Problem Formulation for the

Ecological Risk and Drinking Water Exposure Assessments

in Support of the Registration Review of 

Dinotefuran

USEPA PC# 044312

Dinotefuran (CAS# 165252-70-0) 

N-methyl-N’-nitro-N”-[(tetrahydro-3-furanyl)methyl)]guanidine

Chemical Family: Broad-spectrum furanicotinyl neonicotinoid insecticide; 4A nitroguanidine

Pesticidal Mode of Action: Nicotinic acetylcholine receptor (nAChR) agonist; dinotefuran acts 

on the autonomic nervous system by binding to the postsynaptic 

nicotinic acetylcholine receptor

Prepared by:

Tanja Crk, MA, Biologist

Ronald Parker, PhD., Senior Environmental Engineer 

James Hetrick, Ph.D., Senior Advisor U. S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch 3

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewed by:

Dana Spatz, Branch Chief

Edward Odenkirchen, Senior Biologist

Anita Ullagaddi, Biologist

Date of Completion:

December 13, 2011

Office of Chemical 

Safety and Pollution 

Prevention
Page | 2

1. Purpose

The purpose of this problem formulation is to provide the status of the environmental fate and 

ecological effects of dinotefuran, considering its currently registered uses. This document will 

provide a plan for analyzing data relevant to dinotefuran and for conducting environmental fate, 

ecological risk, endangered species, and drinking water exposure assessments for its registered 

uses. Additionally, this problem formulation is intended to identify data gaps, uncertainties, and 

potential assumptions used to address those uncertainties relative to characterizing the ecological 

risk associated with the registered uses of dinotefuran. 

2. Problem Formulation

2.1. Nature of Regulatory Action

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), all pesticides distributed 

or sold in the United States generally must be registered by the Environmental Protection 

Agency (EPA). In determining whether a pesticide can be registered in the United States, EPA 

evaluates its safety to non-target species based on a wide range of environmental and health 

effects studies. In 1996, FIFRA was amended by the Food Quality Protection Act, and the 

Agency was mandated to implement a new program for the periodic review of pesticides, i.e., 

registration review (http://www.epa.gov/oppsrrd1/registration_review/). The Registration 

Review program is intended to ensure 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 and the environment. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the new Registration Review 

program, the Agency periodically reevaluates pesticides to make sure that as change occurs, 

products in the marketplace can be used safely. 

As part of the implementation of the new Registration Review program pursuant to Section 3(g) 

of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the Agency is beginning its 

evaluation of dinotefuran to determine whether it continues to meet the FIFRA standard for 

registration. This problem formulation for the environmental fate, ecological risk, endangered 

species, and drinking water assessment chapter in support of the registration review will be 

posted in the initial docket which will open the public phase of the review process.

2.1.1. Preliminary Identification of Data Gaps (Summary)

A brief summary of anticipated data gaps is listed below. However, for further justification see 

Tables 17 through 20 as well as the text succeeding the tables; and, for additional data needs see 

Appendix C. The data call-in (DCI) justification tables for pollinator non-guideline studies and 

the pollinator field test are included in Appendix D.
Page | 3

Fate Data Gaps (see Table 17)

• OPPTS Guidance 835.4400 Anaerobic Aquatic Metabolism

Effects Data Gaps (see Tables 18-20 and text succeeding the tables)

• OPPTS Guidance 850.2100 Avian Oral Toxicity (Passerine)

• OPPTS Guidance 850.3040 Field Testing for Pollinators

• Non-GLN Pollinator Larval Toxicity Study

• Non-GLN Lab Pollinator Chronic Feeding Study

• Non-GLN Residues in Pollen and Nectar / Field Residue Analysis Study

• OPPTS Guidance 850.1350 Estuarine/Marine Invertebrate – Life Cycle Test

• OPPTS Guidance 850.5400 Aquatic Plant Growth: Non-vascular Plants

2.2. Previous Assessments

2.2.1. Ecological Risk Assessments

A summary of past risk assessments on dinotefuran is provided below and in Table 1.

Section 3 Actions

Dinotefuran was first registered in the United States in 2004 (revised June 30, DP Barcode 

D285633), when the registrant, Mitsui Chemicals America, Inc., proposed use of the chemical on 

leafy vegetables, turf grasses and various residential uses such as ant bait, fly bait, house and 

garden ready-to-use-spray, total release fogger, cat spot-on, 20% PCOs for pet sleeping areas, 

and Shuriken cockroach gel bait. While there was concern about dinotefuran’s high toxicity to 

bees, the proposed uses were not associated with areas high in pollinating insects and the uses 

did not trigger acute or chronic direct risks to non-endangered or endangered aquatic and 

terrestrial organisms (e.g. mammals, birds, fish, invertebrates, and plants). Based on 

ecotoxicological data on two of its degradates, DN (1-Methyl-3-(tetrahydro-3-furylmethyl) 

guanidinium dihydrogen) was found to be nontoxic to freshwater invertebrates (daphnids) and 

aquatic plants (green algae) and MNG (1-Methyl-2-nitroguanidine) was found to be nontoxic to 

green algae.

New uses were proposed in 2004 (August 9, DP Barcode: D304957) to include cotton, potato, 

head and stem brassica, fruiting vegetables (eggplant, ground cherry, pepino, pepper, tomatillo, 

tomato), cucurbits (choyote, Chinese waxgourd, citron, melon, cucumber, gherkin, muskmelon, 

momordica spp., pumpkin, squash, watermelon), grapes, ornamental plants, lawn, flower beds, 

shrubs, ornamental plant beds, and additional residential uses (apartments, ant hills, automobiles, 

boats, dog houses, houseplants, and indoor/outdoor pests). No increase in exposure or risk from 

these proposed uses was found relative to the new chemical assessment of June 30, 2004 (DP 

Barcode D285633). Risks to bees was not quantitatively assessed. However, given the systemic 

property of dinotefuran and its toxicity to bees, the assessment highlighted EFEDs concern about 

the possibility of long term exposure to bees from residues that remain in pollen and nectar of 

flowering crops.
Page | 4

Use rate increases for previously proposed uses were assessed in 2006 (October 16, DP Barcode: 

D324854) for head and stem brassica, cucurbits, fruiting vegetables, grapes, leafy vegetables, 

and potatoes. The EFED found the changes in the application rates did not result in exposures 

exceeding Levels of Concern (LOCs); the previous two assessments (USEPA June 30, 2004 and 

USEPA August 9, 2004) were cited for reference. Again, the assessment highlighted concerns 

for potential risk to listed species of terrestrial invertebrates and recommended label changes to 

Dinotefuran 20SG that required removal of a precautionary statement for honey bees which was 

inconsistent with another such statement on the same label. The following label statement was 

acceptable: “This product is toxic to bees exposed to treatment and for more than 38 hours 

following treatment. Do not apply this product to blooming, pollen-shedding or nectar-producing 

parts of plants if bees may forage on the plants during this time period, unless the application is 

made in response to a public health emergency declared by appropriate state or federal 

authorities.”

A label amendment was requested by Mitsui Chemicals Agro, Inc. in 2011 (May 3, DP Barcode: 

D378125) to add use of dinotefuran (Dinotefuran 20% turf, ornamental, forestry [amendment],

vegetable transplants in enclosed structures; EPA Reg. No. Reg. No. 86203-111

) onto Christmas 

trees, trees in plantations (conifers and deciduous trees), reforestation nurseries, and forests and 

wooded areas (national, private, and state). Applications are proposed by foliar or broadcast 

spray, soil (drench, injection, and various irrigation methods), basal trunk spray, and tree trunk 

injection. For all application types except tree injection, prior assessment risk conclusions were 

cited, concluding that proposed uses of dinotefuran did not trigger acute risks to non-target nonlisted or listed terrestrial (e.g., birds, mammals, plants) and aquatic species (e.g., fish, aquatic 

invertebrates, plants); in addition, no chronic risks were expected to these taxa, with the 

exception of estuarine/marine fish/invertebrates (no chronic data available). However, the 

assessment of June 30, 2004 (D285633) for the proposed uses of dinotefuran (i.e., leafy 

vegetables, turf, which were also a surrogate for ornamental uses, which were listed on the 

Dinotefuran 20% label in conjunction with the proposed forestry uses) raised a precautionary 

note with regard to the possibility of honey bee concerns and future dinotefuran uses. Overall, 

the screening level analysis conducted for the tree injection use pattern, which assumed total 

mass of chemical applied to the terrestrial and aquatic environments as well as distribution of 

concentrations in tree trunks and leaves, suggested that translocation of dinotefuran from the site 

of injection to edible portions of a tree may result in effects to birds, mammals, and terrestrial 

invertebrates. Potential risks to saltwater invertebrates could not be precluded given the 

sensitivity of the mysid shrimp to relatively low concentrations of dinotefuran and LOC 

exceedances given exposure to certain EECs potentially found in contaminated surface water.

Section 18 Actions

A Section 18 emergency exemption request made by the Texas Department of Agriculture was 

assessed in 2006 (October 31, DP Barcode: D332829) for the use of dinotefuran (Venom 20SG, 

20%a.i. soluble granule formulation) on leafy brassica to control sweet potato whitefly biotype B 

(Bemisia tabaci) in 44 counties in Texas from September 30 to December 31, 2006. The risk 

assessment concluded that the proposed label for leafy brassica does not result in exposures 

exceeding LOCs. A previous assessment was cited (USEPA 2004, DP Barcode D285633) as 

 1 Note that the Reg. No. was revised from 33657-16 to 86203-11.
Page | 5

having similar application rates to those proposed in the section 18 request. However, given 

dinotefuran’s toxicity to honeybees, applicators were advised to consider levels of active 

pollinations in and around areas to be treated, especially the vicinity of blooming crops and 

weeds.

Another Section 18 emergency exemption request made by the Texas Department of Agriculture 

was assessed in 2008 (October 28, DP Barcode: D355010) for the use of dinotefuran (Tenchu

20SG, 20%a.i. soluble granule formulation) on rice to control rice stink bug in 21 counties in 

Texas starting June 10, 2008. The uses exceeded acute restricted use and acute listed species 

LOCs for estuarine/marine aquatic invertebrates and risk to honeybees was assumed should 

exposure occur. 

A Section 18 emergency exemption request made by The Departments of Agriculture [and 

Consumer Services]2 for VA, WV, DE, MD, NC, and PA3 was assessed in 2011 (June 16, DP 

Barcode(s): D388997+) for the use of two dinotefuran formulations (Venom 70 SG Insecticide 

with 70% dinotefuran a.i., soluble dispersible granule, EPA Reg. No. 59639-135 [Valent as 

registrant]; and, Scorpion 35SL Insecticide with 35% dinotefuran a.i., EPA Reg. No. 10163-317, 

respectively [Gowan as registrant]) on commercial pome fruit and stone fruit4 orchards to control 

the brown marmorated stink bug (Halyomorpha halys) from April 15 to October 15. There was a 

potential for risk to listed terrestrial invertebrates from acute and chronic exposure. In addition to 

risk for commercially beneficial insects, all non-target, listed terrestrial invertebrates and the 

organisms that prey on them were potentially at risk. Risks to listed and non-listed 

estuarine/marine invertebrates from chronic exposure could not be precluded, and was, thus, 

assumed. Risks from direct effects to non-target birds (and, thus, reptiles and terrestrial-phase 

amphibians), mammals, terrestrial plants, estuarine/marine fish, freshwater fish (and, thus, 

aquatic-phase amphibians), freshwater invertebrates, estuarine/marine invertebrates (acute 

exposure), and aquatic plants (listed and non-listed) were not expected from the proposed uses. 

