01-7644. 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-1012, must be received on or before April 27, 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-1012 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Dan Rosenblatt, Herbicide 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-1012. 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-1012 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-1012. 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 14, 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.

FMC Corporation, Agricultural Products Group

PP 9F06056

EPA has received a pesticide petition (9F06056) from FMC Corporation, Agricultural Products Group, 1735 Market Street, Philadelphia, PA, 19103 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 180.425 by establishing a tolerance for residues of clomazone, 2-(2-chloroprene)methyl-4,4- diethel-3-isoxazolidinone in or on the raw agricultural commodity sugarcane, cane at 0.05 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 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 clomazone in plants is adequately understood. The metabolism of clomazone has been studied in both monocotyledonous and dicotyledonous plant species, such as corn and soybeans. The residue of significance is the parent compound, clomazone. This picture is consistent with plant metabolism studies in other species (cotton, sweet potatoes and tobacco), all of which have shown a similar metabolic pathway with the residue of significance being clomazone.

2. Analytical method. There is a practical analytical method for detecting and measuring levels of clomazone in or on sugarcane (cane) and its processed parts (molasses, refined sugar) with a limit of detection that allows monitoring of food for residues at or above the levels proposed in this tolerance. Sugarcane and processed parts samples are analyzed using an analytical method consisting of an acid reflux, a C₁₈ solid phase extraction (SPE), a Florisil SPE clean-up followed by gas chromatography (GC)-mass selective detection (MSD). The method limit of quantitation (LOQ) is 0.05 ppm. The method limit of detection (LOD) is 0.01 ppm.

3. Magnitude of residues. FMC conducted a residue study (consisting of 10 trials) to determine the magnitude of the residue of clomazone in/on sugarcane (cane) after Command 3ME was applied once as a postemergence broadcast spray to either plant cane or ratoon cane, but preemergence to weeds, at 1.25 lb. ai/A. The residues found in the treated cane samples ranged from non-detectable (ND) to just above LOD at 0.02 ppm. A second study, applied in the same fashion as described above, was conducted using an exaggerated rate of 2.5 lb. ai/A (2X the intended use rate). Sugarcane (cane) was processed into two fractions, molasses and refined sugar, using simulated commercial practices. Analysis of the processed parts (molasses, refined sugar) yielded no clomazone residues (ND, <0.01 ppm) and no concentration factor. Since no detectable residues were found in molasses, the only identified sugarcane byproduct feedstuff (for beef and dairy cattle), animal feeding studies in cows are not needed.

B. Toxicological Profile

1. Acute toxicity. The following mammalian toxicity studies have been conducted with clomazone technical (unless noted otherwise) to support registrations and/or tolerances of clomazone:

i. A rat acute oral study with an LD₅₀ of 2,077 mg/kg (male) and 1,369 mg/kg (female).

ii. A rabbit acute dermal LD₅₀ of > 2,000 mg/kg.

iii. A rat acute inhalation LC₅₀ of 6.25 mg/L/4 hr (male), 4.23 mg/L/hr (female) and 4.85 mg/L/4 hr (combined sexes).

iv. A primary eye irritation study in the rabbit which showed practically no irritation.

v. A primary dermal irritation study in the rabbit which showed minimal irritation.

vi. A primary dermal sensitization study in the guinea pig which showed no sensitization.

vii. Acute delayed neurotoxicity - clomazone, and its known metabolites, 3 are not structurally related to known neurotoxic substances.

2. Genotoxicity. The following genotoxicity tests were all negative: Ames Assay; CHO/HGPRT Mutation Assay; and Structural Chromosomal Aberration. The Unscheduled DNA Synthesis genotoxicity was negative with activation; weakly positive without activation.

3. Reproductive and developmental toxicity. A two-generation reproduction study was conducted in the rat with a parental systemic NOAEL of 1,000 ppm (50 mg/kg/day) based on decreased body weight and food consumption at 2,000 ppm; and a progeny systemic NOAEL of 1,000 ppm (50 mg/kg/day) based on decreased pup body weight at 2,000 ppm. The reproductive performance NOAEL was >4,000 ppm which was the highest dose tested. There was an unexplained decrease in the fertility index during mating of the F1b generation at 4,000 ppm which was not observed in the F1a litter or repeated in the F2 generation. Additionally, there was one F2a pup at 1,000 ppm which had non-functional hindlimbs and one F2b pup at 4,000 ppm which had extended hindlimbs with no flexion at the ankle. These limb abnormalities were not considered treatment-related for the following reasons: (i) There was no dose response observed, (ii) the findings were not statistically significant, (iii) the findings were not repeated at the 1,000 ppm dose level in the F2b litter or found in the F1a or F1b litters; and (iv) these findings or related hindlimb abnormalities were not observed in developmental studies at gavage dose levels up to 100 mg/kg/day in the rat or 240 mg/kg/day in the rabbit.

