OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION 

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

September 3 , 2014

PC Code: 00510 0

MEMORANDUM DP Barcode: D 422 421

SUBJECT: Addendum to the Problem Formulation for the Environmental Fate and

Ecological Risk, Endangered Species, and Drinking Water Assessments in Support of the Registration Review of Aminopyralid Regarding Tier I Honey Bee Toxicity T esting

FROM: Edward Scollon, PhD, Toxicologist

Environmental Risk Branch I V Environmental Fate and Effects Division ( 7507P)

REVIEWED

BY: T h om as Steeger, PhD, Senior Scie nce Advisor

Environmental Risk Branch I V

Environmental Fate and Effects Division (7507P)

THROUGH: Sarah Winfield

, Acting Branch Chief

Environmental Risk Branch I V Environmental Fate and Effects Division ( 7507P)

TO: Veronica Dutch , Chemical Reviewer Manager

Lee Tanner

, Acting Team Leader Linda Arrington , Branch Chief Risk Management and Implementation Branch V

Pesticide Re

- Evaluation Division (7508P)

This addendum addresses changes to the registration review data gaps identified in the preliminary problem formulation 1 

### and Final Work Plan (FWP 2 

### ) written in support of the Registration Review of aminopyralid . Specifically, this document identifies additional data gaps

for aminopyralid with respect to toxicity tests on honey bees ( Apis mellifera )

.

1 USEPA. 2014. Regi stration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water E xposure Assessments for Aminopyralid, Potassium salt of Aminopyralid, and Triisopropanolamine Salt of Aminopyralid. DP Barcode D415743. http://www.regulations.go v/#!documentDetail;D=EPA

- HQ

- OPP

- 2013

- 0749

- 0011

2 USEPA. 2014 Aminopyralid Final Preliminary Work Plan. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2013

- 0749

- 0012

### Since the preliminary problem formulation was completed , the Agency has issued guidance 3 

### for

assessing the potential risks of pesticides to bees and the data needed to support such

assessments. Th e guidance document indicates that if exposure of bees to a pesticide is expected, a Tier I screening

- level risk assessment should be conducted . The Tier I assessment is intended to be sufficiently conservative such that chemicals which pass the screen represent a relatively low risk of adverse effects to bees. Tier I toxicity data that are generally needed to complete screening

- lev el risk assessments include a suite of laboratory

- based studies of individual bees and consists of the following tests: acute contact toxicity data to adult honey

bees (honey bees serving as a surrogate for other Apis and non

- Apis bees and other insect

po llinators ) , acute and chronic oral toxicity to adult honey bees

, and acute and chronic oral toxicity to honey bee larvae

. If risk concerns are identified in the screening

- level assessment, the

assessment may be refined using data that further define expos ure or through additional data including Tier II semi

- field or full

- field toxicity tests conducted with whole colonies

.

Aminopyralid is registered for use on a variety of agricultural, forest, commercial, and residential areas and may be applied via aircr aft, ground sprayer, hand

- held sprayer, and boom sprayer. Aminopyralid may also be applied to forest plantings via broadcast, high volume spray, spot treatment, stump treatment, girdle treatment, frill treatment, tree wound treatment, and tree injection. These use patterns may result in exposure to blooming non

- target plants and could result in residues in pollen and nectar (which could then be transported to the hive by adult forager bees ). Additionally, aminopyralid is highly persistent and, like other members of the picolinic acid family, is systemic and can move in both xylem and phloem tissue . Although aminopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, in addition to direct contamination of pollen and/or nectar through foliar applications, aminopyralid residues may be translocated to pollen and nectar either through transport from leaf tissues affected by spray drift or from root uptake in plants grown where aminopyralid was previously applied. Residues ca n in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life stages would be expected.

Since exposure of bees to aminopyralid residues is expected, Tier I honey bee laboratory toxicity

data are needed to conduct the screening

- level risk assessment. Acute contact toxicity data are available that indicate aminopyralid residues are practically non

- toxic to honey bees on an acute

contact exposure basis. However, no data are available t o evaluate aminopyralid’s oral toxicity to
either adult or larval bees from either acute or chronic exposure

.

