Document ID: EPA-HQ-OPP-2012-0177-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2012-05-23T04:00Z

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER
EPA Registration Division contact: Shaunta Hill, 703-347-8961, hill.shaunta@epa.gov.  
 Syngenta Crop Protection, LLC PP# 1F7956
EPA has received a pesticide petition (1F7956) from Syngenta Crop Protection, LLC, PO Box 18300, Greensboro, NC, 27419-8300 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to establish a tolerance for residues of cyproconazole in or on the raw agricultural commodities peanut nutmeat at 0.03 parts per million (ppm), peanut hay at 6 ppm, peanut meal at 0.03 ppm, peanut butter at 0.03 ppm, and peanut refined oil at 0.03 ppm.  EPA has determined that the petition contains data or information regarding the elements set forth in section 180.561 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. Syngenta believes the metabolism of cyproconazole as well as the nature of the residues in plants is adequately understood for purposes of the tolerances. Plant metabolism has been evaluated in five diverse crops, wheat, grapes, grapevine seedlings, apples and peanuts which should serve to define the similar metabolism of cyproconazole in a wide range of crops. The plant metabolism pathway for cyproconazole is well understood. Parent metabolite is the major compound found in crops. Comparison of the metabolism of cyproconazole in different plant species shows that the differences between the respective metabolic pathways to be quantitative in nature.

 Analytical method. An adequate analytical method for cyproconazole, AM-0842-0790-0, is available for enforcement purposes.  To summarize the method, 10-gram subsamples are hydrolyzed with 1N HCl for 1 hour at ~90 °C.  The hydrolysates are cooled to room temperature, homogenized with ethanol and centrifuged.  An aliquot of the clear extract is evaporated to the aqueous phase.  The aqueous extract is cleaned using reverse phase (C-18) solid phase extraction (SPE).  An aliquot of the resulting eluate are further purified using aminopropyl (NH2) solid phase extraction.  Determination and quantitation for cyproconazole are conducted using gas chromatography employing mass selective detection (MSD).  The limit of quantitation (LOQ) is 0.01 ppm for all substrates.
A method for analysis of Triazole metabolites is available using Morse Labs Analytical Method No. Meth-160, (MRID No. 46492901), Revision #2.
Residues are quantified by gas chromatography equipped with a nitrogen-phosphorous detector. The limit of quantitation (LOQ) is 0.01 ppm for cyproconazole parent. The analytical method, AM-0842-0790-0, is available in the Pesticide Analytical Manual, Vol. II.
 Magnitude of residues. Twelve successful peanut crop-field trials (1-FL, 2-SC, 2-NC, 3-GA, 3-TX, 1-VA) were conducted in the United States to support the use of a soluble-concentrate (SL) formulation containing the active ingredient cyproconazole. 

Two post foliar broadcast applications were made at a nominal rate of 5.5 oz product/acre per application (equivalent to 0.036 lb a.i. cyproconazole/acre per application).  An exaggerated rate (3X) of 16.5 oz product/acre per application (equivalent to 0.108 lbs a.i cyproconazole/acre per application) was also conducted for ancillary processing data.  All trials were performed utilizing a crop-oil concentrate (COC) or a non-ionic surfactant (NIS) adjuvant (applied 44 days prior to harvest and 30 days prior to harvest).

At each trial site, whole nut and hay samples were harvested from the same treated plot.  At one trial site, additional whole nut and hay samples were collected at 23, 30 (target PHI), 37 and 44 DALA to generate residue decline data.  At two trial sites, an exaggerated rate was employed to evaluate processing concentration factors.  Peanut meal, peanut butter and refined oil processed fractions were generated from whole nut pre-processing samples. 

Residues above the LOQ (Limit of Quantitation) were not found in any of the non-treated control samples of any peanuts matrix with the exception of triazole alanine in nutmeat.  The occurrence of triazole alanine in control samples has been observed in other residue studies and is attributed to the widespread use of the triazoles and the non-specific nature of the common moiety method of analysis.

