[Federal Register Volume 70, Number 80 (Wednesday, April 27, 2005)]
[Notices]
[Pages 21767-21771]
From the Federal Register Online via the Government Publishing 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: [email protected].

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 [email protected], 
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.

[[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