[Federal Register Volume 68, Number 127 (Wednesday, July 2, 2003)]
[Notices]
[Pages 39541-39547]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-16739]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0212; FRL-7312-9]


Indoxacarb; 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-2003-0212, must be 
received on or before August 1, 2003.

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: Rita Kumar, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8291; 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:
    [sbull] Crop production (NAICS 111)
    [sbull] Animal production (NAICS 112)
    [sbull] Food manufacturing (NAICS 311)
    [sbull] 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.

B. How Can I Get Copies of This Document and Other Related Information?

    1. EPA Docket. EPA has established an official public docket for 
this action under docket ID number OPP-2003-0212. 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

[[Page 39542]]

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 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-2003-0212. 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-2003-0212. 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-2003-0212.
    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-2003-0212. 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

[[Page 39543]]

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 
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 19, 2003.
Peter Caulkins,
Director, Registration Division, Office of Pesticide Programs.

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 E. I. Du Pont de Nemours and Company, Du Pont 
Crop Protection, 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.

E. I. Du Pont de Nemours and Company

Du Pont Crop Protection

PP 3F6576

     EPA has received a pesticide petition (PP 3F6576) from E. I. Du 
Pont de Nemours and Company, Du Pont Crop Protection, Wilmington, 
Delaware, proposing pursuant to section 408(d) of the Federal Food, 
Drug and Cosmetic Act, 21 U.S.C. 346a(d), to amend 40 CFR part 180, by 
establishing a tolerance for combined residues of Indoxacarb, [(S)-
methyl 7-chloro-2,5-dihydro-2-[(methoxycarbonyl)[4-
(trifluoromethoxy)phenyl] amino]carbonyl]indeno[1,2e] 
[1,3,4]oxadiazine-4a(3H)- carboxylate] and its R-enantiomer [(R)-methyl 
7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy) phenyl] 
amino]carbonyl]indeno [1,2-e] [1,3,4] oxadiazine-4a(3H)- carboxylate] 
in a 75:25 mixture (DPX MP062), respectively, in or on the raw 
agricultural commodity as follows: grape, 2 ppm and raisin, 6 ppm. An 
analytical enforcement method (LC-UV) is available for determining 
plant residues. 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

     The active ingredient in the end-use formulation, Avaunt[Ograve], 
is a 75:25 mixture of two isomers, indoxacarb (DPX-KN128) and IN-KN127. 
Only one of the isomers, indoxacarb (DPX-KN128), has insecticidal 
activity. Since the insecticidal efficacy is based on the concentration 
of indoxacarb (DPX-KN128), the application rates have been normalized 
on an indoxacarb (DPX-KN128) basis. The proposed tolerance expression 
includes both indoxacarb (DPX-KN128) and IN-KN127 and the residue 
method does not distinguish between the enantiomers, therefore, 
residues are reported as the sum of indoxacarb (DPX-KN128) combined 
with IN-KN127. Residues of indoxacarb (DPX-KN128) combined with IN-
KN127 will be referred to as ``KN128/KN127''.
    1. Plant metabolism The metabolism of indoxacarb in plants is 
adequately understood to support these tolerances. Plant metabolism 
studies in cotton, lettuce, and tomatoes showed no significant 
metabolites. The only significant residue was parent compound.
    2. Analytical method. The plant residue enforcement method detects 
and quantitates indoxacarb in various matrices including sweet corn, 
lettuce, tomato, broccoli, apple, grape, cottonseed, tomato, peanut and 
soybean commodity samples by HPLC-UV. The limit of quantitation in the 
method allows monitoring of crops with indoxacarb residues at or above 
the levels proposed in these tolerances.
    3. Magnitude of residues--a. Grapes. Residue studies were conducted 
at a total of 13 field sites. All studies were done using Avaunt[reg] 
Insecticide containing 30% active ingredient (300 grams (g) DPX-KN128 
per kilogram (kg), weight/weight (w/w). Four broadcast applications of 
Avaunt[reg]. Insecticide were made at each test site at a maximum rate 
of 0.11 lb. active ingredient (a.i.) DPX-KN128/acre/application 
(maximum seasonal use rate of 0.44 lb DPX-KN128/acre). Applications 
were made approximately 5 days apart. Residues were measured as the 
combination of DPX-KN128 and IN-KN127 (enantiomers not resolved by the 
analytical method). Maximum residues of KN128/KN127 in individual 
duplicate samples were 1.72parts per million (ppm) at a pre-harvest 
interval (PHI) of 7 days (range 0.066 to 1.72 ppm.
    b. Grape processing. A grape processing study was also performed in 
California. Grapes received four applications of an exaggerated rate of

