UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION

MEMORANDUM

Date: 2/12/2014

SUBJECT: Aminopyralid. Human Health Assessment Seeping Document in Support of

Registration Review

PC Code: 005100

Decision No.: 482282

Petition No.: NA

Risk Assessment Type: NA 

TXRNo.: NA

MRIDNo.: NA

DP Barcode: D414395

Registration No.: 62719-519

Regulatory Action: Registration Review

Case No.: 7267

CAS No.: 150114-71-9

40 CFR: §180.610

FROM: Douglas Dotson, Ph.D., Chemist

Jaime D'Agostino, Ph.D.,Toxicologist .-

Zaida Figueroa, Industrial Hygienist

Risk Assessment Branch II 

Health Effects Division (7509P) 

Office of Pesticide Programs

THROUGH: Christina Swartz, Branch Chief

Risk Assessment Branch II

Jess Rowland, Acting Associate Director

Dana Vogel, Associate Director 

Health Effects Division (7509P) 

Offic·e of Pesticide Programs

TO: Veronica Dutch, Chemical Review Manager 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs

Attached is the Health Effects Division's (HED) human health risk assessment seeping document 

for aminopyralid to support registration review.
Aminopyralid Registration Review Scoping Document

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Executive Summary

The Health Effects Division Aminopyralid Registration Review Team has evaluated the database 

and the most recent human health risk assessment for the herbicide aminopyralid. HED 

performed this evaluation in order to determine the scope of work necessary to support the 

established tolerances and existing registrations during registration review. The primary source

of information for this evaluation was the most recent human health risk assessment (D359088,

D. Dotson, et al, 10/22/2009).

Aminopyralid, 4-amino-3,6-dichloro-2-pyridinecarboxylic acid, is a systemic postemergence 

herbicide that belongs to the pyridine carboxylic acid class of herbicides. It is currently 

registered for use in rangeland, permanent grass pastures, non-cropland areas, natural areas, 

grazed areas in and around these sites, as well as on wheat and com. In addition, it is registered 

for use on wildlife habitat and industrial vegetation management areas, including right-of-way 

for roads, railroads, and utility lines. Aminopyralid provides systemic postemergence broadspectrum control of a number of key noxious and invasive annual, biennial, and perennial weed 

species, as well as agronomic broadleaf weeds. Aminopyralid can also provide residual weed 

control against re-infestations and can reduce the need for re-treatment depending on the rate 

applied and the target weeds. It can be applied as a broadcast treatment by ground, aerial, and 

handheld equipment.

The toxicology database for aminopyralid is complete, and no additional toxicity studies are 

required. HED's Hazard and Science Policy Council (HASPOC) determined that a subchronic 

inhalation study in the rat is not required for aminopyralid. The toxicology database for 

aminopyralid includes studies with both the acid (XDE-750) and triisopropanolammonium 

(TIPA) salt (GF-871).

An immunotoxicity study was submitted subsequent to the last risk assessment and has been 

reviewed by HED. The immunotoxicity study is considered to be acceptable and has no impact 

on the overall hazard characterization, including doses and endpoints selected (along with 

traditional uncertainty factors) for risk assessment. The toxicology studies with aminopyralid 

indicate that the main target organs in the rat and dog were the stomach, ileum, and cecum 

following administration in subchronic and chronic studies. There is no evidence of 

neurotoxicity, carcinogenicity, or qualitative or quantitative susceptibility of the developing fetus 

or offspring, based on results from the developmental,reproductive, or carcinogenic toxicity 

studies. Therefore, based on the completeness of the database,the lack of susceptibility, the lack 

of neurotoxicity, and the conservative nature ofthe exposure assessment, HED previously 

recommended that the required 1Ox Food Quality Protection Act (FQPA) Safety Factor be 

reduced to 1x.

The residue chemistry database is adequate to support current registration review requirements. 

Adequate metabolism (crops, livestock, and rotational crops), storage stability, magnitude of the 

residue, and processing data are available to support the registered uses. Adequate methods are 

available for enforcement of the currently established tolerances. The tolerance expression has 

been updated to include both coverage and compliance statements.
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The dietary exposure database is adequate to support current registration requirements. The last 

risk assessment provided chronic dietary exposure estimates that are not of concern for all 

population subgroups (D359088, D. Dotson, et al, 10/22/2009). The general U.S. population and 

all subgroups use less than 1% of the cPAD. As part of registration review, HED anticipates 

performing revised dietary exposure analyses to reflect current Agency policy and potentially 

updated drinking water estimates.

The residential exposure database is complete. During registration review, a revised residential 

exposure assessment that includes post-application incidental oral exposure to children (1 <2 

years old) playing on treated recreational sites might be required. This assessment should 

incorporate recently updated Health Effects Division’s 2012 Standard Operating Procedures for 

Residential Pesticide Exposure Assessment. The Agency might revisit the need for a 

quantitative post-application spray drift exposure assessment for aminopyralid during 

registration review.

There is sufficient information available to assess occupational exposure and risk from the 

registered uses. The previous occupational handler assessment covered the relevant exposure 

scenarios and did not result in risk estimates of concern. Revised occupational handler 

assessments might be required during registration review to include revised surrogate unit 

exposures for occupational handlers. An occupational quantitative post-application assessment 

was not conducted previously because a dermal endpoint was not selected for aminopyralid. 

Therefore, a quantitative occupational post-application assessment will not be necessary during 

registration review.

Introduction

HED evaluated the most recent human health risk assessment for aminopyralid in association 

with updates to its toxicity, exposure, and usage databases to determine if sufficient data are 

available, and if further updates are needed, to support registration review. The most recent 

human health risk assessment was performed in 2009 when HED evaluated a request for a new 

use on corn (D359088, D. Dotson, et al, 10/22/2009).

Tolerances for aminopyralid are established in 40 CFR §180.610. For plant commodities, the 

tolerance is established in terms of free and conjugated aminopyralid. Plant commodity 

tolerances range from 0.04 ppm for wheat grain to 50 ppm for grass hay. Livestock commodity 

tolerances are established in terms of aminopyralid only, and range from 0.03 ppm to 0.3 ppm.

The structure, the chemical names, and other identifiers can be found in the chemical identity 

table in Attachment 1.

Hazard Identification/Toxicology

The herbicidal mode of action for aminopyralid is that of a plant growth regulator. It disrupts 

normal growth by acting like a class of plant growth hormones known as auxins. The chemical 

moves systemically throughout the plant and deregulates plant growth metabolic pathways 

affecting the growth process of the plant. This disruption of plant growth processes results in
Aminopyralid Registration Review Scoping Document

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control and death of susceptible plant species. The toxicological mode of action in mammals is 

unknown.

The toxicology database for aminopyralid is complete and no additional toxicity studies are 

required. HED’s HASPOC determined that a subchronic inhalation study in the rat is not 

required for aminopyralid (J. VanAlstine, TXR#005100, 4/17/2013,). The toxicology database 

for aminopyralid includes studies with both the acid (XDE-750) and TIPA salt (GF-871). Unless 

otherwise noted, the acid form was used in the studies discussed in this section.

