01-18098. 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-1033, must be received on or before August 20, 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-1033 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Dan Peacock, Insecticide-Rodenticide Branch, Registration Division (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.” “Regulation 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-1033. 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-1033 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-1033. 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:July 2, 2001

Peter Caulkins,

Acting Director, Registration Division, Office of Pesticide Programs.

Summary of Petition

The petitioner summaries 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.

Syngenta Crop Protection, Inc.

PP 8F4984, 8F5031, 0F6141

EPA has received pesticide petitions (8F4984, 8F5031, 0F6141) from Syngenta Crop Protection, Inc., PO Box 18300 Greensboro, NC 27419-8300 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 pymetrozine in or on the raw agricultural commodities cotton gin byproducts at 3.0 parts per million (ppm), cottonseed at 0.4 ppm, cucurbit vegetables at 0.1 ppm, hops at 5.0 ppm, fruiting vegetables at 0.2 ppm, leafy vegetables (except Brassica) at 6.0 ppm, head and stem Brassica vegetables at 2.0 ppm, leafy Brassica greens at 5.0 ppm and pecans at 0.02 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 supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of pymetrozine in plants is understood for the purposes of the proposed tolerances. Studies in rice, tomatoes, cotton and potatoes gave similar results. The metabolic pathways have demonstrated that pymetrozine, per se, is the residue of concern for tolerance setting purposes.

2. Analytical method. Syngenta has submitted an analytical method (AG-643) for the determination of pymetrozine in crop substrates. The limit of detection (LOD) for the analytical method is 1.0 ng and the limit of quantification (LOQ) is 0.02 ppm. Samples are extracted, purified with solid-phase and liquid-liquid partitions and analyzed by high performance liquid chromotography (HPLC). Analytical method has undergone independent laboratory validation. The pymetrozine Analytical Method AG-643 is proposed as the tolerance enforcement method. Syngenta has also submitted an analytical method (AG-647) for the determination of the major crop metabolite of pymetrozine, GS-23199. GS-23199 is considered a marker for metabolite residues. This metabolite is not proposed as part of the tolerance expression. Samples are extracted, purified with solid-phase and/or liquid-liquid partitions and analyzed by HPLC.

3. Magnitude of residues. Residue data were generated for pymetrozine for tolerance setting and dietary exposure estimates. Data were also generated for a major metabolite, GS-23199. Adequate residue trials were performed for pymetrozine on the uses proposed in this notice of filing.

B. Toxicological Profile

1. Acute toxicity. Pymetrozine has low acute toxicity. The oral LD₅₀ in rats is > 5,820 milligrams/kilogram(mg/kg) for males and females, combined. The rat dermal LD₅₀ is > 2,000 mg/kg and the rat inhalation LC₅₀ is > 1.8 milligrams/liter(mg/L) air. Pymetrozine is not a skin sensitizer in guinea pigs and does not produce dermal irritation in rabbits. It produces minimal eye irritation in rabbits. End-use water-dispersible granule formulations of pymetrozine have similar low acute toxicity profiles.

2. Genotoxicity. Pymetrozine did not induce point mutations in bacteria (Ames assay in Salmonella typhimurium and Escherichia coli) or in cultured mammalian cells (Chinese hamster V79) and was not genotoxic in an in vitro unscheduled DNA synthesis assay in rat hepatocytes. Chromosome aberrations were not observed in an in vitro test using Chinese hamster ovary cells and there were no clastogenic or aneugenic effects on mouse bone marrow cells in an in vivo mouse micronucleus test. These studies show that pymetrozine is not mutagenic or genotoxic.

