### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 2 of 44 1.0 Executive Summary

................................ ................................ ................................ ........... 4
2.0 HED Recommendations

................................ ................................ ................................ .... 7
2.1 Data D eficiencies and Requirements Prior to Registration

................................ ....... 7
2.2 Tolerance Considerations

................................ ................................ .............................. 8
2.2.1 Enforcement Analytical Method

................................ ................................ ............... 8
2.2.2 International Harmonization

................................ ................................ ..................... 8
2.2.3 Recommended Tolerances

................................ ................................ ......................... 9
2.2.4 Revisions to Petitioned

- For Tolerances

................................ ................................ .... 9
2.3 Label Recommendations

................................ ................................ ................................ 9
2.3.1 Re commendations from Residue Reviews

................................ .............................. 10
2.3.2 Recommendations from Occupational Assessment

................................ ............... 10
2.3.3 Recommendations from Residential Assessment

................................ ................... 10
3.0 Introduction

................................ ................................ ................................ ...................... 10
3.1 Chemical Identity

................................ ................................ ................................ ......... 11
3.2 Physical/Chemical Characteristics

................................ ................................ ............. 12
3.3 Pesticide Use Pattern

................................ ................................ ................................ .... 12
3.4 An ticipated Exposure Pathways

................................ ................................ ................. 15
3.5 Consideration of Environmental Justice

................................ ................................ .... 16
4.0 Hazard Characterization and Dose

- Response Assessment

................................ .......... 16
4.1 Summary of Toxicological Effects

................................ ................................ .............. 16
4.2 Safety Factor for Infants and Children (FQPA Safety Factor)

............................... 17
4.2.1 Completeness of the Toxicology Database

................................ .............................. 17
4.2.2 Evidence of Neurotoxicity

................................ ................................ ........................ 18
4.2.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

........ 18
4.2.4 Residual Uncertainty in the Exposure Database

................................ ................... 18
4.3 Toxicity Endpoint and Point of Departure Selections

................................ .............. 19
5.0 Dietary Exposure and Risk Assessment

................................ ................................ ......... 20
5.1 Residues of Concern Summary and Rationale

................................ .......................... 20
5.2 Food Residue Profile

................................ ................................ ................................ .... 21
5.3 Water Residue Profile

................................ ................................ ................................ .. 23
5.4 Di etary Risk Assessment

................................ ................................ .............................. 23
5.4.1 Description of Residue Data Used in Dietary Assessment

................................ .... 24
5.4.2 Percent Crop Treated Used in Dietary Assessment

................................ .............. 24
5.4.3 Acute Dietary Risk Assessment

................................ ................................ ............... 24
5.4.4 Chronic Dietary Risk Assessment

................................ ................................ ........... 24
5.4.5 Cancer Dietary Risk Assessment

................................ ................................ ............. 24
5.4.6 Summary Table

................................ ................................ ................................ ......... 25
6.0 Resident ial (Non

- Occupational) Exposure/Risk Characterization

............................. 25
6.1 Residential Handler Exposure

................................ ................................ .................... 25
6.2 Post

- Application Exposure

................................ ................................ .......................... 26
6. 3 Combined Exposure

................................ ................................ ................................ ..... 27
6.4 Residential Bystander Post

- application Inhalation Exposure

................................ . 28
6.5 Spray Drift

................................ ................................ ................................ .................... 28
7.0 Aggregate Exposure/Risk Characterization

................................ ................................ .. 29
7.1 Acute Aggregate Risk

................................ ................................ ................................ ... 29
7.2 Short

- Term Aggregate Risk

................................ ................................ ........................ 29

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 3 of 44 7.3 Intermediate

- Term Aggregate Risk

................................ ................................ ........... 30
7.4 Chronic Aggregate Risk

................................ ................................ .............................. 30
7.5 Cancer Aggregate Risk

................................ ................................ ................................ 30
8.0 Cumulative Exposure/Risk Characterization

................................ ............................... 30
9.0 Occupational Exposure/Risk Characterization

................................ ............................ 30
9.1 Short

- /Intermediate

- Term Handler Risk

................................ ................................ ... 30
9.2 Short

- /Intermediate

- Term Post

- Application Risk

................................ .................... 36
9.2.1 Dermal Post

- Application Risk

................................ ................................ ................. 36
9.2.2 Inhalation Post

- application Risk

................................ ................................ ............. 37
10.0 References

................................ ................................ ................................ ......................... 38 Appendix A. Toxicology Profile

................................ ................................ ................................ 39
A.1 Toxicology Data Requirements

................................ ................................ ................... 39
A.2 Toxicity Profiles

................................ ................................ ................................ ............ 40 Appendix B. International Residue Limits

................................ ................................ .............. 44

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 4 of 44 1.0 Executive Summary

On behalf of Canyon Group L.L.C. (Canyon), Gowan Company (Gowan) is proposing to add
new uses of the active ingredient (ai), halosulfuron

- methyl, on proso millet a nd crop group 17 ( grasses, forage, fodder, and hay). Halosulfuron

- methyl is a sulfonylurea herbicide which

inhibits the plant enzyme acetolacetate synthase and is used for pre

- and post

- emergent control of annual broadleaf weeds and nutsedges in several a gricultural crops as well as residen tial turf grass and ornamentals

.

The most recent risk assessment for halosulfuron

- methyl was conducted in 2010 for the uses on succulent and dried shelled peas/ beans, tuberous and corm vegetables, bushberries, okra, apples,

and rhubarb (D366410, W. Phang, 4/5/10). In accordance with the 2007 revised 40 CFR Part 158 Toxicology data requirements, an i mmunotoxicity study and a subchronic i nhalation toxicity study were required for halosulfuron methyl . However, HED has waived the inhalation toxicity study data requ irement at this time (TXR0054045 ).

Pending submission of revised Section s B and F , and an analytical standard for the rearrangement ester ( RRE ) of halosulfuron

- methyl , there are no additional toxicology or r esidue chemistry issues that would preclude granting unconditional registration for the requested uses of

halosulfuron

- methyl on proso millet and crop group 17 ( grasses, forage, fodder, and hay).

Proposed Use Profile

Halosulfuron

- methyl is formulated as a water dispersible granule (WG) and applied as postemergence broadcast foliar sprays using ground or aerial equipment. Application through any type of irrigation system is prohibited. Halosulfuron

- methyl may be applied to proso millet
once per season at a maximum application rate of 4 oz /A (0.0313 lb ai/A)

. For pasture and rangeland (crop group 17), halosulfuron

- methyl may be applied once per season at a maximum application rate of 8 oz /A (0.0625 lb ai/A ). The restricted entry interval (REI) is 12 hour s.

These new uses are proposed to be added to three end

- use product (EP) labels: Yukon Herbicide (EPA Reg. No. 81880

- 6) with 12.5% ai by weight, Sandea® Herbicide (EPA Reg. No. 81880

- 18) with 75% ai by weight, and GWN

- 3061 Herbicide (EPA Reg. No. 81880

- 2) with 75% ai by weight.

Exposure Profile Exposures to halosulfuron methyl are expected to occur for acute

- , short

- , intermediate

- , and long

- term (chronic) exposures

. The proposed agricultural use s on proso millet and crop group 17 ( grasses, forage, fodder, and hay) would result in new exposures in both food and drinking water. There 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 and post

- application activities.

Toxicity/Hazard

Halosulfuron

- methyl has low acute toxicity via the oral (Toxicity Category IV), dermal (Toxicity Category I II ), and inhalati on (Toxicity Category IV) routes. Halosulfuron

- methyl is a non

irritant for skin and eyes (Toxicity Category IV) and is not a dermal sensitizer. With repeated

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 5 of 44 dosing, halosulfuron

- methyl produces non

- specific effects, which are frequently characterized b y reduced body weight/body weight gain in the test animals. 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 i n 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 me an litter size was seen in the presence of decreases in body weight and food consumption in maternal animals were observed. However, a clear NOAEL for these effects was established in both rat and rabbit developmental toxicity studies. Halosulfuron

methy l did not produce reproductive effects. No neurotoxic effects were observed in the acute or subchronic neurotoxicity studies. Halosulfuron

- methyl is classified as “not likely to be carcinogenic to humans.” It is negative for mutagenicity in a battery of genotoxicity studies.

T he toxicology database is adequate, with the exception of the requirement for an immunotoxicity study which was required as a condition of registration. The 28

- day inhalation toxicity study, also a condition of registration, was waived.

The toxicity e ndpoints and points 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 en dpoints and points of depart ure 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 a ll three routes of exposure, Margins of Exposure ( MOE s ) and exposures can be combined where appropriate. The level of concern (LOC) for residential and occupational exposures via dermal and inhalation routes i s a MOE less than 100. The FQPA safety factor is 1X.

Dietary Exposure (Food and Water) and Risk Estimates

The residue che mistry 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 acu te reference dose (aRfD) was established for females 13

- 49 years
old , and an acute die tary exposure assessment was only conducted for females 13

- 49 years old

. C onservative acute and chronic dietary exposure assessment s were performed for halosulfuron

methyl using tolerance

- level residues and 100% crop trea ted

. The estimated drinking water

conc entration (EDWC) for rice was 59.2 μ g/L and used directly in both the acute and chronic

assessments . For all processed commodities, DEEM version 7.81 default processing factors
were assumed. The results of the acute and chronic dietary (f ood and drinking water) analyses are below the Agency’s level of concern (LOC) for the general U.S. population and all population subgroups. T he acute dietary (food and drinking water) exposure is estimated at < 1 %
of the acute Population Adjusted D ose (a PAD) for the females 13

- 49 years old. 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 6 % of the cPAD for all infants , the popul ation subgroup with the highest estimated chronic dietary exposure to halosulfuron

- methyl

. Halosulfuron

- methyl is classified as “not likely to be carcinogenic to humans;” therefore, cancer

risk is neither expected nor assessed.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 6 of 44 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.

