Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals 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 certain pesticide chemicals in or on various food commodities.

DATES:

Comments, identified by docket control number PF-943, must be received on or before June 19, 2000.

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-943 in the subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT:

By mail: Joanne I. Miller, Registration Division (7505C), Office of Pesticide Programs, Environmental Protection Agency, Ariel Rios Bldg., 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: (703) 305-6224; e-mail address: miller.joanne@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-943. 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-943 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-943. 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 amendment of the regulation for residues of glufosinate-ammonium, a pesticide chemical, in or on food commodities derived from cotton under section 408 of the Federal Food, Drug, and Comestic Act (FFDCA), 21 U.S.C. 346a. EPA has determined that this request contains data or information regarding the elements set forth in section 408(d)(2); however, EPA has not evaluated 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 additives
• Food additives
• Pesticides and pests
• Reporting and recordkeeping requirements

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 summary identifies an analytical method available to EPA for the detection and measurement of the residues of glufosinate-ammonium in or on cotton commodities.

Aventis CropScience USA

PP 0F6140

A. Residue Chemistry

1. Plant metabolism. The metabolism of glufosinate-ammonium in plants has been investigated and is understood. The crop residue profile following selective use of glufosinate-ammonium on transgenic crops is different from that found in conventional crops. The crop residue observed after non-selective use is the metabolite 3-methylphosphinico-propionic acid which is found only in trace amounts. The principal residue identified in the metabolism studies after selective use of glufosinate-ammonium on transgenic crops is the acetylated derivative of parent material, 2-acetamido-4-methylphosphinico-butanoic acid with lesser amounts of 3-methylphosphinico-propionic acid observed.

2. Analytical method. The enforcement analytical method utilizes gas chromatography for detecting and measuring levels of glufosinate-ammonium and metabolites with a general limit of quantification of 0.05 ppm. This method allows detection of residues at or above the proposed tolerances.

3. Magnitude of residues. Field residue trials were conducted across the five major regions of cotton production in the U.S. Two different treatment regimes were examined to represent use patterns which are the most likely to result in the highest residues. Glufosinate-ammonium derived residues did not exceed 3.4 ppm in undelinted cotton seed and 11.6 ppm in cotton gin byproducts (trash) when sampled at 70 days or more after the last treatment. No significant concentration of the residues occurred in the processed cotton commodities meal and hull and in refined oil the residues were less than the limit of quantitation (LOQ) of the analytical method. Thus, tolerances are not being proposed for the processed commodities from cotton.

B. Toxicological Profile

1. Acute toxicity. Glufosinate-ammonium has been classified as toxicity category III for acute oral, dermal and inhalation toxicity. It is toxicity category III for eye irritation. It is not a dermal irritant (toxicity category IV) nor is it a dermal sensitizer. The oral LD₅₀ is 2 gram/kilogram (g/kg) in male rats and 1.62 g/kg in female rats.

2. Genotoxicity. Based on results of a complete genotoxicity database, there is no evidence of mutagenic activity in a battery of studies, including: Salmonella spp., E. coli, in vitro mammalian cell gene mutation assays, mammalian cell chromosome aberration assays, in vivo mouse bone marrow micronucleus assays, and unscheduled DNA synthesis assays.

3. Reproductive and developmental toxicity. In a developmental toxicity study, groups of 20 pregnant female Wistar rats were administered glufosinate-ammonium by gavage at doses of 0, 0.5, 2.24 10, 50 and 250 mg/kg/day from days 7 to 16 of pregnancy. The no observed adverse effect level (NOAEL) for maternal toxicity is 10 mg/kg/day; the lowest observed adverse effect level (LOAEL) is 50 mg/kg/day based on vaginal bleeding and hyperactivity in dams. In the fetus, the NOAEL is 50 mg/kg/day, based on dilated renal pelvis observations at the LOAEL of 250 mg/kg/day.

In a developmental toxicity study, groups of 15 pregnant female Himalayan rabbits were administered glufosinate-ammonium by gavage at doses of 0, 2.0, 6.3 or 20.0 millgrams/kilogram/day (mg/kg/day) from days 7 to 19 of pregnancy. In maternal animals, decreases in food consumption and body weight gain were observed at the 20 mg/kg/day dose level. The NOAEL for both maternal and developmental toxicity was 6.3 mg/kg/day.

In a multi-generation reproduction study, glufosinate-ammonium was administered to groups of 30 male and 30 female Wistar/Han rats in the diet at concentrations of 0, 40, 120 or 360 ppm. The LOAEL for systemic toxicity is 120 ppm based on increased kidney weights in both sexes and generations. The systemic toxicity NOAEL is 40 ppm. The LOAEL for reproductive/developmental toxicity is 360 ppm based on decreased numbers of viable pups in all generations. The NOAEL is 120 ppm.