3. Reproductive and developmental toxicity. In a teratology study in rats, pymetrozine caused decreased body weights and food consumption in females given 100 and 300 mg/kg/day during gestation. This maternal toxicity was accompanied by fetal skeletal anomalies and variations consistent with delayed ossification. The no-observed-adverse-effect level (NOAEL) for maternal and fetal effects in rats was 30 mg/kg/day. In a rabbit teratology study, maternal death, reduced body weight gain and food consumption were observed at 125 mg/kg/day (highest dose tested). Embryo- and feto-toxicity (abortion in one female and total resorptions in two females) accompanied maternal toxicity. Body weight and food consumption decreases, early resorptions and postimplantation losses were also observed in maternal rabbits given 75 mg/kg/day. There was an increased incidence of fetal skeletal anomalies and variations at these maternally toxic doses. The NOAEL for maternal and fetal effects in rabbits was 10 mg/kg/day. Pymetrozine is not teratogenic in rats or rabbits. In a two generation reproduction study in rats, parental body weights and food consumption were decreased, liver and spleen weights were reduced and histopathological changes in liver, spleen and pituitary were observed at approximately 110-440 mg/kg/day (highest dose tested). Liver hypertrophy was observed in a few parental males at approximately 10-40 mg/kg/day. Reproductive parameters were not affected by treatment with pymetrozine. The NOAEL for reproductive toxicity is approximately 110-440 mg/kg/day. The NOAEL for toxicity to adults and pups is approximately 1-4 mg/kg/day.

4. Subchronic toxicity. Pymetrozine was evaluated in 13-week subchronic toxicity studies in rats, dogs and mice. Liver, kidneys, thymus and spleen were identified as target organs. The NOAEL was 33 mg/kg/day in rats and 3 mg/kg/day in dogs. In mice, increased liver weights and microscopical changes in the liver were observed at all doses tested. The NOAEL in mice was <198 mg/kg/day. No dermal irritation or systemic toxicity occurred in a 28-day repeated dose dermal toxicity study with pymetrozine in rats given 1,000 mg/kg/day. Minimum direct dermal absorption (1.1%) of pymetrozine was detected in rats over a 21 hour period of dermal exposure. Maximum radioactivity left on or in the skin at the application site and considered for potential absorption was 11.9%.

5. Chronic toxicity. Based on chronic toxicity studies in the dog and rat, a reference dose (RfD) of 0.0057 mg/kg/day is proposed for pymetrozine. This RfD is based on a NOAEL of 0.57 mg/kg/day established in the chronic dog study and an uncertainty factor of 100 to account for interspecies extrapolation and interspecies variability. Minor changes in blood chemistry parameters, including higher plasma cholesterol and phospholipid levels, were observed in the dog at the lowest-observed-adverse-effect level (LOAEL) of 5.3 mg/kg/day. The NOAEL established in the rat chronic toxicity study was 3.7 mg/kg/day and was based on reduced body weight gain and food consumption, hematology and blood chemistry changes, liver pathology and biliary cysts.

The carcinogenic potential of pymetrozine has been evaluated in rats and mice. A liver tumor response was observed in male and female mice and female rats at high doses exceeding the maximum tolerated dose. These liver tumors correlated with reversible biochemical (induction of liver metabolizing enzymes) and morphological (hepatocyte and smooth endoplasmic reticulum proliferation) changes and a reversible saturation of metabolic processes. EPA has assigned a cancer classification of “likely” to pymetrozine and calculated a Q1* value. However, Syngenta believes that the mechanism of action leading to liver tumors at maximum tolerated doses is a non-genotoxic threshold event and should be regulated as such.

6. Animal metabolism. The metabolism of pymetrozine in the rat is well understood. Metabolism involves oxidation of substituent groups of the triazine ring yielding ketones and carboxylic acids. Hydrolysis of the enamino bridge between rings results in products that are further metabolized. The metabolic pathways in animals and plants are similar.

7. Metabolite toxicology. The residue of concern for tolerance setting purposes is the parent compound. Metabolites of pymetrozine are considered to be of equal or lesser toxicity than the parent.

8. Endocrine disruption. Pymetrozine does not belong to a class of chemicals known or suspected of having adverse effects on the endocrine system. There is no evidence that pymetrozine has any effect on endocrine function in developmental and reproduction studies. Furthermore, histological investigation of endocrine organs in chronic dog, rat and mouse studies did not indicate that the endocrine system is targeted by pymetrozine.