R esidential Handler: Residential short

- term (1

- 30 days) dermal and inhalation exposures are expected from handler activities associated with the existing uses. HED used data from ORETF and PHED Version 1.1 to assess residential handler exposures. MOEs greater than 100 are deemed adequate to protect residential halosulfuron

- methyl handlers. Short

- term combined (dermal + inhalation) residential handler MOEs range from 7,200 to 190,000 and, therefore

, are not of concern.

R esidential Post

- application: R esidential short

- term dermal and incidental oral exposures are expected from post

- application activities associated with the existing uses. MOEs greater than

100 are deemed adequate to protect adults and children from post

- application residues of

halosulfuron

- methyl

. Short

- term post

- application MOEs for all residential scenarios range from 1,000 to 11,000,000 and, therefore

, are not of concern.

Residential Aggregate 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) pathways. All aggregate MOEs are greater than 100, which indicates that exposure and risk do
not exceed HED’s LOC. The adult and c hildren short

- term aggregate (dietary + residential)

MOEs are 1,800 and 840 , respectively. Intermediate

- term and chronic aggregate risk are expected to be equivalent to chronic exposure via the dietary pathway.

Occupational Exposure and Risk Estimates Ag ricultural 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) a t baseline and do not exceed
HED’s LOC. For proso millet, the baseline short

- term combined (dermal + inhalation) MOEs range from 3,000 to 140,000. Intermediate

- term exposure is unlikely due to the agricultural practices of millet. For pasture and rangel and, t he baseline short

- term combined (dermal + inhalation) MOEs range from 15,000 to 71,000 and t he baseline intermediate

- term combined MOEs range from 200 to 9,600.

Agricultural Post

- application: There is potential for short

- and intermediate

- term occu pational exposure during post

- application activities. There are no risk estimates of concern on day 0 (12 hours after application); a ll scenarios resulted in MOEs greater than the LOC of 100 (ranging from 400 to 160,000) on day 0 (12 hours after application)

. Based on a quantitative post

application assessment , the 12

- hour REI on the proposed label is acceptabl e

.

HED assumes that post

- application inhalation exposures are minimal following applications of

an ai with low vapor p ressure

. Since halosulfuron

- methyl has low acute inhalation toxicity (Toxicity Category IV) and a low vapor pressure , post

- application inhalation exposures and risk

estimates were not quantitatively assessed.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 7 of 44 Environmental Justice Considerations : Potenti al 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 which adult human subjects were intentionally exposed to a pesticide or other chemical. These data

, the Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Expos ure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database; and the Agricultural Re

- entry Task Force (ARTF) database, are subject to ethics review pursuant to 40 CFR 26, have received that review, and are compliant with

a pplicable ethics requirements. For certain studies that review may have included review by the Human Studies Review Board. Descriptions of data sources as well as guidance on their use can

be found at http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

.

2.0 HED Recom mendations

Provided revised Sections B (OPPTS 860.1200), F (OPPTS 860.1550)

, and an analytical

reference standard for the RRE of halosulfuron

- methyl are submitted

, HED can recommend granting an un conditional registration for the requested use of halosulfuron

- methyl on proso millet and pasture and rangeland grasses. Additional data are needed prior to the registration as outlined in Section 2.1 below. The specific tolerance recommendations are discussed in Section 2.2, and label modifications are discussed in Section 2.3.

2.1 Data Deficiencies and Requirements Prior to Registration

The following must be provided prior to a tolerance being established or registration

allowed:

860.1200 Directions for Use For all labels, the preharvest interval (PHI) and pregrazing interval (PGI) for millet forage should be revised to 0

- day PHI.

All labels should be revised to:

o Specify a 37

- day PHI for proso millet hay and a 50

- day PHI for proso millet grain
and straw.

o Specify a 0

- day PGI for grass fora ge for all animals (beef, lactating and non

lactating).

o Because crop oil concentrates (COC) were not used in any of the submitted crop field trials on proso millet or grass, the labels for the 12.5% and 75% WG
formulations should be revised to state that o nly non

- ionic surfactants (NIS) adjuvants may be added to the spray mixtures for these crops.

o Remove the recommended 30

- day pre

- slaughter interval (PSI).

860.1550 Proposed Tolerances A revised Section F must be submitted to reflect the tolerances and correct commodity

definitions as listed in Table 2.2.4

.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 8 of 44 860.1650 Submittal of Analytical Reference Standards

An an alytical reference standard for the RRE of halosulfuron

- methyl must be submitted to the EPA National Pesticide Standards Repository.

The following d ata are required as a condition of registration :

TOXICOLOGY

870.7800 Immunotox icity Study The Immunotoxicity study is required to fulfill current 40 CFR Part 158 data requirements. This study was called in as a condition of registration in the most recent risk assessment (D366410, W. Phang, 4/5/10).

The following d ata should be submitted w ith future uses :

RESIDUE CHEMISTRY

860.1480 Meat/Milk/Poultry/Eggs If future new use requests increase the dietary burden, a new dairy cattle feeding study
will be needed.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

Adequate analytical methods are available for the enforcement of tolerances for residues of

halosulfuron

- methyl in plants (Method RES

- 109

- 97

- 4), and for residues of halosulfuron

- methyl
and its 3

- CSA metabolites in livestock commodities (Method RES

- 046

- 93). Samples from the submitted field trial studies were analyzed for residues of halosulfuron

- methyl using a modified
version of the plant enforcement method (gas chromatography with nitrogen phosphorus or mass selective detection; GC/NPD or GC/MSD) with a petitioner

- validated limit of quantitation (LOQ; determined as the lowest level of method validation; LLMV) of 0.01 ppm. The method

was adequate for data c ollection based on acceptable concurrent method recoveries, and the fortification levels used in concurrent method recovery were adequate to bracket expected
residue levels.

Residues of halosulfuron

- methyl and 3

- CSA are not adequately recovered by FDA Mul tiresidue Method protocols

. The results have been forwarded to FDA.

2.2.2 International Harmonization

There are no Codex, Canadian, or Mexican maximum residue limits ( MRLs ) establish ed for

residues of halosulfuron

- methyl in crop or livestock commodities

. An International Residue
Limit Status sheet is attached (Appendix B ).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 9 of 44 2.2.3 Recommended Tolerances

HED recommends for the following tolerances listed in Table 2.2.3.

Table 2.2.3 . Tolerance Summary for Halosulfuron

- Methyl.
Commodity Proposed /Existing Tolerance (ppm) Recommended

Tolerance (ppm) Comments; Correct Commodity

Definition

Millet, proso, forage 7.0 10 The data supports a tolerance of 10 ppm

with a 0

- day PHI/PGI.

Millet, proso, hay 0.02 0.01
Millet, proso, grain 0.01 0.01
Millet, proso, straw 0.01 0.01
Grass forage, fodder, and hay, Crop group 17 forage 17 20 Grass

, forage, fodder, and hay, group 17, forage
Grass forage, fodder, and hay, Crop group 17 hay 0.90 0.5 Grass, forage, fodder, and hay, group 17, hay



### Additional Livestock Commodity Tolerances That Need to be Proposed/Established

Cattle, meat byproducts 0.1 1 .0
Goat, meat byproducts 0.1 1. 0
Horse, meat byproducts 0.1 1. 0
Sheep, meat byproducts 0.1 1. 0


### Additional Livestock Commodity Tolerances That Need to be Proposed/Established

Cattle, fat None 0.05

Cattle, meat None 0.05

Goat, fat None 0.05

Goat, meat None 0.05

Horse, fat None 0.05

Horse, meat None 0.05

Milk None 0.05
Sheep, fat None 0.05
Sheep, meat None 0.05



### 2.2.4 Revisions to Petitioned

- For Tolerances

Table 2.2.3 compares proposed and recommended tolerance levels. The recommended plant commodity tolerance levels are based on the submitted magnitude of the residue data and the Agency’s tolerance spreadsheet as specified by the Guidance for Setting Pesti cide Tolerances
Based on Field Trial Data SOP. Differences in proposed and recommended tolerances may be attributed to the petitioner having used the North American Free Trade Agreement (NAFTA) tolerance calculation procedures for determining the toleranc e and HED’s use of the OECD tolerance calculation procedures; for grass hay, the petitioner used values below the LOQ in the tolerance calculation whereas HED used LOQ values. Livestock tolerances are derived from reevaluation of the dairy/beef cattle die t with new feed items (millet and grass)

.

2.3 Label Recommendations

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 10 of 44 2.3.1 Recommendations from Residue Reviews

The following label revisions are needed: For all labels, the PHI/PGI for millet forage should be revised to 0

- day PHI.

All labels should be revised to:

o Specify a 37

- day PHI for proso millet hay and a 50

- day PHI for proso millet grain
and straw.

o Specify a 0

- day PGI for grass forage for all animals (beef, lactating and non

lactating).

o Because COC were not used in any of the submitted crop field trials on proso millet or grass, the labels for the 12.5% and 75% WG formulations should be revised to state that only NIS adjuvants may be added to the spray mixtures for these crops.

o Remove the recommended 30

- day PSI.

2.3.2 Recommendations from Occupational Assessment

Th roughout th e GWN

- 3061 (EPA Reg. No. 81880

- 2) label , the instructions often reference the Sandea® (EPA Reg. No. 81880

- 18) label. These references should be corrected.

