[Federal Register Volume 69, Number 129 (Wednesday, July 7, 2004)]
[Notices]
[Pages 40916-40920]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-15206]


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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: [email protected].

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 [email protected], 
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