C. Aggregate Exposure

1. Dietary exposure—i. Food. A tier 3 chronic analysis was conducted for pymetrozine using average (mean) field trial residues for the following crops and crop groups: cotton, pecans, hops, cucurbits, fruiting vegetables, tuberous and corm, Brassica leafy vegetables and leafy vegetables. The average field trial values were adjusted for the percent of crop-treated and residue values for processed commodities were calculated by applying processing factors (either default or empirically-derived) to average field trial values of the raw agricultural commodity. Secondary residues in animal commodities were not included in the exposure assessment since a three-level dairy feeding study in lactating livestock showed no residues at any of the feeding levels and the highest feeding level (10 ppm) was at least 10-fold higher than what would be expected in treated feed. Exposure was evaluated using the Dietary Exposure Evaluation Model (DEEM®) and food consumption information from USDA's 1994-96 Continuing Survey of Food Intake by Individuals (CSFII). Dietary exposure for the general population was 0.5% of the chronic reference dose (cRfD) of 0.0038 mg/kg/day based on a no-observed-adverse-effect level (NOAEL) of 0.38 mg/kg/day from a chronic feeding study in rats and a 100X uncertainty factor. Exposure to the U.S. population for each season, each region and for all ethnic groups in the DEEM® were also compared to the cRfD of 0.0038 mg/kg/day and ranged from 0.4-0.9%. Exposure to all male subpopulations and seniors (55+ years old) ranged between 0.4-0.5% of the cRfD (0.0038 mg/kg/day). Chronic dietary exposure to females, infants and children was compared to a chronic population adjusted dose (cPAD) of 0.0013 mg/kg/day based on the NOAEL of 0.38 mg/kg/day (described above) and a 300X uncertainty factor. The chronic dietary exposure results for the most sensitive female population subgroup, females (13+ years and nursing), was 2.2% of the cPAD. The most sensitive population containing children exclusively was children (1-6 years old) with an exposure of 2.5% of the cPAD. Lifetime cancer risk to pymetrozine was evaluated by comparing exposure to a Q* value of 0.0119. The assessment was conducted as for the chronic assessment described above. Lifetime risk for the U.S. population was 2.24 x 10^-7. The most sensitive adult population was females (13+, nursing) with a lifetime risk of 3.46 x 10^-7. These exposure estimates are conservative since field trial residues were utilized and do not reflect residue reductions expected in normal food commerce, storage or food preparation. Therefore, these results show that there is more than a reasonable certainty of no harm resulting from chronic exposure through the consumption of pymetrozine-treated commodities.

A tier 3 probabilistic acute dietary analysis was conducted with a full distribution of residues for each commodity described above. Each residue distribution was adjusted for percent of crop treated by adding zeroes to the distribution to account for the percent of crop not treated. This acute assessment was conducted using the DEEM® software and food consumption information from USDA's 1994-96 CSFII. Processing factors were used to adjust average field trial values for processed (blended) commodities and were obtained either empirically or from default values. EPA has required that exposure to females (13+ years old) be compared to a NOAEL of 10 mg/kg/day based on a rabbit developmental study and a 300X uncertainty factor. Acute exposure to the most sensitive female subpopulation, females (13-50 years old), was 1.61% of the acute population adjusted-dose (aPAD) of 0.033 mg/kg/day (300X uncertainty factor). For the U.S. population and infants and children, exposures were compared to a lowest-observed-adverse-effect level (LOAEL) of 125 mg/kg/day from an acute neurotoxicity study in rats. Uncertainty factors of 300X and 900X were applied to the LOAEL for the general population and infants and children subgroups, respectively. Acute exposure for the U.S. population was 0.13% of the aPAD of 0.42 mg/kg body weight/day (300X uncertainty factor). For the infants and children populations, the most sensitive population subgroup was non-nursing infants with an exposure of 1.77% of the aPAD of 0.14 mg/kg/day (900X-uncertainty factor). These results show a very large margin of safety associated with the consumption of pymetrozine-treated commodities and even under conservative assumptions all populations receive less than 2% of the acute population adjusted dose.

ii. Drinking water. The acute drinking water exposure to pymetrozine was evaluated based on the crops above using EPA's surface water Tier 1 model (GENEEC). Hops with 3 applications at 0.1875 lb ai/acre was the highest contributor at 4.27 ppb. Using the current aPAD of 0.033 mg/kg for females 13+, the margin of exposure percent (MOE%) of risk cup anticipated is 0.43%. For children the aPAD of 0.14 mg/kg yields an MOE% of risk cup of 0.30%.