2.3.3 Recommendations f rom Residential Assessment

None

3.0 In troduction

Halosulfuron

- methyl is a selective herbicide belonging to the sulfonylurea group of herbicides. It inhibits the action of the plant enzyme acetolactate synthase. The enzyme is not found in

mammals (including humans). Halosulfuron

- methyl i s 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 §180.479 at levels ranging from 0.05 to 2.0 ppm.

Halosulfuron

- methyl is sold in the US as dry flowable/water

- dispersible granule formulations or

as emulsifiable concentrates.

The petitioner, Canyon Group LLC (agent Gowan Company) has submitted a r equest for amended registration of a 12.5% water dispersible granule (WG) formulation of halosulfuron

methyl (Yukon Herbicide; EPA Reg. No. 81880

- 6; MAI containing 55% dicamba) and two 75% WG formulations (Sandea Herbicide, EPA Reg. No. 81880

- 18, and GWN

- 3 061, EPA Reg. No.

81880

- 2) for use on proso millet and pasture and rangeland grasses. The proposed uses reflect foliar broadcast application to proso millet at 0.023

- 0.0313 lb ai/A or to pasture and rangeland grasses at 0.0313

- 0.0625 lb ai/A

. The propose d PHIs/PGIs range from 0 days to 37 days for millet commodities and pasture grass; no PHI has been proposed for millet grain and straw.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 11 of 44 3.1 Chemical Identity

The chemical structure and nomenclature of halosulfuron

- methyl and the 3

- chlorosulfonamide

moi ety ( 3

- CSA ) are presented in Table 3.1

.

Table 3.1. Halosulfuron

- M ethyl Nomenclature

. Chemical structure

Common name halosulfuron

- methyl
Company experimental name MON 12000, NC

- 319

IUPAC name methyl 3

- chloro

- 5

- (4,6

- dimethoxypyrimidin

- 2

- ylcarb amoyl sulf amoyl)

- 1

- methylpyrazole

- 4

- carboxylate

CAS name methyl 3

- chloro

- 5

- [[[[(4,6

- dimethoxy

- 2

- pyrimidinyl)amino]carbonyl]amino]sulfonyl]

- 1

- methyl

- 1 H

- pyrazole

- 4

- carboxylate
CAS registry number 10078 4

- 20

- 1

End

- use product (EP) 75% WDG ( GWN

- 3061 Herbicide ; EPA Reg. No. 81880

- 2)

Chemical structure of

3

- chlorosulfonamide moiety (3

- CSA)

3

- chloro

- 1

- methyl

- 5

- sulfamoyl

- 1 H

- pyrazole

- 4

- carboxylic acid
Rearrangement ester (RRE) of
halosulfuron

- methyl

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 12 of 44 3.2 Physical/Chemical Characteristics

The physicochemical properties of the technical grade of halosulfuron

- methyl are presented in
Table 3.2

.

The octanol/water partition coefficient suggests that halosulfuron

- methyl is not fat soluble. In fact, halosulfuron

- methyl has significant water solubility especially at elevated pH. The low vapor pressure indicates little vaporization.

Halosulfuron

- met hyl, like most other sulfonylurea herbicides, is extremely mobile with a median

K
oc 

### of 104 g/mL and K f 

### (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 potential to leach to groundwater, and also presents concerns for transport to surface water by

r unoff.

3.3 Pesticide Use Pattern

Halosulfuron

- methyl is a sulfonylurea herbicide proposed for pre

- and post

- emergence control of broadleaf weeds and nutsedge. The end

- use products (EPs) relevant to this registration action are Yukon Herbicide (EPA Reg. No. 81880

- 6)

, Sandea® Herbicide (EPA Reg. No. 81880

- 18) and

GWN

- 3061 Herbicid e (EPA Reg. No. 81880

- 2). These products are currently registered to Gowan Company and are classified as WDG formulation s. Sandea® Herbicide and GWN

- 3061
Herbicid e contain 75% halosulfuron

- methyl , whereas, Yukon Herbicide contains 12.5% a.i

.

The petitioner is proposing to add the proso millet and crop group 17 ( grasses, forage, fodder, and hay) to the three labels. The proposed use patterns are presented in Table 3.3. Table

. 3.2. Physicochemical Properties of Halosulfuron

- Methyl

. Parameter Value Reference
Melting point/range 175.5

- 177.2 oC MRID 42139403; D173627 & D180565, 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, K

a 3.61 x 10 - 4 at 22.4 oC
Octanol/water partition coefficient, Log(K OW ) at 23 oC 1.67 at pH 5

- 0.0186 at pH 7

- 0.542 at pH 9
UV/visible absorption spectrum Not available

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 13 of 44 Table 3. 3 Summary of Directions for Use of Halosulfuron

- methyl.
Applic. Timing, Type, and Equip. Formulatio

n [EPA Reg. No.] Applic.

Rate
oz/A (lb ai/A) Max. No.

Applic.

per Season Max.

Seasonal Applic.

Rate
oz/A (lb ai/A) PHI/PGI 1

(Days) Use Directions and

Limitations 2

Proso Millet

Post weed emergence and actively growing weeds; Foliar, Broadcast,

G round or aerial; 12.5% WG

[81880

- 6] 3

- 4 oz/A

(0.0234

- 0.0313 ) Not

specified ( NS ) 4 oz/A

( 0. 0 313 ) Forage

Beef & non

lactating:

0 Lactating dairy:

7

Hay
37 Apply at the 3

- to 5

- leaf stage. A PSI of 30 days is specified

for beef and non

- lactating

animals.

Master Label : Apply in minimum spray

volumes of 5

- 15 gal/A ( GPA ) by air or 1 0 GPA by ground. Do not apply through any type of irrigation system. Avoid disturbing (cultivation)
treated a reas for at least 7

- days following application.

A non

- ionic surfactant is required at 0.25 to 0.5% v/v or a crop oil concentrate may be
used instead at 1% v/v.

Post weed emergence and actively growing

weeds ; Foliar, Broadcast, ground or band application,

aerial 75% WG

[ 81880

- 18 ] 0.5

- 0.67

(0.0234

- 0.0313 ) NS 0.67

( 0.0313 ) 0 Apply at the 2

- leaf through layby stage (before grain head emergence)

.

Master Label: Ground (min. 15 gal/A) or aerial (3

- 15 gal/A)

. Do not apply using air assisted (air blast) field crop sprayers. Do not apply through any type of irrigation system. Do not apply more than 2 oz/A per 12 month period (includes applications to the crop and to row middles/furrows).

A non

- ionic surfactant is

recommended at 0.25 to 0.5% v/v or a crop oil concentrate at
1% v/v.
Use of a COC or silicone

- based adjuvants can result in crop injuryand reduced yields and

are not recommended for
postemergence.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 14 of 44 Table 3. 3 Summary of Directions for Use of Halosulfuron

- methyl.
Applic. Timing, Type, and Equip. Formulatio

n [EPA Reg. No.] Applic.

Rate
oz/A (lb ai/A) Max. No.

Applic.

per Season Max.

Seasonal Applic.

Rate
oz/A (lb ai/A) PHI/PGI 1

(Days) Use Directions and

Limitations 2

Post weed emergence and actively growing

weeds ; Foliar, Broadcast, ground or band application,

aerial 75% WG

[ 81880

- 2] 0.5

- 0.67

(0.0234

- 0.0313 ) NS 0.67

( 0.0313 ) 0 Apply at the 2

- leaf through layby stage (before grain head emergence)

.

Master Label : Apply in minimum spray volumes of 3

- 15 GPA by air or 10 GPA by ground. Do not apply through any type of irrigation system. Avoid disturbing (cultivation)

treated areas for at least 7

- days following application.

A non

- ionic surfactant is required at 0.25 to 0.5% v/v or a crop oil concentrate may be
used instead at 1% v/v.
Pasture and Rangeland Grasses

Post weed

emergence; Foliar, Broadcast,

G round or aerial; 12.5% WG

[ 81880

- 6] 4

- 8 oz/A

(0.0313

- 0.0625 ) NS 8 oz/A

( 0.0625 ) Forage

Beef & non

lactating:

0 Lactating dairy:

14

Hay
37 A PSI of 30 days is specified
for beef and non

- lactating

animals.

Same as the master label under proso millet.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 15 of 44 Table 3. 3 Summary of Directions for Use of Halosulfuron

- methyl.
Applic. Timing, Type, and Equip. Formulatio

n [EPA Reg. No.] Applic.

Rate
oz/A (lb ai/A) Max. No.

Applic.

per Season Max.

Seasonal Applic.

Rate
oz/A (lb ai/A) PHI/PGI 1

(Days) Use Directions and

Limitations 2

Postemergence 3

Foliar broadcast

Ground

or aerial 75% WG

[81880

- 18 ] 0.67

- 1.33

(0.0313

- 0.0625 NS 1.33

( 0.0625 ) Forage

Beef & non

lactating:

0 Lactating dairy:

14

Hay

37 Apply to established pasture and rangeland. A PSI of 30 days is specified for beef and

non

- lactating animals. Ground (min. 1 0 gal/A)

Same as the master label under proso millet, except for g round application use min. 1 0 gal/ A

.

Postemergence 3

Foliar broadcast
Ground

or aerial 75% WG

[81880

- 2] 0.67

- 1.33

(0.0313

- 0.0625 NS 1.33

( 0.0625 ) Forage

Beef & non

lactating:

0 Lactating dairy:

14

Hay
37 Apply to established pasture and rangeland. A PSI of 30 days is specified for beef and

non

- lactating animals.

Same as the master label under proso millet.

1 The proposed use pattern as described in the petition materials under “Residue Chemistry including Reasonable Grounds in Support of Petition” indicates that the proposed pregrazing intervals are: 7 days for all animals for proso millet; and 7 days for lactating animals and 0 days for all other animals for pasture and rangeland grasses.

