HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

MEMORANDUM 

DA T E: September 15, 2015 

OFFICE OF 

CHEMICAL SAFETY AND 

POLLUTION PREVENTION 

SUBJECT: Halosulfuron-Methyl. Human Health Draft Risk Assessment for Registration 

Review. 

PC Code: 128721 

Decision No.: 506514 

Petition No.: NA 

Risk Assessment Type: Single Chemical/Aggregate 

TXRNo.: NA 

MRID No.: NA 

DP Barcode: D428013 

Registration Nos.: Numerous 

Regulatory Action: Registration Review 

Case No.: 7233-1 

CAS No.: I 00784-20-1 

40 CFR: 180.479 

FROM: Nancy 

Meheret 

J. 

Neguss

Keller,

1

_Ri

e, 

sk 

Chemist 

Assessor

/(e/-ie.Y'd 

, Chemist 

J:kjC>rftfc:e. 

~ 

Whang Phang, Toxicologist 1 ~ 

Risk Assessment Branch 3 ' l5 

Health Effects Division (7509P) 

THROUGH: 

Risk 

Christine 

Assessment 

Olinger, 

Branch 

Chief 

3 ./--

( / 

/ 

._/ ~ 

' 

Health Effects Division (7509 

TO: Brittany Pruitt, Chemical Review Manager 

Kelly Sherman, Branch Chief 

Risk Management and Implementation Branch 3 

Pesticide Re-Evaluation Division (7508P) 

The Pesticide Re-Evaluation Division (PRO) has requested a Draft Risk Assessment (DRA) from 

the Health Effects Division (HED) to provide information that supports the registration review of 

halosulfuron-methyl. This assessment addresses the exposures and risk estimates associated with 

all currently registered uses. 

Since the last risk assessment, there have been no changes to the halosulfuron-methyl use profile, 

hazard profile, or residue profile (DP42 l 819, K. Rury, 06110/2015). Nor have there been any 

policy changes that would warrant an update to dietary, residential, aggregate, or occupational 

risk estimates. However, a new assessment for indirect non-occupational spray drift has been 

conducted for registration review. Furthermore, there are no outstanding data deficiencies or 

conditions of registration for halosulfuron-methyl at this time. 

Page I of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

Table of Contents 

1.0 Executive Summary ... ............................... ................................................. ....... ................. 2 

2.0 Use ProfLle ........................................................................................................................... 2 

3.0 Hazard Identificationff oxicology ..................................................................................... 3 

3.1 Summary of Toxicological Effects ................................................................................ 3 

3.2 Safety Factor for Infants and Children (FQPA Safety Factor) ................................. 4 

3.3 Toxicity Endpoint and Point of Departure Selections ................................................ 4 

4.0 Residue Chemistry ...................... ................................................................. .......... .......... .. 7 

4.1 Tolerance Considerations .............................................................................................. 7 

4.2 International Harmonization ........................................................................................ 8 

5.0 Dietary Risk Assessment ................................................................................................... 9 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization ........ ................. ... . 10 

6.1 Spray Drift .................................................................................................................... 10 

6.2 Residential Bystander Post-Application Inhalation Exposure .. .............................. 11 

7.0 Aggregate Exposure/Risk Characterization .................................................................. 11 

8.0 Cumulative Exposure/Risk Characterization ............................................................... 12 

9.0 Occupational Exposure/Risk Characterization ............................................................ 13 

10.0 References .......................................................... ..... .......... .................... ........... ................. 13 

Appendix A. Toxicology Profile for Halosulfuron-Methyl .................................................. 15 

Appendix B. International Residue Limit Status ................................................................. 19 

1.0 Executive Summary 

Halosulfuron-methyl is a sulfonylurea herbicide currently registered for pre- and post-emergence 

control of annual broadleaf weeds and nutsedges on various agricultural crops, as well as 

residential turfgrass and ornamentals. It inhibits acetolactate synthase (ALS), an enzyme found 

in plants and micro-organisms that catalyzes the first step in the synthesis of the branched-chain 

amino acids such as valine, leucine, and isoleucine. ALS is also found in mammals, but its 

function and mode of action are unknown. 

Since the last risk assessment, there have been no changes to the halosulfuron-methyl use profile, 

hazard profile, or residue profile (DP4218 l 9, K. Rury. 06/ 10/2015). Furthermore, there have 

been no policy changes that would warrant an update to dietary, residential, aggregate, or 

occupational risk estimates. However, a new assessment for indirect non-occupational spray 

drift has been conducted for registration review. There are no outstanding data deficiencies or 

conditions of registration for halosulfuron-methyl at this time. There are no risk estimates of 

concern in dietary, residential, occupational, or aggregate assessments. 

2.0 Use Profile 

Currently, the active ingredient (ai), halosulfuron-methyl is only formulated as a waterdispersible granule (WG). This formulation is to be added to water, resulting in a dispersion of 

finely divided herbicide particles suspended in water to be applied for weed control. Currently 

registered labels include one technical label, three agricultural labels, three state labels, and one 

Page 2 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

experimental use permit label. 

In addition to several agricultural food uses, halosulfuron-methyl is also registered for use on 

turf grass, ornamentals, and a variety of non-crop areas including, but not limited to, airports, 

cemeteries, fallow non-crop areas, golf courses, landscaped areas, public recreation areas, 

residential property, roadsides, school grounds, sod or turf seed farms, sports fields, residential 

and commercial landscaped areas with established woody ornamentals, fairgrounds, race tracks, 

tennis courts, campgrounds, and rights-of-way. 

In general, halosulfuron-methyl may be applied up to twice a year. Application timing varies 

depending on the target weed (pre-/post-ernergent to weeds or pre-/post-emergent to crop 

plantings). The application rates range up to 0.10 lb ail A for all registered uses. Depending on 

the use site, halosulfuron-methyl may be applied via ground, aerial, chemigation, or handheld 

equipment. 

3.0 Hazard Identification/Toxicology 

The toxicology database for halosulfuron-methyl is complete and adequate for risk assessment. 

At this time, the requirements for the subchronic inhalation toxicity and immunotoxicity studies 

are waived (TXR 0054045, D. Smegal, 02/22/2012; TXR 0056723, K. Rury, 08/06/2013). New 

toxicity and/or metabolism data have not been received since the last risk assessment, and the 

selected toxicity endpoints and points of departure (PO Os) remain the same. A summary of the 

acute, subchronic, and chronic toxicity profi le is presented in Appendix A. 

3.1 Summary of Toxicological Effects 

With repeated dosing, the available data did not demonstrate a target organ or tissue in any of the 

test animals. Reduction in body weight was seen in the 90-day and I-year oral toxicity studies in 

dogs. Reduced body weights were also seen in rat studies at higher dose levels than those seen 

in dogs. An effect on the hematological parameters was detected in the dog studies, but the 

magnitude of changes was slight and the effect was considered to be marginal. Thus, the slight 

hematological changes were not considered to be adverse. 

