[Federal Register Volume 69, Number 223 (Friday, November 19, 2004)]
[Notices]
[Pages 67731-67735]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-25714]



[[Page 67731]]

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ENVIRONMENTAL PROTECTION AGENCY

[OPP-2004-0363; FRL-7686-5]


Pinoxaden; 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 identification (ID) number OPP-
2004-0363, must be received on or before December 20, 2004.

ADDRESSES: Comments may be submitted electronically, by mail, or 
through hand delivery/courier. Follow the detailed instructions as 
provided in Unit I. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: Jim Tompkins, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 305-5697; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

     You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
Potentially affected entities may include, but are not limited to:
     Crop production (NAICS 111)
     Animal production (NAICS 112)
     Food manufacturing (NAICS 311)
     Pesticide manufacturing (NAICS 32532)
     This listing is not intended to be exhaustive, but rather provides 
a guide for readers regarding entities likely to be affected by this 
action. Other types of entities not listed in this unit could also be 
affected. The North American Industrial Classification System (NAICS) 
codes have been provided to assist you and others in determining 
whether this action might apply to certain entities. If you have any 
questions regarding the applicability of this action to a particular 
entity, consult the person listed under FOR FURTHER INFORMATION 
CONTACT.

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

    1. Docket. EPA has established an official public docket for this 
action under docket ID number OPP-2004-0363. 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, 1801 S. Bell St., 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 in paper, 
will be made available for public viewing in EPA's electronic public 
docket as EPA receives them and without change, unless the comment 
contains copyrighted material, CBI, or other information whose 
disclosure is restricted by statute. When EPA identifies a comment 
containing copyrighted material, EPA will provide a reference to that 
material in the version of the comment that is placed in EPA's 
electronic public docket. The entire printed comment, including the 
copyrighted material, will be available in the public docket.
    Public comments submitted on computer disks that are mailed or 
delivered to the docket will be transferred to EPA's electronic public 
docket. Public comments that are mailed or delivered to the docket will 
be scanned and placed in EPA's electronic public docket. Where 
practical, physical objects will be photographed, and the photograph 
will be placed in EPA's electronic public docket along with a brief 
description written by the docket staff.

C. How and To Whom Do I Submit Comments?

    You may submit comments electronically, by mail, or through 
handdelivery/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

[[Page 67732]]

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 totechnical difficulties 
or needs further information on the substance of your comment. EPA's 
policy is that EPA will not edit your comment, and any identifying or 
contact information provided in the body of a comment will be included 
as part of the comment that is placed in the official public docket, 
and made available in EPA's electronic public docket. If EPA cannot 
read your comment due to technical difficulties and cannot contact you 
for clarification, EPA may not be able to consider your comment.
    i. EPA Dockets. Your use of EPA's electronic public docket to 
submit comments to EPA electronically is EPA's preferred method for 
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/, and follow the online instructions for submitting comments. 
Once in the system, select ``search,'' and then key in docket ID number 
OPP-2004-0363. The system is an ``anonymous access'' system, which 
means EPA will not know your identity, e-mail address, or other contact 
information unless you provide it in the body of your comment.
    ii. E-mail. Comments may be sent by e-mail to [email protected], 
Attention: Docket ID Number OPP-2004-0363. Incontrast to EPA's 
electronic public docket, EPA's e-mail system is not an ``anonymous 
access'' system. If you send an e-mail comment directly to the docket 
without going through EPA's electronic public docket, EPA's e-mail 
system automatically captures your e-mail address. E-mail addresses 
that are automatically captured by EPA's e-mail system are included as 
part of the comment that is placed in the official public docket, and 
made available in EPA's electronic public docket.
    iii. Disk or CD ROM. You may submit comments on a diskor CD ROM 
that you mail to the mailing address identified in Unit I.C.2. These 
electronic submissions will be accepted in WordPerfect or ASCII file 
format. Avoid the use of special characters and any form of encryption.
    2. By mail. Send your comments to: Public Information and Records 
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2004-0363.
    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, 1801 S. Bell St., Arlington, VA, Attention: Docket ID 
Number OPP-2004-0363. 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 theelements 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 supports 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: November 3, 2004
Lois Rossi,
Director, Registration Division, Office of PesticidePrograms.

