Notice of Filing Pesticide Petition to Establish Tolerance for Certain Pesticide Chemicals in or on Food

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice.

SUMMARY:

This notice announces the intial filing of a pesticide petition proposing the establishment of regulations for residues of certain pesticide chemicals in or on various food commodities.

DATES:

Comments, identified by docket control number PF-928, must be received on or before April 28, 2000.

ADDRESS:

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-928 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: James A. Tompkins, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-5697; e-mail address: Tompkins.Jim@epa.gov.

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:

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” 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-928. 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 (703) 305-5805.

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-928 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, Ariel Rios Bldg., 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 (703) 305-5805.

3. Electronically. You may submit your comments electronically by e-mail to: “opp-docket@epa.gov,” 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-928. 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 wil 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 certain pesticide chemicals 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 supports granting of the petition. Additional data may be needed before EPA rules on the petition.

List of Subjects

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

American Cyanamid Company

0F6088

Summary of Petition

EPA has received a pesticide petition (0F6088) from American Cyanamid Company, P.O. Box 400, Princeton, NJ 08543-0400 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 the herbicide imazamox in or on the raw agricultural commodities alfalfa forage, seed and hay, canola seed, legume vegetable crop group and wheat forage, grain, bran, shorts, hay and straw at 2.0, 0.1, 4.0, 0.1, 0.1, 0.4, 0.3, 0.6, 0.6, 0.3, and 0.2 parts per million (ppm), respectively. 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 qualitative nature of the residues of imazamox (AC 299263) in soybeans, alfalfa, canola, peas, and wheat is adequately understood. The metabolism of imazamox has been studied in soybeans, peas, and canola. EPA has concluded that the nature of the residue is adequately understood and the residues of concern are the parent imazamox only. The metabolism of imazamox was also studied in wheat. EPA has concluded that the nature of the residue is adequately understood and the residues of concern are the parent imazamox, and the desmethyl, hydroxy-methyl metabolite CL 263284. The metabolism of imazamox was further studied in alfalfa. EPA has concluded that the nature of the residue is adequately understood and the residues of concern are the parent imazamox, metabolite CL 263284, the carboxylate of the CL 263284 metabolite, CL 312622 and the glucoside of the CL 263284 metabolite, CL 189215.

2. Analytical method. A practical analytical method for detecting and measuring levels of imazamox in soybean seed was submitted to and approved by EPA. This method (M 2248.01) is appropriate for enforcement purposes. A practical analytical method for detecting and measuring levels of imazamox in canola seed was submitted to EPA. This method (M 3076) is appropriate for enforcement purposes. A practical analytical method for detecting and measuring levels of imazamox in legume vegetables (such as dry and succulent edible beans and peas) was submitted to EPA. This method (M 3076 with minor modifications) is appropriate for enforcement purposes. A practical analytical method for detecting and measuring levels of imazamox and its metabolite CL 263284 in wheat grain, forage, hay and straw was submitted to EPA. This method (M 3098) is appropriate for enforcement purposes. A practical analytical method for detecting and measuring levels of imazamox and its metabolites: CL 263284, its (CL 263284) glucose conjugate (CL 189215), and the carboxylate of AC 263284 (CL 312622) in alfalfa seed, forage and hay was submitted to EPA. This method (M 3178) is appropriate for enforcement purposes. All methods have undergone independent laboratory validation as required by PR Notices 88-5 and 96-1.

