Spiromesifen; Notice of Filing a Pesticide Petition to Establish
a Tolerance for a Certain Pesticide Chemical in or on Food
[Federal Register: July 28, 2004 (Volume 69, Number 144)]
[Notices]
[Page 45047-45051]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr28jy04-70]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
[OPP-2004-0197; FRL-7366-2]
Spiromesifen; 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.
-----------------------------------------------------------------------
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-2004-0197, must be
received on or before August 27, 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: Thomas C. Harris, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-9423; e-mail address:
harris.thomas@epa.gov.
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), e.g., agricultural workers;
greenhouse, nursery, and floriculture workers; farmers.
? Animal production (NAICS 112), e.g., cattle ranchers and
farmers, dairy cattle farmers, livestock farmers.
? Food processing (NAICS 311), e.g., agricultural workers;
farmers; greenhouse, nursery, and floriculture workers; ranchers;
pesticide applicators.
? Pesticide manufacturers (NAICS 32532), e.g., agricultural
workers; commercial applicators; farmers; greenhouse, nursery, and
floriculture workers; residential users.
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 identification (ID) number OPP-2004-0197. 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. Note: Due to renumbering of
buildings in area, the street address will change to 1801 South Bell
Street as of June 26, 2004. 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.regulations.gov/ 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
[[Page 45048]]
facility identified in Unit I.B.1. Once in the system, select
``search,'' then key in the appropriate docket ID number.
Certain types of information will not be placed in the EPA Dockets.
Information claimed as CBI and other information whose disclosure is
restricted by statute, which is not included in the official public
docket, will not be available for public viewing in EPA's electronic
public docket. EPA's policy is that copyrighted material will not be
placed in EPA's electronic public docket but will be available only in
printed, paper form in the official public docket. To the extent
feasible, publicly available docket materials will be made available in
EPA's electronic public docket. When a document is selected from the
index list in EPA Dockets, the system will identify whether the
document is available for viewing in EPA's electronic public docket.
Although not all docket materials may be available electronically, you
may still access any of the publicly available docket materials through
the docket facility identified in Unit I.B. EPA intends to work towards
providing electronic access to all of the publicly available docket
materials through EPA's electronic public docket.
For public commenters, it is important to note that EPA's policy is
that public comments, whether submitted electronically or in paper,
will be made available for public viewing in EPA's electronic public
docket as EPA receives them and without change, unless the comment
contains copyrighted material, CBI, or other information whose
disclosure is restricted by statute. When EPA identifies a comment
containing copyrighted material, EPA will provide a reference to that
material in the version of the comment that is placed in EPA's
electronic public docket. The entire printed comment, including the
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and to Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/
edocket/, and follow the online instructions for submitting comments.
Once in the system, select ``search,'' and then key in docket ID number
OPP-2004-0197. 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 opp-docket@epa.gov,
Attention: Docket ID Number OPP-2004-0197. In contrast to EPA's
electronic public docket, EPA's e-mail system is not an ``anonymous
access'' system. If you send an e-mail comment directly to the docket
without going through EPA's electronic public docket, EPA's e-mail
system automatically captures your e-mail address. E-mail addresses
that are automatically captured by EPA's e-mail system are included as
part of the comment that is placed in the official public docket, and
made available in EPA's electronic public docket.
iii. Disk or CD ROM. You may submit comments on a disk or CD ROM
that you mail to the mailing address identified in Unit I.C.2. These
electronic submissions will be accepted in WordPerfect or ASCII file
format. Avoid the use of special characters and any form of encryption.
2. By mail. Send your comments to: Public Information and Records
Integrity Branch (PIRIB) (7502C), Office of Pesticide Programs (OPP),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001, Attention: Docket ID Number OPP-2004-0197.
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-2004-0197. Note: Due to renumbering of buildings in area,
the street address will change to 1801 South Bell Street as of June 26,
2004. 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,
[[Page 45049]]
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: July 9, 2004.
Betty Shackleford,
Acting Director, Registration Division, Office of Pesticide Programs.
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.
