1 OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON

, D.C. 20460

August 27, 2014

PC Code: 117401, 117403, 117404, 117423

MEMORANDUM DP Barcode: 422307

SUBJECT: Addendum to the EFED Registration Revi ew Problem Formulation for Clopyralid Regarding Tier I Honey Bee Toxicity Testing

FROM: Elyssa Arnold, Biologist

Environmental Risk Branch II

Environmental Fate and Effects Division (7507P)

THROUGH: Brian Anderson, Branch Chief

Environmental Risk Branch II

Environmental Fate a nd Effects Division (7507P)

TO: Steven Snyderman, Chemical Reviewer Manager Avivah Jakob, Team Leader Patricia Parrott, Branch Chief Risk Management and Implementation Branch III

Pesticide Re-Evalua tion Division (7508P)

This addendum addresses changes to the data gaps identified in the preliminary problem formulation (USEPA, 2014b) and Preliminary Wo rk Plan (USEPA, 2014a) prepared in support of the Registration Review of clopyralid. Specific ally, this document identifies additional data gaps for clopyralid with respect to toxicity tests on honey bees ( Apis mellifera ).

Since the preliminary problem formulation was published, the Agency has issued guidance for assessing the potential risks of pesticides to bees and the data needed to support such assessments (USEPA et al. , 2014). The guidance document indicates that if exposure of bees to a pesticide is expected, a Tier I screening-level risk assessm ent is conducted. The Tier I

assessment is intended to be su fficiently conservative that chemicals that pass the screen are considered to represent a relatively low risk of a dverse effects to bees. Tier I toxicity data that are needed to complete screening-level risk assessments include a suite of laboratory-based

studies of individual bees and include the followi ng tests: acute contact to xicity data to adult honey bees (honey bees serving as a surrogate for a ll bee species), acute and chronic oral toxicity to adult honey bees, and acute and chronic oral toxicity to honey b ee larvae. If risk concerns are identified in the screening-level assessment, the assessment may be refined using data that2 further define exposure or through additional toxicity data from Tier II semi-field or Tier III fullfield studies conducted with whole colonies.

Clopyralid uses include aerial applications to multiple agricultural cr ops, pastures, rangeland, agricultural fallow/idleland/conservation reserve, forest trees, and nonagricultural uncultivated areas/soils where spray drift ma y land on blooming non-target plants and could result in residues in pollen and nectar. This pollen and nectar could then be trans ported to hives by adult forager bees. Additionally, clopyralid is highly persiste nt and, like other members of the picolinic acid family, is systemic and can move in both xyl em and phloem tissue. Although clopyralid uptake is primarily through the foliage, root uptake is al so possible. Therefore, clopyralid residues may be present in pollen and nectar ei ther through transport from leaf tis sues affected by spray drift or from root uptake from plants grown where clopyra lid was previously applied. Residues may also contaminate pollen and/or nectar through foliar applications. 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, exposur e at all bee life stages would be expected.

Since exposure of bees to clopyr alid residues is expected, Tier I honey bee laboratory toxicity data are needed to conduct the screening-level ri sk assessment. Acute contact and oral toxicity data are available that indicate clopyralid residue s are practically non-toxic to adult honey bees on an acute contact and oral exposure basis. However, no data are available to evaluate clopyralid’s toxicity from the oral exposure route to larval bees on an acute or chronic basis or to

adult bees on a chronic basis.

Therefore, the Environmental Fate and Effects Division (EFED) recommends requesting Tier I laboratory toxicity data on the technical grade active ingredient (TGAI) for acute and chronic oral toxicity for larval honey b ees and for chronic oral toxicity for adult honey bees in order to complete the risk assessment for bees, as is further detailed in the attached data rationale tables. Should the screening level risk assessment iden tify 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-f ield or full-field conditions ( e.g. OCSPP guideline 850.3040) that reduce uncertainty by characterizing clopyr alid’s effects at th e whole-colony level.

References

USEPA, 2014a. Clopyralid Preliminary Work Pla n. Registration Review: Initial Docket, Case

Number 7212. Pesticide Re-evaluation Divisi on, Office of Pesticide Programs, USEPA, Washington D.C. March 20, 2014.

USEPA, 2014b. EFED Registration Review Problem Formulation for Clopyralid.

Environmental Fate and Effect s Division, Office of Pesticide Programs, USEPA, Washington D.C. February 25, 2014. DP Barcode 416098.