Therefore, the Agency is requesting Tier I laboratory toxicity data on the technical grade active ingredient (TGAI) for acute and chronic oral toxicity for both adult and larval honey bees in order to comp l ete the risk assessment for bees

, as is further detailed in the attached data rationale

tables. Should the screenin g level risk assessment identify that there are risk concerns to bees, mitigation measures may need to be considered or the registrant may be required to conduct

more refined studies under semi

- field or full

- field conditions ( e.g. 850.3040 4 

### guideline studi es) that reduce uncertainty by characterizing aminopyralid’s effects at the whole

- colony level.

3 USEPA et al .. 2014. Guidance for Assessing Pesticide Risks to Bees. http://www2.epa.gov/sites/production/files/2014

- 06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf

4 USEPA. 2012. Ecological Effects Test Guidelines OCSPP 850.3040: Field Testing for Pollinators. Office of Chemical Safety an d Pollution Prevention (7101). EPA 712

- C

- 017 January 2012. file:///C:/Users/tsteeger/Downloads/EPA

- HQ

- OPPT

- 2009

- 0154

- 0018%20(3).pdf

### References

USEPA, 201 4

. Preliminary Problem Formulation for the Environmental Fate and Ecological Risk, Endangered Species, and Human Health Drinking Water E xposure for Aminopyralid, Potassium salt of Aminopyralid, and Triisopropanolamine Salt of Aminopyralid . Environmental Fate and Effects Division, Office of Pesticide Programs, USEPA, Washington D.C. February 12,

2014

. D41 5743.

USEPA, PMRA and CDPR, 2014. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management Regulatory Agency, Ottawa, ON, Canada. California Department of Pesticide Regulation, Sacramen to, CA. June 23, 2014.Guideline Number: Non

- Guideline

Study Title: Adult Honey Bee Acute Oral Toxicity

Rationale for Requiring the Data

This study is needed to evaluate potential effects to adult honey bees from acute oral exposure to technical grade active ingredient (TGAI)

. Aminopyralid is registered for use on a variety of agricultural, forest, commercial, and residential areas and may be applied via aircraft, ground sprayer, hand

- held sprayer, and boom sprayer. Aminopyralid may also be appl ied to forest plantings via broadcast, high volume spray, spot treatment, stump treatment, girdle treatment, frill treatment, tree wound treatment, and tree injection. Some of these uses may result in exposure to blooming non

- target plants and could resul t in residues in pollen and nectar (which could then be transported to the hive). Additionally, aminopyralid is highly persistent and

, like other members of the picolinic acid family

, is systemic and can move in both xylem and phloem tissues into pollen and/or nectar and represent a route of exposure to bees . Although aminopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, aminopyralid residues may be present in pollen and nectar either through transport from leaf tissues affected by spray drift or from root uptake in plants grown where aminopyralid was previously applied. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eg gs, larvae and pupae) may be exposed. Therefore, exposure at all bee life stages would be expected.

Since the preliminary Problem Formulation 5 was completed , the Agency finalize d its guidance 6 for

assess ing the risk of pesticides to bees . EPA now requires this study for all use sites where potential exposure to pollinators may occur. A lthough EPA has not developed a guideline for this study, the Organization for Economic Cooperation and Development (OECD) has developed a formal test gui deline for an acute oral toxicity study with adult honey bees (OECD TG213 7 ) that may be used to assess the

acute oral toxicity for adult bees.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision

- making?

The acute oral toxicity data are used in conjunction with acute contact data obtained through OCSPP

850.3020 8 to estimate the acute toxicity of technical grade a ctive ingredient (TGAI) to individual young adult honey bees. The studies also provide slopes for the dose

- response curves that can in turn be used for estimating the likelihood of individual effects

, and sublethal effects observed in the study will be us ed to further characterize effects observed following a single exposure to TGAI . Data obtained from this study will be used in estimating acute risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for risk assessments written in support of R egistration R eview risk assessment as well as for future endangered species assessments. The data w ould allow the Agency better characterize

5 USEPA. 2014. Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Speci es, and Human Health Drinking Water Exposure Assessments for Aminopyralid, Potassium salt of Aminopyralid, and Triisopropanolamine Salt of Aminopyralid. DP Barcode D415743. http://www.regulations. gov/#!documentDetail;D=EPA

- HQ

- OPP

- 2013

- 0749

- 0011

6 USEPA et al .. 2014. Guidance for Assessing Pesticide Risks to Bees. http://www2.epa.gov/sites/production/files/2014

- 06/documents/pollinator_risk_assessment_guidance_06_19_14.pdf

7 OECD. 1998. OECD Guidelines for the Testing of Chemicals Honeybees, Acute Oral Toxicity Test. OECD/OCDE 213 Adopted 21 st September 1998. http://www.oecd

ilibrary.org/docserver/download/9721301e.pdf?expires=1408726996&id=id&accname=guest&c hecksum=29D93505197D8AB40C63E8F0DFB4