I. Bayer Corporation
PP 3F6537
EPA has received a pesticide petition (3F6537) from Bayer
CropScience, 2 T.W. Alexander Drive, Research Triangle Park, NC 27709
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 the following residues:
1. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester, and its enol
metabolite; 4-hydroxy- 3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]
non-3-en-2-one in or on the raw agricultural commodities strawberry at
2.0 parts per million (ppm); vegetable, tuberous and corm, crop subgroup
1C at 0.01 ppm; vegetable, leafy greens (except Brassica), crop subgroup
4A at 10 ppm; vegetable, Brassica, head and stem, crop subgroup 5A at
2.0 ppm; vegetable, Brassica, leafy, crop subgroup 5B at 12 ppm;
vegetable, fruiting, crop group 8 at 0.30 ppm; tomato, paste at 0.60
ppm; vegetable, Cucurbit, crop group 9 at 0.10 ppm; corn, field, grain
at 0.01 ppm; corn, field, forage at 3.0 ppm; corn, field, stover at 5.0
ppm; cotton at 0.50 ppm; and cotton, gin byproducts at 15 ppm.
2. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester, its enol
metabolite; 4-hydroxy-3-(2,4,6-trimethylphenyl)-1-oxaspiro[4.4]non- 3-
en-2-one, and its metabolites containing the 4-hydroxymethyl moiety; 4-
hydroxy-3-[4- (hydroxymethyl)- 2,6-dimethylphenyl]- 1-oxaspiro[4.4]
non-3-en-2-one, moieties in or on the rotational crop commodities
alfalfa, forage at 1.5 ppm; alfalfa, hay at 3.0 ppm; wheat, grain at
0.01 ppm; wheat, forage at 0.20 ppm; wheat, hay at 0.15 ppm; wheat,
straw at 0.25 ppm; wheat, bran at 0.05 ppm; wheat, shorts at 0.03 ppm;
barley, grain at 0.02 ppm; barley, hay at 0.25 ppm; barley, straw at
0.25 ppm; beet, sugar, tops at 0.20 ppm; beet, sugar, roots at 0.02
ppm; and beet, sugar, molasses at 0.05 ppm.
3. Spiromesifen; butanoic acid, 3,3-dimethyl-, 2-oxo-3-(2,4,6-
trimethylphenyl)-1-oxaspiro[4.4]non-3-en-4-yl ester, and its
metabolites containing the enol; 4-hydroxy- 3-(2,4,6-trimethylphenyl)-
1-oxaspiro[4.4] non-3-en-2-one, or 4-hydroxymethyl; 4- hydroxy-3-[4-
(hydroxymethyl)-2,6-dimethylphenyl]- 1-oxaspiro[4.4] non-3-en-2-one,
moieties in or on the raw agricultural commodities cattle, fat at 0.05
ppm; cattle, meat byproducts at 0.05 ppm; milk at 0.01 ppm; and milk,
fat at 0.03 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 supports granting of the
petition. Additional data may be needed before EPA rules on the
petition.
A. Residue Chemistry
1. Plant metabolism. The metabolism of spiromesifen in plants is
adequately understood. Studies have been conducted to delineate the
metabolism of radiolabeled spiromesifen in various crops, all showing
similar results. The residue of concern is spiromesifen and its enol
metabolite.
2. Analytical method. Adequate analytical methodology using LC/MS/
MS detection is available for enforcement purposes.
3. Magnitude of residues. Complete residue data exists for
spiromesifen on these crops and crop groupings. The data support the
requested tolerances.
B. Toxicological Profile
1. Acute toxicity. Oral and dermal LD50 values were
>2,000 mg/kg bw. Inhalation LC50 values were >4,873 mg/
m3 air. Spiromesifen was not irritating to rabbit skin or
eyes but did cause skin sensitization in the Magnusson/Kligman
maximization test in guinea pigs. Acute toxicity studies for
spiromesifen support an overall toxicity Category III.
2. Genotoxicity. Several genotoxicity tests were conducted to test
for point-mutagenic activity, chromosome aberration in vitro and in
vivo, and for DNA repair. All tests conducted were negative, indicating
no evidence of mutagenic or genotoxic potential.
3. Reproductive and developmental toxicity. An oral developmental
toxicity study in rat did not reveal any evidence of teratogenic
potential. The maternal and developmental no observed adverse effect
levels (NOAELs) were 10 mg/kg bw/day. An oral developmental toxicity
study in rabbits demonstrated a maternal NOAEL of 5 mg/kg bw/day, a
developmental NOAEL of 35 mg/kg bw/day and did not reveal any
teratogenic potential. A 2-generation study in rats, with a parental
toxicity NOAEL of 2.2 mg/kg bw/day for males and 3.8 mg/kg bw/day for
females, did not reveal evidence of a primary reproductive
[[Page 45050]]
toxicity potential. The reproductive NOAEL was 36.6 mg/kg bw/day for
males and 14.2 mg/kg bw/day in females.