The degradates MNG and DN (in its stable form, DN-phosphate) were tested on non-vascular 

aquatic plants; and DN-Phosphate was tested on freshwater invertebrates (daphnids). Risk to 

these organisms as a result of exposure to these degradates was not expected.

IR-4 Petition

A new use petition was assessed in 2009 (June 15, DP Barcode: D358860) for the use of 

dinotefuran (Dinotefuran 20SG, EPA Reg. No. 33657-17; Starkle 70SG, EPA Reg. No. 33657-

38; and, Dinotefuran 70SG, EPA Reg. No. 59639-135) on leafy brassica (subgroup 5B), 

including turnip greens. Previous risk assessments (USEPA 2004 D285633, D304957; USEPA 

2006 D324854, D332829) were cited for reference on account of similarity in application rate, 

number of applications and intervals to crops already assessed such as cotton, head and stem 

brassica, grapes and leafy vegetables. The risk conclusions parallel those of previous 

 2 The Department of Agriculture and Consumer Services title applies to VA and NC. The Department of Agriculture 

title applies to all remaining supporting states. 

3 List of counties per state: statewide (PA, MD, VA); New Castle, Kent, Sussex (DE); Berkeley, Hampshire, 

Jefferson, Morgan, Monroe (WV); Henderson, Polk, Cleveland, Lincoln, Wilkes, Alexander, Moore, Montgomery, 

Anson (NC)

4 Pome fruit: apple, pear; Stone fruit: peach, nectarine, plum, apricot, sweet and tart cherry.
Page | 6

assessments, whereby the Agency expressed concern about listed and non-listed non-target 

species of terrestrial invertebrates from the use of dinotefuran. However, the risk to pollinators 

was expected to be limited with this particular use as exposure to blooming, pollen- or nectarproducing parts of plants will not typically occur during leafy brassica crop production. 

Therefore, it was expected that exposure to terrestrial invertebrates would be limited to blooming 

plants near the treatment area and that exposure to pollinators via drift was not discountable.

Table 1. Past Risk Assessments

DP Barcode Year Use site Target Pest Action

285633 2004 Leafy vegetables, turfgrasses, 

ornamentals, residential use

Various (e.g., ants, 

flies, cockroach, 

etc.)

Section 3: New 

Chemical

304957 2004 Cotton, potato, head and stem 

brassica, fruiting vegetables, 

cucurbits, grapes, ornamental 

plants and flower beds, lawn, 

shrubs and additional residential 

uses

Various Section 3: New 

Use

324854 2006 Head and stem brassica, cucurbits, 

fruiting vegetables, grapes, leafy 

vegetables, potatoes

Various Section 3: New 

Use (increasing 

use rates)

332829 2006 Leafy Brassica Sweet potato 

whitefly biotype B 

(Bemisia tabaci)

Section 18

355010 2008 Rice Rice stink bug Section 18

358860 2009 Leafy Brassica Greens (Subgroup 

5B), including turnip greens

Various IR-4 Petition: 

Incremental

Environmental RA

378125 2011 Forestry Uses (Christmas trees, 

trees in plantations, reforestation 

nurseries, forests, woodland areas)

Various Section 3: New 

Use

388997+ 2011 Stone and pome fruit Brown 

marmorated stink 

bug

Section 18

*fruiting vegetables: eggplant, groundcherry, pepino, pepper, tomatillo, tomato

*cucurbits: choyote, Chinese waxgourd, citron, melon, cucumber, gherkin, muskmelon, momordica spp., pumpkin, 

squash, watermelon

*additional residential uses: apartments, ant hills, automobiles, boats, dog houses, houseplants, and indoor/outdoor 

pests

+ 390375, 390381, 390380, 390376, 389144, 390383, 390382, 390379, 390378, 390377, 389436, 390903, 390904

2.2.2. Drinking Water Exposure Assessments

The most recent dinotefuran EFED drinking water assessment was carried out for a Section 18 to 

control a brown marmorated stink bug (BMSB) infestation in pome fruit and stone fruit in 

Virginia, Delaware, North Carolina, West Virginia, Pennsylvania, New Jersey and Maryland (see 

DP Barcode: D389034, May 26, 2011).
Page | 7

Screening-level Estimated Drinking Water Concentrations (EDWCs) simulated with the EFED 

FIRST model for the proposed new uses were approximately 20% higher than the EDWCs 

calculated previously by EFED. Table 2 below includes total (cumulative) concentrations for 

parent dinotefuran and the same four degradates of toxicological concern that were included in 

the previous drinking water assessment. Use on pome and stone fruits resulted in peak and 

annual average (chronic) surface water EDWC of 91.31 and 25.16 μg/L, respectively. This is a 

tier 1 exposure which assumes that peak concentrations for the parent and all four degradates 

occur simultaneously and that the entire drinking water watershed is treated at the same time 

with dinotefuran.

Estimated surface water concentrations were higher than groundwater concentrations. Use on 

pome and stone fruits resulted in an estimated groundwater concentration of 3.5 μg/L based on 

the EFED SCIGROW model.

Table 2. Tier 1 EDWC for Dinotefuran Uses on Pome & Stone Fruits (p&s) and on Turf.1

Crop (Scenario) Percent 

Cropped 

Area (PCA)

Acute (peak) 

Surface Water 

Concentration (ppb)

Annual Average 

Surface Water 

Concentration (ppb)

Ground Water 

Concentration 

(ppb)

Pome and Stone Fruit (0.304 lbs 

ai/A, 2 applications, 7 day interval, 

airblast)

100%2 58.07 9.54 1.91

Turf Grass (0.54 lb ai/A, 1 

application, aerial) 100%2 49.8 8.2 1.71

Degradates

MNG 100%2 4.65 1.96 0.59 (p&s)

0.53 (turf)

DN 100%2 9.36 4.00 0.13 (p&s)

0.12 (turf)

UF 100%2 4.91 2.49 0.22 (p&s)

0.20 (turf)

DN-2-OH3 100%2 14.32 7.17 0.65 (p&s)

0.58 (turf)

Parent + All Degradates

(Pome & Stone Fruits)

(Assuming All Peaks Occur 

Simultaneously)

100%2 91.31 25.16 3.5

1 Parent residues are for the parent compound alone.

2 http://www.epa.gov/oppefed1/models/water/pca_adjustment_dwa.html

3 DN-2-OH represents DN-2-OH+DN-3-OH. These two were reported as one metabolite in the study.

3. Stressor Source and Distribution

Dinotefuran is a systemic, broad-spectrum neonicotinoid insecticide in the nitroguanidine subclass formulated as granules, emulsifiable concentrate, ready-to-use solution, and as a 
Page | 8

pressurized liquid. Agricultural use sites include cucurbits, grapes, pineapple, nut trees, fruiting 

vegetables, brassica vegetables, and leafy vegetables. Non-agricultural use sites include forest 

trees, ornamental plants (flowering and foliage plants, woody 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/industrial buildings.

Exposure of surface waters to dinotefuran is possible through surface water runoff, soil erosion, 

and off-target spray drift. Due to the low adsorption potential of dinotefuran and its degradate 

MNG (Koc’s <45; but DN-Phosphate Koc range from 58 to 2502 in US soils [loam, sandy loam, 

and clay loam]), the exposure to surface and ground water is expected to be high.

There are six major transformation products identified in the laboratory studies (MNG, DN, UF, 

MG-HCl, DN-2-OH + DN-3-OH, and BCDN succinate). The degradate MNG was identified as 

a major product in aerobic soil metabolism and in the terrestrial field dissipation studies. The 

degradate, DN, was identified as a major product in anaerobic soil metabolism and aerobic 

aquatic metabolism studies. The other degradates were mostly photolysates.

EFED will carry out a screening level exposure assessment for parent dinotefuran plus each 

degradate of toxic concern using the EFED GENEEC2 model for the ecological assessment and 

the EFED FIRST model for the human health assessment. Under this tier 1 method, it is assumed 

that the peak concentrations for the parent and all toxic degradates occur simultaneously. If the 

resultant concentrations exceed EFED and/or HED levels of concern (LOC), a tier 2 exposure 

assessment using the formation/decline method in the linked EPA PRZM and EXAMS models 

will be carried out.

3.1. Mode of Action

Dinotefuran, also known as MTI-446, is a broad-spectrum, systemic furanicotinyl insecticide 

belonging to the 4A nitroguanidine class of chemicals and a member of the neonicotinoids that 

were developed as an analog of nicotine. Dinotefuran acts as an agonist at (i.e., it binds to) the 

nicotinic acetylcholine receptor (nAChR) to which the neurotransmitter acetylcholine (ACh) 

would otherwise bind. Acetylcholine (ACh) is the endogenous agonist and excitatory 

neurotransmitter of the cholinergic nervous system. Therefore, dinotefuran acts on the autonomic

nervous system by binding to the postsynaptic nicotinic acetylcholine receptor. Although the 

cholinesterase enzyme itself is not affected by dinotefuran, the nerve is continually stimulated, 

and the end result, paralysis and death, is similar to that caused by cholinesterase inhibitors. 

Dinotefuran is highly water soluble (39,830 mg/L @20o

C) and is readily translocated in plant 

tissue giving it good systemic activity. Dinotefuran has stomach and contact activity and is 

effective against a wide variety of insects including aphids, whiteflies, thrips, leafhoppers, 

leafminer, sawflies, mole crickets, white grubs, lacebugs, billbugs, bettles, mealybugs, stink 

bugs, weevils, and cockroaches (U.S. EPA, 2004).
Page | 9

3.2. Overview of Pesticide Use and Usage

The pesticide use and usage information/trends and text was reproduced here from a Biological 

and Economic Analysis Division (BEAD) memo (USEPA 2011).

Agricultural Usage

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

averaged approximately 4,000 pounds active ingredient for 30,000 acres for an overall average

of 0.1 lbs a.i. application rate per acre. In comparison, the average active ingredient 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.

From 2006-2010, the largest markets in terms of total pounds a.i. applied are wine grapes (35%),

cantaloupes (17%), rice (12%), and watermelons and tomatoes (10% each). The highest total

area treated (TAT) are 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 are

California (43%), Arizona (20%), Texas (18%), and Florida (13%). (proprietary Data, 2006-

2010).

Non-Agricultural Usage

Non-agricultural usage data are not available from our current data sources.

Use 

For current application rates and methods see Table 3 below, which was reproduced from Specific 

Labels and the Dinotefuran EFED Label Data Report developed by BEAD. Crops for which multiple 

seasons within a year are possible, the maximum application rate per year will be modeled on a 

single season per year basis so that the growing season with the maximum amount of rainfall is used 

in modeling.