An immunotoxicity study was recently submitted and has been reviewed by HED (MRID

48364401). The study is acceptable, and the results show no evidence of immunotoxicity. These 

results are consistent with the existing toxicological database which does not indicate that the 

chemical targets the immune system. Given the above information, HED concludes that this new 

immunotoxicity study has no impact on the overall hazard characterization, including doses and 

endpoints selected (along with traditional uncertainty factors) for risk assessment.

The toxicology database for aminopyralid indicates that the stomach, ileum, and cecum are 

targets for this chemical. In subchronic studies in rats and dogs, hyperplasia of the mucosal 

epithelium was observed. In addition, hypertrophy of the mucosal epithelium was observed in 

the subchronic dog study. Following chronic exposure of rats and dogs, hypertrophy (dog) and 

hyperplasia (dog and rat) of the mucosal epithelium was observed, as well as cecal enlargement 

(rat), thickening of the stomach mucosa (dog), slight lymphoid hyperplasia of the gastric mucosa 

(dog), and chronic mucosal inflammation (dog). No adverse effects were observed when the 

TIPA salt was given to rats for 13 weeks. No adverse effects were observed in subchronic or 

chronic feeding studies in mice exposed to the acid form.

Stomach effects were also observed in a developmental toxicity study in rabbits. Ulcers and 

erosions were seen in the glandular mucosa of the stomach in maternal animals. Other effects 

noted were decreased body weights and incoordinated gait. No developmental effects were seen 

in fetuses. In another developmental rabbit study with the TIPA salt, severe inanition 

(exhaustion from lack of food), body weight loss, decreased fecal output, and incoordinated gait 

were observed in maternal animals. Decreased fetal body weights were observed at the next 

highest dose. No effects were noted in developmental toxicity studies in rats with either the acid 

or TIPA salt, or a reproduction study in rats. Therefore, there was no evidence of increased preand/or post-natal quantitative and qualitative susceptibility in the rat or rabbit.

No systemic toxic effects were observed in a 28-day dermal toxicity study in rats; however, 

dermal toxicity was indicated by slight epidermal hyperplasia in males. In an acute neurotoxicity 

study in rats, fecal soiling in males and urine soiling in females were observed at the limit dose. 

No adverse effects were observed in a chronic neurotoxicity study at the highest dose tested.

Aminopyralid is classified as “not likely to be carcinogenic to humans.” No increases in any 

tumors were found in carcinogenicity studies in rats and mice. Aminopyralid was negative in all 

mutagenicity studies, except for an in vitro chromosome aberration assay in Sprague Dawley 

rats. In this assay, the acid form induced chromosome aberrations, but only at cytotoxic
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concentrations. Thus, the clastogenic response was induced secondary to toxicity. An 

acceptable rat metabolism study for aminopyralid is available.

Both the acid and TIPA salt of aminopyralid have low acute toxicity (Toxicity Category IV) via 

oral, dermal, and inhalation routes of exposure. Both forms are not irritating to the skin and are 

not skin sensitizers. The acid form is severely irritating to the eye (Toxicity Category I) while 

the TIPA salt is not irritating to the eye (Toxicity Category IV).

In the most recent risk assessment, the required 10x FQPA Safety Factor was reduced to 1x 

based on: 1) the lack of increased pre- and post-natal susceptibility of rats and rabbits to in utero 

and/or post-natal exposure in the developmental and reproductive toxicity studies; 2) there is no 

evidence of neurotoxicity in the database; and 3) the risk assessment does not underestimate 

exposure because the dietary assessment is based on conservative assumptions such as tolerancelevel residues in foods and upper-bound modeled estimates of residues in drinking water.

These conclusions are not expected to change during registration review. The toxicological 

endpoints and doses used in the most recent human health risk assessment are summarized in 

Attachment 3. The toxicity profile of aminopyralid is summarized in Attachment 4.

Conclusions for Hazard Identification/Toxicology

The toxicity database is complete for the purpose of registration review, and is appropriate for 

assessment of potential carcinogenic, mutagenic, developmental, and reproductive effects. The 

FQPA Safety Factor was reduced to 1x based on a number of factors including the lack of 

susceptibility in developmental and reproduction studies in rats and rabbits, the lack of evidence 

for neurotoxicity, and the conservative assumptions used in the exposure assessments. No new 

toxicity data are required. Although the conclusions are not expected to change, HED will 

consider the appropriateness of the existing endpoints based on current policies and risk 

assessment methodologies during registration review.

Dietary Exposure

The residue chemistry database is adequate to support current registration review requirements 

(D360100, D. Dotson, 10/22/2009). Adequate metabolism (crops, livestock, and rotational 

crops), storage stability, magnitude of the residue, and processing data are available to support 

the registered uses. Adequate methods are available for enforcement of the currently established 

tolerances. No residue chemistry data deficiencies were cited in the previous risk assessment for 

aminopyralid. The previous risk assessment stated that the proposed label for corn should be 

modified to specify that spray or spot applications may not be made after the V6 growth stage, 

and that forage may not be harvested prior to the dent stage of growth. The registrant added 

these restrictions to the label.

For the 2009 risk assessment, HED conducted a chronic dietary exposure assessment for all 

currently registered food uses (D369212, D. Dotson, 10/22/2009). The assessment was 

unrefined and, therefore, conservative. It was based on the assumption that aminopyralid
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residues are present at tolerance levels in all commodities for which tolerances have been 

established, and that 100% of those crops are treated. DEEMTM Version 7.81 default processing 

factors were applied to all processed commodities for which they were available. Drinking water 

was incorporated directly into the dietary assessment using the estimated drinking water 

concentration (EDWC) for surface water. The EDWC is a modeled surface water residue 

estimate provided by the Environmental Fate and Effects Division (EFED; D361926, 7/24/2009, 

R. Baris). It was generated by the Tier 1 FQPA Index Reservoir Screening Tool (FIRST) Model. 

The EDWC includes aminopyralid only. It is the only residue of concern in drinking water for 

risk assessment. The chronic dietary risk estimates were not of concern for the general U.S. 

population and all population subgroups. All subgroups use less than 1% of the cPAD. During 

registration review, HED will likely conduct a new dietary exposure and risk assessment if there 

are significant changes in the drinking water estimates. If an assessment is needed, HED will use 

the most current dietary exposure model and food consumption survey.

Conclusions for Dietary Exposure

No new data are needed to assess potential dietary exposure and risk for aminopyralid. 

However, HED anticipates performing a new dietary exposure assessment during registration 

review. The most current drinking water models will be used for this assessment. In addition, 

the most current version of the dietary model will be used, along with any potential changes in 

endpoints and doses for risk assessment.

Residential Exposure

Residential Handlers

Based on the current registered use pattern, aminopyralid is not applied by homeowners to 

residential or recreational settings; therefore, a residential handler exposure assessment will not 

be needed for registration review.

Residential Post-Application

Aminopyralid is applied by commercial handlers to natural recreation areas (e.g., wildlife 

management areas, campgrounds, trailheads and trails) to control weeds. As there is potential 

for short-term exposure of adults and children from entering areas previously treated with 

aminopyralid, residential post-application exposures associated with the use of aminopyralid to 

control weeds on residential and recreational sites were assessed in 2005 (M. Collantes, 

D305672).

