Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Mindy Ondish (703)605-0723

E. I. du Pont de Nemours and Company

2F8131

EPA has received a pesticide petition (2F8131) from E. I. DuPont de Nemours and Company, DuPont 

Crop Protection, 1007 Market Street, Wilmington, Delaware 19898, proposing pursuant to section 408 

(d) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 346a (d), to amend 40 CFR Part 180.478 by 

establishing a tolerance for residues of the herbicide rimsulfuron: N-((4,6-dimethoxypyrimidin-2-yl) 

aminocarbonyl)-3-(ethylsulfonyl)-2-pyridinesulfonamide in or on the raw agricultural commodities

sorghum grain, forage and stover at 0.01 ppm.

This summary was prepared by the petitioner. EPA has determined that the petition contains data or 

information regarding the elements set forth in Section 408(d)(2) of the FFDCA; however, EPA has not 

fully evaluated the sufficiency of the submitted data at this time or whether the data supports granting the 

petition. Additional data may be needed before EPA rules in the petition.

A. Residue Chemistry 

1. Plant metabolism. 

The qualitative nature of the residues of rimsulfuron in plants is adequately understood; therefore no 

additional metabolism data are required to support the proposed tolerances on sorghum grain, forage and 

stover. 

2. Analytical method. 

Adequate analytical methodology, high-pressure liquid chromatography with ESI-MS/MS detection, is 

available for enforcement purposes. 

3. Magnitude of residues.

Sorghum Grain, Forage and Stover:

The results from 13 trials show that all samples of sorghum grain, forage and stover were <0.01 ppm for 

rimsulfuron after a single application of 0.5 oz rimsulfuron a.i./A. 

B. Toxicological Profile 
Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

1. Acute toxicity. 

Technical rimsulfuron is considered acute toxicology category III based on overall results from several 

studies. This compound is considered acute toxicology category III for acute dermal toxicity and eye 

irritation and acute toxicity category IV for acute oral and inhalation toxicity and skin irritation. Technical 

rimsulfuron is not a dermal sensitizer.

2. Genotoxicty. 

Technical rimsulfuron was negative for genotoxicity in batteries of in vitro and in vivo tests. These tests 

included the following: mutagenicity in bacterial (Ames test) and mammalian (CHO/HGPRT assay) cells; 

in vitro cytogenetics (chromosomal aberration in human lymphocytes); in vivo cytogenetics (bone 

marrow micronucleus assay in mice); and unscheduled DNA synthesis in rat primary hepatocytes.

3. Reproductive and developmental toxicity. 

A two-generation reproduction study was conducted in rats with dietary technical rimsulfuron

concentrations of 0, 50, 3,000 or 15,000 ppm. The study was negative for reproductive toxicity and there 

was no indication that offspring were more susceptible to rimsulfuron administration than parents. The 

NOEL was 3,000 ppm (or 165 to 264 mg/kg/day for P1 and F1 males and females and their offspring). 

This was based on the following effects at 15,000 ppm (830 to 1,316 mg/kg/day): lower food 

consumption and/or food efficiency in P1 males and females and F1 females; decreased mean body 

weights and/or body weight gain by P1 and F1 males and females; lower mean body weights and 

increased incidence of small body size for F2 pups during lactation.

A developmental study was conducted in rats administered technical rimsulfuron by gavage at 0, 200, 

700, 2,000 or 6,000 mg/kg/day. There were no systemic or developmental effects observed up to and 

including the highest dose tested. The NOEL was therefore > 6,000 mg/kg/day.

 

A developmental study was conducted in rabbits administered technical rimsulfuron by gavage at 0, 25, 

170, 500 or 1,500 mg/kg/day. The NOELs for maternal and offspring toxicity were 170 and 500 

mg/kg/day, respectively. The maternal NOEL was based on reduced body weight and mortality at higher 

doses. These maternal effects precluded any evaluation of adverse effects in fetuses at 1,500 mg/kg/day; 

however, there were no systemic or developmental effects observed among fetuses at 500 mg/kg/day and 

below.

4. Subchronic toxicity. 

A 90-day study in mice was conducted at dietary concentrations of 0, 50, 375, 1,500 or 7,500 ppm. The 

NOELs were 375 ppm (56.0 mg/kg/day) for male mice and 7,500 ppm (1,575 mg/kg/day) for female 

mice. The NOEL for males was based on slight reductions in mean body weight gain and food efficiency 

at 1,500 ppm (228 mg/kg/day).

 

Technical rimsulfuron was administered in the diets of rats at 0, 50, 1,500, 7,500 or 20,000 ppm for 90 

days. The NOEL was 1,500 ppm (102 and 120 mg/kg/day for males and females, respectively) based on 
Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

reduced mean body weights and body weight gains and increased relative liver weights at 7,500 ppm (495 

and 615 mg/kg/day for males and females, respectively).