3. Magnitude of residues—i. Magnitude of residues in crops—a. Soybeans, legume, vegetables and canola: No apparent residues of imazamox were observed in soybeans, dry or succulent peas, or dry or succulent beans, or canola at or above 0.05 ppm (the limit of quantification for the analytical methods). The field studies, conducted at 1- 5x the highest intended label use rate, clearly support the proposed tolerances of 0.1 ppm. The requirement for a soybean processing study was waived by EPA based on the results of field trials at rates up to 5x the maximum label rate. In these trials, there was no measurable residue of imazamox in soybean seed above the validated sensitivity of the method (0.05 ppm). In addition, results from the plant metabolism study showed no detectable residues of imazamox in oil obtained from soybean seed that had been treated at an exaggerated use rate.

b. Wheat. A total of 20 field residue trials were conducted in 10 different states. Applications in the trials were consistent with the proposed label directions for use. Analysis of the treated samples showed that the maximum imazamox plus its metabolite CL 253284 was under the proposed tolerances of 0.3 ppm in the grain, 0.4 ppm in the forage, 0.3 ppm in the hay and 0.2 ppm in straw at the proposed labeled pre-harvest intervals (PHI). Wheat grain for processing was obtained from a 5x-rate field study and samples were processed into bran, middling, shorts, flour and aspirated grain fractions. Analysis of the treated samples showed that the total residue of the imazamox parent and the metabolite CL 263284 concentrated in bran and shorts. The appropriate concentration factor for bran and shorts is 2x. The proposed tolerance for these two fractions is at 2x the tolerance for the proposed grain tolerance of 0.3 ppm or 0.6 ppm.

c. Alfalfa. A total of 19 field residue trials were conducted in 12 different states. Applications in the trials were consistent with the proposed label directions for use. Analysis of the treated samples showed that the maximum residues of imazamox plus its three metabolites (CL 263284, CL 263284 glucose conjugate metabolite CL 189215, and CL 263284 carboxylate, CL312622) were under the proposed tolerances of 0.1 ppm in the seed, 2.0 ppm in the forage and 4.0 ppm in the hay at the proposed labeled (PHI)

ii. Magnitude of the residue in animals—a. Ruminants. The maximum dietary burden in beef and dairy cows results from a diet comprised of alfalfa hay and alfalfa forage for a total dietary burden that is significantly lower than levels that would require the proposal of tolerances in ruminants. This conclusion is based on exaggerated rate metabolism studies carried out on imazamox and its significant metabolites. Therefore, an exemption from tolerances in milk, meat and meat by-products under 40 CFR 180.6(a)(3) and (b) is proposed as it is not possible to establish with certainty whether finite residues will be incurred, but there is no reasonable expectation of finite residues.

d. Poultry. The maximum poultry dietary burden results from a diet composed of alfalfa hay (meal) and wheat grain for a total dietary burden that is significantly lower than the levels that would require the proposal of tolerances in poultry. This conclusion is based on the exaggerated rate metabolism studies carried out on imazamox and its significant metabolites. Therefore, an exemption from tolerances in poultry meat, meat by-products, fat and eggs under 40 CFR 180.6(a)(3) and (b) is proposed as it is not possible to establish with certainty whether finite residues will be incurred, but there is no reasonable expectation of finite residues.

B. Toxicological Profile

A complete battery of mammalian toxicity studies supports the tolerances for imazamox on soybeans and the rest of the legume vegetable crop grouping, canola, wheat and alfalfa. The data base is complete, valid and reliable, and all studies have been submitted to and approved by EPA. The toxicological data submitted to support the subject petition as amended include:

1. Acute toxicity. Imazamox technical is considered to be nontoxic (Toxicity Category IV) to the rat by the oral route of exposure. In the acute oral toxicity study in rats, the LD₅₀ value of imazamox technical was greater than 5,000 milligrams/kilograms body weight (mg/kg bwt) for males and females. The results from the acute dermal toxicity study in rabbits indicate that imazamox is slightly toxic (Toxicity Category III) to rabbits by the dermal route of exposure. The dermal LD₅₀ value of imazamox technical was greater than 4,000 mg/kg bwt for both male and female rabbits. Imazamox technical is considered to be nontoxic (Toxicity Category IV) to the rat by the respiratory route of exposure. The 4-hour LC₅₀ value was greater than 6.3 mg/L (analytical) for both males and females. Imazamox technical was shown to be non-irritating to slightly irritating to rabbit skin (Toxicity Category IV). Based on the results of a dermal sensitization study (Buehler), imazamox technical is not considered a sensitizer in guinea pigs.