2 PSI = Preslaughter interval.

3 The labels for the 75% WG formulations also includ e directions for spot treatment applications to grasses which are not presented herein.



### 3.4 Anticipated Exposure Pathways

The Registration Division has requested an assessment of human health risk to support the proposed new use s of halosu l furon

- methyl o n proso millet and crop group 17 ( grasses, forage, fodder, and hay) . Humans may be exposed to halosulfuron

- methyl in food and drinking water,

since halosulfuron

- methyl may be applied directly to growing crops and application may result

in halosulfuron

- methyl reaching surface and ground water sources of drinking water. C urrently,

there are residential uses of halosulfuron

- methyl on turf, so there is likely to be exposure in residential settings. In an occupational setting, applicators may be exposed while handling the pesticide prior to application, as well as during app lication. There is a potential for post

application exposure for workers re

- entering treated fields.

Risk assessments have been previously conducted for halosulfuron

- methyl, dated 4/5/10 (D366410, W. Phang ). This risk assessment considers all of the aforementioned exposure pathways based on the proposed new uses of halosulfuron

- methyl, but also considers the existing uses as well, particularly for the dietary and residential exposure assessments.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 16 of 44 3.5 Co nsideration 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 Low

- Income Populations," ( http://www.eh.doe.gov/oepa/guidance/justice/eo12898.pdf

. As a part of every pesticide risk assessment, OPP considers a larg e 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 consumption,

and activitie s in and around the home that involve pesticide use in a residential setting. Extensive data on food consumption patterns are compiled by the USDA under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk assessments for all registered food uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary exposure to smaller, specialized sub groups 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 ent ering or playing on treated areas postapplication are evaluated. Further considerations are currently in development as OPP has committed resources and expertise to the development of specialized software and models that consider exposure to bystanders an d farm workers as well as lifestyle 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 peas/beans, tuberous
and corm v egetables, bushberry, okra, apples, and rubarb (W. Phang, 04/05/10, D366410). Since then, no new toxicology data have been submitted. The hazard characterization and toxicity endpoints for risk assessment remain unchanged since the 2006 risk assessment f or uses on alfalfa (M. Rust, 9/21/2006, D331643).

4.1 Summary of Toxicological Effects

Halosulfuron

- methyl is a member of the sulfonylurea herbicides, and it i nhibit s acetolactate synthase

, a specific plant enzyme not found in mammals. The mode of act ion in mammals for

halosulfuron

- methyl is undetermined.

The metabolism data indicated that with oral administration, halosulfuron

- methyl was absorbed rapidly with incomple te absorption from the GI tract . Within 72 hours, the absorbed

halosulfuron

- methyl was eliminated in the urine and feces. Desmethyl NC

- 319 and the 5

- hydroxy derivative were the major urinary and fecal metabolites. No tissue retention was demonstrated. The absorption, elimination, an d metabolism showed no sex dependence.

Halosulfuron

- methyl has low acute toxicity (Toxicity Category III

- IV) by 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

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 17 of 44 weight was seen in the chronic oral toxicity study and decreased body weight gain was observed in females in the subchronic oral toxicity study. In the rat and mouse, there was a decreas e 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 dec reases 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

- impl antation losses and decrease in mean litter size was seen in the presence of decreases in body weight and food consumption in maternal animals were observed. However, a clear NOAEL for these effects was established in both rat and rabbit developmental

tox icity studies. Halosulfuron

- methyl did not produce reproductive effects. No neurotoxic effects were observed in the acute or subchronic neurotoxicity studies.

Halosulfuron

- methyl is negative for mutagenicity in a battery of genotoxicity studies. It is classified as “not likely to be carcinogenic to humans” based on lack of evidence for carcinogenicity in mice and rats following long

- term dietary administration.

4. 2 Safety F actor for Infants and Children (FQPA Safety Factor)

A detailed analysis of the data supporting HED’s FQPA evaluation is presented in a previous risk assessment (D331643, M. Rust, 9/21/06). No additional data have been submitted and no new policy changes have been implemented that would change the conclusio ns of the 2006 risk assessment. With the exception of the data requirement for an immunotoxicity study, the conclusions regarding the FQPA Safety Factor in the previous risk assessment are applicable to
the current action and are summarized below. HED ha s determined that reliable data show it would be safe for infants and children to reduce the FQPA safety factor to 1X.

4. 2 .1 Completeness o f the Toxicology Database

The toxicology database for halosulfuron

- methyl is sufficient and of good quality. However, 40 CFR §158 requires an immunotoxicity stud y (OPPTS Guideline 870.7800) for pesticide registration. In the absence of specific immunotoxicity studies, HED has eva luated the available toxicity database to determine whether an additional database uncertainty factor is needed to account for potential immunotoxicity. The toxicology database of this chemical does not show any evidence of biologically relevant effects o n the immune system. The overall weight of the
evid ence suggests that this chemical does not directly target the immune system . HED does not
believe that immunotoxicity testing will result in a NOAEL less than that (10 mg/kg/day) used to
derive the curre nt cRfD of 0.1 mg/kg/day. Consequently, HED believes the existing data are sufficient for endpoint selection for 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.

Further, the 28

- day inhalation toxicity study, also a condition of registration, was waived (Hazard and Science Policy Council (HASPOC) Meeting, TXR # 0054045, DP# D397243, D. Smegal, MPH, 2/22/12).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 18 of 44 4. 2 .2 Evidenc e of N eurotoxicity

Halosulfuron methyl 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 t he limit dose in any of the short

term studies in rats or mice (subchronic oral, 28

- day dermal) or chronic studies . No neurotoxic effects were observed during the acute or subchronic neurotoxicity battery in which animals were dosed at systemically 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

- nat al 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 fetuse s 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 was seen in the presence

of decreases in b ody 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 NO AELs/LOAELs for developmental and maternal toxicities, developmental effects were seen in the presence of maternal toxicity, and the effects were only seen at the high dose. Additionally, in rats developmental effects were seen at a dose which is approach ing the limit

- dose. The degree of concern is 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 a screening level analysis. Th e assessment s utilized tolerance level residues for all crops. In addition, default processing factors were assumed for all commodities , and 100% crop treated was assumed for all commodities. The DEEM analysis also assumed that all drinking
water will contain halosulfuron methyl at the highest EDWC levels modeled by EFED for ground water or surface water. For these reasons it can be conclude d that the DEEM

- FCID analysis does not underestimate risk from chronic exposure to halosulfuron methyl. Similarly,
HED does not believe that the non

- dietary occupational and residential exposure s are underestimated because they are also based on conservati ve assumptions

, including maximum application rates, labeled personal protective equipment ( PPE ) , and standard values for unit

exposures and acreage treated/amount handled

.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 19 of 44 4. 3 Toxicity Endpoint and Point of D eparture Selections

T here have been no chan ges 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

shor t

- 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. The use of a POD derived from oral toxicity study on halosulfuron

- methyl yielded MOEs as low as 4,100 for occupational inhalation exposure and it was protective of the potential inhalation exposure for the proposed uses.

Table 4. 3.1

. Toxicological Doses and Endpoints for Halosulfuron

- M ethyl for Non

- Occupational and

Occupational Human Health Risk Assessments. Exposure/
Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD,

Level of
Concern for
Risk
Assessment Study and Toxicological Effects

Acute Dietary (Females 13

- 49 years of age) NOAEL=

50 mg/kg/day UF A = 10x

UF H = 10x FQPA SF= 1x Acute RfD = 0.5

mg/kg/day

aPAD =0.5 mg/kg/day Developmental 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)

. Acute Dietary (General Population including Infants and Children) N/A N/A N/A 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 Developmental 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 months) 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 cli nical 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 Dermal Toxicity Study

- Rat

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

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 20 of 44 Table 4. 3.1

. Toxicological Doses and Endpoints for Halosulfuron

- M ethyl for Non

- Occupational and

Occupational Human 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 months) + 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 Developmental Toxicity

- Rabbit

LOAEL = 15 0 mg/kg/day based on decreased body weight gain, food consumption, and food efficiency (maternal toxicity).

Inhalation
Intermediate

Term (1

- 6 months) 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 human s" 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 extrapolation for the intermediate term dermal exposure risk. Absorption via the inhalation route is presumed to be equivalent to oral absorption. 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 applicable



### 5.0 Dietary Exposure and Risk Assessment

5.1 Residues of Concern Summary and Rationale

The residues of concern for dietary risk assessment and the tolerance expression are summarized
in Table 5.1. The residue of concern in plants is the parent compoun d, halosulfuron

- methyl.

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

- chlorosulfonamide moiety (3

- CSA) by converting residues to 3

- CSA, tolerances for residues in livestock commodities are expressed in terms of halosulfuron

- methyl and its
metabolites determined as 3

- CSA, expressed as halosulfuron

- methyl equivalents.

The parent compound is an adequate for enforcement , and is the only residue included in the tolerance expression. The 3

- CSA metabolites are also a major residue found in livestock commodities and is included in the dietary risk assessment. Based on the environmental fate data, halosulfuron m ethyl is the only residue included in the drinking water assessment. Further information on the metabolism and degradation may be found in the risk assessment dated 4/5/10 (W. Phang, D366410).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 21 of 44 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



### 5 .2 Food Residue Profile

Crop Field Trials

The submitted magnitude of the residue data , summarized in Table 5.2.1, are adequate for risk assessment and tolerance assessment. For all crops, the number and locations of field trials are adequate. The proso millet trials reflect a single foliar broadcast application of a WG

fo rmulation at a target application rate of 0.0313 lb ai/A; a non

- ionic surfactant ( NIS ) was used

in all trials. The pasture and rangeland grass es trials reflect a single foliar broadcast application
of a WG formulation of halosulfuron

- methyl at a target application rate of 0.0625 lb ai/A ; an NIS
was used in all trials. The Agency’s tolerance spreadsheet, as specified by the Guidance for Setting Pesticide Tolerances Based on Field Trial Data SOP, was used to determine appropriate
tolerance levels.

