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changes in toxicology endpoint and the updated assessment results were included in the 

Reregistration Eligibility Decision document (RED) which was issued in August 1996. 

The 1996 RED addressed exposures and risks associated with occupational exposures to 

amitrole. A dietary (food) exposure assessment was not conducted and is not required at this 

time since there are no food uses for amitrole and dietary (food) exposure is not expected based 

on registered uses. A drinking water assessment has not been performed. EFED will prepare a 

drinking water assessment under Registration Review. The need for a dietary (drinking water) 

exposure assessment will be evaluated based on the results of the EFED assessment. 

A residential exposure assessment was not conducted and is not required at this time, 

since there are no residential uses and no anticipated residential exposures. 

Occupational handler assessments using current standard operating procedures and assumptions 

are needed for currently registered products of amitrole. There is the possibility for postapplication workers to experience exposures to pesticide compounds. In this case, there is no 

dermal endpoint identified for risk assessment. HED believes post-application inhalation 

exposures are negligible. The worker activities for non-agricultural rights-of-way, industrial and 

construction sites, fencerows, and other uncultivated areas are exempt under Worker Protection 

Standard (WPS), therefore no reentry interval is required. An aggregate risk assessment is not 

required because there are no food and no residential uses. There are several outstanding 

toxicology data requirements. If toxicology endpoints or points of departure are revised based 

on any new data, those will be considered in the new amitrole human health risk assessment. 

Data requirements include the following studies: 870.1300 Acute Inhalation, 870.3465 90-Day 

Inhalation, 870.6200a Acute Neurotoxicity, 870.6200b 90-Day Neurotoxicity, and 870.7800 

Immunotoxicity. 

Introduction 

HED has evaluated the existing human health risk assessments for amitrole to determine 

whether sufficient data are available and whether a new human health risk assessment is needed 

to support Registration Review. HED has considered the most recent risk assessments for 

amitrole, updates to its toxicity, exposure and usage databases, and current Agency science 

policies and risk assessment methods. 

Use Profile 

Amitrole is an herbicide applied outdoors for general weed control to non-agricultural 

rights-of-way, industrial and construction sites, fencerows, and other uncultivated areas. 

Tolerances are not currently established for amitrole as there are no registered food or feed uses. 

Amitrole functions as a plant growth regulator. It inhibits carotenoid synthesis, chlorophyll 

formation, and limits the re-growth of buds. Amitrole products are formulated as a water 

dispersible granule and in water soluble bags (formulation type not specified on label). It is 

applied by boom sprayer. There are no residential or homeowner uses and no residential 

exposures from any registered use is anticipated. 
Page 3 of 12 

Chemical Identity 

Amitrole Nomenclature 

Chemical Structure 

Common name Amitrole 

IUPAC name 1-H-1,2,4-triazol-3-ylamine, (formerly 1-H-3-amino1,2,4-triazole) 

CAS name 1-H-1,2,4-triazol-3-amine 

CAS # 61-82-5 

 

Hazard Identification/Toxicology 

 Acute oral, dermal and inhalation studies indicate that amitrole exhibits low acute 

toxicity via the oral and dermal routes (Toxicity Category III/IV). The requirement for an acute 

inhalation study was previously waived based on the availability of a 2-year rat inhalation study. 

However, the 2-year rat inhalation study was categorized as ‘unacceptable’ and is not useful for 

regulatory purposes. This study also suggested that the acute inhalation toxicity was at least 

Toxicity Category III. At this time the acute inhalation study is being required for amitrole in 

order to determine the acute LC50 and to identify the toxicity hazard following acute inhalation 

exposures. 

 Amitrole is a Toxicity Category III primary eye irritant in rabbits. It is a Toxicity 

Category IV primary dermal irritant in rabbits; amitrole is not a skin sensitizer in guinea pigs. 

 The primary target organ is the thyroid. Data from short term studies and chronic studies 

indicate that effects will appear in the thyroid at lower dose levels than any other target organ. 

Eleven short term (oral rat) studies were conducted with amitrole in order to study the effects of 

amitrole on the thyroid. Although none of the studies can individually be categorized as being 

acceptable as a subchronic feeding study, the available data provide an overall weight of the 

evidence of toxicological effects that can be used for making regulatory decisions. 

 Amitrole had been classified as a Group B2-probable human carcinogen by the Office of 

Pesticide Programs Carcinogenicity Peer Review Committee (document dated August 30, 1991). 