[[Page 39544]]

0.555 lb. of indoxacarb per acre, 5X the labeled rate. Samples were 
collected from control and treated plots 7 days after the last 
application. The grape samples were then processed using standard grape 
processing procedures. Samples collected at the processing facility 
were whole fruit, raisins and grape juice. The mean KN128/KN127 
residues in whole fruit, raisins and grape juice treated with the 
exaggerated rate were 1.34 ppm, 3.66 ppm and <0.01 ppm, respectively.

B. Toxicological Profile

    1. Acute toxicity. Based on EPA criteria, indoxacarb is classified 
as follows for toxicity categories:

----------------------------------------------------------------------------------------------------------------
              Guideline                         Title                   Results                  Category
----------------------------------------------------------------------------------------------------------------
81-1                                   Acute oral toxicity      LD50:1,730 milligrams/   Category II
                                                                 kilogram (mg/kg) (M
                                                                 Rat)
                                                                LD50: 268 mg/kg/(F Rat)
-----------------------------------------------------------------------------------------
81-2                                   Acute dermal toxicity    LD50: >5,000 mg/kg       Category IV
                                                                 (Rat)
-----------------------------------------------------------------------------------------
81-3                                   Acute inhalation         LC50:>5.5 (milligrams/   Category IV
                                        toxicity                 per Liter (mg/L) (M
                                                                 Rat) (70% MUP)
-----------------------------------------------------------------------------------------
81-4                                   Primary eye irritation   Effects reversed within  Category III
                                                                 72 hours (Rabbit)
-----------------------------------------------------------------------------------------
81-5                                   Primary dermal           No irritation (Rabbit)   Category IV
                                        irritation
-----------------------------------------------------------------------------------------
81-6                                   Skin sensitization       Sensitizer (Guinea Pig)
----------------------------------------------------------------------------------------------------------------

