Document ID: EPA-HQ-OPP-2021-0634-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2022-05-20T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER  

EPA Registration Division contact: [Heather McFarley (703) 308-8119]

INSTRUCTIONS:  Please utilize this outline in preparing the pesticide petition.  In cases where the outline element does not apply, please insert "NA-Remove" and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simply replace the instructions that appear in green, i.e., "[insert company name]," with the information specific to your action.

TEMPLATE:

[Albaugh, LLC]

[Insert petition number]

	EPA has received a pesticide petition ([insert petition number]) from [Albaugh, LLC], [1535 36[th] St. NE, Ankeny, IA 50021] requesting, 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

(Options (pick one)
   
   	1. by establishing a tolerance for residues of

	2. to establish an exemption from the requirement of a tolerance for

	[oxyfluorfen] in or on the raw agricultural commodity [rice] at [0.01] 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 FDDCA; 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 qualitative nature of the residue in plants is adequately understood based on acceptable metabolism studies conducted on tomatoes (fruiting vegetable), onions (bulb vegetable), and peaches (stone fruit) and rotational crops. The terminal residue of concern is oxyfluorfen.]

	2. Analytical method. [Rice samples were extracted with an acetonitrile:water mixture.  The acetonitrile fraction was collected, and brought to final volume, filtered and analyzed using LC-MS/MS assay.  For grain, the LOQ was 0.01 ppm and the LOD was 0.002 ppm.]

	3. Magnitude of residues. [Sixteen field trials of rice were established in typical rice producing areas of the United States. At each trial location one or more rice plots were treated at a target rate of 1.5 lb ai/A.  Residue levels in rice grain samples were below the limit of detection (<0.002 ppm) for all control and treated plots with the exception of one plot treated with 1.5 lb ai/A at the 4-leaf rice stage in which two rice grain samples showed levels below the method LOQ of 0.010 ppm at 0.004 and 0.002 ppm.  Four additional plots were established for the purpose of producing rice grain for processing.  At the first two plots, the rice was treated at pre-emergence timing eitherat an excess (5x) rate of 7.5 lb. ai/A or at an excess (2X) rate of 5 lb ai/A.  Rice at the second two excess rate plots were treated two times (pre-emergent followed by the 4-leaf stage) at a 2X rate (1.0 lb ai/A+ 2.0 lb ai/A) and a 5X rate (2.5 lb ai/+ 5.0 lb ai/A).  Residue levels in the rice grain from both excess rate treated plots were below the limit of detection of 0.002 ppm (ND).  Because there were no detectable residues in the excess rate treated rice grain, the grain was not processed and concentration factors were not calculated.]

B. Toxicological Profile

	1. Acute toxicity.  [Oxyfluorfen has low acute toxicity via the oral, dermal, and inhalation routes (Toxicity Category IV). It is a slight eye and dermal irritant and is not a dermal sensitizer.]

	2. Genotoxicty. [The technical material (96-99% a.i.) was tested in several genetic toxicology studies which included assessments of gene mutation, chromosomal aberrations, and DNA damage. All assays were negative, except for one Ames assay using the older 72% technical material which was positive only at high, insoluble levels. A subsequent Ames assay with 96% material was negative.]

	3. Reproductive and developmental toxicity. [In a rabbit developmental toxicity study, the relevant maternal and developmental NOAELs were 30 mg/kg bw/day, whereas in rats they were 1000 mg/kg bw/day.  The maternal NOAEL is 30 mg/kg/day. The maternal LOAEL is 90 mg/kg/day, based on decreased number of live fetuses/doe. The developmental NOAEL is 30 mg/kg/day. The developmental LOAEL is 90 mg/kg/day based on decreased number of live fetuses/doe.  In a rat developmental toxicity study, no effects were observed up to the limit dose and the relevant maternal and developmental NOAELs were 1000 mg/kg bw/day.  

In a multigeneration study in rats, the relevant parental, offspring and reproductive NOAELs were 400 ppm (M: 30.9, F: 33 mg/kg bw/day), 400 ppm (M: 30.9, F: 33 mg/kg bw/day) and 1600 ppm (M: 120, F:131 mg/kg bw/day), respectively. Reductions in body weight of offspring and histopathologic alteration of the kidneys of parents were observed with a dose of oxyfluorfen of 120-131 mg/kg/day.  The LOAEL for the reproduction toxicity study was not established.  The LOAEL for offspring is 120-131 mg/kg/day, based on decreased pup body weight and smaller litter size. There were no effects on reproduction parameters in the database.

