[Federal Register Volume 69, Number 18 (Wednesday, January 28, 2004)]
[Notices]
[Pages 4138-4143]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-1238]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0375; FRL-7337-3]


Fenamidone; 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-2003-0375, must be 
received on or before February 27, 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:  Cynthia Giles-Parker, Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 305-7740; 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 are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 32532)
     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.

[[Page 4139]]

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-2003-0375. 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 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 on 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-2003-0375. 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-2003-0375. 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-2003-0375.

[[Page 4140]]

    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-2003-0375. 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 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 
thatsupport 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: January 5, 2004.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

     EPA has received a pesticide petition (1F6300) from Bayer 
CropScience, 2 T.W. Alexander Drive, Research Triangle Park, NC 27709 
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 a tolerance for residues of fenamidone, 4H-Imidazol-4-one, 
3,5-dihydro-5-methyl-2-(methylthio)-5-phenyl-3-(phenylamino)-,(S)-, and 
its metabolites (RPA 412708), (RPA 412636), and (RPA 410193) in or on 
the raw agricultural commodity vegetable, tuberous and corm, subgroup 
1C at 0.05 parts per million (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.
     In the Federal Register of January 4, 2002 (67 FR 592) (FRL-6812-
2) EPA issued a notice of filing of Pesticide Petition (1F6300) from 
Bayer Crop Science (formerly Aventis Crop Science) at the above address 
proposing to amend 40 CFR part 180 by establishing tolerances for 
fenamidone and its metabolites in or on various raw agricultural 
commodities. EPA has received an amended petition to include the above 
raw agricultural commodities subgroup. This notice contains information 
submitted in addition to that contained in the January 4, 2002 notice.

 Bayer CropScience

 PP 1F6300

A. Residue Chemistry

    1. Plant metabolism. The plant metabolism of fenamidone (RPA 
407213) was evaluated in four distinct crops (lettuce, tomatoes, 
potatoes, and grapes) and is adequately understood. In all cases, the 
primary residue was the parent compound. The only significant 
metabolite was (RPA 410193) (17% of the total radioactive residue (TRR) 
in grapes, 9% of the total radioactive residue (TRR) in tomatoes, <1% 
of the total radioactive residue (TRR) in potatoes (haulm or tubers). 
RPA 412708 and RPA 412636 were minor metabolites reported in the 
lettuce and potato studies and may account for part of the unidentified 
residue reported in the grape and tomato metabolism studies.
    2. Analytical method. Although, residue levels approaching the 
proposed tolerances are unlikely, independently validated enforcement 
methods are available for determining residues of fenamidone and 
relevant metabolites. Residues are first extracted from the crop matrix 
by blending or shaking with a mixture of acetonitrile and water. After 
filtration, an aliquot of the extract is rotary evaporated to near 
dryness, then diluted with water. Cleanup is accomplished on a HR-P 
polymeric solid phase extraction (SPE) cartridge and an amino SPE 
cartridge. Residues are quantified by HPLC with tandem mass 
spectrometric detection (LC/MS/MS). The method limits of quantification 
(LOQ) are 0.02 ppm for fenamidone, and its metabolites (RPA 412636), 
(RPA 412708), and (RPA 410193) in potato tubers and processed 
fractions, tomatoes and processed fractions, cucumbers, squash, 
cantaloupes, head and leaf lettuce, onions, spinach, and wheat raw 
agricultural commodities and processed fractions.
    3. Magnitude of residues. Eighteen residue trials were conducted 
with fenamidone on potatoes in 1999. EXP 10623A, a suspension 
concentrate containing 500 grams (g) fenamidone per liter, was applied 
as four broadcast applications of 0.268 lb active ingredient/Acre 
(a.i./A) 300 g a.i./ha each or six broadcast applications of

[[Page 4141]]

