Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 1 of 37 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460 **OFFICE OF CHEMICA**  **L SA FETY**  **AND POLLUTION PREVENTION**  **MEMORANDUM Date**  **:** March 25, 2013 **SUBJECT: Halosulfuron**  **- Methyl**  : Human Health Risk Assessment for Proposed New Uses on Artichoke and Caneberry ( Crop subgroup 13 - 07A) **PC Code:** 128721 **DP Barcode:** D404095 **Decision No.:** 465913 **Registration No. :**  8 1880 - 15 , 81880 - 18, 81880 - 2 **Petition No .:**  2E8050 **Regulatory Action:** Section 3 Registration **Risk A**  **ss essment Typ**  **e :**  Single Chemical/Aggregate **Case No.: NA**  **T XR No.:**  **NA CAS No.:**  10078 4 - 20 - 1 **MRID No.: NA**  **40 CFR:** 180.479 **FROM:** Sheila Heal y, Risk Assessor

Meheret Negussie, Chemist Nancy Tsaur, Chemist, ORE Assessor Risk Assessment Branch 3 Health Effects Division (7509P) **THROUGH:** Chri stine Olinger, Branch Chief

Risk Assessment Branch 3 Health Effects Division (7509P) **TO:** Barbara Madden/ Sidney Jackson (RM 05)

Risk Integration, Minor Use & Emergency Response Branch Registration Division (7505P)Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 2 of 37 **1.0 Executive Summary**  ................................ ................................ ................................ ........... 4 **2.0 HED Recommendations**  ................................ ................................ ................................ .... 7 **2.1 Da**  **ta Deficiencies** ................................ ................................ ................................ ............ 7 **2.2 Tolerance Considerations**  ................................ ................................ .............................. 7 **2.2.1 Enforcement Analytical Method**  ................................ ................................ ............... 7 **2.2.2 International Harmonization**  ................................ ................................ ..................... 7 **2.2.3 Recommended Tolerances**  ................................ ................................ ......................... 7 **2.2.4 Revisions to Petitioned**  **- For Tolerances**  ................................ ................................ .... 8 **2.3 Label Recommendations**  ................................ ................................ ................................ 8 **3.0 Introduction**  ................................ ................................ ................................ ........................ 8 **3.1 Chemical**  **Identity** ................................ ................................ ................................ ........... 9 **3.2 Physical/Chemical Characteristics**  ................................ ................................ ............... 9 **3.3 Pesticide Use Pattern**  ................................ ................................ ................................ ...... 9 **3.4 Anticipated Exposure Pathways**  ................................ ................................ ................. 10 **3.5 Consideration of Environmental Justice**  ................................ ................................ .... 11 **4.0 Hazard Characterization and Dose**  **- Response Assessment**  ................................ .......... 11 **4.1 Summary of Toxicological Effects**  ................................ ................................ .............. 11 **4.2 Safety factor for Infants and Children (FQPA Safety Factor)**  ................................ 12 **4.2.1 Completeness of the Toxico**  **logy Database** ................................ .............................. 12 **4.2.2 Evidence of Neurotoxicity**  ................................ ................................ ........................ 13 **4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal**  ........ 13 **4.2.4 Residual Uncertainty in the Exposure Database**  ................................ ................... 13 **4.3 Toxicity Endpoint and Point of Departure**  **Selections** ................................ .............. 14 **5.0 Dietary Exposure and Risk Assessment**  ................................ ................................ ......... 16 **5.1 Residues of Concern Summary and Rationale**  ................................ .......................... 16 **5.2 Food Residue Profile**  ................................ ................................ ................................ .... 16 **5.3 Water Residue Profile**  ................................ ................................ ................................ .. 17 **5.4 Dietary Risk Assessment**  ................................ ................................ .............................. 17 **5.4.1 Description of Residue Data Used in Dietary Assessment**  ................................ .... 17 **5.4.2 Percent Crop Treated Used in Dietary Assessment**  ................................ .............. 17 **5.4.3 Acute Dietary Risk Assessment**  ................................ ................................ ............... 18 **5.4.4 Chronic Dietary Risk Assessment**  ................................ ................................ ........... 18 **5.4.5 Cancer Dietary Risk Assessment**  ................................ ................................ ............. 18 **5.4.6 Summary Table**  ................................ ................................ ................................ ......... 18 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  ............................. 20 **6.1 Residential Handler Exposure**  ................................ ................................ .................... 20 **6.2.1 Post**  **- Application Exposure**  ................................ ................................ ...................... 21 **6.3 Combined Exposure**  ................................ ................................ ................................ ..... 21 **6.4 Residential Bystander Postapplication Inhalation Exposure**  ................................ ... 22 **6.5 Spray Drift**  ................................ ................................ ................................ .................... 22 **7.0 Aggregate Exposure/Risk Characterization**  ................................ ................................ .. 23 **7.1 Acute Aggregate Risk**  ................................ ................................ ................................ ... 23 **7.2 Short**  **- Term Aggregate Risk**  ................................ ................................ ........................ 23 **7.3 Intermediate**  **- Term Aggregate Risk**  ................................ ................................ ........... 24 **7.4 Chronic Aggregate Risk**  ................................ ................................ .............................. 24 **7.5 Cancer Aggregate Risk**  ................................ ................................ ................................ 24Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 3 of 37 **8.0 Cumulative Exposure/Risk Characterization**  ................................ ............................... 24 **9.0 Occupational Exposure/Risk Characterization**  ................................ ............................ 24 **9.1 Short**  **- and Intermediate**  **- Term Handler Risk**  ................................ ........................... 24 **9.2 Short**  **- and Intermediate**  **- Term Post**  **- Application Risk**  ................................ ............. 28 **9.2.1 Dermal Postapplication Risk**  ................................ ................................ ................... 28 **9.2.2 Inhalation Postapplication Risk**  ................................ ................................ .............. 28 **10.0 References**  ................................ ................................ ................................ ......................... 28 **Appendix A. Toxicology Profile and Executive Summaries** ................................ .................. 30 **A.1 Toxicology Data Requirements**  ................................ ................................ ................... 30 **A.2 Toxicity Profiles**  ................................ ................................ ................................ ............ 31 **Appendix B. Physical/Chemical Properties** ................................ ................................ ............. 35 **Appendix C. Review of Human Research** ................................ ................................ ................ 36 **Appendix D. International Residue Limits** ................................ ................................ .............. 37Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 4 of 37 **1.0 Executive**  **Summary** On behalf of Canyon Group L .L .C. , c/o Gowan Company , the Interregional Research Project No. 4 (IR - 4) of Rutgers University is proposing to add new uses of the active ingre dient (ai), halosulfuron - methyl on caneberry (subgroup 13 - 07A) and artichoke . Halosulfuron - methyl is a sulfonylurea herbicide which inhibits the plant enzy me acetolacetate s ynthase and is used for pre - and post - emergent control of annual broadleaf weeds and nutsedges in several agricultural crops as well as residential turf grass and ornamentals . The most recent risk assessment for halosulfuron - methyl was conducted in 20 12 for uses on Proso Millet and Crop Group 17, Grass, Forage, Fodder, and Hay (D396458, C. Walls , 07/19/12 ). Inaccordance with the 2007 revised 40 CFR Part 15 8 Toxicology data requirements, an i mmunotoxicity

study and a subchronic i nhalation toxicity study are required for halosulfuron methyl. However, HED has waived the inhalation toxicity study data requirement at this time (TXR0054045). Pending submissio n of an anal ytical standard for the rearrangement ester ( RRE ) of halosulfuron methyl, there are no additional toxicology or residue chemistry

issues that would preclude granting unconditional registration for the requested uses of halosulfuron - methyl on caneberry subgroup 13 - 07A and artichoke . Proposed Use Profile Halosulfuron - methyl is formulated as a water dispersible granule (WG) and applied as postemergence broadcast foliar spray s using ground equipment only for caneberries and artichoke s . Application through any type of irrigation system is prohibited. Halosulfuron methyl may

be applied to artichoke at a maximum seasonal application rate of 2 oz/A (0.094 lb ai/A) ; the label does not specify maximum applications per season . For caneberry , halosulfuro n methyl may

be applied twice per season at a maximum annual application rate of 2 oz/A (0.094 lb ai/A). The restricted entry interval (REI) is 12 hours. These new uses are proposed to be added to two end - use product (EP) labels: Sandea® Herbicide (EPA Reg. No. 81880 - 18) with 75% ai by weight and GWN - 3061 Herbicide (EPA Reg. No. 81880 - 2) with 75% ai b y weight. Exposure Profile Based on application rate and label information, exposure to halosulfuron methyl is expected to occur for acute - , s hort - , intermediate - term exposures . Chronic exposure (other than dietary) is not expected for the proposed use patterns. The proposed agricultural use s on caneberry and artichoke would result in new dietary exposures in both food and drinking water. Th ere are also existing residential uses that would result in non - occupational exposure from handler and post application activities. In occupational settings, exposure is also expected during handler activities for proposed uses . Toxicity/Hazard Halosul furon - methyl has low acute toxicity via the oral (Toxicity

Category IV), dermal (Toxicity Category I II ), and inhalation (Toxicity Category IV) routes. Halosulfuron - methyl is a non -Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 5 of 37 irritant for skin and eyes (Toxicity Category IV) and is not a dermal sensi tizer. With repeated dosing, halosulfuron - methyl produces non - specific effects, which are frequently characterized by reduced body weight/body weight gain in the test animals. Inthe prenatal developmental toxicity study in rats, increases in resorptions , soft tissue (dilation of the lateral ventricles) and skeletal variations, and decreases in body weights were seen in the fetuses compared to clinical signs and decreases in body weights and food consumption in the maternal animals at a similar dose level . In the rabbit developmental toxicity study , increases in resorptions and post implantation losses and decrease in mean litter size were seen in the presence of decreases in body weight and food consumption in maternal animals were observed. However, a clear No Observable Adverse Effect Level (NOAEL ) for these effects was established in both rat and rabbit developmental toxicity studies. Halosulfuron - methyl did not produce reproductive effects. No neurotoxic effects were observed in the acute or subchronic neurotoxicity studies. Halosulfuron - methyl is classified as “not likel y to be carcinogenic to humans.” It is negative for mutagenicity in a battery

of genotoxicity

studies. The toxicology

database is adequate, with the exception of the requirement for an immunotoxicity

study . The requirement for a subchronic i nhalation toxicity study has been waived. The toxicity

endpoints and poi nts of departure (POD) for risk assessment were selected for the following exposure scenarios: acute and chronic dietary , short - and intermediate - term incidental oral , dermal and inhalation . A summary of toxicity

endpoints and points of departure is presented in Table 4.3.1. Because of a common effect ( i.e., body weight gain changes ) seen in the studies selected for the endpoints for all three routes of exposure, Margins of Exposure (MOE s ) and exposures can be combined where appropriate. The level of conc ern (LOC) for residential and occupational exposures via dermal and inhalation routes is a MOE less than 100. The Food Quality

