[Federal Register Volume 68, Number 63 (Wednesday, April 2, 2003)]
[Notices]
[Pages 16040-16046]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-7803]


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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2003-0097; FRL-7298-7]


Thiamethoxam; 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-2003-0097, must be 
received on or before May 2, 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: Dani Daniel, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-5409; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

[[Page 16041]]

I. General Information

A. Does this Action Apply to Me?

     You may be potentially affected by this action if you are an 
agricultureal producer, food manufacturer, or pesticide manufactuer. 
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-2003-0097. 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-2003-0097. 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-2003-0097. In contrast to EPA's

[[Page 16042]]

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-2003-0097.
    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-2003-0097. 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 
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: March 24, 2003.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

    The petitioner's summary of the pesticide petitions is printed 
below as required by FFDCA section 408(d)(3). The summary of the 
petitions was prepared by Interregional Research Project 4 (IR-4) and 
represents the view of the petitioners. 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.

 Interregional Research Project 4 (IR-4)

 Syngenta Crop Ptotection Inc.

 PP 2E6505, 2E6363, 2E6508, 3E6524, 1E6349, 9F5051 and 0F6142

     This notice is a summary of pesticide petitions proposing the 
establishment/amendment of a regulation for residues of thiamethoxam 
and its metabolite in or on coffee (imported), pecans, leafy vegetable 
crop group, head and stem brassica subgroup, leafy brassica subgroup, 
succulent beans, stone fruit crop group, sunflower seed, peppermint 
tops and spearmint tops. This summary was prepared by the petitioners.
     EPA has received seven pesticide petitions; four from 
Interregional Research Project 4 (IR-4), 681 U.S. Highway 1 
South, North Brunswick, NJ 08902-3390, PP 2E6505, 2E6363, 2E6508 and 
3E6524 and three from Syngenta Crop Protection Inc., P.O. Box 18300, 
Greensboro, NC 27419-8300, PP 0F6142, 1E6349, and 9F5051 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 180.565 by establishing a 
tolerance for residues of the insecticide thiamethoxam [3-(chloro-5-
thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-
imine] (CAS Reg. No. 153719-23-4) and its metabolite N-(2-chloro-
thiazol-5-ylmethyl)-N'-methyl -N'-nitro-guanidine) in or on the 
agricultural commodities:

A. IR-4 Petitions

    l. PP 2E6505 proposes to establish tolerances for stone fruits, 
group 12 at 0.5 ppm.
    2. PP 2E6363 proposes to establish tolerances for peppermint and 
spearmint, tops at 4.0 ppm.
    3. PP 2E6508 proposes to establish tolerances for beans, succulent 
at 0.02 ppm.
    4. PP 3E6524 proposes to establish tolerances for sunflower, seed 
at 0.02 ppm.

B. Syngenta Petitions

    5. PP 0F6142 proposes to establish tolerances for pecans at 0.02 
ppm.
    6. PP 9F5051 proposes to establish tolerances for:

[[Page 16043]]

    [sbull] Leafy vegetables, group 4 at 2.0 ppm
    [sbull] Head and stem brassica vegetables, subgroup 5A at 1.0 ppm.
    [sbull] Leafy brassica vegetables, subgroup 5B at 2.0 ppm.
    7. PP 1E6349 proposes to establish tolerances for imported green 
and roasted coffee beans and instant coffee at 0.05 ppm.
     EPA has determined that the petitions contain 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 
petitions. Additional data may be needed before EPA rules on the 
petitions.

A. Residue Chemistry

    1. Plant metabolism. The primary metabolic pathways of thiamethoxam 
in plants (corn, rice, pears, and cucumbers) were similar to those 
described for animals, with certain extensions of the pathway in 
plants. Parent compound and CGA-322704 were the major residues in all 
crops. The metabolism of thiamethoxam in plants and animals is 
understood for the purposes of the proposed tolerances. Parent 
thiamethoxam and the metabolite, CGA-322704, are the residues of 
concern for tolerance setting purposes.
    2. Analytical method. Syngenta Crop Protection Inc. has submitted 
practical analytical methodology for detecting and measuring levels of 
thiamethoxam in or on raw agricultural commodities. The method is based 
on crop specific cleanup procedures and determination by liquid 
chromatography with either ultraviolet (UV) or mass spectroscopy (MS) 
detection. The limit of detection (LOD) for each analyte of this method 
is 1.25 nanogram (ng) injected for samples analyzed by UV and 0.25 ng 
injected for samples analyzed by MS, and the limit of quantitation 
(LOQ) is 0.005 ppm for milk and juices and 0.01 ppm for all other 
substrates.
    3. Magnitude of residues. IR-4 has submitted complete residue data 
for thiamethoxam on succulent beans, sunflower seed, peppermint and 
spearmint tops and stone fruits. Syngenta has submitted complete 
residue data for the proposed imported coffee, pecan, leafy vegetable, 
head and stem brassica vegetables, leafy brassica vegetables. Details 
of the Syngenta residue data on these crops were provided in previously 
published Notices of Filing.

