[Federal Register Volume 64, Number 86 (Wednesday, May 5, 1999)]
[Notices]
[Pages 24153-24160]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-11169]


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ENVIRONMENTAL PROTECTION AGENCY

[PF-870; FRL-6072-7]


Notice of Filing of Pesticide Petitions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: This notice announces the initial filing of pesticide 
petitions proposing the establishment of regulations for residues of 
certain pesticide chemicals in or on various food commodities.

DATES: Comments, identified by the docket control number PF-870, must 
be received on or before June 4, 1999.

ADDRESSES: By mail submit written comments to: Public Information and 
Records Integrity Branch, Information Resources and Services Division 
(7502C), Office of Pesticides Programs, Environmental Protection 
Agency, 401 M St., SW., Washington, DC 20460. In person bring comments 
to: Rm. 119, CM #2, 1921 Jefferson Davis Highway, Arlington, VA.
    Comments and data may also be submitted electronically to: opp-
[email protected]. Follow the instructions under ``SUPPLEMENTARY 
INFORMATION.'' No confidential business information should be submitted 
through e-mail.
    Information submitted as a comment concerning this document may be 
claimed confidential by marking any part or all of that information as 
``Confidential Business Information'' (CBI). CBI should not be 
submitted through e-mail. Information marked as CBI will not be 
disclosed except in accordance with procedures set forth in 40 CFR part 
2. A copy of the comment that does not contain CBI must be submitted 
for inclusion in the public record. Information not marked confidential 
may be disclosed publicly by EPA without prior notice. All written 
comments will be available for public inspection in Rm. 119 at the 
address given above, from 8:30 a.m. to 4 p.m., Monday through Friday, 
excluding legal holidays.

FOR FURTHER INFORMATION CONTACT: The product manager listed in the 
table below:

------------------------------------------------------------------------
                                   Office location/
        Product Manager            telephone number          Address
------------------------------------------------------------------------
Dani Daniel...................  Rm. 211, CM #2, 703-    1921 Jefferson
                                 305-5409, e-            Davis Hwy,
                                 mail:daniel.dani@epam   Arlington, VA
                                 ail.epa.gov.
Cynthia Giles-Parker (PM 22)..  Rm. 249, CM #2, 703-    Do.
                                 305-7740, e-mail:
                                 giles-
parker.cynthia@epamai
l.epa.gov.
------------------------------------------------------------------------

SUPPLEMENTARY INFORMATION: EPA has received pesticide petitions as 
follows proposing the establishment and/or amendment of regulations for 
residues of certain pesticide chemicals in or on various food 
commodities under section 408 of the Federal Food, Drug, and Comestic 
Act (FFDCA), 21 U.S.C. 346a. EPA has determined that these petitions 
contain data or information regarding the elements set forth in section 
408(d)(2); however, EPA has not fully evaluated the sufficiency of the 
submitted data at this time or whether the data supports granting of 
the petition. Additional data may be needed before EPA rules on the 
petition.
    The official record for this notice of filing, as well as the 
public version, has been established for this notice of filing under 
docket control number [PF-870] (including comments and data submitted 
electronically as described below). A public version of this record, 
including printed, paper versions of electronic comments, which does 
not include any information claimed as CBI, is available for inspection 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The official record is located at the address in 
``ADDRESSES'' at the beginning of this document.
    Electronic comments can be sent directly to EPA at:
    [email protected]


    Electronic comments must be submitted as an ASCII file avoiding the 
use of special characters and any form of encryption. Comments and data 
will also be accepted on disks in Wordperfect 5.1 file format or ASCII 
file format. All comments and data in electronic form must be 
identified by the docket number (insert docket number) and appropriate 
petition number. Electronic comments on notice may be filed online at 
many Federal Depository Libraries.

List of Subjects

    Environmental protection, Agricultural commodities, Food additives, 
Feed additives, Pesticides and

[[Page 24154]]

pests, Reporting and recordkeeping requirements.

    Dated: April 23, 1999.

Peter Caulkins, Acting

Director, Registration Division, Office of Pesticide Programs.

Summaries of Petitions

    Petitioner summaries of the pesticide petitions are printed below 
as required by section 408(d)(3) of the FFDCA. The summaries of the 
petitions were prepared by the petitioners and represent the views of 
the petitioners. EPA is publishing the petition summaries verbatim 
without editing them in any way. 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.

1. Novartis Crop Protection, Inc.

PP 9F5045

    EPA has received a pesticide petition (9F5045) from Novartis Crop 
Protection, Inc., P.O.Box 18300, Greensboro, NC 27419-8300 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 difenoconazole ((2S,4R)/(2R,4S)/(2R,4R)/
(2S,4S) 1-(2-(4-(4-chlorophenoxy)-2-chlorophenyl)-4-methyl-1,3-
dioxolan-2-yl)methyl-1H-1,2,4-triazole) in or on the raw agricultural 
commodity (RAC) rapeseed at 0.01 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.

A. Residue Chemistry

    1. Plant metabolism. The nature of the residues in plants is 
understood for the purpose of the proposed tolerance. The metabolism of 
14C-difenoconazole has been studied using both phenyl and 
triazole labels in wheat, tomatoes, potatoes, grapes, and spring rape 
The metabolic pathway was the same in these four separate and distinct 
crops.
    2. Analytical method--i. Food. Novartis Crop Protection, Inc. has 
submitted a practical analytical method (AG-575B, master record 
identification (MRID) No. 428065-04) for detecting and measuring levels 
of difenoconazole in or on food with a limit of quantitation (LOQ) that 
allows monitoring of food with residues at or above the levels set in 
the proposed tolerances. EPA has validated this method and copies have 
been provided to FDA for insertion into pesticide analytical manual 
(PAM) II. The method is available to anyone who is interested, and may 
be obtained from the Field Operations Division, Office of Pesticide 
Programs.
    ii. Livestock. Novartis Crop Protection, Inc. has submitted a 
practical analytical method (AG-544A, MRID-43292401) for detecting and 
measuring levels of difenoconazole in or on cattle tissues and milk and 
poultry tissues and eggs, with a LOQ that allows monitoring of food 
with residues at or above the levels set in the proposed tolerances. 
EPA has validated this method and copies have been provided to FDA for 
insertion into PAM II. The method is available to anyone who is 
interested, and may be obtained from the Field Operations Division, 
Office of Pesticide Programs.
    3. Magnitude of residues--i. Food. Six field trials were analyzed 
in concordance with the OPPTS guidelines based on expected reduced 
residues and environmental benefits of seed applications. The six 
trials, held in areas representing approximately 84% of commercial 
United States canola production (Agricultural Statistics, 1991), were 
conducted in Georgia (2%), Minnesota (16%), North Dakota (53%), South 
Dakota (2%), Idaho (6%), and Washington (5%). No residues were detected 
in rape seed at either a 1x or 3x treatment rate.
    ii. Livestock. No tolerances are necessary for grain commodities. 
Tolerances in meat, milk, poultry or eggs were established for 
enforcement purposes.