Protection Act ( FQPA ) safety factor is 1X. Dietary Exposure (Food and W ater) and Risk Estimates The residue chemistry

data and environmental fate data are adequate to assess human exposure. There was no indication of an adverse effect attributable to a single dose for the general U.S. population. However, an acute reference dose (aRfD) was establis hed for females 13 - 49 years old. Conservative acute and chronic dietary exposure assessment s were performed for halosulfuron - methyl using tolerance - level residues and 100% crop treated . The estimated drinking water concentration (EDWC) for rice was 59.2 μ g/L and used directly in both the acute and chronic assessments. For all processed commodities, the Dietary Exposure Evaluation Model ( DEEM ) version 7.81 default processing factors were assumed. The results of the acute and chronic dietary

(food and dri nking water) analy ses are below the Agency ’s level of concern (LOC) for the general U.S. population and all population subgroups. The acute dietary (food and drinking water) exposure is estimated at <1 % of the acute Population Adjusted Dose (aPAD) for the females 13 - 49 years old. The dietary (food and drinking water) exposure is estimated at 2 % of the c hronic Population Adjusted Dose (cPAD) for the general U.S. population and 5.5 % of the cPAD for children 1 - 2 years old , the population subgroup with the h ighest estimated chronic dietary exposure to halosulfuron - methyl . Halosulfuron - methyl is classified as “not likely to be carcinogenic to humans;” therefore, cancer risk was not quantitatively assessed.Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 6 of 37 Residential Exposure and Risk Estimates There are no proposed residential uses at this time; however, there are existing residential turf use s that have been reassessed to reflect updates to HED’s 2012 Residential SOPs along with policy changes for body

weight assumptions. Short - term combined ( dermal + inhalation) residential handler MOEs range from 7,200 to 190,000 and, therefore , are not of concern. Short term post - application MOEs for all residential scenarios range from 1,000 to 11,000,000 and, likewise , are not of concern. Residential Agg

regate Exposure Risk Estimates There is potential for short - term aggregate exposure to halosulfuron methyl via the dietary (which is considered background exposure) and residential (which is considered primary) pathway s. All aggregate MOEs are greater than 100, which indicates that exposure and risk do not exceed HED’s LOC. The adult and children short - term aggregate (dietary + residential) MOEs are 1,800 and 840 , respectivel y. Intermediate - term and chronic aggregate risk are expected to be equivalent to chronic exposure via the dietary pathway . Occupational Exposure and Risk Estimates Agricultural Handlers: There is potential for short - and intermediate - term occupational exposure to halosulfuron - methyl during handling activities (e.g. mixing, loading, application). All handler scenarios result in MOEs greater than the LOC (MOEs ≥ 100) at baseline or with recommended PPE . For artichoke , the baseline short - term combined (dermal + i nhalation) MOEs range from 650 to 14 ,000 ; for caneberry , MOEs range from 650 to 48,000 . For artichoke, the baseline intermediate - term combined (dermal + inhalation) MOEs range from 88 to 1,800; for caneberry , MOEs range from 88 to 6,400. At baseline, the handheld equipment (mechanicall y- pressurized handgun) results in an MOE of 88 for both caneberry and artichoke. However, with recommended PPE of gloves, the MOE increases to 290 . Agricultural Post - application: There is no potential for dermal or inhalation short - and intermediate - term occupational exposure during post - appli cation activities based on the proposed use pattern for artichokes and caneberries . Based on the Agency's current practices, a quantitative non - cancer occupational post - application inhalation exposure assessment was not performed for halosulfuron - methyl at this time. If new policies or procedures are put into place, the Agency

may revisit the need for a quantitative occupational post - application inh alation exposure assessment for halosulfuron - methyl . Environmental Justice Considerations Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment . Dietary and non - dietary

exposures were considered. Review of Human Research This risk assessment relies in part on data from studies in whi ch adult human subjects were intentionally

exposed to a pesticide or other chemical. These studies (listed in Appendix C) have been determined to require a review of their ethical conduct, and one of these studies is also subject to review b y the Human Studies Review Board. All of the listed studies have received the appropriate review.Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 7 of 37 **2.0 HED**  **Recommendations** Provided an anal yt ical reference standard for the RRE of halosulfuron - methyl is submitted , HED recommend s granting an unconditional registration for the requested use of halosulfuron - methyl on artichoke and caneberry . Additional data are needed prior to the registration as outl ined in Section 2.1 below. T olerance recommendation s are discussed in Section 2.2. There are no label modi fications recommended for the proposed new uses. **2.1 Data Deficiencies**  860.1650 Submittal of Analy tical Reference Standards

 An anal ytical reference standard for the rearrangement ester (RRE) of halosulfuron methyl must be submitt ed to the EPA National Pesticide Standards Repository . 875.2100 S ubmittal of Turf Transferable Residue (TTR)

 A TTR study

is required for halosulfuron - methyl at this time since the dermal MOE for children 1 to < 2 years old is less than 10 times the LOC of 100 (MOE = 960), based on default values for the fraction of application rate available for transfer after a turf application (DP404839, N. Tsaur, 02/21/2013) . **2.2 Tolerance Considerations**  **2.2.1 Enforcement An**  **alytical Method** An adequate anal yt ical method is available for enforcement of tolerances for halosulfuron methyl residues in plants. The gas chromatography (GC) method quantifies halosulfuron - methyl as its rearrangement ester (RRE; 1 -H - py razole - 4 - carbox ylic acid, 3 - chloro - 5 - [(4,6 - dimethoxy- 2 - py rimidinyl)amino] - 1 - methyl, methyl ester) using thermionic - specific detection (TSD, nitrogen specific). Monsanto Analy tical Method RES - 109 - 97 - 4 (MRID 44495801) has been validated as an enforcement method by the Anal ytical Chemistry Branch (ACB)/Biological and Economic Analy sis Division ( BEAD ) . The limit of quantitation on rice straw, sugarcane, milo grain, field corn grain, cotton gin b yproducts, and almond nutmeats was estimated to be 0.05 ppm (DP#250584, G. Jeffre y Herndon, 10/28/98). For confirmation, the RRE can be determined b y GC/MS with monitoring at m/z 327. Residues of halosulfuron - methyl and 3 - CSA are not recoverable b y the FDA Multiresidue Protocols. **2.2.2 International Harmonization**  There are currently

no Codex or Canadian maximum residue limits (MRL s) established for residues of halosulfuron - methyl in/on any commodity . **2.2.3 Recommended Tolerances** Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 8 of 37 HED has examined the residue chemistry database for halosulfuron - methyl. Pending submission of a reference standard for the RRE of halosulfuron - methyl (see requirements under Submittal of Analy tical Reference Standards), there are no residue chemistry iss ues that would preclude granting a Section 3 registration for the requested uses on artichoke and caneberry, or the establishment of a tolerance for residues of the halosulfuron - methyl, methyl 3 - chloro - 5 - [[[[(4,6 - dimethoxy- 2 - p yrimidinyl )amino]carbonyl ] - ami no]sulfonyl] - 1 - methyl - 1 H - py razole - 4 - carbox yl ate , including its metabolites and degradates, in/on the commodities below. Compliance with the tolerance levels specified is to be determined by measuring onl y halosulfuron - methyl. **Table 2.2.3**  **. Tolerance Summ**  **ary for Halosulfuron**  **- Me**  **thyl Comm**  **odity Established/Prop**  **osed Tolerance (ppm)**  **Recommended**

**Tolerance (ppm) Comments** 

**Correct Commodity Definition** Artichoke 0.05 0.05 Caneberry subgroup 13 - 07A 0.05 0.05 **2.2.4 Revisions to Petitioned**  **- For Tolerances**  There are no revisions to the tolerance petition (Table 2.2.3). **2.3 Label Recommendations**  The labeled use pattern for caneberries must be clarified (for both products EPA Reg. No. 81880 - 2 and EPA Reg. No. 81880 - 16). The proposed labels indicate that aerial a pplication is just for corn, sorghum, and rice, but the specific use directions/limitations of caneberries do not explicitly state : “Do not apply

by air.” This statement must be added on both labels in the caneberry section. **3.0 In**  **troduction** Halosulfuro n - methyl is a selective herbicide belonging to the sulfonylurea group of herbicides. It inhibits the action of the plant enzy me acetolactate sy

nthase. The enzy

me is not found in mammals (including humans). Halosulfuron - methyl is used for the pre - and postemergence control of annual broadleaf weeds and nutsedges in selected crops, residential turfgrass, and ornamentals. Permanent tolerances are established for a variety of field, fruit, vegetable crop, and livestock commodities under 40 CFR §180.479 at levels ranging from 0. 01 to 20 ppm. Halosulfuron - methyl is sold in the US as dry flowable/water - dispersible granule formulations or as emulsifiable concentrates. The petitioner, IR - 4 on behalf of Canyon Group LLC (agent Gowan Company) has submitted a request for amended registration of two 75% WG formulations (Sandea Herbicide, EPA Reg. No. 81880 - 18, and GWN - 3061, EPA Reg. No. 81880 - 2) for use on artichoke and caneberry . The proposed uses reflect ground application to caneberry at 0.024 - 0.094 lb ai/A or to artichoke at 0.047 - 0.094 lb ai/A . The propose d postharvest intervals ( PHIs ) are 15 day s for caneberry and 5 day s for artichoke .Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 9 of 37 **3.1 Chemical Identity**  **Table 3.**  **1. Test Com** **pound Nom**  **enclature** . Chemical structure

Common name Halosulfuron - methyl Com pany experimental name MON 12000, NC - 319 IUPAC name M ethyl 3 - chloro - 5 - (4,6 - dimethoxy pyrimidin - 2 - ylcarb amoyl sulf amoyl) - 1 - methylpyrazole - 4 - carboxylate CAS name M ethyl 3 - chloro - 5 - [[[[(4,6 - dimethoxy- 2 - pyrimidinyl)amino]carbonyl]amino] sulfonyl] - 1 - methyl - 1 H

- py razole - 4 - carboxylate CAS registry number 100784 - 20 - 1 End - use product (EP) 75% dry flowable SANDEA Herbicide ; EPA Reg. No. 81880 - 18 ) and 75% WG ( GWN - 3061 Herbicide ; EPA Reg. No. 81880 - 2) Chemical structure of 3 - chlorosulfonamide mo iety (3 - CSA)

3 - C hloro - 1 - methyl - 5 - sulfamoyl - 1 H - py razole - 4 - carboxylic acid **3.2 Physical/Chemical Characteristics**  An octanol/water partition coefficient of 1.67 at pH 5 and 23oC suggests that halosulfuron methyl is not fat soluble. In fact, halosulfuron - methyl has significant water solubility especiall y at elevated pH. The low vapor pressure indicates little vaporization. Halosulfuron - methyl, like most oth er sulfonylurea herbicides, is extremel y mobile with a median Koc of 104 g/mL and Kf (Freundlich partition) values ranging from 0.32 to 3.6 in four test soils. Its persistence in soil and water appears to be highly variable. Halosulfuron - methyl has the p otential to leach to groundwater, and also presents concerns for transport to surface water b y runoff. **3.3 Pesticide Use Pattern**  N N C H 3 Cl

N N N H N H O S O O

O C H 3 O C H 3 O O C H 3

N N C H 3 Cl NH 2

S O O O H OHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 10 of 37 Halosulfuron - methyl is a sulfonylurea herbicide proposed for pre - and post - emergence control of broadleaf weeds and nutsedge . The petitioner is proposing to add artichoke and caneberry (sub group 13 - 07A) to these two labels. The proposed use patterns are presented in Table 3.3. **Table 3.3.**  **Summ ary of Directions for Use of**  **Halosulfuron -**  **Methyl .**  Applic. Timing, Ty pe, and Equip. Applic.