Summary of Petition

    The petitioner summary of the pesticide petition is printed below 
as required by FFDCA section 408(d)(3). The summary of the petition was 
prepared by the petitioner and represents the view of the petitioner. 
The petition summary announces the availability of a description of the 
analytical methods available to EPA for the detection and measurement 
of the pesticide chemical residues or an explanation of why no such 
method is needed.

Syngenta Crop Protection

    EPA has received a pesticide petition 4F6817 from Syngenta Crop 
Protection, Inc., P.O. Box 18300, Greensboro, North Carolina, 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 pinoxaden in or on the raw 
agricultural commodities (RAC) wheat grain at 0.70 parts per million 
(ppm), wheat, forage at 3.0 ppm, wheat, hay at 1.75 ppm, wheat, straw 
at 1.5 ppm, barley, grain at 0.70 ppm, barley, hay at 1.25 ppm, and 
barley, straw at 0.60 ppm. EPA has determined that the petition 
contains data or information regarding the elements set forth in 
section 408(d)(2) of the FFDCA;

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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. Metabolism of pinoxaden was studied in wheat 
using radiolabeled pinoxaden. The metabolism in plants is well 
understood and the data is adequate for selection of residues of 
concern for tolerance setting purposes. The metabolic profile in plants 
supports the use of an analytical method that accounts for parent 
pinoxaden and its major metabolites.
    2. Analytical method. Syngenta Crop Protection, Inc., has submitted 
practical analytical methodology for detecting and measuring levels of 
pinoxaden and its three major metabolites. The method is based upon 
commodity specific cleanup procedures and High Performance Liquid 
Chromatography (HPLC) determination with triple stage quadruple mass 
spectrometry (LC/MS/MS). The limit of quantitation (LOQ), as 
demonstrated by the lowest acceptable recovery samples, is 0.01 ppm for 
grain, and 0.02 ppm for forage, hay, and straw.
    3. Magnitude of residues. A magnitude of the residueprogram was 
performed with pinoxaden on full guideline geography to support uses on 
all types of wheat, and barley crops.