     Formulated products are slightly less acutely toxic than 
indoxacarb.
     In an acute neurotoxicity study, indoxacarb exhibited decreased 
forelimb grip strength, decreased foot splay, and some evidence of 
slightly reduced motor activity, but only at the highest doses tested. 
The no adverse effects level (NOAEL) was 100 mg/kg for males and 12.5 
mg/kg for females based on body weight effects in females >50 mg/kg.
    2. Genotoxicty. Indoxacarb has shown no genotoxic activity in the 
following listed in-vitroand in-vivotests:
    i. Ames--Negative
    ii. In-vitro mammalian gene mutation (CHO/HGPRT)--Negative
    iii. In-vitro unscheduled DNA synthesis--Negative
    iv. In-vitro chromosomal aberration--Negative
    v. In-vivo mouse micronucleus--Negative
    3. Reproductive and developmental toxicity. The results of a series 
of studies indicated that there were no reproductive, developmental or 
teratogenic hazards associated with the use of indoxacarb. In a 2-
generation rat reproduction study, the parental NOAEL was 1.5 mg/kg/
day. The parental NOAEL was based on observations of reduced weight 
gain and food consumption for the higher concentration groups of the F0 
generation, and potential treatment-related changes in spleen weights 
for the higher groups of the F1 generation. There was no effect on 
mating or fertility. The NOAEL for fertility and reproduction was 6.4 
mg/kg/day. The offspring NOAEL was 1.5 mg/kg/day, and was based on the 
reduced mean pup weights noted for the F1 litters of the higher 
concentration groups. The effects on pup weights occurred only at a 
maternal effect level and may have been due to altered growth and 
nutrition in the dams. In studies conducted to evaluate developmental 
toxicity potential, indoxacarb was neither teratogenic nor uniquely 
toxic to the conceptus (i.e., not considered a developmental toxin). 
Developmental studies conducted in rats and rabbits demonstrated that 
the rat was more susceptible than the rabbit to the maternal and fetal 
effects of DPX-MP062. Developmental toxicity was observed only in the 
presence of maternal toxicity. The NOAEL for maternal and fetal effects 
in rats was 2 mg/kg/day based on body weight effects and decreased food 
consumption at 4 mg/kg/day. The NOAEL for developmental effects in 
fetuses was >4 mg/kg/day. In rabbits, the maternal and fetal NOAELS 
were 500 mg/kg/day based on body weight effects, decreased food 
consumption in dams and decreased weight and delayed ossification in 
fetuses at 1,000 mg/kg/day.
    4. Subchronic toxicity. Subchronic (90-day) feeding studies were 
conducted with rats, mice, and dogs. In a 90-day feeding study in rats, 
the NOAEL was 3.1 and 2.1 mg/kg/day for males and females, 
respectively. In male rats, the NOAEL was based on decreased body 
weight and nutritional parameters, mild hemolytic anemia and decreased 
total protein and globulin concentration. In female rats, the NOAEL was 
based on decreased body weight and food efficiency.
     In a subchronic neurotoxicity study in rats, there was no evidence 
of neurotoxicity at 11.9 and 6.09 mg/kg/day, the highest dose tested 
for males and females, respectively. The subchronic NOAEL in dogs (5.0 
mg/kg/day, M/F) was based on hemolytic anemia. Erythrocyte values for 
most dogs were within a range that would be considered normal for dogs 
in a clinical setting. Mice were less sensitive to indoxacarb than the 
rats or dogs. NOAELs (23 mg/kg/day, males, 16 mg/kg/day, females) were 
based on mortality (males only); increased reticulocytes and Heinz 
bodies and decreased body weight, weight gain, food consumption, food 
efficiency; and increased clinical signs (leaning to one side and/or 
with abnormal gait or mobility) (females only). In a 28-day repeated 
dose dermal study, the NOAEL was 50 mg/kg/day based on decreased body 
weights, body weight gains, food consumption, and food efficiency in 
females, and changes in hematology parameters, the spleen and clinical 
signs of toxicity in both sexes in rats.
    5. Chronic toxicity. Chronic studies with indoxacarb were conducted 
on rats, mice, and dogs to determine oncogenic potential and/or chronic 
toxicity of the compound. Effects generally similar to those observed 
in the 90-day studies were seen in the chronic studies. Indoxacarb was 
not oncogenic in rats or mice. The chronic NOAEL in male rats was 5 mg/
kg/day based on body weight and nutritional effects. In females, the 
NOAEL of 2.1 mg/kg/day was based on body weight and nutritional 
changes, as well as biologically significant hematologic changes at 3.6 
mg/kg/day and above.

[[Page 39545]]