This B2 Carcinogen classification was based on thyroid tumors in both sexes of multiple strains 

of rats, pituitary tumors in rats, and liver tumors in two strains of mice. The Agency calculated a 

Q1* from the thyroid tumor effects. In 2006, the HED Cancer Assessment Review Committee 

(CARC) re-evaluated the carcinogenic potential of amitrole. The CARC classified amitrole as 

“Not Likely To Be Carcinogenic To Humans At Doses That Do Not Alter Rat Thyroid Hormone 

Homeostasis”. This decision was based on the following: 

i) Treatment-related thyroid follicular cell tumors were seen in male and female rats (multiple 

strains) based on evidence provided collectively from several studies (Keller 1959; Johnson 

1981; Steinhoff 1979; and Tsuda 1976); 
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ii) No treatment-related tumors were seen in male or female mice (Steinhoff and Boehme 1979); 

iii) Amitrole is considered to be nonmutagenic and does not mediate thyroid carcinogenesis through 

a mutagenic mode of action; 

iv) The overall weight-of-the-evidence was considered sufficient to indicate that amitrole induced 

thyroid follicular tumors through an antithyroidal mode of action; 

v) Rats are substantially more sensitive than humans to the development of thyroid follicular cell 

tumors in response to thyroid hormone imbalance. 

Therefore, the previous quantification of carcinogenic potential as B2 is not applicable 

(document dated 5/11/2006; TXR 0054224). 

Based on the overall weight of the evidence found in the genotoxicity database 

(published by Hill et al. 1989 and IARC 2001), amitrole is not considered to be a mutagen or to 

cause thyroid follicular cell carcinogenesis through a mutagenic mode of action. 

For developmental toxicity, four studies are available to the Agency. They consist of an 

oral developmental toxicity study in the rat, two oral developmental toxicity studies in the rabbit 

and a dermal developmental toxicity study in the rabbit. All studies are acceptable for regulatory 

purposes. A 2- generation reproduction study conducted in the rat is available to the Agency. 

The study is acceptable for regulatory purposes. 

Toxicity points of departure (PoDs) were selected for use in risk assessment for short 

term and intermediate term inhalation exposures for the 1996 assessment. For short term 

inhalation occupational exposure (1 to 7 days), the maternal and developmental NOAEL of 4.0 

mg/kg/day from the oral developmental toxicity study in the rabbit was selected as the PoD for 

risk assessment. The maternal LOAEL is 40.0 mg/kg/day based on decreases in body weight 

gain during the dosing period and an increase in abortions. The developmental LOAEL is 40.0 

mg/kg/day based on increases in the number of litters with a variety of malformations and 

variations and decreases in fetal body weight and percent live fetuses/litter. 

For intermediate term inhalation occupational exposure (1 week to several months), the 

NOAEL of 0.90 mg/kg/day from the 2-generation reproduction study was selected. The LOAEL 

was based on clinical signs, death, decreases in mean body weight, body weight gain, food 

consumption, food efficiency and selected absolute and relative organ weights, an increase in 

thyroid weight and activity, follicular cell hypertrophy and hyperplasia and nodular hyperplasia 

and/or adenoma, hepatocellular hypertrophy and other microscopic changes in the adrenals, liver, 

pituitary, mammary gland and kidney, a high incidence of pseudopregnancy, decreases in mating 

and 18 fertility indices, implantation sites/litter and mean pup male/female ratio and a slightly 

higher gestation interval. 

A sub-chronic inhalation study was not performed for amitrole. The previous 

intermediate inhalation assessment used a PoD from an oral study. A route-specific study is 

preferred to route extrapolation. The 90/28-day inhalation study is now required for amitrole. 

Toxicity endpoints for short term and intermediate term occupational dermal exposures 

were not selected for the 1996 assessment. For short and intermediate term dermal exposures, a 

maternal and developmental NOAEL of 1,500 mg/kg/day was identified from the dermal 
Page 5 of 12 

developmental toxicity study. Since the dose selected was so high, a quantitative risk assessment 

was not required for dermal exposure. 

 The requirement for the 90-day dermal study was previously waived. The Less-thanLifetime Committee of the Agency's Office of Pesticide Programs determined (document dated 

July 20, 1995) that results from a dermal absorption study and from the oral and dermal rabbit 

developmental studies indicate that dermal absorption is very low (only up to 1-2%). Therefore, 

it was considered unlikely that a 90-day dermal study conducted with amitrole would provide 

any additional useful data. Based on current policy, the 90-day dermal study waiver is still 

applicable. A 90-day feeding study will not be required in place of the 90-day dermal study 

because sufficient data are available to indicate that a 90-day oral study will not provide any 

additional useful data for the purposes of risk assessment. 