Timing of Application and Application Amounts

Labels indicate the timing of applications and use of the higher specified rates are triggered by severe 

pest pressure. For mealybug control, in the BERRY AND SMALL FRUIT crop group only, the label 

calls for application between budbreak and peaberry size of the fruit.
Page | 10

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

Leafy Brassica Greens and Turnip Greens: 

Broccoli Raab,

Chinese Cabbage (Bok Choy), 

Collards,

Kale,

Mizuna, 

Mustard Greens,

Mustard Spinach, 

Rape Greens, 

Turnip Greens

0.088 to 0.134 lb 

ai/A

@ 7 days interval

0.262 lb ai/A F

No more than 3 

applications 

per season are 

allowed.

G, A

Cotton 0.045 to 0.134 lb 

ai/A

@ 7 days interval

0.268 F G, A

Berry and Small Fruit

(Subgroup 13-07F)

Small Fruit Vine Climbing, except Fuzzy 

Kiwifruit

Amur River Grape

Gooseberry

Grape

Kiwifruit, hardy

Maypop

Schisandra berry

Cultivars, Varieties

and/or hybrids of these

Foliar:

(0.045 to 0.135 lb 

ai/A) @ 14 days 

interval

Or

Soil:

(0.225 to 0.338 1b 

ai/A) @ 14 days 

interval

Foliar:

(0.270 lb ai/A)

Soil:

( 0.338 lb ai/A)

F,S G,A

(T) For 

mealybug 

control, 

apply 

between 

budbreak 

and peaberry 

size.

Berry and Small Fruit

(Subgroup 13-07H)

Low Growing Berry Subgroup, except 

Strawberry

Bearberry

Bilberry

Blueberry Lowbush

Cloudberry

Cranberry

Lingonberry

Muntries

Partridgeberry

Cultivars, varieties and/or

hybrids of these

Foliar:

(0.090 to 0.180 lb 

ai/A) @ 14 days 

interval

Foliar

(0.360 lb a.i./A)

F G,A

(T) For 

mealybug 

control, 

apply 

between 

budbreak 

and peaberry 

size.

Head and Stem Brassica: 

Broccoli, 

Brussels sprouts, 

Cabbage, 

Cauliflower, 

Cavalo Broccolo, 

Chinese broccoli, 

Chinese cabbage, 

Foliar: 

0.045 to 0.179 lb 

a.i./A @ 7 days 

interval

Or

Soil:

0.226 to 0.33 lb 

a.i./A @ 7 days 

Foliar:

0.268 lb a.i./A

Or 

Soil:

0.536 lb a.i./A 

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

G, A

No more 

than 3 

applications 

per growing 

season
Page | 11

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

Chinese mustard cabbage, 

Kohlrabi

interval

Cucurbits: 

Acorn Squash

Balsam Apple

Balsam Pear

Bitter Melon

Butternut Squash

Calabaza

Cantaloupe

Casaba

Chayote

Chinese Cucumber

Chinese Waxgourd

(Chinese Preserving

Melon)

Citron Melon

Crenshaw Melon

Crookneck Squash

Cucumber

Edible Gourd

Gherkin

Golden Pershaw Melon

Honey Balls

Honeydew Melon

Hubbard Squash

Mango Melon

Momordica spp.

Muskmelon

Persian Melon

Pineapple Melon

Pumpkin

Santa Claus Melon

Scallop Squash

Snake Melon

Spaghetti Squash

Straightneck Squash

Summer Squash

True Cantalolupe

Vegetable Marrow

Watermelon

Winter Squash

Zucchini

Foliar: 

0.045 to 0.179 lb 

a.i./A @ 7 days 

interval

Or

Soil: 

0.226 to 0.33 lb 

a.i./A @ 7 days 

interval

Foliar:

0.268 lb a.i./A

Or 

Soil:

0.536 lb a.i./A 

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

G, A

No more 

than 3 

applications 

per growing 

season

Fruiting Vegetables: 

Eggplant, 

Ground Cherry, 

Pepinos, 

Foliar: 

0.045 to 0.179 lb 

ai/A @ 7 days 

interval

Foliar

0.268 lb ai/A

Or 

F, S

Do not 

combine foliar 

G, A
Page | 12

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

Pepper (including bell peppers, chili peppers, 

cooking peppers, pimentos and sweet peppers), 

Tomatillo, Tomato (do not apply to varieties of 

tomatoes which are less than 2 inches in size, such 

as cherry and grape tomatoes)

Or 

Soil: 0.226 to 0.33

lb ai/A @ 7 days 

interval

Soil 

0.536 lb ai/A

app. with soil 

applications, or 

vice versa.

Make no more 

than 3 

applications 

per growing 

season

Grapes Foliar: 

0.132 lb ai/A @ 14 

days interval

Or

Soil: 

lb ai/A 0.33

Foliar 

0.264 lb ai/A

Ground 

0.33 lb ai/A

Overall per 

season:

0.528 lb ai/A

F, S

Make only one 

soil 

application.

G/ airblast, 

A

Leafy Vegetables (Except Brassica Vegetables): 

Amaranth, 

Arugula, Cardoon, 

Celery, Chinese Celery, 

Celtuce, chervil, Edible-leaved & Garland 

Chrysanthemum, Corn Salad, 

Garden & Upland Cress, 

Dandelion, 

Dock, 

Endive, 

Florence Fennel, 

Head & Leaf Lettuce, 

Orach, 

Parsley, Garden & Winter 

Purslane, 

Radichio, 

Rhubarb, 

Spinach, 

New Zealand & Vine Spinach, 

Swiss Chard

Foliar: 0.045 to 

0.134 lb ai/A @ 7 

days interval

Or 

Soil: 

0.226 to 0.33 lb ai/A

@ 7 days interval

Foliar:

0.268 lb ai/A

Or 

Soil 

0.536 lb ai/A

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

Make no more 

than 3 

applications 

per growing 

season

G, A

Tuberous and Corm Vegetables

(Subgroup 1C)

Arracacha

ArrowRoot

Artichoke, Chinese

Artichoke, Jerusalem

Canna, edible

Cassava, bitter and sweet

Chayote (root)

Chufa

Foliar: 

0.045 to 0.068 lb 

ai/A @ 14 days 

interval

Or 

Soil: 

0.293 to 0.338 lb 

ai/A

@ 14 days interval

Foliar

0.203 lb ai/A

Or 

Soil 

0.338 lb ai/A

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

G, A
Page | 13

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

Dasheen (taro)

Ginger

Leren

Potato

Sweet Potato

Tanier

Turmeric

Yam bean

Yam, true

Onion, Bulb and Green

(Subgroups 3-07A and 3-07B)

Bulb onion, Includes:

Daylily, bulb

Fritillaria, bulb

Garlic, bulb

Garlic, Great-headed, bulb

Garlic, serpent, bulb

Lily, bulb

Onion, bulb

Onion, Chinese, bulb

Onion, pearl

Onion, potato, bulb

Shallot, bulb

Cultivars, varieties and/or

hybrids of these

Green onion, includes:

Chive, fresh leaves

Chive, Chinese, fresh leaves

Elegans hosta

Fritillaria leaves

Kurrat

Leady's leek

Leek

Leek, wild

Onion, Beltsville bunching

Onion, fresh

Onion, green

Onion, macrostem

Onion, tree, tops

Onion, Welsh, tops

Shallot, fresh leaves

Cultivars, varieties and/or

hybrids of these

Foliar: 

0.090 to 0.180 lb 

ai/A @ 7 days 

interval

Or 

Soil: 

0.225 to 0.270 lb 

ai/A

@ 7 days interval

Foliar

0.270 lb ai/A

Or 

Soil 

0.270 lb ai/A

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

G, A

Peach and Nectarine

Peach

Nectarine

Foliar: 

0.090 to 0.180 lb 

ai/A @ 7 days 

interval

Foliar:

0.270 lb ai/A

Or 

Soil:

F, S G, A
Page | 14

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

Or 

Soil: 

0.225 to 0.270 lb 

ai/A

@ 7 days interval

0.270 lb ai/A

Overall per 

season:

0.360 lb ai/A

Potato Foliar: 0.066 lb 

ai/A

@ 14 days interval

Or 

Soil: 

0.33 lb ai/A

@ 14 days interval

Foliar:

0.198 lb ai/A

Or 

Soil:

0.33 lb ai/A

F, S

Do not 

combine foliar 

app. with soil 

applications, or 

vice versa.

G w/airblast, 

A

Turfgrass (commercial, residential, 

recreational)

Foliar:

0.54 lb ai/A

0.54 lb ai/A F G

Vegetable Transplants grown in enclosed 

structures, including:

Cucurbits, 

Fruiting Vegetables, 

Head and Stem Brassica and Leafy Vegetables 

(excluding Brassica spp.)

Foliar:

0.18 lb ai/A

0.268 lb ai/A F or Broadcast 

spray

G

Ornamental plants in greenhouses, nurseries, 

interior plantscapes, lath and shadehouses and 

outdoor landscapes (commercial, industrial, 

recreational and residential) or Ornamental 

containerized or in ground plants, including:

Shrubs, 

Bedding Plants, 

Flowering Plants, 

Foliage Plants, 

Ground Covers, 

Evergreens, 

Ornamental Plants and Trees, 

Non-Bearing Fruit Trees, 

Non-Bearing Nut Trees,

Non-Bearing Vines

Foliar:

0.2 lb ai/A

0.54 lb ai/A

0.54 lb ai/A

F / airblast (for 

trees and vines) 

or Broadcast 

spray, S

Do not make 

more than one 

soil application 

per crop cycle 

or three 

months, 

whichever is 

shorter.

G

Pome Fruit and Stone Fruits

Pome Fruits

Stone Fruits

0.203- 0.304 a.i. 

lb/A

(2 @ 7days

0.608 lbs a.i./A 

per season)

F G

Turfgrasses

Residential

Recreational

Commercial

Foliar:

0.54 lbs. a.i./A

Annual max:

0.54 lbs. a.i./A

F G

Watercress Foliar:

(0.090 to 0.180 lb 

ai/A)

Foliar:

0.360 lb ai/A)

F G
Page | 15

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

ORNAMENTAL PLANTS, VEGETABLE 

TRANSPLANTS AND FORESTS

Shrubs including: 

Bedding Plants

Flowering Plants 

Foliage Plants 

Ground Covers

Evergreens 

Ornamental Trees 

Non-Bearing Fruit Trees Non-Bearing Nut 

Trees Non-Bearing Vines

Christmas Trees

Trees in Plantations including:

 Conifers

 Deciduous trees

Eastern Hemlock 

 (Forest/Shelterbelts)

Reforestation Nurseries

Forests and Wooded Areas, National, Private and 

State

(Not for use on house plants grown inside private 

residences)

Foliar:

(0.1 to 0.2 lbs. 

a.i./A)

Soil:

Do not apply more 

than 2.7 lbs (0.54 

lbs. a.i.) per acre of 

nursery, landscape 

or forest per year.

F, S, I (see label, 

EPA Reg. No. 

