Page 2 of 13

applications to manage annual and perennial broadleaf weeds and grasses in non-agricultural 

sites (i.e., forestry, rights of way, non-crop industrial sites, and unimproved turf). 

The toxicology database for this non-food use chemical is adequate and sufficient data are 

available to assess potential risk from occupational exposure; there are no residential uses at this 

time. HED’s Hazard and Science Policy Council (HASPOC) based on a weight of evidence 

approach and considering all of the available hazard and exposure information, granted waivers 

to the newly codified acute and subchronic neurotoxicity studies as well as a subchronic 

inhalation toxicity study (TXR No. 0056431). The only outstanding data is an immunotoxicity 

study. The primary toxic effect of this sulfonyl urea pesticide is hemolytic anemia, which 

represents the most sensitive toxic endpoint for risk assessment. In general, the toxicity data 

available indicate a low level of toxicity. Sulfometuron methyl is not acutely toxic via the oral, 

dermal, or inhalation routes of exposure. It shows minimal eye and skin irritation. Sulfometuron 

methyl is not a dermal sensitizer. 

The exposure database for sulfometuron methyl has been reviewed and determined to be 

complete. Since sulfometuron methyl is a non-food/non-feed chemical, any potential dietary 

exposure is attributed only to drinking water sources. The most recent acute and chronic dietary

assessments (drinking water only) conducted to support of the 2008 Reregistration Eligibility 

Decision (RED) are well below the level of concern. Residential exposure/risk was not assessed 

since label instructions do not allow application to residential or recreational settings. The most 

recent occupational risk estimates are below the level of concern. Sulfometuron methyl has not 

been identified as a member of a common mechanism group for cumulative risk assessment.

Introduction

Sulfometuron methyl [methyl 2-(4,6-dimethylpyrimidin-2-ylcarbamoylsulfamoyl)benzoate], is a 

sulfonylurea herbicide that provides broad spectrum pre- and post-emergence control of annual 

and perennial grasses and broad-leaf weeds in forestry and non-crop situations, including 

vegetative management of rights-of-way and railroads. Similar to other sulfonylurea herbicides, 

sulfometuron methyl’s mode of action involves inhibiting the activity of the enzyme actolactase 

synthase (ALS), which inhibits the production of amino acids required for cell growth in plants. 

All sulfometuron methyl containing products are formulated as a water dispersible granule 

(WDG). Applications of sulfometuron methyl can be made aerially using fixed wing airplane 

and helicopter, and by ground using groundboom, rights-of-way, and hand-held equipment. 

Sulfometuron methyl can also be used to impregnate or coat dry bulk fertilizer for application to 

forested areas. Sulfometuron methyl containing products are not labeled for use by professionals 

in the residential marketplace (i.e., indoor or outdoor residential use sites). There are currently 

16 registered products containing sulfometuron methyl with use rates ranging from 0.023 to 0.38 

lb ai/A. The current registrants for sulfometuron methyl are the following: Alligare LLC; 

Celsius Property B.V.; E.I. DuPont de Nemours & Co. Inc.; Loveland Products Inc.; Makhteshim 

Agan of North America Inc.; and NuFarm Americas Inc.

Since sulfometuron-methyl has no current registrations which may lead to exposures from the 

consumption of Raw Agricultural Commodities (RACs) and/or processed foods, there are no 
Page 3 of 13

tolerances established for this chemical and the requirements of the Food Quality Protection Act 

(FQPA) do not apply. 

The HED Registration Review Team has reviewed the most recent risk assessments and data 

requirements since the RED to determine if additional studies and/or risk assessments are needed 

to support the registration review of sulfometuron methyl. In addition, the Team has conducted a 

screening-level literature search for any information that would aid in assessing the human health 

risks to sulfometuron methyl. 

Hazard Identification/Toxicology

The toxicology database for this non-food use chemical is adequate and sufficient data are 

available to assess potential risk from occupational exposure; there are no residential uses at this 

time. HED’s Hazard and Science Policy Council (HASPOC) based on a weight of evidence 

approach and considering all of the available hazard and exposure information, granted waivers 

to the newly codified acute and subchronic neurotoxicity studies as well as a subchronic

inhalation toxicity study (TXR No. 0056431). The only outstanding study is an immunotoxicity 

study.

