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Pyridalyl (Valent). December 5, 2003. Pesticide tolerance petition. Federal Register.

http://www.epa.gov/fedrgstr/EPA-PEST/2003/December/Day-05/p30164.htm

[Federal Register: December 5, 2003 (Volume 68, Number 234)]
[Notices]
[Page 68044-68049]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05de03-62]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0276; FRL-7334-6]

Pyridalyl; 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-2003-0276, must
be received on or before January 5, 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: Susan Stanton, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number:
(703) 305-5218; e-mail address: <A HREF="mailto:stanton.susan@epa.gov">stanton.susan@epa.gov</A>.

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)
[[Page 68045]]
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-2003-0276. 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 <A HREF="http://www.epa.gov/fedrgstr/">http://www.epa.gov/fedrgstr/</A>.
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 <A HREF="http://www.epa.gov/edocket/">http://www.epa.gov/edocket/</A> 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.1. 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 <A HREF="http://www.epa.gov/edocket/">http://www.epa.gov/
edocket/</A>, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2003-0276. 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 <A HREF="mailto:opp-docket@epa.gov">opp-docket@epa.gov</A>,
Attention: Docket ID number OPP-2003-0276. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that
[[Page 68046]]
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-2003-0276.
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-2003-0276. 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: November 20, 2003.
Susan Lewis,
Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition
The petitioner's summary of the pesticide petition is printed below
as required by FFDCA section 408(d)(3). The summary of the petition was
prepared by the Valent U.S.A. Corporation 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.

Valent U.S.A. Corporation
PP 2F6459, and PP 2E6592
EPA has received pesticide petitions (PP 2F6459, and PP 2E6592)
from Valent U.S.A. Corporation, 1600 Riviera Ave., Suite 200, Walnut
Creek, CA 94596-8025, and IR-4, 681 U.S. Highway #1 South,
North Brunswick, NJ, 08902-3390, 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 tolerances for residues of the
insecticide chemical pyridalyl, pyridine,2-[3-[2,6-dichloro-4-[(3,3-
dichloro-2-propenyl)oxy]phenoxy]propoxy]-5-(trifluoromethyl), in or on
the raw agricultural commodities: Cottonseed at 0.4 parts per million
(ppm); vegetable, fruiting, group 8, at 1.1 ppm; vegetable, leafy,
except Brassica, group 4, at 20.0 ppm; Brassica, head and stem,
subgroup 5A, at 5.0 ppm; Brassica, leafy greens, subgroup 5B, at 30.0
ppm; turnip greens at 30 ppm; meat at 0.04 ppm; meat by-products at
0.05 ppm; animal fat at 1.0 ppm; and whole milk at 0.1 ppm and to
establish tolerances for residues of the insecticide chemical
pyridalyl, pyridine,2-[3-[2,6-dichloro-4-[(3,3-dichloro-2-
propenyl)oxy]phenoxy]propoxy]-5-(trifluoromethyl) plus the metabolite
S-1812-DP, 3,5-dichloro-4-[3-(5-trifluoromethyl-2-pyridyloxy)]propoxy
phenol, in or on the raw agricultural commodity cotton gin by-products
at 23.0 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
petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of pyridalyl in plants is well
understood, having been investigated in cabbage, tomato, and cotton.
The major residue in all crops is pyridalyl. A minor metabolic pathway
in plants involves cleavage of the dichloropropenyl group to the
phenol, S-1812-DP, which can be conjugated. Other minor metabolic
pathways in cotton are oxidation of the dichloropropenyl group to the
acid, S-1812-PhCH2COOH, and hydrolysis to give the pyridone, HTFP,
which can be further hydroxylated to 3-hydroxy-5-
trifluoromethylpyridone (HPDO).

2. Analytical method. Based on the metabolism of pyridalyl in plant
and animals and the toxicology of the parent and metabolite,
quantification of the parent pyridalyl and the metabolite S-1812-DP are
sufficient to determine toxic residues. Practical analytical
[[Page 68047]]
methods for detecting and measuring levels of pyridalyl and its
metabolite S-1812-DP have been developed and validated in all
appropriate agricultural commodities and respective processing
fractions. These analytical methods are suitable for monitoring of food
with residues at the levels proposed for the tolerances. Methods have
also, been developed and validated for determining pyridalyl and S-
1812-DP in animal matrices. The limit of quantitation (LOQ) of
pyridalyl in the crop methods are 0.02 ppm in cottonseed, 0.1 ppm in
cotton gin trash, and 0.02 ppm in vegetables. The LOQs of pyridalyl in
the animal methods are 0.01 ppm in milk, 0.02 ppm in tissues, liver and
kidney, and 0.10 ppm in fat.

