03-850. Bifenazate; 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 Bifenazate in or on various food commodities.

DATES:

Comments, identified by docket ID number OPP-2002-0356, must be received on or before February 14, 2003.

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:

Shaja R. Brothers, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: [phone]; e-mail address: [e-mail].

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 code 111)
• Animal production (NAICS code 112)
• Food manufacturing (NAICS code 311)
• Pesticide manufacturing (NAICS code 32532)

This listing is not intended to be exhaustive, but rather provides a guide for readers regarding entities likely to be affected by this action. Other types of entities not listed in this unit could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether this action might apply to certain entities. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT.

B. How Can I Get Copies of this Document and Other Related Information?

1. Docket. EPA has established an official public docket for this action under docket identification (ID) number OPP-2002-0356. The official public docket consists of the documents specifically referenced in this action, any public comments received, and other information related to this action. Although a part of the official docket, the public docket does not include Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. The official public docket is the collection of materials that is available for public viewing at the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The docket telephone number is [phone].

2. Electronic access. You may access this Federal Register document electronically through the EPA Internet under the “Federal Register” listings at http://www.epa.gov/​fedrgstr/​.

An electronic version of the public docket is available through EPA's electronic public docket and comment system, EPA Dockets. You may use EPA Dockets at http://www.epa.gov/​edocket/​ to submit or view public comments, access the index listing of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in Unit I.B.1. Once in the system, select “search,” then key in the appropriate docket ID number.

Certain types of information will not be placed in the EPA Dockets. Information claimed as CBI and other information whose disclosure is restricted by statute, which is not included in the official public docket, will not be available for public viewing in EPA's electronic public docket. EPA's policy is that copyrighted material will not be placed in EPA's electronic public docket but will be available only in printed, paper form in the official public docket. To the extent feasible, publicly available docket materials will be made available in EPA's electronic public docket. When a document is selected from the index list in EPA Dockets, the system will identify whether the document is available for viewing in EPA's electronic public docket. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in Unit I.B. EPA intends to work towards providing electronic access to all of the publicly available docket materials through EPA's electronic public docket.

For public commenters, it is important to note that EPA's policy is that public comments, whether submitted electronically or in paper, will be made available for public viewing in EPA's electronic public docket as EPA receives them and without change, unless the comment contains copyrighted material, CBI, or other information whose disclosure is restricted by statute. When EPA identifies a comment containing copyrighted material, EPA will provide a reference to that material in the version of the comment that is placed in EPA's electronic public docket. The entire printed comment, including the 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-2002-0356. 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 [e-mail], Attention: Docket ID Number OPP-2002-0356. 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-2002-0356.

3. By hand delivery or courier. Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket ID Number OPP-2002-0356. Such deliveries are only accepted during the docket's normal hours of operation as identified in Unit I.B.1.

D. How Should I Submit CBI To the Agency?

Do not submit information that you consider to be CBI electronically through EPA's electronic public docket or by e-mail. You may claim information that you submit to EPA as CBI by marking any part or all of that information as CBI (if you submit CBI on disk or CD ROM, mark the outside of the disk or CD ROM as CBI and then identify electronically within the disk or CD ROM the specific information that is CBI). Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2.

In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket and EPA's electronic public docket. If you submit the copy that does not contain CBI on disk or CD ROM, mark the outside of the disk or CD ROM clearly that it does not contain CBI. Information not marked as CBI will be included in the public docket and EPA's electronic public docket without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your comments:

1. Explain your views as clearly as possible.

2. Describe any assumptions that you used.

3. Provide copies of any technical information and/or data you used that support your views.

4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide.

5. Provide specific examples to illustrate your concerns.

6. Make sure to submit your comments by the deadline in this notice.

7. To ensure proper receipt by EPA, be sure to identify the docket ID number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation.

II. What Action is the Agency Taking?

EPA has received a pesticide petition as follows proposing the establishment and/or amendment of regulations for residues of a certain pesticide chemical in or on various food commodities under section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition contains data or information regarding the elements set forth in FFDCA section 408(d)(2); however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition.

List of Subjects

• Environmental protection
• Agricultural commodities
• Feed additives
• Food additives
• Pesticides and pests
• Reporting and recordkeeping requirements

Dated: December 20, 2002.

 Debra Edwards,

Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

The petitioner summary of the pesticide petition is printed below as required by FFDCA section 408(d)(3). The summary of the petition was prepared by the petitioner and represents the view of the petitioner. The petition summary announces the availability of a description of the analytical methods available to EPA for the detection and measurement of the pesticide chemical residues or an explanation of why no such method is needed.