B. Toxicological Profile

    1. Acute toxicity. The acute oral LD50 for thiamethoxam 
in the rat is 1,563 milligrams/kilogram body weight (mg/kg bwt). The 
acute dermal LD50 of thiamethoxam is >2000 mg/kg bwt. 
Thiamethoxam is non-toxic at atmospheric concentrations of 3.72 mg/L. 
Thiamethoxam is minimally irritating to the eye, non-irritating to skin 
and is not a dermal sensitizer.
     In an acute neurotoxicity screening study in rats (OPPTS 
Harmonized Guideline 870.6200), the no observed aderse affect level 
(NOAEL) was 100 mg/kg/day with a NOAEL of 500 mg/kg/day based on 
drooped palpebral closure, decrease in rectal temperature and locomotor 
activity and increase in forelimb grip strength (males only). At higher 
dose levels, mortality, abnormal body tone, ptosis, impaired 
respiration, tremors, longer latency to first step in the open field, 
crouched over posture, gait impairment, hypo-arousal, decreased number 
of rears, uncoordinated landing during the righting reflex test, slight 
lacrimation (females only) and higher mean average input stimulus value 
in the auditory startle response test (males only).
    2. Genotoxicty. In gene mutation studies with S. typhimurium and E. 
coli (OPPTS Harmonized Guidelines, 870.5100 and 870.5265), there was no 
evidence of gene mutation when tested up to 5,000 [mu]g/plate and there 
was no evidence of cytotoxicity.
     In a gene mutation study with chinese hamster V79 cells at 
hypoxanthine guanine phophoribosyl transferase (HGPRT) focus (OPPTS 
Harmonized Guideline 870.5300) there was no evidence of a gene mutation 
when tested up to the solubility limit.
     In a CHO cell cytogenetics study (OPPTS Harmonized Guideline 
870.5375) there was no evidence of chromosomal aberrations when tested 
up to cytotoxic or solubility limit concentrations.
     An in vivo mouse bone marrow micronucleus study (OPPTS Harmonized 
Guideline 870.5395) was negative when tested up to levels of toxicity 
in whole animals; however, there was no evidence of target cell 
cytotoxicity. An unscheduled DNA synthesis (UDS) assay (OPPTS 
Harmonized Guideline 870.5550) was negative when tested up to 
precipitating concentrations.
    3. Reproductive and developmental toxicity. A prenatal 
developmental study in the rat (OPPTS Harmonized Guideline 870.3700) 
resulted in maternal and developmental NOAELs of 30 mg/kg/day and 200 
mg/kg/day, respectively. The maternal lowest observed adverse effect 
level (LOAEL) is 200 mg/kg/day based on decreased body weight, body 
weight gain and food consumption. The developmental LOAEL was 750 mg/
kg/day based on decreased fetal body weight and an increased incidence 
of skeletal anomalies.
     A prenatal developmental study in the rabbit (OPPTS Harmonized 
Guideline 870.3700) resulted in maternal and developmental NOAELs of 50 
mg/kg/day. The maternal and developmental LOAEL is 150 mg/kg/day. The 
maternal LOAEL is based on maternal deaths, hemorrhagic discharge, 
decreased body weight and food intake during the dosing period. The 
developmental LOAEL is based on decreased fetal body weights, increased 
incidence of post-implantation loss and a slight increase in the 
incidence of a few skeletal anomolies/variations.
     In a reproduction and fertility effects study in rats (OPPTS 
Harmonized Guideline 870.3800), the parental/systemic NOAEL is 1.84 
(males), 202.06 (females) mg/kg/day; the reproductive NOAEL is 0.61 
(males), 202.06 (females) mg/kg/day and the offspring NOAEL is 61.25 
(males), 79.20 (females) mg/kg/day. The parental/systemic LOAEL is 
61.25 (males), not determined (females) mg/kg/day based on increased 
incidence of hyaline change in renal tubules in F0 and F1 males. The 
reproductive LOAEL is 1.84 (males), not determined (females ) mg/kg/day 
based on increased incidence and severity of tubular atrophy observed 
in testes of the F1 generation males. The offspring LOAEL is 158.32 
(males), 202.06 (females) mg/kg/day based on reduced body weight gain 
during the lactation period in all litters.
    4. Subchronic toxicity. A 90-day oral toxicity study in rats (OPPTS 
Harmonized Guideline 870.3100) resulted in a NOAEL of 1.74 males and 
92.5 (females) mg/kg/day. The LOAEL is 17.64 (male) and 182.1 (female) 
mg/kg/day based on increased incidence of hyaline change of renal 
tubules epithelium (males), fatty change in adrenal gland of females, 
liver changes in females, all at the LOAEL.
     A 90-day oral toxicity study in mice (OPPTS Harmonized Guideline 
870.3100) resulted in an NOAEL of 1.41 (males) and 19.2 (females) mg/
kg/day. The LOAEL was 14.3 (male) and 231 (female) mg/kg/day based on 
increased incidence of hepatocellular hypertrophy. At higher dose 
levels: Decrease in body weight and body weight gain, necrosis of 
individual hepatocytes, pigmentation of Kupffer cells, and lymphocytic 
infiltration of the