B. Toxicological Profile

    The following mammalian toxicity studies were conducted and 
submitted in support of the establishment of tolerances for 
difenoconazole.
    1. Acute toxicity. Difenoconazole has a low order of acute 
toxicity. The oral rat LD50 is 1,453 milligram/kilogram (mg/
kg). The rabbit acute dermal LD50 is > 2,010 mg/kg and the 
rat inhalation LC50 is > 3.285 milligrams per liter (mg/L). 
Difenoconazole is not a skin sensitizer in guinea pig and shows slight 
eye and dermal irritation in the rabbit.
    2. Genotoxicity. There was no evidence of the induction of point 
mutations in an Ames test, no evidence of mutagenic effects in a mouse 
lymphoma test or in a nucleus anomaly test with Chinese hamsters, and 
no evidence of induction of DNA damage in a rat hepatocyte DNA repair 
test or in a human fibroblast DNA repair test.
    3. Reproductive and developmental toxicity. An oral teratology 
study in rats had a maternal no-observed adverse effect level (NOAEL) 
of 16 mg/kg/day based on excess salivation and decreased body weight 
gain and food consumption. The developmental NOAEL of 85 mg/kg/day was 
based on effects seen secondary to maternal toxicity including slightly 
reduced fetal body weight and minor changes in skeletal ossification. 
An oral teratology study in rabbits had a maternal NOAEL of 25 mg/kg/
day based on decreased body weight gain, death, and abortion. The 
developmental NOAEL of 25 mg/kg/day was based on effects seen secondary 
to maternal toxicity including a slight increase in post-implantation 
loss and resorptions, and decreased fetal weight. A 2-generation 
reproduction study in rats had a parental and reproductive NOAEL of 25 
part per million (ppm) based on significantly reduced female body 
weight gain, and reductions in male pup weights at 21-days.
    4. Subchronic toxicity. A 13-week rat feeding study identified 
liver as a target organ and had a NOAEL of 20 ppm. A 13-week mouse 
feeding study also identified liver as a target organ and had a NOAEL 
of 20 ppm. A 26-week dog feeding study further identified liver, and 
also the eyes, as target organs and had a NOAEL of 100 ppm. A 21-day 
dermal study in rabbits had a NOAEL of 10 mg/kg/day based on decreased 
body weight gain at 100 and 1,000 mg/kg/day.
    5. Chronic toxicity. A 24-month feeding study in rats had a NOAEL 
of 20 ppm based on liver toxicity at 500 and 2,500 ppm. An 18-month 
mouse feeding study had an overall NOAEL of 30 ppm based on decreased 
body weight gain and liver toxicity at 300 ppm. A 12-month feeding 
study in dogs had a NOAEL of 100 ppm based on decreased food 
consumption and increased alkaline phosphatase levels at 500 ppm.
    6. Carcinogenicity. A 24-month feeding study in rats had a NOAEL of 
20 ppm based on liver toxicity at 500 and 2,500 ppm. There was no 
evidence of an oncogenic response. An 18-month mouse feeding study had 
an overall NOAEL of 30 ppm based on decreased body weight gain and 
liver toxicity at 300 ppm. There was an increase in liver tumors only 
at dose levels that exceeded the maximum tolerated dose (MTD). The 
oncogenic NOAEL was 300 ppm.
    7. Animal metabolism. The metabolism of difenoconazole is well 
understood. Studies with 14C-difenoconazole in the rat, 
goat, and hen demonstrate that the majority of the

[[Page 24155]]

administered dose (76 to > 98%) is eliminated via the excreta as parent 
and metabolites. Very low concentrations of radioactivity, accounting 
for < 1 to 4% of the applied dose, remain in tissues. The liver and 
kidney typically show the highest radioactivity, but in the rat, the 
highest concentration in any tissue was found in the fat. 
Concentrations in goat milk reached a plateau on day 6 of the study at 
0.043 ppm for the triazole label and 0.007 ppm for the phenyl label 
when goats were fed approximately 5 ppm for 10 days. Similarly, very 
little radioactivity was deposited in eggs; radioactivity reached a 
plateau of 0.248 to 0.299 ppm in yolks after 7 to 8-days, and 0.007 to 
0.153 ppm in whites after 5 days, in hens fed at a rate equivalent to 5 
ppm in the diet for 14 consecutive days. CGA-205375, an alcohol 
resulting from the deketalization of the dioxolane ring of 
difenoconazole, is a major metabolite found in animal tissues, excreta, 
milk, and eggs. The presence of CGA-71019, containing only the triazole 
ring, and CGA-189138, containing only the phenyl ring, indicates that 
bridge cleavage can occur in animals as well as plants. The metabolite 
patterns in the excreta of hens, goats, and rats were similar.
    8. Metabolite toxicology. The residue of concern for tolerance 
setting purposes is the parent compound. Metabolites of difenoconazole 
are considered to be of equal or lesser toxicity than the parent.
    9. Endocrine disruption. Developmental toxicity studies in rats and 
rabbits and a 2-generation reproduction study in rats gave no specific 
indication that difenoconazole may have effects on the endocrine system 
with regard to development or reproduction. Furthermore, histologic 
investigations were conducted on endocrine organs (thyroid, adrenal, 
and pituitary, as well as endocrine sex organs) from long-term studies 
in dogs, rats, and mice. There was no indication that the endocrine 
system was targeted by difenoconazole, even when animals were treated 
with maximally tolerated doses over the majority of their lifetime. 
Difenoconazole has not been found in RAC at the LOQ. Based on the 
available toxicity information and the lack of detected residues, it is 
concluded that difenoconazole has no potential for interfering with the 
endocrine system, and there is no risk of endocrine disruption in 
humans.