The available proso millet data will support tolerances at the LOQ of 0.01 ppm for proso millet hay, grain, and straw commodities, provided the petit ioner proposes a PHI of 50 days for grain and straw. Quantifiable residues were observed in/on forage harvested at 0

- and 7

- day PHIs. Using the OECD tolerance calculation procedures, the recommended tolerances are: 10 ppm (0

- day PHI) for millet forage , 20 ppm for grass forage (based on a 0

- day PGI) and 0.5 ppm for grass hay. HED recommends a tolerance of 10 ppm for millet forage based on residue data using 0

- day PHI. The differences in the proposed and recommended tolerances for these commodities

are due to the petitioner having used the NAFTA tolerance calculation procedures in determining the proposed tolerances. For grass hay, the petitioner used values below the LOQ in the tolerance calculation whereas HED used LOQ values.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 22 of 44 Table 5.2.1. Summary of Residue Data from Proso Millet Crop Field Trials with Halosulfuron

- methyl.
Commodity Total

Rate
lb ai/A (kg ai/ha) PHI

(days) Residue Levels (ppm) 1

n Sample
Min. Sample

Max. LAFT 2 HAFT 2 Median Mean Std.

Dev.

PROSO MILLET (proposed use = 0.0313 lb ai/A total application rate;

PHIs/PGIs = 0 or 7 days (forage) and 37 days (hay) 3

Forage 0.0310

- 0.0314

(0.0347

- 0.0352) 0 5 2.37 5.81 2.42 5.04 2.76 3.14 1.08

7 5 0.0231 0.640 0.0261 0.634 0.0744 0.179 0.256

Hay 36

- 37 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Grain 51

- 67 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

Straw 51

- 67 5 <0.01 <0.01 <0.01 <0.01 0.01 0.01 N/A

PASTURE AND RANGELAND GRASSES (proposed use = 0.0 625 lb ai/A total application rate;

PHIs/PGIs = 0 or 14 days (forage) and 37 days (hay) 4

Grass forage 0.0622

- 0.0651

(0.0697

- 0.0730) 0 12 3.06 11.2 3.24 11.0 6.52 6.66 2.69

6

- 7 12 0.0252 4.89 0.0269 4.57 0.972 1.46 1.50
Grass hay 23

- 37 12 <0.01 0.389 <0.01 0.384 0.0329 0.0702 0.109

1 Except for sample min/max, values reflect per trial averages; n = no. of field trials. For calculation of median, mean, and standard deviation, the LOQ (0.01 ppm) was used for any results reported as <LOQ in Table C.3. N/A = Not applicable.

2 LAFT = lowest average field trial; HAFT = highest average field trial.

3 It is not clear whether the petitioner intends to support a PHI/PGI of 0 days, 7 days, or both for millet forage (refer to 860.1200 for additional details); no PHI has been proposed for grai n and straw.

4 Per OCSPP 860.1000 Table 1, a 0

- day PHI/PGI is required for grass forage.



### Processing Studies

There are no proposed uses that are relevant to this guideline topic.

Storage Stability

Adequate storage stability data for halosulfuron methyl are available to validate the storage

conditions and durations of storage of samples from the crop field trial and processing studies. Corrections to residue values from the residue trials to account for dissipation during storage are
not necessary.

Meat, Milk, Poultry, and Eggs

There are animal feedstuffs associated with the proposed uses on proso millet and grasses. An acceptable feeding study was previously submitted reflecting dosing of lactating dairy cows w ith

halosulfuron

- methyl at 0.5, 1.5, and 5 ppm in the daily diet on a dry weight basis . In the study,

n o quantifiable residues (<0.01 ppm) were found in milk, muscle, or fat at any feeding level; quantifiable residues were found in liver and kidney at all feeding levels. With the recalculated dietary burden for dairy cattle ( from 0.825 ppm to 20 ppm ), the dose rates in the feeding study correspond to ~0.025x, ~0.075x, and ~0.25x the current maximum reasonable dietary burden (MRBD). Based on extrapolation from the highest concentration level (5 ppm) of the feeding study with residues at the LOQ (0.01 ppm) in milk, muscle, and fat, HED has concluded that tolerances at 0.05 ppm can be established for residues of halosulfuron

- methyl in the milk, muscle

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 23 of 44 and fa t of cattle, goats, horses, and sheep based on the reasons stated in the ChemSAC minutes (ChemSAC 06/20/2012). The petitioner must propose a tolerance of 0.05 ppm for these livestock commodities. If future new use requests increase the dietary burden, a new feeding study will be needed.

The available data for liver and kidney are sufficient to assess the existing tolerances for meat byproducts. The data indicate that the established tolerances of 0.1 ppm for the meat byproducts of cattle, goat, horse, a nd sheep are too low and should be increased to 1.5 ppm. No change is needed for the established tolerance of 0.1 ppm for hog meat byproducts, and tolerances for

halosulfuron

- methyl residues in poultry commodities are not required due to low use rates, lo w residues of halosulfuron

- methyl in poultry feed items, and the low transfer rate of residues to poultry tissues.

Rotational Crops

Adequate confined and limited field rotational crop data are available. HED previously

concluded that the residue of conc ern 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 previously concluded that rotational crop

to lerances and 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 a ssessment 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 current
halo sulfuron methyl use on rice since the resulting EWDCs are greater than those estimated for the proposed uses (D394244, J. Meléndez, 5/ 15/12)

.

Table 5.3.1 . Tier I Estimated Drinking Water Concentrations (EDWCs) for human health drinking water risk assessment

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 Acute 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 Acute 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 t he 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

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 24 of 44 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 Treated Used in Dietary Assessment

The acute and chronic dietary analyses assumed that 100% of the crop was treated (100% CT)

5.4.3 Acute Dietary Risk Assessment

An acute dietary (food and drinking water) exposure and risk assessment was conducted using the Dietary Exposure Evaluation Model (DEEM

- FCIDTM, Version 2.03), which use s food consumption data from the U.S. Department of Agriculture’s Continuing Surveys of Food Intakes by Individuals (CSFII) from 1994

- 1996 and 1998. A conservative dietary exposure

assessment was performed for halosulfuron methyl

. The resu lt of the acute dietary (food and drinking water) analysis is below the Agency’s level of concern for females 13

- 49 years old. For the general U.S. population, a n appropriate dose/endpoint attributable to a single dose was not observed in the reviewed oral toxicity stud ies therefore, an acute dietary assessment was not conducted for the general U.S. population. T he acute dietary exposure estimate at the 95 th


### percentile is <1 % of the aPAD for females 13

- 49 years old, the only population subgroup of

concern. The result o f the acute dietary exposure analys 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 2.03. A conservative dietary exposure assessment was performed for halosulfuron methyl

. The results of the chronic dietary (food and drinking water) analysis are below the Agency’s level of concern for the general U.S. population and all population subgroups. T he dietary (food and d rinking water) exposure is estimated at 2 % of the c hronic Population Adjusted Dose (cPAD) for the general U.S. population and 6% of the cPAD for all

infants <1 y ear old , the population subgroup with the highest estimated chronic d ietary exposure

to halosul furon methyl

. The results of the chronic dietary exposure analys e s are reported in
Table 5.4.6

.

5.4.5 Cancer Dietary Risk Assessment

Halosulfuron methyl is classified as “not likely to be carcinogenic to humans;” therefore, no cancer risk is expected.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 25 of 44 5.4.6 Summary Table

Table 5.4.6 . Summary of Dietary Exposure s and Risk s for Halosulfuron

- methyl.

Population Subgroup Acute Dietary

(95th Percentile) Chronic Dietary

Dietary Exposure (mg/kg/day) % aPAD Dietary Exposure (mg/kg/day) % cPAD

General U.S. Population

N/A N/A 0.00 2108 2

All Infants (< 1 year old) 0.005 726 6

Children 1

- 2 years old 0.00 5147 5

Children 3

- 5 years old 0.00 4144 4

Children 6

- 12 years old 0.00 2642 3

Youth 13

- 19 years old 0.001 674 2

Adults 20

- 49 years old 0.001 733 2

Adults 50+ years old 0.001 767 2

Females 13

- 49 years old 0.003 733 <1 0.001 726 2

The population subgroup with the highest estimated exposure/risk is bolded.



### 6.0 Residential (Non

- Occupational) Exposure/Risk Characterization

There are no proposed residential with this petition ; however, there are existing residential turf

use s that have been reassessed in this document to reflect updates to HED’s 2012 Residential SOPs along with policy changes for body weight assumptions. The revision of residential exposures impacts the human health aggregate risk assessment for halosulfuron methyl.

The products registered for use on residential turf include water dispersible granule (WG)

formulations

. The currently registered EPs available for homeowner use include:

1. Nufarm Prosedge Selective Herbicide (EPA Reg. No. 228

- 702)

, 2. Nufarm Prosedge Selective Herbicide (EPA Reg. No. 228

- 711)

, 3. Halosulfuron 75WDG Herbicide (EPA Reg. No. 2749

- 528 )

, 4. GWN

- 3069 Turf Herbicide (EPA Reg. No. 81880

- 1)

, 5. NC

- 319 75WG T Turf Herbicide (EPA Reg. No. 81880

- 17)

, 6. GWN

- 9843 Turf Herbicide (EPA Reg. No. 81880

- 23) , and

7. GWN

- 9861 Turf Herbicide (EPA Reg. No. 81880

- 24)

.