Acute and chronic dietary exposure endpoints were not selected because there are no 

registered food or feed uses for amitrole. 

Screening batteries for acute and subchronic (90 day) neurotoxicity have not been 

submitted for amitrole and are now required under 40 CFR Part 158 guidelines (870.6200). The 

battery is designed to evaluate the potential adverse effects of a pesticide on the nervous system. 

An immunotoxicity study is required as a part of new data requirements in the 40 CFR 

Part 158 for conventional pesticide registration. Because the immune system is highly complex, 

studies not specifically conducted to assess immunotoxic endpoints are inadequate to 

characterize a pesticide’s potential immunotoxicity. While data from hematology, lymphoid 

organ weights, and histopathology in routine chronic or subchronic toxicity studies may offer 

useful information on potential immunotoxic effects, these endpoints alone are insufficient to 

predict immunotoxicity (see Appendix A). 

Dietary Exposures 

A dietary exposure assessment was not previously conducted because amitrole has no 

registered food uses. A dietary assessment for food exposures is not required. EFED will be 

performing a drinking water assessment under Registration Review. The need for a dietary 

assessment (for drinking water exposures only) will be evaluated based on the results of the 

new estimated drinking water concentrations. 

Residential Exposure 

Based on the currently registered uses there are no residential exposures for amitrole. 

Therefore, a residential exposure assessment is not required. 

Aggregate Exposure 

The aggregate risk assessment evaluates the combined risk from dietary exposure (food 

and water) and any non-occupational (residential) uses. Since there are no registered food and 

residential uses of amitrole, an aggregate assessment is not required. 
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Occupational Exposure 

Amitrole (3-amino-1,2,4-triazole), is a non-selective herbicide used to control vegetation 

on a variety of non-crop sites (e.g.,rights-of-way spray). Amitrole is currently formulated as a 

water dispersible granule (86.2 percent active ingredient, Reg. # 33688-10) and as an unspecified 

formulation in a water soluble bag (88.2 percent active ingredient, Reg. # 33688-6). A liquid 

concentrate (21.6 percent ai) was voluntarily canceled by the registrant during development of 

the 1996 RED. 

Applications are made by fixed-boom sprayers attached to tractors/trucks or railroad 

wagons. At this time no products containing amitrole are intended primarily for homeowner use. 

All products containing amitrole are intended for occupational use. 

Handler 

The following scenarios were assessed in 1996 for short and intermediate-term inhalation 

occupational handler exposure: 

 (1) Mixing/loading the liquid formulation for ground equipment application 

 (2) Mixing/loading the wettable powder formulation (in water soluble bags) for ground 

equipment, and 

 (3) Applying the products as a spray with a groundboom sprayer as surrogate for the fixed-boom 

applications. 

 

The handler assessments included inhalation exposures estimates only. A dermal 

exposure assessment was not conducted as part of the 1996 RED. The dermal NOAEL selected 

from the dermal developmental toxicity study in the rabbit was high (1,500 mg/kg/day). 

Therefore, since the dose selected for risk assessment was high, a quantitative dermal exposure 

risk assessment was not required. 

The 1996 assessment indicated that the MOEs for short- and intermediate-term inhalation 

exposures at baseline protection (i.e. no respirator) were not of concern for the Agency. 

Cancer risk estimates were also determined for handlers. At the time of the 1996 RED, 

amitrole was classified as a probable human carcinogen. Since that time, amitrole has been 

reclassified as “not likely to be carcinogenic to humans at doses that do not alter rat thyroid 

hormone homeostasis”. Therefore, a cancer assessment is no longer required. Since the dermal 

data (PHED v.1.1) used for the cancer assessment were rated as ‘low confidence’, the RED 

required a confirmatory dermal exposure study for handlers (Guideline 231; current Guideline 

875.1100, Dermal Exposure) to provide data on mixers and loaders during the use of watersoluble packages and "no glug" containers. An OECD-based study was subsequently submitted 

and reviewed in June 2005 (MRID 46343704; D318601). That review concluded that the study 

was “not well suited for use in risk assessment”. A confirmatory dermal exposure study for 

handlers is no longer required because a cancer dermal assessment is not currently needed. 

Furthermore, if it is determined that dermal exposure scenarios for non-cancer effects need to be 
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assessed under Registration Review the updated dermal exposure assumptions and data from the 

revised PHED or AHETF databases may be considered. 