86203-11, for 

specific details 

on exceptions as 

well as basal 

trunk sprays in 

trees and large 

shrubs)

VEGETABLE TRANSPLANTS

Foliar:

0.09 - 0.18 lb ai/A 

F G

Indoor / Outdoor Non-Food Uses

COMMERCIAL/INDUSTRIAL LAWNS,

COMMERCIAL/INSTITUTIONAL/INDUSTRIA

L PREMISES/EQUIPMENT (INDOOR),

COMMERCIAL/INSTITUTIONAL/INDUSTRIA

L PREMISES/EQUIPMENT (OUTDOOR),

COMMERCIAL STORAGES/WAREHOUSES 

PREMISES,

COMMERCIAL TRANSPORTATION 

FACILITIES-NONFEED/NONFOOD,

DAIRIES/CHEESE PROCESSING PLANT 

PREMISES (NONFOOD CONTACT),

DAIRY FARM MILKING STALLS/PARLORS,

DOGS/CANINES: ADULTS/PUPPIES),

DRAINAGE SYSTEMS,

EATING ESTABLISHMENTS FOOD 

HANDLING AREAS (NONFOOD CONTACT),

Maximum of All 

Uses:

0.54 lb ai/A

F, S, BP, SP, 

CR, BT

Timing: 

When Needed

Product Seasonal 

Max Dose/Year:

0.54 -

Mostly Not 

Specified

A. I. Seasonal 

Max Dose /

Year: 0.54

- Mostly

Not Specified

Doses/ Season:

Not Specified

A, G, B
Page | 16

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

FEED MILLS/FEED PROCESSING PLANTS,

FENCEROWS/HEDGEROWS,

COMMERCIAL/INDUSTRIAL LAWNS,

COMMERCIAL/INSTITUTIONAL/INDUSTRIA

L PREMISES/EQUIPMENT (INDOOR),

COMMERCIAL/INSTITUTIONAL/INDUSTRIA

L PREMISES/EQUIPMENT (OUTDOOR),

COMMERCIAL STORAGES/WAREHOUSES 

PREMISES,

COMMERCIAL TRANSPORTATION 

FACILITIES-NONFEED/NONFOOD,

DAIRIES/CHEESE PROCESSING PLANT 

PREMISES (NONFOOD CONTACT),

DAIRY FARM MILKING STALLS/PARLORS,

DOGS/CANINES: ADULTS/PUPPIES),

DRAINAGE SYSTEMS,

EATING ESTABLISHMENTS FOOD 

HANDLING AREAS (NONFOOD CONTACT),

FEED MILLS/FEED PROCESSING PLANTS,

FENCEROWS/HEDGEROWS,

FOOD/GROCERY/MARKETING/STORAGE/DI

STRIBUTION FACILITY PREMISE,

FOOD PROCESSING PLANT NON-FOOD 

HANDLING AREAS,

FOOD/GROCERY/MARKETING/STORAGE/DI

STRIBUTION FACILITY PREMISE,

FOOD PROCESSING PLANT NON-FOOD 

HANDLING AREAS,

GREENHOUSE-EMPTY,

HOSPITALS/MEDICAL INSTITUTIONS 

PREMISES (HUMAN/VETERINARY) 

INDOOR,

HOUSEHOLD/DOMESTIC DWELLINGS 

INDOOR,

HOUSEHOLD/DOMESTIC DWELLINGS 

CONTENTS INDOOR,

HOUSEHOLD/DOMESTIC DWELLINGS 

NONFOOD HANDLING AREAS INDOOR,

MEAT PROCESSING PLANT PREMISES 

(NONFOOD CONTACT) INDOOR,

NONAGRICULTURAL OUTDOOR, 

BUILDINGS/STRUCTURES,

PATHS/PATIOS,

PET LIVING/SLEEPING QUARTERS,

POULTRY FEEDLOTS,

POULTRY PROCESSING PLANT PREMISES 

(NONFOOD CONTACT),
Page | 17

Table 3. Current Application Rates for Dinotefuran: Registration Numbers: (10163-317, 2217-935, 2217-937, 

499-507, 499-510, 499-526, 499-527, 499-531, 499-537, 499-540, 59639-135, 59639-149, 59639-162, 59639-168, 

59639-169, 59639-170, 73049-441, 73049-442, 73049-443, 73049-446, 73049-450, 83399-10, 83399-6, 83399-9, 

86203-10, 86203-11, 86203-12, 86203-14, 86203-15, 86203-16, 86203-18, 86203-23, 86203-25, 86203-9, 9688-238, 

9688-239, 9688-240, 9688-242, 9688-245, 9688-258, 9688-271, GA080011, KY080024, NJ080003, NY070007, 

PA080006, TN080013, VA080009)

Crop Maximum 

application rate 

per application (lb 

a.i./A)

Maximum 

seasonal 

application rate 

(lb a.i./A)

Foliar (F) Soil 

(S)

Backpack 

(BP) Tree 

injections (I) 

Spot (SP) 

Crack (CR) 

Bait (BT)

allowed?

Ground (G) 

and/or 

Aerial (A) 

allowed for 

foliar 

applications

?

Timing (T)

RECREATIONAL AREAS,

RECREATION AREA LAWNS,

REFUSE/SOLID WASTE CONTAINERS 

(GARBAGE CANS), REFUSE/SOLID WASTE 

SITES (INDOOR), REFUSE/SOLID WASTE 

SITES (OUTDOOR), SEWAGE SYSTEMS 

(INDOOR), SHIPS AND BOATS (INDOOR),

UTILITIES

3.3. Environmental Fate and Transport

Fate properties

Dinotefuran has a molecular weight of 202.2 g/mole, a very high water solubility (39,830 mg/L), 

and a low octanol/water partition coefficient (Kow = 0.283; log Kow = -0.549), suggesting a

potential for low bioaccumulation. The low vapor pressure (1.275 x 10-8 mm Hg) and a low 

Henry’s Law Constant (8.63 x 10-14

atm • M3/mol) suggest that this compound is not expected to 

volatilize substantially from water or soils in the environment. The environmental fate and 

physico-chemical properties of dinotefuran are listed in Table 4.

Table 4. Physicochemical Properties for Dinotefuran

Parameter Value Reference/ Comments

Selected Physical Chemical Parameters

Chemical Classification Nitroguanidine

Pesticide Classification Systemic Insecticide

Molecular Weight 202.2 g/mol MRID # 45640101

Water Solubility (20oC) 39,830 mg/L for parent

 

MRID# 45640112

Vapor pressure (30oC) <1.275x10-8 mm Hg 

(equivalent to <1.7 x 10-6 Pa)

MRID# 45640105

MRID# 45639702

Henry's Law Constant 8.63 x 10-14 Atm m3/mol Calculated

Octanol/Water Partition, Kow 0.283 @25oC MRID # 45639702

log KOW -0.549 MRID # 45639702

Dissociation constant (pKa) 12.6 @20oC (estimated) MRID # 45639702

Melting point 107.5oC MRID # 45639702

pH 5.6 @25oC MRID # 45654201

Density 1.40 g/cm3 @20oC MRID # 45639702
Page | 18

Table 4. Physicochemical Properties for Dinotefuran

Parameter Value Reference/ Comments

Solvent solubility (mg/L at 20°C) g/100 mL Solvent MRID # 45639702

Hexane 9 x 10-7

Heptane 1.05 x 10-6

Xylene 0.0072

Toluene 0.0149

Dichloromethane 6.45

Acetone 6.13

Methanol 6.00

Ethanol 2.01

Ethyl Acetate 0.52

UV/visible absorption spectrum Media Absorbance 

Maximum 

268 nm

€max: Molar

Absorbance 

Coefficient

MRID # 45639702

Acidic 1.0469 12,600

1.0180 12,300

Neutral 1.3017 12,500

1.2668 12,300

Basic 0.8869 10,700

0.9662 11,700

Environmental fate properties for dinotefuran are shown in Table 5. Potential routes of 

dissipation for dinotefuran are aqueous photolysis, leaching, and runoff. It is stable to abiotic 

hydrolysis, but rapidly photodegrades in water half-life 1.8 days. Major photodegradation 

products (>10% applied radioactivity) include 1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl) 

guanidine (UF), 1-methylguanidinium chloride (MG hydrogen chloride) , DN-2-OH + DN-3-

OH, 3-(Methylamino)-9-oxa-2-aza-4-azoniabicyclone-3-ene hydrogen succinate (BCDN 

succinate). DN is a minor photodegradation product (<10% applied radioactivity). Dinotefuran 

is moderately persistent in soil under both aerobic (half-life = 16-100 days) and anaerobic (halflife = 62 days) conditions. Dinotefuran degrades to form 1-methyl-2-nitroguanidine (MNG), 

which subsequently degrades to form nitroguanidine (NG). It is very highly mobile (Koc = 6-45) 

in soil. Because dinotefuran has low sorption coefficients in soil, it has a high potential to leach

and runoff from the application site. The fate of dinotefuran in aquatic environments will depend 

on the type of water body. Aqueous photolysis should be important in clear and shallow bodies 

of water; however, in deep ponds lakes or reservoirs, aquatic metabolism is expected to dominate 

the dissipation processes. Dinotefuran was moderately persistent under actual use conditions in 

CA, NY, and GA field studies. The major degradation product was identified as MNG. 

Although there was no detection of dinotefuran in deep soil samples, MNG was detected in 15 to 

30 cm soil layers in the GA field dissipation study. 
Page | 19

Table 5. Environmental Fate Properties for Dinotefuran

Parameter Value Reference/ Comments

Hydrolysis Half-life stable MRID# 45640102 (s)

MRID# 45640102 (a)

Photodegradation in Water Half-life 1.8 days MRID# 45640105 (s)

Photodegradation in Soil Half-life Stable MRID# 45640109 (u)

Aerobic Soil Metabolism Half-life 38 days , Loamy Sand Soil

17 days, Loam Soil

78 days, Loam soil

89 days, Loamy Sand soil

63 days, Loamy Sand soil

100 days, Loamy Sand soil

87.7 days, Loamy Sand soil 

15.9 days, Silt Loam soil

MRID# 45640111 (s)

MRID# 45640112(s) 

MRID#’s 46751101(a) 

MRID#45640112(a)

MRID# 46711201 (s)

Anaerobic Soil Metabolism Half-life 65 days MRID# 45891616 (s)

Aerobic Aquatic metabolism Half-life 79.3 days

76.0 days 

MRID # 45640117 (s)

Batch Equilibrium

Loam 1.01 42

Texture Kd Koc

Sandy Loam 0.71 45

Clay Loam 1.22 42

Loamy Sand 0.12 6

Silt Loam 0.22 22

MRID# 45640114 (a)

Terrestrial Field Dissipation CA (SL) t1/2 = 65.2 days 

MNG (degradate) was detected in 0-15 

cm soil at 31.5% @ 45 days after 2nd 

application.

GA (SL) t1/2 = 19.4 days 

MNG was detected in 0-15 cm soil at 

5.3% max. mean concentration after 7 

and 30 days after the 2nd application.

NY (SL) t1/2 = 55.9 days 

MNG was detected in 0-15 cm soil at 

6.6% @ 45 and 120 days after the 

Applied 2X @ 0.268 lb a.i/A @ 14-

day interval to bare soil.

second application.

