Environmental Protection Agency (EPA).
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.
Comments, identified by docket identification (ID) number OPP-2005-0108, must be received on or before May 27, 2005.
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.Start Further Info
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: firstname.lastname@example.org.End Further Info End Preamble Start Supplemental 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 Start Printed 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@example.com, 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 Start Printed Page 21769identify 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.Start List of Subjects
List of Subjects
- Environmental protection
- Agricultural commodities
- Feed additives
- Food additives
- Pesticides and pests
- Reporting and recordkeeping requirements
Dated: April 13, 2005.
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)
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 Start Printed Page 21770negative 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 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.Start Printed Page 21771
F. International Tolerances
There are no codex maximum residue levels established for isophorone.End Supplemental Information
[FR Doc. 05-8128 Filed 4-26-05; 8:45 am]
BILLING CODE 6560-50-S