Interregional Research Project Number (IR-4) and Crompton Manufacturing Company, Inc.

PP 3E6517

EPA has received a pesticide petition (3E6517) from the Interregional Research Project Number (IR-4), 681 U.S. Hwy. #1 South, North Brunswick, NJ 08902 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR 180.572 by establishing tolerances for residues of bifenazate, (diazinecarboxylic acid, 2-(4-methoxy-[1,1′-biphenyl]-3-yl),1-methylethylester) in or on the following raw agricultural commodities (RACs): Vegetable, cucurbit, group at 0.6 part per million (ppm); vegetable, fruiting, group at 2.0 ppm; peppermint, tops at 25 ppm; spearmint, tops at 25 ppm; nut, tree, group at 0.2 ppm; almond, hulls at 10 ppm; okra at 2.0 ppm; and pistachio at 0.2 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408(d)(2) of the FFDCA; however, EPA has not fully evaluated the sufficiency of the submitted data at this time or whether the data support granting of the petition. Additional data may be needed before EPA rules on the petition. This notice includes a summary of the petition prepared by Crompton Manufacturing Company, Inc. (formerly Uniroyal Chemical Company), Middlebury, CT 06749.

A. Residue Chemistry

1. Plant metabolism. The nature of the residues of bifenazate in plants is adequately understood. The major residue in all plant metabolism studies is bifenazate. A minor, but significant metabolite is the diazene D3598, which was found to interconvert readily to/from bifenazate in the plant matrix during the analytical procedure.

2. Analytical method. Crompton has developed practical analytical methodology for detecting and measuring residues of bifenazate in or on RACs. As D3598, a significant metabolite, was found to interconvert readily to/from bifenazate, the analytical method was designed to convert all residues of D3598 to the parent compound (bifenazate) for analysis. The method utilizes reversed phase high performance liquid chromotography (HPLC) to separate the bifenazate from matrix derived interferences, and oxidative coulometric electrochemical detection for the identification and quantification of this analyte.

B. Toxicological Profile

1. Acute toxicity. Bifenazate technical, acramite-50WS, and floramite SC have low acute oral, dermal, and inhalation toxicity in laboratory animals. The oral lethal dose LD₅₀ in rats and mice is greater than 5 grams/kilogram (g/kg) for acramite-50WS and the technical material. The oral LD₅₀ of floramite SC is greater than 5 g/kg in males and greater than 2 g/kg in females. The dermal LD₅₀ in rats of bifenazate technical and both formulations is greater than 5 g/kg. The inhalation lethal concentration LC₅₀ in the rats of bifenazate technical, acramite-50WS and floramite SC was found to be greater than 4.4, 5.2, and 1.8 milligrams/liter (mg/L), respectively. In eye irritation studies, acramite-50WS was a slight irritant, and bifenazate technical was non-irritating. Floramite SC was found to be irritating to the eyes. All 3 products were found to be non-irritating to the skin of rabbits and non-sensitizing on the skin of guinea pigs.

2. Genotoxicity. Bifenazate was evaluated and found to be negative in the Ames Reverse Mutation, Mouse Lymphoma, chinese hamster ovary (CHO) chromosome aberration and mouse micronucleus assays.

3. Reproductive and developmental toxicity—i. Rabbit developmental study. A range-finding study conducted in pregnant New Zealand white rabbits at dosage levels of 125, 250, 500, 750, and 1,000 milligrams/kilogram/day (mg/kg/day) demonstrated maternal toxicity at dosage levels of 500 mg/kg/day and greater and abortions at dosage levels of 250 mg/kg/day and greater. Bifenazate was then administered by oral gavage to pregnant New Zealand white rabbits at dosage levels of 10, 50, and 200 mg/kg/day. No test article related effects were seen at any dose level. The no observable adverse effect level (NOAEL) for maternal and developmental toxicity was greater than 200 mg/kg/day.

ii. Rat developmental study. Bifenazate did not produce developmental toxicity when administered by oral gavage to pregnant Sprague-Dawley CD rats at dosage levels of 10, 100, and 500 mg/kg/day. A reduction in maternal body weight gain was seen at dosage levels of 100 and 500 mg/kg/day. Clinical observations at 500 mg/kg/day included red material/staining on body surfaces, pale extremities, and brown discharge. No developmental or teratogenic effects were observed at any dosage level. The NOAEL for maternal toxicity was 10 mg/kg/day and the NOAEL for developmental toxicity was greater than 500 mg/kg/day.