C. Aggregate Exposure

    1. Dietary exposure--i. Food. When the potential dietary exposure 
to difenoconazole from established and pending tolerances (assuming 
100% treated) is calculated, the theoretical maximum residue 
concentration (TMRC) of 0.000583 mg/kg/day utilizes 5.83% of the 
reference dose (RfD) for the overall U. S. population. For the most 
exposed population subgroups, non-nursing infants, the TMRC is 0.001656 
mg/kg/day, utilizing 16.56% of the RfD, followed by children (1-6 years 
old), who are exposed to 14.58% of the RfD. In this analysis, canola 
does not contribute to exposure.
    ii. Drinking water. Other potential sources of exposure of the 
general population to residues of pesticides are in drinking water and 
from non-occupational activities. Difenoconazole is currently used as a 
seed treatment and residues are, therefore, incorporated into the soil. 
The likelihood of contamination of surface water from run-off is 
essentially negligible. In addition, parent and aged leaching, soil 
adsorption/desorption, and radiolabeled pipe studies indicated that 
difenoconazole has a low potential to leach in the soil and it would 
not be expected to reach aquatic environments. For these reasons, and 
because of the low use rate, exposures to residues in ground and 
surface water are not anticipated to contribute significantly to the 
aggregate exposure profile for difenoconazole.
    2. Non-dietary exposure. Non-occupational exposure to 
difenoconazole has not been estimated since the current registration is 
limited to seed treatment. Therefore, the potential for non-
occupational exposure to the general population is insignificant.

D. Cumulative Effects

    Novartis has considered the potential for cumulative effects of 
difenoconazole and other substances of common mechanism of toxicity. 
Novartis has concluded that consideration of a common mechanism of 
toxicity in aggregate exposure assessment is not appropriate at this 
time. Novartis has no reliable information to indicate that the toxic 
effects (generalized liver toxicity) seen at high doses of 
difenoconazole would be cumulative with those of any other compound. 
Thus, Novartis is considering only the potential risk of difenoconazole 
from dietary exposure in its aggregate and cumulative exposure 
assessment.

E. Safety Determination

    1. U.S. population. Using very conservative exposure assumptions 
(tolerance levels for 100% of the United States market) described and 
based on the completeness of the toxicity data base for difenoconazole, 
Novartis calculates that aggregate exposure to difenoconazole utilizes 
< 6% of the RfD for the U.S. population based on chronic toxicity 
endpoints (NOAEL = 1 mg/kg/day). If more realistic assumptions were 
used to estimate anticipated residues and appropriate market share, 
this percentage would be considerably lower, and would be significantly 
lower than 100%, even for the most highly exposed population subgroup. 
EPA generally has no concern for exposures below 100% of the RfD. 
Therefore, Novartis concludes that there is a reasonable certainty that 
no harm will result from daily aggregate exposure to residues of 
difenoconazole over a lifetime of exposure.
    2. Infants and children. Developmental toxicity and 2-generation 
toxicity studies were evaluated to determine if there is a special 
concern for the safety of infants and children from exposure to 
residues of difenoconazole. There was no evidence of embryotoxicity or 
teratogenicity, and no effects on reproductive parameters, including 
number of live births, birth weights, and post-natal development, at 
dose levels that did not cause significant maternal toxicity. In 
addition, there were no effects in young post-weaning animals that were 
not seen in adult animals in the 2-generation reproduction study. 
Therefore, Novartis concludes that it is inappropriate to assume that 
infants and children are more sensitive than the general population to 
effects from exposure to residues of difenoconazole, and also concludes 
that the use of an additional safety factor to protect infants and 
children is unnecessary.

F. International Tolerances

    There are pending Codex maximum residue levels (MRLs) for this 
compound in Mexico for oats, wheat, and barley. There are also MRLs for 
this compound in Australia for carrots at 0.02 ppm, and bananas at 0.05 
ppm.

2. Novartis Crop Protection, Inc.

PP 9F5046

    EPA has received a pesticide petition (9F5046) from Novartis Crop 
Protection, Inc., PO Box 18300, Greensboro, North Carolina 27419 
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 Thiamethoxam in or on the raw 
agricultural commodity (RAC) rape seed at 0.02 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

[[Page 24156]]

has not fully evaluated the sufficiency of the submitted data at this 
time or whether the data supports granting of the petition. Additional 
data may be needed before EPA rules on the petition.

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 major metabolites 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. Novartis Crop Protection Inc. has submitted 
practical analytical methodology for detecting and measuring levels of 
thiamethoxam in or on RAC. The method is based on crop specific cleanup 
procedures and determination by liquid chromatography with either 
ultraviolet (UV) or mass spectrometry (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 parts per million (ppm) for all other 
substrates.
    3. Magnitude of residues. A residue program was performed for 
thiamethoxam on a full geography of canola, using a maximum application 
rate of 400 g.a.i./100 kilogram (kg) seed (0.024 lbs. a.i./acre, at the 
typical seeding rate). Two field trials also included seed treated at 3 
times the normal rate for thiamethoxam. No residues were detected above 
the method LOD for thiamethoxam. The proposed tolerance on canola is 
0.02 ppm for thiamethoxam.