In the prenatal developmental toxicity study in rats, increases in resorptions, soft tissue (dilation 

of the lateral ventricles) and skeletal variations, and decreases in body weights were seen in the 

fetuses compared to clinical signs and decreases in body weights and food consumption in the 

maternal animals at a similar dose level. In the rabbit developmental toxicity study, increases in 

resorptions and post-implantation losses and decreases in mean litter size were observed in the 

presence of decreases in body weight and food consumption in maternal animals. The fetal 

effects seen in developmental toxicity studies in rats and rabbits represented a qualitative 

increase in susceptibility. However, a clear no observed adverse effect level (NOAEL) for these 

effects was established in both rat and rabbit developmental toxicity studies. Halosulfuronmethyl did not produce any effects on reproductive parameters in the two-generation 

reproduction study in rats. Therefore, no quantitative susceptibility was found in studies 

following pre-and/or post-natal exposures. No neurotoxic effects were observed in the acute or 

subchronic neurotoxicity studies up to 2000 mg/kg or 760 mg/kg/day, respectively. In addition, 

Page 3 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

no adverse effect was found in a 21-day dermal toxicity study at doses up to the limit dose (1000 

mg/kg/day). 

Ha losulfuron-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. 

Halosulfuron-methyl has low acute toxicity (Toxicity Category III-IV) by oral, dermal, and 

inhalation routes of exposure. It is not a dennal sensitizer, but it produced transient eye irritation 

which was cleared within 24 hours. 

3.2 Safety Factor for Infants and Children (FQPA Safety Factor) 

The FQPA Safety Factor has been reduced to IX for the following reasons: 

(1) The toxicity database of halosulfuron-methyl is complete and adequate to assess the 

qualitative or quantitative susceptibility in the young; 

(2) There was no quantitative evidence of increased susceptibility following pre- and/or 

post-natal exposure. However, the qualitative susceptibility observed in the 

developmental toxicity studies in rats and rabbits was of low concern because (a) in 

both studies, there were clear NOAELs/lowest observed adverse effect levels 

(LOAELs) for developmental and maternal toxicities; (b) the developmenta l effects 

were seen in the presence of maternal toxicity; and ( c) the effects were only seen at 

the high dose levels. In rats, the developmental effects were seen at a dose (750 

mg/kg/day) which was approaching the limit-dose (1000 mg/kg/day). Furthermore, 

the PODs for risk assessment are protective of the effects which occur at high doses; 

(3) Halosulfuron-methyl produced no evidence of neurotoxicity; and 

(4) There are no residual uncertainties in the exposure database, and exposure estimates 

are unlikely to underestimate risk. 

3.3 Toxicity Endpoint and Point of Departure Selections 

There have been no changes to the prior dose-response assessment and cancer classification 

(DP42 l 8 l 9, K. Rury, 06/ 10/2015). It should be noted that the studies in the halosulfuron-methyl 

database, including those used for endpoint selection, have not been updated to reflect current 

policy and may be considered conservative since these updates would result in higher 

NOAEL/LOAEL values than those currently established. The currently selected PODs are 

protective of the effects observed in the halosulfuron-methyl database and any updates would not 

impact the overall fi ndi ngs of the risk assessment given the current risk picture for halosulfuronmethyl. Furthermore, the risk estimates calculated with these PODs do not present. any risk 

estimates of concern at this time. 

Page 4 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D4280 I 3 

Table 3.3. Summary of Toxicological Doses and Endpoints for Halosulfuron-Methyl for 

Use in Dietary, Non-Occupational and Occupational Human Health Risk Assessments 

RID, Level 

Exposure/ Point of Uncertainty/ of Concern Study and Toxicological Effects Scenario Departure Safety Factors for Risk 

Assessment 

Acute Acute RID = Developmental Toxicity - Rabbit UFA = JOX 0.5 Dietary NOAEL = UFH = !OX mg/kg/day LOA EL = I 50 mg/kg/day based on increased 

(Females I 3- 50 number of resorptions (total and per dam and 

49 years of mg/kg/day FQPA SF = increased post-implantation loss (developmental IX aPAD = 0.5 age) mg/ka/day toxicity). 

Acute 

Dietary No adverse effect attributable to a single dose was identified; therefore, no dose/endpoint was 

(General selected for this exposure scenario. 

Population) 

UFA = IOX Chronic Rfl) 

Chronic NOAEL = UF11 = IOX = 0. 1 Chronic Toxicity - Dog 

Dietary (All 10 FQPA SF= mg/kg/day LOA EL = 40 mg/kg/day based on decreased 

Populations) mg/kg/day cPAD = 0.1 body weight in females. IX 

m!lfkg/dav 

Incidental NOAEL = UFA = JOX Residential Developmental Toxicity - Rabbit 

Oral Short- 50 UFH = !OX LOC for LOA EL = 150 mg/kg/day based on decreased 

Tenn (J-30 mg/kg/day FQPA SF = MOE = JOO food consumption and food efficiency (maternal 

davs) IX toxicitv). 

Dermal 

Short-Term A 21-day dem1al toxicity tested up to the limit dose (I 000 mg/kg/day) demonstrated no adverse (1-30 days) 

Intermediate- effects and there was no evidence of quantitative susceptibility in the halosulfuron-methyl 

Tenn (J-6 database. No dennal toxicity endpoint could be established. 

monthsf 

UFA= IOX Residential Developmental Toxicity - Rabbit Inhalation NOAEL = and 

Short-Term 50 UFH = !OX Occupational LOA EL = 150 mg/kg/day based on decreased 

(1 -30 days) mg/kg/day FQPA SF = LOC for food conswnption and food efficiency (maternal 

IX MOE = 100 toxicity). 

Inhalation UFA = !OX Residential 13 Week Subch ronic Toxicity - Dog 

Intennediate- NOA EL= UF11 = IOX and LOAEL = 40 mg/kg/day based on decreased 

Tenn (1-6 IO FQPA SF = Occupational body weight gains and food efficiency along 

months) mg/kg/day IX LOC for with hematological and clinical chemistry 

MOE = 100 changes. 

Cancer (oral, Classification: "not likely to be carcinogenic to humans" by the oral route, based on no evidence dennal, 

inhalation) of carcinogenicity from studies in rats and mice. 

Toxicity via the inhalation route is presumed to be equivalent to oral toxicity. Point of Departure (POD) = A data 

point or an estimated point that is derived from observed dose-response data and used to mark the beginning of 

extrapolation to determine risk associated with lower environmentally relevant human exposures. NOA EL = no 

observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF,, = 

extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the 

human population (intraspecies). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = acute, c = 

chronic). RfD = reference dose. MOE = margin of exposure. LOC = level of concern. 

Page 5 of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

3.4 Endocrine Disruption 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for halosulfuron-methyl, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

halosulfuron-methyl is subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a "naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate." The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A. or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 2013 1 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. Neither of these 

lists should be construed as a list of known or likely endocrine disruptors. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website.2 

1 See http://www.rcgulations.gov/#!documcntDetail:D=EPA-HO-OPPT-2009-0477-0074 for the final second list of 

chemicals. 