6.1 Residential Handler Exposure

Residential h andler exposure is expected to be short

- term

. Intermediate

- term exposures are not likely because of the intermittent nature of applications by homeowners.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 26 of 44 The quantitative exposure/risk assessment developed for residential handlers is based on the following exposure scenarios:

1. mixing/loading/applyin g WGs with a manually pressurized handgun,

2. mixing/loading/applying WGs with a hose

- end sprayer,

3. mixing/loading/applying WGs with a backpack sprayer, and

4. mixing/loading/applying WGs with a sprinkler can.

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. All risk estimates are greater than the LOC of 100 and

therefore not of concer n (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 Residential 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 Manually

Pressurized

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 ft 2 /1 gallon). 0.023 A = 1000 ft 2

.

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 Total MOE = 1/ [ (1/Dermal MOE) + (1/Inhalation MOE)]. Level of concern = 100.



### 6.2 Post

- Application Exposure

Adults and children performing physical 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 treated

turf.

The scenarios, routes of exposure and lifestages assessed include:

1. Physical activities on turf: adults (dermal) and children 1 to < 2 years old (dermal and incidental oral);

2. Mowing: adults (dermal) and children 11 to < 16 years old (de rmal); and

3. Golfing: adults (dermal) , children 11 to < 16 years old (dermal) , and children 6 to < 11 years old (dermal).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 27 of 44 Table 6.2 presents the post

- application dermal and incidental oral MOE s calculated after applications of halosulfuron

- methyl to turf

. Post

- application risk estimates for all scenarios are greater than the LOC of 100 and therefore not of concern (MOEs range from 960 to 11,000,000)

.

Table 6.2

. Short

- Term Residential Post

- Application Exposure and Risk Estimates for Halosulfuron

- Methyl on Turf.

Lifestage Post

- Application Exposure Scenario Dose a MOE b mg/kg/day Water Dispersible Granule (WG) Formulations max single application rate: 0.14 lb ai/A

Adult

Dermal Physical Activities on Turf 0.0525 1,900 Mowing 0.00107 93,000 Golfing 0.00412 24,000

Child 11 to < 16 years old Mowing 0.00123 81,000 Golfing 0.00480 21,000 Child 6 to < 11 years old Golfing 0.00568 18,000

Child 1 to < 2 year old Physical Activities on Turf 0.104 960

Oral Hand to Mouth 0.00216 23,000

Object to Mouth 0.0000664 750,000

Short

- Term Incidental Soil Ingestion 0.00000474 11,000,000

a Dermal Dose = TTR/DFR (μg/cm 2 ) × CF1 (0.001 mg/μg) × TC (cm 2 /hr) × Exposure Time (hrs) ÷ body weight (kg)

. TC for

p hysical activities on turf: 180,00 0 cm 2 /hr for adults and 49,000 cm 2 /hr for children 1

- 2 years old. TCs for m owing: 5,500

cm 2 /hr for adults and 4,500 cm 2 / hr for children 11 to < 16 years old. TCs for g olfing: 300 cm 2 /hr for adults, 4,400 cm 2 /hr for
children 11 to < 16 years old, and 2,900 cm 2 /h r for children 6 to < 11 years old. Exposure times for physical activities on turf: 1.5 hrs for adults and children. Exposure time for mowing: 1 hr. Exposure time for golfing: 4 hr s. Body weight for adult: 80kg. Body weight for children 11 to < 16 years ol d: 57 kg. Body weight for children 6 to < 11 years old: 32 kg. Body weight for children 1 to < 2: 11 kg.

Hand

- to

- Mouth Dose = hand residue loading (mg/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm 2 )

× exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.5))^(Number of
hand

- to

- mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg). Object

- to

- Mouth Dose = object residue loading (μg/cm 2 ) × unit conversion factor (0.001 mg/μg) × object surface area mouthed / event (10 cm 2 /event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.50))^(# Object

- to

- Mout h Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg). Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg).

b MOE = NOAEL ÷ Daily Dose (mg /kg/day)

. Dermal NOAEL= 100 mg/kg/day . Level of concern = 100.



### 6.3 Combined Exposure

HED combines risk estimates resulting from separate post

- application exposure scenarios when it is likely they can occur simultaneously 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; therefore, the exposures via these routes were combined where appropriate. For residential handlers, dermal and inhalation exposures were combined. For post

- application scenario s, dermal and incidental oral exposures were combined for children 1 to < 2 years old.

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 interspers ed amongst each other across

time. Combining all three of these scenarios with the dermal exposure scenario would be overly

conservative 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.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 28 of 44 All combined (dermal + inhalation) post

- applicat ion scenarios resulted in MOEs greater tha n 100 and were not of concern. Handler dermal 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 th ey 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 (see Table 5)

. 2 Post

- application MOE represents high

- end incidental oral exposure for the relevant exposure duration (see Table 5)

. 3 Total MOE = 1 ÷ [ (1/Dermal MOE) + (1/Inhalation MOE) ] . Dermal NOAEL = 100 mg/kg/day

. Inhalation NOAEL = 50 mg/kg/day.

5 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 Post

- application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure

ass essment was not performed for halosulfuron

- methyl at this time because the chemical is only formulated as a WG, has low vapor pressure ( <1 x 10 - 7 

### mm Hg at 25 oC ) and is applied at a low rate (0.0625 lb ai/A) . However, volatilization of pesticides may be a potential source of post

application inhalation exposure to individuals nearby to pesticide applications. 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 et ings/2009/120109me et ing.html ) and is in the process of evaluating the SAP report. The Agency 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 as sessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative post

- application inhalation exposure assessment

for halosulfuron

- methyl.

6. 5 Spray Drift

Spray drift is always 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 m et hod employed for the previously

registered uses of hal osulfuron

- 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. The Agency is now requiring inte rim mitigation measures for aerial applications that must be placed on product labels/labeling. The Agency has compl et ed its evaluation of the new data base submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is develo ping a policy on how to

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 29 of 44 appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast

, and ground hydraulic m et hods. After the policy is in place, the Agency may impose further refineme nts in spray drift management practices to reduce

off

- targ et drift and risk estimates associated with aerial as well as other application types where appropriate.

Although a quantitative residential post

- application inhalation exposure assessment was no t performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalation
exposure assessment was conducted for residential handlers use on turf . This exposure scenario is representative of a worse case inhalation (drift) expo sure and may be considered protective of most outdoor agricultural and commercial post

- application inhalation exposure scenarios

.

7.0 Aggregate Exposure/Risk Characterization

In accordance with the FQPA, HED must consider and aggregate (add) pesticide exposu res 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 themselves 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 res idential scenarios were aggregated.

7.1 Acute Aggregate Risk

There is potential acute exposure via the diet (food and drinking water). Refer to Section 5.4

. 3.

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) pathways. For adults, these pathways lead to exposure via the oral (backgr ound) and dermal ( post

- application primary) routes. For children, these pathways 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 adult and children short

- term aggregate dietary and residential MOEs are 1,800 and 840 , respectively.

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 (females 13

- 49 yrs old) 100 29,000 NA 1,900 1,800

Child 1 to < 2 years old 100 9,700 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

- mouth residential exposure)]. See Table 6.3

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 30 of 44 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 residential exposure pathway. Therefore, the intermediate

- term aggreg ate 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 residential (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 methyl is classified as “not likely 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, EPA has not made a common mechanism of toxicity finding as

to halosulfuron met hyl and any other substances and halosulfuron methyl does not appear to produce a toxic metabolite produced by other substances. For the purposes of this tolerance action, there fore, EPA has not assumed that hal o su l furon methyl has a common mechanism of

t oxicity 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 by EPA’s Office of Pestici de 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.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

9.1 S hort

- /Intermediate

- Term Handler Risk

Occupational handler exposure to halosulfuron

- methyl is expected for individuals involved in applications to proso millet and pasture/rangeland (mixing, loading, and applying)

. For the proposed uses on proso millet and crop group 17, halosulfuron

- methyl may be applied once post

emergent to weed growth. Specifically, for use on proso millet, halosulfuron

- methyl may only be applied up through layby stage (before grain head emerg ence). For uses on pasture and rangeland, halosulfuron

- methyl may be applied as a broadcast to established grasses.

Halosulfuron may be applied to proso millet and pasture/rangeland for weed control via groundboom or aircraft. The proposed use pattern i s summarized in Table 3

. Handler exposure

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 31 of 44 is expected to be short

- or intermediate

- term based on information provided on the proposed
label. The label states that all handlers must wear the proper personal protective equipment (PPE): a long

- sleeved shirt , long pants, chemical

- resistant gloves, shoes, and socks.

The quantitative exposure/risk assessment developed for occupational handlers is based on the following exposure scenarios:

1. Mixing/loading dry flowables to support groundboom applications,

2. Mixing/loading dry flowables to support aerial applications

, 3. Flagging to support aerial application,

4. Applying sprays with groundboom equipment , and

5. Applying sprays with aerial equipment

.

All handler scenarios result in MOEs greater than the LOC (MOEs ≥ 100) at baseline and do not
exceed HED’s LOC. For proso millet, the baseline short

- term combined (dermal + inhalation)

MOEs range from 3,000 to 140,000. Intermediate

- term exposure is unlikely due to the agricultural practices of millet. Proso millet is only grown once per season and its growing season is generally less than 100 days. For pasture and rangeland, t he baseline s hort

- term combined (dermal + inhalation) MOEs range from 15,000 to 71,000 and t he baseline

intermediate

- term combined MOEs range from 200 to 9,600. Summaries of the short

- and

intermediate

- term risk estimate s for occupational handlers are included in Tabl e s 9.1.1

- 9.1.3

. The maximum application rate with baseline PPE is presented as the worst case for each exposure scenario.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 32 of 44 Table 9.1.1

. B aseline Short

- Term Occupational Exposures and Risk Estimates for Halosulfuron

- Methyl Use on Proso Millet.

