

                                                  



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: 

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

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.

                                                                        
                 











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  broad

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.





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 

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





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 pre- and/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





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 tolerance- level
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





residues are present at tolerance levels in all commodities for which
tolerances have been established, and that 100% of those crops are
treated.  DEEM™ 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 hand-
to-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





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 post-
application 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





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 non- dietary 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).





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 post- application 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





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 SENSOR- Pesticides 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 SENSOR- Pesticides, 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 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





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,”     HYPERLINK
http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf
)  (http://www.hss.ener    HYPERLINK
http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf
)  gy.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





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

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







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. VanAlstineNA4/7/2013Aminopyralid: 
Summary of Hazard and Science Policy Council

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

Requirement of a Subchronic Inhalation StudyD.
DotsonD36010010/22/2009Aminopyralid and Aminopyralid
Triisopropanolammonium (TIPA) Salt. Request to Add Uses on Field Corn to
MilestoneWater) Exposure and Risk Assessment for the Section 3

Registration on Field CornM. CollantesD3056725/24/2005Occupational and
Residential Exposure Risk Assessment for

Proposed Uses of AminopyralidZ. FigueroaD37049710/22/2009Aminopyralid
Occupational Exposure Assessment for the

Registration of Milestone Herbicide for Use on CornR.
BarisD3619267/24/2009Tier I Drinking Water Exposure Assessment for the
Section 3 New

Use of Triisopropanolamine Salt of Aminopyralid on Field Corn and

Field Corn Grown for EnsilageS. RecoreD41593911/12/2013Aminopyralid:
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

                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
          



                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                                                        
                                         Attachment 1.  Chemical
Identity Table









 Aminopyralid Nomenclature. Chemical structure NH2



Cl





OH Cl	N



OCommon nameAminopyralidCompany experimental nameXDE-750IUPAC
name4-amino-3,6-dichloropyridine-2-carboxylic acidCAS
name4-amino-3,6-dichloro-2-pyridinecarboxylic acidCAS registry
number150114-71-9Chemical structure

NH2	HO	CH3



Cl

H3C

.	N OH

Cl	N	OH	OH



O

CH3Common nameAminopyralid, triisopropanolammonium (TIPA) saltPC
Code005209Company experimental nameXDE-750 TIPA saltIUPAC
name4-amino-3,6-dichloropyridine-2-carboxylic acid -
(2RS,2′?RS,2″?RS)-1,1′?,1″?- nitrilotripropan-2-ol (1:1)CAS
name4-amino-3,6-dichloropyridine-2-carboxylic acid compound with
1,1′?,1″?- nitrilotris[2-propanol] (1:1)CAS registry
number566191-89-7End-use product (EP)Milestone

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

Satisfied870.1100   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 yesyes yes yes yes yes yes870.3100   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 noyes yes yes no1

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

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

870.3800   Reproduction
..................................................................yes
yes yesyes yes yes870.4100a Chronic Toxicity (rodent)
...............................................

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

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

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

870.4300   Chronic/Oncogenicity
....................................................yes no yes yes
yesyes yes yes yes yes870.5100   Mutagenicity—Gene Mutation -
bacterial ......................

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

870.5375   Mutagenicity—Structural Chromosomal Aberrations ....

870.5395   Mutagenicity—Mammalian Erythrocyte Micronucleus .

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

870.5915   Mutagenicity—In Vivo Sister Chromatid Exchangeyes yes yes
no no noyes 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



no2870.7485   General Metabolism
.......................................................

870.7600   Dermal Penetration
.........................................................yes noyes
yes870.7800  
Immunotoxicity…………………………………………yesyes1
Requirement fulfilled by 21/28 day study.

2 Requirement fulfilled by chronic neurotoxicity study.





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.









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

Risk Assessments.



Exposure/ Scenario



Point of

Departure

Uncertainty/ FQPA Safety FactorsRfD, PAD,

Level of Concern for Risk Assessment

Study and Toxicological Effects

Dermal Short- Term (1-30 days) Intermediate- Term (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) Intermediate- Term (1-6 months)



NOAEL=104 mg ae/kg/day



UFA= 10x

UFH=10x



Occupational

LOC for MOE

= 100Developmental 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 = triisopropanolammonium salt of aminopyralid.

                                                                



                                                               
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





 

Subchronic, Chronic, and Other Toxicity ProfileGDLNStudy TypeDose
LevelsMRIDResults

870.3100

2001-13 WEEK FEEDING-RAT (XDE-

750) 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 (GF-

871)‡

XDE-750 TIPA*

mg/kg/day=

0, 192, 500, 1000



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 (XDE-

750)

%=0, 0.15, 0.75, 3.0



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).



 

870.3200

2002-28 DAY DERMAL- RAT (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



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



 

870.3700

2004- DEVELOPMENTAL TOX-RABBIT (GF-871)‡

XDE-750 TIPA*

mg/kg/day=

0, 200, 500, 1000



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 FEEDING- DOGS

(XDE-750)

% =0, 0.03, 0.30, 3.0



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 CARCINOGENICITY- MICE (XDE-750)

mg/kg/day =

0, 50, 250, 1000



Acceptable/Guideline

46235628

NOAEL (mg/kg/day): M=1000

LOAEL (mg/kg/day):

not determined.