2. Genotoxicty. Imazamox technical was tested in the following four assays measuring several different endpoints of potential genotoxicity. Collective results from these studies indicate that imazamox does not pose a mutagenic or genotoxic risk.

i. Bacterial Mutagenicity assay - Negative.

ii. In vitro structural chromosomal aberration assay - Negative.

iii. In vitro CHO/HGPRT assay - Negative.

iv. In vivo micronucleus aberration assay - Negative.

3. Reproductive and developmental toxicity. The development toxicity study in rats conducted with imazamox technical showed no evidence of teratogenic effects in fetuses and no evidence of developmental toxicity. Thus, imazamox is neither a developmental toxicant nor a teratogen in the rat. The results from this study supported a no observed adverse effect level (NOAEL) for developmental toxicity of 1,000 mg/kg bwt day, the highest dose tested and limit dose. The NOAEL for maternal toxicity was 500 mg/kg bwt day, based on reduced mean body weights, weight gains and food consumption at 1,000 mg/kg bwt day. Results from a developmental toxicity study in rabbits conducted with imazamox technical also indicated no evidence of teratogenicity or developmental toxicity. Thus, imazamox technical is neither a developmental toxicant nor a teratogen in the rabbit. In the rabbit developmental toxicity study, the NOAEL for maternal toxicity was 300 mg/kg bwt day, based on decreased food consumption at 600 mg/kg bwt day, the next highest dose tested. The NOAEL for developmental toxicity was 900 mg/kg bwt day, the highest dose tested. The results from the two-generation reproduction toxicity study in rats with imazamox technical support a NOAEL for parental and reproductive toxicity of 20,000 ppm (or approximately 1,639 mg/kg bwt day, calculated from the food consumption data), the highest concentration tested. The NOAEL for growth and development of offspring is also 20,000 ppm (or approximately 1,639 mg/kg bwt day. Results from the reproduction study and the developmental toxicity studies conducted with imazamox technical show no increased sensitivity to developing offspring as compared to parental animals, because the NOAELs for growth and development of offspring were equal to or greater than the NOAELs for parental or maternal toxicity.

4. Subchronic toxicity. No treatment-related adverse effects were noted in subchronic toxicity studies at the highest doses tested. A short-term (28-day) dermal study in rabbits was conducted with imazamox technical. No dermal irritation or systemic toxicity was observed at dose levels up to and including 1,000 mg/kg bwt day (highest dose tested), supporting a NOAEL of 1,000 mg/kg bwt day. In a subchronic (13-week) dietary toxicity study in rats with imazamox technical, no signs of systemic toxicity were noted, supporting a NOAEL of 20,000 ppm (or approximately 1,661 mg/kg bwt day, calculated from food consumption data), the highest concentration tested. In a subchronic (90-day) dietary toxicity study in dogs with imazamox technical, no signs of systemic toxicity were noted, supporting a NOAEL of 40,000 ppm (or approximately 1,368 mg/kg bwt day, calculated from the food consumption data), the highest concentration tested.

5. Chronic toxicity. The low order of mammalian toxicity of imazamox technical is also evident from the chronic dietary toxicity studies. These studies showed no increased mortalities or clinical signs of toxicity attributed to imazamox treatment. Moreover, there were no treatment-related effects on food consumption, body weights, organ weights, or hematology, clinical chemistry, urinalysis or ophthalmologic parameters. There was no gross or microscopic evidence of treatment-related lesions or carcinogenicity in the three chronic studies conducted in dogs, mice, or rats.

A 1-year dietary study was conducted with imazamox technical in dogs at dietary concentrations of 0, 1,000, 10,000, and 40,000 ppm. The NOAEL for this study was 40,000 ppm (or approximately 1,165 mg/kg bwt day, based on food consumption), the highest concentration tested.