Hops was also the highest contributor to surface water exposure at 0.31 ppb. Using the current cPAD of 0.0013 mg/kg/day (for females and children) the surface water exposure results in an MOE% of risk cup of 2.38% for children. Using a Q* of 0.0119 the risk to a typical 70 kg adult drinking 2 liters of water per day would be estimated at 1.05 x 10^-7.

2. Non-dietary exposure. Pymetrozine is registered on ornamentals and exposure could occur through post-application re-entry to treated plants. Syngenta believes that risks due to short-term, intermediate-term or chronic exposure are either not applicable or insignificant.

D. Cumulative Effects

The potential for cumulative effects of pymetrozine and other substances that have a common mechanism of toxicity has also been considered. Pymetrozine belongs to a new chemical class known as pyridine azomethines and exhibits a unique mode of action. There is no reliable information to indicate that toxic effects produced by pymetrozine would be cumulative with those of any other chemical including another pesticide. Therefore, Syngenta believes it is appropriate to consider only the potential risks of pymetrozine in an aggregate risk assessment.

E. Safety Determination

1. U.S. population. Using the exposure assumptions and the proposed RfD described above, the aggregate exposure to pymetrozine will utilize 0.5% of the RfD for the U.S. population. The RfD represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risks to human health. EPA generally has no concern for exposures below 100 percent of the RfD. In addition, Lifetime cancer risk for the U.S. population was 2.24 x 10^-7, which is below the level of EPA concern. Therefore, Syngenta concludes that there is a reasonable certainty that no harm will result from aggregate exposure to pymetrozine residues.

2. Infants and children. In assessing the potential for additional sensitivity of infants and children to residues of pymetrozine, data from developmental toxicity studies in the rat and rabbit and a two-generation reproduction study in the rat have been considered.

In a teratology study in rats, developmental toxicity anomalies and variations associated were observed only at maternally toxic doses. Similarly, in a rabbit teratology study, effects were observed only at maternally toxic doses. The NOAELs in the rat and rabbit teratology studies were 30 and 10 mg/kg/day, respectively. In the two-generation rat reproduction study, there were no effects on reproductive parameters. Offspring body weights were slightly reduced and eye opening was slightly delayed at dose levels producing parental toxicity. The NOAEL for parental and offspring toxicity was approximately 1-4 mg/kg/day.

FFDCA section 408 provides that EPA shall apply an additional 10-fold margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity and the completeness of the database unless EPA determines that a different margin of safety will be safe for infants and children. EPA has added an additional 3-fold factor to the acute dietary risk assessment for infants and children due to the lack of a NOAEL in the critical study. An additional 3-fold factor is also needed due to the uncertainty resulting from the data gap for the developmental neurotoxicity study in rats. This latter safety factor is applicable to the following subgroup populations: Females 13-50; infants, children (1-6 years old), and children (7-12 years old) for all risk assessment scenarios for acute and chronic dietary and residential scenarios. No greater additional factor is needed because, using the exposure assumptions described above, the percent of the pymetrozine chronic PAD that will be utilized by the most exposed sub-population (children, 1-6 years old) is 2.5%. Therefore, based on the completeness and reliability of the toxicity database, Syngenta concludes that there is reasonable certainty that no harm will result to infants and children from exposure to pymetrozine residues.

F. International Tolerances

There are no established European (CODEX), Canadian, or Mexican Maximum Residue Limits (MRLs) for pymetrozine. There are provisional MRLs in Germany for hops (10 ppm) and potatoes (0.02 ppm). The European Union is currently evaluating a proposed tolerance of 5 ppm on hops. At this time, international harmonization of residue levels is not an issue.