Document ID: EPA-HQ-OPP-2014-0574-0003
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2015-02-11T05:00Z

EPA REGISTRATION DIVISION - COMPANY NOTICE OF FILING FOR PESTICIDE PETITION

Docket ID Number: EPA-HQ-OPP-2014-0574

EPA Registration Division Contact: Sidney Jackson (703) 305-7610

Interregional Research Project Number 4 
Pesticide Petition Number: 4E8297
	EPA has received a pesticide petition number PP 4E8297 from Interregional Research Project Number 4 (IR-4), IR-4 Project Headquarters, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08450 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 by establishing a tolerance for residues of the herbicide halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidiny)amino] carbonylaminosulfonyl]-3-chloro-1-methyl-1H-pyrazole-4-carboxylate, including its metabolites and degradates, in or on the raw agricultural commodities Fruit, pome, Group 11 - 10 at 0.05 parts per million (ppm) and a tolerance with regional restrictions for Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F at 0.05 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 support granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

	1. Plant metabolism. The metabolism of halosulfuron-methyl as well as the nature of the residues in plants is adequately understood for the purposes of these tolerances.  Metabolism studies were conducted with three crops; field corn, sugarcane and soybeans.  Metabolism depends on the mode of application.  Pre-emergent applications result in rapid soil degradation of halosulfuron-methyl followed by crop uptake of the resulting pyrazole moiety.  The pyrimidine ring binds tightly to soil and is eventually converted to carbon dioxide by microbial degradation.  In post-emergent applications, little metabolism and translocation take place, resulting in un-metabolized parent compound as the major residue on the directly treated foliar surfaces.

	2. Analytical method. A practical analytical method, gas chromatography with a nitrogen-specific detector, is available for enforcement purposes. The analytical method accounts for parent halosulfuron-methyl and for the halosulfuron-methyl rearrangement ester, sometimes referred to as "RRE" and "MON 5781." This product results from the abstraction for the SO2NHCO moiety between the rings, such that the two rings are then joined together only by an NH group. In grapes, the limit of detection (LOD) and limit of quantification (LOQ) was 0.0073 ppm and 0.022 ppm, respectively. The LOD and LOQ in pears were 0.011 ppm and 0.032 ppm active ingredient, respectively.
	3. Magnitude of residues. Studies were conducted to determine the residues of halosulfuron in grapes were conducted in Ithaca, NY (EPA Region 1), Cream Ridge, NJ (EPA Region 2), Vale, NC (EPA Region 2), Prosser, WA (EPA Region 11) and Monroe, OR (EPA region 12).  The plots were treated with two banded applications to the ground (orchard floor) on each side of the grape row at a rate of approximately 0.047 lbs halosulfuron-methyl a.i./A per application at 12 (+/-2) day intervals. A non-ionic surfactant or crop oil concentrate was used in all applications. Grape fruit samples were collected 14(+/-1) days after application except at the NY16 site where samples were taken at 6 days after the last application due to rapid maturation of the fruit. The maximum residue of halosulfuron-methyl in grapes (both fruit and juice) was below the limit of quantitation of 0.05 ppm after a total application rate of approximately 0.094 halosufuron-methyl/A. 

The magnitude of residues on pear were conducted in North Rose, NY (EPA Region 1), Walnut Grove, CA (EPA Region 10), Parlier (EPA Region 10), Sunny Slope, ID (EPA Region 11, two trials), Moxee, WA (EPA Region 11) and Prosser, WA (EPA Region 11). The plots were treated with two banded applications to the ground (orchard floor) on each side of the grape row at a rate of approximately 0.047 lbs halosulfuron-methyl a.i./A per application at 14 (+/-1) day intervals at 14 (+/-1) days prior to harvest. A non-ionic surfactant or crop oil concentrate was used in all applications. Pear fruit samples were collected at 14 (+/_1) days after application. The maximum residue of halosulfuron-methyl in pears were below the limit of quantitation of 0.032 ppm after a total application rate of approximately 0.094 lb halosulfuron-methyl a.i./A.  

B. Toxicological Profile

      1. Acute toxicity.  Halosulfuron-methyl has low acute toxicity via the oral, 
dermal, and inhalation routes.  It is a non-irritant for skin and eyes and is not a dermal sensitizer.