Sulfometuron methyl is not acutely toxic via the dermal (Toxicity Category III), oral or 

inhalation (Toxicity Category IV) routes of exposure. Sulfometuron methyl shows minimal eye 

and skin irritation. It is not a dermal sensitizer. 

The primary toxic effect of this sulfonylurea pesticide is hemolytic anemia (the most sensitive 

toxic endpoint) reported in the chronic oral toxicity study in dogs. This observation is consistent 

with reports in the open literature where hemolytic anemia has been identified as a side effect of 

sulfonyl urea compounds (e.g., chlorpropamide, LY186641) used therapeutically as anti-diabetic 

or anti-tumor agents1. In addition to hemolytic anemia, decreases in body weight were also seen 

in the chronic oral toxicity study beginning on the fourth week of exposure and persisting 

throughout the duration of the study. 

Other studies available in the database include a dermal toxicity study as well as pre-natal 

developmental toxicity studies (in rats and rabbits). In the previous risk assessment, it was 

concluded that the 21-day dermal rabbit study (MRID No. 00126714, classified as acceptablenon-guideline) was determined to be insufficient to assess dermal exposures due to a number of 

deficiencies in the study. However, the HED Sulfometuron Methyl Registration Review Team 

has re-evaluated this study and noted that the deficiencies were not significant, and therefore can 

be considered for dermal risk assessment. 

 

1 1

 J.A. Kopicky and C.H. Packman (1986) The mechanisms of sulfonyul-urea induced immune hemolysis: Case 

report and review of the literature. Amer. J. Hematol.. 23(3): 283-288

Ehlhardt, W.J., et al. (1997) Disposition and metabolism of the sulfonyl urea oncolytic agent LY295501 in mouse, 

rat, and monkey. Drug Met. Disp. (25):6: 701-712

Lee, C.W. et al. (2002). A novel stereo-selective sulfonylurea, 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-

sulfonyl]-4-phenylimidazolidin-2-one, has antitumor efficacy in in vitro and in vivo tumor models. Biochem. 

Pharmacol. 64(3): 473-480
Page 4 of 13

In the rabbit pre-natal developmental toxicity study, a slight increase in the incidence of 

abortions was observed from doses close to or at the limit dose (750 and 1000 mg/kg/day) while 

no evidence of toxicity via the dermal route was reported after 21 days of exposure at a dose 2-

fold higher (2000 mg/kg/day). Given the limited use pattern and low likelihood for chronic 

durations of exposure for this compound, no rodent chronic toxicity or carcinogenicity studies 

are required. Sulfometuron methyl was negative in the mutagenicity/ genetic toxicity studies. 

In the 2008 RED, a NOAEL of 27.5 mg/kg/day established in the chronic toxicity study in rats 

was used as the Point of Departure (POD) for assessing acute and chronic dietary as well as 

dermal and inhalation risks from short-and intermediate term exposures.

Conclusions. The POD, endpoints and FQPA Safety Factor used in the RED will be re-evaluated 

along with the results of the immunotoxicity study during the conduct of the risk assessment for 

registration review.

Dietary Exposure

Since sulfometuron methyl is a non-food use chemical, there are no residue chemistry data 

requirements, and the dietary assessment includes only drinking water. 

Drinking water exposures can potentially occur through run-off resulting from the outdoor 

applications of sulfometuron-methyl made for controlling weeds. The chemical is mobile and 

persistent in the environment dissipating through aerobic and anaerobic degradation/metabolism 

in soil and water with hydrolysis potentially dominant under acidic conditions. Its persistence 

indicates that if sulfometuron methyl reaches surface water bodies it may remain for durations up 

to several months; however, it has a fairly low use rate with treatments only being carried out 

every one to two years which limits exposure, especially over the chronic duration. 

Tier I Estimated Drinking Water Concentrations (EWDCs) were modeled using the FIRST 

(FQPA Index Reservoir Screening Tool; v.1.1.0; dated 1/1/2007) model for estimating surface 

water concentrations and SCI-GROW (Screening Concentration In GROund Water v2.3) model 

for groundwater (D334287, M. Barrett, 10/31/2007). Residues from a number of potential water 

degradates were modeled including: sulfometuron free acid; sulfometuron pyrimidine amine; 

sulfometuron sulfonamide; and saccharin. These residues were combined with the residues of 

the parent compound for a total residue. This approach is conservative and, therefore, unlikely to 

under-estimate the concentration of sulfometuron methyl in drinking water. The highest acute 

ground and surface water EDWCs were found to be 1.1 and 32.4 ppb, respectively. The highest 

chronic ground and surface water EDWCs were found to be 1.1 and 21.8 ppb, respectively. The 

larger values of 32.4 ppb (acute) and 21.8 ppb (chronic) were used to perform the screening level 

drinking water dietary assessments.

