Document ID: EPA-HQ-OPP-2011-0781-0002
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2011-11-09T05:00Z

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

EPA Registration Division contact: Kable Davis at (703) 306-0415

Canyon Group LLC., c/o Gowan Company, 370 South Main St., Yuma, AZ 85364,

      EPA has received a pesticide petition 1F7916 from Canyon Group LLC., c/o Gowan Company, 370 South Main St., Yuma, AZ 85364 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 Halosulfuron-methyl, methyl 5-[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonylaminosulfonyl]-3-chloro-1-methyl-1H-pyrazole-4-carboxylate, and its metabolites and degradates in or on the raw agricultural commodities millet, proso, forage at 7.0 parts per million(ppm); millet, proso, hay at 0.02 ppm; millet, proso, grain at 0.01 ppm; millet, proso, straw at 0.01 ppm; grass forage, fodder, and hay, crop group 17, forage at 17.0 ppm; and grass forage, fodder, and hay, crop group 17, hay at 0.9 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 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, vis.; field corn, sugarcane and soybeans.  Metabolism depends on the mode of application.  Preemergent 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 postemergent applications, little metabolism and translocation take place, resulting in unmetabolized 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. The limit of detection is 0.003 ppm.

	3. Magnitude of residues. Studies were conducted to determine the residues of Yukon (halosulfuron plus dicamba) in proso millet and pasture and rangeland grasses in EPA Regions 1,2,5,6, and 11. Treated plots received one halosulfuron foliar post-emergence broadcast application at the early boot stage of grass. Grass raw agricultural commodity (RAC) forage samples were harvested at maturity 0 days after the application (DAA) and again at 6-7 days DAA.  Grass forage RAC samples were cut 23-37 DAA at typical growth stages for hay and allowed to dry.  Decline forage and hay samples were collected at one site.  The results from these trials show that after one application of at 0.0625 lb  ai/A (0.0701 kg ai/ha) residues of halosulfuron-methyl ranged from 3.06 to 11.2 ppm at 0 DAA and from 0.0252 to 4.89 ppm on forage samples collected 6-7 DAA. Residues of halosulfuron-methyl ranged from ND to 0.389 ppm hay samples collected 23-37 DAA.  The decline data indicate that halosulfuron-methyl residues do not increase with longer preharvest intervals.

B. Toxicological Profile

      1. Acute toxicity.  Acute toxicological studies placed technical-grade halosulfuron-methyl in Toxicity Category III.  The Agency has derived an acute PAD of 0.17 mg/kg based upon a rabbit developmental toxicity study.  The NOAEL was 50 mg/kg, and the Agency applied an Uncertainty Factor of 300 (10X for interspecies extrapolation, 10X for intraspecies variability and 3X due to the lack of a developmental neurotoxicity study.
         
	2. Genotoxicty. 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 NOAELs and 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 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. With repeated dosing, the available halosulfuron methyl 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 and 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. Halosulfuron-methyl has low acute toxicity by oral, dermal, and inhalation routes of exposure. It is not a dermal sensitizer nor is it an eye or skin irritant. The toxicity mode of action in mammals is undetermined. However, available data show that the dog is the most sensitive animal species. In the dog, decreased body weight was seen in the chronic oral toxicity study. In the rat and mouse, there was a decrease in body weight gains at high dose levels in short -term and long-term oral and dermal studies. 

A 1-year chronic oral toxicity study in dogs resulted in a LOAEL of 40 mg/kg/day based on decreased weight gain and a NOAEL of 10 mg/kg/day.  In a 78-week carcinogenicity study in mice, a LOAEL of 972 mg/kg/day was based upon decreased body weight gains and an increased incidence of microconcretion/mineralization in the testis and epididymis in males.  No treatment-related effects were observed in females.  The systemic NOAEL was 410 mg/kg/day, and the study showed no evidence of carcinogenicity.  A combined chronic and carcinogenicity study in rats resulted in a LOAEL of 108 mg/kg/day on males and 56 mg/kg/day in females.  The study showed no evidence of carcinogenicity.

	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 unmetabolized 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, which 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.   The Agency's exposure and risk assessments for these commodities were discussed in FR 70 (168) 51615  -  51623 (August 31, 2005).

	i. Food. Proso millet and crop group17 grass forage fodder and hay do not result in edible food commodities.

	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 estimated drinking water concentrations (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 proso millet is 0.0625 lb halosulfuron ai/A and for pasture/rangeland grasses is  0.313 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. The use of halosulfuron-methyl on proposed here does not alter the Agency's previous calculations.

	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 proso millet and pasture/rangeland grasses does not alter 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 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.
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F. International Tolerances

	FFDCA §408(b)(4) requires the Agency to consider international standards in establishing a tolerance.  While halosulfuron has tolerances in some international countries, there are no Codex MRLs for proso millet and pasture/rangeland grass commodities.