USEPA, PMRA, and CDPR, 2014. Guidance for A ssessing Pesticide Risks to Bees. Office of Pesticide Programs, USEPA, Washington D.C. Health Canada Pest Management Regulatory Agency, Ottawa, ON, Canada. California Departme nt of Pesticide Regula tion, Sacramento, CA. June 23, 2014.3 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 eff ects of technical grade active ingredient (TGAI) on young adult honey bees from repeat exposure. Clopyralid uses include aerial applications to multiple agricultural crops, pastures, rangeland, agricultural fallow/id leland/conservation reserve, forest trees, and nonagricultural uncultivated areas/soils where spray drift may land on blooming non-target plants and result in residues in pollen and nectar (which could then be transported to the hive). Additionally, clopyralid is highly persistent and, like other member s of the picolinic acids family, is systemic and can move in both xylem and phloem tissues into pollen and/ or nectar. Although clopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, clopyralid residues may be present in pollen and nectar either through transport from leaf tissues af fected by spray drift or from root uptake from plants grown where clopyralid was previously applied. Resi dues 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 a ll bee life stages may occur.

Since the preliminary Problem Formulation and Prelim inary Work Plan for clopyralid were signed, the Agency finalized its guidance for assessing the risk of pesticides to bees (USEPA et al. , 2014). EPA now requires this study for all use sites where potential exposure to pollinators may occur. Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standa rdized guidelines for assessing effects from chronic (10- day) exposures to adult bees in the laboratory. Un til a guideline is finalized, a protocol should be submitted to the Agency for review before study in itiation. Clopyralid acid (PC 117403) technical grade active ingredient (TGAI) should be used in this st udy and will be assumed to be representative of the toxicity of the three registered clopyralid salts (PC 117401, PC 117404, PC 117423).

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 studi es are needed at the whole colony level.

These data are needed for risk asse ssments written in support of Registration Review as well as for future endangered species assessments. These data would allo w the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of picolinic acids-class chemicals. These data may help the Agency determine whether any mitigati on is needed. If the Registration Review and any future endangered species risk asse ssments are performed without these data, the Agency would have to assume that picolinic acids-class chemicals "may affe ct" insects, including bees and beneficial pollinators, directly (and threatened or endangered species from ot her taxa indirectly), and uses of clopyralid might

need to be restricted in areas where pollinators could be exposed.4 Guideline Number: Non-Guideline Study Title: Larval Honey Bee Acute and Chronic Oral Toxicity

Rationale for Requiring the Data

These studies are needed to evaluate the potential e ffects of technical grade active ingredient (TGAI) on honey bee larvae from repeat exposure. Clopyralid uses include aerial applications to multiple agricultural crops, pastures, rangeland, agricultural fallow/id leland/conservation reserve, forest trees, and nonagricultural uncultivated areas/soils where spray drift may land on blooming non-target plants and result in residues in pollen and nectar (which could then be transported to the hive). Additionally, clopyralid is highly persistent and, like other member s of the picolinic acids family, is systemic and can move in both xylem and phloem tissues into pollen and/ or nectar. Although clopyralid uptake is primarily through the foliage, root uptake is also possible. Therefore, clopyralid residues may be present in pollen and nectar either through transport from leaf tissues af fected by spray drift or from root uptake from plants grown where clopyralid was previously applied. Resi dues 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 a ll bee life stages may occur.

Since the preliminary Problem Formulation and Prelim inary Work Plan for clopyralid were signed, the Agency finalized its guidance for assessing the risk of pesticides to bees (USEPA et al. , 2014). EPA now requires these studies for all use sites where potentia l exposure to pollinators may occur. Although EPA has not developed a guideline for this study, the 21-da y larval toxicity study currently under development by OECD provides a draft guidance protocol for pote ntially assessing both the acute and chronic toxicity to developing brood (larvae and pupae) from repeat exposure to pesticides. Until a guideline is finalized, protocols should be submitted to the Agency for revi ew before study initiation. Registrants may choose 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. Clopyralid acid (PC 117403) technical grade active ingredient (TGAI) should be used in this study and will be assumed to be representative of the toxicity of the three registered clopyralid salts (PC 117401, PC 117404, PC 117423).

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 toxicity study provides data on the effects of technical grade active ingredient (TGAI) on developing bees from acute (short-term) and chr onic (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 asse ssments written in support of Registration Review as well as for future endangered species assessments. These data would allo w the Agency better characterize the potential for risk to insects (including beneficial pollinators) from the use of picolinic acids-class chemicals. These data may help the Agency determine whether any mitigati ons are needed. If the Registration Review and any future endangered species risk asse ssments are performed without these data, the Agency would have to assume that picolinic acids-class chemicals "may affe ct" insects, including bees and beneficial pollinators, directly (and threatened or endangered species from ot her taxa indirectly), and uses of clopyralid might

need to be restricted in areas wh ere pollinators could be exposed.