Residues of the analytes were determined in or on all of the collected nutmeat and hay samples.  The residues of parent were all <0.01 ppm in nutmeat (30 days after last application) and ranged from 0.04-3.6 ppm in hay.  All degradates in nutmeat and hay, except triazole alaninc, were below or equal to 0.03 ppm.  Triazole alanine ranged from <0.15 to 2.0 ppm in nutmeat and  <0.02 to 0.21 ppm in hay.    

A general overview of the results from the decline trial, i.e. the change, if any, in residue levels as sampling time after the last application increased, are presented in the following table:

Analyte
                             Decline Trial Results

                               Nutmeat Residues
                           (23, 30, 37 and 44 DALA)
                     Hay Residues
(23, 30, 37 and 44 DALA)
 Cyproconazole Parent)
                                  No Residues
                                   Constant
1,2,4-Triazole 
                                  No Residues
                                  No Residues
Triazole Alanine
                                   Constant
                                   Decreased
Triazole Acetic Acid
                                   Constant
                                   Constant
DALA = Days after Last Application

Nutmeat samples at the target DALA of 30 days were processed into meal, refined oil and peanut butter.  The maximum (3X) residues of cyproconazole detected in processed commodities along with corresponding concentration factors are shown in below: 

           SUMMARY OF MAXIMUM RESIDUES IN PROCESSED PEANUT FRACTIONS
Peanut Processing = 3X Rate
                             Nutmeat Pre-Process  
                                  Peanut Meal
                              Peanut Oil, Refined
                                 Peanut Butter
Cyproconazole
Residue (ppm)
                                   <0.01
                                     0.01
                                   <0.01
                                   <0.01

Actual Concentration Factor
                                       
                                      NA
                                      NA
                                      NA
1,2,4-Triazole
Residue (ppm)
                                   <0.01
                                   <0.01
                                   <0.01
                                   <0.01

Actual Concentration Factor
                                       
                                      NA
                                      NA
                                      NA
Triazole Alanine
Residue (ppm)
                                     0.55
                                     1.95
                                   <0.01
                                   <0.25

Actual Concentration Factor
                                       
                                     3.5X
                                      NA
                                      NA
Triazole Acetic Acid
Residue (ppm)
                                     0.01
                                   <0.03
                                   <0.01
                                   <0.01

Actual Concentration Factor
                                       
                                      NA
                                      NA
                                      NA
Actual Concentration = residues in processed commodity / residues in raw commodity (e.g., 1.95/0.55= 3.5X).
NA = Not Applicable