4. Subchronic toxicity. In a sub-chronic oral toxicity study, glufosinate-ammonium was administered to 10 NMRI mice/sex/ dose in the diet at levels of 0, 80, 320 or 1,280 ppm (equivalent to 0, 12, 48, or 192 mg/kg/day) for 13 weeks. Significant (p< 0.05) increases were observed in serum aspartate aminotransferase and in alkaline phosphatase in high-dose (192 mg/kg/day) males. Also observed were increases in absolute and relative liver weights in mid-(48 mg/kg/day) and high-dose males. The NOAEL is 12 mg/kg/day, the LOAEL is 48 mg/kg/day based on the changes in clinical biochemistry and liver weights.

5. Chronic toxicity. In a combined chronic toxicity/oncogenicity study, glufosinate-ammonium was administered to 50 Wistar rats/sex/dose in the diet for 130 weeks at dose levels of 0, 40, 140, or 500 ppm (mean compound intake in males was 0, 1.9, 6.8, and 24.4 mg/kg/day and for females was 0, 2.4, 8.2 and 28.7 mg/kg/day, respectively). A dose-related increase in mortality was noted in females at 140 and 500 ppm, whereas in males increased absolute and relative kidney weights were noted at 140 ppm and 500 ppm. The NOAEL was considered to be 40 ppm. No treatment-related oncogenic response was noted.

In an oncogenicity study, glufosinate-ammonium was administered to 50 NMRI mice/sex/dose in the diet at dose levels of 0, 80, 160 (males only) or 320 (females only) ppm for 104 weeks. The NOAEL for systemic toxicity is 80 ppm (10.82/16.19 mg/kg/day in males/females (M/F)), and the LOAEL is 160/320 ppm (22.60/63.96 mg/kg/day in M/F), based on increased mortality in males, increased glucose levels in males and females, and changes in glutathione levels in males. No increase in tumor incidence was found in any treatment group.

In a chronic feeding study, glufosinate-ammonium technical was fed to male and female beagle dogs for 12 months in the diet at levels of 2.0, 5.0 or 8.5 mg/kg/day. The NOAEL is 5.0 mg/kg/day based on clinical signs of toxicity, reduced weight gain and mortality 8.5 mg/kg/day.

In a rat oncogenicity study, glufosinate-ammonium was administered to Wistar rats (60/sex/group) for up to 24 months at 0, 1,000, 5,000, or 10,000 ppm (equivalent to 0, 45.4, 228.9, or 466.3 mg/kg/day in males and 0, 57.1, 281.5, or 579.3 mg/kg/day in females). The LOAEL for chronic toxicity is 5,000 ppm (equivalent to 228.9 mg/kg/day for male rats and 281.5 mg/kg/day for females), based on increased incidences of retinal atrophy. The chronic NOAEL is 1,000 ppm. Under the conditions of this study, there was no evidence of carcinogenic potential. Dosing was considered adequate based on the increased incidence of retinal atrophy.

6. Animal metabolism. Studies conducted in rats using¹⁴ C-glufosinate-ammonium have shown that the compound is poorly absorbed (5-10%) after oral administration and is rapidly eliminated primarily as the parent compound. The highest residue levels were found in liver and kidney tissues.

The metabolic profile and the quantitative distribution of metabolites was very similar in both goat and hen. The vast majority of the dose was excreted, primarily as parent compound. The very limited residues found in edible tissues, milk and eggs were comprised principally of glufosinate and 3-methylphosphinico-propionic acid (Hoe 061517), with lesser amounts of N-acetyl-L-glufosinate (Hoe 099730) and 2-methylohosphinico-acetic acid (Hoe 064619).

7. Metabolite toxicology. Additional testing has been conducted with the major metabolites, Hoe 061517 and Hoe 099730, as well as the L-isomer of glufosinate-ammonium, identified as Hoe 058192. Based on sub-chronic and developmental toxicity study results, a profile of similar or less toxicity compared to the parent compound, glufosinate-ammonium, was observed.

8. Endocrine disruption. No special studies have been conducted to investigate the potential of glufosinate-ammonium to induce estrogenic or other endocrine effects. However, no evidence of estrogenic or other endocrine effects have been noted in any of the toxicology studies that have been conducted with this product and there is no reason to suspect that any such effects would be likely.

C. Aggregate Exposure

1. Dietary exposure. Tolerances have been established (40 CFR part 180.473) for the combined residues of glufosinate-ammonium and metabolites in or on a variety of raw agricultural commodities. No appropriate toxicological endpoint attributable to a single exposure was identified in the available toxicity studies. EPA, therefore, has no, established an acute reference dose (RfD) for the general population including infants and children. An acute RfD of 0.063 mg/kg/day was established, however, for the females 13+ subgroup. An acute analysis was conducted for the sub-population of females 13+. Chronic dietary analysis was conducted for the usual populations.

i. Food. An acute dietary analysis was conducted using the Dietary Exposure Evaluation Model (DEEM) software and the 1994-1996 CSFII consumption data base. The analysis assumed tolerance level residues for all commodities and 100% of crop treated. This Tier One analysis resulted in an exposure of 0.007432 mg/kg bw/day (95th percentile) for the female 13+ sub-population (the only population of concern) representing 35% utilization of the acute reference dose (RfD).

