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

COMPANY NOTICE OF FILING 

EPA Registration Division contact: Sidney Jackson 703-305-7610

Interregional Research Project Number 4

PP9E7577

EPA has received a pesticide petition PP9E7577 from the Interregional 

Research Project Number 4(IR-4) in cooperation with Canyon Group LLC, c/o 

Gowan Company, 370 South Main Street, Yuma, Arizona 85364 proposing, pursuant 

to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 

346a(d), to amend 40 CFR part 180.479 by establishing a tolerance for residues of

halosulfuron-methyl in or on the raw agricultural commodities pea and bean, succulent 

shelled subgroup 6B; pea and bean, dried shelled, except soybean subgroup 6C;

vegetables, tuberous and corm subgroup 1C; bushberry subgroup 13-07B; apple; 

rhubarb; and okra at 0.05 parts per million (ppm). EPA has determined that the 

petition contains data or information regarding the elements set forth in section 408 (d)(2) 

of FDDCA; however, EPA has not fully evaluated the sufficiency of the submitted data 

at this time or whether the data supports granting of the petition. Additional data may be 

needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of halosulfuron-methyl as well as the 

nature of the residues in plants is adequately understood for the purposes of these 

tolerances. Metabolism studies were conducted with three crops, vis.; field corn, 

sugarcane and soybeans. Metabolism depends on the mode of application. 

Preemergent applications result in rapid soil degradation of halosulfuron-methyl 

followed by crop uptake of the resulting pyrazole moiety. The pyrimidine ring 

binds tightly to soil and is eventually converted to carbon dioxide by microbial 

degradation. In postemergent applications, little metabolism and translocation take 

place, resulting in unmetabolized parent compound as the major residue on the 

directly treated foliar surfaces. Very low residue levels of the metabolite 3-chloro-1-

methyl-5-sulfamoylpyrazole-4-carboxylic acid (3-CSA) are found in grain.

2. Analytical method. A practical analytical method, gas chromatography with 

a nitrogen-specific detector, is available for enforcement purposes. The limit of 

detection is 0.003 ppm.

3. Magnitude of residues. Samples from 13 apple trials, 6 blueberry trials, 4 

rhubarb trials, 9 potato trials, 12 dry bean trials and 12 succulent pea trials were 

analyzed for halosulfuron and its metabolites. Samples from an additional apple 

trial treated a 5X the proposed rate were also analyzed. Combined residues were 
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below 0.05 ppm in every sample.

B. Toxicological Profile

1. Acute toxicity. Acute toxicological studies placed technical-grade 

halosulfuron-methyl in Toxicity Category III. The Agency has derived an acute 

PAD of 0.17 mg/kg based upon a rabbit developmental toxicity study. The NOAEL 

was 50 mg/kg, and the Agency applied an Uncertainty Factor of 300 (10X for 

interspecies extrapolation, 10X for intraspecies variability and 3X due to the lack of 

a developmental neurotoxicity study.

2. Genotoxicty. Bacterial and mammalian microsomal mutagenicity assays 

showed halosulfuron-methyl not to be mutagenic. Gene mutation and chromosomal 

aberration studies were negative. An unscheduled DNA test in primary rat 

hepatocytes was negative. An in vivo mouse micronucleus assay did not cause a 

significant increase in the frequency of micronucleated polychromatic erythrocytes 

in bone marrow cells.

3. Reproductive and developmental toxicity. A developmental toxicity study in 

rats resulted in a developmental LOAEL of 750 mg/kg/day, based on decreases in 

mean litter size and fetal body weight and increases in resorptions, resorptions per 

dam, post-implantation loss and in fetal and litter incidences of soft tissue and 

skeletal variations. The developmental NOAEL in this study was 250 mg/kg/day. 

The maternal LOAEL was 750 mg/kg/day, based on increased incidence of clinical 

observations, reduced body weight gains, and reduced food consumption and food 

efficiency. The maternal NOAEL was 250 mg/kg/day.