B. Toxicological Profile

    1. Acute toxicity. Thiamethoxam has low acute toxicity. The oral 
LD50 in rats is 1,563 millogram kilogram (mg/kg) for males 
and females, combined. The rat dermal LD50 is > 2,000 mg/kg 
and the rat inhalation LC50 is > 3.72 milligrams per liter 
(mg/L) air. Thiamethoxam is not a skin sensitizer in guinea pigs and 
does not produce dermal or eye irritation in rabbits. End-use 
formulations of thiamethoxam have similar low acute toxicity profiles.
    2. Genotoxicty. Thiamethoxam did not induce point mutations in 
bacteria (Ames assay in Salmonella typhimurium and Escherichia coli) or 
in cultured mammalian cells (Chinese hamster V79) and was not genotoxic 
in an in vitro unscheduled DNA synthesis assay in rat hepatocytes. 
Chromosome aberrations were not observed in an in vitro test using 
Chinese hamster ovary cells and there were no clastogenic or aneugenic 
effects on mouse bone marrow cells in an in vivo mouse micronucleus 
test. These studies show that thiamethoxam is not genotoxic.
    3. Reproductive and developmental toxicity. In rat and rabbit 
teratology studies with thiamethoxam there was no evidence of 
teratogenicity. In rabbits, thiamethoxam caused decreased body weights 
(bwt), decreased food consumption and premature death of two females 
administered 150 mg/kg/day during gestation. This maternal toxicity was 
accompanied by reduced fetal bwts and an increase in the incidence of 
minor skeletal anomalies or variations. Reduced maternal bwts and food 
consumption were also noted in females administered 50 mg/kg/day 
thiamethoxam during gestation. There was no indication of developmental 
toxicity at 50 mg/kg/day. The no-observable adverse effect level 
(NOAEL) in rabbits for maternal toxicity was 15 mg/kg/day. The NOAEL 
for developmental toxicity was 50 mg/kg/day. In rats, thiamethoxam 
caused decreased bwts, decreased food consumption and hypoactivity at 
200 and 750 mg/kg/day. Reduced fetal bwts and an increase in the 
incidence of minor skeletal anomalies and variations were observed only 
at 750 mg/kg/day. There was no indication of developmental toxicity at 
200 mg/kg/day. The NOAEL in rats for maternal toxicity was 30 mg/kg/day 
and for developmental toxicity was 200 mg/kg/day. In a 2-generation 
reproduction study in rats, parental bwts and food consumption were 
decreased at 2,500 ppm highest dose tested (HDT). Hyaline changes in 
the kidneys of adult males were observed at 2,500 and 1,000 ppm. 
Reproductive parameters were not affected by treatment with 
thiamethoxam. Effects on offspring were secondary to parental toxicity 
and consisted of slightly reduced offspring bwts at 1,000 ppm and 2,500 
ppm. The NOAEL for systemic toxicity in parental animals and for 
offspring toxicity was 30 ppm (equivalent to 1.3 - 6.4 mg/kg/day).
    4. Subchronic toxicity Thiamethoxam was evaluated in 13-week 
subchronic oral toxicity studies in rats, dogs and mice. Liver, kidneys 
and spleen were identified as target organs. The NOAEL was 25 ppm (1.74 
mg/kg/day) in male rats based on the finding of a hyaline change in the 
kidney at 250 ppm (17.6 mg/kg/day). This kidney effect represents an 
accumulation of alpha-2-microglobulin, which is unique to the male rat 
and not relevant for human risk assessment. The NOAEL was 1,250 ppm 
(92.5 mg/kg/day) for female rats. The NOAEL in dogs was 250 ppm (8.23 
mg/kg/day). The NOAEL in mice was 10 ppm (1.41 mg/kg/day) for males and 
100 ppm (19.2 mg/kg/day) for females. No dermal irritation was observed 
in a 28-day repeated dose dermal toxicity study with thiamethoxam in 
rats given 1,000 mg/kg/day. The dermal NOAEL for systemic toxicity in 
rats was 250 mg/kg/day for males and 60 mg/kg/day for females.
    5. Neurotoxicity. Thiamethoxam did not cause neurotoxicity in an 
acute neurotoxicity study in rats or in a subchronic 13-week 
neurotoxicity study in rats. The NOAEL for systemic toxicity in the 
acute neurotoxicity study was 100 mg/kg. The NOAEL for systemic 
toxicity in the subchronic neurotoxicity study was 95.4 mg/kg/day for 
males and 216.4 mg/kg/day for females.
    6. Chronic toxicity. The carcinogenic potential of thiamethoxam has 
been evaluated in rats and mice. The proposed carcinogenic 
classification for thiamethoxam is as a Group C carcinogen. This 
classification is based on a liver tumor response in male and female 
mice at dose levels exceeding the maximum tolerance dose (MTD) and/or 
causing organ toxicity and induction of liver metabolizing enzymes. A 
NOAEL for liver tumors in mice was established at 20 ppm (2.63 mg/kg/
day). No evidence of carcinogenicity was observed in rats. In the 
absence of a mutagenic activity, it is concluded that the mechanism of 
action leading to liver tumors in mice is not via genotoxic effects. 
Therefore, mouse liver tumors associated with thiamethoxam treatment 
have a threshold level.
    7. Animal metabolism. Metabolism of thiamethoxam has been well 
characterized in animals. Metabolism in rats proceeds primarily via 
hydrolysis of the oxadiazine ring, followed by N-demethylation. Several 
minor pathways of metabolism of thiamethoxam were identified in 
animals. In rats, the majority of the radioactive dose was absorbed and 
then excreted in the urine. Parent compound was the major residue in 
urine. In hens and goats, the metabolite profile was the same as in 
rats, with certain extensions of the pathway.
    8. Metabolite toxicology. The metabolism profile for thiamethoxam 
supports the use of an analytical enforcement method that accounts for 
parent thiamethoxam and CGA-322704. Other metabolites are considered of

[[Page 24157]]

equal or lesser toxicity than parent compound.
    9. Endocrine disruption. Thiamethoxam does not belong to a class of 
chemicals known or suspected of having adverse effects on the endocrine 
system. There is no evidence that thiamethoxam has any effect on 
endocrine function in developmental or reproduction studies. 
Furthermore, histological investigation of endocrine organs in chronic 
dog, rat and mouse studies did not indicate that the endocrine system 
is targeted by thiamethoxam.