3. Magnitude of residues. Magnitude of residues were conducted in
fruiting vegetables tomato and peppers (bell and non-bell), leafy
vegetables (head and leaf lettuce, celery, and spinach), head and stem
brassica vegetables (broccoli and cabbage), mustard greens, and cotton.
Trials were conducted in all of the major use area for each of the
crops as specified in the OPPTS Harmonized Guidelines OPPTS 860.1500
with applications at the maximum use rate for each crop. As a result of
the field trials, the following tolerances for the residues of
pyridalyl are proposed for each of the crop groups, crops or matrices:
Cottonseed at 0.4 ppm; turnip greens at 30 ppm; vegetables, leafy,
except Brassica, group 4 at 20.0 ppm; brassica, head and stem, subgroup
5A at 5.0 ppm; Brassica, leafy greens, subgroup 5B at 30 ppm; and
vegetables, fruiting, group 8 at 1.1 ppm. Tolerances for the residues
of pyridalyl plus the metabolite S-1812-DP are proposed for cotton gin
by-products at 23.0 ppm. Processing studies were conducted with tomato
and cottonseed. No tolerances are proposed for cottonseed and tomato
processing commodities since no concentration factor was observed.
Tolerances for residues of pyridalyl are also proposed for milk at 0.1
ppm; meat at 0.04 ppm; animal fat at 1.0 ppm; and meat by-products at
0.05 ppm.

B. Toxicological Profile
A full battery of toxicology testing including studies of acute,
subchronic, chronic, oncogenicity, developmental, reproductive and
genotoxicity effects is available for pyridalyl. The acute toxicity of
pyridalyl is low by all routes. Subchronic and chronic studies exhibit
no observed adverse effect level (NOAEL) values from a low of 3.4
milligrams/kilogram/day (mg/kg/day) (male rat combined toxicity/
oncogenicity study) to 1,000 mg/kg/day (28-day dermal toxicity study).
Pyridalyl is not oncogenic and the weight-of-evidence indicates it is
not genotoxic. There are no developmental concerns or reproductive
effects.
The lowest acute NOAEL of 50 mg/kg/day is derived from both the
maternal and reproductive toxicity endpoint of the rabbit developmental
toxicity study.
The lowest chronic NOAEL of 40 ppm (2.8 mg/kg/day in males) is
taken from the premating growth period in the 2-generation reproduction
study.
1. Acute toxicity. The acute toxicity of pyridalyl technical is low
by all routes. Pyridalyl was not toxic when administered in limit tests
orally, dermally and via inhalation to rats. It is not a skin irritant
and is only a mild eye irritant. Pyridalyl was positive in skin
sensitization tests. Pyridalyl and its formulated products will be
placed into Toxicity Category III.
2. Genotoxicty. The genotoxic potential of pyridalyl was studied in
vitro in bacteria (ames test), in mammalian cells hypoxanthine-guanine
phosphoribosyl transferase (HGPRT) and mouse lymphoma L5178Y TK+/-), in
the chromosome aberration assay, and in vivo in the unscheduled DNA
synthesis (UDS) test and the mouse micronucleus test. The test systems
assayed did not show any evidence of pyridalyl genotoxicity except the
in vitro mammalian cytogenetics (chromosome aberration) assay. The
weight of the evidence indicates that pyridalyl does not raise
significant genotoxicity concerns.
3. Reproductive and developmental toxicity. Developmental effects
of pyridalyl were studied in rats and rabbits and multigenerational
effects on reproduction were studied in rats.
i. Rat developmental. In a developmental toxicity study conducted
with rats, the maternal NOAEL was 10 mg/kg/day based on the non-acute
effects of reduced body weight gain and food consumption. There were no
developmental effects, and the developmental NOAEL is 250 mg/kg/day,
the highest dose tested (HDT).
ii. Rabbit developmental. In a rabbit developmental toxicity study,
the acute effects of maternal toxicity and decreased fetal weight was
observed at 150 mg/kg/day. The maternal and developmental NOAEL is 50
mg/kg/day.
iii. Reproduction. In a rat reproduction study, there were no
adverse effects of pyridalyl on reproductive parameters in the absence
of parental toxicity. The reproductive, parental and offspring toxicity
NOAEL is 40 ppm.
4. Subchronic toxicity. Subchronic toxicity studies have been
conducted with pyridalyl in the rat, mouse, and dog.
i. Rats. Pyridalyl technical was tested in rats in a 3-month
feeding study. Effects included decreased body weight gain, altered
blood biochemistry, increased relative liver weight and
histopathological changes in the liver, ovary, adrenal and lung. The
NOAEL is 100 ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day in
females).
ii. Mice. A 13-week feeding study in mice was conducted. Effects
included decreased body weight gain, hematological and blood
biochemical effects,increased liver weight, decreased kidney and ovary
weights and histopathological changes in liver, kidney, ovary and
adrenal. The NOAEL is 70 ppm in males (8.169 mg/kg/day) and 700 ppm in
females (86.78 mg/kg/day).
iii. Dogs. A 13-week oral (capsule) toxicity study was conducted in
dogs. Effects included decreased body weight gain, clinical signs
indicative of respiratory distress, hematological and blood
biochemistry effects, increased liver, lung and kidney weights and
histopathological alterations of the lung, kidney, adrenal and liver.
The NOAEL was 10 mg/kg/day.
iv. Dermal rat. A 28-day dermal toxicity study in rats with
pyridalyl did not produce any signs of dermal or systemic toxicity at
1,000 mg/kg/day, the highest dose tested (HDT).