[[Page 16044]]

liver in both sexes; slight hematologic effects and decreased absolute 
and relative kidney weights in males; and ovarian atrophy, decreased 
ovary and spleen weights and increased liver weights in females.
     In a 90-day oral toxicity study in dogs (OPPTS Harmonized 
Guideline 870.3150), the NOAEL is 8.23 (males) and 9.27 (females) mg/
kg/day. The LOAEL is 32.0 (male) and 33.9 (female) mg/kg/day based on 
slightly prolonged prothrombin times and decreased plasma albumin and 
A/G ration (both sexes); decreased calcium levels and ovary weights and 
delayed maturation in the ovaries (female); decreased cholesterol and 
phospholipid levels, testis weights, spermatogenesis, and spermatic 
giant cells in testes (male).
     In a 28-day dermal study in rats (OPPTS Harmonized Guideline 
870.3200), the NOAEL was 250 (male) and 60 (female) mg/kg/day. The 
LOAEL was 1,000 (male) and 250 (female) mg/kg/day based on increased 
plasma glucose, triglyceride levels, and alkaline phosphatase activity 
and inflammatory cell infiltration in the liver and necrosis if single 
hepatocytes in females and hyaline change in renal tubules and a very 
slight reduction in body weight in males. At higher dose levels in 
females, chronic tubular lesions in the kidneys and inflammatory cell 
infiltration in the adrenal cortex were observed.
     In a subchronic neurotoxicity screening study in rats (OPPTS 
Harmonized Guideline 870.6200) the NOAEL was 95.4 (male) and 216.4 
(female) mg/kg/day, both at highest dose tested. The LOAEL was not 
determined. No treatment related observations at any dose level. LOAEL 
was not achieved. May not have been tested at sufficiently high dose 
levels; however, a new study is not required because the weight of the 
evidence from other toxicity studies indicates no evidence of concern.
    5. Chronic toxicity. In a chronic toxicity study in dogs (OPPTS 
Harmonized Guideline 870.4100) the NOAEL was 4.05 (male) and 4.49 
(female) mg/kg/day. The LOAEL was 21.0 (male) and 24.6 (female) mg/kg/
day based on increase of creatinine in both sexes, transient decrease 
in food consumption in females, and occasional increase in urea levels, 
decrease in ALT, and atrophy of seminiferous tubules in males.
     In a mouse carcinogenicity study (OPPTS Harmonized Guideline 
870.4200), the NOAEL was 2.63 (male) and 3.68 (female) mg/kg/day. The 
LOAEL was 63.8 (male) and 87.6 (female) mg/kg/day based on hepatocyte 
hypertrophy, single cell necrosis, inflammatory cell infiltration, 
pigment deposition, foci of cellualr alteration, hyperplasia of kupffer 
cells and increased mitotic activity, also an increase in the incidence 
of hepatocellular adenoma (both sexes). At higher doses, there was an 
increase in the incidence of hepatocelluar adenocarcinoma (both sexes) 
and the number of animals with multiple tumors, evidence of 
carcinogenicity.
     In a combined chronic caricinogenicity study in rats (OPPTS 
Harmonized Guideline 870.4300) the NOAEL was 21.0 (male) and 50.3 
(female) mg/kg/day. The LOAEL was 63.0 (male) and 255 (female) mg/kg/
day based on increased incidence of lymphocytic infiltration of the 
renal pelvis and chronic nephropathy in males and decreased body weight 
gain, slight increase in the severity of hemosiderosis of the spleen, 
foci of cellular alteration in liver and chronic tubular lesions in 
kidney in females. No evidence of carcinogenicity.
     In a hepatic cell proliferation study in mice, the NOAEL was 16 
(male) and 20 (female) mg/kg/day. The LOAEL was 72 (male) and 87 
(female) mg/kg/day based on proliferative activity of hepatocytes. At 
higher dose levels, increases in absolute and relative liver weights, 