4. Subchronic toxicity. A subchronic toxicity feeding study with
rats over 90 days demonstrated a NOAEL of 6.3 and 7.7 mg/kg bw/day for
males and females, respectively, based on reduced body weights, effects
on the lipid metabolism (decrease of triglycerides and cholesterol) and
thyroid effects (colloidal alteration, hypertrophy) at the higher dose
levels. A subchronic feeding study in mice over 14 weeks demonstrated a
NOAEL of 3.2 and 5.1 mg/kg bw/day based on effects on lipid metabolism
(decrease of cholesterol) and adrenal effects (cytoplasmic
eosinophilia). A 14-week feeding study in dogs demonstrated a NOAEL of
9.2 and 9.3 mg/kg bw/day based on liver effects (enzyme induction,
increased liver weights and cytoplasmic change) and thyroid effects
(decreased T4).
5. Chronic toxicity. A 12-month chronic feeding study in rats
demonstrated a NOAEL of 6.5 and 19.3 mg/kg bw/day for males and
females, respectively. A 24-month oncogenicity study in rats
demonstrated a NOAEL of 6.1 and 19.5 mg/kg bw/day for males and
females, respectively. An oncogenicity study in the mouse revealed a
NOAEL of 3.3 and 3.8 mg/kg bw/day for males and females, respectively
based on macroscopic and microscopic adrenal effects. There was no
indication in the rat or mouse for an oncogenic effect of spiromesifen.
A 1-year feeding study with dogs demonstrated a NOAEL of 11.5 and 10.8
mg/kg bw day for males and females, respectively based on decreased
body weights, liver effects (increased liver weight, hepatocellular
cytoplasmic change, vacuoles) adrenal effects (increased incidence of
small cell types).
6. Animal metabolism. Metabolism and pharmacokinetic studies in the
rat demonstrate that spiromesifen residues are rapidly absorbed,
metabolized and eliminated. There was no evidence of accumulation of
residues in any tissues or organs. The primary metabolites are the
enol, which is formed by cleavage of the alkyl ester group, and the 4-
hydroxymethyl metabolite. However, several other metabolites are also
formed.
7. Metabolite toxicology. The residues of concern are spiromesifen,
its enol metabolite and BSN 4-hydroxymethyl, which are products of
metabolism in mammalian systems, as well as in the environment. Since
both products are major metabolites following the oral administration
of spiromesifen to rats, toxicology data for these metabolites are
completely supported by data obtained for spiromesifen.
8. Endocrine disruption. There is no evidence to suggest that
spiromesifen has any primary endocrine disruptive potential.
Reproductive and developmental findings provided no evidence of an
enhanced sensitivity of the young. All prospective endocrine and
endocrine-related changes which were noted were considered a function
of the chemical's biological mode of action, the degree of exposure, a
response secondary to other changes (e.g, enhanced liver metabolism),
an aging or strain-specific phenomenon, or some combination of these
factors.
C. Aggregate Exposure
1. Dietary exposure. For the acute dietary analysis, the acute
reference dose (aRfD) of 2.0 mg/kg/day was derived from a NOAEL of 200
mg/kg based on an acute neurotoxicity study in rats and the application
of an uncertainty factor (UF) of 100 to account for inter-species
extrapolation and intra-species variability. For the chronic dietary
analysis, the chronic reference dose (cRfD), of 0.022 mg/kg/day was
derived from a NOAEL of 2.2 mg/kg/day based on a 2-generation
reproduction toxicity study in rats and the application of an UF of
100. Based on the moderate, exposure-driven, non-primary, and/or animal
specific nature of the endocrine and neurological changes attributed to
exposure to spiromesifen as well as the lack of evidence to support a
primary embryotoxic or teratogenic potential for spiromesifen, an FQPA
safety factor of 1 was applied to the acute and chronic toxicology
values, resulting in an acute population adjusted dose (aPAD) of 2.0
mg/kg/day and a chronic population adjusted dose (cPAD) of 0.022 mg/kg/
day. As a conservative measure, the aPAD and cPAD values were used for
all population sub-groups when conducting the assessments.
