01-28637. 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-1054, must be received on or before December 17, 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-1054, in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Cynthia Giles-Parker, Fungicide 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,” “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-1054. 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-1054, 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-1054. 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 Cosmetic 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: October 30, 2001.

Peter Caulkins,

Acting 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.

PP 1F6250

EPA has received a pesticide petition (PP 1F6250) from BASF Corporation, P. O. Box 13528, Research Triangle Park, NC 27709-3528 proposing, pursuant to section 408(d) of the FFDCA, 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing tolerances for residues of the plant growth regulator mepiquat resulting from the use of mepiquat chloride (N,N-dimethylpiperdinium chloride) or mepiquat pentaborate (N,N-dimethylpiperidinium pentaborate hemi-hydrate) in or on the following raw agricultural and processed commodities: Cottonseed at 2.0 parts per million (ppm); cotton, gin by-products at 6.0 ppm, and meat byproducts of cattle, goat, hog, horse, and sheep at 0.1 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 metabolism. The metabolism of mepiquat chloride in plants and animals is well understood. Based on the identical dissociation behavior of mepiquat pentaborate and mepiquat chloride, the nature of the residue for mepiquat pentaborate would be the same as that for mepiquat chloride (based on analysis of the mepiquat cation). Thus, the nature of residue for mepiquat pentaborate in cotton is supported by the mepiquat chloride studies available in cotton. The residue of concern from mepiquat pentaborate use in cotton consists only of the parent compound.

2. Analytical method. An adequate analytical method for enforcement of the tolerances exists. The analytical method used for quantitative determinations was designed to measure mepiquat chloride or mepiquat pentaborate residues present as mepiquat cation. The metabolism of mepiquat chloride in plants and animals is well understood. Based on the identical dissociation behavior of mepiquat pentaborate and mepiquat chloride, the nature of the residue for mepiquat pentaborate would be the same as that for mepiquat chloride (based on analysis of the mepiquat cation). Thus, the nature of residue for mepiquat pentaborate in cotton is supported by the mepiquat chloride studies available in cotton. The residue of concern from mepiquat pentaborate use in cotton consists only of the parent compound.

3. Magnitude of residues. Adequate field trial data are available to support the established tolerance of 2 ppm mepiquat for cottonseed. The field trials supporting mepiquat chloride will adequately support the establishment of the tolerance for mepiquat pentaborate (as mepiquat).

B. Toxicological Profile

Since the tolerance for mepiquat pentaborate is based on an expression as mepiquat, BASF is relying on the data for mepiquat chloride to support the requirement for all toxicological studies except for the acute studies. Acute toxicology studies were conducted with mepiquat pentaborate technical in support of the end use product. The mepiquat chloride data base is also used in support of the risk assessments presented in this document.

1. Acute toxicity. Based on the acute toxicity data, mepiquat pentaborate does not pose any acute toxicity risks. The acute toxicology studies place mepiquat pentaborate in toxicity category III for acute oral toxicity, acute dermal, acute inhalation toxicity, and primary eye irritation. The primary dermal irritation for mepiquat pentaborate is in toxicity category IV and mepiquat pentaborate is not a skin sensitizer.

2. Genotoxicty. An Ames assay using mepiquat chloride was negative for genotoxicity. A chromosome aberration assay in Chinese Hamster Ovary cells was performed up to the limit dose of 5.0 milligrams/milliliter (mg/mL) without seeing evidence of genotoxicity. An Unscheduled DNA Synthesis assay was performed using primary rat hepatocyte cultures up to a limit dose of 5.0 mg/ml without seeing evidence of genotoxicity.