speckled liver, heptocellular glycogenesis/fatty change, heptocellular 
necrosis, apoptosis and pigmentation were observed.
     In a 28-day feeding study to assess replicative DNA synthesis in 
the male rat, the NOAEL was 711 mg/kg/day. The LOAEL was not 
established. Immunohistochemical staining of liver sections from 
control and high dose animals for proliferating cell nuclear antigen 
gave no indication for a treatment related increase in the fraction of 
DNA syntesizing hepatocytes in S-phase. CGA-293343 did not stimulate 
hepatocyte cell proliferation in male rats.
     In a special study to assess liver biochemistry in the mouse, the 
NOAEL was 17 (male) and 92 (female) mg/kg/day. The LOAEL was 74 (male), 
92 (female) mg/kg/day based on marginal to slight increases in absolute 
and relative liver weights, a slight increase in the microsomal protein 
content of the livers, moderate increases in the cytochrome P450 
content, slight to moderate increases in the activity of several 
microsomal enzymes, slight to moderate induction of cytosolic 
glutathionw S-transfersase activity. Treatment did not affect 
peroxisomal fatty acid B-oxidation.
    6. Animal metabolism. The metabolism of thiamethoxam in rats and 
livestock animals is adequately understood. The residues of concern 
have been determined to be parent thiamethoxam and its metabolite N-(2-
chloro-thiazol-5-ylmethyl)-N'methyl-N-nitro-guanidine.
    7. Metabolite toxicology. For risk assessment purposes, residues of 
the metabolite corrected for molecular weight are considered to be 
toxicologically equivalent to parent thiamethoxam.

C. Aggregate Exposure

    1. Dietary exposure. Permanent tolerances have been established (40 
CFR 180.565) for the combined residues of the insecticide thiamethoxam, 
3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-
oxadiazin-4-imine and its metabolite N-(2-chloro-thiazol-5-ylmethyl)-
N'-methyl-N-nitro-guanidine, in or on a variety of raw agricultural 
commodities levels ranging from 0.02 parts per million (ppm) to 1.5 ppm 
(including barley, canola, corn, cotton, sorghum, wheat, cucurbit 
vegetables, fruiting vegetables, pome fruits, tuberous and corm 
vegetables and livestock commodities).
     Pending tolerances include coffee (imported), grapes, raisins, 
grape juice, pecans, sunflower seed, stone fruits, succulent beans, 
peppermint and spearmint tops, head and stem brassica, leafy brassica 
greens and leafy vegetables.
     Tier III chronic and Tier I acute dietary exposure evaluations 
were made using the Dietary Exposure Evaluation Model 
(DEEMTM), version 7.76 from Exponent. All processing factors 
were taken from the EPA assessment of August 28, 2000 (DP Barcode 
D268606, PC Code 060109). These assessment results include all current 
tolerances and the proposed tolerances on stone fruit, mint, succulent 
beans, sunflower seed, pecans, leafy vegetables, leafy brassica 
vegetables, brassica head and stem vegetables and imported coffee.
     For the Tier I acute assessment, the proposed tolerance residues 
for these commodities (stone fruit, 0.5 ppm; mint, 4.0 ppm; succulent 
beans, 0.02 ppm; sunflower seed, 0.02 ppm; pecans, 0.02 ppm; leafy 
vegetables, 2.0 ppm; leafy brassica vegetables, 2.0 ppm; brassica head 
and stem vegetables, 1.0 ppm; and imported coffee, 0.05 ppm) were used 
along with the published tolerances for all other commodities. One 
hundred percent of crop treated was assumed for all commodities in the 
acute assessment.
     In the chronic assessments, residue values for secondary animal 
commodities, pome fruits, ginger, turmeric, peppers, potatoes, wheat 
and barley were taken from the EPA assessment of August 28, 2000 which

