Docket Number: EPA-HQ-OPP-2011-0920

www.regulations.gov

Dinotefuran Final Work Plan

Registration Review

June 2012

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Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for 

the registration review of dinotefuran. The FWP includes the expected registration review 

timeline. The FWP also addresses any public comments received on the Preliminary Work Plan

(PWP) in the Summary Document, which was posted in the dinotefuran registration review 

docket (EPA-HQ-OPP-2011-0920). The Summary Document, dated December 14, 2011, 

provided information on what EPA knows about the pesticide and what additional risk analyses 

and data or information the Agency believes are needed to make a registration review decision. 

The Agency’s implementation of the registration review program requires review of each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices occur over time. The registration review 

program is intended to make sure that, as the ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/.

Dinotefuran is a broad-spectrum, second generation neonicotinoid insecticide that is currently

registered for agricultural use on a variety of food and feed commodities, including: brassica;

leafy and fruiting vegetables; grapes; curcurbits; pineapple; and nut trees. It is also registered for

non-agricultural use in residential and commercial settings, including: forest trees; ornamentals

(plants, lawns and turf); pets and pet premises; and commercial, institutional, and industrial 

buildings. Dinotefuran was first registered for use in the United States in 2004 and, therefore,

was not subject to reregistration under FIFRA. There are currently thirty-seven FIFRA Section 3 

product registrations, and sixteen Section 24(c) Special Local Need (SLN) registrations for use 

on turf, ornamental, and vegetable transplants in enclosed structures.

Updates Since the Summary Document was Issued:

As mentioned in the dinotefuran PWP, a fur dislodgeability study (Guideline 875.2300) was 

previously required as a condition of registration for dinotefuran dog and cat spot-on products 

(due January 26, 2013). In addition, this study is required in support of registration review. 

After the dinotefuran PWP was issued, a fur dislodgeability study was submitted to the Agency 

and is currently in review. EPA expects to finish its review of this study prior to issuance of the 

registration review data call-in (DCI). Once the study has been reviewed and classified, EPA 

will determine whether or not it should be included in the registration review DCI.

Comments Received on the Preliminary Work Plan:

The dinotefuran docket was open for a 60-day comment period, beginning December 21, 2011

and closing February 21, 2012. During the 60-day comment period, one public comment was 

received regarding dinotefuran. This comment is addressed below and did not result in changes

to the work plan, data requirements, or timeline as described in the dinotefuran Summary 

Document and PWP. Three comments relevant to another neonicotinoid registration review 
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case, clothianidin, were inadvertently posted to the dinotefuran docket and are not addressed in 

this FWP. For further information regarding these comments and the Agency’s response, refer to 

the clothianidin docket (EPA-HQ-OPP-2011-0865).

Comment:

Jeff Durand of Durand Farms in St. Martinville, Louisiana commented that dinotefuran is very 

important to southern Louisiana’s rice crop for controlling rice stinkbugs. In his comments, Mr. 

Durand noted the following: (1) dinotefuran was very effective in controlling rice stinkbugs on 

their 2011 rice crop; (2) he did not observe injury to crawfish which were harvested from his

ponds located close to the dinotefuran-treated rice crops; and, (3) he believes that dinotefuran 

will play a significant part in managing pest resistance because it is a different class of chemistry 

and can be rotated with pyrethroids, in some areas. 

Agency Response:

The Agency thanks Mr. Durand for his comment and will consider this information during 

registration review.

Risk Assessment and Data Needs:

The Agency will require data for use in conducting a comprehensive ecological risk assessment, 

including an endangered species risk assessment, for all uses of dinotefuran. The Agency will 

also require data for use in conducting an updated human health risk assessment for registration 

review. A summary of the issues relevant to the registration review of dinotefuran is given 

below.

Ecological Risk:

• The most recent comprehensive ecological risk assessment for dinotefuran was 

completed in 2004 in support of its initial registration for use on leafy vegetables, turf 

grasses, and various residential uses. All subsequent ecological risk assessments have 

relied on the conclusions of this assessment.

• The most recent ecological risk assessment in support of FIFRA Section 3 registrations 

was completed on May 3, 2011 for forestry uses (Christmas trees, trees in plantations, 

reforestation nurseries, forests, and woodland areas). In June 2011, an ecological risk 

assessment was completed in support of FIFRA Section 18 emergency exemptions for

use on commercial pome and stone fruit to control the brown marmorated stink bug 

during the 2011 growing season; these Section 18 exemptions expired on October 15,

2011.

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for dinotefuran. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether dinotefuran use has “no 

effect” or “may affect” federally listed threatened or endangered species (listed species) 

or their designated critical habitats. When an assessment concludes that a pesticide’s use 
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“may affect” a listed species or its designated critical habitat, the Agency will consult 

with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the 

Services), as appropriate.

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the Services regarding the effects of over 

350 pesticides, including dinotefuran, on over 200 endangered and threatened species 

throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 

11-00293 (N.D.Cal.).