Rate (lb ai/A) Max. No.

Applic. per Season Max. Annual

Applic. Rate (lb ai/A) PHI (day) Use Directions and Limitations Caneberry subgroup 13 - 07A including: blackberry, loganberry, raspberry, black and red, wild raspberry, cultivars, varieties, and/or hybrids of these

Application to either side of crop row , Ground 0.5 - 1 oz

(East of the Rockies) 0.75 - 2 oz (West of the Rockies) SANDEA or GWN 3061 (0.024 - 0.094) 2 2 oz (0.094) 15 Apply a single or sequential application with an interval of 45 days (0.024 - 0.094 lb ai/A) uniformly with ground equipment in a minimum of 15 gals of water per acre to the ground on either side of the row . Do not apply less than 15 days before harvest. Do not apply if excessive weed growth prevents herbicide cont act with ground. Use a non - ionic surfactant with post emergence applications. a Artichoke Application to either side of crop row , Ground only 1 - 2 oz

SANDEA or GWN 3061 (0.047 - 0.094) Not

specified 2 oz

(0.094) 5 Apply at 0.047 - 0.094 lb ai/A uniformly with ground equipment in a minimum of 15 gals of water per acre to the ground on either side of the row and avoiding crop foliage. Do not apply less than 5 days before harvest. Do not apply by air. Use a non - ionic surfactant with post - emergence applications. a **Note to RD** : The labeled use pattern for caneberries must be clarified (for both products EPA Reg. No. 81880 - 2 and EPA Reg. No. 81880 - 16). The proposed labels indicate that aerial application is just for corn, sorghum, and rice, but the specific use direc tions/limitations of caneberries do not explicitly state: “Do not apply by air.” This statement should be added on both labels in the caneberry section. **3.4 Anticipated Exposure Pathways**  The Registration Division has requested an assessment of human health risk to support the proposed new uses of halosulfuron - methyl on artichoke and caneberry ( subgroup 13 - 07A) . Humans may

be exposed to halosulfuron - methyl in food and drinking water, since halosulfuron methyl may

be applied directl y to growing crops and application may result in halosulfuron methyl reaching surface and ground water sources of drinking water. Currently , there are residential uses of halosulfuron - methyl on turf, so there is likely to be exposure in residential settings. In an occupatio nal setting, applicators may be exposed while handling the pesticide prior to application, as well as during application. There is a potential for post - application exposure for workers re - entering treated fields . There is also potential for residential p ost application exposure from turf use.Halosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 11 of 37 Risk assessments have been previousl y conducted for halosulfuron - methyl, dated 07/19/12 (D396458, C. Walls). This risk assessment considers all of the aforementioned exposure pathway s based on the proposed new uses of halosulfuron - methyl, but also considers the existing uses as well, particularl y for the dietary and residential exposure assessments. **3.5 Consideration of Environmental Justice**  Potential areas of environmental justice concerns, to the extent possible, were considered in this human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions to Address Environmental Justice in Minority Populations and L o w - Income Populations," http://www.epa.gov/environmentaljustice/resources/policy /exec_order_12898.pdf

. As a part of every pesticide risk assessment, O PP considers a large variety of consumer subgroups according to well - established procedures. In line with OPP policy , HED estimates risks to population subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water consump tion, and activities in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the U.S. Department of Agriculture’s National Health and Nutrition Examination Survey , What We Eat in America, (NHANES/WWEIA) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are anal yz ed and categorized by subgroups based on age and ethnic group. Additionally , OPP is able to assess dietary exposure t o smaller, specialized subgroups and exposure assessments are performed when conditions or circumstances warrant. Whenever appropriate, non - dietary

exposures based on home use of pesticide products and associated risks for adult applicators and for toddlers, youths, and adults entering or playing on treated areas post - application are evaluated. Further considerations are currentl y in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to b ys tanders and farm workers as well as lifestyl e and traditional dietary patterns among specific subgroups. **4.0 Hazard Characterization and Dose**  **- Response Assessment**  The most recent human health risk assessment was conducted for uses on pros o millet and Crop Group 17 (C. Walls, 07/19/12, D396458). Since then, the requirement for a subchronic inhalation study

has been waived (TXR 0054045) . Additionally , an immunotoxicity waiver has been submitted and is under review . The hazard characterization and toxicity endpoints for risk assessment remain unchanged since the 2006 risk assessment for uses on alfalfa (M. Rust, 9/21/2006, D331643). **4.1 Summary of Toxicological Effects**  Halosulfuron - methyl is a member of the sulfonylurea class of herbici des, and it i nhibit s acetolactate s ynthase , a specific plant enz ym e not found in mammals. The mode of action in mammals for halosulfuron - methyl is undetermined. The metabolism data indicated that with oral administration, halosulfuron - methyl was absorbed rapidly with incomplete absorption from the gastrointestinal tract. Within 72 hours, the absorbedHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 12 of 37 halosulfuron - methyl was eliminated in the urine and feces. Des methyl NC - 319 and the 5 - hydrox y derivative were the major urinary and fecal metabolites. No tissue retention was demonstrated. The absorption, elimination, and metabolism showed no sex dependence. Halosulfuron - methyl has low acute toxicity (Toxicity C ategory III - IV ) b y oral, dermal, and inhalation routes of exposure. It is not a dermal sensitizer. With repeated dosing, the available data show that the dog is the most sensitive mammalian species. In the dog, decreased body weight was seen in the chro nic 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. In the prenatal developmental toxicity study in rats, increases in resorptions, soft tissue (dilation of the lateral ventricles) and skeletal variations, and decreases in body weights were seen in the fetuses compared to clinical signs and decreases in body weights and food consumption in the maternal animals at similar dose level. In the rabbit developmental toxicity study , increases in resorptions and post - implantation losses and decrease in mean litter size was observed in the presence of decreases in b ody weight and food consumption in maternal animals. However, a clear NOAEL for these effects was established in both rat and rabbit developmental toxicity studies. Halosulfuron - methyl did not produce reproductive effects. No neurotoxic effects were obs erved in the acute or subchronic neurotoxicity studies. An estimated dermal absorption rate of 75% is based on results of an oral developmental toxicity study and a 21 - day

dermal toxicity

study in the same species (rat). Halosulfuron - methyl is negative f or mutagenicity

in a battery

of genotoxicity

studies. It is classified as “not likel y t o be carcinogenic to humans” based on lack of evidence for carcinogenicity

in mice and rats following long - term dietary administration. **4. 2**  **Safety factor for Infants and Children (FQPA Safety Factor)**  The FQPA safety factor has been reduced to 1X for the reasons detailed below (4.2.1 - 4.2.4) . **4. 2**  **.1 Completeness**  **o f**  **the Toxicology Database**  The toxicology

database for halosulfuron - methyl is complete with the exception of an immunotoxicity

study . Current data requirements in 40 CFR §158 include an immunotoxicity study (OPPTS Guideline 870.7800) for pesticide registration. A waiver request for this data requirement has been submitted and is under review. Inthe absence of specific immunotoxicity studies, HED has evaluated the available toxicity database to determine whether an additional database uncertainty

factor is needed to account for potential immunotoxicity . The toxicology database o f this chemical does not show any evidence of biologicall y relevant effects on the immune sy stem. The overall weight of the evid ence suggests that this chemical does not directl y target the immune s ys tem . HED does not believe that immunotoxicity testing will result in a NOAEL less than that (10 mg/kg/day) used to derive the current cRfD of 0.1 mg/kg/day . Consequently , HED believes the existing data are sufficient for endpoint selection forHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 13 of 37 exposure/risk assessment scenarios and for evaluation of the requirements under the FQPA, and an additional database uncertainty factor (UF DB ) does not need to be applied at this time. The requirement for a subchronic inhalation study has been waived (TXR 0054045). **4. 2**  **.2 Evidence of N**  **eurotoxicity** Halosulfuron meth yl is not an apparently neurotoxic chemical based on clinical observations of neurotoxicity

during the conduct of developmental or chronic studies. No untoward neurobehavioral signs were observed at doses approaching the limit dose in any of the short term studies in rats or mice (subchronic oral, 2 1 - day dermal) or chronic studies . No neurotoxic effects were observed during acute or subchronic neurotoxicity studies in which animals were dosed at sy stemically

t oxic dose levels . A developmental neurotoxicity study is not required at this time. **4. 2**  **.3 Evidence**  **o f Sensitivity/Su**  **sceptibility in the Developing o r Young Animal**  There was no quantitative evidence for increased susceptibility following pre - and/or post - natal exposure. However, there was qualitative evidence for increased susceptibility . In the rat study , increases in resorptions, soft tissue (dilation of the lateral ventricles) and skeletal variations, and decreases in body weights were seen in the fetuses compared to clinical signs and decreases in body weights and food consumption in the maternal animals. In the rabbit study , increases in resorptions and post - implantation losses and decrease in mean litter size were seen in the presence of decreases in body weight and food consumption in maternal animals. Thus, in both species, the developmental effect was considered to be qualitatively more severe than maternal effects (i.e., qualitative evidence for susceptibility). In both studies, there are clear NOAELs/LOAELs for developmental and maternal toxicities, developmental effects were seen in the presence of maternal toxicity, and the effects were onl y 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 i s low and there are no residual uncertainties for prenatal toxicity in both rats and rabbits. **4. 2**  **.4 Residual**  **Uncertainty in the Exposure Datab ase**  There are no residual uncertainties in the exposure database. Since the dietary and non - dietary exposure estimates were based on several conservative assumptions, HED does not believe that the exposure estimates are underestimated. The dietary assessment s conducted with DEEM FCID were conservative and utilized tolerance level residues for all crops, default processing factors for all commodities , and 100% crop treated was assumed for all commodities. The DEEM anal ys is also assumed that all drinking water will contain halosulfuron methyl at the highest EDWC levels modeled b y the Environmental Fate and Effects Division ( EFED ) for ground water or surface water. For these reasons it can be concluded that the dietary anal ys is does not underestimate risk from exposure to halosulfuron methyl. Similarly , HED does not believe that the non - dietary occupational and res idential exposure s are underestimated because they are also based on conservative assumptions , including maximum application rates, labeledHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 14 of 37 personal protective equipment ( PPE ) , and standard values for unit exposures and acreage treated/amount handled . **4. 3**  **Toxicity Endpoint and Point of D**  **eparture Selections** There have been no changes to the prior dose - response assessment for halosulfuron methyl. The PODs and toxicity

endpoints selected for various exposure scenarios applicable to this risk assessment are summarized in Tables 4.3.1 (Non - Occupational and Occupational). For the short - and intermediate - term inhalation exposure, the toxicity endpoints and points of departure were derived from the oral toxicity studies as indicated in the Table 4.3.1. **Table 4**  **. 3**  **.1 Summary of Toxicological Doses and Endpoints for**  **Halosulfuron -**  **me thyl**  **for Use in Dietary ,** 