 

Dogs were administered technical rimsulfuron in their diets at 0, 250, 5,000 or 20,000 ppm for 90 days. 

The NOEL was 250 ppm (9.63 and 10.6 mg/kg/day for males and females, respectively). This was based 

on slight increases in liver and/or kidney weights, increased urine volume and decreased urine osmolarity 

at 5,000 ppm (193 and 189 mg/kg/day for males and females, respectively).

5. Chronic toxicity. 

An 18-month mouse study was conducted with dietary concentrations of 0, 25, 250, 2,500 or 7,500 ppm 

technical rimsulfuron. This product was not oncogenic in mice. The systemic NOEL was 2,500 ppm (351 

and 488 mg/kg/day for males and females, respectively) based on decreased mean body weights in both 

sexes and increased incidence of spontaneous, age-related artery and tunica degeneration in the testes for 

this mouse strain at the highest dose tested, 7,500 ppm (1,127 and 1,505 mg/kg/day for males and 

females, respectively). The latter was observed in the absence of any effect on spermatogenesis. An 

increased incidence of dilation and cysts in the glandular stomach of males was also observed at 7,500 

ppm.

 

A 2-year chronic toxicity/oncogenicity study was conducted in rats fed diets that contained 0, 25, 300, 

3,000 or 10,000 ppm technical rimsulfuron. This product was not oncogenic in rats. The systemic NOELs 

were 300 ppm (11.8 mg/kg/day) for males and 3,000 ppm (163 mg/kg/day) for females. The NOELs were 

defined by decreased body weight gain and increased relative liver weights at 3,000 ppm (121 mg/kg/day) 

and 10,000 ppm (569 mg/kg/day) for males and females, respectively.

 

Technical rimsulfuron was administered for one year to dogs at dietary concentrations of 0, 50, 2,500 or 

10,000 ppm. The NOELs were 50 ppm (1.6 mg/kg/day) for males and 2,500 ppm (86.5 mg/kg/day) for 

females. The NOEL for males was based on the following effects, which the Agency has previously 

determined were of questionable biological significance, observed at 2,500 ppm (81.8 mg/kg/day): 

increased absolute liver and kidney weights; and increased incidence of seminiferous tubule degeneration 

and increased numbers of spermatid giant cells present in the epididymides. The NOEL for females was 

based on the following effects observed at 10,000 ppm (358.5 mg/kg/day): decreased body weight and 

body weight gain; increased serum cholesterol levels and alkaline phosphatase activity, increased absolute 

liver weight and increased relative liver and kidney weights.

6. Animal metabolism. 

The metabolism of rimsulfuron in animals (rat, goat and hen) is adequately understood and is similar 

among the species evaluated. Rimsulfuron was rapidly eliminated via urinary and fecal excretion in the 

rat. Approximately 60 to 70% of the administered dose to rats was excreted within 24 hours. There were 

no volatile metabolites detected and unmetabolised rimsulfuron was the major component in the urine (42 

- 55%) and feces (5 - 16%). The major metabolic pathway in rats involved a contraction of the 

sulfonylurea bridge followed by dealkylation, hydroxylation and/or conjugation reactions. Cleavage of 

the sulfonylurea bridge was observed; however, it was considered to be a minor pathway. Elimination of 

administered rimsulfuron was similarly rapid for the goat and hen. Tissue residue levels were generally 

less than 0.3% of the administered dose for the rat, goat and hen. There was no evidence of accumulation 

of rimsulfuron or its metabolites in tissues of any of the species or in milk and eggs.
Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

7. Metabolite toxicology. 

There is no evidence that the metabolites of rimsulfuron, as identified in either the plant or animal 

metabolism studies, are of any toxicological significance.

8. Endocrine disruption.

No special studies investigating potential estrogenic or other endocrine effects of rimsulfuron have been 

conducted. However, the standard battery of required toxicology studies has been completed. These 

include an evaluation of the potential effects on reproduction and development, and an evaluation of the 

pathology of the endocrine organs following repeated or long-term exposure to doses that far exceed 

likely human exposures. Based on these studies there is no evidence to suggest that rimsulfuron has an 

adverse effect on the endocrine system.

C. Aggregate Exposure

1. Dietary exposure. 

The residue of concern, as listed at 40 CFR 180.478, is parent rimsulfuron only.

No acute dietary risk assessment was needed since there is no acute tox endpoint.