Exposure Scenario Application

Rate a Area

Treated Daily b Baseline

Dermal Unit Exposures c Baseline

Inhalation

Unit Exposures c Baseline

Dermal

Dose d Baseline

Inhalation

Dose d Baseline

Short

- Term
Dermal

MOE e Baseline

Short

- Term
Inhalation

MOE e Baseline

Short

- Term
Total

MOE f

lb ai/A acres μg/lb ai μg/lb ai mg/kg/day mg/kg/day LOC = 100 LOC = 100 LOC = 100

Mixer/Loader Mixing/Loading Dry
Flowables for Groundboom Application 0.03133 80 227 8.96 0.0071 0.00028 14,000 180,000 13,000

Mixing/Loading Dry
Flowables for Aerial Application 0.03133 350 227 8.96 0.0313 0.0012 3,200 41,000 3,000

Fl agger
Flagging for Aerial Application 0.03133 350 11 0.35 0.0015 0.000048 66,000 1,000,000 63,000

Applicator

Applying Sprays via Groundboom Equipment 0.03133 80 78.6 0.34 0.0025 0.000011 41,000 4,700,000 40,000

Ap plying Sprays via Aerial Equipment * 0.03133 350 5 0.068 0.00068 0.0000093 150,000 5,400,000 140,000

a Application Rates based on proposed uses for halosulfuron

- methyl (EPA Reg. No. 8 1880

- 2,

- 6,

- 18 )

. b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1

.
c Unit Expos ures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. * Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conversion factor (1 mg/1,000 μg) × absorp tion factor (%) / body weight (8 0 kg).

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. ST Dermal NOAEL = 100 mg/kg/day. ST Inhalation NOAEL = 5 0 mg/kg/day.

f Total MOE = 1 / ( (1/Demal MOE) + (1/Inhalation MOE)).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 33 of 44 Table 9.1.2. Baseline Short

- T erm Occupational Exposures and Risk Estimates for Halosulfuron

- Methyl Use on Crop Group 17 (Grass, Forage,

Fodder, and Hay)

.

Exposure Scenario Application

Rate a Area

Treated Daily b Baseline

Dermal Unit Exposures c Baseline

Inhalation

Unit Exposures c Baseline

Dermal

Dose d Baseline

Inhalation

Dose d Baseline

Short

- Term
Dermal

MOE e Baseline

Short

- Term
Inhalation

MOE e Baseline

Short

- Term
Total

MOE f

lb ai/A acres μg/lb ai μg/lb ai mg/kg/day mg/kg/day LOC = 100 LOC = 100 LOC = 100

Mixer/Loader
Mixing/Loading Dry
Flowables for Groundboom Application 0.0625 80 227 8.96 0.014 0.00056 7,000 89,000 6,500

Mi xing/Loading Dry
Flowables for Aerial Application 0.0625 350 227 8.96 0.062 0.0025 1,600 20,000 1,500

Fl agger
Flagging for Aerial Application 0.0625 350 11 0.35 0.0030 0.000096 33,000 520,000 31,000

Applicator

Applying Sprays via Groundboom Equipment 0.0625 80 78.6 0.34 0.0049 0.000021 20,000 2,400,000 20,000

Ap plying Sprays via Aerial Equipment * 0.0625 350 5 0.068 0.0014 0.000019 73,000 2,700,000 71,000

a Application Rates based on proposed uses for halosulfuron

- methyl (EPA Re g. No. 81880

- 2,

- 6,

- 18 )

. b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1

.
c Unit Expos ures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. * Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conversion factor (1 mg/1,000 μg) × absorp tion factor (%) / body weight (8 0 kg).

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. ST Dermal NOAEL = 100 mg/kg/day. ST Inhalation NOAEL = 5 0 mg/kg/day.

f Total MOE = 1 / ( (1/Demal MOE) + (1/Inhalation MOE)).

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 34 of 44 Table 9.1.3. Baseline Intermediate

- Term Occupational Exposures and Risk Estimates for Halosulfuron

- Methyl Use on Crop Group 17 (Grass, Forage,

Fodder, and Hay)

.

Exposure Scenario Application

Rate a Area

Treated Daily b Baseline

Dermal Unit Exposures c Baseline

Inhalation

Unit Exposures c Baseline

Dermal

Dose d Baseline

Inhalation

Dose d Baseline

Int

- Term
Dermal

MOE e Baseline

Int

- Term
Inhalation

MOE e Baseline

Total

Dose Baseline Int

Term Total

MOE f

lb ai/A acres μg/lb ai mg/kg/day LOC = 100 mg/kg/day LOC = 100

Mixer/Loader
Mixing/Loading Dry Flowables for

Groundboom Application 0.0625 80 227 8.96 0.0106 0.00056 940 18,000 0.0112 890

Mixing/Loading Dry Flowables for Aerial Application 0.0625 350 227 8.96 0.047 0.0026 210 4,100 0.0490 200

Flagger

Flagging for Aerial Application 0.0625 350 11 0.35 0.00226 0.000096 4,400 100,000 0.00235 4,300

Applicator
Applying Sprays

via Groundboom Equipment 0.0625 80 78.6 0.34 0.0037 0.000021 2,700 470,000 0.00371 2,700

Applying Sprays
via Aerial Equipment * 0.0625 350 5 0.068 0.0010 0.000019 9,800 540,000 0.00104 9,600

a Application Rates based on proposed uses for halosulfuron

- methyl (EPA Reg. No. 81880

- 2,

- 6,

- 18 )

. b Acres Treated Per Day is taken from Exposure Science Advisory Council (ExpoSAC) Policy No. 9.1

.
c Unit Expo s ures based on PHED Version 1.1 or AHETF data. Baseline = no gloves, no respirator. * Baseline aircraft = engineering controls.

d Dose (mg/kg/day) = daily unit exposure (μg/lb ai) × application rate (lb ai/acre) × amount handled ÷ day (acres/day) × conver sion factor (1 mg/1,000 μg) × absorp tion factor (%) / body weight (8 0 kg). Intermediate

- term dermal absorption factor = 75%.

e MOE = NOAEL (mg/kg/day) / Dose (mg/kg/day). Level of concern = 100. I T Dermal NOAEL = I T Inhalation NOAEL = 1 0 mg/kg/day.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 35 of 44 f Total MOE = NOAEL / ( Demal MOE + Inhalation MOE )

.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 36 of 44 9.2 Short

- /Intermediate

- Term Post

- Application Risk

Based on the proposed use patterns, post

- application exposure to halosulfuron

- methyl is possible. Agricultural workers performing typical post

- application activities (e.g. scouting, hand weeding) may receive exposure to halosulfuron

- methyl residues. For the proposed uses on proso millet and crop group 17, halosulfuron

- methyl may be applied once post

- emergent to weed growth. Specifi cally, for use on proso millet, halosulfuron

- methyl may only be applied up through layby stage (before grain head emergence). For uses on pasture and rangeland,

halosulfuron

- methyl may be applied as a broadcast to established grasses.

9.2.1 Dermal Post

- A pplication Risk

HED’s post

- application exposure estimates are based on surrogate data. The transfer coefficients (TCs) are considered to be central tendency. Maximum application rates were used in this assessment. Overall, the post

- application risk estimates are characterized as being central to high

- end estimates. A ll scenarios resulted in MOEs greater than the LOC of 100 (ranging from

400 to 160 ,000) on day 0 (12 hours after application) and

, therefore

, are not of concern to HED. The post

- applica tion exposure scenarios are summarized in Table 9.2.1 and 9.2.2

.

Table 9.2.1. Short

- Term Post

- Application Exposures and Risk Esti mates for Halosulfuron

- Methyl

.

Activity Transfer

Coefficient Days After

Treatment DFR a Daily Dermal Dose b Dermal MOE c

μg/cm 2 mg/kg/day LOC = 100

Proso Millet



### irrigation (hand set) 1,9 00 0 (12 hours) 0.088 0.0166 6,000



### scouting 1,100 0 (12 hours) 0.088 0.0096 10,000



### hand weeding 7 0 0 (12 hours) 0.088 0.00061 160,000

Crop Group 17 (Pasture and Rangeland)



### irrigation (hand set) 1,9 00 0 (12 hours) 0.175 0.0333 3,000



### scouting 1,100 0 (12 hours) 0.175 0.0193 5,200



### hand weeding 7 0 0 (12 hours) 0.175 0.00123 82,000

a DFR (μg/cm 2 ) = application rate ( 0.0313 or 0.0625 lb ai/acre) × fraction of application rate dislodgeable on day 0 (2 5 %) × (1

- fraction of residue that dissipates daily 10%) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2

. b Short

- Term Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day] body weig ht (8 0 kg adult).

c Short

- Term MOE = NOAEL (mg/kg/day) ÷ Daily Dermal Dose (mg/kg/day). S T NOAEL = 100 mg/kg/day . LOC = 100.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 37 of 44 Table 9.2.2. Intermediate

- Term Post

- Application Exposures and Risk Esti mates for Halosulfuron

- Methyl

.

