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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER EPA Registration Division contact: Mr. Tony Kish, PM - 22, 703 -308 - 9443 State of Florida, Department of Citrus Petition Number: (To be Assigned by EPA) EPA has received a pesticide petition (to be inserted by EPA) ) from State of Florida, Department of Citrus, 60 5 East M ain Street , P.O. Box 9010 , Bartow , FL 3383 1 - 9010 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 temporary tolerance s for residues of 5 - chloro 3 - methyl - 4 -nitro - 1 H

-pyrazole (CMNP) and its metabolite (5 - chloro - 4 -nitro - 1 H -pyrazol - 3 - yl) - methanol (C HNP) in or on the raw agricultural commodities:  oranges at 0.80 parts per million (ppm) and its processed commodities:  orange juice at 0.025 parts per million (ppm)  orange oil at 0.070 parts per million (ppm)  orange dried pulp (also referred to as dried p omace ) at 1.80 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 orange metabolism of CMNP is adequately understood for the purposes of establi shing the proposed tolerances. CMNP metabolites include (5 - chloro - 4 -nitro - 1 H -pyrazol - 3 - yl) - methanol (CHNP) and its glucoside. Based on results of the CMNP orange metabolism study, the residue of concern was defined as CMNP parent compound and its metabol ite comprised of CHNP/CHNP - glucoside. 2. Analytical method. In all plant matrices, the residue of concern, parent CMNP and CHNP/CHNP glucoside, can be determined using HPLC/MS - MS following sample extraction , hydrolysis (to convert CHNP glucoside to its aglycone , CHNP ) and solid -phase clean up . The limits of quantitation (LOQ) for the analytes for the various commodities are as follows:  Oranges

– 0.025 ppm for both CMNP and CHNP/CHNP glucoside  Orange juice - 0.025 ppm for both CMNP and CHNP/CHNP glucoside  Orange oil

– 0.025 ppm for both CMNP and CHNP/CHNP glucoside  Orange dried pulp (p omace )

– 0.025 ppm for both CMNP and CHNP/CHNP glucoside2 3. Magnitude of residues. Field magnitude of residue trials with CMNP were conducted in Florida betwe en 2006 and 2008 at 10 sites in Hamlin, Pineapple, and Valencia oranges . Oranges were harvested at three days post application and samples analyzed for CMNP and its metabolite CHNP (including the glucoside conjugate) . Combined residues of CMNP and CHNP in the raw agricultural commodity averaged 0.194 ppm (ranging from 0.095 to 0.446 ppm) . Two decline trials were conducted in the spring and fall of 2008 where oranges were harvested at 0, 3, 5 and 7 days after application. Combined CMNP and CHNP residues immediately post application averaged 0.419 ppm (ranging from 0.337 to 0.501 ppm) and declined to an average of 0.170 ppm (ranging from 0.164 to 0.176 ppm) at seven days post application. A total of three processing trials , in which oranges harvested three days post - application were sent to a processing center (University of Idaho Food Technology Center) , were con ducted . A subsample of the bulk unwashed oranges was placed into frozen storage and the remaining oranges were processed into orange juice, orange oil and orange dried pulp (also known as dried p omace ) . All four matrices were then sent frozen for analysis and all commodities were analyzed for residues of CMNP and its primary metabolite, CHNP. Combined CMNP and CHNP residues in the raw agricultural commodity averaged 0.123 ppm (ranging from 0.057 to 0.178 ppm) in these studies. There was no detectable residue in any sample of orange juice. There was a single orange oil sample with CMNP residue exceeding the method LOQ . No orange oil sample had detectable residue of CHNP. CMNP and CHNP residues in dried orange pulp ( dried p omace ) averaged 0.867 ppm (ranging from 0.467 ppm to 1.374 ppm) . B. Toxicological Profile 1. Acute toxicity . Acute toxicity endpoints for CMNP technical are as follo ws: Acute oral (up/down) - LD 50 197.1 milligrams/kilogram Acute dermal -rats - LD 50 >5000 milligrams/kilogram Acute inhalation