47D0

8 USEPA. 2012. Ecological Effects Test Guidelines OCSPP 850.3020: Honey Bee Acute Contact Toxicity Test. Office of Chemical Safety and Pollution Prevention (7101). EPA

- 712

- C

- 019. January 2012. http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0154

- 0016Guideline Number: Non

- Guideline

Study Title: Adult Honey Bee Acute Oral Toxicity

Rationale for Requiring the Data

the potential for risk to insects (including beneficial pollinators) from the use of picolinic acids

- class

chemicals. Th ese data may help the Agency determine whether any mitigations are needed. If the

R egistrati on R eview and any future endangered species risk assessments are performed without these data, the Agency would have to assume that picolinic acids

- class chemicals "may affect" insects, including bees and beneficial pollinators, directly (and endangered sp ecies from other taxa indirectly), and uses of aminopyralid might need to be restricted in areas where pollinators could be exposed.

Guideline Number: Non

- Guideline Study Title: Adult Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

This study is needed to evaluate the potential effects of technical grade active ingredient (TGAI) on young adult honey bee s from repeat exposure

. Aminopyralid is registered for use on a variety of agricultural, forest, commercial, and residential areas a nd may be applied via aircraft, ground sprayer, hand

- held sprayer, and boom sprayer. Aminopyralid may also be applied to forest plantings via broadcast, high volume spray, spot treatment, stump treatment, girdle treatment, frill treatment, tree wound trea tment, and tree injection. Some of these uses may result in exposure to blooming non

- target plants and could result in residues in pollen and nectar (which could then be transported to the hive). Additionally, aminopyralid is highly persistent and

, like other members of the picolinic acid family

, is systemic and can be translocated to pollen and/or nectar via transport through both xylem and phloem tissues of plants

. Although aminopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, aminopyralid residues may be present in pollen and nectar either through transport from leaf tissues affected by spray drift or from root uptake in plants grown where amino pyralid was previously applied. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life stages

may occur

.

Since the preliminary Problem Formulation 9 was completed , the Agency finalize d its guidance 10 for

asse ssing risk s to bees . EPA now requires this study for all use sites where potential exposure to pollinators may occur. Although EPA has not developed a gu ideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standardized guidelines for assessing effects from chronic (10

- day) exposures to adult bees in the laboratory.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision

- making?

The 10

- day toxicity study with young adult bees provides data that will be used in estimating chronic risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are need ed for risk assessments written in support of R egistration R eview as well as for future endangered species assessments. The se data would allow the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of picolinic acids

- class chemicals. Th e s e data may help the Agency determine whether any mitigations are needed. If the R egistration R eview and any future endangered species risk assessments are performed without these data, the Agency would have to

9 Ibid USEPA 2014.

10 Ibid USEPA et al . 2014.Guideline Number: Non

- Guideline

Study Title: Adult Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

assu me that picolinic acids

- class chemicals "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of aminopyralid might need to be restricted in areas where pollinators could be exposed.

Guideline Number: Non

- Guideline Study Title: Larval Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

This study is needed to evaluate the potential effects of technical grade active ingredient (TGAI) honey

bee larvae from repeat exposure

. Aminopyralid is registered for use on a variety of agricultural, forest, commercial, and residential areas and may be applied via aircraft, ground sprayer, hand

- held sprayer, and boom sprayer. Aminopyralid may also be applie d to forest plantings via broadcast, high volume spray, spot treatment, stump treatment, girdle treatment, frill treatment, tree wound treatment, and tree injection. Some of these uses may result in exposure to blooming non

- target plants and could result in residues in pollen and nectar (which could then be transported to the hive). Additionally, aminopyralid is highly persistent and

, like other members of the picolinic acid family

, is systemic and can be translocated to pollen and/or nectar via transport through both xylem and phloem tissues of plants . Although aminopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, aminopyralid residues may be present in pollen and nectar either through transport from leaf tissues affected by spray drift or from root uptake in plants grown where aminopyralid was previously applied. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, larvae and pupae) may be exposed. Therefore, exposure at all bee life stages

may occur

.