Residential post-application dermal and inhalation exposure assessments were not required 

because: 1) no dermal endpoint was selected, and 2) inhalation exposure was expected to be 

negligible for outdoor uses associated with treated recreation areas. Risks resulting from handto-mouth transfer, incidental ingestion of pesticide-treated turf grass and soil scenarios were 

assessed using the HED Draft Standard Operating Procedures (SOPs) for Residential Exposure 

Assessments (12/18/97), and the Revisions to the Standard Operating Procedures (SOPs) for
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Residential Exposure Assessment (Science Advisory Council for Exposure Policy 12, Revised 

February 22, 2001). The results of the post-application residential exposure assessment indicate 

no risks of concern, with MOEs >61,000 (LOC = 100).

A revised residential exposure assessment that includes post-application incidental oral exposure 

to children (1 <2 years old) playing on treated recreational sites might be required under 

registration review. This assessment should incorporate recently updated procedures found in

the Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide

Exposure Assessment.

In accordance with the updated Part 158 data requirements (2007), a turf transferrable residue 

(TTR) study is required for all residential or occupational turf uses (e.g., sod farms, golf courses, 

parks, and recreational areas). However, a TTR study is not required for aminopyralid at this 

time because post-application incidental oral exposure calculated previously (D305672, M. 

Collantes, 05/24/2005) resulted in MOEs 10 times as high as the level of concern (e.g., an

MOE> 1,000 compared to the LOC of 100); therefore, using the default residue transfer values 

should provide an adequate margin of safety for any potentially higher residues seen in a 

chemical-specific TTR study.

Spray Drift

The Agency has not considered residential post-application inhalation exposure for aminopyralid 

because there are no registered residential uses at this time. However, residential exposures 

resulting from off-site transport (e.g., spray drift or volatilization) might occur as a result of 

applications of aminopyralid. The Agency is in the process of evaluating these types of 

exposures and might, as appropriate, develop policies and procedures to identify the need for

and, subsequently, the way to incorporate these post-application exposures into the Agency’s risk 

assessments. The Agency might conduct a spray drift assessment and examine the need for a

volatilization assessment for aminopyralid during registration review.

Conclusions for Residential Exposure

The residential exposure database is complete. Based on the current registered uses, a residential 

handler exposure assessment will not be conducted during registration review. However, the 

Agency might conduct a revised residential post-application assessment that includes postapplication incidental oral exposure of children (1 <2 years old) playing on treated recreational 

sites. This assessment should incorporate recently updated procedures found in the Health 

Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide Exposure 

Assessment.

Aggregate Risk Assessment

The most recent aggregate risk assessment was performed in conjunction with the 2009 risk 

assessment. For aggregate assessment, exposure estimates resulting from food, drinking water, 

and residential uses are combined. As no acute endpoint was identified and cancer risk is not a
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concern for aminopyralid, acute and cancer aggregate risk assessments were not performed. 

There are residential uses for aminopyralid on recreational sites (e.g., campgrounds). The nondietary scenarios included in the aggregate assessment consisted of incidental oral exposures 

(e.g., hand-to-mouth transfer of residues, object-to-mouth, and ingestion of soil). These

scenarios are short-term in duration and are applicable to children only. There are no non-dietary 

scenarios for aminopyralid that are appropriate for assessing adults, therefore, the aggregate 

exposure estimates for adults are equivalent to the chronic dietary (food + water) estimates. A 

short-term aggregate risk assessment was performed for various subgroups comprised of children 

less than 12 years old (i.e., all infants <1 year old, children 1-2, children 3-5, and children 6-12). 

The short-term aggregate risk estimates were not of concern. Aggregate MOEs ranged from

25,000-33,000, whereas the LOC was 1,000.

Based on the registered and proposed uses, there are no residential scenarios that are likely to 

result in intermediate-term exposure (30-180 days, continuous). Therefore, HED has not 

conducted an intermediate-term aggregate risk assessment for aminopyralid. Dietary (food + 

water) consumption is the only source of exposure to aminopyralid that is expected to result in 

chronic exposure. Therefore, the long-term aggregate exposure and risk estimates are equivalent 

to the chronic dietary exposure and risk estimates discussed above. The chronic dietary risk 

estimates were not of concern for the general U.S. population and all population subgroups. All 

subgroups use less than 1% of the cPAD.

Conclusions for Aggregate Exposure and Risk

Acute, intermediate-term, and cancer aggregate risk assessments were not performed for 

aminopyralid. The short- and long-term aggregate risk estimates are not of concern to HED for 

any of the population subgroups for which risk estimates were generated. At the time of 

registration review, HED will conduct a new aggregate risk assessment that will be based on 

residential exposures estimated using the updated residential SOPs, and will include any 

potential updates to points of departure or exposure estimates from food and drinking water.

Occupational Exposure

Aminopyralid is registered for use in a variety of non-cropland areas and grazed areas, as well as 

on wheat and corn. It can be applied as a broadcast treatment by ground, aerial, and handheld 

equipment. The Agency has determined that there is a potential for occupational handler and 

post-application exposures resulting from the registered uses of aminopyralid.

Occupational Handlers

The previous exposure and risk assessments evaluated a number of occupational handler 

scenarios that represented the major aminopyralid short- and intermediate-term occupational 

exposures associated with application equipment and formulation type. The risk assessments 

indicated that there are no risks of concern associated with occupational handler scenarios for 

workers wearing baseline clothing (i.e., long pants, long sleeve shirt, shoes plus socks).
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HED will likely reevaluate the occupational handler assessment for aminopyralid to address 

updates to HED’s exposure policies, specifically, revisions to the Agency’s scenario-specific 

surrogate handler exposure data and assumptions for body weights.

Occupational Post-application

The previous risk assessments evaluated a number of representative occupational postapplication scenarios based on the registered uses. HED has determined that there are potential 

dermal exposures of people entering treated sites (e.g., harvesters) after pesticide application is 

complete. However, since no dermal endpoints were selected, a quantitative post-application 

exposure assessment for agricultural workers was not conducted.

In accordance with the updated Part 158 data requirements (2007), one or more dislodgeable 

foliar residue (DFR) studies are required when a pesticide has residential or occupational uses 

that could result in post-application dermal exposure. However, a DFR study is not required for 

aminopyralid at this time because no dermal endpoints were selected, and therefore, a dermal 

post-application exposure assessment is not required.

After application of the product, agricultural workers could be exposed to residues from both the 

aminopyralid salt and the parent acid. Therefore, the restricted entry interval (REI) for 

agricultural occupational exposure is based on the acute toxicity of both aminopyralid acid 

technical and the TIPA salt. Aminopyralid acid is classified as Toxicity Category IV for acute 

dermal irritation and lethality following acute dermal exposure. However, under the 

requirements for the Worker Protection Standard for Agricultural Pesticides (WPS), 

aminopyralid is classified as Toxicity Category I in an acute toxicity eye irritation study. 

According to WPS, a 48-hour REI is assigned to chemicals with acute Toxicity Category I 

classifications. Furthermore, chemicals classified as Toxicity Category I for eye irritation

require the use of protective eyewear. Therefore, HED recommends that during registration 

review the proper REI be included on all registered master labels and all the supplemental labels 

to ensure that the REIs are adequate to protect workers from post-application exposures to 

aminopyralid.