**Occupational and Non**  **- Occupational Hum**  **an Health Risk Assessments Exposure/**  **Scenario Point of** 

**Departure Uncertainty/** 

**FQPA Safety Factors**  **RfD, PAD,**

**Level of Concern for**  **Risk Assessment**  **Study and Toxicological Effects**

Ac ute Dietary (Females 13 - 49 years of age) NOAEL=

50 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Ac ute RfD = 0.5

mg/kg/day aPAD =0.5 mg/kg/day **Developm ental Toxicity**  **- Rabbit** 

LOAEL = 150 mg/kg/day based on decreased mean litter size, increased number of resorptions (total and per dam) and increased postimplantation loss (developmental toxicity) . Ac ute Dietary (General Population including Infants and Children) No adverse effect attributable to a single dose was identified; therefore, no dose/endpoint was

selected for this exposure scenario. Chronic Dietary (All Populations) NOAEL=

10 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Chronic RfD =

0.1 mg/kg/day cPAD = 0.1 mg/kg/day **Chronic Toxicity -**  **Dog**

LOAEL = 40 mg/kg/day based on decreased body weight gains in females. Incidental Oral Short - Term

(1 - 30 days) NOAEL=

50 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential LOC

for MOE = 100 **Developm ental Toxicity**  **- Rabbit** 

LOAEL = 150 mg/kg/day based on decreased body weight gain, food consumption, and food efficiency ( maternal toxicity). Incidental Oral Intermediate Term (1 - 6 mo nths) NOAEL=

10 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential LOC

for MOE = 100 **13 Week Subchronic Toxicity -**  **Dog**

LOAEL = 40 mg/kg/day based on decreased body weight gain s and food efficiency along with hematological and clinical chemistry changes . Dermal Short Term (1 - 30 days) NOAEL=

100 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential and

Occupational LOC for MOE = 100 **21 -**  **Day Derm al Toxicity Study**  **- Rat** 

LOAEL = 1000 mg/kg/day based on decreased body weight gain in males.Halosulfuron - Meth yl

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Page 15 of 37 **Table 4**  **. 3**  **.1 Summary of Toxicological Doses and Endpoints for**  **Halosulfuron -**  **me thyl**  **for Use in Dietary ,** 

**Occupational and Non**  **- Occupational Hum**  **an Health Risk Assessments Exposure/**  **Scenario Point of** 

**Departure Uncertainty/** 

**FQPA Safety Factors**  **RfD, PAD,**

**Level of Concern for**  **Risk Assessment**  **Study and Toxicological Effects**

Dermal Intermediate Term (1 - 6 mo nths) + NOAEL=10

mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential and

Occupational LOC for MOE = 100 **13 Week Subchronic Toxicity**  **- Dog** 

LOAEL = 40 mg/kg/day based on decreased body weight gain s and food efficiency along with hematological and clinical chemistry changes . Inhalation Short - Term (1 - 30 days) NOAEL =

50 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential and

Occupational LOC for MOE = 100 **Developm ental Toxicity**  **- Rabbit** 

LOAEL = 150 mg/kg/day based on decreased body weight gain, food consumption, and food efficiency (maternal toxicity). Inhalation Intermediate Term (1 - 6 mo nths) NOAEL=

10 mg/kg/day UF A= 10x

UF H = 10x FQPA SF= 1x Residential and

Occupational LOC for MOE = 100 **13 Week Subchronic Toxicity -**  **Dog**

LOAEL = 40 mg/kg/day based on decreased body weight gain s and food efficiency along with hematological and clinical chemistry changes . Cancer (oral, dermal, inhalation) **Classification: "not likely to be carcinogenic to hum ans"**  by the oral route, based on no

evidence of carcinogenicity from studies in rats and mice . + : A 75% dermal absorption factor should be used in route - to - route extrap olation for the intermediate term dermal exposure risk. Toxicity via the inhalation route is presumed to be equivalent to oral toxicity . NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human ( inter - species ). UF H = potential variation in sensitivity among members of the human population ( intra - species ). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. N/A = not applicableHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 16 of 37 **5.0 Dietary Exposure and Risk Assessment**  **5.1 Residues of Concern Summary and Rationale**  The nature of the residue in plants is adequatel y understood based on acceptable metabolism studies with corn, sugarcane, and so yb ean; all studies investigated pre - and postemergence uses. The metabolism of halosulfuron - methyl was similar in the three tes ted crops but dependent on the mode of application (pre - or postemergence). When halosulfuron - methyl was applied preemergence, initial breakdown of the herbicide in the soil and preferential uptake of the py razole moieties resulted in the primary residue being 3 - CSA, which has been determined to be less toxic than the parent. With a postemergence application, the major residue was the parent compound with minimal translocation of the herbicide in the plant, except in grain where the major residue was 3 - CS A. Based on the very

low toxicity

of the metabolite 3 - CSA, relatively low toxicity

of the parent compound, and low residue levels of both parent compound and the 3 - CSA metabolite, HED previously

concluded that the residue of concern in plants is the parent compound, halosulfuron methyl. HED has previously

concluded that the residue of concern in ruminants is halosulfuron - methyl. However, because the approved enforcement method for livestock commodities quantifies the parent compound and metabolites containing the 3 - CSA moiety by converting residues to 3 - CSA, tolerances for residues of parent and its metabolites in livestock commodities are determined as 3 - CSA, expressed in halosulfuron - methyl equivalents. H alosulfuron meth ylis th e only residue included in the drinking water assessment. **Table 5.1. Summary of Metabolites and Degradates to be included in th**  **e Risk Assessment and**  **Tolerance Expression** Matrix Residues included in Risk Assessment Residues included in Tolerance Expression Plants Primary Crop Halosulfuron - methyl Halosulfuron - methyl

Rotational Crop Halosulfuron - methyl Halosulfuron - methyl Livestock Ruminant Halosulfuron - methyl * Halosulfuron - methyl, 3 - CSA

Poultry Halosulfuron - methyl * Halosulfuron - methyl, 3 - CSA Drinking Water Halosulfuron - methyl Not Applicable *Residues are determined as 3 - CSA and expressed in halosulfuron - methyl equivalents. **5 .2**  **Food Residue**  **Profile** The submitted magnitude of the residue data , summarized in Table 2.2.3, are in accordance with OCSPP guidelines and adequate for risk assessment and tolerance assessment. For both crops, the number and locations of field trials are adequate. Both artichoke and caneberry trials reflect a single banded postemergence application (b ackpack) of a 75% ai formulation at a targetHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 17 of 37 application rate of ~0.093 lb ai/A. A non - ionic surfactant was used in both trials. The available data will support tolerances at the LOQ of 0.05 ppm for both artich oke and caneberry at respective preharvest intervals of 5 and 13 - 15 day s. The field trial studies are supported b y adequate storage stability data. Adequate confined and limited field rotational crop data are available. HED previously concluded that the residue of concern in rotational crops is halosulfuron - methyl . Based on the absence of the parent compound in the confined studies and in the limited field rotational crop studies, with the exception of one forage sample, HED previousl y concluded that rotational crop tolerances an d restrictions are not required for halosulfuron - methyl. **5.3 Water Residue Profile**  Estimated surface water and groundwater concentrations are shown in Table 5.3.1. The dietary

exposure assessment used the value of 59.2 ppb for acute and chronic assessments. Th e drinking water assessment is based on Tier I surface water model simulation for the halosulfuron - methyl use on rice since the resulting EWDCs are greater than those estimated for the proposed uses (D394244, J. Meléndez, 0 5/15/12 ; D404096, M. Barrett, 03/26/13 ) . **Table 5.3.1 . Tier I Estimated Drinking Water Concentrations (EDWCs) for**  **H uman**  **H ealth**  **D rinking**  **W ater**  **R isk**  **A ssessment**  **DRINKING WATER SOURCE (MODEL USED)**  **USE (rate modeled)**  **MAXIMUM ESTIMATED DRINKING WATER CONCENTRATION (EDWC)**  **c ( ppb)**  Groundwater (SCI - GROW) Fallow ground (0.125 lb a.i./A/season) a Ac ute 0.065 Chronic <0.065 Surface Water (Tier 1 Rice Model v.1.0) Paddy Water/Tail Water; Rice (0.0625 lb a.i./A/season) b Ac ute 59.2 Chronic <59.2 **a** Covers all uses other than rice ; for the corn, fallow ground, and sugarcane use patterns of halosulfuron - methyl, based on a seasonal application 0.125 lb a.i./A. **b** Seasonal rate is 0.0625 lb a.i./A , which is half of the rate of fallow ground . **c** Surface water concentrations calculated by the Tier I Rice Model v1.0 and ground water concentrations calculated by SCI - GROW do not distinguish between peak and chronic concentration . **5.4 Dietary Risk Assessment**  **5.4.1 Description of Residue Data Used in Dietary Assessment**  Conservative acute and chronic dietary exposure assessments were conducted. Tolerance level residues were used for the existing and proposed uses in both the acute and chronic assessments. The EWDC value of 59.2 was used as the drinking water residue in both the acute and chronic assessments. Additionally , DEEM version 7.81 default processing factors were assumed in both assessments, as well. **5.4.2 Percent Crop Treate**  **d Used in Dietary Assessment** The acute and chronic dietary analy ses assumed that 100% of the crop was treated (100% CT)Halosulfuron - Meth yl

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Page 18 of 37 **5.4.3 Acute Dietary Risk Assessment**  An acute dietary

(food and drinking water) exposure and risk assessment was conducted using the D ietary

Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM - FCID) Version 3.16. This software uses 2003 - 2008 food consumption data from the U.S. Department of Agriculture’s (USDA’s) National Health and Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA). A conservative dietary exposure assessment was performed for halosulfuron methyl for the current uses and the proposed new uses on artichoke and caneberry ( Subgroup 13 - 07A ) . The result of the acute dietary (f ood and drinking water) anal ys is is below the Agency ’s LOC for females 13 - 49 years old. For the general U.S. population, an appropriate dose/endpoint attributable to a single dose was not observed in the reviewed oral toxicity

studies therefore, an acute dietary assessment was not conducted. T he acute dietary

exposure estimate at the 95 th percentile is <1 % of the acute population adjusted dose ( aPAD ) for females 13 - 49 years old, the onl y population subgroup of concern. The result of the acute dietary

exposure anal ys is is reported in Table 5.4.6 . **5.4.4 Chronic Dietary Risk Assessment**  A c hronic dietary