Activity Transfer

Coefficient Days After

Treatment DFR a Daily Dermal Dose b Dermal MOE c

μg/cm 2 mg/kg/day LOC = 100

Proso Millet



### irrigation (hand set) 1,9 00 0 (12 hours) 0.088 0.0125 800



### scouting 1,100 0 (12 hours) 0.088 0.00723 1,400



### hand weeding 7 0 0 (12 hours) 0.088 0.000460 22,000

Crop Group 17 (Pasture and Rangeland)



### irrigation (hand set) 1,9 00 0 (12 hours) 0.175 0.0250 400



### scouting 1,100 0 (12 hours) 0.175 0.0145 690



### hand weeding 7 0 0 (12 hours) 0.175 0.000920 11,000

a DFR (μg/cm 2 ) = application rate ( 0.0313 or 0.0625 lb ai/acre) × fraction of application rate dislodgeable on day 0 (2 5 %) × (1

- fraction of residue that dissipates daily 10%) t × 4.54E8 μg/lb × 2.47E

- 8 acre/cm 2

. b Intermediate

- Term Daily Dermal Dose = [DFR (μg/cm 2 ) × Transfer Coefficient × 0.001 mg/μg × 8 hrs/day × dermal absorption 75 %] body weight (8 0 kg adult).

c Intermediate

- Term MOE = NOAEL (mg/kg/day) ÷ Daily Dermal Dose (mg/kg/day) . IT NOAEL = 10 mg/kg/day . LOC = 100.



### Restricted Entry Interval Typically, under WPS for Agricultural Pesticides , a ctive ingredients classified as acute T oxici ty Category III or IV for Acute Dermal, Eye Irritation, and Primary Skin Irritation are assigned a

12

- hour REI . Based on the quantitative post

- application assessment , the 12

- hour REI on the

propose d label is acceptabl e.

9.2.2 Inhalation Post

- application 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 applied 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 treat ed 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 In secticide, 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/scipo ly/SAP/me et ings/2009/120109me et ing.html ) and is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the Agricultural Reentry Task Force. The Agency may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the 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.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 38 of 44 Although a quantitative occupational post

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting 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

Meléndez, J., 05/15/2012, DP394244, “ Halosulfuron methyl Drinking Water Assessment for

Additional Food/Feed U ses on Proso Millet, Pasture and Rangeland Grass Forage, Fodder and Hay (Crop Group 17 )”.

Negussie, M., 06/21/2012, DP393948, “ Halosulfuron

- methyl. Application for Section 3 Registration of Yukon Herbicide (EPA Reg. No. 81880

- 6), Sandea Herbicide ( EPA Reg. No.
81880

- 18 ), and GWN

- 3061 Herbicide ( EPA Reg. No. 81880

- 2) to Add New Uses on Pro so Millet and Pasture and Rangeland Grasses. Summary of Analytical Chemistry and Residue

Data. ”

Tsaur, N., 06/12/ 20 12, 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., 07/12/2012, DP396460, “ Halosulfuron

- methyl. Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Section 3 Registration

Action on Proso Millet and Crop Group 17 (Grass, Forage, Fodder, and Hay).”

Whang, P., 03/01/2012. DP397243. “ Halosulfuron

- Methyl

. Response to a 28

- day inhalation toxicity study waiver request”.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 39 of 44 A ppendix A

. Toxicology P rofile

A.1 Toxicology Data Requirements The requirements (40 CFR 158.340) 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 yes

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
CR

yes yes

yes

yes

-

a 870.3700a Prenatal Developmental Toxicity (rodent)

..................... 870.3700b Prenatal Developmental Toxicity (nonrodent)

............... 870.3800 Reproduction and Fertility Effects

................................ . yes

yes

yes yes

yes

yes 870.4100b Chronic Toxicity (nonrodent)

................................ ........ 870.4200b Carcinogenicity (mouse)

................................ ................ 870.4300 Combined Chronic Toxicity/Carcinogenicity

................ no

yes

yes yes

yes

yes 870.5100 Mutagenicity

— Bacterial Reverse Mutation Test

........... 870.5300 Mutagenicity

— Mammalian Cell Gene Mutation Test

... 870.5xxx Mutagenicity

— Structural Chromosomal Aberrations

.... 870.5xxx Mutagenicity

— Other Genotoxic Effects

......................... yes

yes

yes

yes yes

yes

yes

yes 870.6200a Acute Neurotoxicity Screening Battery (rat)

................. 870.6200b 90

- Day Neurotoxicity Screening Battery (rat)

............... 870.6300 Developmental Neurotoxicity

................................ ........ yes

yes

CR yes

yes

- 870.7485 Metabolism and Pharmacokinetics

................................ 870.7600 Dermal Penetration

................................ ........................ 870.7800 Immunotoxicity

................................ ............................. yes

CR

yes yes

-

yes

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 40 of 44 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 Acute Oral

- Rats 42139413 LD 50 : Males = 10,435 mg/kg Females = 7758 mg/kg Combined = 8866 mg/kg IV

870.1200 Acute Dermal

- Rats 42139415 LD 50 >2000 mg/kg (limit test) III

870.1300 Acute 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 Technical (Repeated dosing and others).

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 determined, F = 772.8 mg/kg/day based on decreased body weigh t 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.

870.4100 (83

- 1b) Chronic oral

toxicity study in dogs 42396211 (1991)/

Acceptable/ Guideline Doses: 0, 0.25, 1.0, 10.0, or 40 mg/kg/day (capsule). NOAEL = 10 mg/kg/day LOAEL = 40 mg/kg/day based on decreased body

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/ 42661418 (1992)/

Acceptable/Guideline NOAEL = M=108.3, F=56.3 mg/kg/day LOAEL = M=225.6, F=138.6 mg/kg/day based on

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 41 of 44 Table A.2. 2. Toxicity Profile of Halosulfuron

- M ethyl Technical (Repeated dosing and others).

Guideline

No. Study Type MRID No. (Date)/Classification/ Doses Results

Carcinogenicity in

rats 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) marginal decrease in body weight gain in both males

and female s.

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 eigh t 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 size, 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/da y 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. Reproductive NOAEL > = 223.2/ 261.4 mg/kg/day

.

870.6200a (82

- 7) Acute

neurotoxicity in 45754701 (1994) and

46199501 (1989)[positive NOAEL = 600 mg/kg. LOAEL = 2000 mg/kg (limit dose) based on mortality

in males.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 42 of 44 Table A.2. 2. Toxicity Profile of Halosulfuron

- M ethyl Technical (Repeated dosing and others).

Guideline

No. Study Type MRID No. (Date)/Classification/ Doses Results

rats. control study]/

Acceptable/ Guideline Doses: 0, 200, 600, or 2000 mg/kg (limit dose)

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 decreased body weight and body weight gain and (F: 315.9 mg/kg/day) in females based on decreased body weight gain.

870.6300 (83

- 6) Metabolism 42139433 (1990)/ Acceptable/ Guide line 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.

870.5100 (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 s ulfuron

- methyl.

870.5300 (84

- 2) Mutagenic

- Gene

Mutation

- Hamster (Chinese) 43616303 (1995)

- Metabolite/

Acceptable (+/

- S9) Conc.: 350

- 3100 microgm/ m L Negative. Conducted with 3

- chlorosulfonamide acid

- the principal soil metabolite of halo s ulfuron

- methyl.

870.5300 (84

- 2) Mutagenic

-

(HGPRT)

- Hamster (Chinese). 42139431 (1991)

- Metabolite/

Unacceptable

Conc.: 100

- 1000 microgm /m L 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/m L 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.

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.

870.5395 (84

- 2) Mutagenic

-

Micronucleus Assay

- Mouse 421 39430 (1989)/ Acceptable

Doses: 500, 1667 0r 5000 mg/kg. Negative. Did not induce significant elevations in the frequencies of micronucleated polychromatic erythrocytes.

### Halosulfuron

- Methyl Human Health Risk Assessment DP No. 396458

Page 43 of 44 Table A.2. 2. Toxicity Profile of Halosulfuron

- M ethyl Technical (Repeated dosing and others).

Guideline

No. Study Type MRID No. (Date)/Classification/ Doses Results

870.5500 (84

- 2) Mutagenic

-

Unscheduled DNA synthesis

- Rat 42139432 (1990)/ Acceptable

(+/

- S9) Conc.: 25

- 1000 microgm/mL Negative. Fail to induce unscheduled DNA synthesis in primary rat hepatocytes.

### Halosulfuron

- M ethyl Human Healt h Risk Assessment DP No. 396458

Page 44 of 44 Appendix B. International Residue Limits



## Halosulfuron

- methyl ( 128721 ; 02/29/2012 )
Summary of US and International Tolerances and Maximum Residue Limits Residue Definition :
US Canada Mexico 2 

### Codex 3



### 40 CFR 180.479
Plant: Halosulfuron

- methyl, methyl 5

- [(4,6

- dimethoxy

- 2

- pyrimidiny)amino]carbonylaminosulfonyl]

- 3

- chloro

- 1

- methyl

- 1H

- pyrazole

- 4

- carboxylate

Livestock: Halosulfuron

- methyl residues containing the 3

- chlorosulfonamide (3

- CSA) moiety, expressed as the stoichiometric equivalent of halosulfuron

- m ethyl None None



### Commodity 1 

### Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico 2 

### Codex 3

Millet, proso, forage 10 Millet, proso, hay 0.01 Millet, proso, grain 0.01 Millet, proso, straw 0.01 Grass, forage, fodder, and hay, group 17, forage 20

Grass, forage, fodder, and hay, group 17, hay 0.5

Cattle, meat byproducts 1.0 Goat, meat byproducts 1.0 Horse, meat byproducts 1.0 Sheep, meat byproducts 1.0 Cattle, fat 0.05 Cattle, meat 0.05 Goat, fat 0.05 Goat, meat 0.05 Horse, fat 0.05
Horse, meat 0.05

Milk 0.05 Sheep, fat 0.05 Sheep, meat 0.05 

### Completed: M. Negussie; 06/21 /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.

3 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the fat portion of the sample. MR Ls indicated as proposed have not been finalized by the CCPR and the CAC.