i. Food. Assessments were conducted to evaluate the potential risks
due to acute and chronic dietary exposure of the entire U.S. population
and selected population subgroups to residues of spiromesifen. These
assessments cover the proposed use of spiromesifen on brassica (head
and stem, broccoli and cabbage; leafy, mustard greens), corn (field),
cotton, cucurbits (cantaloupe, cucumbers, and summer squash), fruiting
vegetables (peppers and tomatoes), leafy greens (head and leaf lettuce
and spinach), potatoes, strawberries, and the rotational crops of
alfalfa, barley, sugarbeets, and wheat. For the acute assessment, the
most highly exposed population subgroup was children 1-6 years with an
exposure equal to 0.4% of the acute reference dose (aPAD) at the 95th
percentile. Acute exposure of the overall US population was equivalent
to 0.3% of the aPAD. For the chronic dietary assessment, the most
highly exposed population subgroup was children 1-6 years, with an
exposure equal to 1.2% of the chronic reference dose (cPAD). Chronic
exposure for the overall U.S. population equated to 0.4% of the cPAD.
These Tier 2 acute and chronic dietary exposure estimates are well
below EPA's level of concern for the overall U.S. population as well as
the various population subgroups.
ii. Drinking water. Spiromesifen is immobile in soil and therefore
will not leach into groundwater. Additionally, due to insolubility in
water and a highly lipophilic nature, any residues in surface water
will rapidly bind to soil particles and remain with sediment where it
is quickly degraded, and therefore not contribute to potential dietary
exposure from drinking water. Estimated environmental concentrations
(EECs) of spiromesifen and its enol metabolite in surface water (Tier
I) were determined using EPA's FIRST screening model (FIFRA Index
Reservoir Screening Tool). EEC predictions of spiromesifen its enol
metabolite in groundwater (Tier I) were made using SCI-GROW (Screening
Concentration in Ground Water). Tier II EEC predictions in surface
drinking water were made using the Pesticide Root Zone Model, PRZM3, in
combination with the Exposure Analysis Modeling System, EXAMS II, and
EPA's Index Reservoir (IR) scenario. Use of spiromesifen (Tier II) on
strawberries and vegetables was simulated in Florida, potatoes in
Minnesota and cotton in Texas and California. Applications of
spiromesifen to field corn were also evaluated in Texas.
The highest predicted Tier I surface water EECs for spiromesifen
were from use on strawberries, with peak (acute) and annual average
(chronic) concentrations of 7.41 and 0.18 ppb, respectively.
Corresponding surface water EECs for the enol metabolite were 37.5 and
19.4 ppb. Strawberries produced the highest EECs under the Tier I
scenario due to the conservative runoff assumptions built into the
model. The highest predicted EECs in ground water were 0.000 ppb for
spiromesifen and 1.09 ppb for the enol, also from the strawberry use
scenario. Tier II EECs were predicted to be highest for strawberries
and vegetables. The highest peak, 4-day, 21-day, 60-day, 90-day, yearly
upper 90th percentile (of the
[[Page 45051]]
annual maximums) and annual average concentrations across all use
scenarios were 1.30 and 1.07 ppb for FL strawberries and 0.66, 0.35,
0.24, 0.07 and 0.05 ppb for Florida vegetables, respectively. EECs of
spiromesifen enol were highest for Florida strawberries, with
corresponding concentrations of 32, 30, 26, 17, 11, 3.9, and 1.7 ppb,
respectively.
The highest acute and chronic concentrations (spiromesifen and enol
in surface water combined) across all use scenarios were used to assess
human health risk from drinking water. Potential risk was estimated by
comparing estimated drinking water concentrations to the acute and
chronic Population Adjusted Dose (PAD) values, while accounting for
differences in body weight and drinking water consumption between
adults and children. These calculations result in risk estimates in the
form of percentages of the acute and chronic PAD values. Tier I acute
risk for adults and children were estimated at 0.06 and 0.23%,
respectively, while Tier II acute estimates were 0.05 and 0.17%,
respectively. Maximum Tier I chronic risk was estimated at 2.5% for
adults and 8.9% for children. Corresponding Tier II chronic risk was
estimated at 0.52% for adults and 1.8% for children (0.81% for children
using the mean of the annual average concentrations over the simulation
period).
2. Non-dietary exposure. Exposure assessments were prepared for
both mixer/loader-applicators and reentry workers based on use of
spiromesifen on various field crops, vegetables and strawberries.