2 hnp://www.epa.gov/endo/ 

Page 6 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

4.0 Residue Chemistry 

The nature of the residue in plants has been adequately delineated based on acceptable 

metabolism studies with com, sugarcane, and soybean treated both pre- and postemergence. 

HED has concluded that the residue of concern for enforcement and risk assessment in plants 

(for the current use pattern) is parent halosulfuron-methyl only. The need for additional plant 

metabolism studies to support future uses will be decided on a case-by-case basis. 

The nature of the residue in livestock has been adequately delineated based on metabolism 

studies with goats and hens. The residue of concern for enforcement in ruminants is parent 

halosulfuron-methyl only; 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. HED previously concluded 

that there is no reasonable expectation of residues in poultry commodities ( l 80.6(a)(3))) and 

therefore tolerances for halosulfuron-methyl residues in poultry commodities are not required. 

This decision is based on the low use rates, low residues of halosulfuron-methyl in poultry 

feedstuffs, and the low transfer rate of residues to poultry tissues for the current uses. 

Adequate analytical methods (GC/NPD) are available for the enforcement of tolerances for 

residues ofhalosulfuron-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). 

The plant method detern1ines halosulfuron-methyl as its rearrangement ester (RRE), and the 

livestock method converts residues of halosulfuron-methyl and metabolites containing the 3-

CSA moiety to 3-CSA for determination. BEAD/ACB conducted successful petition method 

validations (PMVs) for both methods (0250584; G.J. Herndon; 28 October 1998). Residues of 

halosulfuron-methyl and 3-CSA are not adequately recovered by FDA Multiresidue Method 

protocols. 

The analytical reference standards for parent halosulfuron-methyl with expiration date of 

(5/31/2017) and for metabolite 3-CSA with expiration date of (6/21/2017) are currently available 

in EPA's National Pesticide Standards Repository (NPSR), per email communication from 

Gregory Verdin of the Biological and Economic Analysis Division's Analytical Chemistry 

Branch (BEAD/ACB) on May l l, 201 5. 

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

concluded that rotational crop tolerances and restrictions are not required for halosulfuronmethyl. 

4.1 Tolerance Considerations 

Permanent tolerances are established for residues of halosulfuron-methyl in or on a variety of 

plant commodities, at levels ranging from 0.01 ppm in the grain, hay and straw of proso millet, 

to 20 ppm in the forage of grass, forage, fodder and hay group 17(40CFR§180.479[a][2]). 

Permanent tolerances are also established for residues of halosulfuron-rnethyl containing the 3-

Page 7 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

chlorosulfonarnide acid (3-CSA) moiety in ruminant milk, fat, meat and meat byproducts, and in 

hog meat byproducts at 0.05-1.0 ppm (40CFR §1 80.479[a][l]). 

Tolerances are recommended for pome fruit group 11-10 and small vine climbing fruit except 

fuzzy kiwifruit subgroup l 3-07F (Regional Registration). The tolerance expression under 40 

CFR § 180.479 is correct and reflects measurement and compliance of halosulfuron-methyl 

residues. 

The incorrect entry for succulent shelled pea and bean subgroup 6 should be removed from 40 

CFR § I 80.479[a][2]; no such subgroup exists. There is a crop grmm 6 (legume vegetables), as 

opposed to a subgroup 6. The correct entry, succulent shelled pea and bean subgroup 6B, is 

listed immediately beneath the incorrect entry. 

The existing US tolerance for apple (0.05 ppm) needs to be removed from 40CFR§180.479(2) 

since this commodity is included in crop group pome fruits (0.05 ppm). 

The existing US tolerance for pistachio (0.05 ppm) needs to be removed from 40 CFR 

§ 180.4 79(2) since this commodity is included in crop group tree nuts (0.05 ppm). 

The existing US tolerance for okra (0.05 ppm) needs to be removed from 40CFR§180.479(2) 

since this commodity is included in crop group fruiting vegetables (0.05 ppm). 

The existing tolerances for fruiting vegetables and tree nuts need to be revised to establish as 

vegetable, fruiting, group 8-10 and Nut, tree, group 14-12. The proposed tolerance changes are a 

result of revisions in the crop groups. The revisions are presented in Table 2.1. 

Table 4.1. Toler ance Modifi cation Recommendations for Ha losulfuron-Metbyl 

Established Recommended 

Commodity Tolerance Tolerance Comments 

(ppm) (ppm) 

Apple 0.05 None Remove covered by 

Fruit, pome, group 11 - 10 

Pea and bean, succulent 0.05 None Remove incorrect entry shelled, subgroup 6 

Vegetable, fruiting group 8 0.05 0.05 Revise to vegetable, fruiting, group 8-10 

Okra 0.05 None Remove; covered by 

vegetable, fruiting, group 8-10 

Nut, !Tee, group 14 0.05 0.05 Establish as Nut, tree, group 14-12 

Pistachio 0.05 None Remove; covered by 

Nut, tree, group 14-12 

4.2 International Harmonization 

At this time, there are no Codex maximum residue limits (MRLs) established for residues of 

halosulfuron-methyl. The US tolerances for plants are harmonized with Canadian MRLs, except 

asparagus. The tolerance and Canadian MRL for asparagus may be able to be harmonized; the 

registrant should address opportunities for harmonization in their response to this risk 

Page 8 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

assessment. The US has established tolerances on crop group pome fruits whereas Canada has 

established an MRL on apple only. The US livestock tolerances are not harmonized and could 

not be harmonized since the Canadian MRLs are lower. Livestock feedstuffs are not harmonized 

with Canada because Canada does not establish MRLs on feedstuffs. Refer to Appendix B. 

5.0 Dietary Risk Assessment 

The residue chemistry data and environmental fate data are adequate to assess human exposure. 

The most recent dietary exposure assessments previously conducted for the registered uses of 

halosulfuron-methyl are considered up-to date, conservati ve, and based on reliable data that will 

not underestimate exposure/risk (DP426724, K. Rury, 05/25/20 15). Therefore, new dietary 

exposure assessments are not needed for Registration Review. The previous assessments are 

unrefined and were conducted using DEEM-FCID Version 3.16; which uses 2003-2008 food 

consumption data from the U.S. Department of Agriculture's (USDA's) National Health and 

Nutrition Examination Survey, What We Eat in America (NHANES/WWEIA). The acute and 

chronic assessments assumed tolerance-level residues and 100% crop treated (CT) for all 

commodities. Additionally, default processing factors were assumed except for where tolerances 

were established for processed commodities or when processing studies showed no 

concentration. Based on processing studies, the default processing factors were reduced to 1 for 

tomato paste, tomato puree, potato flour, and potato granules/flakes. The highest estimated 

drinking water concentration (EDWC) of 59.2 μg/L was incorporated into both acute and chronic 

assessments. This recommended EDWC resulted from the Tier I surface water model for a 

registered use on rice. 

