[Federal Register: December 10, 2003 (Volume 68, Number 237)]
[Notices]
[Page 68904-68908]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10de03-78]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2003-0385; FRL-7337-6]
Spiroxamine; 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-2003-0385, must be
received on or before January 8, 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: Mary L. Waller, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: (703) 308-9354; e-mail address:waller.mary@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, pesticide manufacturer or
formulator. Potentially affected entities may include, but are not
limited to:
[sbull] Crop production (NAICS 1111)
[sbull] Food manufacturing (NAICS 311)
[sbull] Pesticide manufacturing (NAICS 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket identification (ID) number OPP-2003-0385. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA Dockets.
Information claimed as CBI and other information whose disclosure is
restricted by statute, which is not included in the official public
docket, will not be available for public viewing in EPA's electronic
public docket. EPA's policy is that copyrighted material will not be
placed in EPA's electronic public docket but will be available only in
printed, paper form in the official public docket. To the extent
feasible, publicly available docket materials will be made available in
EPA's electronic public docket. When a document is selected from the
index list in EPA Dockets, the system will identify whether the
document is available for viewing in EPA's electronic public docket.
Although not all docket materials may be available electronically, you
may still access any of the publicly available docket materials through
the docket facility identified in Unit I.B. EPA intends to work towards
providing electronic access to all of the publicly available docket
materials through EPA's electronic public docket.
For public commenters, it is important to note that EPA's policy is
that public comments, whether submitted electronically or 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
[[Page 68905]]
copyrighted material, will be available in the public docket.
Public comments submitted on computer disks that are mailed or
delivered to the docket will be transferred to EPA's electronic public
docket. Public comments that are mailed or delivered to the docket will
be scanned and placed in EPA's electronic public docket. Where
practical, physical objects will be photographed, and the photograph
will be placed in EPA's electronic public docket along with a brief
description written by the docket staff.
C. How and To Whom Do I Submit Comments?
You may submit comments electronically, by mail, or through hand
delivery/courier. To ensure proper receipt by EPA, identify the
appropriate docket ID number in the subject line on the first page of
your comment. Please ensure that your comments are submitted within the
specified comment period. Comments received after the close of the
comment period will be marked ``late.'' EPA is not required to consider
these late comments. If you wish to submit CBI or information that is
otherwise protected by statute, please follow the instructions in Unit
I.D. Do not use EPA Dockets or e-mail to submit CBI or information
protected by statute.
1. Electronically. If you submit an electronic comment as
prescribed in this unit, EPA recommends that you include your name,
mailing address, and an e-mail address or other contact information in
the body of your comment. Also include this contact information on the
outside of any disk or CD ROM you submit, and in any cover letter
accompanying the disk or CD ROM. This ensures that you can be
identified as the submitter of the comment and allows EPA to contact
you in case EPA cannot read your comment due to technical difficulties
or needs further information on the substance of your comment. EPA's
policy is that EPA will not edit your comment, and any identifying or
contact information provided in the body of a comment will be included
as part of the comment that is placed in the official public docket,
and made available in EPA's electronic public docket. If EPA cannot
read your comment due to technical difficulties and cannot contact you
for clarification, EPA may not be able to consider your comment.
i. EPA Dockets. Your use of EPA's electronic public docket to
submit comments to EPA electronically is EPA's preferred method for
receiving comments. Go directly to EPA Dockets at http://www.epa.gov/edocket/
, and follow the online instructions for submitting comments.
Once in the system, select`` search,'' and then key in docket ID number
OPP-2003-0385. 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-2003-0385. 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-2003-0385.
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-2003-0385. 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.
[[Page 68906]]
List of Subjects
Environmental protection, Agricultural commodities, Feed additives,
Food additives, Pesticides and pests, Reporting and recordkeeping
requirements.
Dated: November 26, 2003.
Peter Caulkins,
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.
Bayer CropScience
PP 3E6783
EPA has received a pesticide petition (PP 3E6783) from Bayer
CropScience, 2 T.W. Alexander Drive, P.O. Box 12014, Research Triangle
Park, NC 27709roposing, 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 Spiroxamine, 8-(1,1-
Dimethylethyl)-N-ethyl-N-propyl-1,4-dioxaspiro[4,5]decane-2-methanamine
in or on the raw agricultural commodity hop, dried cone - import at
50.0 parts per million (ppm). EPA has determined that the petition
contains data or information regarding the elements set forth in
section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated
the sufficiency of the submitted data at this time or whether the data
supports granting of the petition. Additional data may be needed before
EPA rules on the petition.