B. Toxicological Profile

    1. Acute toxicity. Pinoxaden technical and the end-use formulation 
have very low acute toxicity by oral, dermal, and inhalation exposure 
routes. For pinoxaden technical, the oral LD50 in rats is 
>5,000 millgrams/kilogram (mg/kg). The rat dermal LD50 is 
>2,000 mg/kg and the rat inhalation LC50 is 5.22 milligrams/
liter (mg/L) air. Pinoxaden technical is irritating to the eye and non-
irritating to the skin. The end-use formulation is mildly to moderately 
irritating to the eye and skin, the oral LD50 in rats is 
3,129 mg/kg, the rat dermal LD50 is >2,000 mg/kg and the rat 
inhalation LC50 is >5 mg/L. Neither the technical nor the 
formulation are skin sensitizers.
    2. Genotoxicty. Pinoxaden has been tested for its potential to 
induce gene mutation and chromosomal changes in six different test 
systems. Pinoxaden technical was negative in a bacterial gene mutation 
assay, a mouse lymphoma mammalian cell mutation assay and an 
unscheduled DNA synthesis (UDS) assay in rat hepatocytes. In in vitro 
tests for chromosome aberrations in Chinese hamster ovary cells, a 
small dose related increase was observed at dose levels that produced 
cytotoxicity. To assess the biological significance of this single 
positive in vitro finding, two in vivo tests were performed. When 
tested in a micronucleus test in bone marrow cells of the mouse at dose 
levels up to a limit dose of 2,000 mg/kg, pinoxaden did not induce 
micronuclei, and produced no significant toxicity in the animals. In an 
in vivo UDS study in rats, pinoxaden was negative in this assay for DNA 
repair. Based on the complete database, it is concluded that pinoxaden 
is not genotoxic.
    3. Reproductive and developmental toxicity. Pinoxadenproduced no 
evidence of reproductive toxicity. In a rat multi-generation 
reproduction study, pinoxaden technical was administered orally by 
gavage to rats at dosages of 0, 10, 50, 250, and 500 mg/kg/day over two 
generations. At 500 mg/kg, parental toxicity was observed as decreased 
body weight gain (F0 males) and kidney pathology accompanied 
by increased water consumption (F0 and F1 males 
and females.) At 500 mg/kg/day, F1 and F2 pups 
had lower body weight gain during lactation. Changes in organ weights 
were seen in pups at this dose level, but no treatment-related adverse 
findings were observed for pups ineither generation upon histologic 
examination. At 10, 50 and 250 mg/kg/day, there was no indication of 
any adverse effects of treatment. On the basis of the results obtained 
in this study, the no observed adverse effect level (NOAEL) for both 
sexes and generations was 250 mg/kg/day. There were no effects on the 
reproductive parameters and the NOAEL for reproductive toxicity was 
>500 mg/kg/day. Offspring effects were minor and were observed only at 
dose levels that produced parental toxicity. There were no indications 
of any differences in sensitivity to pinoxaden exposure between the 
different generations or between parental animals andoffspring, and it 
is concluded that pinoxaden does not cause reproductive toxicity.
    In a rat teratogenicity study, pinoxaden technical was administered 
by gavage to 24 pregnant rats per group at dose levels of 0, 3, 30, 300 
or 800 mg/kg/day from days 6 through 20 of gestation. Maternal body 
weight gain was significantly reduced at the top two dose levels 
compared to controls. There was no effect of treatment on the number of 
implantation sites, post-implantation loss, live litter size, and sex 
ratios, and no significant findings were observed in the maternal 
animals upon necropsy. Gravid uterus weights, carcass weights and net 
weight change from day 6 post coitum were significantly reduced at the 
top dose level. In the presence of the maternal toxicity, mean fetal 
body weights were reduced at 800 mg/kg/day, and slightly reduced 
ossification was observed at both 800 and 300 mg/kg bw/day. There were 
no treatment-related external or visceral observations in the fetuses. 
Pinoxaden, was not teratogenic in rats when tested under the conditions 
of this study. The no observed effect level (NOEL) for both maternal 
and developmental toxicity was 30 mg/kg/day.
    Pinoxaden, was evaluated in rabbit developmental toxicity studies. 
In an initial guideline rabbit study, pinoxaden technical was 
administered by gavage to pregnant rabbits at dose levels of 0, 10, 30, 
and 100 mg/kg/day from days 7 through 28 of gestation. Maternal body 
weight gain was significantly reduced at 100 mg/kg/day. Fetal body 
weight was reduced at the 100 mg/kg dose level. A second guideline 
developmental toxicity study was conducted in the rabbit at 0, 10, 30, 
and 100 mg/kg/day. Maternal toxicity was observed at 30 and at 100 mg/
kg/day in the form of reduced overall weight gain compared to control 
animals. There was no effect of treatment on the number, growth or 
survival of the fetuses in utero and no evidence for an adverse effect 
on fetal development. There were no treatment-related fetal external, 
visceral or skeletal findings. In conclusion, the full set of studies 
indicated that pinoxaden is not teratogenic in rabbits. The maternal 
NOEL was 10 mg/kg/day, and the NOEL for developmental toxicity was 30 
mg/kg/day.
    In conclusion, there is no evidence that developing offspring are 
more sensitive than adults to the effects of pinoxaden, and it is 
concluded, that pinoxaden does not cause primary developmental toxicity 
or reproductive toxicity.
    4. Subchronic toxicity. Pinoxaden technical was evaluated in a 
number of subchronic studies. In a 3-month gavage study in rats the 
NOAEL was 300 mg/kg, the highest dose tested. Higher doses in a 28-day 
rat study caused kidney toxicity at 600 mg/kg, with a NOAEL of 300 mg/
kg. In a 3-month gavage study in mice, the NOAEL was 100 mg/kg. Effects 
at higher dose levels involved reduced body weights at 1,000 mg/kg, 
reduced hemoglobin at doses greater than or equal to 400 mg/kg (females 
only) and renal tubule basophilia and increased water consumption in 
males at 1,000 mg/kg. In a 3-month study in dogs the NOAEL was 100 mg/
kg, and inappetance, body weight loss and gastro-intestinal effects 
were seen at 250 mg/kg. In a 28-day dermal (rat) study,