Acute 

There was no indication of an adverse effect attributable to a single dose for the general U.S. 

population. However, an aRfD was established for females 13-49 years old, and an acute dietary 

exposure assessment was conducted for that population subgroup. The unrefined acute dietary 

exposure estimate at the 95th percentile is <1 % of the acute population adjusted dose (aPAD) for 

females 13-49 years old, and is below HED's level of concern (< 100% of the aPAD). The 

results are sununarized below in Table 5.0 (DP426724, K. Rury, 05/25/2015). 

Chronic 

The unrefined chronic dietary (food and drinking water) exposure to halosulfuron-methyl is 

below HED's level of concern (<100% of the chronic population adj usted dose (cPAD)) for the 

general U.S. population and all population subgroups. The chronic dietary exposure estimates 

are 2.1% of the cPAD for the general U.S. population and 5.7% of the cPAD for children 1-2 

years old, the most highly exposed population subgroup. The results are summarized below in 

Table 5.0 (DP426724, K. Rury, 05/25/2015). 

Page 9 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

Table 5.0. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Halosulfuron-Metbyl 

Acute Dietary Chronic Dietary (95th Percentile) 

Population Subgroup Dietary Exposure Dietary Exposure 

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

General U.S. Population 0.002091 2.1 

All Infants (<I year old) 0.004987 5.0 

Children 1-2 years old 0.005740 5.7 

Children 3-5 years old 

NIA 

0.004025 4.0 

NIA 

Children 6-12 years old 0.002488 2.5 

Youth 13-1 9 years old 0.001597 1.6 

Adults 20-49 years old 0.001817 1.8 

Adults 50-99 years old 0.001767 1.8 

Females 13-49 years old 0.004139 <J 0.00181 2 1.8 

The subpopu lation(s) with the highest risk estimates. The highest risk estimate is bolded. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization 

There are existing residential uses that have been previously assessed according to HED's 2012 

Residential SOPs3 along with policy changes for body weight assumptions (DP42 l 8 l 9, K. Rury, 

0611012015). The most protective worst-case residential handler scenario 

(mixer/loader/applicator exposure of a liquid formulation via backpack sprayer or manuallypressurized handwand to turf) resulted in a margin of exposure (MOE) of230,000 which exceeds 

the level of concern (i.e. the LOC is an MOE < l 00), and is therefore not of concern to HE D. 

The most protective worst-case residential short-term post-application incidental oral scenario 

(hand-to-mouth exposure from turf treated with a liquid formul ation) for children resulted in an 

MOE of24,000 which exceeds the LOC. and is therefore not of concern to HED. 

6.1 Spray Drift 

Off-target movement of pesticides can occur via many types of pathways and it is governed by a 

variety of factors. Sprays that are released and do not deposit in the application area end up offtarget and can lead to exposures to those it may directly contact. They can also deposit on 

surfaces where contact with residues can eventually lead to indirect exposures (e.g. children 

playing on lawns where residues have deposited next to treated fields). The potential risk 

estimates from these residues can be calculated using drift modeling coupled with methods 

employed for residential risk assessments for turf products. 

The approach to be used for quantitatively incorporating spray drift into risk assessment is based 

on a premise of compliant applications which, by definition, should not result in direct exposures 

to individuals because of existing label language and other regulatory requirements intended to 

prevent them.4 Direct exposures would include inhalation of the spray plume or being sprayed 

3 Ava i I able: http://www.epa.gov/pest icides/scicnce/rcsident ia I-exposure-sop. htm I 

~This approach is consistent with the requ irements o f the EPA's Worker Protection Standard which, 

when inc luded on all labels, precludes direct exposure pathways. 

Page 10 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

directly. Rather, the exposures addressed here are thought to occur indirectly through contact 

with impacted areas, such as residential lawns, when compliant applications are conducted. 

Given this premise, exposures for children (I to 2 years old) and adults who have contact with 

turf where residues are assumed to have deposited via spray drift thus resulting in an indirect 

exposure are the focus of this analysis analogous to how exposures to turf products are 

considered in risk assessment. 

EPA Reg. No. 81880-24 is an existing label for use on turf, thus it was evaluated to detennine 

whether the risk assessment for that use may be considered protective of any type of exposure 

that would be associated with spray drift. If the maximum application rate on crops, adjusted by 

the amount of drift expected, is less than or equal to existing turf application rates, the existing 

turf assessment is considered protective of spray drift exposure. For halosulfuron-methyl, the 

registered residentia l uses on turf result in estimated exposure levels that are greater than the 

potential exposure from spray drift; therefore, no new residential assessment needs to be 

completed. The currently registered maximum single application rate of halosulfuron-methyl for 

al I registered crops is 0.094 lb ail A The highest degree of spray drift noted for any application 

method immediately adjacent to a treated field (Tier 1 output from the aerial application using 

fine to medium spray quality) results in a deposition fraction of 0.26 of the application rate. A 

quantitative spray drift assessment for halosulfuron-methyl is not required because the maximum 

application rate to a crop/target site multiplied by the adjustment factor for drift of 0.26 is less 

than the maximum direct spray residential turf application rate 0.136 lb ai/ A 5 for any 

halosulfuron-methyl products. The turf post-application MO Es have been previously assessed 

and are based on the 2012 Residential SOPs. 

6.2 Residential Bystander Post-Application Inhala tion Exposure 

Volatilization of pesticides may be a source of post-application inhalation exposure to 

individuals nearby 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, and received the SAP's final report on 

March 2, 20 I 0 (http://www.epa.gov/scipoly/SAP/meetings/2009/ 120109meeting.html). The 

agency has evaluated the SAP report and has developed a Volatilization Screening Tool and a 

subsequent Volatilization Screening Analysis.6 During Registration Review, the agency will 

utilize this analysis to determine if data (i.e., flux studies, route-specific inhalation toxicological 

studies) or further analysis is required for mesosulfuron-methyl. 

7.0 Aggregate Exposure/Risk Characterization 

Acute 

The acute risk estimate for females 13-49 years old, resulting from aggregate exposure to 

halosulfuron-methyl in food and drinking water, is below the Agency's LOC and is < l % of the 

aP AD. There was no indication of an adverse effect attributable to a single dose for the general 

U.S. population. 

5 0.094 lb ai/A x 0.26 = 0.0244 lb ai/A ::5 0.1 36 lb ai/A 

6 Available at: http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-20 14-0219. 

Page 11 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

Short- and Intermediate Term 

There is potential short- and intermediate-term exposure to halosulfuron-methyl via the dietary 

pathway (which is considered background exposure) and the residential pathway (which is 

considered the primary pathway). For adults, since a dermal hazard was not identified, the 

exposure pathways include only the dietary and inhalation (residential handler) routes. For 

children, the exposure pathway includes the dietary exposure and the incidental oral postapplication residential pathway. All aggregate MO Es are greater than I 00; therefore, aggregate 

exposure to halosulfuron-methyl is not of risk concern. The most conservative scenario was 

chosen for each population (e.g. M/L/A via handheld equipment to turf for adults; and hand-to 

mouth exposure to treated turf for children 1 to < 2 years old). The MO Es for adults and 

children 1 to <2 are 25,000 and 6,400, respectively (DP425728, K. Rury, 05/25/2015; 

DP396460, N. Tsaur, 06/ 12/2012). 