Hemolytic effects were present only through the 6-month evaluation and 
only in females. The regenerative nature of indoxacarb-induced 
hemolytic anemia was demonstrated by the absence of significant changes 
in indicators of circulating erythrocyte mass at later evaluations. In 
mice, the chronic NOAEL of 2.6 mg/kg/day for males was based on 
deceased body weight and weight gain effects and food efficiency at 
13.8 mg/kg/day and above. The NOAEL for females was 4.0 mg/kg/day based 
on body weight nutritional effects, neurotoxicity, and clinical signs 
at 20 mg/kg/day. In dogs, the chronic NOAEL was about 2.3 and 2.4 mg/
kg/day in males and females, respectively based on hemolytic effects 
similar to those seen in the subchronic dog study.
    6. Animal metabolism--i. Livestock animal metabolism. Animal 
metabolism has been studied in the rat, hen, and cow and is well 
understood. In contrast to crops, indoxacarb is extensively metabolized 
in animals.
    ii Poultry. In poultry, hens were fed at 10 ppm/day for 5 days, 87-
88% of the total administered dose was excreted; parent comprised 51-
54% of the total dose in excreta. Concentration of residues in eggs 
were low, 0.3-0.4 of the total dose, as was the concentration of 
residues in muscle, 0.2% of the total dose. Parent and metabolite IN-
JT333 were not detected in egg whites; only insecticidally inactive 
metabolites were identified. Parent and IN-JT333 were found in egg 
yolks; however, their concentrations were very low-0.01-0.02 ppm. 
Concentrations of parent and IN-JT333 in muscle were at or below the 
limit of quantitation, (LOQ) (0.01 ppm).
    iii. Cattle. For the cow study, the cattle were fed at 10 ppm/day 
for 5 days; approximately 20% of the total administered dose was 
excreted in urine and 53-60% was excreted in feces in 5 days. Four-
tenths to 1.2% of the total dose in urine was parent indicating 
extensive metabolism; parent represented 46-68% of the fecal activity. 
Thus, most residues were not absorbed; those residues that were 
absorbed were extensively metabolized. Less than 1% of the total 
administered dose was in milk, most of which was parent compound. The 
insecticidally active metabolite IN-JT333 was not found in milk. 
Residues in muscle represented less than 0.01% of the total 
administered dose most of which was parent. IN-JT333 was not detected 
in muscle. No other metabolites were seen above 10% of the dose, thus 
only parent and IN-JT333 were monitored in the cattle feeding study.
    iv. Cattle feeding study. A cattle feeding study was conducted with 
indoxacarb at doses of 7.5 ppm, 22.5 and 75 ppm. The mean KN128/KN127 
concentrations were proportional to the dosing level in whole milk, 
skim milk, cream, muscle, fat, liver and kidney. Based on final residue 
values for the respective commodities contributing to the cattle diet, 
the anticipated dietary burden in dairy cattle is 51.7 ppm and the 
anticipated dietary burden in beef cattle is 49.1 ppm. The proposed 
grape use will not increase the animal dietary burden. Based on 
standard curves constructed from data in the cattle feeding study, 
KN128/KN127 concentrations at the 51.7 ppm feeding level are 0.123 ppm 
for whole milk, 0.033 ppm for skim milk and 1.46 ppm for cream. The 
KN128/KN127 concentrations at the 49.1 ppm feeding level are 0.046 ppm 
for muscle, 1.37 ppm for fat, 0.012 ppm for liver and 0.026 ppm for 
kidney. Tolerances have been established at 1.5 ppm in fat (cattle, 
goat, horse, sheep and hog), 0.05 ppm in meat, 0.03 ppm in meat by-
products, 0.15 ppm in milk and 4.0 ppm in milk fat.
    7. Metabolite toxicology. In rats, indoxacarb was readily absorbed 
at low dose (5 mg/kg), but saturated at the high dose (150 mg/kg). 
Indoxacarb was metabolized extensively, based on very low excretion of 
parent compound in bile and extensive excretion of metabolized dose in 
the urine and feces. Some parent compound remained unabsorbed and was 
excreted in the feces. No parent compound was excreted in the urine. 
The retention and elimination of the metabolite IN-JT333 from fat 
appeared to be the overall rate determining process for elimination of 
radioactive residues from the body. Metabolites in urine were cleaved 
products (containing only one radiolabel), while the major metabolites 
in the feces retained both radiolabels. Major metabolic reactions 
included hydroxylation of the indanone ring, hydrolysis of the 
carboxylmethyl group from the amino nitrogen and the opening of the 
oxadiazine ring, which gave rise to cleaved products. Metabolites were 
identified by mass spectral analysis, NMR, ultraviolet (UV), and/or by 
comparison to standards chemically synthesized or produced by 
microsomal enzymes.
    8. Endocrine disruption. Lifespan, and multigenerational 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 
indoxacarb is negligible.