The peanut magnitude of residue data supports the proposed tolerances for peanut nutmeat (0.03 ppm), peanut hay (6 ppm), peanut butter (0.03 ppm), peanut meal (0.03 ppm) and peanut refined oil (0.03 ppm).
B. Toxicological Profile
 Acute toxicity. Cyproconazole exhibits low toxicity. Data indicated the following: a rat acute oral LD50 of 350 mg/kg (females) (Cat II); a rabbit acute dermal LD50 >2,000 mg/kg (Cat III); a rat inhalation LC50 >5.6 mg/L (Cat IV); minimal skin irritant (Cat IV) and mild eye irritant (Cat III) in rabbits. Cyproconazole is not a skin sensitizer.
 Genotoxicty. Cyproconazole does not induce gene mutations in bacterial or mammalian cells in vitro. One in vitro chromosome aberration test in CHO cells revealed some evidence of a clastogenic effects, but this finding was not substantiated in a series of additional studies.  Cyproconazole was negative in two further in vitro chromosome aberration tests, and did not show evidence of aneugenic activity in yeast. In addition, it was negative in unscheduled DNA synthesis and SHE cell transformation assays. With in vivo testing, cyproconazole was negative in a dominant lethal assay, a mouse micronucleus assay and a bone marrow cytogenicity test.
 Reproductive and developmental toxicity.
   i. In a developmental toxicity study, pregnant female rats were gavaged withtechnical cyproconazole (95.6% purity) at levels of 0, 6, 12, 24, 48 mg/kg/day. The maternal NOAEL was 6 mg/kg/day, and the LOAEL was 12 mg/kg/day based on decreased body weight gain during dosing. The development NOAEL was 6 mg/kg and the development LOAEL was 12 mg/kg/day based on increased incidence of supernumerary ribs.
   ii. In a developmental toxicity study, pregnant female New Zealand White rabbits were gavaged with technical cyproconazole (94.8%) at levels of 0, 2, 10 and 50 mg/kg/day. The maternal NOAEL was 10 mg.kg/day and maternal LOAEL was 50 mg/.kg/day based on decrease body weight gains. The developmental NOAEL was 2 mg/kg/day and the developmental LOAEL was 10 mg/kg/day based on increased incidence of malformed fetuses, primarily at the high dose (50 mg/kg/day).
iii.   In a rat 2-generation reproduction study, technical cyproconazole (95.6% purity) was administered to 26 male and 26 female F0 and F1 rats per group for 10 and 12 weeks, respectively, during the pre-mating period via the diet at 0, 4, 20 or 120 ppm. Treatment of males continued for three weeks after termination of mating and females were treated until necropsy (post-weaning). The system NOAEL for parental toxicity was set at 20 ppm (1.7 mg/kg) based on liver effects at 120 ppm (10.6 mg/kg). For reproductive toxicity, the NOAEL was >120 ppm (>10.6mg/kg).
      4. Subchronic toxicity. 
      i. In a 90-day oral feeding study, rat were administered technical cyproconazole (95.7% purity) at levels of 0, 20, 80 and 320 ppm (0, 1, 4 and 16 mg/kg/day). Cyproconazole inhibited body weight gain, increased blood sodium, increased liver weights and produced histological changes in the liver at the high dose. Increased blood creatinine and decreased calcium levels were observed at the high and low dose, but not at the mid-dose. Effects were reversed after cessation of dosing and a four week recovery period. The NOAEL for this study was 20 ppm (1.5 mg/kg/day).
      ii. In a later 90-day oral feeding study, rat were administered technical cyproconazole (95.5% purity) at levels of 0, 20, 350, 700 and 1400 ppm (equivalent to 0/0, 1.4/1.6, 24.7/29.6, 52.8/57.3, and 106.8/118.1 mg/kg/day in males/females). The LOAEL was 350 ppm based on increased liver weight and increased incidence of liver hypertrophy in both sexes and increased incidence of liver fatty change in male. The NOAEL was 20 ppm, corresponding to a daily dietary intake of 1.4/1.6 mg/kg body weight in males/females.
      iii. A 13-week feeding study was conducted with dogs treated at 0, 20, 100 and 500 ppm technical cyproconazole (95.6% purity)in which the NOAEL was 20 ppm (0.8 mg/kg/day) and the LOAEL was 100 ppm (4 mg/kg/day) based on adverse liver effects. At the highest dose, treatment related changes also included slack muscle tone, depressed body weight gain, and significant differences in clinical chemistry and hematology parameters compared to controls.
      iv. In a 21-day dermal study, rabbits were exposed dermally to technical cyproconazole (95.6% purity) at doses of 50, 250, and 1250 mg/kg. The NOAEL was 250 mg/kg and the LOAEL was 1250 mg/kg. Effects included depressed body weight gain and food consumption and increased levels of AST, creatinine and cholesterol.
      5. Chronic toxicity. 
      i.	 In a 1-year chronic feeding study, dogs were fed a diet containing technical cyproconazole (95% purity) at levels of 0, 30, 100, or 350 ppm. A NOAEL of 30 ppm (1.0 mg/kg/day) and an LOAEL of 100 ppm (3.2 mg/kg/day) was attained based on liver effects.