Ta ble 7.0. Short-Term Aggregate Risk Calcula tions 

NOAEL LOC for Average Food and Residential Total Aggregate 

Population Aggregate Water Exposureb Exposurec Exposured MOE 

(food and 

mg/kg/day 

Risk' mg/kg/day residential)c 

Adultsf 0.001817 0.000215 0.002032 25,000 

Ch ildren 50 100 

(I to 2 years old) 0.00574 0.00207 0.007810 6,400 

a Adults and Children Level of Concern= I 00 (based on inter- and intra- species uncertainty factors, each at I OX). 

b Adults= 0.00 I 817 (Adults 20-49). Children = 0.00574 mg/kg/day (Children 1-2 years old). 

c Residential MOE based on residential handler exposure (for adults) and post-application exposure from 

application to residential lawns (for children). 

d Total Exposure = Average Food and Water Exposure + Residential Exposure 

e Aggregate MOE = Short Tenn Oral NOAEL (50 mg/kg/day) + Total Exposure. 

f Adults (20-49) was selected from the chronic dietary exposure assessment as the most protective adult 

subpopulation. 

8.0 Cumulative Exposure/Risk Characterization 

In 2015, EPA 's Office of Pesticide Programs released a guidance document entitled, Pesticide 

Cumulative Risk Assessment: Framework for Screening Analysis 

[http://www.epa.gov/oppfead l/cb/csb _page/updates/2015/framework-for-screeninganalysis.html). This document provides guidance on how to screen groups of pesticides for 

cumulative evaluation using a two-step approach beginning with the evaluation of available 

toxicological information and if necessary, followed by a risk-based screening approach. This 

framework supplements the existing guidance documents for establishing common mechanism 

groups (CMGs)ftJ and conducting cumulative risk assessments (CRA)l2l. The Agency has 

utilized this framework to evaluate the SUs of which halosulfuron-methyl is a member 

(OP428798, J. D' Agostino, 09/09/2015). Although the SUs share some chemical and 

1

1

1 Guidance For Identifying Pesticide Chemicals and Other Substances That Have a Common 

Mechanism a/Toxicity (USEPA, 1999) 

1

2

1 Guidance on Cumulative Risk Assessment of Pesticide Chemicals That Have a Common 

Mechanism of Toxicily (USEPA, 2002) 

Page 12 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

toxicological characteristics, the toxicological database does not support a testable hypothesis for 

a common mechanfam of action. No further mechanistic data are required and no further 

cumulative evaluation is necessary. 

9.0 Occupational Exposure/Risk Characterization 

Dermal exposure during handling activities was not considered because systemic toxicity was 

not observed at the limit dose in the 2 1-day dermal toxicity study in rats and there was no 

evidence of quantitative susceptibility in the halosulfuron-methyl database. The occupational 

handler exposure and risk estimates indicate that short- and intermediate-term non-cancer 

inhalation MO Es are not of concern to HED (i.e., MO Es ~ 100) at baseline (no respirator) attire 

(DP403362, C. Walls, 01118/2013). The lowest MOE of 1,200 represents the most protective 

worst-case occupational scenario: mixing/loading dry flowables (water-dispersible granules) to 

support aerial applications to high acreage crops (i.e. rice). These risk estimates are not of 

concern to HED. 

Dermal exposure during post-application activities was not considered because systemic toxicity 

was not observed at the limit dose in the dermal study and there was no evidence of quantitative 

susceptibility in the halosulfuron-methyl database. Based on the Agency's current practices, a 

quantitative occupational post-application inhalation exposure assessment was not performed for 

halosulfuron-methyl at this time. If new policies or procedures are put into place, the Agency 

may revisit the need for a quantitative occupational post-application inhalation exposure 

assessment for halosulfuron-methyl. 

10.0 References 

Barrett, M., 04115/2015, DP421820, Halosulfuron-methyl Drinking Water Assessment for 

Additional Food/Feed Uses on Pome Fruits Group 11-10 and Climbing Vines Subgroup 13-

07F. 

Rury, K., 08/06/20 13, TXR0056723, Sulfonylureas: Summary of Hazard and Science Policy 

Council (HASPOC) Meeting on July 18, 2013: Recommendations on Data Requirement for 

lmmunotoxicity Studies for Sulfonyfurea Pesticides. 

Rury, K., 05/25/2015, DP426724, Halosulfuron-lvfethyl. Acute and Chronic Aggregate Dietary 

(Food and Drinking Water) Exposure and Risk Assessments for the Section 3 Registration 

Action on Pome Fruit Group 11-10 and Fruit, Small Vine Climbing Subgroup J3-07F. 

Rury, K., 06/ 10/2015, DP421819, Halosulfuron-lv!ethyl. Human Health Risk Assessment for a 

Proposed Use on Pome Fruit Crop Group 11-10 and Small Fruit Vine Climbing Subgroup, 

Except Fuzzy Kiwifruit, Subgroup I 3-07F. 

Rury, K., 05/25/2015, DP425728, Halosulfuron-lv!ethyl. Occupational and Residential Exposure 

Assessment for a Proposed Use on Pome Fruit Crop Group 11-10 and Small Fruit Vine 

Climbing Subgroup, Except Fuzzy Kiwifruit, Subgroup 13-07 F. 

Page 13 of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 042801 3 

Smegal, D., 02/22/2012, TXR0054045, Halosulfuron-methyl: Summa1y of Hazard and Science 

Policy Council (HASPOC) Meeting of February 9, 2012: Recommendations on waiver 

requests/or 28-day inhalation study. 

Tsaur, N., 06/ 12/2013, DP396460, Halosulfuron-Methyl. Occupational Exposure Assessment for 

Proposed New Uses on Proso Mille/ and Crop Group 17 (Grass, Forage, Fodder. and Hay) 

with An Updated Residential Exposure Assessment of All Existing Residential Uses. 

Page 14 of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

Appendix A. Toxicology Profile for Halosulfuron-Methyl 

Table A.1. Toxicology Data Requirements 

Technical 

Required Submitted 

870.1100 Acute Oral Toxicity ......................................................... yes yes 

870.1200 Acute Dermal Toxicity .................................................... yes yes 

870.1 300 Acute Inhalation Tox icity ................................................ yes yes 

870.2400 Primary Eye Irritation ...................................................... yes yes 

870.2500 Primary Dermal Irritation ................................................ yes yes 

870.2600 Dermal Sensitization ....................................................... yes yes 

870.3100 90-Day Oral Toxicity in Rodents .................................... yes yes 

870.3150 90-Day Oral Toxicity in Nonrodents ............................... yes yes 

870.3200 21 /28-Day Dermal Toxicity ............................................. yes yes 

870.3250 90-Day Dermal Toxicity .................................................. no no 

870.3465 90-Day Inhalation Toxicity ............................................. CR" waivedb 

870.3700a Prenatal Developmental Toxicity (rodent) ...................... yes yes 