C. Aggregate Exposure

    Tolerances for indoxacarb are proposed to support agricultural use 
on grapes. There are residential uses of indoxacarb pending (fire ant 
bait), however, the risk from that use has been found to be negligible.
    1. Dietary exposure. The chronic reference dose (RfD) of 0.02 mg/kg 
bwt/day is based on a NOAEL of 2.0 mg/kg bwt/day from the subchronic 
rat feeding study, the subchronic rat neurotoxicity study, and the 
chronic/carcinogenicity study, using an uncertainty factor of 100. The 
acute RfD for the general population is 0.12 mg/kg/day, based on the 
NOAEL of 12.5 mg/kg in the acute neurotoxicity study and an uncertainty 
factor of 100. The acute RfD for females 13-50 years of age is 0.02 mg/
kg/day, based on the NOAEL of 2 mg/kg/day observed in the developmental 
rat toxicity study and using an uncertainty factor of 100.
    i. Food. Chronic dietary exposure assessment. Chronic dietary 
exposure resulting from the currently approved use of indoxacarb on 
apples, Crop group 5 (brassica vegetables), cotton, pears, peppers, 
sweet corn, tomatoes, eggplant, alfalfa, head and leaf lettuce, 
peanuts, potatoes, soybeans, cranberries (current Section 18 use) and 
the proposed use on grapes are well within acceptable limits for all 
sectors of the population. The Chronic Module of the Dietary Exposure 
Evaluation Model (DEEMTM, Exponent, Inc., formerly Novigen 
Sciences, Inc., Version 7.76) was used to conduct the assessment with 
the reference dose (RfD) of 0.02 mg/kg/day. The analysis used overall 
mean field trial values, processing factors and projected peak percent 
crop treated values. Secondary residues in milk, meat and poultry 
products were also included in the analysis. The chronic dietary 
exposure to indoxacarb is 0.000089 mg/kg/day, and utilizes 0.4% of the 
RfD for the overall U.S. population. The exposure of the most highly 
exposed subgroup in the population, children age 1-6 years, is 0.000238 
mg/kg/day, and utilizes 1.2% of the RfD. The table below lists the 
results of this analysis, which indicate large margins of safety for 
each population subgroup and very low probability of effects resulting 
from chronic exposure to indoxacarb.

------------------------------------------------------------------------
                                                  Maximum
                                                  Dietary
                   Subgroup                       Exposure      % RfD
                                                (mg/kg/day)
------------------------------------------------------------------------
U.S Population                                     0.000089          0.4
------------------------------------------------------------------------

[[Page 39546]]

 
Non-Nursing Infants (<1 year old)                  0.000063          0.3
------------------------------------------------------------------------
Children (1-6 years)                               0.000238          1.2
------------------------------------------------------------------------
Children (7-12 years)                              0.000126          0.6
------------------------------------------------------------------------
Females (13+, nursing)                             0.000073          0.4
------------------------------------------------------------------------
Males (13-19 years)                                0.000090          0.5
------------------------------------------------------------------------

    ii. Acute dietary exposure. Acute dietary exposure resulting from 
the currently approved use of indoxacarb on apples, Crop Group 5 
(brassica vegetables), cotton, pears, peppers, sweet corn, tomatoes, 
eggplant, alfalfa, head and leaf lettuce, peanuts, soybeans, potatoes, 
cranberries (current Section 18 use) and the proposed use on grapes are 
well within acceptable limits for all sectors of the population. The 
Dietary Exposure Evaluation Model (DEEMTM, Exponent, Inc., 
formerly Novigen Sciences, Inc., Version 7.76) was used to conduct the 
assessment. Margins of exposure (MOE) were calculated based on an acute 
NOAEL of 2 mg/kg/day for women of childbearing age and a NOAEL of 12 
mg/kg/day for children and the general population (Pesticide Fact Sheet 
for Indoxacarb). The Tier 3 analysis used distributions of field trial 
residue data adjusted for projected peak percent crop treated. 
Secondary residues in milk, meat and poultry products were also 
included in the analysis. The results of this analysis are given in the 
table below. The percent of the acute population adjusted dose (a PAD) 
for all population subgroups shows that an adequate margin of safety 
exists in each case. Thus, the acute dietary safety of indoxacarb for 
established and the follow-on use clearly meets the Food Quality 
Protection Act (FQPA) standard of reasonable certainty of no harm and 
presents acceptable acute dietary risk.

------------------------------------------------------------------------
                                                  99.9th Percentile of
                                                        exposure
                                               -------------------------
                   Subgroup                                    % Acute
                                                  Exposure    population
                                                (mg/kg/day)    adjusted
                                                             dose (aPAD)
------------------------------------------------------------------------
U.S. population                                    0.008795          7.3
------------------------------------------------------------------------
All infants                                        0.024729         20.6
------------------------------------------------------------------------
Non-nursing (<1 year)                              0.026036         21.7
------------------------------------------------------------------------
Children (1-6 years)                               0.013973         11.6
------------------------------------------------------------------------
Children (7-12 years)                              0.006882          5.7
------------------------------------------------------------------------
Females (13-19 years)                              0.005119         25.6
------------------------------------------------------------------------
Females (20+, not pregnant or nursing)             0.005358         26.8
------------------------------------------------------------------------
Females (13-50 years)                              0.005307         26.5
------------------------------------------------------------------------