(food and drinking water) exposure and risk assessment was conducted using DEEM - FCIDTM, Version 3.16. A conservative dietary exposure assessment was performed for halosulfuron methyl for the current uses, and proposed new uses on artichoke and caneberry ( Subgroup 13 - 07A ) . The results of the chronic dietary (food and drinking water) anal ys is are below the Agency ’s level of concern for the general U.S. population and all population subgroups. T he dietary (food and drinking water) exposure is estimated at 2 % of the c hronic Population Adjusted Dose (cPAD) for the general U.S. population and 5.5% of the cPAD for all children 1 - 2 years old , the most h ighly exposed population subgroup . The results of the chronic dietary exposure anal ys e s are reported in Table 5.4.6 . **5.4.5 Cancer Dietary Risk Assessment**  Halosulfuron meth ylis classified as “not likel y to be carcinogenic to humans;” therefore, cancer risk was not assessed. **5.4.6 Summary Table**  **Table 5.4.6. Summary of Dietary** ( Food and Drinki ng Water) **Exposure and Risk for Halosulfuron**  **- Methyl**  **Population Subgroup**  **Acute Dietary (95th**  **Percentile) Chronic Dietary**  **Cancer Dietary**  **Exposure (m**  **g/kg/day) % aPAD** * **Dietary Exposure**  **(m g/kg/day)**  **% cPAD*** **Dietary Exposure**  **(m g/kg/day)**  **Risk** General U.S. Population N/A N/A 0.002050 2.0 N/A N/AHalosulfuron - Meth yl

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Page 19 of 37 **Table 5.4.6. Summary of Dietary** ( Food and Drinki ng Water) **Exposure and Risk for Halosulfuron**  **- Methyl**  **Population Subgroup**  **Acute Dietary (95th**  **Percentile) Chronic Dietary**  **Cancer Dietary**  **Exposure (m**  **g/kg/day) % aPAD** * **Dietary Exposure**  **(m g/kg/day)**  **% cPAD*** **Dietary Exposure**  **(m g/kg/day)**  **Risk** All Infants (< 1 year old) 0.004871 4.9 Children 1 - 2 years old **0.005508 5.5**  Children 3 - 5 years old 0.003884 3.9 Children 6 - 12 years old 0.002433 2.4 Youth 13 - 19 years old 0.001579 1.6 Adults 20 - 49 years old 0.001791 1.8 Adults 50+ years old 0.001737 1.7 Females 13 - 49 years old 0.003733 <1 0.001785 1.8 V alues for the highest exposed population for each type of risk assessment are boldedHalosulfuron - Meth yl

Human Health Risk Assessment DP No. D404095

Page 20 of 37 **6.0 Residential (Non**  **- Occupational) Exposure/Risk Characterization**  There are no proposed residential uses with this petition ; however, there are existing residential turf use s that have been reassessed in the most recent risk assessment (C. Walls, D 396458, 07/19/12) to reflect updates to HED’s 2012 Residential SOPs along with policy changes for body weight assumpti ons. The revision of residential exposures impacts the human health aggregate risk assessment for halosulfuron methyl. **6.1 Residential Handler Exposure**  There are no proposed residential uses at this time. A ll of the existing residential uses have been previously reassessed to reflect updates to the HED 2012 Residential SOPs 1 along with policy changes for body

weight assumptions (N. Tsaur, DP394460, 06/12/12) . There are no registered products that would lead to any residential handler or post - applicatio n risk estimates of concern. Summaries of the short - term combined (dermal + inhalation) risk estimate s for residential handlers are included in Table 6.1 . The maximum application rate for each exposure scenario is present ed as the worst case scenario. A ll risk estimates are greater than the LOC of 100 and therefore not of concern (MOEs range from 7,200 to 190,000). **Table 6.1. Short**  **- Term Residential Handler Exposure and Risk Estimates for Water Dispersible Granule** 

**Application of Halosulfuron -**  **Methyl on Re sidential Turf.**  Exposure Scenario Application

Rate a Area

Treated Daily b Baseline Unit

Exposure b Baseline Dose d Baseline MOE e Total MOE f Dermal Inhal ation Dermal Inhalation lb ai/A Acres mg/lb ai mg/kg/day Dermal Inhalation ManuallyPressurized H andwand 0.14 0.115 69 1 . 1 0.0135 0.000215 7,400 230,000 7,200 Hose - End S prayer 0.14 0.50 13 . 4 0.022 0.0114 0.0000187 8,800 2,700,000 8,800 Backpack Sprayer 0.14 0.115 69 1 . 1 0.0135 0.000215 7,400 230,000 7,200 Sprinkler C an 0.14 0.023 13 . 4 0.022 0.000523 0.000000859 190,000 58,000,000 190,000 a Application Rates based on maximum application rates of registered residential turf uses for halosulfuron - methyl. b Based on HED’s SOPs: Lawns/Turf (January 2012). 0.115A = 5 gallons × (label rate: 1000 ft2/1 gallon). 0.023 A = 1000 ft2

. c Baseline Dermal: no gloves, short pants. Inhalation: no respirator. d Dose (mg/kg/day) = daily unit exposure (mg/lb ai) x application rate (lb ai/A) × area treated (Acres/day) × absorption factor (%) ÷ body weight (80 kg). Dermal absorption factor = 100%. No inhalation absorption factor. e MOE = NOAEL ÷ daily dose (mg/kg/ day). ST Dermal NOAEL = 100 mg/kg/day . ST Inhalation NOAEL = 50 mg/kg/day. f To tal MOE = 1/ [ (1/Dermal MOE) + (1/I nhalation MOE)]. Level of concern = 100.

1 Available: http://www.epa.gov/pesticides/science/residential - exposure - sop.htmlHalosulfuron - Meth yl

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Page 21 of 37 **6.2.1 Post**  **- Application Exposure**  Adults and children performing phy sical post - application activities on turf (e.g. golfing, mowing) may receive dermal exposure to halosulfuron - methyl residues. Young children 1 to <2 years old may also receive incidental oral post - application exposure to halosulfuron - methyl from treate d turf. The scenarios, routes of exposure , and lifestages previousl y assessed include: Phy sical activities on turf, adults (dermal) and children 1 to < 2 ye ars old (dermal and incidental oral); Mowing, adults (dermal) and children 11 to < 16 years old (de rmal); and Golfing , adults (dermal) , children 11 to < 16 ye ars old (dermal) , and children 6 to < 11 ye ars old (dermal). Post application risk estimates for all residential scenarios are greater than the LOC of 100 and therefore not of concern (MOEs range from 960 to 11,000,000) . **6.3 Combined Exposure**  HED combines risk estimates resulting from separate post - application exposure scenarios when it is likely they can occur on the same day based on the use pattern and the behavior associated with the exposed population and when the toxicological effects are similar. For halosulfuron methyl, the toxicological effects are similar for the dermal, inhalation, and incidental oral routes; theref ore, the exposures via these routes were combined where appropriate. For residential handlers, dermal and inhalation exposures were combined. For post - application scenarios, dermal and incidental oral exposures were combined for children 1 to < 2 years o ld. The incidental oral scenarios (i.e., hand - to - mouth, object - to - mouth, and soil ingestion) should be considered inter - related and it is likely that they occur interspersed amongst each other across time. Combining all three of these scenarios with the dermal exposure scenario would be overlyconservative because of the conservative nature of each individual assessment. Therefore , the post - application exposure scenarios that were combined for children 1 to < 2 years old are the dermal and hand - to - mouth scenarios. This combination should be considered a protective estimate of children’s exposure to pesticides used on turf. All combined (dermal + inhalation) post - application scenarios resulted in MOEs greater tha n 100 and were not of concern. Handler d ermal exposure is not combined with post - application dermal exposure because a homeowner is unlikely to be conducting post - application activities on the same day in which they

apply the chemical. Table 6.3 shows the combined residential risk estimates for adults and children. **Table 6.3**  **. Short**  **- Term** **Residential Exposures for the Halosulfuron**  **- Methyl**  **Combined Risk Estimates** Population Handler MOEs 1 Residential Handler Total MOE 3 Post - A pplication MOEs 2 Residential Post Application Total MOE 4 Dermal Inhalation Dermal Inhalation Oral Adult 7,400 230,000 7,200 1,900 N/A N/A 1,900 Child 11 to < 16 years old N/A 21,000 21,000 Child 6 to < 11 years old 18,000 18,000 Child 1 to < 2 years old 960 23,000 920 1 Handler MOE represents high - end handler exposure, where the exposure duration is appropriate to assess. 2 Post - application MOE represents high - end incidental oral exposure for the relevant exposure duration.Halosulfuron - Meth yl

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Page 22 of 37 3 Total MOE = 1 ÷ [ (1/Dermal MOE) + (1/Inhalation MOE) ] . Dermal NOAEL = 100 mg/kg/day . Inhalation NOAEL = 50 mg/kg/day. 4 Total MOE = 1÷ [(1/Dermal MOE) + (1/Incidental Oral MOE) ] . Dermal NOAEL = 100 mg/kg/day. Incidental Oral NOAEL = 50 mg/kg/day. **6.4 Residential Bystander Postapplication Inhalation Exposure**  Based on the Agency's current practices, a quantitative post - application inhalation exposure a ssessment was not performed for halosulfuron - methyl at this time primarily because the chemical is only

formulated as a WG, has low acute inhalation toxicity (Tox icity Category IV), has low vapor pressure ( <1 x 10 - 7 mm Hg at 25 oC ), and has a low proposed use rate (0.094 lb ai/A). However, volatilization of pesticides may be a source of post - application inhalation exposure to individuals nearb y pesticide applicati ons. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 2

. The Agency is in the process of evaluating the SAP report and may , as appropriate, develop policies and procedures to identify the need for and, subsequently , the way to incorporate post - application inhalation exposure into the Agency's risk asses sments. If new policies or procedures are developed, the Agency may revisit the need for a quantitative post - application inh alation exposure assessment for halosulfuron - methyl . **6. 5**  **Spray Drift** Spray drift is alway s a potential source of exposure to residents nearby to spraying operations. This is particularly

the case with aerial application, but, to a lesser extent, could also be a potential source of exposure from the ground application metho d employed for halosulfuron methyl. The Agency

has been working with the Spray Drift Task Force, EPA Regional Offices , and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices (see the Agency ’ s Spray Drift website for more information 3

. The Agency has completed its evaluation of the new database submitted by the Spray

Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply

the data and the AgDRIFT computer model to its risk assessments for pesticides applied b y air, orchard airblast , and ground hydraulic methods. After the policy is in place, the Agency

may impose further refinements in spray drift management practices to reduce of f - target drift with specific products with significant risk estimates associated with drift. Although a quantitative residential post - application inhalation exposure assessment was not performed as a result of pesticide drift from neighboring treated agri cultural fields, an inhalation exposure assessment was performed for flaggers. This exposure scenario is representative of a wors t case inhalation (drift) exposure and may be considered protective of most outdoor agricultural and commercial post - applicati on inhalation exposure scenarios . It is noted that the 0.14 lb ai/acre application rate for turf was modeled to estimate post application residential exposure of children. As this rate is equal to or higher than many of

2 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html 3 Available: http://www.epa.gov/opp00001/factsheets/spraydrift.htmHalosulfuron - Meth yl

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Page 23 of 37 agricultural application rates, this scenario is protective of any exposure of farm children vi a spray drift from agricultural halosulfuron - methyl applications. **7.0 Aggregate Exposure/Risk Characterization**  In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposures and risks from three major sources: food, drinking water, and residential exposures. In an aggregate assessment, exposures from relevant sources are added together and compared to quantitative estimates of hazard ( e.g. a NOAEL or PAD), or the risks th emselves can be aggregated. When aggregating exposures and risks from various sources, HED considers both the route and duration of exposure. For halosulfuron - methyl, potential exposures from food, drinking water, and residential scenarios were aggregate d. **7.1 Acute Aggregate Risk**  Refer to Section 5.4.3 which discusses acute dietary (food and drinking water) exposure in detail. The dietary

route alone is relevant for acute exposure and risk assessment; the acute dietary exposure and risk assessment con ducted for halosulfuron - methyl is screening - level, wherein the assessment assign s tolerance level residue value s to all food commodities proposed to be treated with halosulfuron - methyl and modeled residue values to all drinking water. No aggregate risk co ncerns were identified. **7.2 Short**  **- Term Aggregate Risk**  There is potential short - term exposure to halosulfuron - methyl via the dietary (which is considered background exposure) and residential (which is considered primary) pathway s. For adults, these pathway s lead to exposure via the oral (background) and dermal (post - application primary) routes. For children, these pathway s lead to exposure via the oral (background), and incidental oral and dermal (primary) routes. MOEs are greater than 100, which indicates that exposure and risk do not exceed HED’s level of concern. The recommended residential exposure for use in the aggregate assessment of adults and children 1 to <2 ye ars old reflects the combined post - application dermal plus hand - to - mouth exposures fro m turf treated with liquid applications. The adult and children short - term aggregate dietary and residential MOEs are 1,800 and 840 , respectivel y. **Table 7.2. Short -**  **Term Aggregate Risk Calculations** Population Short - Term Scenario

LOC for Aggregate Risk 1 Dietary

MOE 2 MOE Oral Residential Exposure 3 MOE

Dermal Residential Exposure 4 Aggregate

MOE (food, water, and residential) 5 Adult 100 28 ,000 NA 1,900 1, 8 00 Child 1 to < 2 years old 100 9,1 00 23,000 960 840 1 LOC = 100 (based on inter - and intra - species uncertainty factors total ing 100X). 2 MOE die tary = [(short - term oral NOAEL 50 mg/kg/day)/(chronic dietary exposure)]. See Tables 4.3.1 and 5.4.6 3 MOE oral = [(short - term oral NOAEL)/(hand - to - mo uth residential exposure)]. See Table 6.3Halosulfuron - Meth yl

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Page 24 of 37 4 MOE de rmal = [(short - term dermal NOAEL)/(high end dermal residential exposure)]. See Table 6.3 5 MOE Aggregate = 1/[(1/MOE dietary) + (1/MOE oral) + (1/MOE dermal) ] **7.3 Intermediate**  **- Term Aggregate Risk**  Intermediate - term exposure is not expe cted for the adult or child residential exposure pathway . Therefore, the intermediate - term aggregate risk would be equivalent to the chronic dietary exposure estimate. Refer to Section 5.4.4. **7.4 Chronic Aggregate Risk**  Chronic exposure is not expected for the adult re sidential (dermal and inhalation) exposure pathway . Therefore, the chronic aggregate risk would be equivalent to the chronic dietary exposure estimate . Refer to Section 5.4.4. **7.5 Cancer Aggregate Risk**  Halosulfuron meth ylis classified as “not likel y to be carcinogenic to humans;” therefore, an aggregate cancer assessment was not conducted. **8.0 Cumulative Exposure/Risk Characterization**  Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, E PA has not made a common mechanism of toxicity finding as to halosulfuron methyl and any other substances and halosulfuron methyl does not appear to produce a toxic metabolite produced b y other substances. For the purposes of this tolerance action, there fore, EPA has not assumed that halosulfuron methyl has a common mechanism of toxicity with other substances. For information regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the policy statements released b y EPA’s Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA’s website at http://www.epa.g ov/pesticides/cumulative/. **9.0 Occupational Exposure/Risk Characterization**  **9.1 Short**  **- and**  **Intermediate -**  **Term Handler Risk**  For caneberries and artichokes, h alosulfuron - methyl is proposed to be applied up to two times per season, pre - and post - emergent to weed growth at a maximum application rate of 2 oz/A (0.094 lb ai/A) . The maximum handheld rate is proposed at 0.0094 lb ai/gal (based on a minimum of 10 gallons of water per acre). Handlers m ay appl y either of the EPs as a foliar spray using onl y ground equipment for caneberries and artichokes. Since chemigation was both permitted and prohibited on the labels, it was assessed to be protective .Halosulfuron - Meth yl

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Page 25 of 37 Based on the anticipated use patterns and current labeling, typ es of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed uses. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios: mixing/loading dry flowables to support groundboom and chemigatio n applications; applying spray s with groundboom equipment; and mixing/loading/appl yi ng sprays for ground - directed application via mechanicall y- pressurized handguns . All handler scenarios result in MOEs greater than the L OC (MOEs ≥ 100) at baseline or with recommended PPE, and are not of concern to HED. At baseline, short - term combined (dermal + inhalation) MOEs range from 650 to 48,000. With the exception of handheld equipment, baseline intermediate - term combined (dermal + inhalation) MOEs range from 12 0 to 6,400. At baseline, the handheld equipment (mechanically- pressurized handgun) results in an MOE of 88. However, with required PPE of gloves, the MOE is 290 . Tables 9.1.1 and 9.1.2 summarize the risk estimates for the proposed uses.Halosulfuron - Meth yl

Human Health Risk Assessment DP No. 404095

Page 26 of 37 **Table 9.1.1**  **. Short**  **- Term**  **Occupational Handler Non -**  **Cancer E xposure and Risk Estimates for Halosulfuron**  **- Methyl at Baseline**  Exposure Scenario Crop or Target Dermal Unit

Exposure a Inhalation Unit

Exposure a Maximum

Application Rate b Area Treated or Amount Hand led Dailyc Dermal Inhalation Total

Dose d MOE e Dose f MOE g MOE h μg/lb ai mg/kg/day mg/kg/day Mixer/Loader at Baseline Mixing/Loading Dry Flowables for Groundboom Application Caneberries, Artichokes 227 8.96 0.094 lb ai/A 80

acres 0.0213 4,700 0.000840 60,000 4,400 Mixing/Loading Dry Flowables for Chemigation Application Caneberries, Artichokes 350 acres 0.0931 1,100 0.00368 14,000 1,000 Applicator at Baseline Applying Sprays via Groundboom Caneberries, Artichokes 78.6 0.34 0.094 lb ai/A 80

acres 0.00738 14,000 0.0000319 1,600,000 14,000 Mixer/L oader/Applicator at Baseline M/L/A for Ground - Directed Application via Mechanically Pressurized Handgun Caneberries, Artichokes 1300 3.9 0.0094 lb ai/gal 1000

gallons 0.153 650 0.000458 110,000 650 a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012). Level of mitigation: baseline. b Based on registered or proposed label (Reg. No. 81880 - 2). c Exposure Science Advisory Council Policy #9.1. d Dermal Dose = Dermal Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/ μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg). e Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). ST Dermal NOAEL = 100 mg/kg/day. LOC = 100. f Inhalation Dose = I

nhalation Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/ μg) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) ÷ BW (80 kg). g Inhalation MOE = I

nhalation NOAEL (mg/kg/day) ÷ I nhalation Dose (mg/kg/day). ST Inhalation NOAEL = 50 mg/kg/day. LOC = 100. h Total MOE = 1 ÷ (1/Dermal MOE + 1/I nhalation MOE).Halosulfuron - Meth yl

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Page 27 of 37 **Table 9.1.2 .**  **Interm ediate**  **- Term**  **Occupational Handler Non -**  **Cancer E xposure and R** **isk Estimates for Halosulfuron -**  **Methyl** Exposure Scenario Crop or Target Dermal Unit

Exposure a Inhalation Unit

Exposure a Maximum

Application Rate b Area Treated or Amount Handled Dailyc Dermal Inhalation Total

Dose d MOE e Dose f MOE g MOE h μg/lb ai mg/kg/day mg/kg/day Mixer/Loader at Baseline Mixing/Loading Dry Flowables for Groundboom Application Caneberries, Artichokes 227 8.96 0.094 lb ai/A 80

acres 0.0159 630 0.000840 12,000 600 Mixing/Loading Dry Flowables for Chemigation Application Caneberries, Artichokes 350 acres 0.0698 140 0.00368 2,700 130 Applicator at Baseline Applying Sprays via Groundboom Caneberries, Artichokes 78.6 0.34 0.094 lb ai/A 80

acres 0.00553 1,800 0.0000319 310,000 1,800 Mixer/L oader/Applicator at Baseline M/L/A for Ground - Directed Application via Mechanically Pressurized Handgun Caneberries, Artichokes 1300 3.9 0.0094 lb ai/gal 1000

gallons 0.114 88 0.000458 22,000 **88** Mixer/L oader/Applicator with Recommended PPE (Single Layer + Gloves) M/L/A for Ground - Directed Application via Mechanically Pressurized Handgun Caneberries, Artichokes 390 3.9 0.0094 lb ai/gal 1000

gallons 0.0343 290 0.000458 22,000 290 a Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” (March 2012 ) . Level of mitigation: b aseline. b Based on registered or proposed label (Reg. No. 81880 - 2 ). c Exposure Science Advisory Council Policy #9.1. d Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled (A or gal/day) × DAF ( 75 %) ÷ BW ( 80 kg). e Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day). IT Dermal NOAEL = 1 0 mg/kg/day. LOC = 100. f Inhalation Dose = I

nhalation Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Ar ea Treated or Amount Handled (A or gal/day) ÷ BW ( 80 kg). g Inhalation MOE = I

nhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). IT Inhalation NOAEL = 1 0 mg/kg/day. LOC = 100. h Total MOE = NOAEL (mg/kg/day) ÷ Dermal Dose + I nhalation Dose.Halosulfuron - Meth yl