3. Reproductive and developmental toxicity. In a 2-generation reproductive toxicity study, Wistar rats were fed mepiquat chloride in their diets at concentrations of 0, 500, 1,500, or 5,000 parts per million (ppm) for 10 weeks (F0) or 14 weeks (F1) before mating, and during mating, gestation, and lactation. The F0 parents were mated a second time 2 weeks after weaning the first litter. The doses corresponding to the dietary concentrations are 51.2 and 48.6, 153.1 and 146.6, and 499.3 and 574.5 milligrams/kilograms/day (mg/kg/day), respectively for F0 and F1 males and 54.0 and 53.3, 163.6 and 162.0, and 530.0 and 626.5 mg/kg/day, respectively for F0 and F1 females. The lowest observed adverse effect level (LOAEL) for systemic toxicity is 5,000 ppm (499 mg/kg/day) for male and female rats based on neurological impairment, decreased body weight and body weight gain in the adults, and retarded growth of F0 and F1 pups. The corresponding no observed adverse effect level (NOAEL) is 1,500 ppm (147 mg/kg/day). The OPP's Reference Dose (RfD)/Peer Review Committee concluded on May 2, 1996, that, because of the retarded growth of the pups in the 5,000 ppm (499 mg/kg/day) group, the systemic NOAEL of 1,500 ppm (147 mg/kg/day) would also be regarded as the reproductive NOAEL.

4. Subchronic toxicity. Two 90-day feeding studies in the rat and a 90-day feeding study in the dog are available. The first rat study saw no compound-related adverse effects at the high dose tested (HDT) of 4,632 ppm (330 mg/kg/day). Thus, a second study was performed with only a control and 12,000 ppm (889 mg/kg/day) dose group. Adverse effects were seen in this study and so the rodent subchronic LOAEL/NOAEL is 12,000/4,632 ppm (889/330 mg/kg/day). A subchronic dog study found a LOAEL/NOAEL of 3,000/1,000 ppm (95.3/32.4 mg/kg/day).

5. Chronic toxicity. On May 2, 1996, the OPP's RfD/Peer Review Committee recommended that the RfD for mepiquat chloride be established at 0.6 mg/kg/day. This value was based on the systemic NOAEL of 1,800 ppm (58.4 mg/kg/day) from the 1-year dog feeding study and the uncertainty factor (UF) of 100.

i. Chronic feeding—nonrodent. In a chronic toxicity study, mepiquat chloride (99.5%) was administered to beagle dogs in the diet at dose levels of 0, 200, 600 or 1,800 ppm (0, 6.3, 19.9 or 58.4 mg/kg/day, respectively) for 12 months. There were no significant treatment-related effects. In order to establish a LOAEL, a second chronic toxicity study was conducted at dose levels of 0 or 6,000 ppm (170 mg/kg/day) for 12 months. Based on the results of the two chronic dog studies, the NOAEL is 1,800 ppm (58.4 mg/kg/day) and the LOAEL is 6,000 ppm (170 mg/kg/day). This endpoint is used for the acute dietary and chronic RfD.

ii. Chronic feeding—rats. In a chronic feeding study, mepiquat chloride (58%) was administered for 24 months in the diet to Wistar rats at concentrations of 0, 290, 2,316, or 5,790 ppm (active ingredient), equivalent to doses of 0, 13, 106, 268 mg/kg/day for males and 0, 18, 146, or 371 mg/kg/day for females, respectively. The NOAEL is 2,316 ppm (105 mg/kg/day). The LOAEL is 5,790 ppm (268 mg/kg/day).

iii. Carcinogenic effects. The carcinogenic potential of mepiquat chloride was evaluated by the OPP's RfD/Peer Review Committee on May 2, 1996. The Committee classified mepiquat chloride into Group E (evidence of noncarcinogenicity for humans), based on a lack of carcinogenicity in acceptable studies with two animal species, rat and mouse.

6. Animal metabolism. In a metabolism study, mepiquat chloride, labeled with C¹⁴ (radiochemical purity: 98%), was administered to young adult Sprague-Dawley rats either intravenously or orally. Mepiquat chloride was absorbed rapidly from the stomach, distributed evenly in the intra-and extracellular compartments of the blood, demonstrated high bioavailability via the oral route, was excreted mostly in urine, and did not accumulate in tissues. Urine, feces and bile samples from various treatments were used for studies of the metabolic fate of mepiquat chloride. In all cases, only the unchanged compound could be detected. Therefore, there was no biotransformation of mepiquat chloride in vivo. The potential metabolites, such as 1-methylpiperidine or piperidine, were not detected.