[[Page 16045]]

uses average field trial residue data with 
1/89/21/13/23/85/83/8 LOQ substitutions for all non-detectable 
residues. In addition, a residue value of 0.011 ppm 
(1/89/21/13/23/85/83/8 LOQ) and a percent crop treated value 
of 6.6% were used for all corn commodities. For the remaining 
registered and the proposed commodities listed above, the following 
residue data was used in the DEEMTM: Cucurbit, leafy and 
brassica vegetables and tomatoes - average field trial residues from 
soil-only application residue studies; stone fruits, mint, succulent 
beans, sunflower seed, and coffee - average field trial residue data 
with 1/89/21/13/23/85/83/8 LOQ substitutions for non-
detectable residues; and pecans - the proposed tolerance.
     In regard to the cucurbit vegetables and tomatoes, the current 
tolerances are based upon soil and foliar uses; however, Syngenta is 
currently limiting the use of thiamethoxam in these crops to soil only 
applications - thus, the refinement in DEEMTM inputs 
described above. Likewise, the proposed tolerances on leafy vegetables, 
leafy brassica vegetables and head and stem brassica vegetables are 
based upon soil and foliar applications of thiamethoxam; however, 
Syngenta is currently pursuing only the soil application use - thus, 
the refinement of DEEM inputs described above. Syngenta will pursue 
foliar applications for these crops at a later date; therefore, the 
proposed and current tolerances on these crops remain based upon soil 
and foliar applications.
     All consumption data for these assessments was taken from the 
USDA's Continuing Survey of Food Intake by Individuals (CSFII) with the 
1994-96 consumption data base and the supplemental CSFII children's 
survey (1998) consumption data base. For the chronic assessments, the 
following percent of crop treated values were used for the proposed 
uses: Coffee, 16.7%; sunflower, 15%; mint, 10%; leaf lettuce, 24.6%; 
head lettuce, 32%; spinach and cress, 15.6%; all other leafy 
vegetables, 19.4%; broccoli, 26.2%, cabbage, 15.3%; all other brassica 
vegetables 17.2%; beans, 20%; stone fruits, 15%; and pecans, 100%. A 
percent crop treated value of 5% was used for apples and a value of 
6.6% was used for all corn commodities. All other percent of crop 
treated values were taken from the August 28, 2000 EPA assessment.
    i. Food. For the purposes of assessing the potential dietary 
exposure under the proposed tolerances, Syngenta Crop Protection has 
estimated aggregate exposure from all crops for which tolerances are 
established or proposed. The Tier I acute assessment utilized tolerance 
values and 100% of crop treated values. The Tier III chronic 
assessments utilized the residue and percent of crop treated values 
described above.
    a. Acute exposure. An acute reference dose of 0.10 mg/kg bwt/day 
for all population subgroups was based on a NOAEL of 100 mg/kg bwt/day 
from an acute neurotoxicity study in rats and an uncertainty factor of 
100X (100X for combined interspecies and intraspecies variability). An 
additional Food Quality Protection Act (FQPA) safety factor of 10X was 
applied to all population subgroups due to the absence of a 
developmental neurotoxicity study. For the purpose of aggregate risk 
assessment, the exposure value was expressed in terms of margin of 
exposure (MOE). The MOE was calculated by dividing the NOAEL by the 
exposure for each population subgroup. In addition, exposure was 
expressed as a percent of the acute reference dose (%aRfD). Acute 
exposure to the most exposed subpopulation (children 1-6 years old) 
resulted in a MOE of 6,452 (15.5% of the aRfD of 0.10 mg/kg/ bwt/day) 
at the 95th percentile of exposure. Since the benchmark MOE 
for this assessment was 1,000, and since EPA generally has no concern 
for exposures below 100% of the aRfD, Syngenta believes that there is a 