 

870.4300

2004-2 YEAR TOXICITY/ CARCINOGENICITY- RAT

(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 

Acceptable/Guideline

46235636

Negative

870.5100

2004-BACTERIAL REVERSE MUTATION ASSAY (GF-871)

XDE TIPA *

33, 100, 333, 1000, 3330,

5000 

Acceptable/Guideline

46235637

Negative

870.5300

2004-IN VITRO MAMMALIAN CELL GENE MUTATION TEST

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

1000, 1500, 2070 1000, 2000, 4000 

Acceptable/Guideline

46235801

Negative

870.5300

2004-IN VITRO MAMMALIAN CELL GENE MUTATION TEST (GF-871)

XDE TIPA *

250, 500, 1000, 2000,

4000 

Acceptable/Guideline

46235804

Negative



 

870.5375

2002-IN VITRO MAMMALIAN CELL CHROMOSOME ABERRATION TEST (XDE-750)

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

1035, 2070 125, 250, 500, 750, 1000,

1400, 1700, 2070 μ?g/mL without metabolic activation and 0, 62.5,

125, 500, 1000 or 2070 μ?g/mL with metabolic activation (2nd assay);

400, 600, 800, 1000,

1200, 1400, 1600, 1700,

1800, 2070 μ?g/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 

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



 

870.7485

2004-METABOLISM AND PHARMACOKINETICS- RAT (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 (urine-50%, feces-43%, tissues-0.1%, cage wash-

3%), 95% in high dose (urine-41%, feces-43%, tissues-1%, cage wash-

10%), and 95% in the repeated low dose (urine-

59%, feces-33%, tissues-

0.1%, 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- IMMUNOTOXICITY- RAT (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

Non- Guideline

XDE-750, Triisopropanolammonium salt,

Dissociation and Metabolism in Male Fischer 344 Rats

mg/kg/day=

50 or 96

46235833

14C-XDE-750 and 14C- XDE-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).





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 NameFormulation

% ai or ae

Use site62718-518Aminopyralid TechnicalLiquid

95.3%Wheat (including durum), permanent

grass pastures, rangeland, fallow cropland, conservation reserve areas,
industrial sites, rights-of-way, non- irrigation ditch banks,

wildlife/natural areas, grazed areas62719-519MilestoneEmulsifiable
Concentrate

21.1%Wheat (including durum), corn,

rangeland, permanent grass pastures (including grasses grown for hay),
conservation reserve areas, non- cropland industrial sites, rights-of-
way, non-irrigation ditch banks, wildlife/natural areas, grazed
areas62719-525CleanwaveEmulsifiable Concentrate

1.92%Wheat (including durum)62719-537Milestone VMEmulsifiable
Concentrate

21.1%Non-cropland areas industrial sites,

rights-of-way, non-irrigation ditch banks, wildlife/natural areas,
grazed areas62719-572Milestone 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 areasFL070003CleanwaveEmulsifiable
Concentrate

1.92%Grass, forage, hay, pastures



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 Mexico1 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.CommodityTolerance (ppm) /Maximum Residue Limit
(mg/kg)USCanadaMexico1Codex2Corn, field, forage0.30Corn, field,
grain0.20

Corn, field, stover

0.203 fodder (dry) of cereal

grains)Grain, aspirated fractions0.2Grass, forage25

Grass, hay

5070 hay or fodder (dry) of

grassesWheat, bran0.10.10.3 wheat bran, unprocessedWheat,
forage2.0Wheat, grain0.040.040.1

Wheat, hay

4.03 fodder (dry) of cereal

grains)Wheat, straw0.250.3 straw of cereal grainsUS [40 CFR
3,6-dichloro-2- pyridinecarboxylic acidSame as above

CommodityTolerance (ppm) /Maximum Residue Limit
(mg/kg)USCanadaMexico1Codex2Cattle, fat0.020.02Cattle, kidney0.30.31

Cattle, meat

0.020.020.1 meat (from mammals

other than marine mammals)Cattle, meat byproducts,

except kidney

0.020.020.05 edible offal

mammalian (except kidney)Goat, fat0.020.02Goat, kidney0.30.31

Goat, meat

0.020.020.1 meat (from mammals

other than marine mammals)



 Summary of US and International Tolerances and Maximum Residue Limits.
Residue Definition: US Canada Mexico1 Codex2 Goat, meat byproducts,
except kidney 

0.020.020.05 edible offal

mammalian (except kidney)Horse, fat0.020.02Horse, kidney0.30.3

Horse, meat

0.020.020.1 meat (from mammals other than marine mammals)Horse, meat
byproducts, except kidney

0.020.020.05edible offal mammalian

(except kidney)Milk0.030.03Sheep, fat0.020.02Sheep, kidney0.30.31

Sheep, meat

0.020.020.1 meat (from mammals other than marine mammals)Sheep, meat
byproducts, except kidney

0.020.020.05 edible offal

mammalian (except kidney)MRLs With No US EquivalentBarley0.1Eggs0.01
(*)Kidney of pigs1Oats0.1Poultry meat0.01 (*)Poultry, edible offal
of0.01 (*)Straw of cereal grains0.3Triticale0.1Completed: : M. Negussie;
08/29/131 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.