7. Metabolite toxicology. No additional studies were required for metabolite toxicology.

8. Endocrine disruption. No specific tests have been conducted with mepiquat to determine whether the chemical may have an endocrine like effect in humans. However, there were no significant findings in other relevant tests (developmental and reproductive toxicity tests) which would suggest that mepiquat produces endocrine like effects.

C. Aggregate Exposure

1. Dietary exposure. The mepiquat chloride RED indicates that EPA has found no dietary risks of concern for mepiquat chloride for the general U.S. population nor any subgroup. Pursuant to the requirements under the Food Quality Protection Act (FQPA) of 1996, the Agency has determined that the use of mepiquat will not pose dietary risks to infants and children due primarily to the chemical's low toxicity and its low usage rate.

i. Food—a. Chronic dietary exposure. A Dietary Risk Evaluation System (DRES) chronic exposure analysis was conducted by EPA for the RED. The analysis was performed using tolerance level residues and the three expired grape and raisin temporary tolerances previously established for an Experimental Use Permit and an assumption of 100% crop treated to estimate the Theoretical Maximum Residue Contribution (TMRC) for the general population and 22 subgroups. No Anticipated Residue (AR) information was used in this analysis. Existing tolerances result in a Theoretical Maximum Residue Contribution (TMRC) which represents less than 1% of the RfD for the U.S. general population and each of the 22 subgroups, including non-nursing infants (< 1-year old). The TMRC calculation results in a significant overestimate of human dietary exposure.

Another dietary assessment was performed, by the Agency, for mepiquat chloride assuming tolerance levels residues and 100% crop treared on cotton, grape, meat, fat, and meat by-products (D260557, November 1, 1999, W. Cutchin). Risk estimates for exposure to mepiquat chloride were below HED's level of concern.

These chronic analyses for mepiquat are worst case estimates of dietary exposure with all residues at tolerance level and 100% of the commodities assumed to be treated with mepiquat. Based on the risk estimates calculated in these analyses, it has been concluded that dietary exposure to mepiquat does not pose any risk concerns.

b. Acute dietary exposure. The margin of exposure (MOE) is a ratio of the NOAEL to the exposure. Generally, the Agency concludes that there is no dietary concern when the acute dietary margins of exposure are greater than 100. The results of the acute analysis conducted for the RED indicate that mepiquat in the diet represents no serious risk concern for acute exposure. All MOEs were well above the Agency's level of concern for acute dietary risk (ranging from a low of 3,893 for infants to a high of 29,200 for females 13+ years old).

ii. Drinking water. Neither a Maximum Contaminant Level (MCL) nor a Hazard Advisory (HA) has been established for mepiquat. According to the EPA's Pesticides in Ground Water Database, there have been no mepiquatchloride detections reported in monitoring wells. Based on its low application rate, relatively rapid degradation rate, and soil binding ability, the Agency does not expect mepiquat to contaminate ground water or surface water. Consequently neither a chronic or acute drinking water assessment was performed.

2. Non-dietary exposure. Mepiquat has no residential or other non-occupational uses that might result in exposures to humans.

D. Cumulative Effects

EPA has addressed the issue of the potential risk from the cumulative effects of mepiquat chloride and other pesticides with a common mechanism of toxicity in the RED document. In assessing the potential risks, the Agency first considered structural similarities and common effects that exist between mepiquat chloride and other related compounds such as paraquat, diquat and difenzoquat. The Agency then considered other compounds which could potentially result in neurotoxic effects similar to mepiquat chloride.