– rats

– LC 50 >2.03 milligrams/Liter Eye irritation

– rabbits Ocular irritation persisted for 21 days Skin irritation

– rabbits Slight irritation cleared by 7 days Dermal sensitization (Buehler) - Guinea Pig Not a contact sensitizer A 28 day dermal toxicity study in the rat in which CMNP was administered to at least 10% of the skin surface at doses of 0, 30, 75, 150, and 250 mg/kg bw/day resulted in a NOAEL of 250 mg/kg bw/day for both sexes. 2. Genotoxic i ty. A battery of mutagenicity studies with CMNP yielded negative results in reverse mutation assay (Salmonella typhimurium ), mammalian cell cytogenetics assay (chromosome aberration), and rat bone micronucleus assay.3

3. Reproductive and developmental toxicity. A developmental toxicity study was conducted with CMNP using rats gavaged with doses of 0, 5, 50, or 100 mg/kg bw/day from days 6 through 19 of gestati on. The maternal toxicity LOAEL was 50 mg/kg bw/day based on liver effects . The maternal NOAEL was 5 mg/kg bw/day. The developmental LOAEL was 100 mg/kg bw/day based on fetal variations. The developmental NOAEL was 50 mg/kg bw/day. A developmental toxicity study was conducted with CMNP using rabbits gavaged with doses of 0, 5, 25, 75, or 125 mg/kg bw/day. The maternal toxicity NOAEL was 75 mg/kg bw/day and LOAEL was 125 mg/kg bw/day based upon reduced body weight gain, reduced feed consumption, and c l inical signs. The developmental toxicity NOAEL was 75 mg/kg bw/day and LOAEL was 125 mg/kg bw/day based upon reduced fetal body weight. A two - generation reproduction study was conducted in rats in which CMNP was administered at dietary doses of 0, 6.7, 5 0, or 100 mg/kg bw/day. The LOAEL for male and female adults was 50 mg/kg bw/day based upon findings in livers and kidneys. The NOAEL for male and female adults was 6.7 mg/kg bw/day. For developmental toxicity, the LOAEL was 100 mg/kg bw/day based upon offspring systemic toxicity (in the presence of parental systemic toxicity). The developmental NOAEL was 50 mg/kg bw/day. 4. Subchronic toxicity Ninety day feeding studies have been conducted with CMNP in rats, mice, and dogs. In the rat study, CMNP was administered in the diet at doses of 0, 5, 15, or 75 mg/kg bw/day. The NOAEL was 15 mg/kg bw/day and the LOAEL was 75 mg/kg bw/day based upon liver and kidney findings. In the mouse study, CMNP was administered in the diet at doses of 0, 5, 150, or 300 mg/kg bw/day. The NOAEL was 5 mg/kg bw/day and the LOAEL was 150 mg/kg bw/day based upon liver effects. In the dog study, CMNP was administered via capsule at 0, 5, 15, or 75/60 mg/kg bw/day. The dose of Group 4 was lowered from 75 to 60 mg/kg bw/day at study day 14 based on reduced food consumption. The LOAEL was 75/60 mg/kg bw/day based upon reduced body weight gain. The NOAEL was 15 mg/kg bw/day. 5. Chronic toxicity. A 52 - week chronic toxicity study was conducted in dogs in which CMNP was administered in gelatin capsules at doses of 0, 5, 15, or 60 mg/kg bw/day. There were no deaths during this study. There were no definitive effects related to CMNP on clinical observations, hematologic parameters, urinalysis parameters, ophthalmology, org ans weights or gross or microscopic pathology. The LOAEL was 60 mg/kg bw/day based upon reduced body weight gains in both sexes. The NOAEL was 15 mg/kg bw/day. 6. Animal metabolism. In a rat metabolism study, 14 C - CMNP was administered in a single oral gavage dose of 10 mg/kg body weight in an aqueous methylcellulose solution. Urine, cage rinse, feces, and expired air were collected for up to 168 hours post dosing. Over 8 5% of dosed radioactivity was recovered in the urine and feces. The bulk of th e dosed radioactivity was recovered during the first 24 hours. The total radioactivity recovered was >95% for both sexes. CMNP was extensively metabolized in the rat with the maj or metabolite being identified as CMNP sulfonic acid. Minor routes of met abolism included formation of glucuronic acid conjugates, oxidation to form CHNP4