0.178 lb a.i./A 200 g a.i./ha each, for a maximum seasonal use rate for 
1.068 lb a.i./Acre 1,200 g a.i./ha). Applications were made 
approximately 5 days apart. The target pre-harvest interval (PHI) was 
14 days. No quantifiable residues of fenamidone or metabolites were 
found in any tuber sample above the LOQ (0.02 ppm). The extent of 
potential residue concentration in processed potato fractions was 
estimated by processing potatoes after application of fenamidone at 5X 
the maximum seasonal use rate. The potato tuber or the potato chips 
despite the exaggerated application rated. Only parent fenamidone (RPA 
407213) residues were found in the wet peel at levels of 0.043 to 0.049 
ppm with an estimated concentration factor of 4.6. Trace residues of 
two fenamidone metabolites were found only in the potato flake 
fraction, RPA 412708 at 0.029 to 0036 ppm and RPA 412636 at 0.026 ppm. 
When corrected to account for the exaggerated application rate, residue 
levels of processed fractions were less than the RAC LOQ of 0.02 ppm.

B. Toxicological Profile

    1. Acute toxicity. A complete battery of acute toxicity studies for 
fenamidone has been conducted. The acute oral toxicity study in rats 
resulted in a lethal dose (LD)50 of <5,000 milligrams/
kilogram (mg/kg) (males) and >2,028 mg/kg (females). The acute dermal 
toxicity study in rats resulted in a LD50 of >2,000 mg/kg 
for both males and females. The acute inhalation study in rats resulted 
in a lethal concentration (LC)50 of >5 milligrams/Liter (mg/
L) for males and females. Fenamidone was not irritating in the primary 
eye irritation or primary dermal irritation studies. The dermal 
sensitization study in guinea pigs was negative. In an acute 
neurotoxicity study in rats, fenamidone was not neurotoxic at doses up 
to the limit dose of 2,000 mg/kg. The no observed adverse effect level 
(NOAEL) was 500 mg/kg for males and 125 mg/kg for females.
    2. Genotoxicity. Mutagenicity studies conducted include: A 
Salmonella typhimurium reverse mutation assay (negative at the limits 
of cytotoxicity and solubility with and without activation); in vitro 
unscheduled DNA synthesis test in rat liver (negative at the limits of 
cytotoxicity); in vitro chromosome aberrations test in human 
lymphocytes (positive at the limits of cytotoxicity and solubility); 
TK+/-mouse lymphoma assay (positive with activation, negative without); 
in vivo mouse micronucleus test (negative with toxicity at 2,000 mg/
kg); and an in vivo unscheduled DNA synthesis assay in the rat 
(negative at up to 2,000 mg/kg with toxicity at the high dose level). 
Based on the data cited above, fenamidone is not considered mutagenic.
    3. Reproductive and developmental toxicity. A teratology study was 
conducted with rats administered (orally) fenamidone on gestation days 
6-15 at dose levels of 0, 25, 150, or 1,000 mg/kg/day. High dose dams 
had significantly decreased body weight and food consumption. High dose 
fetal body weights were less than controls and correlated with slightly 
delayed skeletal ossification secondary to maternal toxicity. The NOAEL 
for maternal and developmental toxicity is 150 mg/kg/day. The lowest 
observed adverse effect level (LOAEL) was 1,000 mg/kg/day. A teratology 
study was conducted with rabbits administered (orally) fenamidone on 
gestation days 6-19 at dose levels of 0, 10, 30, or 100 mg/kg/day. The 
maternal NOAEL was 10 mg/kg/day. The maternal LOAEL was 30 mg/kg/day, 
based on increased maternal liver weights at 30 and 100 mg/kg/day. 
Fenamidone demonstrates no reproduction study was conducted with rats 
administered (orally) in the diet fenamidone at dose levels of 0, 3.9, 
63.8, 328.3 mg/kg/day (males) and 0, 5.15, 84.4, 459.6 mg/kg/day 
(females). The NOAEL for maternal and offspring toxicity was 5/15 mg/
