi-generation
reproduction study which showed increased FSH and LH levels, a delay in
the time to vaginal opening in the F1
[[Page 40920]]
generation, and reduced ovary and adrenal weights in the parental
generation. However, there were no effects on reproductive performance
or survival of the offspring in the study. At levels that are expected
to be found in the environment, flonicamid will not cause any
endocrine-related effects.C. Aggregate Exposure
1. Dietary exposure. Potential dietary exposures from food were
estimated using the proposed tolerances for all crops using the Dietary
Exposure Evaluation Model (DEEM-FCIDTM) and percent crop
treated of 100%. The following raw agricultural commodities were
included: Head and stem Brassica, mustard greens, leaf lettuce, head
lettuce, celery, spinach, cotton, potatoes, fruiting vegetables,
cucurbits, stone fruits, pome fruits and resulting secondary residues
in meat, milk, poultry and eggs.
a. Food. Acute dietary exposure was compared to the acute
population adjusted dose (aPAD) of 3.0 mg/kg/day based on the NOEL of
300 mg/kg from the acute neurotoxicity study in rats and a 100-fold
uncertainty factor. The U.S. population exposure is 0.31% of the aPAD
and the most highly exposed subpopulation is children 1-2 years of age
with 0.93% of the aPAD 95th percentile.
Based on the available data, an appropriate chronic population
adjusted dose (cPAD) is 0.073 mg/kg/day based on the NOEL of 7.32 mg/
kg/day from the chronic toxicity study in rats and a 100-fold
uncertainty factor. The U.S. population exposure is 3.6% of the cPAD
and the most highly exposed subpopulation exposure is children 1-2
years of age with 12.2% of the cPAD.
b. Drinking water. A drinking water level of comparison (DWLOC) was
calculated by subtracting the chronic/acute food exposures calculated
using DEEMTM from the cPAD/aPAD to obtain the acceptable
chronic/acute exposure to flonicamid in drinking water. The estimated
average and maximum concentration of flonicamid in surface water is
1.07 parts per billion (ppb) and 7.33 ppb, respectively. These are both
well below the lowest chronic (641 ppb) and acute (29,720 ppb) DWLOC
values for flonicamid. Therefore, taking into account all proposed
uses, it can be concluded, with reasonable certainty that residues of
flonicamid in food and drinking water will not result in unacceptable
levels of human health risk.
2. Non-dietary exposure. There are currently no residential uses of
flonicamid registered or pending action that need to be added to the
total risk from exposure.
D. Cumulative Effects.
In consideration of potential cumulative effects of flonicamid and
other substances that may have a common mechanism of toxicity, to our
knowledge there are currently no available data or other reliable
information indicating that any toxic effects produced by flonicamid
would be cumulative with those of other chemical compounds; thus, only
the potential risks of flonicamid have been considered in this
assessment of its aggregate exposure. If ISK Biosciences Corporation
learns of any other compound with the same mechanism of toxicity they
will submit information for the EPA to consider concerning potential
cumulative effects of flonicamid consistent with the schedule
established by EPA in the Federal Register of August 4, 1997 (62 FR
42020), and other EPA publications pursuant to the Food Quality
Protection Act.
E. Safety Determination
1. U.S. population. Using conservative exposure assessment
analyses, the acute dietary exposure estimates are well below the aPAD
of 3 mg/kg bwt/day for all population subgroups. In addition, the
chronic dietary exposure estimates for the various population groups
are well below the cPAD of 0.073 mg/kg bwt/day. Based on this
information, ISK Biosciences Corporation concludes, that there is
reasonable certainty that no harm will result from acute or chronic
exposure to flonicamid.
2. Infants and children. Based on the available developmental and
reproductive data on flonicamid, ISK Biosciences Corporation concludes,
that reliable data support use of the standard 100-fold uncertainty
factor, and that an additional uncertainty factor is not needed to
protect the safety of infants and children under the Food Quality
Protection Act (FQPA). Although, the reproduction study indicated signs
of toxicity to some reproductive organs/systems at the high dose of
1,800 ppm in the diet, other signs of toxicity such as effects on the
kidney accompanied these; there were no effects observed at a dose
level of 300 ppm. There were no effects on reproduction or survival at
any dose level. Since acute and chronic aggregate exposure assessments
are well below the aPAD and cPAD respectively, there is reasonable
certainty that no harm will result to infants and children from
aggregate exposure to flonicamid residues.
F. International Tolerances
There are no Canadian or Mexican residue limits or Codex MRLs for
the insecticide flonicamid and its metabolites TFNA, TFNA-AM and TFNG.
[FR Doc. 04-15206 Filed 7-6-04; 8:45 am]
BILLING CODE 6560-50-S