C. Aggregate Exposure

    1. Dietary exposure--Food and drinking water. Chronic and acute 
dietary exposure to thiamethoxam was based on the occurrence of no 
detectable residues of thiamethoxam or its major metabolite resulting 
from the use of Helix on canola. There is no adverse exposure to 
thiamethoxam in the diet when chronic and acute assessments are made 
using tolerance level residues for canola oil (analytical method limit 
of quantitation (LOQ)), and 100% market share. The inclusion of the 
maximum concentration of thiamethoxam in water, taken from the highest 
estimated residue observed from the generic expected environmental 
concentration (GENEEC) and screening concentration In GROund (SCI-GROW) 
models, led to a maximum chronic exposure of 0.000019 mg/kg bwt/day in 
the most sensitive population subgroup, non-nursing infants (< 1-year 
old). This is only 0.1% of the proposed reference dose (RfD) of 0.013 
mg/kg bwt/day. The inclusion of the water concentration estimate in the 
acute exposure assessment led to a margin of exposure (MOE) (NOAEL/
exposure) of 264,491 at the 99.9th percentile of the most sensitive 
population subgroup, all infants (< 1-year old). The results of these 
analyses show that there is reasonable certainty that no harm will 
result from the exposure to dietary residues of thiamethoxam (including 
drinking water) from the use of Helix on canola.
    2. Non-dietary exposure. There are no other uses currently 
registered for thiamethoxam that would lead to exposure from non-
dietary sources. The proposed uses involve application of thiamethoxam 
to canola seed as part of the Helix product in an agricultural 
environment. A discussion of exposure from non-dietary sources will be 
made when future uses of thiamethoxam are proposed.

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, Novartis believes it is appropriate to consider 
only the potential risks of thiamethoxam in an aggregate risk 
assessment.

E. Safety Determination

    1. U.S. population. Using the exposure assumptions and the proposed 
RfD described above, the aggregate exposure (including drinking water) 
to thiamethoxam from the application of helix to canola will utilize < 
0.1% of the RfD for the U.S. population. Therefore, Novartis concludes 
that there is reasonable certainty that no harm will result from 
aggregate exposure to thiamethoxam residues from the use of helix on 
canola.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of thiamethoxam, data 
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat have been considered.
    In teratology studies, delayed fetal development was apparent only 
at maternally toxic doses of thiamethoxam in rats and rabbits. In 
rabbits, 150 mg/kg/day was clearly toxic to does, causing death, weight 
loss, reduced food consumption and perineal or vaginal discharge. 
Developmental toxicity occurred secondary to maternal toxicity and 
consisted of reduced fetal bwts and an increase in minor skeletal 
anomalies or variations. Maternal toxicity was also noted at 50 mg/kg/
day, consisting of reduced bwts and food consumption and total 
resorptions in one female. There was no indication of developmental 
toxicity at 50 mg/kg/day. The NOAEL for maternal toxicity was 15 mg/kg/
day and for developmental toxicity was 50 mg/kg/day in rabbits. In 
rats, 200 and 750 mg/kg/day caused maternal toxicity, but developmental 
toxicity secondary to maternal toxicity was observed only at 750 mg/kg/
day. The NOAEL for maternal toxicity was 30 mg/kg/day and for 
developmental toxicity was 200 mg/kg/day.
    In a rat multigeneration study, parental toxic effects were noted 
at 2,500 ppm (250 mg/kg/day). and 1,000 ppm (100 mg/kg/day). Offspring 
bwts were reduced in males and females at 2,500 ppm (250 mg/kg/day) and 
in females (F1 only) at 1,000 ppm (100 mg/kg/day). The NOAEL for 
systemic toxicity in adult males was 30 ppm (approximately 3 mg/kg/day, 
range = 1.3 - 4.3 mg/kg/day) and in adult females was 1,000 ppm 
(approximately 100 mg/kg/day, range = 59.3 - 219.6 mg/kg/day). The 
NOAEL for toxicity to offspring was 30 ppm (approximately 3 mg/kg/day, 
range = 1.3 - 4.3 mg/kg/day). These studies show no evidence that 
developing offspring are more sensitive to than adults to the effects 
of thiamethoxam.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
database. Based on the current toxicological requirements, the database 
for thiamethoxam relative to pre- and post-natal effects for children 
is complete. Further, for thiamethoxam, the developmental studies 
showed no increased sensitivity in fetuses as compared to maternal 
animals following in utero exposures in rats and rabbits, and no 
increased sensitivity in pups as compared to the adults in the multi-
generation reproductive toxicity study. Therefore, it is concluded that 
an additional uncertainty factor is not warranted to protect the health 
of infants and children and that an RfD of 0.013 mg/kg/day is 
appropriate for assessing aggregate risk to infants and children of 
thiamethoxam.
    Assuming tolerance level residues and 100% of crops treated, only 
0.1% of the thiamethoxam chronic RfD is utilized in the population 
subgroup all infant (< 1-year old) when helix is used as a seed 
treatment on canola. Therefore, based on the completeness and 
reliability of the toxicity database, Novartis concludes that there is 
reasonable certainty that no harm will result to infants and children 
from aggregate exposure to thiamethoxam residues.

F. International Tolerances

    There are no Codex maximum residue level (MRLs) established for 
residues of thiamethoxam on canola.

3. Norvartis Crop Protection, Inc.

PP 9F5051

    EPA has received a pesticide petition (PP 9F5051) from Novartis 
Crop Protection, Inc. Greensboro, North Carolina, 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

[[Page 24158]]

a tolerance for residues of Thiamethoxam in or on the raw agricultural 
commodity (RAC) fruiting vegetables at 0.25 parts per million (ppm), 
tomato paste at 0.80 ppm, head and stem brassica vegetables at 1.0 ppm, 
leafy brassica greens at 2.0 ppm, cucurbit vegetables at 0.2 ppm, leafy 
vegetables, tuberous and corm vegetables at 0.02 pm, barley hay at 0.05 
ppm, barley straw at 0.03 ppm, cottonseed at 0.05 ppm, cotton gin by-
products at 1.0 ppm, pome fruit at 0.2 ppm, wheat forage at 0.5 ppm, 
wheat grain, wheat straw, wheat hay, barley grain, sorghum grain, 
sorghum forage and sorghum fodder at 0.02 ppm and milk at 0.02 ppm. EPA 
has 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 
supports granting of the petition. Additional data may be needed before 
EPA rules on the petition.