Under Registration Review, a handler assessment should be performed for mixing, 

loading, and applying water dispersible granules. The exposure scenario for this use was 

not previously assessed for amitrole. In addition, because of updates to standard operating 

procedures and exposure assumptions, occupational assessments should be revisited for all 

currently registered amitrole formulations. If toxicology endpoints or points of departure 

are revised based on any new data, those will be considered in the new assessment. 

Post-application 

In general, amitrole is used in areas, such as rights-of-way, industrial areas, and other non-crop 

areas, where frequent or routine entry by persons who contact treated surfaces is unlikely. For 

the 1996 risk assessment, EPA determined that such post-application exposures do not appear to 

pose an unreasonable risk to persons entering treated areas, as long as entry is not permitted 

immediately after application. Typically there is the possibility for post-application workers to 

experience post-application exposures to pesticide compounds. In this case, there is no dermal 

endpoint identified for risk assessment. HED believes post-application inhalation exposures are 

negligible. The worker activities for non-agricultural rights-of-way, industrial and construction 

sites, fencerows, and other uncultivated areas are exempt under Worker Protection Standard 

(WPS), therefore no reentry interval is required. For the above reasons, a post-application risk 

assessment is not necessary. 

Previously, the Agency was concerned about the post-application exposures to workers 

following applications of amitrole on commercial or research nurseries. EPA established an 

interim 24-hour restricted-entry interval within the scope of the Worker Protection Standard 

(WPS) and required confirmatory data (132-1(a) Foliar Residue Dissipation; 133-3 

Postapplication Dermal Passive Dosimetry Exposure; and 133-4 Postapplication Inhalation 

Passive Dosimetry Exposure). There are no nursery use sites listed on the current labels and the 

confirmatory data are no longer required. 

Incident Report 

A summary report for incidents of amitrole has been provided in the memorandum 

“Amitrole Review of Human Incidents” (D386310, K. Oo, 3/1/11). The evaluation of the OPP 

Incident Data System (IDS) indicated no incidents identified in the United States from 2002 thru 

2010 for the single chemical amitrole. In Aggregate IDS, from 2002 to February 2011, there are 

five cases reported for amitrole. Because it falls within the categories reported as counts (which 

includes minor, unknown or no effects), there is no unique report that provides details about the 

incident and single chemical incidents are not distinguished from multiple chemical incidents; 

however, a high frequency of incidents indicates there is a high potential for exposure and vice 

versa. For amitrole, there appears to be a low potential for exposure. Amitrole is not included in 

the Agricultural Health Study (AHS), and therefore, does not provide information for this report. 

There does not appear to be a concern at this time that would warrant further investigation. The 
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Agency will continue to monitor the incident information and if a concern is triggered, additional 

analysis will be included in the risk assessment. 

Cumulative 

Amitrole is a triazole-derived herbicide. There is a triazole-metabolite aggregate 

assessment for the triazole class of chemicals. Amitrole has not been included in this assessment 

because it is not expected to form the free triazole, triazole-alanine or triazole acetic acid 

metabolites. Furthermore, the toxicity profile of amitrole is distinct from the triazole 

metabolites, producing primarily thyroid hyperplasia with a NOAEL of 0.35 mg/kg/day in 

chronic studies. Conversely, the triazole metabolites produce neurotoxicity, developmental 

toxicity, blood cell toxicity and skeletal deformations. . 

Unlike other pesticides for which EPA has followed a cumulative risk approach based on 

a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding 

as to amitrole and any other substances. For the purposes of this registration review assessment 

of data needs, EPA has not assumed nor determined that amitrole has a common mechanism of 

toxicity with other substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see the policy statements released by EPA’s Office of Pesticide Programs concerning 

common mechanism determinations and procedures for cumulating effects from substances 

found to have a common mechanism on EPA’s website at: 

http://www.epa.gov/pesticides/cumulative/. If, in the future, the Agency determines that new 

information on amitrole is available that could potentially impact a cumulative risk assessment 

and result in a risk of concern, the Agency will revisit the need for a cumulative risk assessment. 

Human Studies 

The Amitrole RED relied in part on data from studies in which adult human subjects 

were intentionally exposed to a pesticide or other chemical. These studies were used in 

developing the PHED Surrogate Exposure Guide which was used to estimate exposure to 

workers. The studies have been determined to require a review of their ethical conduct and have 

received the appropriate review. 

The 1996 amitrole risk assessment did not rely directly on any human toxicology studies 

for endpoint selection, PoDs, or determining the uncertainty factors. The 1996 RED did 

summarize the results of a 1974 IARC monograph in which a person ingested amitrole and a 

1982 dermal study in which workers were exposed to amitrole. If after considering these, or any 

other human study, we decide to rely on one or more for risk assessment, we will ensure that all 

regulatory requirements are met, including EPA ethics and Human Studies Review Board 

(HSRB) reviews of the data. 