MRID# 45640118 (a)

Accumulation in Fish, max. BCF NA Waived (KOW = 0.28)

* (a) = acceptable study that fulfills guideline requirement; (s) = supplemental study (u)=unacceptable; NA=Not Available; 

N/A=Not Applicable

The degradation products of dinotefuran are shown in Table 6 (as well as Appendix A). MNG,

is the major degradation product in soil. DN, UF, MG hydrogen chloride, DN-2-OH+DN-3-OH, 

and BCDN succinate are major degradation products in aquatic environments. These 

degradation products are formed through metabolism (i.e., DN) or photodegradation (i.e., DN, 

UF, MG hydrogen chloride, DN-2-OH+DN-3-OH, and BCDN). 

MNG contains the nitro guanidine structure and therefore is considered to possess similar 

toxicity as the parent. DN is also structurally similar to the parent and therefore is considered to 

exhibit similar toxicity as the parent. Given the structures of the remaining degradates, they are 

expected to be less toxic than the parent (MARC memo USEPA 2004, D293759).
Page | 20

Table 6. Dinotefuran Degradates Identified in Environmental Fate Studies 

Short 

names

Structure Study Name

Results (calculated or observed halflife, degradates, and quantities, in 

% applied)

MNG

Aerobic Soil Metabolism

Maximum 23.96% at 42 days 

(preliminary study)

Maximum 13.7% at 225 days 

(conducted on radiolabeled parent), 

study termination

Terrestrial Field Dissipation

Maximum 31.5% at 45 days after 2nd

application; study termination at 170 

days after 2nd application

DN

Anaerobic Soil Metabolism

Maximum 29.2% at 120 days in 

Switzerland soil

Aerobic Aquatic Metabolism

Maximum 23.1% at 180 days in river 

system and 32.6% at 103 days in pond 

system

Photolysis in Water Maximum 7.5% at 11 days

UF Photolysis in Water Maximum 10.6% at 13.8 days (last 

test interval) 

MG 

hydrogen 

chloride

Photolysis in Water

Maximum 10.2% at 1.8 days, and 

0.8% at 13.8 days (final sampling 

interval)

DN-2-OH 

+ DN-3-

OH1

Photolysis in Water

Maximum 28.2% at 13.8 days (study 

termination)

BCDN 

Succinate Photolysis in Water

Maximum 16.1% at 1.8 days and 

4.5% at 13.8 days (study termination)

Environmental fate properties for MGN are shown in Table 7. Potential routes of dissipation 

include photodegradation, leaching, and runoff. MGN is stable to abiotic hydrolysis at pH 4, 7, 

and 9. It rapidly photodegrades (t1/2= 2.4 days) in water. MGN is moderately persistent (t1/2= 

66.9 to 166 days) in soil and persistent (t 1/2= 459 days) in aquatic environments. It has low 

soil:water portioning coefficients (Kd < 1; Koc <31), suggesting a potential for leaching and 

runoff. Field dissipation studies showed MGN residue detections in the 15-30 cm soil layer in a 

GA field study. These data suggest a leaching potential under actual use conditions. 

 

N

H

H2N

N

CH3

NO2

O N

H

NH

N

H

CH3

H3PO4

O N

H

O

N

H

CH3

NH

N

H

H2N

CH3

ClH

O

H

N NH

HN

OH

COOH

COOH

2

HN N

O

HN

CH3

COOH

COOH
Page | 21

Table 7. Physicochemical and Environmental Fate Properties for Dinotefuran

Degradation Product-MGN 

Parameter Value Reference/ Comments

Selected Physical Chemical Parameters

Water Solubility (20oC) 11,480 mg/L MRID# 45640112

MRID# 45639702, 45639706, 

45639707 (USEPA Pesticide 

Fact Sheet, 2004)

Hydrolysis Half-life

 pH 4-9 (50oC)

 

stable MRID# 45640103 (s)

Photodegradation in Water Half-life 2.4 days MRID# 45640107 (s)

Aerobic Soil metabolism Half-life 66.9 days in Silt Loam soil 

166 days in Sandy Loam soil

72.5 days in Clay Loam soil

MRID# 46711202 (s)

Aerobic Aquatic metabolism t1/2 459.3 days MRID # 45640117 (USEPA 

Pesticide Fact Sheet, 2004)

Mobility in Soils

Loam 0.75 31

Texture Kd KOC

Sandy Loam 0.12 8

Clay Loam 0.70 24

Loamy Sand 0.16 8

Silt loam 0.16 16

MRID# 45640116 (s)

* (a) = acceptable study that fulfills guideline requirement; (s) = supplemental study; (u) = unacceptable study; NA=Not 

Available; N/A=Not Applicable

Environmental fate properties for DN-phosphate5 are shown in Table 8. Potential routes of 

dissipation include photodegradation, microbial-mediated metabolism, leaching, and runoff. Nphosphate is stable to abiotic hydrolysis at pH 4, 7, and 9). Photodegradation is slow (t1/2= 53.4 

to stable days) in water at pH 5, 7, and 9. It is moderately persistent (t1/2= 114 days) in soil and 

aquatic environments. DN-phosphate has low soil:water portioning coefficients (Kd < 3; Koc 58-

413) in loam and sandy loam textured soils. Higher soil:water partitioning coefficients (Kd: 7 -

72; Koc: 270-2502) were found in clay textured soils. These data suggest the extent leaching or 

runoff of DN-phosphate is dependent on soil properties such as texture and organic carbon 

content. 

 5 DN phosphate (1-methyl-3-(tetrahydro-3-furylmethyl)guanidinium dihydrogen phosphate) was identified as a 

degradation product of dinotefuran in photodegradation in soil (MRID 45640109), photodegradation in water 

(MRID 45640106, 45640105) and anaerobic soil metabolism (MRID 45891616) studies. Although the phosphorus 

is not an elemental constituent of parent dinotefuran, DN phosphate was formed as a salt of orthophosphate and 1-

methyl- 3-(tetrahydro-3-furylmethyl)guanidinium. Because the DN phosphate salt will dissociate in soil and aquatic 

environments to form (1-methyl-3-(tetrahydro-3-furylmethyl)guanidinium) and phosphoric acid, it is not expected to 

alter the environmental fate or toxicity of the organic moiety of DN phosphate (1-methyl-3-(tetrahydro-3-

furylmethyl)guanidinium). 
Page | 22

Table 8. Physicochemical and Environmental Fate Properties for Dinotefuran

Degradation Product DN-Phosphate

Parameter Value Reference/ Comments

Selected Physical Chemical Parameters

Water Solubility (20oC) 619,400 mg/L MRID# 45640112

MRID# 45639702, 45639706, 

45639707 (USEPA Pesticide 

Fact Sheet, 2004)

Hydrolysis Half-life

DN-Phosphate pH 4-9 (50oC)

stable MRID# 45640104 (s)

Photodegradation in Water Half-life 

pH 5

pH7

pH9

53.4 days 

Stable (533.2 days) 

Stable

MRID# 45640108 (s)

Aerobic Soil Metabolism Half-life

DN

114 days MRID# 45640117 (USEPA 

Pesticide Fact Sheet, 2004)

Aerobic Aquatic metabolism t1/2 114 days MRID# 45640117 (USEPA 

Pesticide Fact Sheet, 2004)

Mobility in Soils

DN-Phosphate Loam 2.08 87

Texture Kd KOC

Sa ndy Loam 2.07 58

Clay Loam 72.54 2502

Sandy Loam 2.93 413

Clay 7.11 270

MRID# 45640113 (s)

* (a) = acceptable study that fulfills guideline requirement; (s) = supplemental study; (u) = unacceptable study; NA=Not 

Available; N/A=Not Applicable

Environmental fate properties for UF are shown in Table 9. The potential route of dissipation is 

microbial-mediated metabolism. UF is stable to abiotic hydrolysis and photodegradation. It is 

moderately persistent in (t1/2= 60 days) in soil. 

Table 9. Physicochemical and Environmental Fate Properties for Dinotefuran

Degradation Product UF

Parameter Value Reference/ Comments

Selected Physical Chemical Parameters

Water Solubility (20oC) 4,171 mg/L for UF MRID# 45640112

MRID# 45639702, 45639706, 

45639707 (USEPA Pesticide 

Fact Sheet, 2004)

Hydrolysis Half-life

UF

Stable MRID# 45640102 (USEPA 

Pesticide Fact Sheet, 2004)

Photodegradation in Water Stable (~500 days) MRID# 45640105 (USEPA 

Pesticide Fact Sheet, 2004)

Aerobic Soil Metabolism Half-life 60 days (at mean) MRID# 45640111 (USEPA 

Pesticide Fact Sheet, 2004)

* (a) = acceptable study that fulfills guideline requirement; (s) = supplemental study; (u) = unacceptable study; NA=Not 

Available; N/A=Not Applicable
Page | 23

4. Receptors

Consistent with the process described in the Overview Document (USEPA, 2004), the risk 

assessment for dinotefuran will rely on a surrogate species approach. Toxicological data 

generated from surrogate test species, which are intended to be representative of broad 

taxonomic groups, are used to extrapolate the potential effects on a variety of species (receptors) 

included under these taxonomic groupings. The report of the Metabolism Assessment Review 

Committee (MARC, USEPA 2004 TXR No. 0052304 DP Barcode D293759) concluded that 

parent, MNG, DN, UF, DN-2-OH, and DN-3-OH are residues of concern in drinking water and 

that the parent, DN, UF, and PHP are residues of concern in plants. Therefore, the toxicity and 

potential exposure to non-target organisms to the parent and degradates (where data is available)

will be quantified and a total toxic residues (TTR) approach will be employed. The most 

sensitive endpoints from the available toxicity data for dinotefuran will be used to quantify risk.

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature are used to evaluate the potential direct and indirect effects of 

dinotefuran to aquatic and terrestrial receptors. This includes toxicity on the technical grade 

active ingredient, degradates, and when available, formulated products (e.g., “Six-Pack” studies). 

The open literature studies are identified through EPA’s ECOTOXicology (ECOTOX) database,

which employs a literature search engine for locating chemical toxicity data for aquatic life, 

terrestrial plants, and wildlife. However, a preliminary review of the open literature was not 

performed for the problem formulation as no ECOTOX run was available. It is expected that an 

ECOTOX run will be available at the time of the risk assessment. The evaluation of both sources 

of data may also provide insight into the direct and indirect effects of dinotefuran on biotic 

communities from loss of species that are sensitive to the chemical and from changes in structure 

and functional characteristics of the affected communities. A search of the EPA Ecotox database

(http://cfpub.epa.gov/ecotox/quick_query.htm) yielded two studies, one aquatic and one 

terrestrial, which have not been reviewed:

• Barbee, G.C. and M.J. Stout. 2009. (Ref. #120043; Aquatic test #: 787594). TGAI (purity 

98.9% a.i.). Procambarus clarkii (red swamp crayfish). 96-hour LC50 2.032 mg a.i./L 

(0.969-2.951 mg a.i./L). Pest Management Science 65(11): 1250-1256.

• Iwasa, T., N. Motoyama, J.T. Ambrose, and R.M. Roe. 2004. (Ref. #95986; Terrestrial 

test #: 444482). TGAI. Apis mellifera (honey bee). 24-hour LD50 0.075 μg a.i./bee 

(0.0628-0.0896 μg a.i./bee). Crop Protection 23: 371-378.