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Page 28 of 37 **9.2 Short**  **- and**  **Intermediate -**  **Term Post**  **- Application**  **Risk 9.2.1**  **Dermal Postapplication Risk** Dermal post - application exposure is not expected from caneberries or artichokes treated with halosulfuron - methyl because the label indicates that contact with the planted crop should be avoided . The REI specified on the proposed label is based on the acute toxic ity of halosulfuron - methyl. Halosulfuron - methyl is classified as Toxicity Category I II via the dermal route and Toxicity Category IV for skin irritation potential. It is not a skin sensitizer. Short - and intermediate - term post - appli cation risk estimates were not of concern on day 0 (12 hours following application) for all post - application activities. Under 40 CFR 156.208 (c) (2) (iii), ai’s classified as Acute III or IVfor acute dermal, eye irritation and primary skin irri t ation are assigned a 12 - hour REI. Therefore, the [156 subpart K] Worker Protection Statement interim REIof 12 hours is adequate to protect agricultural workers from post - application exposures to halosulfuron - methyl. **9.2.2 Inhalation Postapplication Risk**  Based on the Agency's current practices, a quantitative occupational post - application inhalation exposure assessment was not performed for halosulfuron - methyl at this time because the chemical has low vapor pressure (<1 x 10 - 7 mmHg at 25oC) and is applie d at a low rate (0.0625 lb ai/A) . However, there are multiple potential sources of post - application inhalation exposure to individuals performing post - application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009. The Agency received the SAP’s final report on March 2, 2010 (http://www.epa.gov/scipoly /SAP/me etings/2009/120109me eting.html ) and is in the proce ss of evaluating the SAP report as well as available post - application inhalation exposure data generated b y the Agricultural Reentry Task Force. The Agency may, as appropriate, develop policies and procedures to identify the need for and, subsequently , th e way to incorporate occupational post - application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post - application inhalation exposure assessment for halosulfuron - methyl. Although a quantitative occupational post - application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resultin g from mixing/loading pesticides is likely to result in higher exposure than post - application exposure. Thus , handler inhalation exposure estimates would be protective of most occupational post - application inhalation exposure scenarios. **10.0 References**  Barrett, M., 03/26/2013, DP404096, Halosulfuron methyl Drinking Water Assessment for Additional Food/Feed Uses on Artichokes and Caneberry Subgroup 13 - 07A .Halosulfuron - Meth yl

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Page 29 of 37 Cheng, L., 11/26/2012, DP405659, Halosulfuron - methyl. Section 3 Registration on Artichoke and Can eberry Subgroup 13 - 07A. Summary of Analytical Chemistry and Residue Data. Meléndez, J., 05/15/2012, DP394244, Halosulfuron methyl Drinking Water Assessment for Additional Food/Feed Uses on Proso Millet, Pasture and Rangeland Grass Forage, Fodder and Hay (Crop Group 17). Negussie, M., 03/11/2013, DP405660, Halosulfuron - methyl. Acute and Chronic Aggregate Dietary (Food and Drinking W ater) Exposure and Risk Assessments for the Section 3 Registration Action on Artichoke and Caneberry Subgroup 13 - 07A . Smegal, D., 02/22/2012, TXR 0054045, **Halosulfuron -** **methyl**: Su mmary of hazard and Science Policy Council (HASPOC) Meeting of February 9, 2012: Recommendations on waiver requests for 28 - day inhlataion study. . Tsaur, N., 02/21 /20 13 , DP 404839 , **Halosulfuron -**  **Methyl .**  Occupational and Residential Exposure Assessment for Proposed IR - 4 Uses on Caneberry (subgroup 13 - 07A) and Artichokes. Ts aur, N., 06/12/2012, DP396460, Halosulfuron-Methyl **.** Occupational Exposure Assessment for Proposed New Uses on Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay) with An Updated Residential Exposure Assessment of All Existing Residential Uses . Walls, C., 07/19/2012, DP396458, **Halosulfuron -**  **Methyl**: Human Health Risk Assessment for Proposed New Uses o n Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay).

.Halosulfuron - Meth yl

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Page 30 of 37 **A ppendix**  **A .**  **Toxicology Profile and Executive Summaries A.1**  **Toxicology Data Requirements** The requirements (40 CFR 158.500 ) for Food Use for Halosulfuron - methyl are in Table 1. Use of the new guideline numbers does not imply that the new (1998) guideline protocols were used. **Study Technical**  **Required Satisfied**  870.1100 Acute Oral Toxicity ................................ ....................... 870.1200 Acute Dermal Toxicity ................................ .................. 870.1300 Acute Inhalation Toxicity ................................ .............. 870.2400 Acute Eye Irritation ................................ ....................... 870.2500 Acute Dermal Irritation ................................ ................. 870.2600 Skin Sensitization ................................ .......................... yes yes yes yes yes yes Y es

yes yes yes yes yes 870.3100 90 - Day

Oral Toxicity in Rodents ................................ .. 870.3150 90 - Day

Oral Toxicity in Nonrodents ............................. 870.3200 21/28 - Day Dermal Toxicity ................................ ........... 870.3250 90 - Day

Dermal Toxicity ................................ ................ 870.3465 90 - Day

Inhalation Toxicity ................................ ........... yes yes yes no CR Y es

yes yes

-

- a 870.3700a Prenatal Developmental Toxicity (rodent) ..................... 870.3700b Prenatal Developmental Toxicity (nonrodent) ............... 870.3800 Reproduction and Fertility Effects ................................ . yes yes yes Y es

yes yes 870.4100b Chronic Toxicity (nonrodent) ................................ ........ 870.4200b Carcinogenicity (mouse) ................................ ................ 870.4300 Combined Chronic Toxicity/Carcinogenicity ................ no yes yes Y es

yes yes 870.5100 Mutagenicity

—Bacterial Reverse Mutation Test .......... 870.5300 Mutagenicity

—Mammalian Cell Gene Mutation Test .. 870.5375 Mutagenicity

— Structural Chromosomal Aberrations ... 870.5395 Mutagenicity

—Other Genotoxic Effects ....................... yes yes yes yes Y es

yes yes yes 870.6200a Acute Neurotoxicity Screening Battery (rat) ................. 870.6200b 90 - Day

Neurotoxicity Screening Battery (rat) ............... 870.6300 Developmental Neurotoxicity ................................ ........ yes yes no Y es

yes

- 870.7485 Metabolism and Pharmacokinetics ................................ 870.7600 Dermal Penetration ................................ ........................ 870.7800 Immunotoxicity ................................ ............................. yes no no Y es

- no a Inhalation requirement is waived for the current and proposed uses (D. Smegal, TXR 0054045, 02/22/12)Halosulfuron - Meth yl

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Page 31 of 37 **A.2 Toxicity Profile**  **s Table**  **A.2. 1. Acute Toxicity of Halosulfuron**  **- M**  **ethyl Technical .**  **OPPTS No.**  **Study Type MRID**  **Results Toxicity**  **Category** 870.1100 Ac ute Oral - Rats 42139413 LD 50 : Males = 10,435 mg/kg Females = 7758 mg/kg Combined = 8866 mg/kg IV 870.1200 Ac ute Dermal - Rats 42139415 LD 50 >2000 mg/kg (limit test) III 870.1300 Ac ute Inhalation - Rats 42139417 LC 50 >6 mg/L IV 870.2400 Primary Eye Irritation Rabbits 42139419 Mild transient (<24 hr) irritation involving the conjunctiva and iris. IV 870.2500 Primary Skin

Irritation - Rabbits 42139421 Non - irritant IV 870.2600 Dermal Sensitization Guinea pigs 42139423 Not a skin sensitizer (maximization test) N/A **Table A.2.**  **2. Toxicity Profile of Halosulfuron -**  **M ethyl Techni**  **cal .**  **Guideline No.**  **Study Type MRID No.**  **(Date)/Classification/ Doses Results**  870.3100 (82 - 1) Subchronic oral

toxicity study in rats 43616301 (1995)/

Acceptable/ Guideline Doses: 0, 100, 1000, 10000, or 20000 ppm (diet) (M/F: 6.7/7.6, 66.5/75.8, 682.8/772.8, 1400/1578 mg/kg/day) NOAEL = M > 1400, F = 75.8 mg/kg/day LOAEL = M not determi ned, F = 772.8 mg/kg/day based on decreased body weight gains.

870.3100 (82 - 1) Subchronic oral

toxicity study in rats (28 day range finder) 42171501 (1988)/

Acceptable/

Nonguideline Doses: 0, 100, 400, 1600, or 6400 ppm (diet) (M/F: 7.4/8.9, 28.8/37.3, 116/147, 497/640 mg/kg/day) NOAEL = M = 116, F =147 mg/kg/day LOAEL = M = 497, F = 640 mg/kg/day based on decreased body weight gains, decreased organ weights and changes in clinical chemistry parameters. 870.3150 (82 - 1) Subchronic oral

toxicity study in nonrodents - dogs 42171502 (1991)/

Acceptable/

Nonguideline Doses: 0, 2.5, 10, 40, and 160 mg/kg/day (capsule) NOAEL = 10 mg/kg/day LOAEL = 40 mg/kg/day based on decreased body weight gains and food efficiency along with hematology and clinical chemistry changes. 870.3200 (82 - 2) 21 - day dermal

toxicity in rats 42661417 (1990)/

Acceptable/ Guideline Doses: 0, 10, 100, or 1000 mg/kg/day NOAEL = 100 mg/kg/day LOAEL = 1000 mg/kg/day based on a dose - related decrease in total body weight gain in males. Total body weight gain was also decreased in the 100 mg/kg/day group females, but the 1000 mg/kg/day group females were comparable to the control group. 870.3 465 (82 - 4 ) 90 - day inhalation

study in rats This data requirement has been waived (TXR D. Smegal, TXR 0054045, 02/22/12 )

870.4100 (83 - 1b) Chronic oral

toxicity study in 42396211 (1991)/

Acceptable/ Guideline NOAEL = 10 mg/kg/day LOAEL = 40 mg/kg/day based on decreased bodyHalosulfuron - Meth yl

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Page 32 of 37 **Table A.2.**  **2. Toxicity Profile of Halosulfuron -**  **M ethyl Techni**  **cal .**  **Guideline No.**  **Study Type MRID No.**  **(Date)/Classification/ Doses Results**  dogs Doses: 0, 0.25, 1.0, 10.0, or 40

mg/kg/day (capsule). w eight gains in males and females, decreased relative food efficiency in females along with hematological and clinical chemistry changes. 870.4300 (83 - 5) Combined

