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

www.regulations.gov

Dinotefuran Summary Document

Registration Review: Initial Docket

December 2011

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TABLE OF CONTENTS

 Page 

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 12

III. Summary of Data Gaps 19

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection 

Agency's current position based on the following documents:

1. Registration Review: Problem Formulation for Environmental Fate, Ecological Risk, 

Endangered Species, and Drinking Water Exposure Assessments for Dinotefuran. 

December 13, 2011.

2. Dinotefuran: Human Health Assessment Scoping Document in Support of Registration 

Review. September 15, 2011. 

3. Dinotefuran: Review of Human Incidents. July 26, 2011.

4. Dinotefuran (044312) Screening Level Usage Analysis (SLUA). February 4, 2011.

5. BEAD Chemical Profile for Registration Review: Dinotefuran (044312). July 20, 2011.

6. Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration 

Review Work Planning. May 23, 2011.

Additional supporting documents for dinotefuran may be found in the registration review docket

EPA-HQ-OPP-2011-0920 located on the internet at www.regulations.gov.
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I. PRELIMINARY WORK PLAN – Dinotefuran

Introduction:

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides sold or distributed in the United States generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. 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 the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

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

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

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

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of dinotefuran.

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.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates requiring data for use in conducting a comprehensive ecological risk 

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

Agency also anticipates requiring 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.
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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 

(BMSB) 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 

“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 United States Fish and Wildlife Service 

and the National Marine Fisheries Service 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 anticipates 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)
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• In an attempt to address protection of pollinators and other beneficial insects, EPA is 

anticipating requiring data to assess bees as a representative for all beneficial insects. In 

moving forward with addressing potential risk to these organisms, EPA will consider the 

recommendations of the Society of Environmental Toxicology and Chemistry (SETAC) 

Workshop on Pesticide Risk Assessment for Pollinators, and is working with its federal 

and state partners, industry, and academia to determine appropriate assessment 

methodology. For compounds, such as dinotefuran, which (1) show acute toxicity to bees 

and (2) have exposure routes for bees, EPA anticipates requiring toxicity and exposure 

studies to allow for evaluation of risks to pollinators. The registrant should consult with 

EPA on the conduct of these studies.

• 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 anticipated 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 does not 

anticipate requiring additional toxicity data in support of registration review. However, 

the Agency anticipates reevaluating toxicological endpoints (points of departure), 

uncertainty factors, and updating 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.
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• 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. 

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 previously been identified as a conditional requirement for the registration 

of dinotefuran dog and cat spot-on products. The Agency has reviewed draft protocols 

for conducting this study based on the use of dinotefuran spot-on products for dogs and 

cats. However, submission of the final study remains outstanding and, per the conditions 

of registration, is due January 26, 2013. This study is also needed for use in this

registration review and will be included in the registration review DCI.

• The Agency anticipates revising residential and occupational handler and postapplication 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 anticipates 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 anticipated risk assessment and data needs.
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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 

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
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Registration Review for Dinotefuran – Projected Registration Review Timeline

Activities Estimated Date

Close Public Comment 2012 – February

Case Development

Final Work Plan 2012 – May

Issue DCI 2013 – Jan. – March

Data Submission 2016 – Jan. – March

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

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments, as well as any additional information or data provided in a 

timely manner, prior to issuing a Final Work Plan for dinotefuran.

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs 

or disparities between U.S. tolerances and MRLs in key export markets, providing as much 

specificity as possible regarding the nature of the concern.

Water Quality:

Dinotefuran is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act1

. In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for dinotefuran2

. More information on impaired water bodies and 

TMDLs can be found on the Agency’s website3. The Agency invites submission of water 

quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process4

 1

in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES 3 http://www.epa.gov/owow/tmdl/

4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to dinotefuran, compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population.