Acute and chronic dietary risk assessments were completed using the Dietary Exposure 

Evaluation Model (DEEM-FCIDTM, v. 2.03) software (D346139, W. Britton, 12/20/2007). Since 

FQPA requirements are not applicable, screening level risk estimates are expressed as Reference 

Doses (RfDs) rather than Population Adjusted Doses (PADs). For the acute dietary analyses 

performed, the most highly exposed population subgroup was all infants < 1 year old at 2.3% of 
Page 5 of 13

the aRfD with an exposure of 0.0064 mg/kg/day. The population subgroup with the highest 

estimated exposure for the chronic analyses performed was also all infants < 1 year old which 

occupied < 1% of the cRfD with an exposure of 0.0015 mg/Kg/day. 

The acute and chronic screening-level drinking water dietary assessment indicates that exposures 

to sulfometuron methyl are below the level of concern for the US population and all population 

subgroups. 

Conclusions. There are no residue chemistry data requirements for sulfometuron methyl. If 

drinking water concentration estimates are updated in the future, a revised dietary assessment 

may be required. Further, a revised dietary assessment may also be required if there are any 

revisions to the toxicological points of departure or uncertainty factors. 

Residential Exposure

Sulfometuron methyl containing products are not labeled for use by professionals in the 

residential marketplace (i.e., indoor or outdoor residential use sites). Therefore, a residential 

exposure/risk assessment is not required. 

Conclusion. No residential exposure data requirements for sulfometuron methyl because these 

types of exposures are not anticipated. 

Occupational Exposure

Sulfometuron methyl is used to control annual and perennial broadleaf weeds and grasses in nonagricultural sites (i.e., forestry, rights of way, non-crop industrial sites, and unimproved turf). 

Due to the manner in which it is used, occupational exposures would be anticipated for those 

involved in the application process (e.g., mixing/loading product for aerial application). 

Occupational exposures to workers re-entering sulfometuron methyl treated areas are not 

anticipated because the chemical is a non-selective herbicide used in non-agricultural areas, such 

as forestry or railroad rights-of-way and, therefore, contact with previously treated areas is 

unlikely. All sulfometuron methyl containing products are formulated as WDGs. Applications 

of sulfometuron methyl can be made aerially by fixed wing airplane and helicopter, and by 

ground using groundboom, rights-of-way, and hand-held equipment. Additionally, sulfometuron 

methyl can be used to impregnate or coat dry bulk fertilizer for application to forested areas. 

Product application rates range from 0.023 to 0.38 lb ai/A. Based upon the use pattern of 

sulfometuron methyl, HED anticipates both short- (1 to 30 days) and intermediate-term (1 to 6 

months) occupational exposures. Long-term handler exposures (greater than 6 months) are not 

expected to occur. 

Occupational handler exposures for the WDG formulations were considered in the most recent 

occupational risk assessments. The majority of handler exposure scenarios assessed (dermal and 

inhalation combined) resulted in margins of exposure (MOEs) ≥ 100 at some level of personal 

protection and, therefore, were not of concern. The exposure scenario mixing/loading of WDGs 

for aerial application to forestry and non-crop areas results in a combined MOE = 90 at the 
Page 6 of 13

maximum level of personal protection (double layer with gloves) and, therefore, is slightly below 

the level of concern.

Short- and intermediate-term dermal and inhalation exposures/risks were also estimated for 

occupational handlers for the dry bulk fertilizer impregnation use. Two steps were assessed for 

the mixing of sulfometuron methyl active ingredient: 1) mixing the product with water to form a

slurry and 2) mixing of the slurry in a closed rotary drum mixer with the dry bulk fertilizer (urea 

and blended). Aerial application of impregnated fertilizer for forestry was also assessed. None 

of the exposure scenarios assessed for the impregnation of mixing/loading or application of dry 

bulk fertilizer, urea or blended, with sulfometuron methyl active ingredient were of concern (i.e., 

an MOE ≥ 100) at some level of personal protective equipment (PPE). 