5. Chronic toxicity. Pyridalyl has been tested in chronic studies
with dogs, rats and mice.
i. Rats. In a 104-week combined chronic/oncogenicity study in rats,
effects included decreased body weight gain, increased frequency of
rearing (high dose females only), hematological alterations and
histopathological alterations of the spleen. No oncogenicity was found.
The NOAEL for this study is 100 ppm (3.4 mg/kg/day in males and 4.1 mg/
kg/day in females).
ii. Mice. Pyridalyl was administered in the diet to mice for 78-
weeks. Effects included decreased body weight gain and food
consumption/efficiency, and increased liver and kidney weights. The
NOAEL of the study was 50 ppm (5.04 mg/kg/day in males and 4.78 mg/kg/
day in females)
iii. Dogs. Pyridalyl was administered for 12-months by capsule to
dogs. There were alterations in blood biochemistry (alkaline
phosphatase and alanine aminotransaminase) and increased liver weights.
The NOAEL of the study was 20 mg/kg/day.
iv. Carcinogenicity. Pyridalyl did not produce carcinogenicity in
chronic studies with rats or mice. Valent anticipates that the
oncogenicity
[[Page 68048]]
classification of pyridalyl will be ``E'' (no evidence of
carcinogenicity for humans).
6. Animal metabolism. Rats metabolize and rapidly eliminate
14C S-1812. Most of the administered dose was eliminated
within 48 hours mainly in the feces. There were no apparent sex-related
differences in either the rate of elimination of 14C S-1812
or in the metabolite distribution. There was no apparent enzymatic
induction as the metabolic pattern was unchanged by multiple (14-day)
administrations of 14C S-1812 at 5 mg/kg/day.
7. Metabolite toxicology. Two metabolites of pyridalyl, 2-hydroxy-
5-trifluoromethylpyridine (HTFP) and HPDO that occur in extremely low
levels in plants and animals, were also tested for genetic toxicity.
Each metabolite was tested in an in vitro bacterial (Ames test) and
mammalian HGPRT assay mutagenesis assay as well as in an in vitro
chromosome aberration test. Both metabolites were positive in the
bacterial assay, but were negative in the mammalian mutagenesis assay.
One metabolite, HPDO, was positive in the chromosome aberration test.
The biological significance of this finding is uncertain given that
only low levels of these compounds are detectible in plants or animals
and that pyridalyl does not appear to be carcinogenic at high and
chronic doses.
8. Endocrine disruption. Data from the rat reproduction and
subchronic studies indicated that pyridalyl may effect lipid metabolism
and, consequently, hormone levels. These in vivo results suggested that
S-1812 may have a modulating activity on steroid biosynthesis at doses
generally exceeding MTD.
To further understand these finding, two additional, non-guideline,
mechanistic studies were conducted. A detailed analysis of the effect
of S-1812 on serum steroid hormone levels was performed in rats exposed
for 4 weeks to dose levels equivalent to those used in the rat
reproduction study. And an in vitro study was conducted in rat primary
Leydig cell and ovary cell cultures to investigate the effects of S-
1812 on the production of hormones and on the activity of enzymes that
catalyze sex steroid hormone biosynthesis. These studies support the
conclusion that S-1812 is not an endocrine disruptor in in vivo
mammalian systems. Although, very weak inhibition of a single steroid
biosynthesis pathway was observed in the in vitro study, effects
possibly related to this conversion in mammalian systems were observed
only at dose levels that greatly exceeded the maximum tolerated dose.
C. Aggregate Exposure
1. Dietary exposure. Acute and chronic dietary analyses were
conducted to estimate exposure to potential pyridalyl residues in or on
the following crops and crop groups: Cottonseed, turnip greens,
vegetables, leafy, except Brassica, group 4, Brassica, group 5 and
vegetables, fruiting, group 8. using the Cumulative and Aggregate Risk
Evaluation System (CARES) Version 1.3. Exposure estimates to water were
made based upon modeling First Index Screening Tool Reservoir (FIRST
model).
i. Food--a. Acute. The acute dietary exposure estimate of pyridalyl
residues in food at the 99.9th percentile was calculated to
be 43% of the acute Reference Dose (aRfD) with a margin of exposure of
235. The population subgroup with the highest exposure was non-nursing
infants. The aRfD was defined as the NOAEL from a developmental
toxicity study in rabbits and includes an uncertainty factor of 100
(NOAEL = 50 mg/kg body weight (bwt)/day, aRfD = 0.5 mg/kg/day).