A. Residue Chemistry
1. Plant metabolism. A hop plant metabolism study has been
conducted, and the nature of the residue is adequately understood. An
animal metabolism study is not required since the proposed crop to be
treated with Spiroxamine is not fed to livestock.
2. Analytical method. A method to determine the total residues of
Spiroxamine using gas chromatography has been submitted to the EPA. In
addition, Spiroxamine has been evaluated using the multi-residue
methodologies as published in the FDA Pesticide Analytical Manual,
Volume I.
3. Magnitude of residues. Eight field trials were conducted on
fields in typical hop-growing regions in Germany to assess the residue
levels of Spiroxamine, 8-(1,1-dimethylethyl)-N-ethyl-N-propyl-1,4-
dioxaspiro[4,5]decane-2-methanamine, in/on hops following foliar
applications. A formulation containing Spiroxamine (KWG 4168 500 EC)
was applied in two spray applications as an emulsifiable concentrate
formulation containing 500 grams (g) active ingredient/liter(L), with
an application rate of 1.5 liters/hectare (L/ha) and 3,000 L of water/
ha. This corresponded to a total applied amount of the active
ingredient of 0.750 kilograms (kg)/ha. The applications were carried
out at growth stages 75-79 and 77-81, respectively (corresponding to a
9-10 day interval between applications).
Duplicate composite samples of hop cones were collected at a 10-day
preharvest interval (PHI) from each plot. In addition, single samples
were collected on day 0 and, in four of the trials, on days 6 and 13
after treatment. Hop cones were analyzed both fresh and, on days 10 and
13, after kiln drying. The highest total residue value of Spiroxamine
(defined as parent and metabolites converted to aminodiol equivalents)
in dried hop cones was 30 ppm (highest individual value)/24.5 ppm
(highest average value [HAFT] from two samples in a single trial) at a
10-day PHI. The total Spiroxamine residues in hop cones appeared to
decline with time. Note: The residue trials submitted with this
petition are being submitted as a national submission in Germany in the
European Union (EU). The European procedure for calculating a maximum
residue limit (MRL) differs from the procedure used in the USA.
Although no final decision has yet been made by the European
authorities at the present time, an evaluation of the dried hop cone
data according to EU principles leads to an MRL proposal equivalent to
50 ppm total residues of Spiroxamine. In order to avoid possible trade
conflicts, it is proposed that the U.S. tolerances be harmonized with
the expected EU-MRL.
Samples from two of the above field trials were also processed into
beer (four individual processing trials). Average total residues for
the dried hop cones prior to processing in these trials were 9.5 and 16
ppm, respectively. In beer, the total residues of Spiroxamine were
below the level of detection (i.e., <0.05 ppm) in all four trials.
B. Toxicological Profile
1. Acute toxicity--KWG 4168 (Spiroxamine) Technical. The acute oral
LD50 in male rats was 595 milligrams/kilogram (mg/kg) and in
female rats was >500 but <560 mg/kg. The acute dermal LD50
in rats was >1,600 and 1,068 mg/kg for males and females, respectively.
The 4-hour inhalation LC50 in rats was 2.772 and 1.982
milligrams/liter (mg/L) for males and females, respectively. Irritation
studies in rabbits revealed Spiroxamine was severely irritating to the
skin while not irritating to the eye. Spiroxamine exhibited a skin-
sensitizing potential in guinea pigs in both the Magnusson/Kligman
maximization test and the Buehler patch test.
2. Genotoxicty. The genotoxic action of Spiroxamine was studied in
bacteria and mammalian cells with the aid of various in vitro test
systems (Salmonella microsome test, forward mutation assay, cytogenetic
study with Chinese hamster ovary cells and unscheduled DNA synthesis
test) and in one in vivo test (micronucleus test). None of the tests
revealed any evidence of a mutagenic or genotoxic potential of
Spiroxamine. The compound did not induce point mutations, DNA damage or
chromosome aberrations.
3.Reproductive and developmental toxicity. In a reproduction study
using rats, Spiroxamine was administered for two generations at dietary
concentrations of 20, 80 or 300 ppm. Reproductive effects such as
reduced litter size at birth and clinical signs of toxicity occurred at
the high dose in conjunction with maternal toxicity. The parental and
reproductive NOAELs were 20 ppm (equal to 2.13 milligrams per kilogram
of bodyweight per day (mg/kg bw/day)) and 80 ppm (equal to 9.19 mg/kg
bw/day), respectively.
