Docket # : EPA - HQ - OPP - 2009 - 0797

COMPANY NOTICE OF FILING EPA Registration Division contact: Sidney Jackson 703 -3 05 - 7 6 10 Interregional Research Project Number 4 PP 9E7577 EPA has received a pesticide petition PP 9E75 77 from the Interregional Research Project Number 4(IR- 4 ) in cooperation with C anyon Group LLC , c/o Gowan Comp any, 370 South Main Street, Yuma, Arizona 85364 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. 479 by establishing a tolerance for resid ues of halosulfuron - methyl in or o n the raw agricultural commodities pea and bean, succulent shelled subgroup 6B ; pea and bean, dried shelled, except soybean subgroup 6C ; vegetables, tuberous and corm subgroup 1C ; bushberry subgroup 13 - 07B ; apple ; rhubarb ; and okra at 0 . 0 5 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 metabolism of halosulfuron - m ethyl 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 applicati on. 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 degradatio n. In postemergent applications, little metabolism and translocation take place, resulting in unmetabolized parent compound as the major residue on the directly treated foliar surfaces. Very low residue levels of the metabolite 3 - chloro - 1 - methyl- 5 - sulfam oylpyrazole - 4 - carboxylic acid (3 - CSA) are found in grain. 2. Analytical method. A practical analytical method, gas chromatography with a nitrogen - specific detector, is available for enforcement purposes. The limit of detection is 0.003 ppm. 3. Magnitude of residues

. Samples from 13 apple trials, 6 blueberry trials, 4 rhubarb trials, 9 potato trials, 12 dry bean trials and 12 succulent pea trials were analyzed for halosulfuron and its metabolites. Samples from an additional apple trial treated a 5X the proposed rate were also analyzed. Combined r esidues were2

below 0.05 ppm in every sample . B. Toxicological Profile 1. Acute toxicity. Acute toxicological studies placed technical- grade halosulfuron - methyl in Toxicity Category III. The A gency 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 D NA 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. A developmental toxicity study in rats resulted in a developmental LOAEL of 750 mg/kg/day, based on decreases in mean litter size and fetal body weight and increases in resorptions, resorptions per dam, post- implantation loss and in fetal and litter incid ences of soft tissue and skeletal variations. The developmental NOAEL in this study was 250 mg/kg/day. The maternal LOAEL was 750 mg/kg/day, based on increased incidence of clinical observations, reduced body weight gains, and reduced food consumption an d food efficiency. The maternal NOAEL was 250 mg/kg/day. A developmental toxicity study in rabbits resulted in a developmental LOAEL of 150 mg/kg/day, based on decreased mean litter size and increases in resorptions, resorptions per dam and post- implantation loss. The developmental NOAEL was 50 mg/kg/day. The maternal LOAEL was 150 mg/kg/day, based on reduced body weight gain and reduced food consumption and food efficiency, and the maternal NOAEL was 50 mg/kg/day. A dietary 2 - generation reproduction s tudy in rats resulted in parental toxicity at 223 mg/kg/day in males and 261 mg/kg/day in females, based on decreased body weights, decreased body weight gains, and reduced food consumption during the premating period. Very light effects were noted in body weight of the offspring at this dose. This effect was considered to be developmental toxicity (developmental delay) rather than a reproductive effect. No effects were noted on reproductive or other developmental toxicity parameters. The systemic/devel opmental toxicity LOAEL was 223 mg/kg/day in males and 261 mg/kg/day in females; the systemic/developmental toxicity NOAEL was 50 mg/kg/day in males and 59 mg/kg/day in females. The reproductive NOAEL was greater than or equal to 223 mg/kg/day for males and 261 mg/kg/day for females. 4. Subchronic toxicity. A 90 - day feeding study in rats resulted in a NOAEL of3

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. 5. Chronic tox icity. 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 treatmentrelated 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. The Agency has derived a chronic PAD of 0.03 mg/kg/day based upon a NOAEL of 1 0 mg/kg/day in the dog study and an Uncertainty Factor of 300. 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 o f 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 t oxicity studies have shown that the metabolite 3 - CSA is of lower toxicity t han 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, h alosulfuron - methyl and all of its metabolites are h ydrolyzed 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 whethe r 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 reproductio n studies, which suggest that halosulfuron - methyl produces effects characteristic of the estrogen disruption. C. Aggregate Exposure 1. Dietary exposure. Tolerances have previously been established for residues in a variety of raw agricultural comm odities (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 d iscussed in FR 70 (168) 51615

– 51623 (August 31, 2005).4

i. Food. No detectable residues were observed in soybeans treated even at an exaggerated use rate. Therefore, the proposed use of halosulfuron - methyl on soybeans does not alter the Agency’s pr evious conclusions regarding risk resulting from dietary exposure. ii. Drinking water

. The Agency has not conducted a comprehensive dietary exposure analysis of halosulfuron - methyl in drinking water. The Agency, however, has estimated concentrations in surface water using the First Index Reservoir Screening Tool (FIRST) or the Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/EXAMS). Concentrations in ground water were estimated using the Screening Concentration in Ground Water Mod eling System (SCI - GROW). None of these models include s consideration of the impact of processing (dilution and treatment) of raw water. The Agency conservatively estimated maximum residues of 0.105 ppm in surface water and 0.000065 ppm in ground water. The use of halosulfuron - methyl on soybeans 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 + residential) MOE of less than 300. However, the Agency has previously calculated aggregate MOEs of 3,100 or greater. The proposed use of halosulfuron - methyl on soybeans does not alter the Agency’s previous calcul ations. Similarly, an intermediate - term aggregate risk assessment evaluates risks that are likely to result from exposures of 1 to 6 months. Again the same effect upon which endpoints were defined (decreased bodyweight gain) was observed across all route s of exposure, and the Agency’s level of concern for intermediate- term aggregate exposure is an MOE of less than 300 . The Agency has previously calculated an intermediate - term aggregate risk of 819 for the most highly exposed subgroup. Therefore, short- t erm and intermediate - term aggregate exposure is not of concern. 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 Determination5 1. U.S. population. The Agency has evaluated acute aggregate risk assessment only for females 13

– 50 years old. The Agency has calculated that exposure to this subpopulation occupies 1% of the aPAD. There is no indication that halosulfuron methyl could cause a dverse effects to the general population from a single dose. EPA previously concluded that chronic exposure occupies 3% of the cPAD for the general U.S. population, 8% for infants <1 year old and 4% for children 1 - 5. EPA previously concluded that interme diate - term aggregate exposure results in MOEs greater than 480 for all population subgroups, whereas the Agency’s Level of Concern is MOEs below 300. Halosulfuron - methyl is not carcinogenic. 2. Infants and children

. The Agency has not set a special FQ PA safety factor for infants and children. The Agency has concluded that an acute risk assessment for infants and children is not required. Short- term, i ntermediate - term and chronic exposure assessments for infants and children indicate that risk is b elow the Agency’s level of concern. Therefore, based on these risk assessments, the Agency has concluded that there is a reasonable certainty that no harm will result to the general population and to infants and children from aggregate exposure to halosulfuron - methyl residues. F. International Tolerances Mexico and Japan each has a Maximum Residue Level (MRL) of 0.05 ppm for halosulfuron - methyl on dry beans. Japan has also set provisional MRL s for halosulfuron - methyl of 0.02 ppm on apples, bluebe rries, peas and potatoes. There are no Canadian, Codex or EU MRLs for these commodities.