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

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

870.4 1 OOa Chron ic Toxicity (rodent) ............................................... n/a - 870.41 OOb Chronic Toxicity (non-rodent) ........................................ yes yes 

870.4200a Oncogenicity (rat) ........................................................... n/a - 870.4200b Oncogenicity (mouse) .................................................... yes yes 

870.4300 Chronic/Oncogenicity (rat) .............................................. yes yes 

870.5100 Mutagenicity- Bacterial Reverse Mutation Test ............ yes yes 

870.5300 Mutagenicity- Mammalian Cell Gene Mutation Test .... yes yes 

870.5375 Mutagenicity- Structural Chromosomal Aberrations ..... yes yes 

870.5395 Mutagenicity-Other Genotoxic Effects ......................... yes yes 

870.6 1 OOa Acute Delayed Neurotoxicity (hen) ................................ no no 

870.61 OOb 90-Day Neurotoxicity (hen) ............................................ no no 

870.6200a Acute Neurotoxic ity Screening Battery (rat) .................. yes yes 

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

870.6300 Developmental Neurotoxicity .......................................... no no 

870.7485 General Metabolism ........................................................ yes yes 

870.7600 Dermal Penetration .......................................................... no no 

870.7800 lmmunotoxicity ............................................................... yes waivedc 

a CR = conditionally required. 

b The Hazard and Science Policy Council (HASPOC) determined that a subchronic inhalation study is not required 

at this time for halosulfuron-methyl (TXR#0054045, 02/22/20 12). 

c The Hazard and Science Policy Council (HASPOC) determined that an immunotoxieity study is not required at 

this time for halosulfuron-methyl (TXR#0056723 , 08/06/2013). 

Page 15 of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

Table A.2. Acute Toxicity Profile - Test Substance 

Guideline No. Study Type MRID Results Toxicity 

Category 

LDso: Males= I 0,435 mg/kg 

870. 11 00 Acute oral - rat 42139413 Females= 7758 mg/kg IV 

Combined = 8866 mg/kg 

870.1 2 00 Acute dermal - rat 42 1394 15 LDso >2000 mg/kg (limit test) Ill 

870.1300 Acute inhalation - rat 42139417 LCso>6 mg/L IV 

870.2400 Acute eye irritation - rabbit 42139419 Mild transient (<24 hr) irritation IV involving the conjunctiva and iris. 

870.2500 Acute dennal irritation - rabbit 42139421 Non-irritant IV 

870.2600 Skin sensitization - guinea pig 42139423 Not a skin sensitizer NIA (maximization test) 

Table A.3. Subchronic, Chronic and Other Toxicity Profile of Halosulfuron-Methyl 

Guideline Study Type MRID Number (year)/ Results Number Classification/Doses 

870.3 100 Subchronic oral 4361630 I ( 1995)/ Acccptablc/Guidcline OAEL = M ::'.: 1400. F = 75.8 

(82-1) toxicity study in Doses: 0. I 00. I 000. I 0000. or 20000 mg/kg/day 

rats ppm (diet) (M/F: 6.717.6. 66.5175.8. LOAEL = M not determined. F = 772.8 

682.81772.8. 1400/ 1578 mg/kg/day) mg/kg/day based on decreased body 

weight gains. 

870.3100 Subchronic oral 42 17 1501 (1988)/ NOAEL = M = 11 6, F =147 mg/kg/day 

(82-1 ) toxicity study in Acccptablc/Nonguideline LOAEL = M = 497, F = 640 mg/kg/day 

rats (28 day range- Doses: 0. I 00. 400. 1600. or 6400 ppm based on decreased organ weights and 

lindcr) (diet) changes in clinical chemistry 

(M/F: 7.4/8.9. 28.8/37.3. 1161147. parameters. 

497/640 mg/kg/dav) 

870.3150 Subchronic oral 42171502 ( 1991 )/ Acceptable/Guideline NOAEL = 10 mg/kg/day 

(82-1 ) toxicity study in Doses: 0. 2.5. I 0. 40. and 160 LOAEL = 40 mg/kg/day based on !bwt. 

nonrodcnts - dogs mg/kg/day (capsule) cholesterol. & albumin levels. The 

decrease was panicularly marked at the 

next higher dose level. 160 mg/kg/day. 

870.3200 2 1-day dermal 426614 17 (1990)/ Acceptable/Guideline No adverse effects was seen at the 

(82-2) toxicity in rats Doses: 0. I 0. I 00. or I 000 mg/kg/day highest dose level. NOAEL = 1000 

mg/kg/day (Highest dose tested) 

(limit dose) 

870.3465 90-day inhalation The requirement of this study was waived (TXR 0054045: 02/22112) (82-4) study in rats 

870.4100 Chronic oral 42396211 ( 199 1 )/ Acceptable/Guideline NOAEL = JO mg/kg/day 

(83-1 b) toxicity study in Doses: 0. 0.25. 1.0. I 0.0. or 40 LOA EL = 40 mg/kg/day based on ! bwt 

dogs ( I-year) mg/kg/day (capsule). (9-13%): !R.BC. hematocrit. & 

hemoglobin: ! cholesterol 

426614 18 (1992)/ NOAEL = M= 108.3. F=56.3 mg/kg/day 

Page 16 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

Table A.3. Subchronic, Chronic and Other Toxicity Profile of Halosulfuron-Methyl 

Guideline Study Type MRID Number (year)/ 

Results Number Classification/Doses 

870.4300 Combined Acceptable/Guideline LOAEL = M=225.6. F= l38.6 

(83-5) Chronic/ Doses: 0. I 0. I 00, I 000. or 2500. 5000 mg/kg/day based on marginal decrease 

Carcinogenicity in (males only) ppm (diet) in body weight gain in both males and 

rats (M/F: 0.44/0.56, 4.415.6. 43.8/56.3, f..:ma les. 

I 08.3/ 138.6, 225.6 (M) mg/kg/day) 

No evidence of carcinogenicity. 

870.4200 Carcinogenicity 42661419 ( 1992)/ Acceptable/Guideline NOAEL = M=4 IO.O. F > 1214.6 

(83-2) study in mice Doses: 0, 30. 300. 3000, or 7000 ppm mg/kg/day 

(diet) LOAEL = M=97 I .9, F> 12 14.6 

(WF: 4.0/5.2. 4 1.1151.0, 410.0/509.1. or mg/kg/day based on necropsy lindings 

971.9/1214.6 mg/kg/day) (increase incidence of 

microconcretion/mineralization in the 

testis and epididymis). 

No evidence or carcinogenicity. 

870.3700 Developmental 42139425 ( 1990)/ Acceptablt:/Guideline Maternal NOAEL = 250 mg/kg/day. 

(83-3) toxicity in rats Doses: 0. 75. 250. or 750 mg/kg/day Maternal LOAEL = 750 mg/kg/day. 

(gavage) based on increased incidence of clinical 

observations. 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 liner size. 

increased fetal and litter incidences of 

soft tissue and skeletal variations. 

