1 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

September 8, 2014 

PC Code: 046679 

MEMORANDUM DP Barcode: 422679

SUBJECT: Addendum to the EFED Registration Review Problem Formulation for 

Fenamidone Regarding Tier I Honey Bee Toxicity Testing 

TO: Christina Scheltema, Chemical Reviewer Manager 

 Avivah Jakob, Team Leader 

 Patricia Parrott, Branch Chief 

Risk Management and Implementation Branch III 

Pesticide Re-Evaluation Division (7508P) 

THROUGH: Dana Spatz, Branch Chief 

Environmental Risk Branch 3 

 Environmental Fate and Effects Division (7507P) 

FROM: Katherine Stebbins, Biologist 

Rosanna Louie-Juzwiak, Risk Assessment Process Leader 

 Environmental Risk Branch 3 

Environmental Fate and Effects Division (7507P) 

 

This addendum addresses changes to the data needs identified in the preliminary problem 

formulation (USEPA, 2014b) and Preliminary Work Plan (USEPA, 2014a) prepared in support 

of the Registration Review of fenamidone. Specifically, this document identifies additional data 

needs for fenamidone 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 assessment is conducted. The Tier I 

assessment is intended to be sufficiently conservative that chemicals that pass the screen are 

considered to represent a relatively low risk for potential adverse effects to bees. Tier I toxicity 

data that are needed to complete screening-level risk assessments include a suite of laboratorybased studies of individual bees and include the following tests: acute contact toxicity data to 

adult honey bees (honey bees serving as a surrogate for all bee species), acute and chronic oral 

toxicity to adult honey bees, and acute and chronic oral toxicity to honey bee larvae. If risk 
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concerns are identified in the screening-level assessment, the assessment may be refined using 

data that further define exposure or through additional toxicity data from Tier II semi-field or 

Tier III full-field studies conducted with whole colonies. 

Fenamidone uses include seed treatments, and foliar applications made by ground, chemigation, 

and aerial equipment to multiple agricultural crops, where residues in pollen and nectar can 

occur in both on the target field, as well as from spray drift that may land on blooming non-target 

plants. While fenamidone degrades somewhat rapidly in the environment (to degradates that 

appear to be less toxic), fenamidone has partial systemic activity with some movement in the 

plant, so it is uncertain how persistent fenamidone may remain within the plant. As such, 

residues may be present in pollen and nectar through transport from previous fenamidone 

applications. Residues can in turn be brought back to bee colonies by adult forager bees 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 fenamidone residues is expected, Tier I honey bee laboratory toxicity 

data are needed to conduct the screening-level risk assessment. Acute contact and oral toxicity 

data are available that indicate fenamidone residues are practically non-toxic to adult honey bees 

on an acute contact and oral exposure basis. However, no data are available to evaluate 

fenamidone’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 bees 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 identify that there are risk concerns to bees, more 

refined studies under semi-field or full-field conditions (e.g. OCSPP guideline 850.3040) that 

reduce uncertainty by characterizing fenamidone’s effects at the whole-colony level may be 

needed. 

References 

USEPA, 2014a. Fenamidone Preliminary Work Plan. Registration Review: Initial Docket, Case 

Number 7033. Pesticide Re-evaluation Division, Office of Pesticide Programs, USEPA, 

Washington D.C. March 6, 2014. 

USEPA, 2014b. Registration Review - Preliminary Problem Formulation for the Ecological Risk 

Assessment and Drinking Water Exposure Assessment to be conducted for Fenamidone. 

Environmental Fate and Effects Division, Office of Pesticide Programs, USEPA, Washington 

D.C. February 6, 2014. DP Barcode 417865. 

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, Sacramento, CA. 

June 23, 2014. 
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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 bees from repeat exposure. Fenamidone uses include seed treatments, and foliar applications 

made by ground, chemigation, and aerial equipment to multiple agricultural crops, where residues in 

pollen and nectar can occur in both on the target field, as well as from spray drift that may land on 

blooming non-target plants. While fenamidone degrades somewhat rapidly in the environment (to 

degradates that appear to be less toxic), fenamidone has partial systemic activity with some movement in 

the plant, so it is uncertain how persistent fenamidone may remain within the plant. As such, residues may 

be present in pollen and nectar either through transport from previous fenamidone applications. Residues 

can in turn be brought back to bee colonies by adult forager bees 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 the preliminary Problem Formulation and Preliminary Work Plan for fenamidone 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 standardized guidelines for assessing effects from chronic (10-

day) exposures to adult bees in the laboratory. Until a guideline is finalized, a protocol should be 

submitted to the Agency for review before study initiation. Fenamidone technical grade active ingredient 

(TGAI) should be used in this 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 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 needed for risk assessments written in support of Registration Review as well as for future 

endangered species assessments. These data would allow the Agency better characterize the potential for 

risk to insects (including beneficial pollinators) from the use of fenamidone and other imidazole-class 

chemicals. These data may help the Agency determine whether any mitigation is needed. If the 

Registration Review and any future endangered species risk assessments are performed without these 

data, the Agency would have to assume that fenamidone "may affect" insects, including bees and 

beneficial pollinators, directly (and threatened or endangered species from other taxa indirectly), and uses 

of fenamidone might need to be restricted in areas where pollinators could be exposed. 

 
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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 effects of technical grade active ingredient (TGAI) on 

honey bee larvae from repeat exposure. Fenamidone uses include seed treatments, and foliar applications 

made by ground, chemigation, and aerial equipment to multiple agricultural crops, where residues in 

pollen and nectar can occur in both on the target field, as well as from spray drift that may land on 

blooming non-target plants. While fenamidone degrades somewhat rapidly in the environment (to 

degradates that appear to be less toxic), fenamidone has partial systemic activity with some movement in 

the plant, so it is uncertain how persistent fenamidone may remain within the plant. As such, residues may 

be present in pollen and nectar either through transport from previous fenamidone applications. Residues 

can in turn be brought back to bee colonies by adult forager bees 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 the preliminary Problem Formulation and Preliminary Work Plan for fenamidone 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 potential exposure to pollinators may occur. Although EPA 

has not developed a guideline for this study, the 21-day larval toxicity study currently under development 

by OECD 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. Until a guideline is finalized, 

protocols should be submitted to the Agency for review 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. Fenamidone technical grade active ingredient (TGAI) should be used 

in this 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 toxicity study 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 Registration Review as well as for future 

endangered species assessments. These data would allow the Agency better characterize the potential for 

risk to insects (including beneficial pollinators) from the use of fenamidone and other imidazole-class 

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

Registration Review and any future endangered species risk assessments are performed without these 

data, the Agency would have to assume that fenamidone "may affect" insects, including bees and 

beneficial pollinators, directly (and threatened or endangered species from other taxa indirectly), and uses 

of fenamidone might need to be restricted in areas where pollinators could be exposed.