b. Chronic. The chronic dietary exposure estimate of pyridalyl
residues in food at the 100th percentile was calculated to
be 1.4% of the chronic Reference Dose (cRfD) with a margin of exposure
of 732. The population subgroup with the highest exposure was children
1-2 years old. The cRfD was defined as the NOAEL from the 2-generation
reproduction study in rats including an uncertainty factor of 100
(NOAEL = 2.8 mg/kg bwt/day, cRfD = 0.028 mg/kg/day).
These values are based on proposed tolerance level residues
adjusted for percentages of the crop treated. No adjustments were made
for common washing, cooking or preparation practices and as such are
very conservative values.
ii. Drinking water. Since pyridalyl is applied outdoors to growing
agricultural crops, the potential exists for the parent or its
metabolites to reach groundwater or surface water that may be used for
drinking water. Screening Concentration in Groundwater (SCIGROW)
simulation predicted zero S-1812 concentration in ground water
indicating that S-1812 will not leach. This result is expected due the
very high Koc value of pyridalyl. For the surface water FIRST (version
1.0) simulation produced peak day concentration (acute) of 0.15 parts
per billion (ppb). The peak FIRST concentration was used for both the
acute and chronic exposure assessment. Based on these modeled drinking
water concentrations, the worst-case acute/chronic dietary exposure
from drinking water is estimated to be negligible (0.02% of the aRfD,
and 0.003% of the cRfD for children).
2. Non-dietary exposure. Pyridalyl is proposed only for
agricultural uses and no homeowner or turf uses. Thus, no non-dietary
risk assessment is necessary.
D. Cumulative Effects
Section 408(b)(2)(D)(v) requires that the Agency must consider
``available information'' concerning the cumulative effects of a
particular pesticide's residues and ``other substances that have a
common mechanism of toxicity.'' Available information in this context
include not only toxicity, chemistry, and exposure data, but also
scientific policies and methodologies for understanding common
mechanism of toxicity and conducting cumulative risk assessments. For
most pesticides, although, the Agency has some information in its files
that may turn out to be helpful in eventually determining whether a
pesticide shares a common mechanism of toxicity with any other
substances, EPA does not at this time have methodologies to resolve the
complex scientific issues concerning common mechanism of toxicity in a
meaningful way for most registered pesticides.
E. Safety Determination
1. U.S. population. Using the conservative assumption described
above, based on the completeness and reliability of the toxicity data,
it is concluded that aggregate exposure to the proposed uses of
pyridalyl will utilize at most 43% of the acute RfD and 2% of the
chronic RfD for the U.S. population and is likely to be much less, as
more realistic data and models are developed. The Agency has no cause
for concern if total acute residue contribution is less than 100% of
the aRfD, because the RfD represents the level at or below which daily
aggregate exposure over a lifetime will not pose appreciable risk to
human health. Therefore, there is a reasonable certainty that no harm
will occur to the U.S. population from aggregate exposure to residues
of pyridalyl under the proposed use patterns.
2. Infants and children. The toxicological data base for evaluating
prenatal and postnatal toxicity for pyridalyl is complete with respect
to current data requirements. There are no special prenatal and
postnatal toxicity concerns for infants and children, based on the
results of the rat and rabbit developmental toxicity studies or the 2-
generation reproductive toxicity study in rats. Using the conservative
[[Page 68049]]
assumption described above, based on the completeness and reliability
of the toxicity data, it is concluded that, aggregate exposure to the
proposed uses of pyridalyl will utilize at most 43% of the aRfD for
non-nursing infants (the most highly exposed subgroup) and 2% of the
cRfD for children 1-2 (the most highly exposed subgroup). The drinking
water contribution to dietary exposure is insignificant. Therefore,
there is a reasonable certainty that no harm will occur to infants and
children from aggregate exposure to residues of pyridalyl.
F. International Tolerances
There are currently no international tolerances for pyridalyl.

[FR Doc. 03-30164 Filed 12-4-03; 8:45 am]
BILLING CODE 6560-50-S