In a developmental toxicity study in rats, Spiroxamine was
administered by oral gavage at dose levels of 0, 10 and 25 mg/kg bw/day
and in a supplemental study at doses of 0 and 150 mg/kg bw/day. Severe
maternal toxicity occurred at 150 mg/kg bw/day resulting in the deaths
of 21 of 25 animals. Embryotoxicity (palatoschisis and omphalocele) was
observed at the high dose in conjunction with the severe maternal
toxicity. The two lower dose levels did not reveal any maternal or
developmental toxicity. The results of these studies showed that the
dose of 150 mg/kg bw/day was too high to obtain unequivocal results
with respect to embryotoxicity and teratogenicity.
In another oral developmental toxicity study in rats, Spiroxamine
was administered by gavage during gestation
[[Page 68907]]
at doses of 0, 10, 30 or 100 mg/kg bw/day. Developmental toxicity
occurred in conjunction with distinct maternal toxicity at the highest
dose tested. The maternal NOAEL was 30 mg/kg bw/day based on reduced
body weight gain and feed intake at 100 mg/kg bw/day. The NOAEL for
developmental toxicity was 30 mg/kg bw/day based on delayed
ossification, slightly reduced fetal weights and three cases of
palatoschisis at 100 mg/kg bw/day.
In oral developmental toxicity studies in rabbits, Spiroxamine was
administered by gavage during gestation at doses of 0, 5, 20 or 80 mg/
kg bw/day and in a supplemental study at doses of 0 and 80 mg/kg bw/
day. The maternal NOAEL was 20 mg/kg bw/day based on clinical findings,
reduced body weight gain, reduced food intake and lethality at 80 mg/kg
bw/day. The NOAEL for developmental toxicity was 20 mg/kg bw/day based
on marginal developmental toxicity (reduced fetal weight and a slight
increased rate of spontaneous malformations) at the highest dose level.
In a dermal developmental toxicity study in rats, Spiroxamine was
administered for 6 hours/day during gestation at doses of 0, 5, 20 or
80 mg/kg. Reduced body weight gain occurred in dams at 20 mg/kg and
greater. Dose-related skin reactions were observed at all treated
doses. Developmental toxicity, such as wavy ribs, occurred in
conjunction with maternal toxicity at the highest dose tested. The
NOAELs for systemic and local maternal toxicity were 5 and <5 mg/kg,
respectively. The NOAEL for developmental toxicity was 20 mg/kg.
Spiroxamine did not reveal any teratogenic potential associated with
dermal application.
4. Subchronic toxicity.In subacute dermal toxicity studies, rabbits
were treated with Spiroxamine at doses ranging from 0.05 to 5 mg/kg bw/
day for 6 hours/day over a period of 3 weeks. Systemic effects were not
observed in these studies. Local irritation, increased skin fold
thickness, and histopathological findings of the skin occurred in these
studies. The overall NOAELs for local and systemic effects were 0.2 and
5 mg/kg bw/day, respectively.
In a 90-day feeding study, mice were administered Spiroxamine at
dietary concentrations of 0, 20, 80, 320 or 1,280 ppm. Effects observed
included clinical signs of toxicity, decreased body weight and food
consumption, changes in hematological parameters, hyperplastic changes
in the epidermis of the auricles and/or tail, and effects on the liver,
kidney, and urinary bladder. The NOAEL was 20 ppm (equal to 6.2 mg/kg
bw/day) for male mice based on marginally reduced body weight
development at 80 ppm. The NOAEL for female mice was 80 ppm (equal to
28.5 mg/kg bw/day) based on slight morphological findings in the liver
at 320 ppm.
In another subchronic mouse study, Spiroxamine was administered by
oral gavage at doses of 0, 60, 180 or 240 mg/kg. Effects observed
included clinical signs of toxicity, and effects of the liver, urinary
bladder and hyperplastic changes in the epidermis of the auricles and
tails. Evidence of liver enzyme induction was seen in all treatment
groups. The NOAEL was <60 mg/kg bw/day for both males and females.
Spiroxamine was administered to rats in a subchronic feeding study
at dietary concentrations of 0, 25, 125 or 625 ppm over a period of 13
weeks. Effects included clinical signs of toxicity, reduced body weight
gains, changes in hematological parameters, and effects on the liver,
urinary bladder, esophagus and forestomach. The NOAEL for both male and
female was 25 ppm (equal to 1.9 and 2.7 mg/kg bw/day, respectively)
based on histopathological findings in the esophagus and forestomach at
125 ppm.