reasonable certainty that no harm will result from acute dietary (food) 
exposure to residues arising from the current and proposed uses for 
thiamethoxam chronic exposure.
    b. Chronic exposure. The chronic reference dose (cRfD) for 
thiamethoxam is 0.0006 mg/kg/ bwt/day for all population subgroups and 
is based on a NOAEL of 0.6 mg/kg/bwt/day from a two generation rat 
reproduction study. An uncertainty factor of 100X (for combined 
interspecies and intraspecies variability) and an additional FQPA 
safety factor of 10X was applied due to evidence of increased 
susceptibility to young rats following prenatal/postnatal exposure. 
Exposure was expressed as MOE and percent of the reference dose (%RfD). 
Chronic exposure to the most exposed subpopulation (non-nursing 
infants) resulted in a MOE of 11,538 (8.6% of the cRfD of 0.0006 mg/kg/
bw/day). Since the benchmark MOE for this assessment was 1,000 and 
since EPA generally has no concern for exposures below 100% of the RfD, 
Syngenta believes that there is a reasonable certainty that no harm 
will result from chronic dietary (food) exposure to residues arising 
from the current and proposed uses for thiamethoxam.
    c. Lifetime exposure. The Q* value for thiamethoxam is 0.0377 (mg/
kg/day)-1 and is based on benign and malignant heptocellular 
tumors in mice in an 18-month carcinogenicity study. Lifetime exposure 
to the U.S. population resulted in a lifetime risk of 8.17 x 
10-7 which represents 81.7% of EPA's lifetime risk limit of 
1.0 x 10-6.
    ii. Drinking water. EPA used the Pesticide Root Zone/Exposure 
Analysis Modeling System (PRZM/EXAMS) to estimate pesticide 
concentrations in surface water and SCI-GROW, which predicts pesticide 
concentrations in ground water. None of these models include 
consideration of the impact processing (mixing, dilution, or treatment) 
of raw water for distribution as drinking water would likely have on 
the removal of pesticides from the source water. The primary use of 
these models by the Agency at this stage is to provide a coarse screen 
for sorting out pesticides for which it is highly unlikely that 
drinking water concentrations would ever exceed human health levels of 
concern. Based on the SCI-GROW and PRZM/EXAMS models, EPA calculated 
that estimated environmental concentrations of thiamethoxam at the 
highest use rate (0.125 lb a.i./acre) are 1.9 parts per billion (ppb) 
for acute and chronic exposure to ground water and 11.4 ppb and 0.77 
ppb for acute and chronic exposure, respectively, to surface water. 
Based on field and laboratory data as well as on going prospective 
ground water monitoring studies, Syngenta believes that the potential 
exposure to ground water is much lower than that predicted by the 
conservative SCI-GROW model.
     Preliminary results from the prospective ground water monitoring 
studies have indicated no detections of thiamethoxam in ground water. 
EPA determined estimated environmental concentrations (EECs) are used 
for comparison to Drinking Water Levels of Comparison (DWLOC).
    a. Acute drinking water risk. Acute DWLOCs were calculated based on 
an acute populated adjusted dose (aPAD) of 0.1 mg/kg/day. For the acute 
assessment, the children (1-6 yrs) subpopulation generated the lowest 
acute DWLOC of approximately 845 ppb. EPA has determined that the 
surface water acute EEC is 11.4 ppb and the ground water EEC is 1.9 
ppb. Since the surface water value is greater than the ground water 
value, the surface water value will be used for comparison purposes and 
will protect for any concerns for ground water concentrations. Since 
the acute DWLOC of 845 ppb is considerably higher than the acute EEC of 
11.4 ppb, Syngenta believes that EPA should not have a concern for 
acute risk to either surface or ground water.