[[Page 67734]]

the NOAEL was 1,000 mg/kg, the highest dose tested, and only a mild, 
low-grade inflammatory response at the treatment site was noted. In a 
90-day subchronic neurotoxicity study in rats, pinoxaden was not 
neurotoxic when administered by gavage at dose levels of 0, 10, 100 and 
500 mg/kg/day. There were no treatment-related neurobehavioral or motor 
activity effects, no macroscopic findings and no microscopic findings 
in central or peripheral nervous tissue. In addition, pinoxaden was 
devoid of any acute neurotoxic effects when administered to rats at a 
single oral dose of up to 2,000 mg/kg.
    5. Chronic toxicity. Pinoxaden was not oncogenic in rats or mice. 
In a 2-year combined carcinogenicity/chronic toxicity study in rats, 
pinoxaden technical was administered by daily gavage at dose levels of 
0, 1, 10, 100, 250, and 500 mg/kg/day. Toxicity was observed in the 
form of decreased body weight (500 and 250 mg/kg/day), depressed 
survival (500 and 250 mg/kg/day males only), and kidney pathological 
changes (500, 250, and 100 mg/kg/day). The kidney pathology was 
associated with changes in blood chemistry parameters and other 
associated effects. A minor and sporadic epithelial thickening of the 
duodenum was observed mainly at 250 and 500 mg/kg. There was no 
evidence of a carcinogenic effect in this study. In conclusion, chronic 
treatment of pinoxaden to rats produced effects in only one major 
target organ at high dose levels, involving chronic progressive 
nephropathy and associated effects related to kidney toxicity. The NOEL 
was 10 mg/kg for males and females based on kidney effects at 100 mg/kg 
and above, and pinoxaden was not carcinogenic.
    In an 18-month mouse oncogenicity study, pinoxaden technical was 
administered by gavage at dose levels of 0, 5, 40, 300 and 750 mg/kg 
body. Toxicity was observed in the form of decreased body weight gain 
at 300 mg/kg/day (females only) and 750 mg/kg/day (males and females), 
decreased survival rates (40, 300 and 750 mg/kg/day males), minor 
hematology effects (300 and 750 mg/kg), increased liver weights (300 
and 750 mg/kg, with increased glycogen deposition) and increased kidney 
weights (750 mg/kg in females only). Increased epithelial thickening 
occurred in the small intestine of males and females at 300 and 750 mg/
kg. The reduced survival at the higher dose levels in males was a 
consequence of the gavage dosing procedure, as demonstrated by macro- 
and micropathology evidence of lung involvement as the single major 
factor contributing to death. Other than increased mortality in males, 
there were no treatment-related effects at 40 mg/kg/day. The NOEL for 
this study was 5 mg/kg for both males and females, and pinoxaden was 
not carcinogenic.
    In a 12-month chronic oral toxicity study in dogs, pinoxaden 
technical was administered by capsule at dose levels of 0, 5, 25 or 125 
mg/kg/day. At 25 and 125 mg/kg/day, treatment-related clinical 
observations were limited to an increased incidence of salivation at 
dosing and minor gastrointestinal effects, which were not considered 
adverse. There were noadverse effects on body weights or food 
consumption. Minor changes in hematology and blood clinical chemistry 
parameters were observed at 25 and 125 mg/kg/day compared to control 
animals. However, due to the small magnitude of the effects and the 
absence of any treatment-related effects on organ weights or any 
pathology findings, these clinical pathology changes are considered to 
be of no toxicological significance. There were no treatment-related 
micropathology changes seen at any dose level. The NOAEL in this study 
was 125 mg/kg/day.
    6. Animal metabolism. Animal metabolism of pinoxaden is well 
understood. Pinoxaden is rapidly absorbed and excreted when 
administered to rats, and tissue residues are extremely low, with no 
accumulation upon repeated dosing. Similar rapid absorption and 
excretion was seen in mice and rabbits. The metabolic pathway is 
similar in rodents, rabbits, goats and hens.
    7. Metabolite toxicology. Toxicity of pinoxaden metabolites has 
been tested and is well understood. The toxicological profile of all 
metabolites supports the proposed definition of residue.
    8. Endocrine disruption. Pinoxaden does not belong to a class of 
chemicals known or suspected of having adverse effects on the endocrine 
system. There is no evidence that pinoxaden has any effect on endocrine 
function in developmental or reproductive studies. Furthermore, 
histological investigation of endocrine organs in chronic dog, mouse, 
and rat studies did not indicate that the endocrine system is targeted 
by pinoxaden.