Chronic/ Carcinogenicity in rats 42661418 (1992)/

Acceptable/Guideline Doses: 0, 10, 100, 1000, or 2500, 5000 (males only) ppm (diet) (M/F: 0.44/0.56, 4.4/5.6, 43.8/56.3, 108.3/138.6, 225.6 (M) mg/kg/day) NOAEL = M=108.3, F=56.3 mg/kg/day LOAEL = M=225.6, F=138.6 mg/kg/day based on marginal decrease in body weight gain in both males and females. **No evidence of carcinogenicity.** 870.4200 (83 - 2) Carcinogenicity

study in mice 42661419 (1992)/

Acceptable/ Guideline Doses: 0, 30, 300, 3000, or 7000 ppm (diet) (M/F: 4.0/5.2, 41.1/51.0, 410.0/509.1, or 971.9/1214.6 mg/kg/day) NOAEL = M=410.0, F > 1214.6 mg/kg/day LOAEL = M=971.9, F>1214.6 mg/kg/day based on decreased body w eight gains and necropsy findings (increase incidence of microconcretion/mineralization in the testis and epididymis). **No evidence of carcinogenicity.** 870.3700 (83 - 3) Developmental

toxicity in rats 42139425 (1990)/

Acceptable/ Guideline Doses: 0, 75, 250, or 750 mg/kg/day (gavage) Maternal NOAEL = 250 mg/kg/day. Maternal LOAEL = 750 mg/kg/day, based on increased incidence of clinical observations, reduced body weight gains, reduced food consumption and food efficiency. Developmental NOAEL = 250 mg/kg/day. Developmental LOAEL = 750 mg/kg/day, based on decreased mean fetal body weight and mean litter size, increased fetal and litter incidences of soft tissue and skeletal variations. 870.3700 (83 - 3b) Developmental

toxicity study in rabbits 42139426 (1990)/

Acceptable/ Guideline Doses: 0, 15, 50, or 150 mg/kg/day (gavage) Maternal NOAEL = 50 mg/kg/day Maternal LOAEL = 150 mg/kg/day based on reduced body weight gain, food consumption and food efficiency. Developmental NOAEL = 50 mg/kg/day Developmental LOAEL = 150 mg/kg/day based on group decreased mean litter siz e, increased number of resorptions and resorptions per dam, and increased postimplantation loss. 870.3700 (83 - 3b) Developmental

toxicity study in rabbits 43621901 (1995) 3 -

chlorosulfonamide acid Metabolite/ Acceptable/Guideline Doses: 0, 30, 300, or 1000 mg/kg/day Maternal Toxicity NOAEL => 1000 mg/kg/day Maternal Toxicity LOAEL > 1000 mg/kg/day Developmental Toxicity NOAEL => 1000 mg/kg/day Developmental Toxicity LOAEL > 1000 mg/kg/day 870.3800 (83 - 4) Two - Generation

reproduction study in rats 42139427 (1991)/

Acceptable/ Guideline Doses: 0, 100, 800, or 3600 ppm (diet) ( F 0 Males: 6.3, 50.4, and 223.2 mg/kg/day; F 0 Females: 7.4, 58.7, and 261.4 mg/kg/day) Parental/Systemic NOAEL = M=50.5, F=58.7 mg/kg/day Parental/Systemic LOAEL = M=223.2, F=261.4 mg/kg/day based on decreased body weights, body weight gains, and reduced food consumption during the premating period in both sexes. Offspring NOAEL = 51/59 mg/kg/day Offspring LOAEL = 223.2/261.4 mg/kg/day based on decreased body weight in the F 1 pups and marginal decreased body weight in F 2 pups.Halosulfuron - Meth yl

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Page 33 of 37 **Table A.2.**  **2. Toxicity Profile of Halosulfuron -**  **M ethyl Techni**  **cal .**  **Guideline No.**  **Study Type MRID No.**  **(Date)/Classification/ Doses Results**  Reproductive NOAEL > = 223.2/261.4 mg/kg/day . 870.6200a (82 - 7) Acute

neurotoxicity in rats. 45754701 (1994) and

46199501 (1989)[positive control study]/ Acceptabl e/ Guideline Doses: 0, 200, 600, or 2000 mg/kg (limit dose) NOAEL = 600 mg/kg. LOAEL = 2000 mg/kg (limit dose) based on mortality in males.

870.6200b (82 - 7) Subchronic

neurotoxicity study in rats. 45754702 (1992)/

Acceptable/ Guideline Doses: M: 0, 100, 1000, or 10,000 ppm; F: 0, 100, 1000, or 4000 ppm (diet) (M/F: 0/0, 6.3/8.1, 62.8/82.6, or 706.0/315.9 mg/kg/day) NOAEL = M = F = 1000 ppm (M/F: 62.8/82.6 mg/kg/day). LOAEL = M = 10,000 ppm; F =4000 ppm (M: 706.0 mg/kg/day) in males based on decre ased body weight and body weight gain and (F: 315.9 mg/kg/day) in females based on decreased body weight gain. 870. 7485 (83 - 6) Metabolism 42139433 (1990)/ Acceptable/ Guideline 5 or 250 mg/kg single dose or 5 mg/kg/day repeated doses Absorption was rapid, incomplete and similar in both sexes. Elimination was most ly by urine and feces within 72 hours, appearing to be independent of dose and sex. Desmethyl NC - 319 and the 5 - hydroxy derivative were the major urinary and fecal metabolites . 870. 7800 ( 83 - 6) Immunotoxicity A waiver request for this data requirement has been submitted and is under review. 870.5100 (84 - 2 a) Mutagenic - Ames

Salmonella typhimurium and E. Coli . 42139428 (1991)/ Acceptable

(+/ - S9) 5 strains S. typh. Conc.: 1 - 10000 microgm/plate; E. Coli WpuvrA Conc.: 333 - 10000 microgram

/plate Negative. Concentrations => 5000 micro g m /plate found to be insoluble and/or cytotoxic.

870.5100 (84 - 2 a) Mutagenic - Gene

Mutation 43616302 (1995)/ Acceptable

(+/ - S9) 5 strains S. typh. Conc.: 50 - 5000 microgm/plate Negative. Conducted with 3 - chlorosulfonamide acid - the principal soil metabolite of halo sulfuron - methyl. 870.5300 (84 - 2) Mutagenic - Gene

Mutation - Hamster (Chinese ) 43616303 (1995) - Metabolite/

Acceptable (+/ - S9) Conc.: 350 - 3100 microgm/mL Negative. Conducted with 3 - chlorosulfonamide acid - the principal soil metabolite of halo sulfuron - methyl. 870.5300 (84 - 2) Mutagenic -

(HGPRT) - Hamster (Chinese). 42139431 (1991) - Metabolite/

Unacceptable Conc.: 100 - 1000 microgm /mL Conclusions indefinite due to partly to relatively high negative and low positive control values, solubility problems with test article. 870.5300 (84 - 2) Mutagenic -

(HGPRT) - Hamster (Chinese). 42661420 (1993)/ Acceptable

(+/ - S9) Conc.: 50 - 900 micro g m/mL Negative. Did not induce forward mutations at the HGPRT locus in Chinese Hamster ovary cells. Concentrations above 700 ug/mL were insoluble. 870.5375 (84 - 2) Mutagenic - In

vitro Clastogenic - Ham s ter (Chinese) 42139429 (1989)/ Acceptable

(+/ - S9) Conc.: 449 - 1810 micro g m/mL Negative. No chromosomal aberrations.Halosulfuron - Meth yl

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Page 34 of 37 **Table A.2.**  **2. Toxicity Profile of Halosulfuron -**  **M ethyl Techni**  **cal .**  **Guideline No.**  **Study Type MRID No.**  **(Date)/Classification/ Doses Results**  870.5395 (84 - 2) Mutagenic -

Micronucleus Assay - Mouse (CD - 1) 43616304 (1995) -

Metabolite/Acceptable Doses: 1250, 2500 or 5000 mg/kg Negative. Conducted with 3 - chlorosulfonamide acid the principal soil metabolite of halo s ulfuron - methyl. No overt toxicity for the treated animals or cytotoxicity for the target organ (bone marrow cells) was observed. 8 70.5395 (84 - 2) Mutagenic -

Micronucleus Assay - Mouse 42139430 (1989)/ Acceptable

Doses: 500, 1667 0r 5000 mg/kg. Negative. Did not induce significant elevations in the frequencies of micronucleated polychromatic erythrocytes. 870.5500 (84 - 2) Mutagenic -

Unscheduled DNA sy nthesis - Rat 42139432 (1990)/ Acceptable

(+/ - S9) Conc.: 25 - 1000 microgm/mL Negative. Fail to induce unscheduled DNA synthesis in primary rat hepatocytes.Halosulfuron - Meth yl

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Page 35 of 37 **Appendix B**  **. Physical/Chemical Properties**  **Table C1 .**  **Physicochemical Properties of Halosulfuron**  **- methyl**  **.** Parameter Value Reference Melting point/range 175.5 - 177.2 oC MRID 42139403; DP#s 173627 & 180565, 7/30/92, G.J. Herndon pH 4.11 at 25 oC (1% w /v slurry) Density 1.618 g/mL at 25 oC Water solubility at 20 oC pH 5 0.0015 g/100 mL pH 7 0.165 g/100 mL pH 9 0.747 g/100 mL Solvent solubility at 20 oC methanol 0.1616 g/100 mL n - hexane 0.001278 g/100 mL Vapor pressure <1 x 10 - 7 mm Hg at 25 oC Dissociation constant, Ka 3.61 x 10 - 4 at 22.4 oC Octanol/water partition coefficient, Log(KOW) at 23 oC 1.67 at pH 5

- 0.0186 at pH 7

- 0.542 at pH 9 UV/visible absorption spectrum Not availableHalosulfuron - Meth yl

Human Health Risk Assessment DP No. 404095

Page 36 of 37 **Appendix C**  **. Review of Human Research**  This risk assessment relies in part on data from studies in which adult human subjects were intentionally

exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involving exposure to many different pesticides, comprise generic pesticide exposure databases such as PHED and the Outdoo r Residential Exposure Task Force (ORETF). EPA has reviewed all the studies supporting these multi - pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentall y unethical or s ignificantly deficient relative to the ethical standards prevailing at the time the research was conducted. All applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no re gulatory

barrier to continued reliance on these studies.Halosulfuron - Meth yl

Human Health Risk Assessment DP No. 404095

Page 37 of 37 **Appendix D**  **. International Residue Limits** 



### Halosulfuron - me thyl (PC Code 128721); 10 / 3 1/2012 Table A. 1 Summary

of US and International Tolerances and Maximum Residue L imits Residue Definition : US Canada Mexico 2 Codex 40 CFR 180. 479 (a) (2) : Tolerances are established for residues of the herbicide halosulfuron - methyl , methyl 3 - chloro - 5 - [[[[(4,6 - dimethoxy - 2 - pyrimidinyl)amino]carbonyl]amino]sulfon yl] - 1 - methyl - 1 H

-pyrazole - 4 - carboxylate , including its metabolites and degradates, in the table below . Compliance with the tolerance levels specified in the following table is to be determined by measuring only halosulfuron - methyl . None None

Commodity 1 Tolerance (ppm) /Maximum Residue Limit (mg/kg) US Canada Mexico 2 Codex Artichoke 0.05 Caneberry

subgroup 13 - 07A 0.05

Completed: M. Negussie ; 11/21 /2012 1 Includes only commodities of interest for this action. Tolerance values should be the HED recommendations and not those proposed by the applicant. 2 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.