A developmental toxicity study in rabbits resulted in a developmental LOAEL of 

150 mg/kg/day, based on decreased mean litter size and increases in resorptions, 

resorptions per dam and post-implantation loss. The developmental NOAEL was 

50 mg/kg/day. The maternal LOAEL was 150 mg/kg/day, based on reduced body 

weight gain and reduced food consumption and food efficiency, and the maternal 

NOAEL was 50 mg/kg/day.

A dietary 2-generation reproduction study in rats resulted in parental toxicity at 223 

mg/kg/day in males and 261 mg/kg/day in females, based on decreased body 

weights, decreased body weight gains, and reduced food consumption during the 

premating period. Very light effects were noted in body weight of the offspring at 

this dose. This effect was considered to be developmental toxicity (developmental 

delay) rather than a reproductive effect. No effects were noted on reproductive or 

other developmental toxicity parameters. The systemic/developmental toxicity 

LOAEL was 223 mg/kg/day in males and 261 mg/kg/day in females; the 

systemic/developmental toxicity NOAEL was 50 mg/kg/day in males and 59 

mg/kg/day in females. The reproductive NOAEL was greater than or equal to 223 

mg/kg/day for males and 261 mg/kg/day for females.

4. Subchronic toxicity. A 90-day feeding study in rats resulted in a NOAEL of 
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116 mg/kg/day in males and 147 mg/kg/day in females. The LOAEL was 497 

mg/kg/day for males and 640 mg/kg/day in females.

5. Chronic toxicity. A 1-year chronic oral toxicity study in dogs resulted in a 

LOAEL of 40 mg/kg/day based on decreased weight gain and a NOAEL of 10 

mg/kg/day. In a 78-week carcinogenicity study in mice, a LOAEL of 972 mg/kg/day 

was based upon decreased body weight gains and an increased incidence of 

microconcretion/mineralization in the testis and epididymis in males. No treatmentrelated effects were observed in females. The systemic NOAEL was 410 mg/kg/day, 

and the study showed no evidence of carcinogenicity. A combined chronic and 

carcinogenicity study in rats resulted in a LOAEL of 108 mg/kg/day on males and 

56 mg/kg/day in females. The study showed no evidence of carcinogenicity. The 

Agency has derived a chronic PAD of 0.03 mg/kg/day based upon a NOAEL of 10 

mg/kg/day in the dog study and an Uncertainty Factor of 300.

6. Animal metabolism. The Agency has determined that the nature of the 

residue in ruminants is adequately understood. In the tissues and milk of goats, the 

major extractable residue was the unmetabolized parent compound. The Agency 

has not required tolerances for residues in poultry. In the rat metabolism study, 

parent compound was absorbed rapidly but incompletely. Excretion was relatively 

rapid at all doses tested, and the majority of the radioactivity was eliminated in the 

urine and feces within 72 hours. Fecal elimination was the result of unabsorbed 

parent compound.

7. Metabolite toxicology. Various toxicity studies have shown that the 

metabolite 3-CSA is of lower toxicity than the parent compound, and the Agency 

has concluded that it should not be included in the tolerance expression. However, 

in the residue analytical method for animal products, halosulfuron-methyl and all of 

its metabolites are hydrolyzed to 3-CSA, which is analyzed and the results expressed 

as parent equivalents. The tolerance expression for plant commodities consists of 

only parent compound.

8. Endocrine disruption. No specific tests have been conducted with 

halosulfuron-methyl to determine whether the chemical may have an effect in 

humans that is similar to an effect produced by a naturally occurring estrogen, or 

other endocrine effects. However, there were no significant findings in relevant 

toxicology studies, e.g., teratology and reproduction studies, which suggest that 

halosulfuron-methyl produces effects characteristic of the estrogen disruption.