Additional Information:

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining its risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates

e. frequency of application, application intervals, and maximum number of 

applications per season and per year 

f. geographic limitations on use

2. use or potential use distribution (e.g., geographical distribution of relevant uses)

3. use history and reason for changes in use 

4. median and 90th

5. application timing (date of first application and application intervals) by use site –

national, state, and county

percentile reported use rates (lbs ai/1000 sq ft) from usage data –

national, state, and county

6. sub-county use site location data

7. usage/use information for non-agricultural uses, especially turf and ornamentals

8. directly acquired county-level usage data (not derived from state level data)

a. maximum reported use rate (lbs ai/1000 sq ft) from usage data – county

b. percent use site treated – county

c. median and 90th

d. total pounds per year – county

percentile number of applications – county

e. the year the pesticide was last used in the county/sub-county area

f. the years in which the pesticide was applied in the county/sub-county area

9. typical application interval (days)

10. state or local use restrictions

11. information on invertebrate resistance to this insecticide
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12. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency

13. monitoring data

14. additional usage information on the following registered sites: warehouses, 

commercial/industrial machinery, bathrooms, and garbage areas.

Next Steps:

After the 60-day comment period closes, the Agency will review and respond to any comments 

received in a timely manner, and then issue a Final Work Plan for dinotefuran.
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II. FACT SHEET

Background Information:

• Registration review case number: 7441

• PC code: 044312

• CAS number: 165252-70-0

• Dinotefuran was first registered in the U.S. in 2004 and, therefore, was not subject to 

reregistration under FIFRA.

• Technical registrants: Mitsui Chemicals, Inc.; Valent Biosciences Corp.; ICR, Inc.

• There are currently thirty-seven FIFRA Section 3 product registrations (3 technical, 2 

formulation intermediates, 2 manufacturing-use, and 30 end-use product registrations);

and sixteen active Special Local Need (SLN) registrations under FIFRA Section 24(c).

• Permanent tolerances are established for residues of dinotefuran, including its metabolites 

and degradates (expressed as dinotefuran), in and/or on food and/or feed commodities 

under 40 CFR §180.603. Also, a time-limited tolerance for residues of dinotefuran in 

and/or on rice is established under 40 CFR §180.603, which is scheduled to expire on 

December 31, 2012.

• Pesticide Re-evaluation Division (PRD) Chemical Review Manager (CRM): Steven 

Snyderman, snyderman.steven@epa.gov. 

• Registration Division (RD) Product Manager (PM): John Hebert, hebert.john@epa.gov.

Use & Usage Information: For additional details on label rates and use sites, refer to the 

following documents: BEAD Chemical Profile for Registration Review: Dinotefuran, July 20, 

2011; Dinotefuran Screening Level Usage Analysis (SLUA), February 4, 2011; and Appendix A: 

Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review Work Planning, 

May 23, 2011.

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

currently registered for agricultural use on the following food/feed commodities: 

brassica, cotton, leafy and fruiting vegetables, grapes, curcurbits, pineapple, potatoes, and 

nut trees. It is also registered for non-agricultural use in residential and commercial 

settings, which include: forest trees; ornamental plants (flowering and foliage plants, 

wood shrubs, vines and trees); ornamental lawns and turf; pets and pet premises; animal 

premises; domestic dwellings; picnic areas; transportation vehicles; food handling 

establishments; hospitals; and commercial, institutional, and industrial buildings. In 

addition, there are a number of SLN registrations, which are registered for use on turf, 

ornamentals, and vegetable transplants in enclosed structures. 

• Dinotefuran is formulated as an intermediate, soluble concentrate, granular, soluble 

granule, bait, gel, and read-to-use (RTU) spray.

• Based on market pesticide usage data from 2006-2010, the annual total agricultural usage

averaged approximately 4,000 pounds active ingredient (a.i.) over 30,000 acres for an 
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average of 0.1 lbs. a.i. application rate per acre. In comparison, the average application 

rate in lbs. a.i. per acre is 0.1 for wine grapes, 0.2 for cantaloupes, 0.1 for rice, and 0.2 for 

both watermelons and tomatoes. Non-agricultural usage data were not available from 

Agency data sources.

• From 2006-2010, the largest markets in terms of total pounds a.i. applied were wine 

grapes (35%), cantaloupes (17%), rice (12%), and watermelons and tomatoes (10% 

each). The highest total area treated (TAT) were wine grapes (41%), rice (19%), 

cantaloupes (11%), watermelons (7%), and tomatoes (6%). On average, the states with 

the most agricultural usage in terms of pounds a.i. applied were California (43%), 

Arizona (20%), Texas (18%), and Florida (13%). 