iii. Rat reproduction study. Bifenazate showed no effects on reproduction when fed to 2-generations of male and female Sprague-Dawley CD rats at dietary concentrations of 20, 80, and 200 ppm. At a dosage level of 200 ppm there was a reduction in body weight gain in F0 males and females. Food consumption was unaffected. There was a reduction in body weight gain in F1 females at all dosage levels and in F1 males at 80 and 200 ppm in the absence of effects on food consumption. Since the 20 ppm F1 males did not have a significant reduction in body weight gain, this dosage level can be considered a NOAEL for systemic adult toxicity. The reduction in body weight gain in the F1 females at 20 ppm would not be considered biologically significant because no effects were observed on reproductive parameters or in the F2 litter. The reproductive and developmental NOAEL was greater than 200 ppm (10 mg/kg/day).

4. Subchronic toxicity—i. Thirteen-week rat feeding study. Bifenazate was fed to male and female Sprague Dawley CD rats for 13 weeks at dietary concentrations of 40, 200, and 400 ppm. At dosage levels of 200 and 400 ppm there was a reduction in red blood cell (RBC) count and hemoglobin (Hgb). Food intake was reduced for 200 ppm females and 200 and 400 ppm males. Histopathological effects were seen in the liver, spleen, and adrenal cortex in males and females at 200 and/or 400 pm. The maximum tolerated dose (MTD) was exceeded in females at 200 ppm and in males and females at 400 ppm. The NOAEL for subchronic toxicity in rats was 40 ppm (2 mg/kg/day).

ii. Neurotoxicity assessment. No treatment related effects were seen on neuro-behavior in a Standard Functional Observation Battery conducted at weeks 8 and 13 of the rat feeding study. No overt signs of anti-cholinergic activity, and no statistically significant effects on cholinesterase (ChE) activity were seen in rats in a 2-week feeding study at dose levels up to 400 ppm. Plasma, erythrocyte and brain ChE activity were evaluated in male and female rats fed bifenazate-treated diet at 0, 20, 200, or 400 ppm for 2 weeks. All animals survived until study termination and effects were only seen on body weight gain and food consumption. The NOAEL for cholinergic inhibition was greater than 400 ppm (20 mg/kg/day).

iii. Thirteen-week dog feeding study. Bifenazate was fed to male and female Beagle dogs for 13 weeks at dietary concentrations of 40, 400, and 1,000 ppm. At dosage levels of 400 and 1,000 ppm there was a reduction in RBC count, Hgb and hematocrit (HCT). Liver weights were increased at 400 and 1,000 ppm and centrilobular hepatocellular hypertrophy was seen in females at 400 ppm and males and females at 1,000 ppm. The NOAEL for subchronic toxicity in dogs was 40 ppm (1 mg/kg/day).

5. Chronic toxicity—i. Dog chronic feeding study. Bifenazate was fed to male and female Beagle dogs for 1-year at dietary concentrations of 40, 400, and 1,000 ppm. At dose levels of 400 and 1,000 ppm, there was a reduction in food consumption in males and reduced body weight gain in males and females. There was a reduction in RBC count, Hgb, and HCT and an increase in bilirubin at 400 and 1,000 ppm. Histopathological effects on bone marrow, kidney, and liver were also seen at these dose levels. The NOAEL for chronic toxicity in dogs was 40 ppm (1 mg/kg/day).

ii. Rat chronic feeding/carcinogenicity study. Bifenazate was not carcinogenic in rats when fed to male and female Sprague-Dawley CD rats for 2 years at dietary concentrations of 20, 80, and 160 in females or 20, 80, and 200 ppm in males. Body weight gain was reduced in males and females at the high dosage levels. A reduction in RBC count and an increase in splenic pigment were seen in females at 160 ppm, while high dose males exhibited a reduction in total cholesterol and an increase in splenic pigment. At a dose level of 80 ppm there was a reduction in body weight gain, a decrease in RBC count and an increase in splenic pigment in females. There was no increase in tumor incidence in males or females as a result of bifenazate administration. The NOAEL for chronic toxicity in rats was 20 ppm (1 mg/kg/day).

iii. Mouse carcinogenicity study. Bifenazate was not carcinogenic when fed to male and female CD-1 mice for 18 months at dietary concentrations of 10, 100, and 175 ppm in females and 10, 100, and 225 ppm in males. Body weight gain was reduced in males and females at the high dose level. A reduction in RBC, total leukocyte and lymphocyte counts was seen in males at 225 ppm. There was no increase in tumor incidence in males or females as a result of bifenazate administration.