C. Aggregate Exposure

    1. Dietary exposure. The potential for chronic and acute dietary 
exposure from pinoxaden through food and water sources is addressed 
below.
     i. Food. Dietary (food) risk evaluations for pinoxaden were 
performed using field trial residues. A percent of crop treated value 
of 20% was estimated for wheat and barley based upon Syngenta's 
estimates of economic, pest, and competitive pressures. Wheat and 
barley are the only RAC included in the assessment. For the chronic 
assessments, the average wheat and barley field trial residue values 
were utilized. For the acute assessment, the two highest field trial 
residues were averaged and this highest average field trial residue 
(HAFT) was used in the assessment for all non-blended and partially 
blended commodities. All dietary exposure evaluations were made using 
the Dietary Evaluation Model (DEEMTM, version 7.87) from 
Exponent, Inc. and the USDA's Continuing Survey of Food Intake by 
Individuals (1994-96) with the supplemental 1998 children's survey. 
Chronic exposure was compared to a chronic reference dose of 0.10 mg/kg 
bw/day is based upon a NOAEL of 10 mg/kg bw/day from the chronic rat 
study. The acute reference dose of 0.3 mg/kg bw/day for the 
subpopulation of women 13-49 years of age is based upon the 
developmental NOAEL of 30 mg/kg/day in developmental toxicity studies 
in rabbits. For all other subpopulations, the acute reference dose of 
1.5 mg/kg bw/day is based upon a NOAEL for acute effects at 150 mg/kg/
day in a range finding rabbit developmental toxicity study. A 100x 
uncertainty factor was assumed for both the chronic and acute 
assessments. The chronic exposures were expressed as a percent of a 
reference dose of 0.10 mg/kg bw/day. The acute exposures (at the 99.9th 
percentile) were expressed as a percent of a reference dose of 0.3 mg/
kg bw/day for women 13-49 years of age and 1.5 mg/kg bw/day for all 
other subpopulations. Secondary residues in animal commodities were 
calculated by constructing diets for beef and dairy cattle, poultry and 
swine in order to calculate anticipated residues in meat, fat, milk and 
pork. The beef cattle diet was used to calculate meat, fat and organ 
meats residues. The dairy cattle diet was used to estimate residues in 
milk. The swine diet was used for secondary residues in pork 
commodities and the poultry diet was used for residues in poultry 
commodities. The chronic animal diet was calculated using averaged 
field trial residues where as the acute animal diet used averaged field 
trial residues on blended commodities such as grain and the HAFT on 
non-blended commodities such as hay, straw and forage. Beef (cattle and 
dairy) and swine transfer factors were derived from a lactating goat 
metabolism study, where the