followed by conjugation with glucuronic acid and sulfonic acid, dechlorination and gluthathione conjugation followed by further metabolism to form a mercapturic acid conjugate . N - acetyl amino - CMNP (5 - chloro - 3 - methyl - 1 H -pyrazole - 4 - acetamide) was also detected as a minor metabolite in urine. 7. Metabolite toxicology . Pathways of metabolism of CMNP can be characterized by Phase I oxidation and Phase II conjugation reaction s involving glutathione conjugation and glucuronidation as well as nitroreduction/acetylation . The conjugated metabolites are all much more highly polar entities than parent compound and can be considered metabolically detoxified and excretable. The toxi c ities of CHNP and N - acetyl - amino - CMNP w ere assessed during the conduct of CMNP required mammalian toxicity studies. 8. Endocrine disruption . No consistent treatment effects were observed on the endocrine system in CMNP toxicology studies. C. Aggregate Exposure 1. Dietary exposure. Calculated maximum residue levels (MRLs) in oranges and orange products, potential residues in meat and milk products, potential maximum residues in surface and ground waters, and dietary exposures and risks were assessed with the Dietary Exposure Evaluation Model (DEEM

– FCID, Version 2.16), based on the CSFII Food Consumption 1994

– 1996 and 1998. The assessment was a conservative Tier I screening level assessment: 100% of all orange products were assumed to contain the MRL (including oranges produced in states where CMNP registration is not being pursued) ; 100% of meat and milk commodities were assumed to be derived from livestock fed dried p ulp (also known as dried p omace ) at the MRL; 100% of surface and gro und water was assumed to contain the maximum residue modeled and summed from GENEEC2 and SCI GROW; and, the lowest observed NOAEL was used for both the acute and chronic assessment (5 mg/kg BW/day). i. Food. The lowest toxicology no observed adverse e ffect level (NOAEL) of 5 mg/kg bw/day was conservatively used for both acute and chronic assessments. The reference dose (RfD) was assumed to be based on typical 10X intraspecies and 10X interspecies uncertainty factors. ii. Drinking water. Potential CMNP residues in surface and ground water were conservatively calculated using GENEEC2 for surface water and SCI - GROW for ground water. Residues were assumed to occur in all water consumed from all surface and ground water sources at the highest concentration sum of the GENEEC2 and SCI - GROW models.5 2. Non - dietary exposure . CMNP will be used only on commercially grown oranges in Florida. CMNP has no non - food or residential uses that could result in non - dietary exposure requiring aggregation. B ystander exposure was not considered a concern. Potential exposure to drift during application was considered negligible when compared with the open - cab airblast operator. Exposure to drifted residues would be negligible when compared with the exposure o f hand -harvesters. Due to the low volatility of CMNP, exposure to volatilized vapors is considered unlikely. Therefore, these routes of exposure were not quantified. The exposure of mixer/loaders handling the liquid product (open -pour) was assessed with the EPA Guide to the Pesticide Handlers Exposure Database. When wearing a baseline clothing ensemble of shoes, socks, long pants, long - sleeved shirt and chemical resistant gloves, margins of exposure (MOE) based on the 28 - day rat dermal NOAEL of 250 mg/kg BW/day exceeded 25,000 and inhalation MOEs based on the 28 - day rat dietary NOAEL of 15 mg/kg BW/day exceeded 29,000. Margins of exposure for the open - cab airblast operator in the same clothing ensemble exceeded 2,400 and 7,700 by the dermal and inhalati on routes. Hand -harvesting was conservatively modeled with the EPA convention of a transfer coefficient of 3,000 cm 2/ hr for hand -thinning tree fruits, a task EPA considers to have greater exposure potential than handharvesting. At the baseline clothing ensemble (with bare hands), dermal MOEs ranged from >430 at day 2 postapplication to ~870 at day 7, the most likely span of days of reentry. Inhalation exposure for low volatility products is typically not assessed. D. Cumulative Effects CMNP is not known to have a common mechanism of toxicity with other products. A cumulative assessment was not necessary. E. Safety Determination 1. U.S. population. In the acute DEEM assessment of dietary plus drinking water exposure, the MOE for the US p opulation was ~1,950 at the 95 th percentile of exposure. The MOE for females 13

– 49 years old was ~2,200. In the chronic assessment, the MOE for the US population was ~5,300. 2. Infants and children . In the acute assessment, the most highly expose d subpopulation at the 95 th percentile was non nursing infants <1 year old, with a MOE of ~600. In the chronic assessment, the most highly exposed subpopulation was children 3

– 5 years old, with a MOE of ~1,470. Based on the toxicology studies, fetuses and juvenile animals do not appear to be more sensitive than adult animals. F. International Tolerances Maxium residue levels (MRL) in oranges or processed fractions have not been established for CMNP in any country.