[[Page 16046]]

    b. Chronic drinking water risk. Chronic DWLOCs were calculated 
based on a cPAD of 0.0006 mg/kg/day. For the chronic assessment, the 
non-nursing infants subpopulation generated the lowest chronic DWLOC of 
approximately 5.5 ppb. EPA has determined that the surface water 
chronic EEC is 0.77 ppb and the ground water EEC is 1.9 ppb. Since the 
ground water value is greater than the surface water value, the ground 
water value will be used for comparison purposes and will protect for 
any concerns for surface water concentrations. Since the chronic DWLOC 
of 5.5 ppb is higher than the chronic EEC of 1.9 ppb, Syngenta believes 
that EPA should not have a concern for chronic risk to either surface 
or ground water.
    c. Lifetime drinking water risk. Based on currently registered and 
proposed uses for thiamethoxam, Syngenta has determined a DWLOC of 2.0 
ppb. At the currently registered maximum use rate of 0.125 lbs. a.i. 
per acre per growing season, EPA has used the SCI-GROW model to predict 
a ground water EEC of 1.9 ppb. Thus, the ground water EEC is below the 
lifetime DWLOC for the general population. The Agency used a screening 
level model designed to estimate pesticide concentrations in shallow 
ground water. A number of factors demonstrate that the actual lifetime 
exposure through drinking water will be less than the lifetime DWLOC. 
These reasons are as follows:
    [sbull] Thiamethoxam is a systemic pesticide. EPA's Tier I ground 
water model assumes that all of the product that is applied to the crop 
is available for run off. Syngenta has submitted data to show that a 
percentage (15-25%) of the product is absorbed by the plant, resulting 
in that much less product available to leach into ground water. 
Although, data submitted is on only two crops (beans and cucumbers), it 
is likely that the total amount of thiamethoxam available for ground 
water leaching is less than the amount EPA uses as a model input.
    [sbull] Although, the Agency model is based on aerobic soil half 
lives, EPA's lifetime risk assessment is for lifetime exposure. Data 
indicate the anaerobic aquatic half-life for thiamethoxam is shorter 
than the aerobic soil half-life and longer than the aerobic aquatic 
half-life. Although, EPA is unable to predict, with a high degree of 
certainty, what happens to thiamethoxam ground water over time, this 
does provide some support for the expectation that concentrations in 
ground water will decline between annual applications.
    [sbull] Shallow ground water modeling is not the perfect model for 
representing all drinking water from ground water sources. It is likely 
to be an over estimate of most drinking water concentrations, which 
tend to originate from deeper sources. EPA's experience is that the 
model is reasonably accurate for shallow drinking water, but it is less 
accurate for estimating concentrations in drinking water from deeper 
sources.
    [sbull] The Agency has established conditions of registration for 
the previous uses that include two prospective ground water studies and 
a retrospective monitoring study, so that the reasonable certainty of 
no harm finding will be sustained. Preliminary results have indicated 
no detections of thiamethoxam in ground water.
    [sbull] The dietary food risk is based on residue data derived from 
the average of field trials, which were performed at a higher 
application rate than what was accepted by EPA. It is not unusual in 
the Agency's experience for field trial data to be an order of 
magnitude above actual monitoring. Since thiamethoxam has only recently 
been registered, actual monitoring data are not yet available. It is 
likely that the actual risk contribution from food will be much lower 
than current data indicate, which would result in a larger lifetime 
DWLOC. Syngenta expects that this refined lifetime DWLOC would be 
larger than the EECs for the proposed uses. Based on the previous 
points, Syngenta does not expect that the general population would be 
exposed to levels exceeding the lifetime DWLOC.
    2. Non-dietary exposure. Thiamethoxam is not currently registered 
for use on any sites that would result in residential exposure.

D. Cumulative Effects

     The potential for cumulative effects of thiamethoxam and other 
substances that have a common mechanism of toxicity has also been 
considered. Thiamethoxam belongs to a new pesticide chemical class 
known as the neonicotinoids. There is no reliable information to 
indicate that toxic effects produced by thiamethoxam would be 
cumulative with those of any other chemical including another 
pesticide. Therefore, Syngenta believes it is appropriate to consider 
only the potential risks of thiamethoxam in an aggregate risk 
assessment.

E. Safety Determination

     Syngenta concludes, as described above, that there is reasonable 
certainty that no harm to the U.S. population will result from 
aggregate acute or chronic dietary exposure to thiamethoxam residues 
including the proposed commodities.

F. International Tolerances

     There are no codex MRLs established for residues of thiamethoxam.
[FR Doc. 03-7803 Filed 4-1-03; 8:45 am]
BILLING CODE 6560-50-S