A chronic feeding/carcinogenicity study was conducted with imazamox technical in male and female rats at dietary concentrations of 0, 1,000, 10,000, and 20,000 ppm. The NOAEL for systemic toxicity and carcinogenicity was 20,000 ppm (or approximately 1,167 mg/kg bwt day, based on food consumption) the highest concentration tested.

A chronic feeding/carcinogenicity study was conducted with imazamox technical in male and female mice at dietary concentration of 500, 3,500, and 7,000 ppm. The NOAEL for systemic toxicity and carcinogenicity was 7,000 ppm (or approximately 1,201 mg/kg bwt day, based on food consumption), the highest concentration tested.

In the dietary exposure analysis for AC 299263 in/on Soybeans (PP 6F4649) dated March 24, 1997, EPA determined that AC 299263 cancer classification is classified as not likely (to induce tumors in humans) according to the proposed new guidelines.

6. Animal metabolism. The qualitative nature of the residues of imazamox and its metabolites CL 263284 and CL 263284 carboxylate CL 312622 in animals is adequately understood. Based on metabolism studies with goats, hens and rats, there is no reasonable expectation that measurable imazamox-related residues will occur in meat, milk, poultry or eggs from the proposed use.

7. Metabolite toxicology. No toxicologically significant metabolites were detected in plant or animal metabolism studies for soybeans or the rest of the crops in the legume vegetable crop grouping: (6) or canola. Therefore, no metabolites need to be regulated in these crops.

The plant metabolism study in wheat indicated very low residues of concern. A very small amount of the metabolite CL 263284 was found in the wheat grain.

The plant metabolism in alfalfa indicated very low residues in the alfalfa seed. However, the parent imazamox underwent metabolism to the metabolite CL 263284 (the same metabolite seen in wheat). This metabolite was captured by a glucose molecule to form the glucose conjugate CL 189215 and the hydroxymethyl AC 263284 was also further oxidized to the carboxylate metabolite CL 312622.

Both metabolites, CL 263284 and CL 312622 were present in the rat metabolism study.

No additional toxicologically significant metabolites were detected in any plant or animal studies.

8. Endocrine disruption. Collective organ weight data and histopathological findings from the two-generation rat reproductive study, as well as from the sub-chronic and chronic toxicity studies conducted in two or more animal species, demonstrate no apparent estrogenic effects or effects on the endocrine system. There is no information available that suggests that imazamox would be associated with endocrine effects.

C. Aggregate Exposure

1. Dietary exposure. The potential dietary exposure to imazamox has been calculated from the proposed tolerances for use on soybeans and other members of the legume vegetables crop grouping (6), canola, wheat and alfalfa. These very conservative chronic dietary exposure estimates used the tolerance value for all the raw agricultural commodities. In addition these estimates assume that 100% of the crops contain imazamox residues.

i. Food. The Theoretical Maximum Residue Concentrations (TMRC) of imazamox on or in soybeans and other members of the legume vegetable crop grouping (6), canola, alfalfa, wheat grain, and its processed fractions are; 0.00577 mg/kg bwt day for the general U.S. population; 0.000573 mg/kg bwt day for non-nursing infants; 0.001306 mg/kg bwt day for children 1 to 6 years of age; and 0.000887 mg/kg bwt day for children 7 to 12 years of age.

ii. Drinking water. As a screening level assessment for aggregate exposure, EPA evaluates Drinking Water Level of Comparison (DWLOC), which is the maximum concentration of a chemical in drinking water that would be acceptable in light of total aggregate exposure to that chemical. Based on the chronic reference dose (RfD) of 3.0 mg/kg bwt day, determined by EPA, and the EPA's default factors for body weight and drinking water consumption, the DWLOCs have been calculated to assess the potential dietary exposure from residues of imazamox in water. For the adult population, the chronic DWLOC was 104,980 parts per billion (ppb), and for children, the DWLOC was estimated to be 29,987 ppb.