Recent and Ongoing Actions:

• As a condition of registration for the dinotefuran dog and cat spot-on products, a fur 

dislodgeability study (GDLN 875.2300) is required and is due January 26, 2013. The 

Agency has reviewed draft protocols for conducting this study based on the use of spoton products for dogs and cats; however, submission of the final study remains 

outstanding. Additionally, this study is needed in support of registration review.

• During the 2011 growing season, seven Section 18 emergency exemptions were granted

to control Brown Marmorated Stink Bugs (BMSB) on stone and pome fruit in several 

states. The emergency exemptions were in effect from April 15 to October 15, 2011.

• On October 31, 2011, a Section 18 emergency exemption for use on rice to control stink 

bugs, expired and is no longer in effect.

• On September 30, 2011, EPA sent letters to registrants with pet spot-on pesticide 

products, informing them on how to make necessary label changes for their products. In 

the spring of 2009, EPA observed a significant increase in incident reports associated 

with pet spot-on products. EPA investigated this increase, received additional 

information on those incidents from the pet spot-on pesticide registrants, and conducted 

an intensive evaluation of the incidents and the pet spot-on products themselves. 

Examples of label changes EPA believes may be necessary for pet products include: 

repeating the words “dog” and “cat” throughout the label (as appropriate), including the 

word “only” with size and breed restrictions, adding “do not allow your dog (or cat) to 

ingest this product,” incorporating a large, clear picture of the appropriate animal in the 

weight range for the product as packaged on the front panel of the label, and placing the 

breed and weight restrictions on the vial itself. EPA expects registrants to submit revised 

labels addressing all changes described in its letter no later than six months from the 

receipt of the September 30, 2011 letter. For more information on EPA’s increased 

restrictions on pet spot-on products, please visit: 

http://www.epa.gov/pesticides/health/pets.htm
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• On April 21, 2011, the Agency received a petition (Petition No. 1E7863) to establish 

tolerances on the following proposed commodities: low growing berry subgroup 13-07H, 

except strawberry; watercress; green onion subgroup 3-07B; bulb onion subgroup 3-07A; 

peach; tuberous and corn vegetable subgroup 1C; small fruit, vine climbing, subgroup 13-

07F, except fuzzy kiwifruit; chives; and tea. For further details regarding this pending 

action, please refer to docket EPA-HQ-OPP-2011-0433.

Ecological Risk Assessment Status: 

The key findings of the most recent ecological risk assessments for dinotefuran are summarized 

below. For a detailed discussion of the ecological risk assessment status, 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, in the dinotefuran registration review docket EPA-HQ-OPP-2011-0920.

• The most 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 2004 assessment concluded that acute and chronic 

risk estimates to non-endangered and endangered aquatic and terrestrial organisms

(mammals, birds, fish, invertebrates, plants) did not exceed the Agency’s level of concern 

(LOC). The Agency acknowledged that dinotefuran is highly toxic to honey-bees but 

that the registered uses assessed were not associated with areas high in pollinating 

insects; and, therefore, not likely to result in exposure to pollinators at that time. 

Dinotefuran’s degradates, DN (1-Methyl-3-(tetrahydro-3-furylmethyl) guanidinium 

dihydrogen) and MNG (1-Methyl-2-nitroguanidine), were found to be nontoxic to 

freshwater invertebrates (daphnids) and aquatic plants (green algae).

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

was conducted in May of 2011, for forestry uses (Christmas trees, trees in plantations, 

reforestation nurseries, forests, and woodland areas). For all application types, except 

tree injection, the Agency cited the conclusions of its prior risk assessments; and 

concluded that the forestry uses did not exceed the Agency’s LOC for acute risks to nontarget terrestrial and aquatic species. In addition, chronic risks did not exceed the 

Agency’s LOC for these taxa, with the exception of estuarine/marine fish and 

invertebrates (no chronic data were available and, therefore, risk could not be precluded).