	4. Subchronic toxicity. [Mild liver toxicity was described in the 1997 subchronic rat study which used the 98% technical material. Increased liver weight was accompanied by very slight increases in liver enzyme activities and minimal histopathologic changes. Similar effects also occurred in the other subchronic and chronic rat, mouse, and dog studies. There were typically few histopathological lesions seen in the liver, although hepatocyte necrosis did occur in the mouse and dog studies.]

	5. Chronic toxicity. [Adverse effects on the liver marked the LOEL in all three chronic toxicity studies with NOELs of 18.5, 57, and 3 mg/kg/day seen in the dog, rat, and mouse studies, respectively. A statistically significant positive dose-related trend for liver adenomas and carcinomas was observed in the chronic mouse study.  The study was used to set the Q1* (7.32 x 10[-2] (mg/kg/d)[-1])]

	6. Animal metabolism. [The metabolism of oxyfluorfen was studied in rats.  Oxyfluorfen is rapidly absorbed, distributed, metabolized, and excreted following oral administration in rats. Recovery of radioactivity was high for most groups (84.34-99.58% of administered dose). The feces was the major route of excretion with up to ten metabolites found in the fececes.  Major metabolites were formed by o-deethylation, reduction of the nitro group, conjugation, and diphenyl ether cleavage.]

	7. Metabolite toxicology. [Oxyfluorfen does not produce a toxic metabolite and therefore no toxicity data exist for metabolites of oxyfluorfen.]

	8. Endocrine disruption. [The toxicity studies required by EPA for the registration of pesticides measure numerous endpoints with sufficient sensitivity to detect potential endocrine modulating activity. No effects have been identified in acute, subchronic, chronic, reproductive, or developmental toxicity studies to indicate any endocrine modulating activity by oxyfluorfen.  More importantly, the multi-generation reproduction study in rodents is a complex study design which measures a broad range of endpoints in the reproductive system and in developing offspring that are sensitive to alterations by chemical agents. Oxyfluorfen has been tested in two separate multigeneration studies and each time the results demonstrated that oxyfluorfen is not a reproductive toxin.  Oxyfluorfen is on List 2 for the EDSP Tier I battery of screening assays.]

C. Aggregate Exposure

	1. Dietary exposure. [Highly refined chronic and cancer dietary (food and drinking water) exposure and risk assessments for oxyfluorfen were conducted.  The assessment used the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM-FCID) Version 3.16, which uses 2003-2008 food consumption data from the U.S. Department of Agriculture's (USDA's) National Health and Nutrition Examination Survey/What We Eat in America, (NHANES/WWEIA).]

	i. Food. [The risk assessment incorporated the average percent crop treated estimates: almond 65%; apple 5%; apricot 35%; artichoke 40%; avocado 1%; broccoli 35%; cabbage 30%; caneberry 15%; cauliflower 55%; cherry 20%; corn 1%; cotton 1%; date 1%; grape raisin 40%; grape 20%; grape wine 40%; onion 75%; peaches 25%; pear 15%; pecan 1%; pistachio 40%; plums/prunes 45%; soybean 1%; and walnut 60%. For the remaining commodities, the applicant assumed 100% crop treated. No acute dietary exposure and risk analysis is required since no toxicological effect was observed from acute (single) dose exposure via the dietary route suitable for assessing acute risk for either the general population or for females 13-49 years of age. The chronic dietary exposure and risk estimates are highly refined and incorporate mean residue level from monitoring data from the United States Department of Agriculture's (USDA's) Pesticide Data Program (PDP), average percent crop treated (%CT) estimates reported by the Biological and Economic Analysis Division (BEAD), and HED's 2018 default processing factors. PDP data were used for a majority of commodities due to the significant impact on the cancer dietary exposure estimates. 