A developmental toxicity study in rats given gavage doses of 100, 300 and 600 mg/kg/day and with maternal and fetal NOAELs of 100 mg/kg/day. The maternal NOAEL is based on decreased locomotion, genital staining and runny eyes and the developmental NOAEL is based on increased incidence of delayed ossification at 300 mg/kg/day. This study was negative for teratogenicity at all doses tested.

A developmental toxictiy study in rabbits given gavage doses of 30, 240 and 700 mg/kg/day with maternal and fetal NOAELs of 240 mg/kg/day. The maternal NOAEL is based on a decrease in body weight and the developmental NOAEL is based on an increase in the number of fetal resorptions at 700 mg/kg/day. This study was negative for teratogenicity at all doses tested.

In all cases, the reproductive and developmental NOAELs were equal to the parental NOAELs, thus indicating that clomazone does not pose any increased risk to infants or children.

4. Subchronic toxicity. In a 90-day feeding subchronic study in mice the NOAEL was 20 ppm (<2.9 mg/kg/day) based on liver cytomegaly at 20 ppm.

5. Chronic toxicity. A 12-month feeding study in the dog with a NOAEL of 500 ppm (14.0 mg/kg/day for males; 14.9 mg/kg/day for females) based on increased blood cholesterol and liver weights at 2,500 ppm.

A 24-month chronic feeding/oncogenicity study in the rat with a NOAEL of 100 ppm (4.3 mg/kg/day for males; 5.5 mg/kg/day for females) based on increased liver weights and increased liver cytomegaly at 500 ppm. There were no oncogenic effects observed under the conditions of the study. A 24-month chronic feeding/oncogenicity study in the mouse with a NOAEL of 100 ppm (15 mg/kg/day) based on an increase in the white blood cell count. There were no oncogenic effects observed under the conditions of the study.

Using the Guidelines for Carcinogen Risk Assessment, it is proposed that clomazone be classified as Group E for carcinogenicity (no evidence of carcinogenicity) based on the results of carcinogenicity studies in two species. In 24-Month Feeding/ Oncogenicity studies in rats and mice at dosages up to 2,000 ppm, there was no evidence of caricnogenicity. The NOAEL in the 24-Month Feeding/oncogenicity study in the rat was 100 ppm (4.3 mg/kg/day for males and 5.5 mg/kg/day for females). The NOAEL in the 24-Month Feeding/Oncogenicity study in mice was 100 ppm (15 mg/kg/day). The studies were negative for carcinogenic effects at all dosage levels tested.

The Reference Dose (RfD) for clomazone has been established at 0.043 mg/kg/day. The RfD for clomazone is based on the 24-Month Feeding/Carcinogenicity Study in the Rat with a NOAEL of 4.3 mg/kg/day and an uncertainty factor of 100.

6. Animal metabolism. The metabolism of clomazone in animals is adequately understood. Clomazone degrades rapidly and extensively in rats, goats and poultry to a variety of metabolites which were readily excreted from the body via excreta.

7. Metabolite toxicology. No clomazone related metabolite residues have been identified as being of toxicological concern. The residue of significance is parent. Clomazone, has been thoroughly investigated in a full battery of studies including acute, genetic, reproduction, developmental and oncogenic tests. These studies have demonstrated that clomazone has low acute toxicity, an overall absence of genotoxicity and does not cause reproductive toxicity, developmental toxicity or carcinogenicity.

8. Endocrine disruption. No specific tests have been conducted with clomazone to determine whether the herbicide may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects. It should be noted, however, that the chemistry of clomazone is unrelated to that of any compound previously identified as having estrogen or other endocrine effects. Additionally, a standard battery of required studies has been completed. These studies include an evaluation of the potential effects on reproduction and development, and an evaluation of the pathology of the endocrine organs following repeated or long-term exposure. No endocrine effects were noted in any of these studies with clomazone.

C. Aggregate Exposure

1. Dietary exposure—Food. i. For purposes of assessing the potential dietary exposure, EPA has estimated aggregate exposure based on the Theoretical Maximum Residue Contribution (TMRC) from the established tolerances for clomazone. The TMRC is a worst case estimate of dietary exposure since it is assumed that 100% of all crops for which tolerances are established are treated and that pesticide residues are present at the tolerance levels. Dietary exposure to residues of clomazone in or on food will be limited to residues on cabbage (0.1 ppm), cottonseed (0.05 ppm), cucumber (0.1 ppm), succulent peas (0.05 ppm), peppers (0.05 ppm), pumpkins (0.1 ppm), soybeans (0.05 ppm), winter squash (0.1 ppm), summer squash (0.1 ppm), sweet potato (0.05 ppm), snap beans (0.05 ppm) rice (0.05 ppm) and sugar (from cane) (0.05 ppm). Various feedstuffs from cotton and soybeans are fed to animals, thus exposure of humans to residues might result if such residues carry through to meat, milk, poultry or eggs. No tolerances are proposed for meat, milk, poultry or eggs since no detectable residues from clomazone have been found in animal feed items in the past or were found in any sugarcane processed animal feed products. Although the RAC bagasse was once a feed item, EPA has concluded that it is now mainly used for fuel. Accordingly molasses is the only sugarcane feed contributing fraction. As noted above, in conducting this exposure assessment, EPA has made very conservative assumptions, i.e., 100% of crops treated will contain clomazone residues and those residues would be at the level of the tolerance. It is FMCs opinion that these assumptions result in an overestimate of human exposure.