      ii.	In a 2-year combined chronic feeding/carcinogenicity study, rats were administered technical cyproconazole (95.6% purity) at levels of 0, 20, 50 or 350 ppm (males: 0, 1.0, 2.2 and 15.6 mg/kg/day; females: 0, 1.2, 2.7 and 21.8 mg/kg/day) for 118 weeks (males) and 121 weeks (females). The NOAEL for systemic toxicity was 50 ppm and the LOAEL was 350 ppm based on decreased body weights in the high dose females and increased incidence of fatty infiltration of the liver in the high dose males. There was no evidence of carcinogenicity due to cyproconazole treatment in this chronic study in rats. EPA initially concluded that the dose levels were inadequate for the assessment of the carcinogenic potential of cyproconazole in the rat. Since then an additional 90-day feeding study in rats at higher dose levels was conducted to evaluate the advisibility of dosing at dose levels above 350 ppm in a chronic study. Evaluation of these studies against more recent guidance (2003 - 2005) on criteria for selection of an adequate top dose in a carcinogenicity study indicates that the top dose in the existing chronic/carcinogenicity study in rats was appropriate to assess the carcinogenic potential of cyproconazole.
      iii.	A mouse carcinogenicity study was conducted in which cyproconazole (95.1% purity) was administered in the diet at levels of 0, 5, 15, 100 or 200 ppm for 81 weeks (males) and 88 weeks (females). The NOAEL for systemic toxicity was 15 ppm (1.8 mg/kg for males and 2.6 mg/kg for females). The LOAEL was 100 ppm(13.2 mg/kg for males and 17.7 mg/kg for females) based on a significantly increased incidence of hepatic single cell necrosis and diffuse hepatocytic hypertrophy in both sexes. There was an increased incidence of liver adenomas and carcinomas in both sexes at dose levels of 100 and 200 ppm. The mode of action for cyproconazole-induced liver tumors in mice has been determined to be based on a non-genotoxic, receptor-mediated process that would not be operative at lower doses such as those at which humans could be exposed. Therefore, a non-linear reference dose approach to chronic as well as cancer risk assessment is appropriate cyproconazole.
      6. Animal metabolism. The absorption, distribution, excretion and metabolism of cyproconazole in rats, goats and hen were investigated. Cyproconazole was shown to be well absorbed and extensively metabolized in the rat. The elimination from most tissues occurred relatively rapidly with the majority of radioactivity appearing in the feces as a result of biliary elimination.
      7. Metabolite toxicology. The primary residue of concern was cyproconazole parent.  Cyproconazole is a triazole fungicide. The Agency does have concern about potential toxicity to 1,2,4-traizole and two conjugates, triazole alanine and triazolyl acetic acid, metabolites common to most of the triazole fungicides.  EPA will be conducting a human health assessment for aggregate exposure to 1,2,4-triazole and for aggregate exposure to the two conjugates.
      8. Endocrine disruption. There is no indication from the mammalian toxicology database for any endocrine disrupting effect of cyproconazole. A Cyproconazole immunotox study is being scheduled around the lab capacity resources of the contract labs to fulfil the new 40 CFR Part 158 guideline requirement.  
  C. Aggregate Exposure
      1. Dietary exposure.   Tier I acute, short-term and chronic risk assessments were performed for the fungicide cyproconazole (1H-1,2,4-triazole-1-ethanol, alpha-(4-chlorophenyl)-alpha-(1-cyclopropylethyl)-) using the Dietary Exposure Evaluation Model (DEEM-FCIDTM, version 2.16) from Exponent. These exposure assessments include all current and pending uses plus a proposed use on peanuts.  Current MRLs were used for meat, milk, and egg commodities.  Percent of crop treated values were conservatively estimated to be 100% for all uses.  Estimated drinking water concentrations (EDWCs) were incorporated directly into the dietary exposure assessments; since the surface water EDWCs exceed the ground water EDWC, the surface water values were used.  All consumption data for these assessments was taken from the USDA's Continuing Survey of Food Intake by individuals (CSFII) with the 1994-96 consumption database and the Supplemental CSFII children's survey (1998) consumption database.  
      i. Food.  
Acute Exposure:     The cyproconazole acute dietary (food only) risk assessment was performed using an acute reference dose (aRfD) of 0.02 mg/kg-bw/day (females 13 to 50 years old), based upon a developmental toxicity study in New Zealand White rabbits, with a no observed adverse effect level (NOAEL) of 2.0 mg/kg/day and an uncertainty factor of 100X.  The 100X safety factor includes intra- and inter-species variations.  No additional FQPA safety factor was applied.  For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure.  In addition, exposure was also expressed as a percent of the acute reference dose (%aRfD).  At the 95th percentile, acute (food only) exposure for females 13 - 49 years old resulted in a MOE of 4,272 or 2.3% of the aRfD (Benchmark MOE = 100; aRfD = 0.02 mg/kg-bw/day).  The aRfD for the general population, including infants and children, was not established since an endpoint of concern attributable to a single dose was not identified (Registration #05MN14, "Section 18 Quarantine Exemption for the Application of Cyproconazole to Soybeans," DP#318617, US EPA, OPPTS, 27-Sept- 2005).  Since the benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark MOE or below 100% of the aRfD, Syngenta believes that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from all current, pending and proposed uses of cyproconazole.