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 major metabolites 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. Novartis Crop Protection Inc. has submitted 
practical analytical methodology for detecting and measuring levels of 
thiamethoxam in or on RAC. The method is based on crop specific cleanup 
procedures and determination by liquid chromatography with either 
ultraviolet (UV) or mass spectrometry (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. A residue program was performed for 
thiamethoxam on a full geography of cucumbers, cantaloupes and squash 
as representative cucurbit crops, tomatoes and peppers as 
representative fruiting vegetable crops, head lettuce, leaf lettuce, 
celery and spinach as representative leafy vegetable crops, broccoli 
and cabbage as representative head and stem brassica vegetable crops, 
mustard greens as a representative leafy brassica green vegetable crop, 
potatoes as a representative crop of tuberous and corm vegetables, and 
apples and pears as representative pome fruit crops. A seed treatment 
residue program was performed for thiamethoxam on sorghum, wheat, 
barley and cotton where seed was treated using specific seed treatment 
formulations. Cotton was also treated via foliar application. Field 
residue trials were performed for thiamethoxam on tobacco using both an 
in-furrow transplant drench and a post-foliar spray. Novartis also 
completed a three-level dairy study and calculated the rate of transfer 
of residues of thiamethoxam from residues in the animal feed to beef 
and dairy commodities.

B. Toxicological Profile

    1. Acute toxicity. Thiamethoxam has low acute toxicity. The oral 
LD50 in rats is 1,563 milligram kilogram (mg/kg) for males 
and females, combined. The rat dermal LD50 is > 2,000 mg/kg 
and the rat inhalation LC50 is > 3.72 milligrams per liter 
(mg/L) air. Thiamethoxam is not a skin sensitizer in guinea pigs and 
does not produce dermal or eye irritation in rabbits. End-use 
formulations of thiamethoxam have similar low acute toxicity profiles.
    2. Genotoxicty. Thiamethoxam did not induce point mutations in 
bacteria (Ames assay in Salmonella typhimurium and Escherichia coli) or 
in cultured mammalian cells (Chinese hamster V79) and was not genotoxic 
in an in vitro unscheduled DNA synthesis assay in rat hepatocytes. 
Chromosome aberrations were not observed in an in vitro test using 
Chinese hamster ovary cells and there were no clastogenic or aneugenic 
effects on mouse bone marrow cells in an in vivo mouse micronucleus 
test. These studies show that thiamethoxam is not genotoxic.
    3. Reproductive and developmental toxicity. In rat and rabbit 
teratology studies with thiamethoxam there was no evidence of 
teratogenicity. In rabbits, thiamethoxam caused decreased body weights 
(bwts), decreased food consumption and premature death of two females 
administered 150 mg/kg/day during gestation. This maternal toxicity was 
accompanied by reduced fetal bwts and an increase in the incidence of 
minor skeletal anomalies or variations. Reduced maternal body weights 
(bwts) and food consumption were also noted in females administered 50 
mg/kg/day thiamethoxam during gestation. There was no indication of 
developmental toxicity at 50 mg/kg/day. The no-observable adverse 
effect level (NOAEL) in rabbits for maternal toxicity was 15 mg/kg/day. 
The NOAEL for developmental toxicity was 50 mg/kg/day. In rats, 
thiamethoxam caused decreased bwts, decreased food consumption and 
hypoactivity at 200 and 750 mg/kg/day. Reduced fetal bwts and an 
increase in the incidence of minor skeletal anomalies and variations 
were observed only at 750 mg/kg/day. There was no indication of 
developmental toxicity at 200 mg/kg/day. The NOAEL in rats for maternal 
toxicity was 30 mg/kg/day and for developmental toxicity was 200 mg/kg/
day. In a 2-generation reproduction study in rats, parental bwts and 
food consumption were decreased at 2,500 ppm highest dose tested (HDT). 
Hyaline changes in the kidneys of adult males were observed at 2,500 
and 1,000 ppm. Reproductive parameters were not affected by treatment 
with thiamethoxam. Effects on offspring were secondary to parental 
toxicity and consisted of slightly reduced offspring bwts at 1,000 ppm 
and 2,500 ppm. The NOAEL for systemic toxicity in parental animals and 
for offspring toxicity was 30 ppm (equivalent to 1.3 - 6.4 mg/kg/day).
    4. Subchronic toxicity. Thiamethoxam was evaluated in 13-week 
subchronic oral toxicity studies in rats, dogs and mice. Liver, kidneys 
and spleen were identified as target organs. The NOAEL was 25 ppm (1.74 
mg/kg/day) in male rats based on the finding of a hyaline change in the 
kidney at 250 ppm (17.6 mg/kg/day). This kidney effect represents an 
accumulation of alpha-2-microglobulin, which is unique to the male rat 
and not relevant for human risk assessment. The NOAEL was 1,250 ppm 
(92.5 mg/kg/day) for female rats. The NOAEL in dogs was 250 ppm (8.23 
mg/kg/day). The NOAEL in mice was 10 ppm (1.41 mg/kg/day) for males and 
100 ppm (19.2 mg/kg/day) for females. No dermal irritation was observed 
in a 28-day repeated dose dermal toxicity study with thiamethoxam in 
rats given 1,000 mg/kg/day. The dermal NOAEL for systemic toxicity in 
rats was 250 mg/kg/day for males and 60 mg/kg/day for females.
    5. Neurotoxicity. Thiamethoxam did not cause neurotoxicity in an 
acute neurotoxicity study in rats or in a subchronic 13-week 
neurotoxicity study in rats. The NOAEL for systemic toxicity in the 
acute neurotoxicity study was 100 mg/kg. The NOAEL for systemic 
toxicity in the subchronic neurotoxicity study was 95.4 mg/kg/day for 
males and 216.4 mg/kg/day for females.
    6. Chronic toxicity. Chronic toxicity studies with thiamethoxam 
have been conducted in rats and dogs. In the dog,