[[Page 67735]]

animals were dosed with 121 ppm pinoxaden. Poultry transfer factors 
were derived from a hen metabolism study, where the animals were dosed 
with 97 ppm pinoxaden.
    The results were favorable in both acute and chronic assessment 
scenarios. Acute exposures at the (99.9th percentile) were 0.11% of the 
acute reference dose (0.3 mg/kg bw/day) for women 13-49 years of age, 
and less than 0.05% for all other subpopulations. The chronic exposure 
values were negligible (<0.05% of the chronic reference dose of 0.10 
mg/kg bw/day for all subpopulations).
    ii. Drinking water. The acute estimated environmental 
concentrations of pinoxaden (including the major degradates) in surface 
and ground water are 1.366 ppb (PRZM/EXAMS) and 0.003234 ppb (SCI-
GROW), respectively. The acute Population Adjusted Dose (aPAD) for 
pinoxaden (plus degradates) is 0.3 mg/kg bw/day for women 13-49 years 
of age and 1.5 mg/kg bw/day for all other population subgroups. From 
the acute dietary exposure analysis, the highest acute food exposure 
from the uses of pinoxaden was 0.000509 mg/kg/day at the 99.9th 
percentile for the 20-49 years old subpopulation. Using this 
information, acute drinking water levels of comparison (DWLOC acute) 
were calculated for pinoxaden and the major degradates, ranging from 
8,990 to 52,487 ppb. Based on this analysis, pinoxaden (plus 
degradates) estimated environmental concentrations (EECs) do not exceed 
the calculated acute DWLOCs. The chronic estimated environmental 
concentration of pinoxaden (including the major degradates) in surface 
water is 0.21137 ppb (annual average value from PRZM/EXAMS). The 
chronic PAD for pinoxaden (plus degradates) is 0.10 mg/kg bw/day. From 
the chronic dietary exposure analysis, the highest exposure estimate of 
0.000047 mg/kg bw/day was determined for the children 1-2 years old 
subpopulation. Based on the EPA's ``Interim Guidance for Conducting 
Drinking Water Exposure and Risk Assessments'' document (62 FR 63662, 
December, 2, 1997), chronic DWLOC chronic were calculated for pinoxaden 
(plus degradates), ranging from 999.5 to 2999.4 ppb. Based on this 
analysis, pinoxaden (plus degradates) EECs do not exceed the calculated 
chronic DWLOCs.
     2. Non-dietary exposure. There are no sources ofnon-dietary 
exposure, as pinoxaden will be registered for agricultural uses only 
and will not be available for any residential or public uses.

D. Cumulative Effects

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

E. Safety Determination

     1. Infants and children. In assessing the potential for additional 
sensitivity of infants and children to residues of pinoxaden, data from 
developmental toxicity studies in the rat and rabbit and a two-
generation reproduction study in the rat have been considered. In a 
multi-generation reproductive study, there were no indications of any 
differences in sensitivity to pinoxaden exposure between the different 
generations or between animals and offspring. The parental NOAEL for 
both sexes was considered to be 250 mg/kg/day. Offspring effects were 
not observed at dose levels that did not produce parental toxicity. 
Pinoxaden was not teratogenic and not directly toxic to the progeny in 
a developmental toxicity study in rats. The NOEL for both maternal and 
developmental toxicity was 30 mg/kg/day. Pinoxaden was not teratogenic 
in rabbits, and the maternal NOEL was 10 mg/kg/day. The NOEL for 
fetuses was 30 mg/kg/day. Since the NOEL for fetal effects was higher 
than the NOEL for maternal effects, there was no indication of a 
greater sensitivity of fetuses to pinoxaden administration. 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 
prenatal and postnatal toxicity and the completeness of the database. 
Based on the current toxicological requirements, the database for 
pinoxaden relative to prenatal and postnatal effects for children is 
complete. Further, 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 RfDs of 0.3 mg/kg/day (acute exposures to women 
13-50 yrs of age), 1.5 mg/kg/day (acute exposures to general 
population) and 0.10 mg/kg/day (chronic expsoures) are appropriate for 
assessing aggregate risk to infants and children of pinoxaden. Chronic 
and acute aggregate exposures to all infants (<1 year old) is less than 
0.2% of the acute and chronic RfDs. Therefore, based on the 
completeness and reliability of the toxicity database, Syngenta 
concludes that there is reasonable certainty that no harm will result 
to infants and children from aggregate exposure to pinoxaden residues.

F. International Tolerances

    There are no tolerances or maximum residue limits set for pinoxaden 
in any country at the time of this filing.

[FR Doc. 04-25714 Filed 11-18-04; 8:45 am]
BILLING CODE 6560-50-S