Conclusions. No occupational exposure data gaps were identified during the Registration 

Review scoping process for sulfometuron methyl. There are no significant changes identified 

which would require an update of the occupational exposure risk assessment. A task force effort

by the Agricultural Handlers Exposure Task Force (AHETF) may provide improved exposure 

data relative to that in the Pesticide Handlers Exposure Database (PHED), which was used 

previously to assess occupational risks. Any changes to the exposure data may elicit the need for 

an update of sulfometuron methyl occupational exposures/risks during registration review. 

Public Health and Pesticide Epidemiology Data

HED has reviewed the OPP Incident Data System (IDS) to determine if there were significant 

incidents related to sulfometuron methyl and human health (Recore, 2012). Based on the low 

frequency and severity of incident cases reported for sulfometuron methyl, there does not appear 

to be a concern at this time that would warrant further investigation. The Agency will continue 

to monitor the incident information and if a concern is triggered, additional analysis will be 

included in the risk assessment.

Tolerance Assessment and International Harmonization

Sulfometuron methyl is a non-food use chemical; therefore, there are no tolerances and 

international harmonization is not an issue. 

Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

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 

assessment, OPP considers a large variety of consumer subgroups according to well-established 

procedures. In line with OPP policy, HED estimates risks to population subgroups from 

pesticide exposures that are based on patterns of that subgroup’s food and water consumption, 

and activities in and around the home that involve pesticide use in a residential setting. 

Extensive data on food and drinking water consumption patterns are compiled by the USDA 

under the Continuing Survey of Food Intake by Individuals (CSFII) and are used in pesticide risk 
Page 7 of 13

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 subgroups and 

exposure assessments are performed when conditions or circumstances warrant. 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 and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

Human Studies

Past sulfometuron methyl risk assessments relied in part on data in generic databases from 

studies in which adult human subjects were intentionally exposed to a pesticide to determine 

their dermal and inhalation exposure. Many such studies, involving exposure to many different 

pesticides, are included in generic pesticide exposure databases such as the Pesticide Handler 

Exposure Database (PHED), the Agricultural Reentry Task Force (ARTF), and the Outdoor 

Residential Exposure Task Force (ORETF). Also, there will be a reliance on the work of the 

Agricultural Handlers Exposure Task Force (AHETF) for revisions to the occupational handler 

risk assessments possibly needed in the future. These studies have been determined to require a 

review of their ethical conduct and have received the appropriate review.

Endocrine Disruption

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (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.

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. 

This list of chemicals was selected based on the potential for human exposure through 

pathways such as food and water, residential activity, and certain post-application agricultural 

scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Sulfometuron methyl is not among the group of 58 pesticide active ingredients on the initial list 

to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all 

pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data callins for all pesticide active ingredients. 
Page 8 of 13

For further information on the status of the EDSP, the policies and procedures, the list of 67 

chemicals, the test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.

Data Requirements

No dietary or occupational exposure data are needed at this time. The acute and subchronic 

neurotoxicity studies, as well as the 28-day inhalation toxicity study, were waived by the Hazard 

and Science Policy Council (HASPOC) on August 2, 2012 and are, therefore, no longer required. 

The following toxicity studies are required:

870.7800 Immunotoxicity Study

The rationale for requiring this studies are attached to this document.

References

Author

DP 

Barcode/ 

Record No.

Date Title

Britton, W. D385620 8/11/2008

Sulfometuron Methyl: Phase 3 Amendment of “Sulfometuron 

Methyl: HED Chapter of the Reregistration Eligibility Decision 

Document (RED).”

Britton, W. D346173 8/11/2008

Sulfometuron Methyl: Addendum to “Sulfometuron Methyl: 

Occupational and Residential Exposure Assessment for the 

Reregistration Eligibility Decision (Non-Food).” 

Britton, W. D345025 12/20/2007

Sulfometuron Methyl: Occupational and Residential Exposure 

Assessment for the Reregistration Eligibility Decision (NonFood). 

Britton, W. D346139 12/20/2007

Sulfometuron Methyl: Acute and Chronic Screening-Level 

Drinking Water Only Dietary Risk Assessment for the NonFood/Non-Feed Use Reregistration Eligibility Decision (RED).