With one substance, difenzoquat, there appears to be similar neurotoxic effects. The Agency has concluded that the cumulative effects from the combined dietary exposure to mepiquat and difenzoquat would be virtually nil because the chronic dietary exposure for all population subgroups is less than 1% of the RfD for both difenzoquat and mepiquat chloride. The acute dietary MOE range for difenzoquat is 16,000 to 50,000 while the acute dietary MOE range for mepiquat chloride is 3,900 to 29,000.

In evaluating other chemicals with neurotoxic effects similar to mepiquat chloride, the Agency determined that it is unlikely that these other chemicals share a common mode/mechanism of toxicity with mepiquat chloride, or that cumulative risk assessment would be required. Although the mode/mechanism of toxicity of mepiquat chloride has not been well defined, the effects noted on the nervous system appear to be secondary to general systemic toxicity that occurs at high dose levels. Based on available data and structure-activity relationship analyses, mepiquat chloride would be considered to have minimal neurotoxic activity.

E. Safety Determination

1. U.S. population. In the mepiquat chloride RED, EPA has determined that the established tolerances for mepiquat chloride meet the safety standards under the FQPA amendments to section 408(b)(2)(D) for the general population. In reaching this determination, EPA has considered the available information on the aggregate exposures (both acute and chronic) from the feed use on cotton, as well as the possibility of cumulative effects from mepiquat chloride and other chemicals with a similar mode/mechanism of toxicity. BASF does not believe that the use of mepiquat pentaborate on cotton alters these conclusions.

Since there are no residential or lawn uses of mepiquat, no dermal or inhalation exposure is expected in and around the home. No acute toxicity endpoints of concern have been identified for mepiquat.

In assessing chronic dietary risk, EPA estimates that mepiquat residues in food account for <1% of the RfD and residues in drinking water are not expected. Thus, the aggregate exposures from all sources of mepiquat (in this case, only dietary is relevant) account for <1% of the RfD for the general population. Therefore, the Agency concludes that aggregate risks for the general population resulting from mepiquat uses are not of concern.

In evaluating the potential for cumulative effects, EPA compared structural similarities and toxic effects seen in mepiquat chloride studies with other related compounds. With one substance, difenzoquat, there appears to be similar neurotoxic effects. However, the Agency has concluded that the cumulative effects from the combined dietary exposure to mepiquat chloride and difenzoquat would be virtually nil because the chronic dietary exposure for all population subgroups is less than 1% of the RfD for both difenzoquat and mepiquat chloride.

2. Infants and children. In the RED, EPA has determined that the established tolerances for mepiquat chloride (including the previously established temporary tolerances for grapes) meet the safety standard under the FQPA amendment to section 408(b)(2)(C) for infants and children. The safety determination for infants and children considers the factors noted above for the general population, but also, takes into account the possibility of increased dietary exposure due to the specific consumption patterns of infants and children, as well as the possibility of increased susceptibility to the toxic effects of mepiquat chloride residues in this population subgroup.

In the developmental studies, effects were seen in the fetuses only at the same or higher dose levels than effects on the mothers. In the reproduction study, no effects on reproductive performance were seen. Also, because the NOAELs from the developmental and reproduction studies were equal to or greater than the NOAEL used for establishing the RfD, EPA concludes that it is unlikely that there is additional risk concern for immature or developing organisms. Finally, the Agency has no epidemiological information suggesting special sensitivity of infants and children to mepiquat chloride. Therefore, EPA finds that the uncertainty factor (100X) routinely used in RfD calculations is adequately protective of infants and children, and an additional uncertainty factor is not warranted for mepiquat.

EPA estimates that mepiquat residues in the diet of infants and children account for less than 1% of the RfD and residues in drinking water are not expected. Thus, the chronic aggregate exposure from all sources of mepiquat account for less than 1% for infants and children. The acute dietary MOE for infants and children exposed to mepiquat is 3,893. Therefore, the Agency concludes that aggregate risks for infants and children resulting from mepiquat uses are not of concern.

F. International Tolerances

There are no Codex, Canadian, or Mexican tolerances established for mepiquat on cotton. Thus, international harmonization is not an issue for these tolerances.