C. Aggregate Exposure

1. Dietary exposure. Tolerances have previously been established for residues 

in a variety of raw agricultural commodities (40 CFR 180.479). Additionally, 

tolerances have been established for halosulfuron-methyl and its metabolites in the 

meat byproducts of cattle, goats, hogs, horses and sheep. The Agency’s exposure 

and risk assessments for these commodities were discussed in FR 70 (168) 51615 –

51623 (August 31, 2005).
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i. Food. No detectable residues were observed in soybeans treated even at an 

exaggerated use rate. Therefore, the proposed use of halosulfuron-methyl on 

soybeans does not alter the Agency’s previous conclusions regarding risk resulting 

from dietary exposure.

ii. Drinking water. The Agency has not conducted a comprehensive dietary 

exposure analysis of halosulfuron-methyl in drinking water. The Agency, however, 

has estimated concentrations in surface water using the First Index Reservoir 

Screening Tool (FIRST) or the Pesticide Root Zone Model/Exposure Analysis 

Modeling System (PRZM/EXAMS). Concentrations in ground water were 

estimated using the Screening Concentration in Ground Water Modeling System 

(SCI-GROW). None of these models includes consideration of the impact of 

processing (dilution and treatment) of raw water. The Agency conservatively 

estimated maximum residues of 0.105 ppm in surface water and 0.000065 ppm in 

ground water. The use of halosulfuron-methyl on soybeans proposed here does not 

alter the Agency’s previous calculations.

2. Non-dietary exposure. Halosulfuron-methyl is registered for use on 

residential turfgrass and landscaped areas. The short-term aggregate risk 

assessment estimates risks that are likely to result from exposures up to 30 days. 

The same toxicological effect upon which endpoints were defined (decreased 

bodyweight gain) was observed across all routes of exposure. The Agency’s level of 

concern is a short-term aggregate (food + water + residential) MOE of less than 300. 

However, the Agency has previously calculated aggregate MOEs of 3,100 or greater. 

The proposed use of halosulfuron-methyl on soybeans does not alter the Agency’s 

previous calculations.

Similarly, an intermediate-term aggregate risk assessment evaluates risks that are 

likely to result from exposures of 1 to 6 months. Again the same effect upon which 

endpoints were defined (decreased bodyweight gain) was observed across all routes 

of exposure, and the Agency’s level of concern for intermediate-term aggregate 

exposure is an MOE of less than 300. The Agency has previously calculated an 

intermediate-term aggregate risk of 819 for the most highly exposed subgroup. 

Therefore, short-term and intermediate-term aggregate exposure is not of concern.

D. Cumulative Effects

EPA has not made a common mechanism of toxicity finding regarding 

halosulfuron-methyl and any other substance. Halosulfuron-methyl does not 

appear to produce a toxic metabolite that is produced by any other substance. 

Therefore, for the purposes of this tolerance action, EPA has not assumed that 

halosulfuron-methyl has a common mechanism of toxicity with other substances.

E. Safety Determination
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1. U.S. population. The Agency has evaluated acute aggregate risk assessment 

only for females 13 – 50 years old. The Agency has calculated that exposure to this 

subpopulation occupies 1% of the aPAD. There is no indication that halosulfuronmethyl could cause adverse effects to the general population from a single dose. 

EPA previously concluded that chronic exposure occupies 3% of the cPAD for the 

general U.S. population, 8% for infants <1 year old and 4% for children 1-5. EPA 

previously concluded that intermediate-term aggregate exposure results in MOEs 

greater than 480 for all population subgroups, whereas the Agency’s Level of 

Concern is MOEs below 300. Halosulfuron-methyl is not carcinogenic.

2. Infants and children. The Agency has not set a special FQPA safety factor 

for infants and children. The Agency has concluded that an acute risk assessment 

for infants and children is not required. Short-term, intermediate-term and chronic 

exposure assessments for infants and children indicate that risk is below the 

Agency’s level of concern. Therefore, based on these risk assessments, the Agency 

has concluded that there is a reasonable certainty that no harm will result to the 

general population and to infants and children from aggregate exposure to 

halosulfuron-methyl residues.

F. International Tolerances

Mexico and Japan each has a Maximum Residue Level (MRL) of 0.05 ppm 

for halosulfuron-methyl on dry beans. Japan has also set provisional MRLs for 

halosulfuron-methyl of 0.02 ppm on apples, blueberries, peas and potatoes. There

are no Canadian, Codex or EU MRLs for these commodities.