A summary of the most sensitive data representing non-target organisms exposed to dinotefuran

in aquatic and terrestrial habitats is provided later in this document. A description of ecological 

incident data and of ecosystems potentially at risk are also provided. Appendix B provides a 

detailed summary of all available toxicity data. 

4.1. Effects to Aquatic Organisms

Aquatic Animals (Acute/Chronic)

The data submitted by the registrant show that dinotefuran (technical MTI-446) is practically 

nontoxic on an acute basis to freshwater and estuarine/marine fish (96-hour LC50 > 99 mg a.i./L), 

as well as freshwater invertebrates (D. magna 48-hour LC50 > 968.3 mg a.i./L; MRID 45639709) 
Page | 24

and saltwater mollusks (eastern oyster 96-hr EC50 > 141 mg a.i./L; MRID 45639711); no 

sublethal effects were noted in these studies. The degradate of dinotefuran (DN phosphate) is 

also considered practically non-toxic to the freshwater invertebrate (D. magna 48-hour LC50 > 

110.6 mg a.i./L; MRID 45639710); however, in the same acute study, on the basis of 10% 

immobility in the highest concentration tested a NOAEC of 10 mg a.i./L was determined. 

However, on an acute basis dinotefuran appears to be highly toxic to the estuarine/marine 

invertebrates (mysid shrimp LC50 = 0.79 mg a.i./L; MRID 45639713). 

Chronic toxicity testing on freshwater fish (rainbow trout; MRID 45639719) and invertebrates 

(D. magna; MRID 45639718) showed no treatment related effects and NOAECs of > 6.36 mg 

a.i./L and > 95.3 mg a.i./L, respectively. Since estuarine/marine chronic toxicity studies were not 

submitted for this compound there is uncertainty regarding chronic risk to estuarine/marine fish, 

but a major uncertainty regarding chronic risk to estuarine/marine invertebrates. Based on the 

available data the estuarine/marine invertebrates (mysid, LC50 = 0.79 mg a.i./L) are significantly 

more sensitive to dinotefuran than freshwater invertebrates (Daphnia, LC50 >110.6 mg a.i./L) on 

an acute exposure basis. Given that the acute and chronic endpoints for the freshwater 

invertebrate are non-definitive, estimates for the chronic saltwater invertebrates on the basis of 

an acute-to-chronic ratio would not be reliable. Therefore, a chronic mysid study is needed to 

address this uncertainty.

Table 10. Acute effect concentrations (LC50/EC50) for aquatic animals following exposure to dinotefuran

Species Measurement 

Endpoint

Time LC50/EC50 MRID / OPPTS 

GLN#

Waterflea

Daphnia magna

Mortality/Immobility

(Test substance: DN 

phosphate, metabolite 

of dinotefuran)

48 hr LC50 > 110.6 mg a.i./L

NOEAC: 10 mg a.i./L

LOAEC: 110.6 mg a.i./L

Endpoint(s) affected: After 48 hours, 

there was 10% immobility in the 110.6 

mg a.i./L treatment group which was 

the basis for a NOAEC of 10 mg a.i./L. 

The control and other treatment groups 

had 0% immobility.

45639710

(Acceptable/ 

Practically nontoxic1

)

850.1010

Mysid 

Americamysis bahia

Mortality (TGAI: 

99.2%)

96 hr LC50: 0.79 mg a.i./L

NOAEC: 0.49 mg a.i./L

LOAEC: 1.0 mg a.i./L

Endpoint(s) affected: Mortality, 

sublethal effects

(Sub)lethal effects: At 96 hours, 

mortality was 5% in the contol and 5, 

5, 0, 5, 75, and 100% for the test 

concentrations, respectively. Erratic 

swimming and loss of equilibrium were 

observed in surviving mysids from the 

1.0 and 2.0 mg a.i./L treatment levels 

during the test. Lethargic mysids were 

observed in the 1.0 mg a.i./L treatment 

level.

45639713

(Acceptable/ 

Highly toxic1

)

850.1035

1

Based on EC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic
Page | 25

Aquatic Plants

Toxicity testing on aquatic vascular plants (L. gibba; MRID 45639731) showed no treatment 

related effects yielding 7-day EC50 and NOAEC values of > 110 mg a.i./L and ≥ 110 mg a.i./L, 

respectively. Non-vascular plant (P. subcapitata) acute toxicity testing on two degradates MNG 

(MRID 45639733) and DN (DN-phosphate; MRID 45639734) also showed no treatment related 

effects and thus 96-hour EC50 and NOAEC values of > 98.7/ ≥98.7 mg a.i./L and > 100.4 / 

≥100.4 mg a.i./L, respectively. However, testing with the TGAI (MTI-446, dinotefuran) 

indicated a significant effect on cell density for P. subcapitata at the two highest test 

concentrations yielding a 96-hour NOAEC of 25 mg a.i./L; the EC50 for cell density, biomass, 

and growth rate endpoints, however, is >97.6 mg a.i./L (the highest concentration tested).
Page | 26

Table 11. Effect concentrations (EC50/NOAEC) for aquatic plants following exposure to dinotefuran

Species Measurement 

Endpoint

Time EC50/NOAEC MRID / OPPTS 

GLN#

Vascular

Duckweed 

Lemna gibba

Dry weight, 

growth rate, 

biomass

(TGAI: 99.2

7-

day

All endpoints:

EC50 >110 mg a.i./L

NOAEC ≥ 110 mg a.i./L

Endpoints affected: None

(Sub)lethal effects: Compared to the 

control, frond dry wt decreased by 21.5, 

2.9, 12.9, 2.3, and 4.3%, biomass 

decreased by 11.2, 3, 17.5, 12.5, and 

8.4%, growth rate decreased by 4.8, 2.3, 

6.9, 4.7, and 3.2%.

45639731

(Supplemental1)

850.4400

Non-vascular

Green Algae 

Pseudokirchneriella 

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Cell density, 

biomass, growth 

rate (TGAI: 

97.26%)

96 hr EC50 > 97.6 mg a.i./L

EC05: 21 mg a.i./L

NOAEC: 25 mg a.i./L

Endpoint(s) affected: Cell density.

(Sub)lethal effects:

Cell density significantly reduced in the 

two highest test concentrations, thus the 

determination of NOAEC of 25 mg a.i./L. 

The 96-hr %inhibition of growth rate was 

1.5, 0, 0.5, 1.6, and 2.0%; of AUG curve 

was 12, -3.2, -1.1, 5.9, and 3.6% for test 

concentrations, respectively. Shape of 

cells was unaffected.

45639732

(Acceptable)

850.5400

Green Algae 

Pseudokirchneriella 

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Metabolite

MNG

96 hr EC50 > 98.7 mg a.i./L

NOAEC ≥ 98.7 mg a.i./L

Endpoints affected: None. 

(Sub)lethal effects: Compared to the 

control, 96-hr %inhibition for cell density 

was 34, -8, and 23%, for growth rate was 

20, -1.7, and 8.3%, for biomass was 30, -

9.8, and 14%

45639733

(Supplemental2)

850.5400

Green Algae 

Pseudokirchneriella 

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Metabolite DN 

(DN-Phosphate)

96 hr EC50 > 100.4 mg a.i./L

NOAEC ≥ 100.4 mg a.i./L

Endpoints affected: None. 

(Sub)lethal effects: Compared to the 

control, 96-hr %inhibition for cell density 

was 31, -6, and 1%, for growth rate was 

7, 0, and 2%, for biomass was 15, 2, and 

4%

45639734

(Supplemental2)

850.5400

1 The study is scientifically sound, but does not satisfy guideline requirements for a tier II acute toxicity study with 

aquatic vascular plants because there were an insufficient number of plants per replicate, test concentrations were 

not analytically determined, and replicate data were only provided for frond number.

2 As there is no requirement for testing with a degradate, the study is classified as supplemental.
Page | 27

4.2. Effects to Terrestrial Organisms

Terrestrial Toxicity Summary (Acute/Chronic)

Dinotefuran was tested on various species of birds (Japanese quail, northern bobwhite quail, and 

mallard duck for acute oral and dietary studies; and, bobwhite quail and mallard duck for chronic 

reproduction studies). The parent compound is practically nontoxic to Japanese quail (LD50 > 

2,000 mg a.i./kg-bw; MRID 45639720) and bobwhite quail (LD50 > 2,250 mg a.i./kg-bw; MRID 

47353601) on an acute oral basis and to mallard duck (LC50 > 5,000 mg a.i./kg-diet; whereby the 

mean test item intake

Birds

6 is 997.9 mg a.i./kg-diet per day; MRID 45639722) and Japanese quail 

(LC50 > 5,000 mg a.i./kg-diet; whereby the mean test item intake is 1301 mg a.i./kg-diet per day; 

MRID 45639721) on a subacute dietary basis. However, sublethal effects (somnolence up to 3 

hours after administration of the test compound) were observed in the highest test concentration 

(2,000 mg a.i./kg-bw) of the acute oral Japanese quail study leading to a NOAEL determination 

of 1,000 mg a.i./kg-bw. Sublethal effects were not noted in the bobwhite quail acute oral, mallard 

duck or Japanese quail acute dietary studies. Although there appeared to be no significant 

treatment-related effects on bobwhite quail (MRID 45639724) reproductive parameters, chronic 

testing on mallard duck (NOAEC = 2,150 mg a.i./kg-diet; MRID 45639723) showed significant 

reductions in the percentages of number of hatchlings/eggs laid, eggs set, and 14-day old 

survivors. 

Dinotefuran is slightly to practically nontoxic on an acute basis to mammals (laboratory rat) 

(female LD50 = 2000 mg/kg-bw; MRID 45639823). Chronic studies indicated effects on rats and 

rabbits. A 2-generation reproduction study for MTI-446 (dinotefuran) technical on the rat 

indicated a reproductive NOAEL of 3,000 mg/kg-diet (MRID 45639913) based on decreased 

uterine weights and microscopic alterations in the uterus and estrous cyclicity in Fo and F1

females, slight increases in abnormal sperm morphology in Fo and F1 males, and slight decreases 

in testicular sperm count in Fo males and sperm mortality in F1 males. The developmental 

toxicity NOAEL for MTI-446 (dinotefuran) technical on rabbits is ≥ 300 mg/kg-bw/day, while 

the maternal toxicity NOAEL is 52 mg/kg-bw/day based on decreased body weight gain, 

decreased food consumption, and gross necropsy findings (pale discoloration of the liver and 

gray white plaques in the stomach). The rabbit study is included here to illustrate that sublethal 

effects as a result of chronic exposure to dinotefuran occur in multiple mammalian species; both 

the rat and rabbit studies may be utilized in risk description of a future risk assessment. The 

degradates MNG and DN were not tested on birds or mammals.

Mammals

Dinotefuran technical, MTI-446, (MRID 45639725) is highly toxic to bees on an acute 

Terrestrial Invertebrates

contact

basis (48-hr LD50 = 0.047 μg ai /bee) and on an acute oral basis (48-hr LD50 = 0.023 μg ai/bee). 