• The Agency is requiring the following data for use in conducting a comprehensive 

ecological risk assessment, including an endangered species assessment, for the 

registration review of dinotefuran:

o GDLN 835.4400 – Anaerobic Aquatic Metabolism

o GDLN 850.1350 – Estuarine/Marine Invertebrates – Life Cycle Test (mysid)

o GDLN 850.2100 – Acute Avian Oral Toxicity (passerine)

o GDLN 850.3040 – Field Testing for Pollinators

o Non-GDLN – Pollinator Larval Toxicity Study (Special Study)

o Non-GDLN – Laboratory Pollinator Chronic Feeding Study (Special Study)

o Non-GDLN – Residues in Pollen and Nectar/Field Residue Analysis (Special 

Study)

• The EPA is aware of registrant-submitted studies and other open literature studies 

regarding the potential effects of neonicotinoid insecticides on insect pollinators and 

specifically on honey bees. The Agency is also aware of concerns regarding the potential 

association between the use of neonicotinoids and honey bee losses characterized as 

Colony Collapse Disorder (CCD) and the broader phenomenon of declining honey bee 

health globally. While a number of factors (e.g., nutrition, habitat loss, disease, parasites, 

bee management practices, and pesticides) have been hypothesized, no single factor has 

yet to be identified as the “cause” of declines. 

As part of the review process, EPA examines the effects of chemicals on bees based on 

both laboratory and when appropriate, field studies to determine whether individual bees 

and entire bee colonies may be affected by the use of a compound and to support risk 

mitigation decisions. EPA is currently revising its process for assessing pesticide risks to 

bees to reflect advancements in the state of the science that underlie bee exposure and 

effects assessments. Interim guidance (USEPA 20111

 1 USEPA. 2011. Pesticides: Science and Policy. Interim Guidance on Honey Bee Data Requirements. 

) on factors to consider when 

evaluating exposure and effects to bees is available to ecological risk assessors. In 2012, 

EPA will present to a FIFRA Scientific Advisory Panel (SAP) a proposed process for 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biology_tech_team/honeybee

_data_interim_guidance.htm
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quantifying risks to honeybees and identifying exposure and effect studies needed to 

inform that process. Based on input from the SAP, EPA will incorporate its revised 

assessment process to quantify risks to bees in a similar manner as that used to evaluate 

risks to other taxa. 

As EPA’s understanding of the science evolves, its need for data and its evaluation of 

those data will evolve as well. Therefore, as with all taxa, EPA reserves the right to 

require additional data it deems necessary to inform its understanding of potential 

ecological risks and support its associated risk management decisions. Additional data 

requirements for pollinators may extend beyond those identified in problem formulations 

and preliminary work plans written in support of the registration review process. 

• The Agency has also identified additional information needs (i.e., independent laboratory 

validation, purity of test compounds, missing study information) regarding several 

existing studies, which are described in “Appendix C” of the Problem Formulation; and, 

is interested in receiving information to supplement these existing data. This 

information, though not considered data gaps, will be useful in refining potential 

ecological risks and reducing the use of default assumptions for the registration review of 

dinotefuran.

• Please refer to the December 13, 2011 document, Registration Review – Preliminary 

Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, 

and Drinking Water Assessments for Dinotefuran, located in docket EPA-HQ-OPP-2011-

0920 for a detailed discussion of the risk assessment and data needs.

Human Health Risk:

• The most recent human health risk assessment for dietary, residential and aggregate 

exposure of dinotefuran was conducted in May of 2011 in support of the FIFRA Section 

18 emergency exemptions for use on pome and stone fruits. The most recent human 

health risk assessment for occupational exposure (in support of FIFRA Section 3 

registrations) was conducted in February 2011 for forestry uses.

• The existing human health toxicity database is sufficient and the Agency will not require 

additional toxicity data in support of registration review. However, the Agency will reevaluate toxicological endpoints (points of departure) and uncertainty factors, and update

the human health toxicity profile at the time of the risk assessment, as needed.

• During registration review, a revised dietary (food and drinking water) risk assessment 

may be needed to incorporate refined estimated drinking water concentrations (EDWCs), 

updated food residues and Pesticide Data Program (PDP) data, and any changes to 

toxicological points of departure or uncertainty factors.

• The residential and occupational exposure databases for dinotefuran are adequate with 

the exception of the following study, which is needed for use in this registration review. 
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This study will be used to assess exposure of dinotefuran to humans handling pets treated 

with spot-on products.

o GDLN 875.2300 - Fur Dislodgeability 

This study has been identified previously as a conditional requirement for the registration 

of dinotefuran dog and cat spot-on products.

• The Agency will revise residential and occupational handler and post-application risk 

assessments using standards and exposure and/or risk assessment policies/procedures that 

are in place at the time of the risk assessment, including any changes to the points of 

departure or the uncertainty factors.