Chronic exposure:     The cyproconazole chronic dietary (food only) risk assessment was performed for all population subgroups using a chronic reference dose (RfD) of 0.01 mg/kg-bw/day, based upon a chronic feeding study in dogs with a no observed adverse effect level (NOAEL) of 1.0 mg/kg/day and an uncertainty factor of 100X.  The 100X safety factor includes intra- and inter-species variations.  No additional FQPA safety factor was applied.  For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup.  In addition, exposure was expressed as a percent of the chronic reference dose (%RfD).  Chronic (food only) exposure to the U.S. population resulted in a MOE of 3,069 or 3.3% of the cRfD (Benchmark MOE = 100; cRfD = 0.01 mg/kg-bw/day).  The most exposed subpopulation was children (1-2 years old) with a MOE of 877 or 11.4% of the cRfD (Benchmark MOE = 100; cRfD = 0.01 mg/kg-bw/day).  Since the benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures above the benchmark MOE or below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from all current, pending and proposed uses for cyproconazole.
ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of cyproconazole were determined using Tier l SCI-GROW which estimates pesticide concentration in ground water and Tier II PRZM/EXAMS which estimates pesticide concentration in surface water.  EDWCs of cyproconazole from the currently registered uses plus the proposed use on peanuts were determined.   For ground water, the currently registered use on roses provided the highest EDWC of 2.65 ppb (acute and chronic).  For surface water, the currently registered use on roses provided the highest EDWCs of 60.579 ppb for acute and 55.285 ppb for chronic.  Since the surface water EDWCs exceed the ground water EDWC, the surface water values were used for risk assessment purposes and will be considered protective for any ground water exposure concerns.  
Acute Exposure from Drinking Water:  The acute surface water EDWC of 60.579 ppb was input directly into the DEEM-FCID(TM) software as "water, direct and indirect, all sources" to model the acute drinking water exposures.  Exposure contributions at the 95th %-ile of exposures were determined by taking the difference between the aggregate (food + drinking water) exposures and the food (alone) exposures for each population subgroup.  Acute drinking water exposure for females 13-49 years, the only sub-group for which an endpoint is available, resulted in a MOE of 724 or 13.8% of the aRfD (Benchmark MOE = 100; aRfD =0.02 mg/kg-bw/day).  Since the benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures above the benchmark MOE or below 100% of the aRfD, Syngenta believes that there is a reasonable certainty that no harm will result from acute drinking water exposure to residues arising from the current and proposed uses for cyproconazole.