Agricultural worker margins of exposure (MOE) estimates were
conservatively based on a no-observable-effect level (NOEL) of 1.06 mg/
kg/day, maximum label rates, and a dermal absorption value of 2.25%. An
occupational exposure uncertainty factor of 100 was used in the
assessment. All margins of exposure (total) exceeded 100, indicating
that these uses of spiromesifen pose no significant risk to workers who
mix, load and apply this product, or to those who reenter treated areas
to perform post-application activities. These data support the use of a
single layer of clothing for mixer/loaders and applicators, gloves for
mixer/loaders, and a 12-hour REI for reentry workers.
Exposure assessments were also conducted for both applicators and
reentry based on use of spiromesifen for ornamentals, greenhouse and
nursery applications. There are no indoor residential uses for
spiromesifen, and therefore no assessments were performed for indoor
residential use. All margins of exposure (total) exceeded 100,
indicating that these uses of spiromesifen pose no significant risk to
workers who mix, load and apply this product, or to those who reenter
treated areas to perform post-application activities. These data
support the use of a single layer of clothing for mixer/loaders and
applicators, gloves for mixer/loaders, and reentry activities to be
performed immediately after the application spray dries.
D. Cumulative Effects
Spiromesifen represents a new class of chemistry, ketoenoles. There
are no known registered chemicals within this class. Bayer will submit
information, if necessary, for EPA to consider concerning potential
cumulative effects of spiromesifen consistent with the schedule
established by EPA at 62 FR 42020 (Aug. 4, 1997) (FRL-5734-6) and other
EPA publications pursuant to the Food Quality Protection Act.
E. Safety Determination
1. U.S. population. Based on the exposure assessments described
above and on the completeness and reliability of the toxicity data, it
can be concluded that total aggregate exposure to spiromesifen from all
label uses will utilize less than 10 percent of the RfD for chronic
dietary exposures and that margins of exposure in excess of 100 exist
for aggregate exposure to spiromesifen for non-occupational exposure.
EPA generally has no concerns for exposures below 100 percent of the
RfD, because the RfD represents the level at or below which daily
aggregate exposure over a lifetime will not pose appreciable risks to
human health. Margins of exposure of 100 or more also indicate an
adequate degree of safety. Thus, it can be concluded that there is a
reasonable certainty that no harm will result from aggregate exposure
to spiromesifen residues.
2. Infants and children. In assessing the potential for increased
sensitivity of infants and children, data from developmental studies in
both rat and rabbit and a 2-generation reproduction study in the rat
can be considered. The developmental toxicity studies evaluate any
potential adverse effects on the developing animal resulting from
pesticide exposure of the mother during prenatal development. The
reproduction study evaluates any effects from exposure to the pesticide
on the reproductive capability of mating animals through two
generations, as well as any observed systemic toxicity. None of these
studies conducted with spiromesifen indicated developmental or
reproductive effects. The toxicology data which support these uses of
spiromesifen include the following: An oral developmental toxicity
study in rat that did not reveal any evidence of teratogenic potential.
Maternal and developmental NOAELs were 10 mg/kg bw/day. An oral
developmental toxicity study in rabbits demonstrated a maternal NOAEL
of 5 mg/kg bw/day, a developmental NOAEL of 35 mg/kg bw/day and did not
reveal any teratogenic potential. A two-generation study in rats, with
a parental toxicity NOAEL of 2.2 mg/kg bw/day, did not reveal evidence
of a primary reproductive toxicity potential. The reproductive NOAEL
was 14.2 mg/kg bw/day. FFDCA Section 408 provides that EPA may apply an
additional safety factor for infants and children. The additional
safety factor may be used when prenatal and postnatal threshold effects
were observed in studies or to account for incompleteness of the
toxicity database. Based on the toxicological data requirements, the
data relative to prenatal and postnatal effects in children is
complete. No indication of increased susceptibility of younger animals
was observed in any of the above studies. For the population with the
highest exposure, children 1-6 years old, the acute dietary exposure at
the 95th percentile was 0.4% of the aPAD, equivalent to an MOE of
24845. Acute exposure of the overall US population was equivalent to
0.3% of the aPAD. For the chronic dietary analysis, the most highly
exposed population subgroup was children 1-6 years old, with an
exposure equal to 1.2% of the cPAD. Chronic exposure for the overall
U.S. population equated to 0.4% of the cPAD.
F. International Tolerances
Codex maximum residue levels (MRLs) are not yet established for
spiromesifen.
[FR Doc. 04-16720 Filed 7-27-04; 8:45 am]
BILLING CODE 6560-50-S