6. Animal metabolism. In rat,¹⁴ C-bifenazate,¹⁴ C-phenyl hydrazine carboxylic acid, 2-(4-methoxy-1,1-biphenyl-3-yl)-1-methylethyl ester was extensively metabolized when it was given orally in 2 dose levels low (10 mg/kg), and high (1,000 mg/kg). Although ⅔ of the dosed radioactivity was excreted in the feces, bifenazate depicted a good degree of absorption as indicated from the level of radioactivity in the bile. In the bile radioactivity study, about 70% of the C-14 was collected from the cannulated bile ducts of low dosed rats indicating an active level of absorption and enterohepatic circulation.

7. Metabolite toxicology. In a single dose oral toxicity limit test in rats, the oral LD₅₀ of the diazene product of bifenazate was estimated to be approximately 5,000 mg/kg. At 2 hours and at 7 days post-dosing, no effects were seen on erythrocyte cholinesterase inhibition (ChEI) in male or female rats. In addition, no effect on plasma ChEI was seen in male rats at 7 days only. Since this effect was seen only in plasma of females at one time point, it is most likely a pseudo-cholinesterase effect without biological significance. In a dermal toxicity screen, the LD₅₀ of the diazene was estimated to be >2,000 mg/kg.

8. Endocrine disruption. There are no known reported adverse reproductive or developmental effects in domestic animals or wildlife as a result of exposure to this chemical. A standard battery of required toxicity tests have been conducted on bifenazate. No effects were seen in the reproduction or developmental studies to indicate that bifenazate has an effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure. Based on dietary, drinking water, and non-occupational exposure assessments, there is reasonable certainty of no harm to the U.S. population, any population subgroup, or infants and children from chronic exposure to bifenazate.

i. Food. Chronic dietary exposure was estimated using dietary exposure evaluation model DEEM^TM tolerance levels, and 100% crop treated. Processing factors were used for apple and grape juice. The chronic dietary exposure to the U.S. population (total) was estimated as 0.003093 mg/kg bwt/day, and was 30.9% of the reference dose (RfD). Exposure to non-nursing infants, the highest exposed population subgroup, was 0.007238 mg/kg bwt/day (72.4% of the RfD), and exposure to children was 0.006627 mg/kg bwt/day (66.3% of the RfD).

ii. Drinking water. The residue of concern in drinking water was determined to be D1989. Chronic estimated environmental concentrations (EECs) of D1989 in surface water and ground water were generated using FIRST and the screening concentration in ground water (SCI-GROW) (1 application at 0.75 lbs active ingredient/acre). The FIRST model generated an EEC of 0.114 part per billion (ppb), whereas, the SCI-GROW model generated an EEC of 0.0119 ppb. These EEC values are much lower than the drinking water levels of concern (LOC) (227 ppb for adults, 27.6 ppb for infants and children). Therefore, exposure to potential residues in drinking water is expected to be negligible.

2. Non-dietary exposure. Food uses described in this petition are strictly agricultural, and will not add to any residential non-dietary exposure that may exist.

D. Cumulative Effects

The mechanism/mode of action of bifenazate on the mammalian RBC, which is the target organ in the species tested, remains to be elucidated. The lack of information on bifenazate mode of action precludes an assessment of cumulative effects.

E. Safety Determination

1. U.S. population. Based on the toxicology data base and available information on anticipated residues, chronic dietary exposure to the U.S. population (total) was 30.9% of the RfD. Exposure to potential residues in drinking water is expected to be negligible, as drinking water levels of concern (DWLOCs) are substantially higher than modeled acute and long-term EECs. The margin of exposure (MOEs) from the limited potential for short-term exposure from residential uses was >1,000. Based on these assessments, it can be concluded that there is reasonable certainty of no harm to the U.S. population or any population subgroup from exposure to bifenazate.

2. Infants and children. The chronic dietary exposure was 72.4% of the RfD for infants, and 66.3% for children. Exposure to potential residues in drinking water is expected to be negligible, as DWLOCs are substantially higher than modeled acute and long-term EECs. The MOEs from the limited potential for short-term exposure from residential uses was >1,000. Based on these assessments, it can be concluded that there is reasonable certainty of no harm to infants and children from exposure to bifenazate.

F. International Tolerances

There are no Codex or other international maxium residue levels (MRLs) on tolerances for the requested uses with the exception of cherries in Japan. In Japan, the following MRLs have been established: Citrus 0.2 and 1.0; apple 2.0; pear 2.0; peach 0.2; cherry 3.0; strawberry 3.0; watermelon 0.2; and tea 2.0. There are no other current MRLs or tolerances for bifenazate.