kg/day. The maternal NOAEL was based on decreased body weight and food 
consumption. The pup NOAEL is based on F1 pup body weight decrease. The 
reproductive NOAEL was >328.3 mg/kg/day (males) and >459.6 mg/kg/day 
(females). Fenamidone is not considered a reproductive toxicant at non-
maternally toxic dose levels and shows no evidence of endocrine 
effects.
    4. Subchronic toxicity. In a 13-week range-finding study, 
fenamidone was administered in the diets of male and female rats at 
dose levels of 0, 4.05, 10.41, 68.27, 343.93 mg/kg/day to males and 0, 
4.81, 12, 83.33, 380.68 mg/kg/day to females. The NOAEL is 68.27 mg/kg/
day (males) and 83.33 mg/kg/day (females) and the LOAEL is 343.93 mg/
kg/day for males and 380.63 mg/kg/day for females based on adaptive 
liver changes at 68.27 mg/kg/day and increased liver and thyroid 
weights at the highest dose tested. In a 13-week subchronic feeding 
study, fenamidone was administered in the diet to mice at dose levels 
of 0, 11.33, 44.5, 220.2, 1,064.3 mg/kg/day to males and 0, 13.7, 54.1, 
273.9, 1,375.2 mg/kg/day to females. The NOAEL is 44.5 mg/kg/day (males 
and 54.1 mg/kg/day (females) and the LOAEL is 220.2 mg/kg/day (males) 
and 273.9 mg/kg/day (females) based on 14% increase in liver weight at 
the high dose. In a 28-day subchronic dermal study, fenamidone was 
applied to skin of male and female New Zealand white rabbits at doses 
of 0 or 1,000 mg/kg/day for 6 hours/day, 5 days/week. Treatment 
produced a slight decrease in food consumption 8-10%) and body weight 
(6%) in males only. In a 13-week study, fenamidone was administered in 
the diets of male and female dogs at 0, 10, 100, and 500 mg/kg/day. 
Based on clinical symptoms at the high dose, the NOAEL is 100 mg/kg/day 
and the LOAEL is 500 mg/kg/day. In a subchronic neurotoxicity study, 
there was no evidence of neurotoxicity when fenamidone technical was 
administered to rats for 13 weeks at dosage levels up to 5,000 ppm 
(395.6 and 414.2 mg/kg/day), the maximum tolerance dose (MTD). The 
NOAEL for the study was 1,000 ppm (equivalent to 74.2 and 83.4 mg/kg/
day).
    5. Chronic toxicity. A 1-year oral study was conducted with dogs 
administered fenamidone at dose levels of 0, 10, 100, 1,000 mg/kg/day 
in capsules. The NOAEL is 100 mg/kg/day for both sexes, based on 
significantly increased liver weights and biliary hyperplasia in the 
high dose. The LOAEL is 1,000 mg/kg/day. A 2-year combined chronic 
toxicity/carcinogenicity study was conducted with fenamidone 
administered in the diet to rats at dosed of 0, 2.83, 7.07, 47.68, 
260.13 mg/kg/day (males) and 0, 3.63, 9.24, 60.93, 335.10 mg/kg/day 
(females). The NOAEL for systemic toxicity s 2.83 mg/kg/day (males) and 
3.36 mg/kg/day (females). The LOAEL is 7.07 mg/kg/day (males and 9.24 
mg/kg/day (females). No statistically significant, linear dose response 
was observed for any tumor incidence. A 104-week combined 
carcinogenicity study in mice was conducted with mice administered 
fenamidone in the diet at dose levels of 0, 9.5, 47.5, 535.5, 1,100.2 
mg/kg/day (males) and 0, 12.6, 63.8, 680.5, 1,393.2 mg/kg/day 
(females). The NOAEL was 9.5 mg/kg/day (males ) and 12.6 mg/kg/day 
(females). The LOAEL for carcinogenicity was 47.5 mg/kg/day (males) and 
63.8 mg/kg/day (females). The NOAEL is based on non-neoplastic liver 
changes and decreased body weight gain at the top two dose levels. 
Fenamidone demonstrates no potential for carcinogenic effects in 
mammals.
    6. Animal metabolism. Metabolism studies conducted with goat and 
hen demonstrate that fenamidone is rapidly metabolized and excreted. 
Residue levels in edible animal tissues (meat, milk and eggs) are 
negligible and do accumulate in those tissues. The metabolic pathway 
proceeds via

