01-8140. 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 control number PF-1006, must be received on or before May 4, 2001.

ADDRESSES:

Comments may be submitted by mail, electronically, or in person. Please follow the detailed instructions for each method as provided in Unit I.C. of the SUPPLEMENTARY INFORMATION. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-1006 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Sidney Jackson, Registration Division, Minor Use Inerts and Emergency Response Branch, (7505C), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: [phone]; e-mail address: [e-mail].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

You may be affected by this action if you are an agricultural producer, food manufacturer or pesticide manufacturer. Potentially affected categories and entities may include, but are not limited to:

Categories	NAICS codes	Examples of potentially affected entities
Industry	111	Crop production
	112	Animal production
	311	Food manufacturing
	32532	Pesticide manufacturing

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 the table could also be affected. The North American Industrial Classification System (NAICS) codes have been provided to assist you and others in determining whether or not this action might apply to certain entities. If you have 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 Additional Information, Including Copies of this Document and Other Related Documents?

1. Electronically. You may obtain electronic copies of this document, and certain other related documents that might be available electronically, from the EPA Internet Home Page at http://www.epa.gov/​. To access this document, on the Home Page select “Laws and Regulations,” “Regulations and Proposed Rules,” and then look up the entry for this document under the “Federal Register—Environmental Documents.” You can also go directly to the Federal Register listings at http://www.epa.gov/​fedrgstr/​.

2. In person. The Agency has established an official record for this action under docket control number PF-1006. The official record consists of the documents specifically referenced in this action, any public comments received during an applicable comment period, and other information related to this action, including any information claimed as confidential business information (CBI). This official record includes the documents that are physically located in the docket, as well as the documents that are referenced in those documents. The public version of the official record does not include any information claimed as CBI. The public version of the official record, which includes printed, paper versions of any electronic comments submitted during an applicable comment period, is available for inspection in the Public Information and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA, from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is [phone].

C. How and to Whom Do I Submit Comments?

You may submit comments through the mail, in person, or electronically. To ensure proper receipt by EPA, it is imperative that you identify docket control number PF-1006 in the subject line on the first page of your response.

1. By mail. Submit your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460.

2. In person or by courier. Deliver your comments to: Public Information and Records Integrity Branch (PIRIB), Information Resources and Services Division (7502C), Office of Pesticide Programs (OPP), Environmental Protection Agency, Rm. 119, Crystal Mall #2, 1921 Jefferson Davis Highway, Arlington, VA. The PIRIB is open from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The PIRIB telephone number is [phone].

3. Electronically. You may submit your comments electronically by e-mail to: [e-mail], or you can submit a computer disk as described above. Do not submit any information electronically that you consider to be CBI. Avoid the use of special characters and any form of encryption. Electronic submissions will be accepted in Wordperfect 6.1/8.0 or ASCII file format. All comments in electronic form must be identified by docket control number PF-1006. Electronic comments may also be filed online at many Federal Depository Libraries.

D. How Should I Handle CBI That I Want to Submit to the Agency?

Do not submit any information electronically that you consider to be CBI. You may claim information that you submit to EPA in response to this document as CBI by marking any part or all of that information as 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 version of the official record. Information not marked confidential will be included in the public version of the official record without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person identified 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 control 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 Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this petition contains data or information regarding the elements set forth in 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: March 20, 2001.

James Jones,

Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

The petitioner summary of the pesticide petition is printed below as required by section 408(d)(3) of the FFDCA. The summary of the petition was prepared by the petitioner and represents the view of the petitioners. EPA is publishing the petition summary verbatim without editing it in any way. 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 #4 (IR-4)

0E6081

EPA has received a pesticide petition (0E6081) from the Interregional Research Project #4 (IR-4), Technology Centre of New Jersey, Rutgers, the State University of New Jersey, 681 U.S. Highway #1 South, North Brunswick, NJ 08021-3390 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 establishing a tolerance for residues of pyriproxyfen, 2-[1-methyl-2-(4-phenoxyphenoxy)ethoxy pyridine, in or on the raw agricultural commodity pistachio at 0.02 parts per million (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.

A. Residue Chemistry

1. Plant and animal metabolism. Metabolism of¹⁴ C-pyriproxyfen labelled in the phenoxyphenyl ring and in the pyridyl ring has been studied in cotton, apples, tomatoes, lactating goats, and laying hens (and rats). The major metabolic pathways in plants is aryl hydroxylation and cleavage of the ether linkage, followed by further metabolism into more polar products by further oxidation and/or conjugation reactions. However, the bulk of the radiochemical residue on raw agricultural commodity samples remained as parent. Comparing metabolites detected and quantified from cotton, apple, tomato, goat and hen (and rat) shows that there are no significant aglycones in plants which are not also present in the excreta or tissues of animals. The residue of concern is best defined as the parent, pyriproxyfen.