[[Page 24159]]

minor changes in blood chemistry parameters, including increased plasma 
creatinine and plasma urea levels, and decreased alanine 
aminotransferase activities, occurred at the lowest-observable adverse 
effect level (LOAEL) of 750 ppm (21.0 mg/kg/day). The NOAEL in the dog 
was 150 ppm (4.05 mg/kg/day). The NOAEL established in the rat chronic 
toxicity study was 30 ppm (1.29 mg/kg/day) for males, based on kidney 
changes, (hyaline change, chronic tubular lesions, basophilic 
proliferation and lymphocytic infiltration) at the LOAEL of 500 ppm 
(21.0 mg/kg/day). These kidney changes are attributed to an 
accumulation of alpha-2-microglobulin, which is specific to the male 
rat, and not relevant to humans. In the female rat, the NOAEL was 1,000 
ppm (50.3 mg/kg/day) based on decreased bwts and hemosiderosis of the 
spleen at the LOAEL of 3,000 ppm (155 mg/kg/day).
    7. Carcinogenicity. The carcinogenic potential of thiamethoxam has 
been evaluated in rats and mice. The proposed carcinogenic 
classification for thiamethoxam is as a Group C carcinogen. This 
classification is based on a liver tumor response in male and female 
mice at dose levels exceeding the maximum tolerance dose (MTD) and/or 
causing organ toxicity and induction of liver metabolizing enzymes. A 
NOAEL for liver tumors in mice was established at 20 ppm (2.63 mg/kg/
day). No evidence of carcinogenicity was observed in rats. In the 
absence of a mutagenic activity, it is concluded that the mechanism of 
action leading to liver tumors in mice is not via genotoxic effects. 
Therefore, mouse liver tumors associated with thiamethoxam treatment 
have a threshold level.
    8. Animal metabolism. Metabolism of thiamethoxam has been well 
characterized in animals. Metabolism in rats proceeds primarily via 
hydrolysis of the oxadiazine ring, followed by N-demethylation. Several 
minor pathways of metabolism of thiamethoxam were identified in 
animals. In rats, the majority of the radioactive dose was absorbed and 
then excreted in the urine. Parent compound was the major residue in 
urine. In hens and goats, the metabolite profile was the same as in 
rats, with certain extensions of the pathway.
    9. Metabolite toxicology. The metabolism profile for thiamethoxam 
supports the use of an analytical enforcement method that accounts for 
parent thiamethoxam and CGA-322704. Other metabolites are considered of 
equal or lesser toxicity than parent compound.
    10. Endocrine disruption. Thiamethoxam does not belong to a class 
of chemicals known or suspected of having adverse effects on the 
endocrine system. There is no evidence that thiamethoxam has any effect 
on endocrine function in developmental or reproduction studies. 
Furthermore, histological investigation of endocrine organs in chronic 
dog, rat and mouse studies did not indicate that the endocrine system 
is targeted by thiamethoxam.

C. Aggregate Exposure

    1. Dietary exposure. Chronic dietary exposure was estimated using a 
Tier I approach by inputting tolerance level residues into the dietary 
exposure evaluation model (DEEMTM) software. The Tier I 
assessment was partially refined by adjusting for projected percent 
crop-treated information, and was made using the department of 
agriculture (USDA) National Food consumption Survey, Continuing Survey 
of Food Intakes by Individuals (CSFII) 1994-96. The maximum total 
exposure to the U. S. population (48 States, all seasons) was 
calculated to be 4.1% of the reference dose of 0.013 mg/kg bwt/day. The 
maximum exposure to the most sensitive population sub-group, children 
(1-6 years) was 9.5% of the reference dose (RfD). The inclusion of the 
maximum concentration of thiamethoxam in water, taken from the highest 
estimated concentration observed from the generic expected 
environmental concentration (GENEEC) and screening concentration In 
GROund water (SCI GROW) models, led to a maximum chronic dietary 
exposure of 4.5% in the United States population and 10.0% in children 
(1-6 years old).
    Acute dietary exposure was calculated using a Tier III, 
probabilistic assessment. A distribution of residue data points was 
included for the typically non-blended commodities of vegetables 
(tuberous, fruiting, cucurbit, brassica and leafy), pome fruits, meat 
and milk, while the average field trial value was used for the 
typically blended commodities of grains (wheat, sorghum, and barley), 
seed oil (cotton and canola), apple juice and tomato paste and puree. 
The acute assessment used adjustment for percent of crop treated, and 
was made using the DEEM software with the Monte Carlo analysis and the 
CSFII 1994-96 food consumption survey. The margin of exposure (MOE) 
(NOAEL/exposure) for the United States population (all seasons) at the 
99.9th percentile of the exposure distribution was 4,995 using the 
NOAEL value of 15 mg/kg bwt/day. At the 99.9th percentile, the MOE for 
the most sensitive population sub-group (non-nursing infants < 1-year 
old) was 1,012. Inclusion of the drinking water value to the acute 
assessment led to an MOE of 4,904 at the 99.9th percentile of the 
United States population, and 1,008 for the population sub-group non-
nursing infants < 1-year old. The results of these analyses show that 
there is reasonable certainty that no harm will result from exposure to 
dietary residues (including drinking water) of thiamethoxam.
    2. Non-dietary exposure. Novartis also requests registrations for 
the use of thiamethoxam on dogs, turf and ornamentals. Novartis has 
identified potential non-dietary exposures to toddlers for these uses. 
These exposures include the following scenarios:
    i. Incidental non-dietary ingestion of residues on lawns from hand-
to-mouth transfer.
    ii. Ingestion of thiamethoxam treated grass.
    iii. Incidental ingestion of pesticide residues on pets from hand-
to-mouth transfer.
    According to current EPA policy, these exposures are considered to 
be short-term oral exposures. EPA does not expect incidental ingestion 
of pesticide residues on pets from hand-to-mouth transfer to occur 
during the same period as the exposures from the turf uses. Thus, 
Novartis considered these exposures in separate estimates of risk. 
According to current EPA policy, if an oral endpoint is needed for 
short-term risk assessment (for incorporation of food, water, or oral 
hand-to-mouth type exposures into an aggregate risk assessment), the 
acute oral endpoint (acute RfD = 15 mg/kg bwt/day) will be used to 
incorporate the oral component into aggregate risk. Short-term 
aggregate exposure is defined by EPA to be average food and water 
exposure (chronic exposure) plus residential exposure. The short-term 
risk estimates for the population subgroup children, 1 to 6-years old, 
is summarized below. This population subgroup was chosen because it has 
the highest chronic food exposure and because toddlers have the highest 
exposure from the residential uses. From the results below, Novartis 
concludes there is no concern associated with the aggregate exposure to 
thiamethoxam.
    3. Short-term aggregate exposure and risk including turf for 
children 1 to 6- years old--i. Dietary exposure estimate including 
water is 0.001296 mg/kg bwt/day.
    ii. Residential exposure from turf is calculated to be 0.00497 mg/
kg bwt/day.
    iii. Total exposure equals 0.0063 mg/kg bwt/day.