[[Page 4142]]

cleavage of the amino-phenyl group and the thiomethyl group with 
further metabolism by hydroxylation. There is also evidence that 
glucuronide and sulfate conjugates are formed. A single low dose (3 mg/
kg), a single high dose (300 mg/kg) and a low dose 3 mg/kg administered 
for 15 consecutive days were fed to rats. Fenamidone was relatively 
well absorbed at a nominal dose of 3 mg/kg in both sexes and 
intensively metabolized by phase 1 oxidation, reduction and hydrolysis 
and 2 conjugation reactions. The elimination of radiolabeled fenamidone 
was relatively rapid with the majority of the administered dose being 
excreted via the biliary route (for the low dose experiments). The 
comparison of the levels of radioactivity recovered in bile kinetic and 
absorption, distribution, metabolism and excretion (ADME) studies 
suggested that a part of the radioactivity excreted via the bile could 
be reabsorbed and subsequently re-excreted via the urine. High levels 
of radioactivity measured in blood samples from the tissue kinetics 
also supported this hypothesis. At the high dose level fenamidone was 
not very well absorbed; some 50-60% of the radioactivity was present as 
parent compound in the feces. Radioactivity was widely distributed in 
the tissues with predominance in the thyroids, blood, liver, kidneys, 
fat and pancreas. Fenamidone is therefore expected to be rapidly and 
extensively metabolized and excreted in mammals.
    7. Metabolite toxicology. The major dietary metabolites of 
fenamidone, (RPA 412708), (RPA 410193) and (RPA 412636), were evaluated 
for mammalian toxicity in an acute oral toxicity study, a 90-day 
repeated dose study and in genotoxicity tests. The metabolites are 
considered to be of comparable toxicity to the parent fenamidone.
    8. Endocrine disruption. Chronic, lifespan, and multi-generational 
bioassays in mammals and acute and subchronic studies on aquatic 
organisms and wildlife did not reveal endocrine effects. Any endocrine 
related effects would have been detected in this definitive array of 
required tests. The probability of any such effect due to agricultural 
uses of fenamidone is negligible.

C. Aggregate Exposure

    1. Dietary exposure. Fenamidone is registered for use on head and 
leaf lettuce, and has been proposed previously to support uses on the 
bulb vegetable crop group, potatoes, and the cucurbit crop group. Wheat 
tolerances were also proposed to cover any potential plant-back 
residues. An import tolerance for wine grapes was also proposed to 
cover potential residues in imported wine. There are no residential 
uses proposed for fenamidone. Therefore, the aggregate exposure would 
consist of any potential exposures to fenamidone residues from the 
above food crops, from drinking water, and from imported wine. The 
acute reference dose (aRfD) of 0.13 mg/kg/day is based on a NOAEL of 
125 mg/kg/day from the neurotoxicity study in rat and a 10X database 
uncertainty factor (UF) recently applied by the Agency for lack of a 
developmental neurotoxicity study. The chronic reference dose (cRfD) of 
0.002 mg/kg/day from the 2-year rat chronic study and the UF of 10X.
    i. Food. Acute and chronic dietary analyses were conducted to 
estimate exposure to potential fenamidone residues in/on the crops and 
crop groups of tuberous and corm vegetables, head and leaf lettuce, 
onions and bulb vegetables, cucurbits and tomatoes as target crops, and 
wheat as a rotational crop. Tier III analysis were conducted for both 
the acute and chronic scenarios using the DEEMTM Exponent, 
Inc. software. The acute dietary exposure estimates at the 
95th percentile of exposure for the U.S. population was 5.5% 
of the acute Reference Dose (aRfD). The U.S. population subgroup with 
the highest exposure was toddlers 1-2 years at 9.3% of the aRfD. 
Chronic dietary exposure estimates from potential residues of 
fenamidone for the U.S. population was 8.0% of the chronic RfD. The 
sub-population with the highest exposure was children 1-6 years at 10-
2% of the RfD.
    ii. Drinking water. EPA's Standard Operating Procedure (SOP) for 
Drinking Water Exposure and Risk Assessments was used to perform the 
drinking water assessment. This SOP uses a variety of tools to conduct 
drinking water assessments, including water models such as SCI-GROW, 
FIRST PRZMS/EXAMS, and available monitoring data. If monitoring data 
are not available, then the models are used to predict potential 
residues in surface water and ground water and the highest levels are 
assumed to be the drinking water residue. In the case of fenamidone, 
monitoring data do not exist, therefore, SCI-GROW and FIRST were used 
to estimate a water residue. The calculated drinking water levels of 
comparison (DWLOC) for acute and chronic exposure for all adults and 
children exceed the modeled drinking water estimated concentration 
(DWEC). The acute DWLOC values are 4,301 parts per billion (ppb) for 
the general population and 1,179 ppb for infants and children, compared 
to the worst-case acute DWEC of 50 ppb. The chronic DWLOC values are 27 
ppb for the general population and 29 ppb for infants and children, 
compared to a worst-case chronic DWEC of 11 ppb. These drinking water 
levels of comparison are based on conservative dietary (food) exposures 
and are typically expected to be much higher under actual use 
scenarios.
    2. Non-dietary exposure. Fenamidone is not registered for 
residential uses (food or non-food), thereby eliminating any potential 
for residential exposure or non-occupational exposure.