Similarly, the dinotefuran formulation, MTI-446 20%WG (MRID 45639726, with control; 

MRID 45639727, without negative but with solvent control) is also highly toxic to bees on an 

acute contact (48-hr LD50 = 0.061 μg a.i./bee and 0.024 μg a.i./bee, respectively) and on an acute 

oral

 6 The test item intake (TII) was calculated based on food consumption and the nominal test item concentration in the 

diet. For the dietary studies, these values were calculated by the study author.

basis (48-hour LD50 = 0.032 μg a.i./bee and 0.0076 μg a.i./bee, respectively). The RT25 (or 
Page | 28

residual time to cause 25% mortality) derived from the exposure to residues on alfalfa study 

(MRID 45639728) with the formulation MTI-446 20% WG indicated that bees were most 

sensitive to the 8 hour aged residue (RT25 = 4.8 hours) and least sensitive to treatment when 

exposed to 48 hour aged residue (RT25 = 90 hours). When translocated from pollen and nectar to 

bee hives, residues of dinotefuran can be detected in stored honey inside hives at least 85 days 

after application (honeybee field study, MRID 48120501), which suggests the occurrence of 

long-term chronic exposure inside the hive and has implications for overwintering success. In 

addition, exposure to dinotefuran formulation MTI-446 20% SG applications (of varying 

exposure periods) led to survivorship and reproductive effects on non-Apis terrestrial 

invertebrates including parasitoid wasp (Aphidius rhopalosiphi, MRID 45640121), predaceous 

bug (Orius laevigatus, MRID 45640122), and predatory mite (an arachnid, Typhlodromus pyri,

MRID 45640120) indicating LC50 values of 6.89x10-5 lbs a.i./A, 1.19x10-5 lbs a.i./A, and 0.027 

lbs a.i./A, respectively. It is important to note that the lowest non-definitive chronic endpoint 

NOAEC (<1.21 x 10-6 lbs a.i./A) reported for the predaceous bug study implies that we do not 

know, at this time, how much lower the application would need to be to elicit no response in 

terrestrial invertebrates. For additional comparative analyses including a comparison of 

dinotefuran and imidacloprid toxicities to insects refer to USDA Forest Service risk assessment 

(Durkin 2009; MRID 47814402). For further details on the toxicity studies see Appendix B.
Page | 29

Table 12. Acute effect concentrations (LD50/LC50) for terrestrial organisms following exposure to dinotefuran.

Species Measurement 

Endpoint

Time LD50/LC50 MRID / OPPTS 

GLN#

Birds

Japanese quail

Coturnix japonica

Oral Toxicity

(TGAI: 97.26%)

14 day LD50 > 2000 mg a.i./kg-bw

NOAEL: 1000 mg a.i./kg-bw

No mortality observed. All ♂ & ♀ 

birds showed somnolence up to 3 

hours after gavage in 2000 mg 

a.i./kg-bw level which was the basis 

for a NOAEL of 1000 mg a.i./kg-bw; 

otherwise, none

45639720

(Supplemental/ 

Practically nontoxic3

)

850.2100

Mammals

Rat

Rattus norvegicus

Oral Toxicity

(TGAI: 99.1%)

14 day ♂ LD50 = 2,804 mg/kg-bw

♀ LD50 = 2,000 mg/kg-bw

Endpoint(s) affected: Morbidity.

45639823

(Acceptable/ 

Toxicity category 

III)

870.1100

Rat Acute Inhalation 

Toxicity (TGAI: 

99.1%)

4 hours 

(exposure) 

14 day 

(observation)

LC50 > 4.09 mg a.i./L

(Sub)lethal effects: None.

45639902

(Acceptable / 

Toxicity category 

IV)

870.1300

Rat Acute Inhalation 

Toxicity (TEP: 

Dinotefuran 

75SG, 74.6%)

Limit test

4 hours 

(exposure) 

14 day 

(observation)

LC50 > 2.34 mg form/L

LC50 > 1.75 mg a.i./L

(Sub)lethal effects: No mortalities. 

Transient incidence of congested 

breathing at day1 and dark material 

around facial area.

46396307

(Acceptable / 

Toxicity category 

IV)

870.1300

Rat Acute Inhalation 

Toxicity (TEP: 

Dinotefuran 

35SL; 35.3%)

Limit test

4 hours 

(exposure) 

14 day 

(observation)

LC50 > 2.02 mg form/L

LC50 > 0.71 mg a.i./L

(Sub)lethal effects: None.

47814506 

(Acceptable / 

Toxicity category 

IV)

870.1300

Honey bee

Apis mellifera

Acute Oral

(EUP, MTI-446 

20% WG: 

21.4%)

48 hour LD50 = 0.0076 μg a.i./bee

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 13, 

3, 17, 43, 97, and 90% mortality was 

observed in the test treatments, 

respectively. Solvent control 

mortality was 20%. However, a 

45639727

(Supplemental2; 

highly toxic1

)

850.3020
Page | 30

concurrent dimethoate test had 13% 

mortality in the solvent control. At 4 

hours, there were stumbling and/or 

knockdown bees observed in every 

treatment and control group, except 

for the 0.00056 μg a.i./bee

*An important note is that the 

control mortality exceeded 10% (an 

OECD requirement), but not the 

20% guideline limit set for an acute 

contact study (OPPTS 850.3020).

Honey bee

Apis mellifera

Acute Contact 

(EUP, MTI-446 

20% WG: 

21.4%)

48 hour LD50 = 0.024 μg a.i./bee

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 3, 

3, 7, 43, 63, and 87% mortality was 

observed in the test treatments, 

respectively. Solvent control 

mortality was 0%. At 4 hours, there 

were stumbling and knockdown bees 

in the 0.036 and 0.08 μg a.i./bee 

groups.

45639727

(Acceptable / Highly 

toxic1

)

850.3020

1 Based on acute contact LD50 (μg a.i./bee) <2 highly toxic; 2-10.99 moderately toxic; ≥11 practically non-toxic 2 The study is a non-guideline study and does not fulfill an OPP guideline requirement. 3

Acute Oral (avian/mammal): Based on LD50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately toxic; 

501-2000 slightly toxic; >2000 practically nontoxic
Page | 31

Table 13. Chronic effect concentrations (NOAEC/LOAEC) for terrestrial animals (birds/mammals) following 

exposure to dinotefuran

Species Measurement 

Endpoint

Time NOAEC/

LOAEC

MRID / OPPTS 

GLN#

Birds

Mallard duck

Anas platyrhynchos

1-generation 

reproduction; 

dietary study 

(TGAI: 99.3%)

20 

weeks

NOAEC: 2150 mg a.i./kg-diet

LOAEC: 5270 mg a.i./kg-diet

Endpoint(s) affected: number of 

hatchlings/eggs laid and set, 14-day old 

survivors/eggs set

(Sub)lethal effects: One incidental mortality in 

control. Incidental injuries due to pen-wear. 

Reproductive effects resulted in endpoint 

determination.

45639723

(Acceptable)

850.2300

Mammals

Rat

Rattus norvegicus

2-Generation

Reproduction; 

dietary study 

(TGAI: 98.9%)

Repro. NOAEL = 3,000 mg/kg-diet 

(241-269 mg/kg-bw/day ♂;

267-292.6 mg/kg-bw/day ♀)

Repro. LOAEL = 10,000 mg/kg-diet

(822.1-934.7 mg/kg-bw/day ♂;

907-1004.8 mg/kg-bw/day ♀)

Endpoint(s) affected/Sublethal effects: 

Decreased uterine weights, microscopic 

alteration in uterus and vagina of Fo ♀; 

decreased numbers of primordial follicles in 

F1 ♀, altered estrous cyclicity in Fo ♀; slight 

increases in abnormal sperm morphology in 

Fo and F1 ♂, and slight decreases in testicular 

sperm count in Fo ♂ and sperm mortality in F1 

♂.

45639913 

(definitive test)

45639914 (rangefinding test)

(Acceptable)

870.3800

Rabbit

New Zealand white

Prenatal 

development; 

gavage study 

(TGAI: 92.9%)

Average weight of 

pregnant females 

across all doses: 

3.485 kg (3485 g)

Maternal NOAEL = 52 mg/kg-bw/day

Maternal LOAEL = 125 mg/kg-bw/day

Endpoint(s) affected: None. No statistically 

significant effects on developmental endpoints

Sublethal effects: Maternal toxicity was 

evident at doses of 125 and 300 mg/kgbw/day. Decreased bw gain (80% of controls) 

in ♀ in the 125 mg/kg-bw/day group at 

gestation days 6-18 and transient decrease in 

food consumption (84-90% of controls) after 

initiation (gestation days 6-10). Other findings 

include: liver discoloration, stomach plaque, 

transient neurological signs

45654208 

(definitive test)

45639911 (range 

finding test)

45639912 (range 

finding test)

(Acceptable)

870.3700
Page | 32

Terrestrial plant testing (Tier I seedling emergence OPPTS 850.4100, MRID 45639729, and 

vegetative vigor OPPTS 850.4150, MRID 45639730) on ten species indicated no effects as a 

result of a single application of LX1414-01 MTI-446 20% SG (20% dinotefuran) Lot # 01i-6252 

at a rate of 0.54 lbs a.i./A. For some plants, considered endpoints exhibited reductions relative to 

the controls which were < 25% which indicates that further testing (i.e., Tier II) is not required. 

The 14-day EC25 and NOAEL for both studies were >0.54 lbs a.i./A and ≥ 0.54 lbs a.i./A, 

respectively.

Terrestrial Plants

4.3. Incident Databases Review

Data on ecological incidents can be obtained through three incident databases: 1) the Ecological 

Incident Information System v. 2.1.1 (EIIS) maintained by EFED; 2) the Avian Incident 

Monitoring System (AIMS) maintained by the American Bird Conservancy; and, 3) the Incident 

Data System (IDS), a component of the PRISM database maintained by ITRMD.

No incidents have been reported (i.e., no records were found) in which dinotefuran has been 

associated with some type of environmental effect; this is the case for all three incident databases 

searched. The absence of documented incidents does not necessarily mean that such incidents did 

not occur. 

Mortality incidents must be seen, reported, investigated, and submitted to the Agency in order to 

be recorded in the incident databases. Incidents may not be noticed because the carcasses 

decayed, were removed by scavengers, or were in out-of-the-way or hard-to-see locations. Due 

to the voluntary nature of incident reporting, an incident may not be reported to appropriate 

authorities capable of investigating it. In addition, incident reports for non-target organisms 

typically provide information only on mortality events and plant damage. Sublethal effects in 

organisms such as abnormal behavior, reduced growth and/or impaired reproduction are rarely 

reported, except for phytotoxic effects in terrestrial plants. EPA’s changes in the registrant 

reporting requirements for incidents in 1998 may account for a reduced number of reported 

incidents. Registrants are now only required to submit detailed information on ‘major’ fish, 

wildlife, and plant incidents. Minor fish, wildlife, and plant incidents, as well as all other nontarget incidents, are generally reported aggregately and are not included in EIIS. In addition, 

there have been changes in state monitoring efforts due to a lack of resources. Reporting by 

states is only voluntary, and individuals discovering incidents may not be informed on the 

procedure of reporting these occurrences. Therefore, the number of reports listed in the EIIS 

database is believed to be only a small fraction of the total incidents involving mortality and 

other damage to non-target plants and animals from pesticide use. Although there were no 

reported incidences for this chemical, this does not rule out any existing risks that may 

potentially impact nontarget organisms.
Page | 33

4.4. Ecosystems Potentially at Risk

The ecosystems at risk are often extensive in scope; therefore, it may not be possible to identify 

specific ecosystems during the development of a nation-wide ecological risk assessment. 