      2. Genotoxicty. Carcinogenicity studies in rats and mice show no increase in treatment-related tumor incidence, and halosulfuron-methyl was classified as "not likely to be carcinogenic to humans." Halosulfuron-methyl is negative for mutagenicity in a battery of genotoxicity studies.  Bacterial and mammalian microsomal mutagenicity assays showed halosulfuron-methyl not to be mutagenic.  Gene mutation and chromosomal aberration studies were negative.  An unscheduled DNA test in primary rat hepatocytes was negative.  An in vivo mouse micronucleus assay did not cause a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow cells.

      3. Reproductive and developmental toxicity. Although the halosulfuron methyl data indicated an increase in qualitative susceptibility in fetuses following prenatal exposure in rats and rabbits, the developmental effects were seen in the presence of maternal effects and clear no-observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) were established for both maternal and developmental effects. In addition, the developmental effects in rats were seen at doses approaching the limit dose (1000 mg/kg). It was concluded that the degree of concern was low and there was no residual uncertainty in either the rat or rabbit developmental toxicity study. The Food Quality Protection Act (FQPA) safety factor was reduced to 1X.
      
	4. Subchronic toxicity. A 90-day feeding study in rats resulted in a NOAEL of 116 mg/kg/day in males and 147 mg/kg/day in females.  The LOAEL was 497 mg/kg/day for males and 640 mg/kg/day in females. Decreased body weight gain was observed in females in the subchronic oral toxicity study. In the rat and mouse, there was a decrease in body weight gains at high dose levels in short- and long-term oral and dermal studies. The results of both acute and subchronic neurotoxicity studies showed no neurotoxic effects. There was no quantitative evidence for increased susceptibility following pre- and/or post-natal developmental effects.

       5. Chronic toxicity. With repeated dosing, available data show that the dog is the most sensitive mammalian species.  In the dog, decreased body weight was seen in the chronic oral toxicity study.  Carcinogenicity studies in rats and mice show no increase in treatment-related tumor incidence, and halosulfuron-methyl was classified as "not likely to be carcinogenic to humans." 

	6. Animal metabolism. The Agency has determined that the nature of the residue in ruminants is adequately understood.  In the tissues and milk of goats, the major extractable residue was the non-metabolized parent compound.  The Agency has not required tolerances for residues in poultry.  In the rat metabolism study, parent compound was absorbed rapidly but incompletely.  Excretion was relatively rapid at all doses tested, and the majority of the radioactivity was eliminated in the urine and feces within 72 hours.  Fecal elimination was the result of unabsorbed parent compound.

	7. Metabolite toxicology. Various toxicity studies have shown that the metabolite 3-CSA is of lower toxicity than the parent compound, and the Agency has concluded that it should not be included in the tolerance expression.  However, in the residue analytical method for animal products, halosulfuron-methyl and all of its metabolites are hydrolyzed to 3-CSA, which is analyzed and the results expressed as parent equivalents.  The tolerance expression for plant commodities consists of only parent compound.

	8. Endocrine disruption. No specific tests have been conducted with halosulfuron-methyl to determine whether the chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other endocrine effects.  However, there were no significant findings in relevant toxicology studies; e.g., teratology and reproduction studies to suggest that halosulfuron-methyl produces effects characteristic of the estrogen disruption. Halosulfuron is not on the initial EPA screening list and a test order has not been issued.

C. Aggregate Exposure

	1. Dietary exposure. Tolerances have previously been established for residues in a variety of raw agricultural commodities (40 CFR 180.479).  Additionally, tolerances have been established for halosulfuron-methyl and its metabolites in the meat byproducts of cattle, goats, hogs, horses and sheep.   

      i. Food. Chronic Dietary Exposure. A chronic dietary analysis for 
halosulfuron-methyl was conducted by the Agency using tolerance levels and 100% CT for all existing uses on April 5, 2010.  The estimated drinking water concentrations EDWCs for surface water from EPA's Environmental Fate and Effects division (EFED), 59.2 parts per billion (ppb) based on modeled use on rice, was incorporated directly into the exposure analysis.  The drinking water estimate should be considered highly conservative.  The results of the analysis indicate that chronic risk from the dietary exposure to halosulfuron-methyl does not exceed EPA Health Effects Division (HED)'s level of concern (LOC) for the general U.S. population or any population subgroup.  The estimated risk for the general U.S. population is 2% of the chronic population adjusted dose (cPAD), and the highest exposure is to all infants (<1 year old) at 5% of the cPAD. The addition of residues in Fruit, pome, group 11-10 and Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F at the LOD or LOQ and, therefore would not be expected to contribute significantly to chronic dietary exposure.