D. Cumulative Effects

     Section 408(b)(2)(D)(v) requires that, when considering whether to 
establish, modify, or revoke a tolerance, the Agency consider 
``available information'' concerning the cumulative effects of a 
particular pesticide's residues and other substances that have a common 
mechanism of toxicity. There is no available data to determine whether 
fenamidone has a common mechanism of toxicity with other substances or 
how to include this pesticide in a cumulative risk assessment. Unlike 
other pesticides for which EPA has followed a cumulative risk approach 
based on a common mechanism of toxicity, fenamidone does not appear to 
produce a toxic metabolite produced by other substances. For the 
purposes of this tolerance petition, therefore, it has not been assumed 
that fenamidone has a common mechanism of toxicity with other 
substances.

E. Safety Determination

    1. U.S. population. Using the assumptions and data described above, 
based on the completeness and reliability of the toxicity data, it is 
concluded that, the dietary exposure from the proposed uses of 
fenamidone will utilize at most 8.0% of the aRfD or cRfD for the U.S. 
population. EPA generally has no concern for exposures below 100% of 
the RfD because the RfD represents the level at or below which daily 
aggregate exposure over a lifetime will not pose appreciable risk to 
human health. Drinking water levels of comparison based on the dietary 
and aggregate exposures are greater than highly conservative estimated 
levels, and would be expected to be well below the 100% level of the 
RfD, if they occur at all. Therefore, there is a reasonable certainty 
that no harm will occur to the U.S. population from aggregate exposure 
of food and drinking water to residues of fenamidone.
    2. Infants and children. In consideration of the toxicology data 
base as discussed above, EPA has determined that there is no extra

[[Page 4143]]

sensitivity of infants and children, and therefore, the default FQPA 
safety factor can be removed. However, the Agency has applied a data 
base uncertainty factor of 10X to account for the current lack of 
developmental neurotoxicity study. Using the assumptions and data 
described in the exposure section above, the percent of the aRfD and 
cRfD that will be used for exposure to residues of fenamidone in food 
for infants and children (the most highly exposed subgroups) is 10.2%. 
There are no non-dietary concerns for infants and children. As with 
adults, drinking water levels of comparison are higher than the worst-
case drinking water estimated concentrations and are expected to use 
well below 100% of the reference dose.

[FR Doc. 04-1238 Filed 1-27-04; 8:45 am]
BILLING CODE 6560-50-S