Chronic Exposure from Drinking Water:  The chronic surface water EDWC of 55.285 ppb was input directly into the DEEM-FCID(TM) software as "water, direct and indirect, all sources" to model the chronic drinking water exposures.  Chronic drinking water exposure to the U.S. population resulted in a MOE of 858 or 11.7% of the cRfD (Benchmark MOE = 100; cRfD = 0.01 mg/kg-bw/day).  Chronic drinking water exposure to the most exposed subpopulation (infants, <1 year old) resulted in a MOE of 262 or 38.2% of the cRfD (Benchmark MOE = 100;  cRfD = 0.01 mg/kg-bw/day).  Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures above the benchmark MOE or below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from the current and proposed uses for cyproconazole.

	Cancer.  Cyproconazole has been classified as "not likely to be a human carcinogen" based on the revised Cancer Guidelines.  Therefore, no cancer risk assessment was performed for cyproconazole.
  
iii. Non-dietary exposure. Cyproconazole is a broad spectrum fungicide that can be used in recreational (golf course) settings.  There is a potential for post-application residential exposure to adults and youths playing golf on treated turf. The cyproconazole non-dietary risk assessment was performed using a short-term dermal endpoint of 10 mg/kg-bw/day, based upon a NOAEL from a 28 day dermal rat study and an uncertainty factor of 100X for intra- and inter-species variability; no additional FQPA safety factor was applied.  For the purpose of the aggregate risk assessment, exposure values were expressed in terms of margin of exposure (MOE), calculated by dividing the 10 mg/kg-bw/day endpoint by the exposure for each population subgroup.  The most exposed population subgroups from the non-dietary (residential) assessments was for adults (20-49 years old) and youths (13-19 years old)  attributable to short-term dermal post-application exposures, with MOEs of 243 and135, respectively.  Since the benchmark MOE for this assessment was 100 and since EPA generally has no concern for non-dietary exposures above the benchmark MOE, Syngenta believes that there is a reasonable certainty that no harm will result from non-dietary exposures from all current residential uses for cyproconazole.
 D. Cumulative Effects
Cumulative Exposure to Substances with a Common Mechanism of Toxicity.  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".  An ongoing series of studies being conducted by the U.S. Triazole Task Force (USTTF) are designed to provide the Agency with more complete toxicological and residue information for 1,2,4 triazole and two conjugates, triazolylalanine and triazolyl acetic acid, metabolites common to most of the triazole fungicides.  Upon completion of review of those data, EPA will prepare a more sophisticated assessment based on the revised toxicological and exposure databases.  For the purposes of this tolerance action, the EPA has not assumed that difenoconazole has a common mechanism of toxicity with other substances.

 E. Safety Determination
 US. Population. The acute dietary exposure analysis (food plus water) showed that exposure from all current, pending and proposed cyproconazole uses would result in a MOE of 619 or 16.2 % of the aRfD (Benchmark MOE = 100; aRfD = 0.02 mg/kg-bw/day) for females 13 - 49 years old, which exceeds the benchmark MOE of 100.  An aRfD for the general population, including infants and children, was not established since an endpoint of concern attributable to a single dose was not identified.  The chronic dietary exposure analysis (food plus water) showed that exposure from all current, pending, and proposed cyproconazole uses resulted in a MOE of 671 or 14.9 % of the cRfD (Benchmark MOE = 100; cRfD = 0.01 mg/kg-bw/day) for the general U.S. population, which also exceeds the benchmark MOE of 100.  The short-term aggregate exposure analysis (food plus water plus non-dietary residential exposures) showed that exposure from all established and proposed uses of cyproconazole resulted in a MOE of 235 for adults 20-49 years old, which exceeds the benchmark MOE of 100.  Based on the completeness and reliability of the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current, pending, and proposed uses of cyproconazole.

      2. Infants and children.  An acute reference dose (aRfD) for infants and children was not established, since an endpoint of concern attributable to a single dose was not identified.  The chronic aggregate dietary (food plus water) exposure analysis showed that exposure from all current, pending, and proposed cyproconazole uses would result in a MOE of 234 or 42.8 % of the cRfD (Benchmark MOE = 100; cRfD = 0.01 mg/kg-bw/day)for the most sensitive subpopulation, infants <1 year old, which exceeds the benchmark MOE of 100.  The short-term aggregate exposure analysis (food plus water plus non-dietary residential exposures) showed that exposure from all established and proposed uses of cyproconazole resulted in a MOE of 133 for youth 13-19 years old, which exceeds the benchmark MOE of 100.  Based on the completeness and reliability of the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure to residues arising from all current, pending, and proposed uses of cyproconazole.

F. International Tolerances
There are currently no Maximum Residue Limits (MRLs) set for cyproconazole for crops by the Codex Alimentarius Commission.  International MRLs for the fungicide cyproconazole have been established for crops including soybeans, corn, wheat, leafy vegetables, and coffee in a number of countries including Argentina, Australia, Brazil, China, France, Germany, Hungary, Italy, Japan, South Africa, and Spain.