[Federal Register: April 27, 2005 (Volume 70, Number 80)]
[Notices]
[Page 21767-21771]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27ap05-82]
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ENVIRONMENTAL PROTECTION AGENCY
[OPP-2005-0108; FRL-7710-1]
Isophorone; Notice of Filing a Pesticide Petition to Establish a
Tolerance for a Certain Pesticide Chemical in or on Food
AGENCY: Environmental Protection Agency (EPA).
ACTION: Notice.
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SUMMARY: This notice announces the initial filing of a pesticide
petition proposing the establishment of regulations for residues of a
certain pesticide chemical in or on various food commodities.
DATES: Comments, identified by docket identification (ID) number OPP-
2005-0108, must be received on or before May 27, 2005.
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: Kathryn Boyle, Registration Division
(7505C), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-6304; e-mail address: boyle.kathryn@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)
Animal production (NAICS 112)
Food manufacturing (NAICS 311)
Pesticide manufacturing (NAICS 32532)
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Get Copies of this Document and Other Related Information?
1. Docket. EPA has established an official public docket for this
action under docket ID number OPP-2005-0108. 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
[[Page 21768]]
2, 1801 S. Bell St., Arlington, VA. This docket facility is
open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal
holidays. The docket telephone number is (703) 305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public
comments, access the index listing of the contents of the official
public docket, and to access those documents in the public docket that
are available electronically. Although, not all docket materials may be
available electronically, you may still access any of the publicly
available docket materials through the docket facility identified in
Unit I.B.1. Once in the system, select ``search,'' then key in the
appropriate docket ID number.
Certain types of information will not be placed in the EPA
Dockets. Information claimed as CBI and other information whose
disclosure is restricted by statute, which is not included in the
official public docket, will not be available for public viewing in
EPA's electronic public docket. EPA's policy is that copyrighted
material will not be placed in EPA's electronic public docket but will
be available only in printed, paper form in the official public docket.
To the extent feasible, publicly available docket materials will be
made available in EPA's electronic public docket. When a document is
selected from the index list in EPA Dockets, the system will identify
whether the document is available for viewing in EPA's electronic
public docket. Although, not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.
EPA intends to work towards providing electronic access to all of the
publicly available docket materials through EPA's electronic public
docket.
For public commenters, it is important to note that EPA's policy
is that public comments, whether submitted electronically or 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 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-2005-0108. 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-2005-0108. 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-2005-0108.
3. By hand delivery or courier. Deliver your comments to: Public
Information and Records Integrity Branch (PIRIB), Office of Pesticide
Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall
2, 1801 S. Bell St., Arlington, VA, Attention: Docket ID
number OPP-2005-0108. 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
[[Page 21769]]
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: April 13, 2005.
Lois Rossi,
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 Isophorone Task Group (ITG) and represents
the view of the petitioner. The summary may have been edited by EPA if
the terminology used was unclear, the summary contained extraneous
material, or the summary unintentionally made the reader conclude that
the findings reflected EPA's position and not the position 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.
The Isophorone Task Group (ITG)
PP 4E6894
EPA has received a pesticide petition (PP 4E6894) from The
Isophorone Task Group (ITG) of the Ketones Panel of the American
Chemistry Council, 1300 Wilson Blvd, Arlington, VA 22209 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 amending the
existing exemption from the requirement of a tolerance for isophorone
(CAS Reg. No. 78-59-1) to limit the use of isophorone to rice, spinach
and sugar beets. EPA has determined that the petition contains data or
information regarding the elements set forth in section 408(d)(2) of
the FFDCA; however, EPA has not fully evaluated the sufficiency of the
submitted data at this time or whether the data support granting of the
petition. Additional data may be needed before EPA rules on the
petition.