In two subchronic feeding studies in dogs, Spiroxamine was
administered at dietary concentrations of 0, 25, 750 or 1,500 ppm and
at 0, 150, 250 or 500 ppm over a period of 13 weeks. Toxicological
effects included changes in clinical chemistries, increased relative
liver weights, and histopathological findings in the liver. The overall
NOAELs from these studies were 500 ppm (equal to 16.9 mg/kg bw/day) and
750 ppm (equal to 21.29 mg/kg bw/day) for males and females,
respectively, based on liver effects.
5.Chronic toxicity. In a chronic dog study, Spiroxamine was
administered at dietary concentrations of 0, 25, 75, 1,000 or 2,000 ppm
for a period of 52 weeks. Effects included opthalmological findings,
changes in clinical chemistries, mild anemia, and histopathological
findings (eye and liver). The NOAEL for both sexes was 75 ppm (equal to
2.47 and 2.48 mg/kg bw/day for males and females, respectively) based
on eye and liver effects.
Rats were administered Spiroxamine for 2 years at dietary
concentrations of 0, 10, 70 or 490 ppm. Effects included reduced body
weight gains, a slight increase in mortality and histopathological
findings in the esophagus and urinary bladder. The NOAEL for both sexes
was 70 ppm (equal to 4.22 and 5.67 mg/kg bw/day for males and females,
respectively) based on esophagus and urinary bladder effects.
The carcinogenicity potential of Spiroxamine was investigated in
rats and mice at maximum dietary concentrations of 490 ppm (equal to
32.81 mg/kg bw/day) and 600 ppm (equal to 149.8 mg/kg bw/day),
respectively. No evidence of an oncogenic potential of Spiroxamine was
found in the long-term studies in rats and mice.
6. Animal metabolism. Rats were gavaged with 1 or 100 mg/kg radio-
labeled technical Spiroxamine. Seventy percent of the oral low dose was
absorbed. Within 48 hours of dosing, over 97% of the dose was excreted
in urine and feces. At sacrifice (48 hours post dosing), the
radioactivity remaining in the body was below 1% in the low dose groups
and approximately 1% and 2% in the male and female rats, respectively,
from the high dose group. Concentrations found in tissues and organs
were relatively low: i.e., they do not exceed 0.04 mirograms/gram
([mu]g/g). The highest concentrations were found in liver, thymus and
adrenals. Slightly smaller concentrations were observed in the thyroid,
spleen, fat, ovaries and uterus. The main metabolite in all dose groups
is Spiroxamine oxidized to the carboxylic acid in the t-butyl-moiety.
The identification rate was approximately 77% of the recovered
radioactivity in all dose groups.
7. Metabolite toxicology. Toxicological studies have been conducted
on KWG 4168 N-oxide, a plant and animal metabolite of Spiroxamine. In
an acute oral toxicity study on KWG 4168 N-oxide using female rats, the
LD50 was 707 mg/kg. In a subacute toxicity study, rats were
administered KWG 4168 N-oxide at dietary concentrations of 0, 30, 150
and 1,000 ppm. The highest concentration resulted in treatment-related
effects. The main targets were the epithelia of the digestive tract and
the urinary bladder. A mild liver enzyme induction was observed without
any correlating gross- or micropathological findings. In a subchronic
study, rats were administered KWG 4168 N-oxide at dietary
concentrations of 0, 25, 125 and 625 ppm, and KWG 4168 at 625 ppm.
Toxic effects were observed at 625 ppm for both test substances.
Similar effects included delayed body weight development, changes in
clinical chemistries and micropathological findings of the esophagus
and stomach. The effects were less pronounced for KWG 4168 N-oxide when
compared to KWG 4168 (parent). Effects noted only in animals treated
with KWG 4168 included changes in hematological
[[Page 68908]]
parameters and micropathological findings of the urinary bladder
(females). The mutagenic potential of KWG 4168 N-oxide was studied in
vitro in bacteria and mammalian cells. It did not cause mutations in
vitro in the Ames assay, the V-79-HPRT gene mutation assay, or produce
clastogenicity in the chromosome aberration assay with or without
metabolic activation.
8. Endocrine disruption. The toxicology data base for Spiroxamine
is current and complete. Studies in this data base include evaluation
of the potential effects on reproduction and development, and an
evaluation of the pathology of the endocrine organs following short- or
long-term exposure. These studies revealed no primary endocrine effects
due to Spiroxamine.