Barrett, M. D334287 10/31/2007 Tier 1 Sulfometuron Methyl Drinking Water Assessment for 

Reregistration Eligibility Decision Document

Recore, S. D402495 8/1/2012 Sulfometuron Methyl: Review of Human Incidents

Bradbury, S. Case No. 

3136 9/2008 Reregistration Eligibility Decision (RED) Sulfometuron Methyl
Page 9 of 13

Attachments

Table A. Chemical Identity

Chemical Structure

Empirical Formula C15H16N4O5S

Common Name Sulfometuron Methyl

IUPAC name methyl 2-(4,6-dimethylpyrimidin-2-

ylcarbamoylsulfamoyl)benzoate

CAS Name methyl 2-[[[[(4,6-dimethyl-2-

pyrimidinyl)amino]carbonyl]amino]sulfonyl]benzoate

CAS Registry Number 74222-97-2

Chemical Class Pyrimidinylsulfonylurea Herbicides

Table A.2. Physiochemical Properties

Parameter Value Reference

Molecular Weight 364.4

The Pesticide Manual: A World 

Compendium, 9th ed., 1991, C.R. 

Worthington, ed. The British Crop 

Protection Council, Surrey, UK pg. 774

Melting point 203-205°C

Physical state Colorless Solid

Vapor pressure (25°C) 6.0 x 10-5 mm Hg

Water solubility (25°C) 70 ppm

Log Kow (25°C) 1.2

Appendix B: Sulfometuron Methyl Toxicology 

Table B.1. Acute Toxicity Profile - Test Substance1

Guideline No.

Study Type MRID

No.(s)

Results Toxicity Category

870.1100 Acute oral rat 43089201 LD50 >5g/kg IV

870.1200 Acute dermal rabbit 43089202 LD50 >2g/kg III

870.1300 Acute inhalation rat 43089203 LC50 >5.0 mg/L IV

870.2400 Acute eye irritation rabbit 00071412 Minimal irritant III

870.2500 Acute dermal irritation rabbit 41672808 Not a dermal 

irritant2

IV

870.2600 Skin sensitization rabbit 43089204 Not a dermal 

sensitizer

N/A

1 All studies were conducted on technical grade Sulfometuron methyl, of at least 98.8%, purity.
Page 10 of 13

2 Minimal skin irritation was noted in the acute dermal toxicity study (MRID No. 43089202) and an older 

dermal irritation study of a 75% formulation (MRID No. 00071411)
Page 11 of 13

Table B.2. Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

870.3200 21-Day dermal 

toxicity (rabbit)

00126714 (1983) 

Acceptable/non-guideline 

M/F: 0, 125, 500, 2000 

mg/kg/day

NOAEL = 2000 mg/kg/day

LOAEL = Not observed

870.3700a Prenatal 

developmental 

(rabbit)

00078798 (1981) 

Acceptable/non-guideline 

F:0, 30, 100, 300 

mg/kg/day

Maternal NOAEL =300 mg/kg/day (HDT)

LOAEL = 750 mg/kg/day based on abortion 

observed in the range-finding study.

Developmental NOAEL =300 mg/kg/day

LOAEL not observed

Prenatal 

developmental 

(rabbit) – Rangefinding study

00078797 (1981)

F: 100, 300, 750, 1000 

mg/kg/day

Maternal LOAEL = 750 mg/kg/day based on 

abortion

870.3700b Prenatal 

developmental in 

(rat)

00078796 (1981) 

Unacceptable/guideline 

Run I F: 0, 5,000, 20,000, 

40,000 and 60,000 ppm 

Run II & III F: 0, 50, 

1000 and 5,000 ppm (433 

mg/kg/day) 

Maternal NOAEL> 433 mg/kg/day LOAEL 

not observed

Developmental NOAEL>433 mg/kg/day

LOAEL not observed

870.4100b Chronic toxicity 

(dog)

00129051 (1983) 

Acceptable/guideline 

M: 0, 5.2, 27.5, 152.6 

mg/kg/day 

F: 0, 5.3, 28.3, and 148.5 

mg/kg/day 

NOAEL = 27.5mg/kg/day 

LOAEL = 148.5 mg/kg/day, based on hemolytic 

anemia in both sexes, decreased body-weight 

gain in males, and increased alkaline 

phosphatase in males and females. Effects on 

body weight were observed beginning on the 

fourth week of exposure (and persisting 

throughout the study).