    iii. Drinking water. Indoxacarb is highly unlikely to contaminate 
groundwater resources due to its immobility in soil, low water 
solubility, high soil sorption, and moderate soil half-life. Based on 
the PRZM/EXAMS and SCI-GROW models the estimated environmental 
concentrations (EECs) of indoxacarb and its R-enantiomer for acute 
exposures are estimated to be 6.84 parts per billion (ppb) for surface 
water and 0.0025 ppb for ground water. The EECs for chronic exposures 
are estimated to be 0.316 ppb for surface water and 0.0025 ppb for 
ground water. Drinking water levels of comparisons (DWLOCs), 
theoretical upper allowable limits on the pesticide's concentration in 
drinking water, were calculated to be much higher than the EEC's. The 
chronic DWLOC's ranged from 198 to 697 ppb. The acute DWLOC's ranged 
from 440 to 3,890 ppb. Thus, exposure via drinking water is acceptable.
    2. Non-dietary exposure. Indoxacarb product registrations for 
residential non-food uses are pending. Non-occupational, non-dietary 
exposure for DPX-MP062 has been estimated to be extremely small. 
Therefore, the potential for non-dietary exposure is insignificant.

D. Cumulative Effects

    EPA's consideration of a common mechanism of toxicity is not 
necessary at this time because there is no indication that toxic 
effects of indoxacarb would be cumulative with those of any other 
chemical compounds. Oxadiazine chemistry is new, and indoxacarb has a 
novel mode of action compared to currently registered active 
ingredients.

E. Safety Determination

    1. U.S. population. Dietary and occupational exposure will be the 
major routes of exposure to the U.S. population, and ample margins of 
safety have been demonstrated for both situations. The chronic dietary 
exposure to indoxacarb is 0.000089 mg/kg/day, which utilizes 0.4% of 
the RfD for the overall U.S. population, using mean field trial values, 
processing factors and projected peak percent crop treated values. The 
percent of the acute population adjusted dose (7.3% aPAD) for the 
overall U.S. population shows that an adequate margin of safety exists. 
Using only pesticide handlers exposure data base (PHED) data levels A 
and B (those with a high level of confidence), margin of exposure 
(MOEs) for occupational exposure are 650 for mixer/loaders and 1,351 
for airblast applicators (worst-case). Based on the completeness and 
reliability of the toxicity data and the conservative exposure 
assessments, there is a reasonable certainty that no harm will result 
from the aggregate exposure of residues of indoxacarb including all 
anticipated dietary exposure and all other non-occupational exposures.
    2. Infants and children. Chronic dietary exposure of the most 
highly exposed subgroup in the population, children age 1-6 years, is 
0.000238 mg/kg/day or 1.2% of the RfD. For infants (non-nursing, <1 
yr.), the exposure accounts for 0.3% of the RfD. For acute exposure at 
the 99.9th percentile (based on a Tier 3 assessment) the exposure was 
0.013973 mg/kg/day (11.6% a PAD) for children 1-6 and 0.026036 mg/kg/
day (21.7% a PAD) for non-nursing infants. There are residential uses 
of indoxa carb pending, but exposure is calculated to be extremely 
minimal. The estimated levels of indoxa carb in drinking water are well 
below the below the DWLOC. Based on the completeness and reliability of 
the toxicity data, the lack of toxicological endpoints of special 
concern, the lack of any indication that children are more sensitive 
than adults to indoxa carb, and the conservative exposure assessment, 
there is a reasonable certainty that no harm will result to infants and 
children from the aggregate exposure of residues of indoxa carb, 
including all anticipated dietary exposure and all other non-
occupational exposures. Accordingly, there is no need to apply an 
additional safety factor for infants and children.

[[Page 39547]]

F. International Tolerances

     To date, no international tolerances exist for indoxacarb.
[FR Doc. 03-16739 Filed 7-1-03; 8:45 am]
BILLING CODE 6560-50-S