Based on the Agency’s current practices, a quantitative post-application inhalation exposure 

assessment was not performed for aminopyralid. However, if new policies or procedures are put 

into place, the Agency might revisit the need for a quantitative occupational post-application 

inhalation exposure assessment for aminopyralid during registration review.

Conclusions for Occupational Exposure and Risks

Updated occupational handler exposure assessments will likely be required under registration 

review based upon revisions to the Agency’s scenario-specific surrogate handler exposure data 

and assumptions for body weights. No occupational post-application dermal exposure 

assessment will be required under registration review; however, the Agency might revisit the 

need for a quantitative occupational post-application inhalation exposure assessment. HED 

recommends that, during registration review, the proper REI be included on all registered master
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labels and all the supplemental labels to ensure that the REIs are adequate to protect workers 

from post-application exposures to aminopyralid.

Public Health and Pesticide Epidemiology Data

For this evaluation, the Agency consulted both the OPP Incident Data System (IDS) and the 

Centers for Disease Control and Prevention/National Institute for Occupational Safety and 

Health (CDC/NIOSH) Sentinel Event Notification System for Occupational Risk-Pesticides

(SENSOR) databases for pesticide incident data on the active ingredient aminopyralid (Memo, 

D415939, S. Recore, 11/12/2013). The purpose of the database search was to identify potential 

patterns in the frequency and severity of the health effects attributed to aminopyralid exposure. 

Aminopyralid is not included in the Agricultural Health Study (AHS); and therefore, that study 

does not provide information for this report.

For the Main IDS, from January 1, 2008 to September 11, 2013, there were 3 incidents reported 

for single chemical only in the database. There were 11 additional incidents reported involving 

more than one chemical. The incidents reported were classified as moderate severity. Overall, 

there are few incidents involving aminopyralid reported to IDS. In Aggregate IDS, from January

1, 2008 to September 11, 2013, there were 35 reported incidents involving aminopyralid.

The SENSOR-Pesticides database covers 11 states from 1998-2009, although reporting varies 

from state to state. Cases of pesticide-related illnesses are ascertained from a variety of sources 

including reports from local Poison Control Centers, state Department of Labor workers’ 

compensation claims when reported by physicians, reports from State Departments of 

Agriculture, and physician reports to state Departments of Health. A query of SENSORPesticides from 1998 to 2009 revealed that two cases involving aminopyralid were reported. 

Both cases involved multiple active ingredients and were low in severity.

Based on the low frequency and severity of incident cases reported in both IDS and SENSORPesticides, 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

Tolerances for residues of aminopyralid in or on agricultural commodities are established in

40CFR §180.610. For plant commodities, the tolerances are established as follows: “Tolerances 

are established for residues of the herbicide aminopyralid, 4-amino-3,6-dichloro-2-

pyridinecarboxylic acid, including its metabolites and degradates, in or on the commodities in

the table below. Compliance with the tolerance levels specified below is to be determined by 

measuring only free and conjugated aminopyralid.” For animal commodities, the tolerances are 

established as follows: “Tolerances are established for residues of the herbicide aminopyralid, 4-

amino-3,6-dichloro-2-pyridinecarboxylic acid, including its metabolites and degradates, in or on
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the commodities in the table below. Compliance with the tolerance levels specified below is to 

be determined by measuring only aminopyralid.”

The Codex Alimentarius Commission (Codex) has established maximum residue limits (MRLs) 

for aminopyralid on both plant and livestock commodities. The Codex residue definition is the 

same for both types of commodities: aminopyralid and its conjugates that can be hydrolyzed, 

expressed as aminopyralid. In the cases where the U.S. and Codex have established MRLs for 

the same commodities, the MRLs are not harmonized. Codex has established MRLs for 

commodities that do not have U.S. tolerances. Canada has established MRLs for wheat grain, 

wheat bran, and several livestock commodities. The Canadian residue definitions and MRLs are 

all harmonized with those of the U.S. The harmonized tolerances include those for wheat grain, 

wheat bran, and livestock commodities. Canada does not set MRLs in livestock feed items, so 

there is no issue with harmonization for these commodities. The international residue limit

status sheet can be found in Attachment 6.

During registration review, HED will revisit the tolerances and harmonize them with the Codex 

MRLs, when possible. The U.S. tolerances for some of the wheat and livestock commodities are 

slightly lower than the Codex MRLs for the same commodities. The U.S. could potentially 

harmonize with Codex by making slight increases to the tolerances for wheat grain, hay, and 

straw. The same is true for the meat and meat byproducts of cattle, goats, horses, and sheep.

Environmental Justice

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

human-health risk assessment, in accordance with U.S. Executive Order 12898, “Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations,” 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). The OPP

typically considers the highest potential exposures from the legal use of a pesticide when 

conducting human-health risk assessments, including, but not limited to, people who obtain 

drinking water from sources near agricultural areas, the variability of diets within the U.S., and 

people who might be exposed when harvesting crops. Should these highest exposures indicate 

potential risks of concern, OPP further refines the risk assessments to ensure that the risk 

estimates are based on the best available information.

Cumulative Risk Assessments

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 aminopyralid and any other substances, and aminopyralid does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this action, therefore, EPA has not 

assumed that aminopyralid 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
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and procedures for cumulating effects from substances found to have a common mechanism on

EPA’s website at http://www.epa.gov/pesticides/cumulative/.

Human Studies

The previous aminopyralid risk assessments relied in part on data from studies in which adult 

human subjects were intentionally exposed to a pesticide or other chemical. Studies such as the 

Pesticide Handlers Exposure Database, Outdoor Residential Exposure Task Force, and 

Agricultural Handler Exposure Task Force have been reviewed by the Agency and found, on the 

basis of available evidence, to have been neither fundamentally unethical nor significantly 

deficient relative to standards of ethical research conduct prevailing when they were conducted. 

There is no barrier in EPA’s “Protection of Human Subjects” Regulation to reliance on these 

studies.

Risk Assessment Updates, Data Deficiencies, and Label Revisions

No data deficiencies were identified for aminopyralid.

EPA anticipates conducting the following risk assessment updates during registration review: 

Toxicology:

 HED will consider the appropriateness of the existing endpoints based on current policies 

and risk assessment methodologies.

Residue Chemistry:

 None. Dietary

Exposure:

 Revised dietary exposure analyses might be required to reflect updated dietary exposure 

models and updated drinking water estimates.

Occupational/Residential Exposure:

 HED anticipates conducting revised occupational exposure assessments to reflect the use 

of the most recent handler exposure data and updated body weights.

 The Agency might conduct a revised residential post-application assessment that 

incorporates recently updated procedures found in the Health Effects Division’s 2012

Standard Operating Procedures for Residential Pesticide Exposure Assessment.
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References

Memoranda Relevant to Registration Review

Author Barcode Date Title

D. Dotson D359088 10/22/2009 Aminopyralid. Human Health Risk Assessment for the Proposed

Use on Field Corn (PP#8F7455)

J. VanAlstine NA 4/7/2013 Aminopyralid: Summary of Hazard and Science Policy Council

(HASPOC) Meeting of March 28, 2013: Recommendations on the

Requirement of a Subchronic Inhalation Study

D. Dotson D360100 10/22/2009 Aminopyralid and Aminopyralid Triisopropanolammonium (TIPA) 

Salt. Request to Add Uses on Field Corn to Milestone®(EPA Reg. 

