Isophorone; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food, 21767-21771 [05-8128]
Download as PDF
<![CDATA[
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Notices
not affect the final regulatory decision,
were undergoing final editing at that
time. In addition, subsequent to
signature, EPA identified several minor
errors and ambiguities in the document.
Therefore, for the sake of accuracy, the
Agency also has included the
appropriate error corrections,
amendments, and clarifications. None of
these additions or changes alter the
conclusions documented in the March
31, 2005 phenmedipham RED. All of
these changes are described in detail in
an errata memorandum which is
included in the public docket for
phenmedipham.
EPA is applying the principles of
public participation to all pesticides
undergoing reregistration and tolerance
reassessment. The agency’s Pesticide
Tolerance Reassessment and
Reregistration; Public Participation
Process published in the Federal
Register on May 14, 2004 (69 FR 26819)
(FRL–7357–9), explains that in
conducting these programs, the Agency
is tailoring its public participation
process to be commensurate with the
level of risk, extent of use, complexity
of issues, and degree of public concern
associated with each pesticide. EPA can
expeditiously reach decisions for
pesticides like phenmedipham, which
pose no risk concerns, and require no
risk mitigation. Once EPA assesses uses
and risks for such low risk pesticides,
the Agency may go directly to a decision
and prepare a document summarizing
its findings, such as the phenmedipham
RED.
The reregistration program is being
conducted under Congressionally
mandated time frames, and EPA
recognizes the need both to make timely
decisions and to involve the public in
finding ways to effectively mitigate
pesticide risks. Phenmedipham,
however, poses no risks that require
mitigation. The Agency therefore is
issuing the phenmedipham RED, its risk
assessments, and related support
materials simultaneously for public
comment. The comment period is
intended to provide an opportunity for
public input and a mechanism for
initiating any necessary amendments to
the RED. All comments should be
submitted using the methods in Unit I.
of the SUPPLEMENTARY INFORMATION, and
must be received by EPA on or before
the closing date. These comments will
become part of the Agency Docket for
phenmedipham. Comments received
after the close of the comment period
will be marked ‘‘late.’’ EPA is not
required to consider these late
comments.
EPA will carefully consider all
comments received by the closing date
VerDate jul<14>2003
16:41 Apr 26, 2005
Jkt 205001
and will provide a Response to
Comments Memorandum in the Docket
and electronic EDOCKET. If any
comment significantly affects the
document, EPA also will publish an
amendment to the RED in the Federal
Register. In the absence of substantive
comments requiring changes, the
phenmedipham RED will be
implemented as it is now presented.
B. What is the Agency’s Authority for
Taking this Action?
Section 4(g)(2) of FIFRA as amended
directs that, after submission of all data
concerning a pesticide active ingredient,
‘‘the Administrator shall determine
whether pesticides containing such
active ingredient are eligible for
reregistration,’’ before calling in product
specific data on individual end-use
products and either reregistering
products or taking other ‘‘appropriate
regulatory action.’’
Section 408(q) of the Federal Food,
Drug, and Cosmetic Act (FFDCA), 21
U.S.C. 346a(q), requires EPA to review
tolerances and exemptions for pesticide
residues in effect as of August 2, 1996,
to determine whether the tolerance or
exemption meets the requirements of
section 408(b)(2) or (c)(2) of FFDCA.
This review is to be completed by
August 3, 2006.
List of Subjects
Environmental protection, Pesticides
and pests.
April 5, 2005.
Debra Edwards,
Director, Special Review and Reregistration
Division, Office of Pesticide Programs.
[FR Doc. 05–8325 Filed 4–26–05; 8:45 am]
BILLING CODE 6560–50–S
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
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
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–
PO 00000
Frm 00038
Fmt 4703
Sfmt 4703
21767
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
E:\FR\FM\27APN1.SGM
27APN1
21768
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Notices
#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
https://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 https://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
VerDate jul<14>2003
16:41 Apr 26, 2005
Jkt 205001
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 email 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
PO 00000
Frm 00039
Fmt 4703
Sfmt 4703
comments to EPA electronically is
EPA’s preferred method for receiving
comments. Go directly to EPA Dockets
at https://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
E:\FR\FM\27APN1.SGM
27APN1
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Notices
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.
VerDate jul<14>2003
16:41 Apr 26, 2005
Jkt 205001
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
https://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
PO 00000
Frm 00040
Fmt 4703
Sfmt 4703
21769
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 14Cisophorone 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
E:\FR\FM\27APN1.SGM
27APN1
21770
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Notices
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 noobserved 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-globulinassociated 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
VerDate jul<14>2003
16:41 Apr 26, 2005
Jkt 205001
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
https://www.epa.gov/iris/subst/
PO 00000
Frm 00041
Fmt 4703
Sfmt 4703
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 µg/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 µg/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.
E:\FR\FM\27APN1.SGM
27APN1
Federal Register / Vol. 70, No. 80 / Wednesday, April 27, 2005 / Notices
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
ENVIRONMENTAL PROTECTION
AGENCY
[OPP–2004–0183; FRL–7709–9]
Thiram; Notice of Receipt of Request
to Amend to Terminate Uses of Certain
Pesticide Registrations
Environmental Protection
Agency (EPA).
ACTION: Notice.
AGENCY:
SUMMARY: In accordance with section
6(f)(1) of the Federal Insecticide,
Fungicide, and Rodenticide Act
(FIFRA), as amended, EPA is issuing a
notice of receipt of a request by the
registrant to voluntarily terminate use of
certain products containing the
pesticide thiram. The request would
terminate thiram use in or on apples.
The request would not terminate the last
thiram product registered for use in the
U.S. EPA intends to grant this request at
the close of the comment period for this
announcement unless the Agency
receives substantive comments within
the comment period that would merit its
further review of the request, or unless
the registrant withdraws their request
within this period. Upon acceptance of
this request, any sale, distribution, or
use of products listed in this notice will
be permitted only if such sale,
distribution, or use is consistent with
the terms as described in the final order.
DATES: Comments, identified by docket
ID number OPP–2004–0183, 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:
Craig Doty, Special Review and
Reregistration Division (7508C), Office
of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460–
0001; telephone number: (703) 308–
0122; fax number: (703) 308–8041; email address:doty.craig@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
This action is directed to the public
in general, and may be of interest to a
VerDate jul<14>2003
16:41 Apr 26, 2005
Jkt 205001
wide range of stakeholders including
environmental, human health, and
agricultural advocates; the chemical
industry; pesticide users; and members
of the public interested in the sale,
distribution, or use of pesticides. Since
others also may be interested, the
Agency has not attempted to describe all
the specific entities that may be affected
by this action. 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–2004–0183. The official public
docket consists of the documents
specifically referenced in this action,
any public comments received, and
other information related to this action.
Although a part of the official docket,
the public docket does not include
Confidential Business Information (CBI)
or other information whose disclosure is
restricted by statute. The official public
docket is the collection of materials that
is available for public viewing at the
Public Information and Records
Integrity Branch (PIRIB), Rm. 119,
Crystal Mall #2, 1801 S. Bell St.,
Arlington, VA. This docket facility is
open from 8:30 a.m. to 4:00 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
https://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 https://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.
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
PO 00000
Frm 00042
Fmt 4703
Sfmt 4703
21771
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 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
E:\FR\FM\27APN1.SGM
27APN1
]]>Agencies
[Federal Register Volume 70, Number 80 (Wednesday, April 27, 2005)]
[Notices]
[Pages 21767-21771]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-8128]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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 https://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 https://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 https://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 https://
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 https://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.
[[Page 21771]]
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