The chronic reference dose (cRfD) of 0.818 mg/kg/day is based on the NOEL of 81.8 mg/kg/day from a 

one-year beagle dog tox study and a 100X safety factor. 

a. Food. 

i. Acute

For the general U.S. population, acute dietary exposure assessments were not considered relevant for 

rimsulfuron for the following reasons: rimsulfuron presents very low acute toxicity based on animal 

testing; and no detectable residues have been demonstrated in edible portions of treated crops.

ii. Chronic

There is no population in the chronic risk assessment for rimsulfuron, either dietary (food only) or 

aggregate (food and water), with an exposure greater than 0.1% of the chronic reference dose.

b. Drinking water.

Chronic drinking water exposure analyses were calculated for rimsulfuron using EPA screening 

concentration models for ground water SCI-GROW and surface water FIRST. Results indicate that a 

reasonable certainty exists that rimsulfuron residues in drinking water will not contribute significantly to 

the aggregate human risk.

The predicted chronic concentration for rimsulfuron maximum surface water value was 0.74 ppb, and a 

maximum ground water value was 0.0522 ppb. When the surface water concentration was included in the 

chronic dietary risk assessment, no population including the general U.S. population and all 
Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

subpopulations had an exposure greater 0.1% of the chronic reference dose (cRfD), indicating a 

significant margin of safety. 

No acute dietary endpoint was identified. Therefore, an acute drinking water risk assessment is not 

considered necessary. One can conclude with reasonable certainty that residues of Rimsulfuron in 

drinking water do not contribute significantly to the aggregate acute human health risk.

2. Non-dietary exposure. 

Rimsulfuron is not registered for any uses that could result in non-occupational, non-dietary exposure to 

the general population.

D. Cumulative Effects

Rimsulfuron belongs to the sulfonylurea class of crop protection chemicals. Other structurally similar 

compounds in this class are registered herbicides. However, the herbicidal activity of sulfonylureas is due 

to the inhibition of acetolactate synthase (ALS), an enzyme found only in plants. This enzyme is part of 

the biosynthesis pathway leading to the formation of branched chain amino acids. Animals lack ALS and 

this biosynthetic pathway. This lack of ALS contributes to the relatively low toxicity of sulfonylurea 

herbicides in animals. There is no reliable information that would indicate or suggest that rimsulfuron has 

any toxic effects on mammals that would be cumulative with those of any other chemical.

E. Safety Determination

1. U.S. population. 

Based on the completeness and reliability of the toxicology database and using the conservative 

assumptions presented earlier, EPA has established a chronic RfD of 0.818 mg/kg/day. This RfD is based 

on the systemic NOEL of 81.8 mg/kg/day for males in a 1-year toxicity study in beagle dogs. It has been 

concluded that the aggregate exposure for existing crops plus the tolerances being proposed would utilize 

less than 0.1% of the RfD. Generally, exposures below 100% of the RfD are of no concern because it 

represents the level at or below which daily aggregate dietary exposure over a lifetime will not pose 

appreciable risk to human health. Thus, there is reasonable certainty that no harm will result from 

aggregate exposures to rimsulfuron residues.

2. Infants and children. 

In assessing the potential for additional sensitivity of infants and children to residues of rimsulfuron, data 

from the previously discussed developmental and multigeneration reproductive toxicity studies were 

considered.

Developmental studies are designed to evaluate adverse effects on the developing organism resulting

from pesticide exposure during pre-natal development. Reproduction studies provide information relating 

to reproductive and other effects on adults and offspring from pre-natal and post-natal exposures to the 

pesticide. The studies with rimsulfuron demonstrated no evidence of developmental toxicity at exposures 

below those causing maternal toxicity. This indicates that developing animals are not more sensitive to 

the effects of rimsulfuron administration than adults.

 
Pesticide Petition for Tolerances for Rimsulfuron AGRICULTURAL COMMODITIES

Sorghum Grain, Forage and Stover

FFDCA section 408 provides that EPA may apply an additional uncertainty factor for infants and children 

in the case of threshold effects to account for pre- and post-natal toxicity and the completeness of the 

database. Based on current toxicological data requirements, the database for rimsulfuron relative to preand post-natal effects for children is complete. In addition, the NOEL upon which the RfD is based is 

much lower than the NOELs defined in the reproduction and developmental toxicology studies. 

Conservative assumptions utilized to estimate aggregate dietary exposures of infants and children to 

rimsulfuron demonstrated that less than 0.1% of the RfD would be utilized for the highest exposed group, 

Children 1-2 years old. 

Based on these conservative analyses, there is reasonable certainty that no harm will result to infants and 

children from aggregate exposures to rimsulfuron.

F. International Tolerances

A number of international tolerances (or Maximum Residue Levels, MRL's) have been 

established for rimsulfuron including the following:

Countries Crop Tolerance/MRL

Austria, Italy Corn 0.1 ppm

Austria, Italy, Canada Potatoes 0.1 ppm

Belgium, Denmark, Germany, Spain Potatoes 0.05 ppm

Germany, Spain, Portugal, Canada Tomatoes 0.05 ppm