No. 62719-519). Summary of Analytical Chemistry and Residue 

Data

D. Dotson D369212 10/22/2009 Aminopyralid Chronic Aggregate Dietary (Food and Drinking

Water) Exposure and Risk Assessment for the Section 3

Registration on Field Corn

M. Collantes D305672 5/24/2005 Occupational and Residential Exposure Risk Assessment for

Proposed Uses of Aminopyralid

Z. Figueroa D370497 10/22/2009 Aminopyralid Occupational Exposure Assessment for the

Registration of Milestone Herbicide for Use on Corn

R. Baris D361926 7/24/2009 Tier I Drinking Water Exposure Assessment for the Section 3 New

Use of Triisopropanolamine Salt of Aminopyralid on Field Corn and

Field Corn Grown for Ensilage

S. Recore D415939 11/12/2013 Aminopyralid: Tier I Review of Human Incidents

Attachments

Attachment 1. Chemical Identity Table Attachment 2. 

Toxicology Data Requirements Attachment 3. 

Aminopyralid Endpoint Selection Table Attachment 4. 

Toxicity Profile Table

Attachment 5. Summary of Occupational Uses Based on Registered Labels for Aminopyralid

Attachment 6. International Residue Limit Status
Aminopyralid Registration Review Scoping Document

Page 14 of 27

Attachment 1. Chemical Identity Table

Aminopyralid Nomenclature.

Chemical structure NH2

Cl

OH 

Cl N

O

Common name Aminopyralid

Company experimental name XDE-750

IUPAC name 4-amino-3,6-dichloropyridine-2-carboxylic acid

CAS name 4-amino-3,6-dichloro-2-pyridinecarboxylic acid

CAS registry number 150114-71-9

Chemical structure

NH2

HO CH3

Cl

H3C

.

N 

OH

Cl N OH OH

O

CH3

Common name Aminopyralid, triisopropanolammonium(TIPA) salt

PC Code 005209

Company experimental name XDE-750 TIPA salt

IUPAC name 4-amino-3,6-dichloropyridine-2-carboxylic acid - (2RS,2′RS,2′′RS)-1,1′,1′′-

nitrilotripropan-2-ol (1:1)

CAS name 4-amino-3,6-dichloropyridine-2-carboxylic acid compound with 1,1′,1′′-

nitrilotris[2-propanol] (1:1)

CAS registry number 566191-89-7

End-use product (EP) Milestone® (2 lb ae/gal SL; EPA Reg. No. 62719-519)
Aminopyralid Registration Review Scoping Document

Page 15 of 27

Attachment 2. Toxicology Data Requirements

The requirements (40 CFR 158.340) for aminopyralid residential and occupational use are shown 

below. Use of the new guideline numbers does not imply that the new (1998) guideline

protocols were used.

Test Technical

Required Satisfied

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

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

870.1300 Acute Inhalation Toxicity...............................................

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

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

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

yes 

yes 

yes 

yes 

yes 

yes

yes 

yes 

yes 

yes 

yes 

yes

870.3100 Oral Subchronic (rodent)................................................

870.3150 Oral Subchronic (nonrodent)..........................................

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

870.3250 90-Day Dermal...............................................................

870.3465 90-Day Inhalation...........................................................

yes 

yes 

no 

yes 

no

yes 

yes 

yes 

no

1

---

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

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

870.3800 Reproduction ..................................................................

yes 

yes 

yes

yes 

yes 

yes

870.4100a Chronic Toxicity (rodent)...............................................

870.4100b Chronic Toxicity (nonrodent).........................................

870.4200a Oncogenicity (rat)...........................................................

870.4200b Oncogenicity (mouse) ....................................................

870.4300 Chronic/Oncogenicity ....................................................

yes 

no 

yes 

yes 

yes

yes 

yes 

yes 

yes 

yes

870.5100 Mutagenicity—Gene Mutation - bacterial......................

870.5300 Mutagenicity—Gene Mutation - mammalian.................

870.5375 Mutagenicity—StructuralChromosomal Aberrations....

870.5395 Mutagenicity—Mammalian Erythrocyte Micronucleus.

870.5550 Mutagenicity—Unscheduled DNA Synthesis................

870.5915 Mutagenicity—In Vivo Sister Chromatid Exchange

yes 

yes 

yes 

no 

no 

no

yes 

yes 

yes 

yes 

yes

--

870.6100a Acute Delayed Neurotox. (hen)......................................

870.6100b 90-Day Neurotoxicity (hen) ...........................................

870.6200a Acute Neurotox. Screening Battery (rat)........................

870.6200b 90 Day Neurotox. Screening Battery (rat)......................

870.6300 Develop. Neuro ..............................................................

no 

no 

yes 

yes 

no

---

---

yes

no

2

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

870.7600 Dermal Penetration.........................................................

yes 

no

yes 

yes

870.7800 Immunotoxicity................................................ yes yes

1 Requirement fulfilled by 21/28 day study.

2 Requirement fulfilled by chronic neurotoxicity study.
Aminopyralid Registration Review Scoping Document

Page 16 of 27

Summary of Toxicological Doses and Endpoints for Aminopyralid for Use in Dietary and Non-Occupational

Human Health Risk Assessments.

Exposure/ 

Scenario

Point of

Departure

Uncertainty/ 

FQPA Safety 

Factors

RfD, PAD,

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(General 

Population, 

including 

Infants and 

Children and 

females 13-49)

N/A N/A N/A

A toxic effect attributable to a single dose

was not seen in the toxicity database; 

therefore, an acute endpoint has not been 

identified.

Chronic 

Dietary (All 

Populations)

NOAEL= 50 

mg/kg/day

UFA= 10x 

UFH=10x 

FQPA SF=1x

Chronic RfD

=0.5 mg/kg/day

cPAD

=0.5 mg/kg/day

Chronic toxicity/carcinogenicity study in

rats (XDE-750) 

LOAEL=500 mg/kg/day

based on cecal enlargement, slight 

mucosal hyperplasia in males and slightly 

decreased body weights

Incidental Oral

Short-Term (1-

30 days) 

IntermediateTerm (1-6 

months)

NOAEL=104 

mg ae/kg/day

UF = 10x 

UFH=10x 

FQPA SF=1x

Residential

LOC for MOE

= 100

Developmental rabbit study (GF-871)

LOAEL=260 mg/kg/day

based on severe inanition (exhaustion 

resulting from lack of food) and body 

weight loss, decreased fecal output, and 

mild incoordinated gait.

Dermal ShortTerm (1-30 

days) 

IntermediateTerm (1-6 

months)

N/A N/A N/A

28-day dermal toxicity study in rats.

No systemic toxicity seen at the limit dose

(1,000 mg/kg/day) (XDE-750) 

Dermal risks are not of concern.