ii. Drinking water. It is unlikely that there will be exposure to residues of clomazone through drinking water supplies. A field mobility study was conducted at a loamy sand location. Clomazone was found only in the top 0-1 ft. soil samples during the 61 day study period. No clomazone residue (<0.02 ppm) was detected in the deeper soil levels (1-2, 2-3 and 3-4 ft.). Mathematical modeling (PESTANS) was also applied to the loamy sand site. PESTANS showed very limited potential for movement of clomazone. That is, clomazone did not move lower than the top seven inches of soil over the first 30 days with 10 inches of precipitation and 100% recharge. Predictions were also obtained for other soil types including sand, sandy loam, silt loam and clay loam. These outputs yielded a similar conclusion, that clomazone has low potential for downward movement with its highest mobility being sand. The field leaching study and PESTANS modeling results were further confirmed by field dissipation studies conducted in silt loam (IL and AR), sandy loam (NJ), sandy clay loam (NC), silty clay loam (IA) and silt loam (LA) soils. Results of these studies demonstrated that clomazone tended to remain in the top soil layer (0-6 ), with residues in the 6-12 layer being at or below method sensitivity (0.10 ppm) and generally declining to non-detectable. An aquatic field dissipation study was conducted at locations in AR and TX, having silty clay loam and loam soils characteristics respectively. Soil samples were taken over a period of 12 months following the herbicide application. Detectable residues of clomazone were found only in the 0-6 horizon. Should movement into surface water occur, potential for clomazone residues to be detected in drinking water supplies at significant levels is minimal. Results from an aquatic field dissipation study (static water situation) demonstrated half-lives of 12-13 days, indicating even shorter durations are likely under flowing water situations. Accordingly, there is no reasonable expectation that there would be an additional incremental aggregate dietary contribution of clomazone through groundwater or surface water.

2. Non-dietary exposure. Clomazone is only registered for use on food crops. Since the proposed use on sugarcane is consistent with existing registrations, there will be no non-dietary, non-occupational exposure.

D. Cumulative Effects

Clomazone is an isoxazolidinone herbicide. No other registered chemical exists in this class of chemistry. Therefore, given clomazone s unique chemistry low acute toxicity, the absence of genotoxic, oncogenic, developmental or reproductive effects, and low exposure potential (see Sections A and C), the expression of cumulative human health effects with clomazone and other natural or synthetic pesticides is not anticipated.

E. Safety Determination

1. U.S. population. Using the conservative exposure assumptions described above, based on the completeness and reliability of the toxicology data, it is concluded that aggregate exposure due to existing registered uses, and pending uses, of clomazone will utilize less than 1% of the RfD for the U.S. population. Additionally, an analysis concluded that aggregate exposure to clomazone adding sugarcane at a 0.05 ppm tolerance level will utilize 0.04 percent of the RfD for the U.S. population. EPA generally has no concern for exposures below 100% of the RfD because the RfD represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose appreciable risks to human health. It is concluded that there is a reasonable certainty that no harm will result from aggregate exposure to residues of clomazone, including all anticipated dietary exposure.

2. Infants and children. Based on the current toxicological data requirements, the database relative to pre- and post-natal effects for children is complete (See Section B.3). Further, for clomazone, the NOAEL in the two year feeding study which was used to calculate the RfD (0.043 mg/kg/day) is already lower than the NOAELs from the reproductive and developmental studies by a factor of more than 10-fold. Therefore, it can be concluded that no additional uncertainty factors are warranted and that the RfD at 0.043 mg/kg/day is appropriate for assessing aggregate risk to infants, children as well as adults.

Using the conservative exposure assumptions described above, FMC has concluded that the percent of the RfD that will be utilized by aggregate exposure to residues of clomazone in/on sugarcane for non-nursing infants (<1 year old), the population subgroup most sensitive, is 0.114 and the percent of the RfD that will be utilized by the children (1-6 years old) population subgroup is 0.086. The percent of the RfD utilized for infants and children for sugarcane plus all other current and pending (i.e., rice, tanier, cassava and arracacha) clomazone tolerances is 0.872 and 0.510 respectively.

Based on the above information, FMC has concluded that there is a reasonable certainty that no harm will result to infants, children or adults from dietary food consumption exposure to clomazone residues from either sugarcane sourced foods alone or sugarcane sourced foods plus all other clomazone treated human dietary food sources.

F. International Tolerances

There are Codex residue limits for residues of clomazone in or on oilseed rape, potatoes, tobacco, soybeans, rice, cottonseed, sugarcane and peas.