Gene 

Mutation

Salmonella/ 

Microsome assay 

00078792 (1979) 

Acceptable/guideline in 

strains TA 1535, TA 

1537, TA 98 and TA 100 

in the presence or absence 

of activation.

No mutagenic activity for all strains of bacteria 

tested.

Gene 

mutation 

Chinese Hamster 

Ovary

00078793 (1981)

Acceptable/guideline

CHO cell line was used to 

detect mutations for 

HGPRT

No mutagenic activity with or without 

activation.

Chromosome 

aberration

Chinese Hamster 

Ovary in vitro 

cytogenetic assay

00146846 (1981)

Acceptable/guideline

CHO in vitro assay with 

and without activation

No increase in chromosome damage and 

aberrations.
Page 12 of 13

Table B.2. Subchronic, Chronic and Other Toxicity Profile

Guideline 

No. 

Study Type MRID No. (year)/ 

Classification /Doses

Results

Unscheduled 

DNA 

synthesis

Unscheduled DNA 

synthesis in rat 

hepatocytes in vitro

00146847 (1983)

Acceptable/guideline

No induction of UDS was observed.

Table B.3 Summary of Toxicological Doses and Endpoints for Sulfometuron Methyl for 

Use in Dietary and Occupational Human Health Risk Assessments

Exposure/

Scenario

Point of 

Departure

Uncertainty 

Factors

RfD, Level of 

Concern for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary (all 

population 

subgroups) NOAEL= 27.5 

mg/kg/day

UFA= 10 x

UFH=10 x

Acute RfD = 

0.275 mg/kg/day

Chronic 1-year dog study

LOAEL = 148.5 mg/kg/day based 

on decreases in body weight in 

males (beginning on the fourth 

week of exposure and persisted 

throughout), hemolytic anemia and 

a slight increase in alkaline 

phosphatase in males and females. 

Chronic Dietary (All 

Populations) 

Chronic RfD = 

0.275 mg/kg/day

Dermal Short- (1-30 

days) and 

Intermediate-Term 

(1-6 months)

(no residential uses) NOAEL= 27.5 

mg/kg/day

UFA= 10x

UFH= 10x

LOC for 

Inhalation Short- (1- MOE = 100

30 days) and 

Intermediate-Term 

(1-6 months)

(no residential uses) 

Cancer (oral, 

dermal, inhalation) No data available for assessment. 

Rationale for Requiring an Immunotoxicity Study

Guideline Number: 870.7800

Study Title: Immunotoxicity

Rationale for Requiring the Data

This is a new data requirement under 40 CFR Part 158 as a part of the data requirements for 

registration of a pesticide (food and non-food uses). 

The Immunotoxicity Test Guideline (OPPTS 870.7800) prescribes functional immunotoxicity 

testing and is designed to evaluate the potential of a repeated chemical exposure to produce 

adverse effects (i.e., suppression) on the immune system. Immunosuppression is a deficit in the 

ability of the immune system to respond to a challenge of bacterial or viral infections such as 

tuberculosis (TB), Severe Acquired Respiratory Syndrome (SARS), or neoplasia. Because the 

immune system is highly complex, studies assessing functional immunotoxic endpoints are 
Page 13 of 13

helpful in fully characterizing a pesticide’s potential immunotoxicity. These data will be used 

in combination with data from hematology, lymphoid organ weights, and histopathology in 

routine chronic or subchronic toxicity studies to characterize potential immunotoxic effects. 

Practical Utility of the Data

How will the data be used?

These animal studies can be used to select endpoints and doses for use in risk assessment of all 

exposure scenarios and are considered a primary data source for reliable reference dose 

calculation. For example, animal studies have demonstrated that immunotoxicity in rodents is 

one of the more sensitive manifestations of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) among 

developmental, reproductive, and endocrinologic toxicities. Additionally, the EPA has 

established an oral reference dose (RfD) for tributyltin oxide (TBTO) based on observed 

immunotoxicity in animal studies (IRIS, 1997).

How could the data impact the Agency's future decision-making?

If the immunotoxicity study shows that the test material poses either a greater or a diminished 

risk than that given in the interim decision’s conclusion, the risk assessments for the test 

material may need to be revised to reflect the magnitude of potential risk derived from the new 

data.

If the Agency does not have these data, a 10X database uncertainty factor may be applied for 

conducting a risk assessment from the available studies.