Inhalation 

Short- Term 

(1-30 days) 

IntermediateTerm (1-6 

months)

NOAEL=104 

mg ae/kg/day

UFA= 10x 

UFH=10x 

FQPA SF=1x

Residential

LOC for MOE

= 100

Developmental rabbit study (GF-871)

LOAEL=260 mg/kg/day

based on severe inanition (exhaustion 

resulting from lack of food) and body 

weight loss, decreased fecal output, and 

mild incoordinated gait.

Cancer (oral,

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies.

Attachment 3. Endpoint Selection Tables

Summary of Toxicological Doses and Endpoints for Use in Human Risk Assessments

A

Point of Departure = 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. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = 

uncertainty factor. UFA = 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. N/A = not applicable. Ae = acid 

equivalent. XDE-750 = acid form of aminopyralid. GF-871 = triisopropanolammonium salt of aminopyralid.
Aminopyralid Registration Review Scoping Document

Page 17 of 27

Summary of Toxicological Doses and Endpoints for Aminopyralid for Use in Occupational Human Health

Risk Assessments.

Exposure/ 

Scenario

Point of

Departure

Uncertainty/ 

FQPA Safety 

Factors

RfD, PAD,

Level of 

Concern for 

Risk 

Assessment

Study and Toxicological Effects

Dermal ShortTerm (1-30 

days) 

IntermediateTerm (1-6 

months)

N/A N/A N/A

28-day dermal toxicity study in rats.

No systemic toxicity seen at the limit dose

(1,000 mg/kg/day) (XDE-750) 

Dermal risks are not of concern.

Inhalation 

Short- Term 

(1-30 days) 

IntermediateTerm (1-6 

months)

NOAEL=104 

mg ae/kg/day

UFA= 10x

UFH=10x

Occupational

LOC for MOE

= 100

Developmental rabbit study (GF-871)

LOAEL=260 mg/kg/day

based on severe inanition (exhaustion 

resulting from lack of food) and body 

weight loss, decreased fecal output, and 

mild incoordinated gait.

Cancer (oral,

dermal, 

inhalation)

Classification: “Not likely to be Carcinogenic to Humans” based on the absence of significant

tumor increases in two adequate rodent carcinogenicity studies.

Point of Departure = 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. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from 

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

(intraspecies). PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. ). FQPA SF = 

FQPA Safety Factor. MOE = margin of exposure. LOC = level of concern. N/A = not applicable. Ae = acid 

equivalent. XDE-750 = acid form of aminopyralid. GF-871 = triisopropanolammoniumsalt of aminopyralid.
Aminopyralid Registration Review Scoping Document

Page 18 of 27

Attachment 4. Toxicity Profiles

Acute Toxicity Profile - Aminopyralid Technical (XDE-750).

Guideline No. Study Type MRID(s) Results Toxicity

Category

870.1100 Acute oral-rat 46235603 LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1200 Acute dermal-rabbit 46235605 LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1300 Acute inhalation-rat 46235607 LC50 = >5.5 mg/L 

(both sexes)

IV

870.2400 Acute eye irritation-rabbit 46235609 Corneal opacity in 1/3 

unresolved through day 35

I

870.2500 Acute dermal irritation-rabbit 46235611 non-irritant IV

870.2600 Skin sensitization-guinea pig 46235613 Not a sensitizer N/A

Acute Toxicity Profile - Aminopyralid Triisopropanolammonium Salt (GF-871).

Guideline No. Study Type MRID(s) Results Toxicity

Category

870.1100 Acute oral-rat 46235604 LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1200 Acute dermal-rabbit 46235606 LD50 = >5000 mg/kg/bw

(both sexes)

IV

870.1300 Acute inhalation-rat 46235608 LC50 = >5.79 mg/L (both 

sexes)

IV

870.2400 Acute eye irritation-rabbit 46235610 No positive signs of corneal 

opacity, iritis or conjunctivitis 

observed

IV

870.2500 Acute dermal irritation -rabbit 46235612 Slight erythema observed at 24 

hours and 72 hours, resolving 

by study day 7

IV

870.2600 Skin sensitization-guinea pig 46235614 Not a sensitizer N/A
Aminopyralid Registration Review Scoping Document

Page 19 of 27

Subchronic, Chronic, and Other Toxicity Profile

GDLN Study Type Dose Levels MRID Results

870.3100 2001-13 WEEK 

FEEDING-RAT (XDE750) with 4 week recovery 

period

mg/kg/day =

0, 10, 100, 500, 1000

Acceptable/Guideline

46235621 NOAEL (mg/kg/day): 

M=500, F= 1000

LOAEL (mg/kg/day): 

M=1000 based on 

hyperplasia of the

mucosal epithelium of the 

ileum and cecum. F=not

determined

870.3100 2004-13 WEEK 

FEEDING-RAT (GF871)‡

XDE-750 TIPA*

mg/kg/day=

0, 192, 500, 1000

¶ ACID EQUIVALENT 

(ae)

mg ae/kg/day=

0, 100, 260, 520

Acceptable/Guideline

46235622 NOAEL (mg/kg/day):

520

LOAEL (mg/kg/day): not 

determined

870.3100 2001-13 WEEK 

FEEDING-MOUSE 

(XDE-750)

mg/kg/day =

0, 10, 100, 500, 1000

Acceptable/Guideline

46235618 NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not 

determined

870.3150 2002-13 WEEK 

FEEDING-DOG (XDE750)

%=0, 0.15, 0.75, 3.0

§ ppm= 0, 1500, 7500,

30000

mg/kg/day =

M: 0, 55, 282, 1070

F: 0, 53, 232, 929

Acceptable/Guideline

46235623 NOAEL (mg/kg/day): 

M=282, F= 232

LOAEL (mg/kg/day): 

M=1070, F=929 based

on stomach

histopathology (slight 

diffuse hyperplasia and 

hypertrophy of the 

mucosal epithelium).
Aminopyralid Registration Review Scoping Document

Page 20 of 27

870.3200 2002-28 DAY DERMALRAT (XDE-750)mg/kg/day =

0, 100, 500, 1000

Acceptable/Guideline

46235626 Systemic: NOAEL 

(mg/kg/day):

1000

LOAEL: (mg/kg/day) not 

determined

Dermal: NOAEL 

(mg/kg/day): 

M=100, F=1000

LOAEL (mg/kg/day): 

M=500, based on 

histopathological changes 

(slight epidermal 

hyperplasia).