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, 
Page 9 of 12 

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 reregistration decision, 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), amitrole 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. Amitrole is not 

among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on 

the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/. 

Conclusions/Future Actions Needed 

The actions needed in the future Registration Review for amitrole are listed below. 

Hazard Identification and Endpoint Selection

There are several outstanding toxicology data requirements. If toxicology endpoints or points of 

departure are revised based on any new data, those will be considered in the new amitrole 

assessment. Data requirements include: 870.1300 Acute Inhalation, 870.3465 90-Day 

Inhalation, 870.6200a Acute Neurotoxicity, 870.6200b 90-Day Neurotoxicity (Sub chronic), and 

870.7800 Immunotoxicity. 

Dietary Exposure and Risk

A dietary (food) exposure assessment is not required. The need for a dietary (drinking water) 

exposure assessment will be evaluated based on the results of the EFED drinking water 

assessment. 
Page 10 of 12 

Residential Exposure and Risk

A residential risk assessment is not required. 

Aggregate Exposure and Risk

An aggregate exposure assessment is not required. 

Occupational Exposure and Risk

Occupational assessments using current standard operating procedures and assumptions are 

needed for currently registered formulations of amitrole. If toxicology endpoints or points of 

departure are revised based on any new data, those will be considered in the new assessment. 

Incident Report

An updated incident report is not required at this time. 

Data Requirements 

Toxicity:

870.1300 Acute Inhalation 

870.3465 90/28-Day Inhalation 

870.6200a Acute Neurotoxicity 

870.6200b 90-Day Neurotoxicity 

870.7800 Immunotoxicity 

870.1300 Acute Inhalation: The requirement for an acute inhalation study was previously 

waived because a 2-year rat inhalation study was available which, while categorized as 

‘unacceptable’ and not useful for regulatory purposes, suggested that the acute inhalation toxicity 

was at least Toxicity Category III. At this time the acute inhalation study is being required for 

amitrole in order to determine the acute LC50 and to identify the toxicity hazard following acute 

inhalation exposures. 

 

870.3465 90/28-Day Inhalation: A subchronic inhalation study was not performed for amitrole. 

The previous intermediate inhalation assessment used a PoD from an oral study. A routespecific study is preferred to route extrapolation. The 90-day inhalation study is required for 

amitrole. The study can be reduced to a 28-day protocol if the data plateaus during the testing, or 

if exposure potential is not expected to exceed 28 days. 

870.6200a Acute Neurotoxicity and 870.6200b 90-Day Neurotoxicity (Sub chronic): Screening 

batteries for acute and subchronic (90 day) neurotoxicity have not been submitted for amitrole 

and are now required under 40 CFR Part 158 guidelines (870.6200). The battery is designed to 

evaluate the potential adverse effects of a pesticide on the nervous system. 

870.7800 Immunotoxicity: An immunotoxicity study is required as a part of new data 

requirements in the 40 CFR Part 158 for conventional pesticide registration. Because the 

immune system is highly complex, studies not specifically conducted to assess immunotoxic 
Page 11 of 12 

endpoints are inadequate to characterize a pesticide’s potential immunotoxicity. While data from 

hematology, lymphoid organ weights, and histopathology in routine chronic or subchronic 

toxicity studies may offer useful information on potential immunotoxic effects, these endpoints 

alone are insufficient to predict immunotoxicity (see Appendix A). 

References 

HED Chapter of the Reregistration Eligibility Document (RED) for Amitrole (T. Myers, 

12/26/95, HED doc no. 011752). 

Occupational and Residential Exposure Assessment and Recommendations for the Reregistration 

Eligibility Document for Amitrole (J. Evans, 12/6/95, D219471). 

Amitrole: Toxicology Endpoint Selection Document (rev 5/21/96, HED doc no.013093). 

Reregistration Eligibility Decision (RED) Amitrole (8/96). 

Amitrole: Fifth Report of the Cancer Assessment Review Committee (J. Kidwell, 5/11/06, TXR 

No. 0054224). 

1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health Aggregate Risk 

Assessment in Support of Reregistration and Registration Actions for Triazole-derivative 

Fungicide Compounds (DP Number: 322215)
Page 12 of 12 

Appendix A 

Rationale for Requiring Immunotoxicity Testing

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 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-tetrachlorodibenzop-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 this data, a 10X database uncertainty factor may be applied 

for conducting a risk assessment from the available studies.