870.3700 Developmental 42139426 ( 1990)/ Acceptable/Guideline Maternal NOl\EL = 50 mg/kg/clay 

(83-3b) toxicity st11dy in Doses: 0. I 5, 50. or 150 mg/kg/day Maternal LOAEL = 150 mg/kg/day 

rabbits (gavagc) 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 Developmental 4362190 1(1995)3-chlorosulfonamide Maternal Toxicity NOAEL => 1000 

(83-3b) toxicity study in acid mg/kg/day 

rabbits Metabolite/ Maternal Toxicity LOA EL > I 000 

Acceptable/Guideline mg/kg/day 

Doses: 0, 30, 300. or I 000 mg/kg/day Developmental Toxicity NOAEL => 

I 000 mg/kg/day 

Developmental Toxicity LOAEL > 

1000 mg/kg/day 

870.3800 Two-Generation 42139427 ( 1991 )/ Acceptable/Guideline Parental/Systemic NOAEL = M=50.5, 

(83-4) reproduction study Doses: 0. I 00. 800, or 3600 ppm (diet) F=58. 7 mg/kg/day 

in rats ( Fo Males: 6.3. 50.4. and 223.2 Parental/Systemic LOAEL = M::223.2, 

mg/kg/day: Fo Females: 7.4, 58.7, and f =26 l .4 mg/kg/day based On decreased 

261.4 mg/kg/day) body wei,e.hts and reduced food 

Page 17 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

Table A.3. Subchronic, Chronic and Other Toxicity Profile of Halosulfuron-Methyl 

Guideline Study Type MRlD Number (year)/ Results Number Classification/Doses 

consumption during the premating 

period in both sexes. 

Offspring NOAEL = 5 1/59 mg/kg/day 

Offspring LOAEL = 223.2/261.4 

mg/kg/day based on decreased body 

weight in the F1 pups and marginal 

decreased body weight in F2 pups. 

Reproductive NOAEL > = 223.2/261.4 

mg/kg/day. 

870.5 100 Mutagcnic - Ames 42139428 ( 199 1)/ Acceptable Negative. Concentrations=> 5000 

(84-2 a) Salmonella (+/-S9) 5 strains S. typh. Cone.: I - microgm/platc found to be insoluble 

~12himurium and 10000 μglplatc: E. Coli WpuvrA Cone.: and/or cytotoxic. 

E. Coli. 333 - I 0000 ~lg/p ate 

870.5100 Mutagcnic - Gene 43616302 ( 1995)/ Acceptable Negative. Conducted with 3-

(84-2 a) Mutation (+/-S9) 5 strains S. typh. Cone.: 50 - chlorosulfonamide acid-the principal 

5000 ~1 g/platc soil metabolite ofhalosulfuron-methyl. 

870.5300 Mutagenic - Gene 43616303 ( 1995) - Metabolite/ Negative. Conducted with 3-

(84-2) Mutation - Acceptable chlorosulfonamide acid-the principal 

Hamster (Chinese) (+/-S9) Cone.: 350-3 100 itJ?/mL soil metabolite of halosulfuron-methyl. 

870.5300 Mutagcnic - 42139431 ( 199 1)- Metabolite/ Conclusions indefinite due partly to 

(84-2) (HGPRT) - Unacceptable relatively high negative and low 

Hamster Cone.: 100-1000 μg/mL positive control values. solubility 

(Chinese). problems with test article. 

870.5300 Mutagcnic - 42661420 ( 1993)/ Acceptable Negative. Did not induce forward 

(84-2) (HGPRT)- (+/-S9) Cone.: 50-900 μg/mL mutations at the l IGPRT locus in 

I lamstcr Chinese 1 lamster ovary cells. 

(Chinese). Concentrations above 700 ug/mL were 

insoluble. 

870.5375 Mutagcnic - In 42139429 ( 1989)/ Acceptable Negative. No chromosomal aberrations. 

(84-2) vitro Clastogenic - {+/-S9) Cone.: 449-1810 μg//mL 

Hamster (Chinese) 

870.5395 Mutagcnic - 43616304 ( 1995) - Negative. Conducted with 3-

(84-2) Micronucleus Metabolite/Acceptable chlorosulfonamide acid-the principal 

Assay - Mouse Doses: 1250. 2500 or 5000 mg/kg soil metabolite ofhalosulfuron-mcthyl. 

(CD-I ) No overt toxicity for the treated animals 

or cytotoxicity for the target organ 

(bone marrow cells) was observed. 

870.5395 Mutagenic - 42 139430 (1989)/ Acceptable cgative. Did not induce significant 

(84-2) Micronuclcus Doses: 500. 1667 Or 5000 mg/kg. elevations in the frequencies of 

Assay - Mouse mieronucleated polychromatic 

crvthrocvtes. 

870.5500 Mutagcnic - 42 139432 ( 1990)/ Acceptable cgativc. Fail to induce unscheduled 

(84-2) Unscheduled DNA (+/-S9) Cone.: 25-1000 μg/mL DNA synthesis in primary rat 

synthesis - Rat hcpatocytcs. 

870.6200a Acute 45754701 (1994) and 46199501 NOAEL = 600 mg/kg. 

(82-7) ncurotoxicity in ( 1989)[ positive control study]/ LOAEL = 2000 mg/kg (limit dose) 

rats. Acceptable/Guideline based on mortality in males. 

Doses: 0. 200. 600. or 2000 mg/kg (limit 

dose) 

Page 18 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D42801 3 

Table A.3. Subchronic, Chronic and Other Toxicity Profile of Halosulfuron-Methyl 

Guideline Study Type MRJD Number (year)/ Results Number Classification/Doses 

870.6200b Subchronic 45754702 (1992)/ Acceptable/Guideline NOA EL= M = F = I 000 ppm (M/F: 

(82-7) neurotoxicity Doses: M: 0. I 00. I 000. or I 0.000 ppm: 62.8/82.6 mg/kg/day). 

study in rats. F: 0. 100. 1000. or 4000 ppm (diet) LOAEL = M = 10.000 ppm: F =4000 

(M/F: 010. 6.3/8. I. 62.8/82.6, or ppm (M: 706.0 mg/kg/day) in males 

706.0/3 15.9 mg/kg/day) based on decreased body weight and 

body weight gain and (F: 315.9 

mg/kg/day) in females based on 

decreased body wei~ht gain. 

870.7485 Metabolism 42139433 ( 1990)/ Acceptable/Guideline Absorption was rapid. incomplete and 

(83-6) 5 or 250 mg/kg single dose or 5 similar in both sexes. Elimination was 

mg/kg/day repeated doses mostly by urine and feces within 72 

hours. appearing to be independent of 

dose and sex. Desmethyl NC-319 and 

the 5-hydroxy derivative were the major 

urinary and fecal metabolites. 