F=not determined

870.3700 2001-

DEVELOPMENTAL 

TOX-RAT

(XDE-750)

mg/kg/day =

0, 100, 300, 1000

Acceptable/Guideline

46235629 Maternal: NOAEL 

(mg/kg/day): 1000

LOAEL (mg/kg/day): not 

determined

Developmental: NOAEL 

(mg/kg/day): 1000

LOAEL (mg/kg/day): not 

determined

870.3700 2004-

DEVELOPMENTAL 

TOX-RAT

(GF-871)‡

XDE-750 TIPA*

mg/kg/day=

0, 200, 500, 1000

¶ ACID EQUIVALENT 

(ae)

mg ae/kg/day=

0, 104, 260, 520

Acceptable/Guideline

46235631 Maternal: NOAEL 

(mg/kg/day): 520

LOAEL (mg/kg/day): not 

determined

Developmental: NOAEL 

(mg/kg/day): 520

LOAEL (mg/kg/day): not 

determined

870.3700 2002-

DEVELOPMENTAL

TOX-RABBIT (XDE-750)

mg/kg/day =

0, 25, 100, 250 (phase 1)

mg/kg/day =

0, 500, 750 (phase 2) 

Acceptable/Guideline

46235630 Maternal: NOAEL 

(mg/kg/day): 250

LOAEL (mg/kg/day): 500 

based on decrease in body 

weight (GD 7-10), 

decreased food 

consumption,

incoordinated gait

(23/26), and ulcers and 

erosions of the stomach.

Developmental: NOAEL 

(mg/kg/day): 500

LOAEL (mg/kg/day): not 

determined
Aminopyralid Registration Review Scoping Document

Page 21 of 27

870.3700 2004-

DEVELOPMENTAL 

TOX-RABBIT (GF-871)‡

XDE-750 TIPA*

mg/kg/day=

0, 200, 500, 1000

¶ ACID EQUIVALENT 

(ae)

mg ae/kg/day=

0, 104, 260, 520

Acceptable/Guideline

46235632 Maternal: NOAEL 

(mg/kg/day): 104

LOAEL (mg/kg/day): 260 

based on severe inanition 

and body weight loss, 

decreased fecal output, 

and mild incoordinated 

gait.

Developmental: NOAEL 

(mg/kg/day): 260

LOAEL (mg/kg/day): 520 

based on decreased fetal 

body weights.

870.3800 2003-2-GENERATION 

REPRODUCTION-RAT 

(XDE-750)

mg/kg/day =

0, 50, 250, 1000

Acceptable/Guideline

46235635 Parental: NOAEL

(mg/kg/day):

1000

LOAEL (mg/kg/day): not 

determined

Reproductive: 

NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day): not 

determined

Offspring: NOAEL

(mg/kg/day):

1000

LOAEL (mg/kg/day): not 

determined

870.4100 2003-1 YEAR FEEDINGDOGS

(XDE-750)

% =0, 0.03, 0.30, 3.0

§ ppm= 0, 300, 3000,

30000

mg/kg/day = M:

0, 10, 99, 967

F: 0, 9, 93, 1038

Acceptable/Guideline

46235627 NOAEL (mg/kg/day): 

M=99, F= 93

LOAEL (mg/kg/day): 

M=967, F=1038

based on thickening of 

stomach mucosa 

(females), and stomach 

histopathology in all 

animals (slight diffuse 

hyperplasia and

hypertrophy of the

mucosal epithelium, slight

lymphoid hyperplasia of

the gastric mucosa and

very slight/slight chronic 

mucosal inflammation).

870.4200 2003-18 MONTH 

CARCINOGENICITYMICE (XDE-750)

mg/kg/day =

0, 50, 250, 1000

Acceptable/Guideline

46235628 NOAEL (mg/kg/day): 

M=1000

LOAEL (mg/kg/day):

not determined.
Aminopyralid Registration Review Scoping Document

Page 22 of 27

870.4300 2004-2 YEAR 

TOXICITY/ 

CARCINOGENICITYRAT

(XDE-750)

mg/kg/day =

0, 50, 500, 1000

Acceptable/Guideline

46235615 NOAEL (mg/kg/day):50

LOAEL (mg/kg/day): 500 

based on cecal 

enlargement, slight 

mucosal hyperplasia 

(males) and slightly 

decreased body weights.

870.5100 2004-BACTERIAL 

REVERSE MUTATION 

ASSAY (XDE-750)

0, 100, 333, 1000, 3300 

or 5000 μg/plate 

(Salmonella-Escherichia 

coli) in the presence and 

absence of metabolic 

activation (+ S9).

Acceptable/Guideline

46235636 Negative

870.5100 2004-BACTERIAL 

REVERSE MUTATION 

ASSAY (GF-871)

XDE TIPA *

33, 100, 333, 1000, 3330,

5000 μg/plate 

(Salmonella-Escherichia 

coli) in the presence and 

absence of metabolic 

activation (+ S9).

Acceptable/Guideline

46235637 Negative

870.5300 2004-IN VITRO 

MAMMALIAN CELL 

GENE MUTATION TEST

0, 31, 63, 125, 250, 500,

1000, 1500, 2070 μg/mL 

(1st assay); 250, 500,

1000, 2000, 4000 μg/mL 

(2nd assay), both in the 

presence and absence of 

metabolic activation (+ 

S9).

Acceptable/Guideline

46235801 Negative

870.5300 2004-IN VITRO 

MAMMALIAN CELL 

GENE MUTATION TEST 

(GF-871)

XDE TIPA *

250, 500, 1000, 2000,

4000 μg/mL in the 

presence and absence of 

metabolic activation (+ 

S9).

Acceptable/Guideline

46235804 Negative
Aminopyralid Registration Review Scoping Document

Page 23 of 27

870.5375 2002-IN VITRO 

MAMMALIAN CELL

CHROMOSOME 

ABERRATION TEST 

(XDE-750)

0, 32, 65, 129, 259, 518,

1035, 2070 μg/mL with 

and without metabolic 

activation (1st assay); 0,

125, 250, 500, 750, 1000,

1400, 1700, 2070 μg/mL 

without metabolic 

activation and 0, 62.5,

125, 500, 1000 or 2070 

μg/mL with metabolic 

activation (2nd assay);

400, 600, 800, 1000,

1200, 1400, 1600, 1700,

1800, 2070 μg/mL

without metabolic 

activation (3rd assay).

Acceptable/Guideline

46235802 XDE induced 

chromosome aberrations, 

but only at cytotoxic 

concentrations; the 

clastogenic response was 

induced secondary to 

toxicity.

870.5375 2004-IN VITRO 

MAMMALIAN CELL 

CHROMOSOME 

ABERRATION TEST 

(GF-871)

XDE TIPA *

1000, 2000, 4000 μg/mL 

with and without 

metabolic activation (+ 

S9); 0, 500, 1000, 2000

μg/mL without metabolic

activation.

Acceptable/Guideline

46235803 Negative

870.5395 2002-MAMMALIAN 

ERYTHROCYTE 

MICRONUCLEUS TEST 

(XDE-750)

mg/kg/day = 0, 500,

1000 or 2000

Acceptable/Guideline

46235805 Negative

870.5395 2004-MAMMALIAN 

ERYTHROCYTE 

MICRONUCLEUS TEST 

(GF-871)

mg/kg/day = 0, 500,

1000, or 2000

Acceptable/Guideline

46235806 Negative

870.6200 2001-ACUTE 

NEUROTOXICITY-RAT 

(XDE-750)

mg/kg/day =

0, 500, 1000, 2000

Acceptable/Guideline

46235616 NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day):

2000

based on fecal soiling in 

males and urine soiling in 

females.