• In previous assessments, risk to honey-bees had not been quantitatively assessed. 

However, given that dinotefuran is highly toxic to bees and is systemic in nature, the 

Agency identified potential concerns for the possibility of long-term exposure to bees 

from residues that remain in pollen and nectar of flowering crops. For the tree injection 

use, the Agency conducted a screening level analysis, which concluded that translocation 

of dinotefuran from the site of injection to edible parts of a tree may result in effects to 

birds, mammals, and terrestrial invertebrates. Potential risks to saltwater invertebrates 
15

could not be precluded given the sensitivity of the mysid shrimp to relatively low 

concentrations of dinotefuran.

• Several ecological risk assessments were completed to assess Section 18 emergency 

exemptions. The most recent of which, was completed on June 16, 2011 for use on stone 

and pome fruit to control BMSB. The Agency concluded that there was potential risk to 

listed terrestrial invertebrates from acute and chronic exposure; and for commercially 

beneficial insects, all non-target listed terrestrial invertebrates and the organisms that prey 

on them. Risks to listed and non-listed estuarine/marine invertebrates from chronic 

exposure could not be precluded, and was thus assumed. Risks were below the Agency’s 

LOC for: non-target birds, reptiles, terrestrial-phase amphibians, mammals, terrestrial 

plants, estuarine/marine and freshwater fish and invertebrates, and aquatic plants.

Human Health Risk Assessment Status:

The key findings of the most recent human health risk assessments for dinotefuran are 

summarized below. For a detailed discussion of the human health risk assessment status, please 

refer to the September 15, 2011 document, Dinotefuran: Human-Health Assessment Scoping 

Document in Support of Registration Review, in docket EPA-HQ-OPP-2011-0920. 

• 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 exemption for use on pome and stone fruits to control the BMSB. 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.

Hazard Characterization: 

• Available toxicity data indicate that the main target tissues are the nervous system and the 

spleen/thymus. Nervous system toxicity manifested as clinical signs and decreased motor 

activity seen after acute dosing (in both rats and rabbits) and increased motor activity 

seen after repeated dosing. These findings are consistent with effects on the nicotinic 

cholinergic nervous system. Decreased spleen and thymus weights were observed in all 

species tested, but no evidence of functional immunotoxicity was observed in recently 

submitted immunotoxicity (rat and mouse) studies. 

• No adverse effects in fetuses were seen in the developmental toxicity studies. There was 

a qualitative increase in sensitivity in rat pups in the reproductive toxicity study.

• Dinotefuran is not considered to be mutagenic, and it has been characterized by EPA as 

“not likely” to be a human carcinogen.

• EPA selected toxicity endpoints based on the most sensitive effect, decreased thymus 

weight (chronic toxicity dog study). An additional 10X uncertainty factor (UF) was 

applied in the absence of a NOAEL in this study. This endpoint (decreased thymus 
16

weight) has been subject to comprehensive reevaluation (2005 FIFRA Scientific 

Advisory Panel entitled, A Comparison of the results of Studies on Pesticides from 1- or 

2-year Dog Studies with dog studies of Shorter Duration) and, as such, may not be 

appropriate for future dinotefuran risk assessments. 

Dietary (Food and Drinking Water): 

• In 2011, EPA conducted unrefined acute and partially refined chronic dietary 

(food and drinking water) exposure assessments for the general U.S. population 

and various subgroups. Acute and chronic dietary exposure estimates were below 

EPA’s levels of concern for all population subgroups.

Residential: 

• In 2011, residential handler and post-application exposure assessments were conducted 

for all currently registered uses of dinotefuran; risks were below the Agency’s level of 

concern for all assessed uses.

Aggregate: 

• In 2011, aggregate exposure assessments were performed for acute and chronic dietary 

exposure (food and drinking water), and residential intermediate-term exposure to 

children (from dermal and incidental oral exposures) and adults (from dermal and 

inhalation exposures). Risks were below the Agency’s level of concern for all assessed

uses.

Occupational:

• In 2011, occupational handler and post-application exposure assessments were conducted 

for all registered uses. Risks were below the Agency’s level of concern for all assessed

uses.