An EDWC was based on the coffee and forestry surface water model. The addition of rice as a new use does not affect the chronic dietary (food and drinking water) exposure seen in previous assessments and risk estimates do not exceed HED's LOC (less than 100% of the cPAD) for the general US population and all population subgroups. The most highly exposed population subgroup was all infants (< 1 year old) at 1.4% of the cPAD.  The Agency has classified oxyfluorfen as a Group C, "possible" human carcinogen. The cancer dietary exposure and risk estimate is highly refined and incorporates mean residue levels from PDP monitoring residues, average %CT estimates, and default processing factors. A modeled EDWC from EFED for the coffee scenario was used in the assessment. The addition of rice as a new use does not significantly affect the cancer dietary (food and drinking water) exposure seen in previous assessments for the general US population and all population subgroups.]

	ii. Drinking water. [The petitioner used screening level water exposure models in the dietary exposure analysis and risk assessment for oxyfluorfen in drinking water. These simulation models take into account data on the physical, chemical, and fate/transport characteristics of oxyfluorfen.  A modeled EDWC from EFED for the coffee scenario was used in the assessment. The maximum use rate of oxyfluorfen on rice is 1.5 lb ai/A and is no greater than the maximum annual application rates approved for other crops. The addition of rice as a new use does not significantly affect the cancer dietary (food and drinking water) exposure seen in previous assessments for the general US population and all population subgroups.]

	2. Non-dietary exposure. [Oxyfluorfen is a broad spectrum pre- and post-emergent herbicide used to control annual broadleaf and grassy weeds in corn, cotton, soybeans, fruit, nut trees and ornamentals.  There are no residential uses of oxyfluorfen on rice.]

D. Cumulative Effects

	[EPA has not made a common mechanism of toxicity finding as to oxyfluorfen and any other substances, and oxyfluorfen does not appear to produce a toxic metabolite produced by other substances. For the purposes of this action, therefore, EPA has not assumed that oxyfluorfen has a common mechanism of toxicity with other substances.]

E. Safety Determination

	1. U.S. population. [EPA must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard (e.g., a NOAEL or PAD), or the risks themselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure.

	Acute aggregate risk:  No acute population adjusted dose (aPAD) was selected for the general U.S. population or any population subgroups (including infants and children); therefore, no acute aggregate risk assessment was conducted.

Short-term Aggregate risk:  Since there are no homeowner uses of oxyfluorfen, residential post-application exposure is expected to be negligible. Therefore, the short-term aggregate risk for children is equal to the dietary (food and drinking water) risk estimates and are not of concern. There are no short-term aggregate risks of concern for adults.

Chronic Aggregate risk:  The chronic aggregate risk assessment combines exposures to oxyfluorfen in food and drinking water only. The chronic (food and drinking water) exposure and risk estimates were <2% of the cPAD for all population subgroups; therefore, there are no chronic aggregate risk estimates of concern.

Cancer Aggregate risk: A cancer aggregate assessment was conducted for the most highly exposed adult population subgroup, the General US population, with a cancer dietary (food and drinking water) exposure estimate of 0.000071 mg/kg/day. The cancer dietary exposure and risk estimate is highly refined and incorporates mean residue levels from PDP monitoring residues, average %CT estimates, and default processing factors. A modeled EDWC from EFED for the coffee scenario was used in the assessment. The addition of rice as a new use does not significantly affect the cancer dietary (food and drinking water) exposure seen in previous assessments for the general US population and all population subgroups.

Based on these risk assessments, the petitioner concludes that there is a reasonable certainty that no harm will result to the general population from aggregate exposure to oxyfluorfen residues from the use on rice.]

	2. Infants and children. [EPA has evaluated the toxicity database of oxyfluorfen with respect to the potential for special sensitivity of infants and children and concludes that there is low concern for pre- and postnatal susceptibility. The FQPA safety factor has been reduced to 1X because: (1) the toxicity database is adequate to characterize potential pre- and post-natal risk for infants and children; (2) there were no signs of neurotoxicity in the oxyfluorfen database; (3) no reproductive effects were observed in rats; (4) although there were developmental/offspring effects in the reproductive and developmental studies, these were seen in the presence of maternal/parental toxicity; and (5) the PODs selected for risk assessment purposes are protective of the developmental/offspring effects seen in the database. The chronic (food and drinking water) exposure and risk estimates were <2% of the cPAD for all population subgroups. The addition of rice as a new use does not significantly affect the cancer dietary (food and drinking water) exposure seen in previous assessments for the general US population and all population subgroups. Based on these risk assessments, the petitioner concludes that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to oxyfluorfen residues.]

F. International Tolerances

	[There are no Codex or Mexican MRLs for oxyfluorfen on rice.]