C. Aggregate Exposure
1. Dietary exposure. An aggregate risk assessment was conducted for
all pending uses (grape, hop (domestic and imported) and banana
(imported)) to assess the potential acute and chronic dietary exposure
resulting from applications of Spiroxamine to these crops. Novigen
Sciences, Inc.'s Dietary Exposure Evaluation Model (DEEM[reg]) was used
to estimate the chronic and acute dietary exposure.
For the acute dietary analysis, the proposed acute reference dose
(aRfD) of 0.1 mg/kg/day was used. This aRfD is based on NOELs of 10 mg/
kg from an acute oral toxicity and an acute neurotoxicity screening
study and applying a 100-fold uncertainty factor.
For the chronic dietary analysis, the proposed chronic reference
dose (cRfD) of 0.02 mg/kg/day was used. This cRfD is based on a
parental toxicity NOEL of 2.13 mg/kg/day from the two-generation
reproduction study and the application of a 100-fold uncertainty
factor.
Results from the acute and chronic dietary exposure analyses
described below demonstrate a reasonable certainty that no harm to the
overall U.S. population or any population subgroup will result from the
use of Spiroxamine on grape, hop and banana.
i. Food. An acute, Tier 1 dietary (food) risk assessment was
conducted using the highest residue values and 100% crop treated. The
estimated percent of the aRfD for the overall U.S. population (all
seasons) at the 95 percentile is 8.5%. The most highly exposed
population subgroup, non-nursing infants, had an exposure equal to
33.3% of the aRfD at the 95 percentile. These exposure estimates in are
within EPA's criteria of acceptability.
A chronic, Tier 1 dietary (food) risk assessment was conducted
using average residue values and 100% crop treated. The estimated
percent of the cRfD for the overall U.S. population (all seasons) is
9.1%. For the most highly exposed population subgroup, children 1 to 6)
years old, the exposure consumed 30.6% of the cRfD. These exposure
estimates are within EPA's criteria of acceptability.
ii. Drinking water. No monitoring data are available for residues
of Spiroxamine in ground water, and EPA has established no health
advisory levels or maximum contaminant levels for residues of
Spiroxamine in drinking water.
Studies show low to no soil mobility for Spiroxamine and its
primary metabolites. In addition, field studies show that Spiroxamine
and its degradates do not leach below the 6-inch depth level, and show
very low potential to leach into ground water. Therefore, it can be
concluded with reasonable certainty that no harm will result from acute
or chronic aggregate exposure to Spiroxamine residues in drinking
water.
2. Non-dietary exposure. Spiroxamine is not registered nor are
registrations pending for uses that would result in non-dietary
exposure.
D. Cumulative Effects
Spiroxamine belongs to a new class of chemistry know as
spiroketalamines. Therefore, for this tolerance petition, it is assumed
that Spiroxamine does not have a common mechanism of toxicity with
other substances and only the potential risks of Spiroxamine in its
aggregate exposure are considered.
E. Safety Determination
1. U.S. population. Based on the above aggregate food exposure
estimates for the overall U.S. population (8.5% of the aRfD and 9.1% of
the cRfD), the low potential for Spiroxamine and its degradates to
leach into ground water, and the completeness of the toxicity data
base, there is reasonable certainty that no harm to the U.S. population
will result from aggregate exposure to Spiroxamine.
2. Infants and children. In assessing the potential for additional
sensitivity of infants and children to residues of Spiroxamine, data
from developmental toxicity studies in mice, rats, rabbits and a two-
generation reproduction study in the rat are considered. The
developmental toxicity studies are designed to evaluate adverse effects
on the developing organism resulting from maternal pesticide exposure
during gestation. Reproduction studies provide information relating to
effects from exposure to the pesticide on the reproductive capability
of mating animals and data on systemic toxicity.
Based on the above, aggregate food exposure estimates for the most
highly exposed population subgroups, i.e., non-nursing infants and
children (1-6 years old), consumed 33.3% and 30.6% of the aRfD and
cRfD, respectively. This, in combination with the low potential for
Spiroxamine and its degradates to leach into ground water, and on the
completeness of the toxicity data base, there is reasonable certainty
that no harm to infants and children will result from aggregate
exposure to Spiroxamine.
F. International Tolerances
There are no established Codex, Canadian or Mexican MRLs for
Spiroxamine.
[FR Doc. E3-00489 Filed 12-8-03; 8:45 am]
BILLING CODE 6560-50-S