Ruminant and poultry metabolism studies demonstrated that transfer of administered¹⁴ C-residues to tissues was low. Total¹⁴ C-residues in goat milk, muscle and tissues accounted for less than 2% of the administered dose, and were less than 1 ppm in all cases. In poultry, total¹⁴ C-residues in eggs, muscle and tissues accounted for about 2.7% of the administered dose, and were less than 1 ppm in all cases except for gizzard.

2. Analytical method. The gas-chromotography/nitrogen-phosphorous specific flame ionization detector (NPD) and high-pressure liquid chromotography/fluorescence (FLD) method RM-33N-2 is adequate for collecting data on residues of pyriproxyfen in/on nutmeat. Adequate method validation data have been submitted for this method and EPA has successfully validated the analytical method for analysis of nutmeat. The limit of quantitation (LOQ) is 0.02 ppm for residues of pyriproxyfen in/on nutmeat.

3. Magnitude of residues. Pyriproxyfen residue data from tree nut field studies were used as surrogate data for pistachio. Data from six field trials conducted in California during 1997 depicting residues of pyriproxyfen in/on almonds were reviewed by the Agency and found to be acceptable. Residues of pyriproxyfen were non-detectable (<0.01 ppm) in/on 12 samples of nutmeat. In the studies conducted at 2x the proposed application rate, residues of pyriproxyfen were <0.01 ppm in/on three samples of nutmeat, and one sample bore residues at the limit of detection (LOD) (0.01 ppm). Data are available from four field trials on walnuts conducted in California during 1996 Residues of pyriproxyfen and 4'-OH-PYR were non-detectable (<0.01 ppm) in/on eight walnut samples harvested approximately 21 days after the last of three broadcast applications of the 0.86 lb/gal EC formulation at approximately 50 grams active ingredient (ai)/acre (A)/application (0.33 pound ai/A/season); 1x the maximum proposed seasonal rate. Residues of pyriproxyfen in/on eight samples of walnuts treated as described above were each less than the LOQ (<0.02 ppm).

B. Toxicological Profile

1. Acute toxicity. The acute toxicity of technical grade pyriproxyfen is low by all routes, classified as Category III for acute inhalation toxicity eye irritation, and Category IV for acute oral and dermal toxicity, and skin/eye irritation. Pyriproxyfen is not a skin sensitizing agent.

2. Genotoxicity. Pyriproxyfen was negative in the following tests for mutagenicity: Ames assay with and without S9 activation, in vitro unscheduled DNA synthesis in HeLa S3 cells, in vitro gene mutation in V79 Chinese hamster cells, and in vitro chromosomal aberration with and without S9 activation in Chinese hamster ovary cells.

3. Reproductive and developmental toxicity. In the rat developmental toxicity study, maternal toxicity (decreases in food consumption, body weight, and body weight gain with increases in water consumption was observed at doses of 300 milligrams (mg)/kilogram (kg)/day and greater, the no observed adverse effect level (NOAEL) for prenatal developmental toxicity was 100 mg/kg/day with increased incidences of skeletal variations and unspecified visceral variations at 1,000 mg/kg/day. A rabbit teratology study resulted in a maternal NOAEL of 100 mg/kg/day, with no developmental effects observed in the rabbit fetuses.

In a 2-generation reproduction toxicity study in rats, parental toxicity (decreased body weight, weight gain and food consumption in both sexes and both generations and increased liver weight in both sexes of the F1 generation and liver and kidney histopathology in F1 males was observed at the highest dose tested (HDT) (5,000 ppm) (equivalent to 386 mg/kg/day for males and 442 mg/kg/day for females and 519 mg/kg/day for males and 554 mg/kg/day for females F1 generation.) The parental NOAEL is established at 1,000 ppm and the reproductive NOAEL is established at 5,000 ppm.

4. Subchronic toxicity. Subchronic oral toxicity studies conducted with pyriproxyfen technical in the rat, mouse and dog indicate a low level of toxicity. Effects observed at high dose levels consisted primarily of decreased body weight gain; increased liver weights; histopathological changes in the liver and kidney; decreased red blood cell counts, hemoglobin and hematocrit; altered blood chemistry parameters; and, at 5,000 and 10,000 ppm in mice, a decrease in survival rates. The NOAELs from these studies were 400 ppm (23.5 mg/kg/day for males, 27.7 mg/kg/day for females) in rats, 1,000 ppm (149.4 mg/kg/day for males, 196.5 mg/kg/day for females) in mice, and 100 mg/kg/day in dogs.