Human Studies:

• Past dinotefuran risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has 

reviewed all the studies supporting these multi-pesticide generic exposure databases, and 

has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards 

prevailing at the time the research was conducted. All applicable requirements of EPA’s 

Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies.
17

Cumulative:

• EPA has not yet determined whether or not dinotefuran shares a common mechanism of 

toxicity with any other chemical substances. If the Agency determines that new 

information on dinotefuran is available that could potentially affect a cumulative risk 

assessment and result in a risk of concern, the Agency will revisit the need for a 

cumulative assessment.

Incidents:

• A summary report listing reported human incidents for dinotefuran has been provided in 

the docket item entitled Dinotefuran: Review of Human Incidents, July 26, 2011. The

Agency consulted the Office of Pesticide Programs (OPP) Incident Data Systems (IDS) 

for pesticide incident data on the active ingredient dinotefuran. In Aggregate IDS, from 

January 1, 2006 to June 13, 2011, 94 incidents involving dinotefuran were identified. 

Aggregate IDS only includes counts of incidents classified as “minor,” “unknown,” or 

“no effects,” and no additional details about the incidents are provided. For the main 

IDS, from January 1, 2006 to June 13, 2011, three cases were reported for the single 

chemical dinotefuran (classified as moderate severity); and two incidents involving more 

than one chemical were reported. Based on the low frequency and severity of incident 

cases, there does not appear to be a concern at this time that would warrant further 

investigation. However, the Agency will continue to monitor the incident information for 

dinotefuran and will conduct additional analyses if needed.

• The Agency has conducted a preliminary review of the Ecological Incident Information 

System (EIIS), which is maintained by OPP, and the Avian Monitoring Information 

System (AIMS), which is maintained by the American Bird Conservancy. No incidents 

have been reported in which dinotefuran has been associated with some type of 

environmental effect.

Tolerances and International Harmonization: 

• Tolerances are established for residues of dinotefuran under 40 CFR §180.603 for use on 

various food and feed crops. 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.

• A time-limited tolerance for residues of dinotefuran in and/or on rice is established under 

40 CFR §180.603, which is scheduled to expire on December 31, 2012.
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Data Call-In Status: 

• No Data Call-Ins (DCIs) have previously been issued for dinotefuran.

Labels:

• Dinotefuran Section 3 product labels can be obtained from the Pesticide Product Label 

System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home
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III. SUMMARY OF ANTICIPATED DATA GAPS – Dinotefuran

The table below summarizes all anticipated data needs for dinotefuran identified in Section I of 

this document (Preliminary Work Plan), the Registration Review – Preliminary Problem 

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

Water Assessments for Dinotefuran, dated December 13, 2011, and the Dinotefuran: HumanHealth Assessment Scoping Document in Support of Registration Review, dated September 15, 

2011. 

Table 1. Summary of Current Data Gaps for Dinotefuran 

Guideline 

Number Anticipated Data Requirement Test Material

Study 

Duration5

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)6 TGAI 12

850.3040 Field Testing for Pollinators7 TEP 24

Non-Guideline

(Special Study) Pollinator Larval Toxicity Study8 TGAI 12

Non-Guideline

(Special Study) Laboratory Pollinator Chronic Feeding Study8 TGAI 12

Non-Guideline

(Special Study) Residues in Pollen and Nectar/Field Residue Analysis8, 9 TGAI; Degra. 36

875.2300 Fur Dislodgeability Study TGAI 1/26/201310

 5 Measured from receipt of DCI

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

study initiation. 

7 The anticipated DCI will provide that the test crop is to be one on which bees will actively forage for both nectar 

and pollen (e.g., cotton, melon, alfalfa).

8 The anticipated DCI will provide that the registrant is to consult with the Agency prior to initiation of these studies 

and 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 has satisfied the 

anticipated Agency data requirements. 9 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.

10 The Fur Dislodgeability Study, in addition to being a data gap for the registration review of dinotefuran is 

required as a condition of a previous dinotefuran registration. Conditions stipulated a due date of January 26, 2013 

and the Agency still requires the study by this date.