[[Page 24160]]

    iv. Percent Acute RfD consumed is 0.04%
    4. Short-term aggregate exposure and risk including pet use for 
children 1 to 6-years old--i. Dietary exposure estimate including water 
is 0.001296 mg/kg bwt/day.
    ii. Predicted hand to mouth transfer is 0.0341 mg/kg bwt/day.
    iii. Total exposure equals 0.035 mg/kg bwt/day.
    iv. Percent Acute RfD consumed is 0.23%.

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, Novartis believes it is appropriate to consider 
only the potential risks of thiamethoxam in an aggregate risk 
assessment.

E. Safety Determination

    1. U. S. population. Using the chronic exposure assumptions and the 
proposed RfD described above, the aggregate exposure (including 
drinking water) to thiamethoxam to the U. S. population (48 States, all 
seasons) was calculated to be 4.5% of the RfD of 0.013 mg/kg bwt/day. 
Therefore, Novartis concludes that there is reasonable certainty that 
no harm will result from aggregate chronic exposure to thiamethoxam 
residues.
    2. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of thiamethoxam, data 
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat have been considered.
    In teratology studies, delayed fetal development was apparent only 
at maternally toxic doses of thiamethoxam in rats and rabbits. In 
rabbits, 150 mg/kg/day was clearly toxic to does, causing death, weight 
loss, reduced food consumption and perineal or vaginal discharge. 
Developmental toxicity occurred secondary to maternal toxicity and 
consisted of reduced fetal bwts and an increase in minor skeletal 
anomalies or variations. Maternal toxicity was also noted at 50 mg/kg/
day, consisting of reduced bwts and food consumption and total 
resorptions in one female. There was no indication of developmental 
toxicity at 50 mg/kg/day. The NOAEL for maternal toxicity was 15 mg/kg/
day and for developmental toxicity was 50 mg/kg/day in rabbits. In 
rats, 200 and 750 mg/kg/day caused maternal toxicity, but developmental 
toxicity secondary to maternal toxicity was observed only at 750 mg/kg/
day. The NOAEL for maternal toxicity was 30 mg/kg/day and for 
developmental toxicity was 200 mg/kg/day.
    In a rat multigeneration study, parental toxic effects were noted 
at 2,500 ppm (250 mg/kg/day) and 1,000 ppm (100 mg/kg/day). Offspring 
bwts were reduced in males and females at 2,500 ppm (250 mg/kg/day) and 
in females (F1 only) at 1,000 ppm (100 mg/kg/day). The NOAEL for 
systemic toxicity in adult males was 30 ppm (approximately 3 mg/kg/day, 
range = 1.3 - 4.3 mg/kg/day) and in adult females was 1,000 ppm 
(approximately 100 mg/kg/day, range = 59.3 - 219.6 mg/kg/day). The 
NOAEL for toxicity to offspring was 30 ppm (approximately 3 mg/kg/day, 
range = 1.3 - 6.4 mg/kg/day). These studies show no evidence that 
developing offspring are more sensitive to than adults to the effects 
of thiamethoxam.
    FFDCA section 408 provides that EPA may apply an additional safety 
factor for infants and children in the case of threshold effects to 
account for pre- and post-natal toxicity and the completeness of the 
database. Based on the current toxicological requirements, the database 
for thiamethoxam relative to pre- and post-natal effects for children 
is complete. Further, for thiamethoxam, the developmental studies 
showed no increased sensitivity in fetuses as compared to maternal 
animals following in utero exposures in rats and rabbits, and no 
increased sensitivity in pups as compared to the adults in the multi-
generation reproductive toxicity study. Therefore, it is concluded that 
an additional uncertainty factor is not warranted to protect the health 
of infants and children and that an RfD of 0.013 mg/kg/day is 
appropriate for assessing aggregate risk to infants and children of 
thiamethoxam.
    Assuming tolerance level residues and adjusting for the percent of 
crops treated, only 7.0% of the thiamethoxam chronic RfD is utilized in 
the population subgroup all infant (> 1-year old). Therefore, based on 
the completeness and reliability of the toxicity database, Novartis 
concludes that there is reasonable certainty that no harm will result 
to infants and children from aggregate exposure to thiamethoxam 
residues.

F. International Tolerances

    There are no Codex maximum residue levels (MRLs) established for 
residues of thiamethoxam on fruiting vegetables, tomato paste, head and 
stem brassica vegetables, leafy brassica greens, cucurbit vegetables, 
leafy vegetables, tuberous and corm vegetables, barley grain, barley 
hay, barley straw, cottonseed, cotton gin by-products, pome fruit, 
wheat grain, wheat forage, wheat straw, wheat hay, sorghum grain, 
sorghum forage, sorghum fodder, or milk. (Dani Daniel)
[FR Doc. 99-11169 Filed 5-4-99; 8:45 am]
BILLING CODE 6560-50-F