• The Agency will be revising the aggregate risk assessment using standards and exposure 

and/or risk assessment policies/procedures that are in place at the time of the risk 

assessment; including any changes to the points of departure or the uncertainty factors; 

and potential changes to dietary exposure estimates from food and/or drinking water

(e.g., updated EDWCs).

• Residential and occupational bystander inhalation exposure may occur as a result of 

dinotefuran aerial applications and/or off-site transport (e.g., spray drift or volatilization). 

The Agency is examining its policies and procedures regarding inhalation risk 

assessment, and will re-evaluate the need for residential and occupational bystander risk 

assessments based on current Agency policy at the time of the risk assessment.

• The tolerance expression in 40 CFR §180.603 has been reviewed to ensure that it 

appropriately covers the metabolites and degradates of dinotefuran and that it specifies 

the residues to be measured for each commodity.

• There are no established or proposed international Codex, Canadian, or Mexican MRLs 

for dinotefuran. However, should MRLs be established, the Agency will work to 

harmonize tolerances/MRLs, where possible, in key export markets during registration 

review.

• Please refer to Dinotefuran. Human Health Scoping Document in Support of 

Registration Review, September 15, 2011, located in the docket, for a detailed discussion 

of the risk assessment and data needs for human health.

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 
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susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for dinotefuran, EPA reviewed 

these data and selected the most sensitive endpoints for relevant risk assessment scenarios from 

the existing hazard database. However, as required by FFDCA section 408(p), dinotefuran is 

subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Dinotefuran is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for dinotefuran. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website:

http://www.epa.gov/endo/.

Timeline:

EPA has created the following estimated timeline for the completion of the dinotefuran 

registration review.

Registration Review for Dinotefuran – Projected Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and Public Comment Period 2011 – December

Close Public Comment 2012 – February

Case Development

Final Work Plan 2012 – June

Issue DCI 2013 – Jan. – March

Data Submission 2016 – Jan. – March
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Registration Review for Dinotefuran – Projected Registration Review Timeline

Activities Estimated Date

Open Public Comment Period for Draft Risk Assessments 2017 – July – Sept.

Close Public Comment Period 2017 – Oct. – Dec.

Registration Review Decision

Open Public Comment Period for Proposed Registration Review 

Decision 

2018 – Jan. – March

Close Public Comment Period 2018 – April – June

Registration Review Decision and Begin Post-Decision Follow-up 2018

Total (years) 7

Next Steps:

The Agency will require ecological effects and human health studies through a DCI, which is 

expected to be issued in early 2013. This new information will be used to conduct risk 

assessments for all registered uses of dinotefuran.
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Summary of Data Needs – Dinotefuran:

The table below summarizes the data needs for dinotefuran. For additional discussion of the data 

needs, see the Registration Review – Preliminary Problem Formulation for Ecological Risk and 

Environmental Fate, Endangered Species, and Drinking Water Assessments for Dinotefuran, 

December 13, 2011, and Dinotefuran. Human Health Scoping Document in Support of 

Registration Review, December 15, 2011.

Table 1. Data Needs for Dinotefuran Registration Review 

Guideline 

Number Data Requirement Test Material

Estimated 

Timeframe 

(Months 

from receipt 

of DCI)

835.4400 Anaerobic Aquatic Metabolism TGAI 24

850.1350 Estuarine/marine Invertebrates – Life Cycle (mysid species) TGAI 12

850.2100 Avian Oral Toxicity (passerine species)2 TGAI 12

850.3040 Field Testing for Pollinators3 TEP 24

Non-Guideline

(Special Study) Pollinator Larval Toxicity Study4 TGAI 12

Non-Guideline

(Special Study) Laboratory Pollinator Chronic Feeding Study4 TGAI 12

Non-Guideline

(Special Study) Residues in Pollen and Nectar/Field Residue Analysis4, 5 TGAI 36

875.2300 Fur Dislodgeability TGAI

January 26, 

2013

(In review)

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 2 The DCI will require the submission of a study protocol for review and approval by the Agency prior to study 

initiation. 

3 The DCI will require that the test crop be one on which bees will actively forage for both nectar and pollen (e.g., 

cotton, melon, alfalfa).

4 The DCI will require the submission of a study protocol for review and approval by the Agency prior to study 

initiation. The registrant should not assume that any California Department of Pesticide Regulation data have 

satisfied the Agency data requirements. 5 The Agency recommends residue studies of leaves, fruit, seeds, wax, sap, as well as blooming, pollen-shedding, 

and nectar producing parts (i.e., flowers and, if present, extra floral nectarines) on pollinator-attractive crops on 

which the compound is registered for use.

6 In addition to being a data requirement for the registration review of dinotefuran, GLN 875.2300, fur 

dislodgeability is required as a condition of registration for dinotefuran dog and cat spot-on products. Conditions 

stipulate a due date of January 26, 2013 and the Agency still requires the study by this date. This study was recently 

submitted to the Agency and is currently in review. Once the study has been fully reviewed and classified, EPA will 

determine whether or not it should be included in the registration review DCI.