Chronic dietary analysis was conducted to estimate exposure to potential glufosinate-ammonium residues in or on registered and proposed commodities. The DEEM software and the 1994-1996 USDA food consumption data were used. Tolerance level residues were assumed for all commodities and conservative percent crop treated values were incorporated for major crops (25% corn, 15% soybean, 10% potatoes, 20% cotton), whereas 100% of the crop was assumed to be treated for all other registered or pending uses. Chronic dietary exposure estimates from residues of glufosinate-ammonium for the US Population utilized approximately 25% of the chronic RfD. The sub-population with the highest exposure was children 1-6 utilizing approximately 67% of the chronic RfD. This analysis was based on highly conservative assumptions. The Agency has no concerns with RfD utilization up to 100%.

ii. Drinking water. US EPA's Standard Operating Procedure (SOP) for Drinking Water Exposure and Risk Assessments was used to perform the drinking water assessment. The models screening concentrations in ground water (SCI-GROW) and EPA's Pesticide Root Zone Model (PRZM)-EXAMS were used to estimate the concentration of glufosinate-ammonium which might occur in water. The acute drinking water level of comparison (DWLOC) for females 13+ is 408 parts per billion (ppb). In comparison, the acute drinking water estimated concentrations (DWEC) calculated by Generic expected environmental concentration (GENEEC) is 45 ppb, nearly an order of magnitude below the DWLOC.

The chronic DWLOC calculated for adults is 184 ppb and that for children/toddlers is 24 ppb. The chronic DWEC calculated using a worst case scenario is 11 ppb (GENEEC). Thus, the drinking water estimated concentration represents only 11% of the DWLOC for adults and 46% of that for children/toddlers. The DWLOC are based on highly conservative dietary (food) exposures and are expected to be much higher in real world situations reducing further the percent utilization of the DWLOC even more favorable.

2. Non-dietary exposure. Glufosinate-ammonium is currently registered for use on the following non-food sites: areas around ornamentals, shade trees, Christmas trees, shrubs, walks, driveways, flower beds, farmstead buildings, in shelter belts, and along fences. It is also registered for use as a post-emergent herbicide on farmsteads, areas associated with airports, commercial plants, storage and lumber yards, highways, educational facilities, fence lines, ditch banks, dry ditches, schools, parking lots, tank farms, pumping stations, parks, utility rights-of-way, roadsides, railroads, and other public areas and similar industrial and non-food crop areas. It is also registered for lawn renovation uses.

The EPA has determined that there are no acute or chronic non-dietary exposure scenarios. Further, the Agency has determined that it is not appropriate to aggregate short- and intermediate-term non-dietary exposure with dietary exposures in risk assessments because the end-points are different.

D. Cumulative Effects

Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider “available information” concerning the cumulative effects of a particular pesticide's residues and “other substances that have a common mechanism of toxicity.” EPA has indicated that, at this time, the Agency does not have available data to determine whether glufosinate-ammonium has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, glufosinate-ammonium does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance petition, therefore, it has not been assumed that glufosinate-ammonium has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. Using the conservative assumptions described above, based on the completeness and reliability of the toxicity data, it is concluded that chronic dietary exposure to the registered and proposed uses of glufosinate-ammonium will utilize at most 25% of the chronic RfD for the US Population. The actual exposure is likely to be much less as more realistic data and models are developed. Exposures below 100% of the RfD are generally assumed to be of no concern because the RfD represents the level at or below which daily aggregate exposure over a lifetime will not pose appreciable risk to human health.

The acute population of concern, female 13+ utilizes 35% of the acute RfD. This is a Tier One highly conservative assessment and actual exposure is likely to be far less. DWLOC based on dietary exposures are greater than highly conservative estimated levels, and would be expected to be well below the 100% level of the RfD, if they occur at all.

EPA has concluded that it is not appropriate to aggregate non-dietary exposures with dietary exposures in a risk assessment because the toxicity end-points are different.

Therefore, there is a reasonable certainty that no harm will occur to the US Population from aggregate exposure (food, drinking water and nonresidential) to residues of glufosinate-ammonium and metabolites.

2. Infants and children. The toxicological data base is sufficient for evaluating prenatal and postnatal toxicity for glufosinate-ammonium. There are no prenatal or postnatal susceptibility concerns for infants and children, based on the results of the rat and rabbit developmental toxicity studies and the 2-generation reproduction study. Based on clinical signs of neurological toxicity in short and intermediate dermal toxicity studies with rats, EPA has determined that an added FQPA safety factor of 3x is appropriate of assessing the risk of glufosinate-ammonium derived residues in crop commodities.

Using the conservative assumptions described in the exposure section above, the percent of the chronic reference dose that will be used for exposure to residues of glufosinate-ammonium in food for children 1-6 (the most highly exposed sub group) is 67%. Infants utilize 43% of the chronic RfD. As in the adult situation, DWLOC are higher than the worst case drinking water estimated concentrations and are expected to use well below 100% of the RfD, if they occur at all.

Therefore, there is a reasonable certainty that no harm will occur to infants and children from aggregate exposure to residues of glufosinate-ammonium.

F. International Tolerances

Maximum residue limits (Codex MRLs) for glufosinate-ammonium and metabolites in or on cotton commodities have not been established by the Codex Alimentarius Commission.