870.6200 2003-CHRONIC 

NEUROTOXICITY-RAT 

(XDE-750)

mg/kg/day =

0, 5, 50, 500, 1000

Acceptable/Guideline

46235617 NOAEL (mg/kg/day):

1000

LOAEL (mg/kg/day):

not 

determined
Aminopyralid Registration Review Scoping Document

Page 24 of 27

870.7485 2004-METABOLISM 

AND 

PHARMACOKINETICSRAT (XDE-750)

mg/kg/day = 

Low dose: 50

High dose: 1000

Repeated low dose:

50 (unlabelled)

for 14 days, 50 (labelled)

on day 15

Acceptable/Guideline

46235807 Recovery after 168 hrs:

96% in low dose (urine50%, feces-43%, tissues0.1%, cage wash3%), 95% in high dose 

(urine-41%, feces-43%, 

tissues-1%, cage wash10%), and 95% in the 

repeated low dose (urine59%, feces-33%, tissues0.1%, cage wash-3%). 

XDE -750 represented

>96% of administered 

dose (AD) in urine and

100% AD in feces. Three 

unknown components (>

4%) found in urine were

also found in dose 

formulations.

870.7800 2010-

IMMUNOTOXICITYRAT (XDE-750)

mg/kg/day = 0 or 1038

Acceptable/Guideline

48364401 Systemic NOAEL 

(mg/kg/day):

Not determined

LOAEL (mg/kg/day):

1038 based on increased 

cecum size

Immunotoxicity NOAEL 

(mg/kg/day):

1038

LOAEL (mg/kg/day): 

Not determined

NonGuidelineXDE-750, 

Triisopropanolammonium 

salt,

Dissociation and 

Metabolism in Male 

Fischer 344 Rats

mg/kg/day=

50 or 96

46235833 14C-XDE-750 and 14CXDE-750-TIPA, when 

administered orally to 

rats, were bioequivalent 

in terms of absorption, 

distribution, metabolism, 

and excretion of the

amino-dichloro-picolinate 

portion of the molecule(s).
Aminopyralid Registration Review Scoping Document

Page 25 of 27

Attachment 5. Summary of Occupational Uses Based on Registered Labels for

Aminopyralid

Summary of Occupational Uses Based on Registered Labels for Aminopyralid.

EPA Reg. No. Registration Name

Formulation

% ai or ae Use site

62718-518 Aminopyralid Technical Liquid

95.3%

Wheat (including durum), permanent

grass pastures, rangeland, fallow 

cropland, conservation reserve areas, 

industrial sites, rights-of-way, nonirrigation ditch banks,

wildlife/natural areas, grazed areas

62719-519 Milestone Emulsifiable Concentrate

21.1%

Wheat (including durum), corn,

rangeland, permanent grass pastures 

(including grasses grown for hay), 

conservation reserve areas, noncropland industrial sites, rights-ofway, non-irrigation ditch banks, 

wildlife/natural areas, grazed areas

62719-525 Cleanwave Emulsifiable Concentrate

1.92%

Wheat (including durum)

62719-537 Milestone VM Emulsifiable Concentrate

21.1%

Non-cropland areas industrial sites,

rights-of-way, non-irrigation ditch 

banks, wildlife/natural areas, grazed 

areas

62719-572 Milestone VM Plus (alternate

name Capstone)

Emulsifiable Concentrate

1.15%

Rangeland, permanent grass pastures,

conservation reserve areas, forests, 

non-cropland areas industrial

sites, rights-of-way, fencerows, 

nonirrigation, ditch banks, 

wildlife/natural areas, grazed areas

FL070003 Cleanwave Emulsifiable Concentrate

1.92%

Grass, forage, hay, pastures
Aminopyralid Registration Review Scoping Document

Page 26 of 27

Attachment 6. International Residue Limit Status

Aminopyralid (005100; 11-8-2013)

Summary of US and International Tolerances and Maximum Residue Limits.

Residue Definition:

US Canada Mexico

1 Codex2

40 CFR 180.610 (a) (1)

Plants: Free and conjugated 

Aminopyralid (4-amino-3,6-dichloro-2-

pyridinecarboxylic acid)

Plants:4-amino-3,6-

dichloro-2-

pyridinecarboxylic 

acid (free and 

conjugated)

aminopyralid and its

conjugates that can be 

hydrolysed, expressed as 

aminopyralid.

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico

1 Codex2

Corn, field, forage 0.30

Corn, field, grain 0.20

Corn, field, stover 0.20

3 fodder (dry) of cereal

grains)

Grain, aspirated fractions 0.2

Grass, forage 25

Grass, hay 50 70 hay or fodder (dry) of

grasses

Wheat, bran 0.1 0.1 0.3 wheat bran, unprocessed

Wheat, forage 2.0

Wheat, grain 0.04 0.04 0.1

Wheat, hay 4.0 3 fodder (dry) of cereal

grains)

Wheat, straw 0.25 0.3 straw of cereal grains

US [40 CFR §180.610(a)(2)] Canada Mexico

1 Codex2

Livestock: Aminopyralid Livestock: 4-amino3,6-dichloro-2-

pyridinecarboxylic 

acid

Same as above

Commodity Tolerance (ppm) /Maximum Residue Limit (mg/kg)

US Canada Mexico

1 Codex2

Cattle, fat 0.02 0.02

Cattle, kidney 0.3 0.3 1

Cattle, meat 0.02

0.02 0.1 meat (from mammals

other than marine 

mammals)

Cattle, meat byproducts,

except kidney

0.02

0.02 0.05 edible offal

mammalian (except kidney)

Goat, fat 0.02 0.02

Goat, kidney 0.3 0.3 1

Goat, meat 0.02

0.02 0.1 meat (from mammals

other than marine 

mammals)
Aminopyralid Registration Review Scoping Document

Page 27 of 27

Summary of US and International Tolerances and Maximum Residue Limits.

Residue Definition:

US Canada Mexico

1 Codex2

Goat, meat byproducts, 

except kidney

0.02

0.02 0.05 edible offal

mammalian (except kidney)

Horse, fat 0.02 0.02

Horse, kidney 0.3 0.3

Horse, meat 0.02

0.02 0.1 meat (from mammals 

other than marine 

mammals)

Horse, meat byproducts, 

except kidney

0.02

0.02 0.05edible offal mammalian

(except kidney)

Milk 0.03 0.03

Sheep, fat 0.02 0.02

Sheep, kidney 0.3 0.3 1

Sheep, meat 0.02

0.02 0.1 meat (from mammals 

other than marine 

mammals)

Sheep, meat byproducts, 

except kidney

0.02

0.02 0.05 edible offal

mammalian (except kidney)

MRLs With No US Equivalent

Barley 0.1

Eggs 0.01 (*)

Kidney of pigs 1

Oats 0.1

Poultry meat 0.01 (*)

Poultry, edible offal of 0.01 (*)

Straw of cereal grains 0.3

Triticale 0.1

Completed: : M. Negussie; 08/29/13

1 Mexico adopts US tolerances and/or Codex MRLs for its export purposes.

2 * = absent at the limit of quantitation; Po = postharvest treatment, such as treatment of stored grains. PoP = 

processed postharvest treated commodity, such as processing of treated stored wheat. (fat) = to be measured on the 

fat portion of the sample. MRLs indicated as proposed have not been finalized by the CCPR and the CAC.