5. Chronic toxicity. Pyriproxyfen technical has been tested in chronic studies with dogs, rats and mice. Pyriproxyfen technical was administered to dogs in capsules at doses of 0, 30, 100, 300 and 1,000 mg/kg/day for 1-year. Dogs exposed to dose levels of 300 mg/kg/day or higher showed decreased weight gain, increased absolute and relative liver weight, mild anemia, increased cholesterol and triglycerides in both sexes and slight anemia in males. The NOAEL in this study was 100 mg/kg/day. Pyriproxyfen technical was administered to mice at doses of 0, 120, 600 and 3,000 ppm in diet for 78-weeks. The NOAEL for systemic effects in this study was 600 ppm (84 mg/kg/day in males, 109.5 mg/kg/day in females), and a lowest observed adverse effect (LOAEL) of 3,000 ppm (420 mg/kg/day in males, 547 mg/kg/day in females) was established based on an increase in kidney lesions.

In a 2-year study in rats, pyriproxyfen technical was administered in the diet at levels of 0, 120, 600, and 3,000 ppm. The NOAEL for systemic effects in this study was 600 ppm (27.31 mg/kg/day in males, 35.1 mg/kg/day in females). A LOAEL of 3,000 ppm (138 mg/kg/day in males, 182.7 mg/kg/day in females) was established based on a depression in body weight gain in females.

6. Animal metabolism. The absorption, tissue distribution, metabolism and excretion of¹⁴ C-labeled pyriproxyfen were studied in rats after single oral doses of 2 or 1,000 mg/kg bw (phenoxyphenyl and pyridyl label), and after a single oral dose of 2 mg/kg bw (phenoxyphenyl label only) following 14 daily oral doses at 2 mg/kg bw of unlabelled material. For all dose groups, most (88-96%) of the administered radiolabel was excreted in the urine and feces within two days after radiolabeled test material dosing, and 92-98% of the administered dose was excreted within seven days. Seven days after dosing, tissue residues were generally low, accounting for no more than 0.3% of the dosed¹⁴ C. Radiocarbon concentrations in fat were the highest in tissues analyzed. Recovery in tissues over time indicates that the potential for bioaccumulation is minimal. There were no significant sex or dose-related differences in excretion or metabolism.

7. Endocrine disruption. Pyriproxyfen is specifically designed to be an insect growth regulator and is known to produce juvenoid effects on arthropod development. However, according to Valent this mechanism-of-action in target insects and other some arthropods has no relevance to any mammalian endocrine system. While specific tests, uniquely designed to evaluate the potential effects of pyriproxyfen on mammalian endocrine systems have not been conducted, the toxicology of pyriproxyfen has been extensively evaluated in acute, sub-chronic, chronic, developmental, and reproductive toxicology studies including detailed histopathology of numerous tissues. The results of these studies show no evidence of any endocrine-mediated effects and no pathology of the endocrine organs. Consequently, Valent concludes that pyriproxyfen does not possess estrogenic or endocrine disrupting properties applicable to mammals.

8. Neurotoxicity. Neither neurotoxic symptoms nor any other indication of neurotoxicity has been observed in any of the acute, subchronic, chronic, developmental, or reproductive studies performed with pyriproxyfen.

9. Toxicological endpoints. EPA has established a reference dose (RfD) for pyriproxyfen of 0.35 mg/kg bw/day, based on the NOAEL from the rat 2-year chronic/carcinogenicity study and a safety factor of 100. However, the Agency has not yet identified acute or short term toxicity endpoints of concern for oral, inhalation, or dermal exposure. Pyriproxyfen is classified as Category E: Not carcinogenic in two acceptable animal studies.

C. Aggregate Exposure

1. Dietary exposure. An evaluation of chronic dietary exposure to include drinking water has been performed for the U.S. Population and various sub-populations including infants and children. Because no acute dietary endpoint for pyriproxyfen residues was determined, the Agency concludes that there is a reasonable certainty of no harm from acute exposure from drinking water.

i. Food. Chronic dietary exposure to pyriproxyfen residues was calculated for the U.S. population and 26 population subgroups assuming tolerance level residues and 100% of the crop treated. Chronic dietary exposure was at or below 0.705 % of the reference dose. Generally speaking, the Agency has no cause for concern if total residue contribution for published and proposed tolerances is less than 100 percent of the RfD.