Chronic drinking water exposure analyses were calculated using EPA screening models (SCI-GROW for ground, water and GENEEC for surface water). The calculated peak GENEEC value is 0.44 ppb and the SCI-GROW value is 0.055 ppb. For the U.S. adult population, the estimated exposures of imazamox residues in surface water and ground, water are approximately 0.0004% and 0.00005%, respectively, of the DWLOC. For children, the estimated exposures of imazamox residues in surface water and ground water are approximately 0.002% and 0.0002%, respectively of the DWLOC. Therefore, the exposures to drinking water from imazamox use are negligible.

Based on the dietary and drinking water assessments, aggregate exposure to residues of imazamox in food and water can be considered to be negligible.

2. Non-dietary exposure. There is no available information quantifying non-dietary exposure to imazamox. However, based on the physical and chemical characteristics of the compound, the proposed use pattern and available information concerning its environmental fate, non-dietary exposure is not expected.

D. Cumulative Effects

Imazamox belongs to the imidazolinone class of compounds. The herbicidal activity of the imidazolinones is due to the inhibition of acetohydroxy acid synthase (AHAS), an enzyme only found in plants. AHAS is part of the biosynthetic pathway leading to the formation of branched chain amino acids. Animals lack AHAS and this biosynthetic pathway. This lack of AHAS contributes to the extremely low toxicity of imazamox in mammals. Although other registered imidazolinones have a similar herbicidal mode of action, there is no information available to suggest that these compounds exhibit a similar toxicity profile in the mammalian system. We are aware of no information to indicate or suggest that imazamox has any toxic effects on mammals that would be cumulative with those of any other chemical. Since imazamox is relatively non-toxic, cumulative effects of residues of imazamox and other compounds are not anticipated. Therefore, for the purposes of this tolerance petition no assumption has been made with regard to cumulative exposure with other compounds having a common mode of herbicidal action.

E. Safety Determination

1. U.S. population. Based on a RfD of 3.0 mg/kg bwt day determined from a NOAEL of 300 mg/kg bwt day, from the rabbit developmental toxicity study and a safety (uncertainty) factor of 100, the worse case estimate of chronic dietary exposure of imazamox from soybeans, the other members of the legume vegetable crop grouping (6), canola, wheat and alfalfa will utilize approximately 0.02% of the RfD for the general 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. The complete and reliable toxicity data and the conservative chronic exposure assumptions support the conclusion that there is a reasonable certainty of no harm from dietary (food) exposure to imazamox residues. Moreover, as exposure to residues of imazamox via water is negligible, there is a reasonable certainty of no harm from aggregate exposure to imazamox residues.

2. Infants and children. The conservative estimates, as described above, indicate that dietary exposure of imazamox from soybeans, the other members of the legume vegetable crop grouping, canola, wheat and alfalfa will utilize: approximately 0.02% of the RfD for non-nursing infants; approximately 0.04% of the RfD for children ages 1 to 6; and approximately 0.03% of the RfD for children ages 7 to 12.

No developmental, reproductive, or fetotoxic effects were noted at the highest doses of imazamox tested in guideline reproductive or developmental toxicity studies. The only maternal effects in the rat and rabbit teratology studies were decreased body weights, body weight gains and/or absolute and relative feed consumption in the higher dose groups of each study.

Based on the current toxicological data requirements, the data base relative to prenatal and postnatal effects for children is complete, valid and reliable. Results from the teratology studies and the two-generation reproduction study support NOAELs for fetal/developmental effects or reproductive/offspring effects, respectively, equivalent to the highest concentrations tested. As such, there is no increased sensitivity of infants and children to residues of imazamox. Therefore, an additional safety (uncertainty) factor is not warranted, and the RfD of 3.0 mg/kg bwt day, which utilizes a 100-fold safety factor, is appropriate to assure a reasonable certainty of no harm to infants and children.

F. International Tolerances

There is no Codex Maximum Residue Level Established for Residues of Imazamox on any Crops.