Since the preliminary Problem Formulation 11 was completed , the Agency finalize d its guidance 12 for

asse ssing risk s to bees . EPA now requires this study for all use sites where potential exposure to pollinators may occur. A lthough EPA has not developed a guideline for this study, the 21

- day larval toxicity study currently under development by OECD 13 provides a draft guidance protocol for potentially assessing both the acute and chronic toxicity to developing brood (larvae and pupae) from repeat exposure to pesticides.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s futur e decision

- making?

The 21

- day toxicity stud y provides data on the effects of technical grade active ingredient (TGAI) on developing bees from acute (short

- term) and chronic (longer term) exposure and will be used for estimating

risk to individual (solitary) bees as well as bee colonies (social bees). Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for risk assessments written in support of R egistration R eview as well as for future endangered species assessments. The se data would allow the Agency better characterize the potential for

11 Ibid USEPA 2014.

12 Ibid USEPA et al . 2014.

13 OECD. 2013. OECD Draft Guidance Document Honey Bee ( Apis mellifera ) Larval Toxicity Test, Repeated Exposure. Revision of June 2013 draft GD, 25 November 2013. http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013.pdfGuideline Number: Non

- Guideline

Study Title: Larval Honey Bee Chronic Oral Toxicity

Rationale for Requiring the Data

risk to insects (including beneficial pollinators) from the use of picolin ic acids

- class chemicals. Th e s e data may help the Agency determine whether any mitigations are needed. If the R egistration R eview and any future endangered species risk assessments are performed without these data, the Agency would have to assume that pic olinic acids

- class chemicals "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of aminopyralid might need to be restricted in areas where pollinators could be exposed.Guideline Number: Non

- Guideline

Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity

Rationale for Requiring the Data

This study is needed for the assessment to evaluate risks to honey bees if the registered uses will result in bee exposure. Aminopyralid is registered for use on a variety of agricultural, forest, commercial, and residential areas and may be applied via a ircraft, ground sprayer, hand

- held sprayer, and boom sprayer. Aminopyralid may also be applied to forest plantings via broadcast, high volume spray, spot treatment, stump treatment, girdle treatment, frill treatment, tree wound treatment, and tree injecti on. Some of these uses may result in exposure to blooming non

- target plants and could result in residues in pollen and nectar (which could then be transported to the hive). Additionally, aminopyralid is highly persistent and

, like other members of the pi colinic acid family

, is systemic and can move in both xylem and phloem. Although aminopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, aminopyralid residues may be present in pollen and nectar either through trans port from leaf tissues affected by spray drift or from root uptake in plants grown where aminopyralid was previously applied. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and developing brood ( i.e. , eggs, la rvae and pupae) may be exposed. Therefore, exposure at all bee life stages would be expected.

Since the Problem Formulation was completed , the Agency finalize d its framework to assess risk to pollinators (USEPA, 2014). EPA now requires this study for all use sites where potential exposure to pollinators may occur. Registrants may request a waiver of the study if use practices significantly restrict exposure of the pesticide to bees.

Although EPA has not developed a guideline for this study, the 21

- day larval toxicity study currently under development by OECD provides both acute and chronic oral toxicity data on developing bee brood and (when this guidance is finalized) may be used to satisfy the requirement for both acute and chronic oral toxicity to honey bee larvae. Registrants are at liberty though to submit a separate acute (single dose) larval toxicity study following OECD TG 237 as well as the 21

- day repeat dose chronic toxicity study.

Practical Utility of the Data

How will the data be used and how could the data impact the Agency’s future decision

- making?

The 21

- day larval toxicity study under development by OECD provides both acute and chronic toxicity data on developing bee brood and will yield a median lethal dose (LD 50 ) for assessing acute toxicity during the early part of the study as well as a 21

- day no

- observed adverse effect level (NOAEL) and

lowest

- observed adverse effect level (LOAEL) for assessing chronic effects . Effects on survival and development (adult bee emergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to individual brood. Risk estimates based on these data will be considered along

with other lines of eviden ce to determine whether higher

- tier studies are needed at the whole colony level.

These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency better characterize the pot ential for risk to insects (including beneficial pollinators) from the use of picolinic acids

- class chemicals. This data may help the Agency determine whether any mitigations are needed. If the registration review and any future endangered species risk as sessments are performed without these data, the Agency would have to assume that picolinic acids

- class chemicals "may affect" insects, including bees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of amin opyralid might need to be restricted in areas where pollinators could be exposed.