A. Residue Chemistry
1. Plant metabolism. In the World Heath Organization's
Environmental Health Criteria 174: Isophorone (see http://www.inchem.org/documents/ehc/ehc/ehc174.htm
), a metabolism study of
14C-isophorone on rice and beans was summarized. In this study, the
decline of isophorone concentration was determined in plants treated
with pesticides containing isophorone as a carrier. 14C-Isophorone was
sprayed on bean and rice plants at a rate equivalent to 7.5 kg/ha, with
plant samples taken periodically and assayed for radioactivity. No
attempt was made to characterize the metabolites or degradation
products. In bean plants, total 14C residues declined rapidly from 60
ppm one hour after application to below 0.1 ppm on day 42. Beans
harvested on day 56 had no detectable residues. In a similar manner,
residues in rice plants declined from 7.3 ppm one hour after spraying,
to 0.12 ppm on day 128. Analysis of the immature rice heads on days 110
and 128 showed no radioactivity. A second study of 14C-isophorone on
sugar beets was also described. Plants treated at the 2-leaf stage were
found to have only 10% of the 14C on day 30 compared to the initial
value. Again, rapid degradation of radioactivity was observed. On day
90, radioactive residues in the plant were below 0.01 ppm. The results
also suggested some uptake of radio-labeled material from the soil,
likely due to uptake of small organic fragments, or 14C resulting from
degradation of isophorone in the soil. The summary of these studies
coupled with the known physical properties, rapid environmental
degradation and volatility of isophorone support the ITG's assumption
that no residues of isophorone remain in rice grain or sugar beets when
they are consumed by humans.
2. Analytical method. ITG is requesting an exemption from the
requirement of a tolerance; therefore, an analytical method is not
needed.
B. Toxicological Profile
1. Acute toxicity. The acute toxicity of isophorone in laboratory
animals is low to moderate: oral LD50 1,500 milligrams/
kilogram/body weight (mg/kg bwt); dermal LD50 1,200 mg/kg
bwt; and inhalation LC50 >7,000 milligrams/cubic meter (mg/
m3). Isophorone is an eye irritant and a respiratory irritant but does
not irritate the skin. It is not a sensitizer in animal studies.
2. Genotoxicity. The majority of in vitro genotoxicity studies
revealed clearly negative results, with the exception of mouse lymphoma
assays, in which both positive and negative results were observed.
Positive results in these lymphoma assays observed in the absence of S9
were associated with considerable cytotoxicity. In vivo assays have
been negative. Based on the weight-of-evidence of the negative in vitro
results, negative in vivo results and
[[Page 21770]]
negative DNA binding data, the overall conclusion is that isophorone is
not mutagenic.
3. Reproductive and developmental toxicity. There is no evidence
indicating that isophorone interferes adversely with reproduction. No
changes were observed in pregnancy rates, litter sizes, pups
abnormalities or in histopathological examinations of the reproduction
organs after long-term studies. In inhalation teratogenicity studies
with rats and mice, the no-observed adverse effect levels (NOAELs) for
maternal toxicity were 289 mg/m3 (based on < 7% reductions in body
weight gains). Isophorone was neither embryotoxic nor teratogenic up to
the highest test concentration of 664 mg/m3].
4. Subchronic toxicity. In subchronic studies, oral administration
of high doses of isophorone caused no significant toxic effects, and
NOAELs were based on reduced body weight gains. The lowest no observed
adverse effect level (NOAEL) for subchronic dietary exposure was 102.5
mg/kg/day in male CFE rats. In B6C3F1 mice, the subchronic NOAEL was
500 mg/kg bwt/day in females and 1,000 mg/kg/day in males. The
subchronic NOAEL in dogs was >150 mg/kg bwt/day. After 4-week
inhalation exposure in rats, nose and eye irritation and blood and
liver changes were observed, and the NOAEL was < 208 mg/m3.
5. Chronic toxicity. In an oral gavage chronic toxicity/
oncogenicity study conducted by the National Toxicology Program at dose
levels of 0, 250 and 500 mg/kg/day in F344 rats and B6C3F1 mice, there
was some evidence of carcinogenicity of isophorone in male rats (kidney
tumors, preputial gland carcinomas). The kidney tumors in male rats
were attributed to an 2u-globulin-associated mechanism that is unique
to male rats and is, therefore, irrelevant for human risk assessment.
At the high dose level, an increased incidence of male rat preputial
gland carcinomas (5/50 vs 0/50 in controls) was reported. There was
equivocal evidence of carcinogenicity for male mice (liver tumors,
mesenchymal tumors of the integumentary system). There was no evidence
of carcinogenicity of isophorone in female rats and mice. Isophorone is
classified as Category ``C'' (possible human carcinogen) with a Q* =
6.08 x 10-4.