870. 7800(83-

6) 

lmmunotoxicity This requirement of this study was waived (TX: 0056723: 08/06/20 13) 

Appendix B. International Residue Limit Status 

Table B.1. Summary of US Tolerances and International Maximum Residue Limits 

Residue Definition 

us Canada Mexico' Codex 

40 CFR 180.479 (a) ( 1): Compliance with Methy l 3-chloro-5-[[[[( 4,6- None 

the tolerance levels specified in the dimethoxy-2-

following table is to be determined by pyrimidiny l)amino]carbonyl]a 

measuring only those halosulfuron-methyl mino]sulfony l]-1-methy l- I Hresid ues containing the 3- pyrazole-4-carboxylate 

chlorosu lfonamide (3-CSA) moiety, 

expressed as the stoichiometric equiva lent 

of halosulfuron-methyl 

Commodity Tolerance (p/Jm) /Maximum Residue Limit (mf!/kf!) 

us Canada Mexico' Codex 

Cattle, fat 0.05 0.01 

Cante, meat 0.05 

Cattle, meat byproducts 1.0 0.2 

Goat, fat 0.05 0.0 1 

Goat, meat 0.05 

Goat, meat byproducts 1.0 0.2 

Ho!?., meat byproducts 0.1 

Horse. fat 0.05 0.01 

Horse, meat 0.05 

Horse, meat byproducts 1.0 0.2 

Milk 0.05 

Sheeo, fat 0.05 0.01 

Sheeo, meat 0.05 

Sheep, meat byproducts 1.0 0.2 

Page 19 of22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. 0428013 

Table B.1. Summary of US Tolerances and International Maximum Residue Limits 

US (40 CFR § 180.479(a)(2)] Canada Mexico' Codex 

(2) Compliance with the tolerance levels Same as above None 

specified in the following table is to be 

detennined by measuring only halosulfuronmethyl 

Commodity Tolerance (pom) /Maximum Residue Limit (mKlkg) 

us Canada Mexico 1 Codex 

Alfalfa, forage 1.0 

Alfalfa, hay 2.0 

Almond, hulls 0.2 

Apple 0.05 0.05 

Artichoke 0.05 

Asparagus 0.8 I 

Bean, dry, seed 0.05 0.05 Dry (adzuki beans. beans, 

blackeyed peas, 

broad beans, catjang seeds, 

chickpeas, cowpea seeds, guar 

seeds, kidney beans, lablab beans, 

lima beans, moth beans, mung 

beans, navy beans, pink beans, 

pinto beans, rice beans, southern 

peas, tepary beans, urd beans, 

grain lupin 

Bush berry, subgroup 13-078 0.05 0.05 aronia berries, buffalo 

currants, Chilean guavas, currants 

elderberries, European barberries, 

gooseberries, highbush 

(blueberries, cranberries), 

honeysuckle, huckleberries, 

jostaberries, J uneberries 

(Saskatoon berries), lingonberries, 

lowbush blueberries, native 

currants. salal berries. sea 

buck thorn 

Caneberry subgroup 13-07 A 0.05 0.05 Blackberries, loganberries, 

raspberries, wild raspberries 

Com, field, forage 0.2 

Corn, field, grain 0.05 0.05 

Com, field, stover 0.8 

Com , DOD, grain 0.05 0.05 

Com, pop, stover 0.8 

Corn, sweet, forage 0.2 

Corn, sweet, kernel plus cob with 0.05 0.05 husks removed 

Corn, sweet, stover 0.8 

Cotton. gin bvoroducts 0.05 

Cotton, undelinted seed 0.05 

Grass, forage, fodder, and hay, group 20 

17, forage 

Grass, forage , fodder, and hay, group 0.05 

17,hay 

Page 20 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D4280 13 

Table B.1. Summary of US Tolerances and International Maximum Residue Limits 

Melon subgroup 9A 0.1 0.1 citron melons, cantaloupes, 

muskmelons (other than those 

listed in this item), watermelons 

Millet, proso, forage 10 

Millet, proso, grain 0.01 0.01 

Millet, proso, hay 0.01 

Millet, proso, straw 0.01 

Nut, tree, group 14 0.05 0.05 African tree nuts, almond 

nuts, beechnuts, black walnuts, 

Brazil nuts, Brazilian pine nuts, 

bunya nuts, bur oak nuts, 

butternuts, Cajou nuts, candlenuts, 

cashew nuts, chestnuts, 

chinquapin nuts, coconuts, 

coquito nuts, dika nuts, English 

walnuts, ginkgo nuts, Guiana 

chestnuts, hazelnuts (filbert), 

heartnuts, hickory nuts, Japanese 

horse-chestnuts, macadamia nuts, 

mongongo nuts, monkey-pot nuts, 

monkey puzzle nuts, Okari nuts, 

Pachira nuts, peach palm nuts, 

pecan nuts, pequi nuts, Pili nuts, 

pine nuts, pistachio nuts, Sapucaia 

nuts, tropical almond nuts, yellow 

horn nuts 

Okra 0.05 0.05 

Pea and bean, succulent shelled, 0.05 

subgroup 6 

Pea and bean, succulent shelled, 0.05 0.05 edible podded Uackbeans, 

subgroup 68 moth beans, runner beans, snap 

beans, sword beans, wax beans, 

vardlong beans) 

Pistachio 0.05 0.05 

Rhubarb 0.05 0.05 

Rice, grain 0.05 

Rice, straw 0.2 

Sorghum, grain, forage 0.05 

Sorghum, grain, grain 0.05 0.05 

Sorghum, grain, stover 0.1 

Soybean, seed 0.05 

Squash/Cucumber subgroup 98 0.5 0.5 balsam apples, balsam pears 

Chayote (fruit), Chinese 

cucumbers, Chinese waxgourd, 

cucumbers, edible gourds (other 

than those listed in this item), 

pumpkin, summer squash, west 

Indian gherkins, winter squash 

Sugarcane, cane 0.05 

Page 21 of 22 
HALOSULFURON-METHYL Human Health Risk Assessment DP No. D428013 

Table B.1. Summary of US Tolerances and International Maximum Residue Limits 

Vegetable, fruiting, group 8 0.05 0.05 African eggplants, bell 

peppers, bush tomatoes, coconas, 

currant tomatoes, eggplants, 

garden huckleberries, goji berries, 

groundcherries, martynias, 

naranjillas, nonbell peppers, 

okras. pea eggplants, pepinos. 

roselles, scarlet eggplants, 

sun berries. tomati llos, tomatoes, 

tree tomatoes 

Vegetable, tuberous and corm, 0.05 

subgroup IC 

Recommended Tolerances 

40CFR § I 80.479(a)(2) 

Fruit, pome, group 11-10 0.05 0.05 apple 

40CFR §I 80.479(c) 

Fruit. small, vine climbing, except 0.05 

fuzzy kiwifruit, sub.group 13-0?F. 

MRls witlt NO US Equivale11t 

Agave I 

Bamboo shoots I 

Celtuce I 

Edible fems I 

Fresh Florence fennel leaves and I stalks 

Kohlrabies I 

Palm hearts I 

Prickly pear pads I 

Sea kales I 

Completed by: M. Negussie; 06/16/2015 1 Mex ico adopts US tolerances and/or Codex MRLs for its export purposes. 

Page 22 of 22