Acute Dietary Exposure. An acute dietary exposure analysis for halosulfuron-methyl was conducted using tolerance-level residues and 100 percent crop treated (PCT) for all existing on April 5, 2010.  EDWCs from EFED (59.2 ppb based on modeled use on rice) were incorporated directly into the exposure analysis.  The only population with a toxicological endpoint attributable to a single dose of halosulfuron-methyl was females 13-49 years old.  The results of the analysis indicate that acute risk from the dietary exposure to halosulfuron-methyl is less than 1% of the acute population adjusted dose (aPAD) for females 13-49 years old, and therefore did not exceed HED's LOC.

	ii. Drinking water. Based on the First Index Reservoir Screening Tool (FIRST), Pesticide Root Zone Model / Exposure Analysis Modeling System (PRZM/ EXAMS)and Screening Concentration in Ground Water (SCI -GROW) models, the EDWCs of  halosulfuron methyl are Tier I  EDWCs based on a maximum annual application rate of  0.125 lb active ingredient ai/A. The seasonal use proposed on Fruit, pome, group 11-10 and Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F is 0.094 lb halosulfuron ai/A, well below the maximum annual rate used in the models derived for estimating drinking water concentrations. For acute and chronic dietary risk assessment, the water concentration value of 59.2 ppb was used to assess the contribution to drinking water.
	
2. Non-dietary exposure. Halosulfuron-methyl is registered for use on residential turfgrass and landscaped areas.  The short-term aggregate risk assessment estimates risks that are likely to result from exposures up to 30 days.  The same toxicological effect upon which endpoints were defined (decreased bodyweight gain) was observed across all routes of exposure.   The Agency's level of concern is a short-term aggregate (food, water and residential) MOE of less than 300.  However, the Agency has previously calculated aggregate MOEs of 3,100 or greater.  The proposed uses of halosulfuron-methyl on Fruit, pome, group 11-10 and Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F should have negligible effect on the Agency's previous calculations.

D. Cumulative Effects

	EPA has not made a common mechanism of toxicity finding regarding halosulfuron-methyl and any other substance.  Halosulfuron-methyl does not appear to produce a toxic metabolite that is produced by any other substance.  Therefore, for the purposes of this tolerance action, EPA has not assumed that halosulfuron-methyl has a common mechanism of toxicity with other substances.

E. Safety Determination

	1. U.S. population. Chronic dietary (food and drinking water) exposure to halosulfuron methyl is below EPA's level of concern for the general U.S. population and all population subgroups.  The Agency determined the chronic reference dose (RfD) for halosulfuron methyl at 0.1 mg/kg/day for all populations based on the chronic dog study NOAEL at 10/mg/kg/day and 100x uncertainty factor.  The chronic dietary exposure estimates are 2% of the cPAD for the general U.S. population and 5% of the cPAD for all infants (<1 year old), the most highly exposed population subgroup, much lower than the LOC at 100% of the cRfD.  

	2. Infants and children. In rat and rabbit developmental toxicity studies and a 2-generation reproduction toxicity study in rats there was no quantitative evidence for increased susceptibility following pre-natal and/or post natal exposure. In those studies, NOAELs/ LOAELs for halosulfuron developmental and maternal toxicities, and developmental effects were seen in the presence of maternal toxicity, and the effects were only seen at the high dose. Additionally, in rats, developmental effects were seen at a dose which is approaching the limit-dose. The degree of concern is low and there is no residual uncertainty for prenatal toxicity in both rats and rabbits.

F. International Tolerances

	FFDCA §408(b)(4) requires the Agency to consider international standards in establishing a tolerance.  There is no established Codex maximum residue level (MRL) specifically for Fruit, pome, group 11-10 and Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F.  However, a default MRL of 0.01 ppm has been maintained for apples. There is no Codex MRL for Fruit, pome, group 11-10 and Fruit, small vine climbing, except fuzzy kiwifruit, subgroup 13-07F (http://www.mrldatabase.com/results.cfm - retrieved 6/15/2013).