6. Animal metabolism. Upon oral and inhalation administration,
isophorone is well absorbed and rapidly distributed throughout the body
of rats and rabbits. While part of the absorbed dose is excreted
unchanged via the urine and exhaled air, metabolites are mainly
excreted as glucuronides in the urine. The tendency of isophorone to
bioaccumulate is very low; within 24 hours after administration of an
oral dose of isophorone, more than 93% was excreted by rats.
7. Endocrine disruption. No evidence of estrogenic or other
endocrine effects has been noted in any of the standard developmental
toxicity, subchronic or chronic toxicity/oncogenicity studies that have
been conducted with this product and there is no reason to suspect that
any such effects would be likely.
C. Aggregate Exposure
1. Dietary exposure. A dietary risk assessment was carried out for
isophorone for exposures resulting from rice, sugar beet, and spinach
products using the Cumulative and Aggregate Risk Evaluation System
(CARES). In this assessment, a ``worst case'' residue of 0.1 mg/kg, a
very conservative level of quantitation (LOQ) from radioactive
metabolism studies, was assumed for rice, spinach and sugar beets as an
upper bound estimate of possible residues for a dietary analysis. In
addition, it was assumed that 10% of the rice and spinach crops, and
89% of sugar beets were treated with formulations containing isophorone
at the highest possible rate of 7 lbs/acre. The chronic exposure
results in margins of exposure (MOEs) larger than 1,000 and cancer
risks of fewer than 1 cancer in a million.
2. Drinking water. Dietary exposure was aggregated with the
drinking water exposure derived from measured values. Since ``real
world'' data were available in the literature this assessment was
considered a more realistic view than modeling of the exposure and risk
which would result from isophorone. The chronic assessment from
aggregate exposure results in non-cancer MOEs larger than 1,000 and
cancer risks of fewer than 1 cancer in a million.
D. Cumulative Effects
Currently, no methodologies are available to resolve the complex
scientific issues concerning common mechanisms of toxicity and
cumulative exposure and risk. EPA has begun a pilot process to study
this issue further through the examination of particular classes of
pesticides. Thus, ITG believes it is appropriate to consider only the
potential risks of isophorone in its exposure assessment.
E. Safety Determination
1. U.S. population. The Agency's Integrated Risk Information System
(see http://www.epa.gov/iris/subst/0063.htm) reports a chronic oral
reference dose (RfD) of 0.2 mg/kg/day. This value was based on the use
of the NOAEL of 150 mg/kg/day from the 90-day feeding study in dogs,
with an uncertainty factor (UF) of 1,000. In addition to the standard
100X UF for interspecies and intraspecies variability, an additional
10X UF was applied to account for the use of a subchronic study.
(Calculation of the RfD using the Lowest Effect Level (LEL) from a
chronic rat study (time-weighted average dose of 179 mg/kg/day) with an
additional 10X UF for use of a LEL produces essentially the same
result.) Generally, and under FQPA, EPA has no concerns for exposures
below 100% of the RfD because the RfD represents the level at or below
which daily exposure over a lifetime will not pose appreciable risk to
human health. Based on the RfD, the calculated drinking water level of
concern (2,999 [mu]g/L/day) is 2.75-fold above the most conservative
estimate of potential human exposure resulting from consumption of
ditch water following direct application of pesticide formulations
containing isophorone (1,100 [mu]g/L). In addition, based on an
aggregate of the CARES dietary assessment and drinking water
assessments from ground water and surface water, less than 0.1% of the
RfD would be consumed. Therefore, there is reasonable certainty that no
harm will result to the general U.S. population from aggregate exposure
to isophorone residues.
2. Infants and children. In assessing the potential for additional
safety of infants and children to possible residues of isophorone, data
from the developmental toxicity studies in mice and rats, and the lack
of effects on reproductive organs in long-term studies were considered.
The developmental studies are designed to evaluate adverse effects on
the developing organism resulting from exposure during prenatal
development. Detailed histologic examination of reproductive organs
from repeated dose studies identifies target organ effects that would
indicate potential adverse effects on reproduction and the well being
of offspring. Based on the existing data base for isophorone, no
adverse effects on development or reproductive organs were observed.
Using conservative exposure assessments, the percent RfD utilized by
potential exposure to isophorone is < 0.1%, with an aggregate MOE of
937,500, well above an acceptable MOE of 100.
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F. International Tolerances
There are no codex maximum residue levels established for
isophorone.
[FR Doc. 05-8128 Filed 4-26-05; 8:45 am]
BILLING CODE 6560-50-S