ii. Drinking water. Since pyriproxyfen is applied outdoors to growing agricultural crops, the potential exists for pyriproxyfen or its metabolites to reach ground or surface water that may be used for drinking water. Because of the physical properties of pyriproxyfen, it is unlikely that pyriproxyfen or its metabolites can leach to potable groundwater. To quantify potential exposure from drinking water, surface water concentrations for pyriproxyfen were estimated using GENEEC 1.3. The average 56-day concentration predicted in the simulated pond water was 0.16 ppb. Using standard assumptions about body weight and water consumption, the chronic exposure to pyriproxyfen from this drinking water would be 4.57 x 10^-6 and 1.6 x 10^-5 mg/kg bw/day for adults and children, respectively; 0.0046 percent of the RfD (0.35 mg/kg/day) for children. Based on this worse case analysis, Valent concludes that the contribution of water to the dietary risk is negligible.

2. Non-dietary exposure. Pyriproxyfen is the active ingredient in numerous registered products for household use — primarily for indoor, non-food applications by consumers. The consumer uses of pyriproxyfen typically do not involve chronic exposure. Instead, consumers are exposed intermittently to a particular product (e.g., pet care pump spray) containing pyriproxyfen. Since pyriproxyfen has a relatively short elimination half-life, cumulative toxicological effects resulting from bioaccumulation are not plausible following short-term, intermittent exposures. Further, pyriproxyfen is short-lived in the environment and this indoor domestic use of pyriproxyfen provides only relatively short-term reservoirs. Thus, consumer use of these products results in acute and short term intermittent exposures.

No acute dermal, or inhalation dose or endpoint was identified in the toxicity data for pyriproxyfen. Similarly, doses and endpoints were not identified for short and intermediate term dermal or inhalation exposure to pyriproxyfen. There are reasonable certainties of no harm from acute, short term, and intermediate term dermal and inhalation occupational and residential exposures due to the lack of significant toxicological effects observed. Thus, no detailed exposure and risk analyses for non-dietary exposures to pyriproxyfen are necessary.

D. Cumulative Effects

According to Valent there are no other pesticidal compounds that are structurally related to pyriproxyfen and have similar effects on animals. In consideration of potential cumulative effects of pyriproxyfen and other substances that may have a common mechanism of toxicity, there are currently no available data or other reliable information indicating that any toxic effects produced by pyriproxyfen would be cumulative with those of other chemical compounds. Thus, only the potential risks of pyriproxyfen have been considered in this assessment of aggregate exposure and effects. Valent will submit information for EPA to consider concerning potential cumulative effects of pyriproxyfen consistent with the schedule established by EPA at 62 Federal Register 42020 (August 4, 1997) and other subsequent EPA publications pursuant to the Food Quality Protection Act.

E. Safety Determination

1. U.S. population—i. Chronic dietary exposure and risk. Using the Tier I dietary exposure assessment, calculated chronic dietary exposure resulting from residue exposure from existing and proposed uses of pyriproxyfen is minimal. The estimated chronic dietary exposure from food for the overall U.S. Population and many non-child/infant subgroups is from 0.000338 to 0.000652 mg/kg bw/day, 0.097 to 0.186 per cent of the RfD. Addition of the small but worse case potential chronic exposure from drinking water (calculated above) increases exposure by only 4.57 x 10^-6 mg/kg bw/day and does not change the maximum occupancy of the RfD significantly. Generally, the Agency has no cause for concern if total residue contribution is less than 100 percent of the RfD. It can be concluded that there is a reasonable certainty that no harm will result to the overall U.S. Population and infants and children from aggregate, chronic exposure to pyriproxyfen residues.

ii. Acute dietary exposure and risk. An acute dietary dose and endpoint was not identified. Thus, the risk from acute aggregate exposure is considered to be negligible.

iii. Non-dietary exposure and aggregate risk. Acute, short term, and intermediate term dermal and inhalation risk assessments for residential exposure are not required due to the lack of significant toxicological effects observed.

2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of pyriproxyfen, FFDCA section 408 provides that EPA shall apply an additional margin of safety, up to ten-fold, for added protection for infants and children in the case of threshold effects unless EPA determines that a different margin of safety will be safe for infants and children.

The toxicological data base for evaluating pre- and post-natal toxicity for pyriproxyfen is complete with respect to current data requirements. There are no special pre- or post-natal toxicity concerns for infants and children, based on the results of the rat and rabbit developmental toxicity studies or the 2-generation reproductive toxicity study in rats. Valent concludes that reliable data support use of the standard 100-fold uncertainty factor and that an additional uncertainty factor is not needed for pyriproxyfen to be further protective of infants and children.

F. International Tolerances

There are no Codex MRLs for pyriproxyfen.