However, in general terms, terrestrial ecosystems potentially at risk could include the treated 

field and immediately adjacent areas that may receive drift or runoff. Areas adjacent to the 

treated field could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or 

grasslands, woodlands, riparian habitats and other uncultivated areas. 

Aquatic ecosystems potentially at risk include water bodies adjacent to or downstream from the 

treated field and could include impounded bodies such as ponds, lakes and reservoirs, or flowing 

waterways such as streams or rivers. For uses in coastal areas, aquatic habitat also includes 

marine ecosystems, including estuaries. 

5. Assessment Endpoints

Assessment endpoints represent the actual environmental value that is to be protected, defined by 

an ecological entity (species, community, or other entity) and its attribute or characteristics 

(USEPA, 1998). For dinotefuran, the ecological entities may include the following: birds, 

mammals, terrestrial-phase amphibians, reptiles, freshwater fish and invertebrates, aquatic-phase 

amphibians, estuarine/marine fish and invertebrates, terrestrial plants, terrestrial invertebrates, 

and aquatic plants. The attributes for each of these entities include survival, growth, and 

reproduction.

6. Conceptual Model

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically 

significant concentrations. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure.

The conceptual model for dinotefuran provides a written description and visual representation of 

the predicted relationships between dinotefuran, potential routes of exposure, and the predicted 

effects for the assessment endpoint. A conceptual model consists of two major components: risk 

hypothesis and a conceptual diagram (USEPA, 1998).
Page | 34

6.1. Risk Hypothesis

A risk hypothesis describes the predicted relationship among the stressor, exposure, and 

assessment endpoint response along with the rationale for their selection. For dinotefuran, the 

following ecological risk hypothesis is being employed for this ecological risk assessment:

Based on the application methods, mode of action, fate and transport, and the sensitivity 

of non-target aquatic and terrestrial species, dinotefuran has the potential to reduce 

survival, reproduction, and/or growth in non-target terrestrial and aquatic organisms

(i.e., invertebrates directly and the organisms that prey on them indirectly) when used in 

accordance with the current labels. These non-target organisms include federally-listed 

threatened and endangered species as well as non-listed species. 

6.2. Conceptual Diagram

The environmental fate properties of dinotefuran indicate that runoff, spray drift and direct spray 

represent potential transport mechanisms of dinotefuran to aquatic and terrestrial habitats where 

non-target organisms may be exposed. These transport mechanisms (i.e., sources) are depicted 

in the conceptual models below along with the receptors of concern and the potential attribute 

changes in the receptors due to exposure to dinotefuran. In addition, given its systemic 

properties dinotefuran is expected to translocate within a treated plant to various tissues 

(including, but not limited to, edible portions such as fruit, seed, nectar, and pollen) post 

application. 

Sediment exposure

Although dinotefuran and degradate aerobic soil and aquatic metabolism studies indicate that 

half-lives of these compounds are high and indicate persistence (for example, parent dinotefuran: 

t1/2 range approximately 16-100 days for aerobic soil metabolism and 76-79 days for aerobic 

aquatic metabolism), no Kd value is ≥50 L/kg, no available log Kow is ≥3, and no Koc ≥1,000 

L/kg OC, which implies that, on the basis of fate data alone, acute and chronic sediment 

exposures will likely not lead to risk concerns for sediment-dwelling organisms (according to 

USEPA 2011). The only exception is DN-phosphate for a US (MN) clay loam soil for which Kd

is 72.5 and Koc is 2,502 which are outliers in the soil data for this degradate of dinotefuran

(MRID 45640113). However, toxicity data available on DN-phosphate indicate no effect to 

green algae (96-hr EC50>100.4 mg a.i./L, MRID 45639734) and an effect on mobility to 10% of 

treatment organisms (Daphnia) at the highest tested concentration, which led to a 48-hr NOAEC 

of 10 mg a.i./L (MRID 45639710), which would suggest that sediment toxicity studies would not 

be required.

Nevertheless, additional toxicity information on imidacloprid (USEPA 2008; USDA 2005)

suggests that the midge (Chironomus tentans, spiked water study, MRID 42256304, EC50: 0.069 

mg/L, 96-hr LC50: 0.0105 mg/L, 10-day growth NOAEC: 0.00067 mg/L) and the amphipod 

crustacean (Hyalella azteca, MRID 42256303, 96-hr EC50: 0.055 mg/L, 96-hr LC50: 0.526 mg/L) 

are of comparable sensitivity to imidacloprid as is the saltwater mysid (Mysidopsis bahia, MRID 

42055319, LC50: 0.037 mg/L; MRID 42055322, NOAEL >0.0006 mg/L and LOAEC: 0.0013 

mg/L). Furthermore, these organisms are more sensitive to imidacloprid relative to the water flea 
Page | 35

(Daphnia magna, MRID 42055317, 48-hr EC50: 85 mg/L; MRID 42055321, 21-day 

immobilization NOAEC: 1.3 mg/L). Given a similar response to dinotefuran, whereby greater

sensitivity of the saltwater mysid shrimp (LC50 = 0.79 mg a.i./L; MRID 45639713) is observed 

relative to the daphnia (48-hour LC50 > 968.3 mg a.i./L; MRID 45639709), it is assumed that 

sediment dwelling organisms (midge and amphipod) will have comparable toxicity to 

dinotefuran as does the mysid shrimp. Therefore, on the basis of toxicity data for dinotefuran and 

imidacloprid, acute and chronic sediment exposures could potentially lead to risk concerns for 

sediment-dwelling organisms. Furthermore, a similar toxicity trend is also observed for 

chemicals in the same class (neonicotinoids) as dinotefuran and imidacloprid, thiamethoxam and 

clothianidin (see Table 14). As a result, data from the mysid shrimp will be used as surrogate 

for the sediment-dwelling organisms unless confirmatory data on the sediment-dwelling 

organisms is submitted.

Table 14. Comparative toxicity of neonicotinoids to aquatic invertebrates. Most sensitive endpoints reported with 

MRID number in brackets

Species

Guideline No.

(A-Acute;

C-chronic)

Dinotefuran

(PC Code: 

044312)

Imidacloprid

(PC Code: 129099)

Thiamethoxam

(PC Code: 060109)

Clothianidin

(PC Code: 044309)

Midge 

(Chironomus sp.) 

[Freshwater]

850.1735 (A)

Non-Gln (C)

Acute and chronic 

data not available

Acute: 

48-hr LC50 = 0.069 

mg/L

48-hr NOAEC = 

0.001 mg/L

[MRID 42256304]

Chronic: 

Invalid study

[MRID 42256304]

Acute: 

48-hr EC50: 0.035 

mg/L 

NOAEC: 0.013 mg/L

[MRID 44714918]

Acute:

48-Hr EC50 = 0.022 

mg/L

NOAEC = 0.0068 

mg/L

[MRID 45422414]

Chronic:

10-d NOAEC = 0.001 

mg/L

(Pore water)

10-d NOAEC = 0.14 

mg/L

(Bulk sediment)

10-d NOAEC = 1.65 

mg/L (OC 

Normalized)

[MRID 46826902]

Amphipod 

crustacean 

(Hyalella azteca) 

[Freshwater]

850.1735 (A)

Non-Gln (C)

Acute and chronic 

data not available

Acute: 

96-hr EC50 = 0.055 

mg/L

96-hr LC50 = 0.526 

mg/L

[MRID 42256303]

Chronic data not 

available

Acute and chronic 

data not available

Acute and chronic 

data not available

[Saltwater]

850.1740 (A)

Non-Gln (C)

Estuarine 

Amphipod

Acute and chronic 

data not available

Acute and chronic 

data not available

Acute and chronic 

data not available

Acute data not 

available

Chronic:

10-d NOAEC = 

0.0085 mg/L
Page | 36

(Leptocheirus 

plumulosus)

(Bulk sediment)

10-d NOAEC = 

0.0204 mg/L

(Pore Water)

10-d NOAEC = 0.315 

mg/L TOC (OC 

Normalized)

[MRID 47199401]

Saltwater mysid

(Mysidopsis bahia)

850.1035 (A)

850.1350 (C)

Acute: 

LC50 = 0.79 mg/L

[MRID 

45639713]

Chronic data not 

available

Acute: 

LC50 = 0.037 mg/L

[MRID 42055319]

Chronic:

NOAEL> 0.0006 

mg/L

LOAEC = 0.0013 

mg/L

[MRID 42055322]

Acute:

96-hr LC50: 6.9 mg/L 

NOAEC: <2.0 mg/L

[MRID 44714922]

Chronic data not 

available

Acute:

96-Hr LC50 = 0.053 

mg/L

NOAEC < 0.04 mg/L

[MRID 45422403]

Chronic:

39-d NOAEC = 

0.0051 mg/L

LOAEC = 0.0097 

mg/L

[MRID 45422405]

Water flea

(Daphnia magna)

850.1010 (A)

850.1300 (C)

Acute: 

48-hr LC50>968.3 

mg/L

[MRID 

45639709]

Chronic:

21-day NOAEC > 

95.3 mg/L

[MRID 

45639718]

Acute: 

48-hr EC50 = 85 mg/L

[MRID 42055317]

Chronic:

21-day 

immobilization 

NOAEC = 1.3 mg/L

LOAEC = 3.6 mg/L

[MRID 42055321]

Acute:

48-hr EC50: >106 

mg/L

NOAEC: 36 mg/L

[MRID 44714919]

Chronic:

NOAEC: 50 mg/L

LOAEC: 101 mg/L

(based on number of 

neonates produced)

[MRID 44714924]

Acute:

96-Hr EC50 > 119 

mg/L

[MRID 45422338]

Chronic:

21-d NOAEC = 0.12 

mg/L

[MRID 45422412]

Groundwater exposure

Currently, the Agency does not have a routine method for quantifying the exposure and risk 

associated with the ground water route of exposure to aquatic receptors. Therefore, 

consideration of the ground water exposure pathway would be limited to a qualitative 

assessment. However, the importance of the movement of the pesticide and/or major 

degradate(s) of concern into ground water is based on available laboratory, field, and/or 

monitoring data. The data suggest that the parent compound, for example, is stable to hydrolysis 

at 25o

C and pH 4-9; and, persistent in soil (t1/2 range is approximately 16-100 days for aerobic 

soil metabolism [MRID 45640111, 45640112, 46751101, 46711201], which is greater than 2 

weeks as prescribed in USEPA 2011 guidance, and the t1/2 range is approximately 65 days for 

anaerobic soil metabolism [MRID 45891616]). Given this information, dinotefuran and the given 

degradates are expected to enter and persist in groundwater. Upper-bound estimates of the 

concentrations that might be found in groundwater due to the use of dinotefuran on leafy 

vegetables (using Tier I groundwater model, SCIGROW 2.3) are as follows: 2.75 ppb (parent 

dinotefuran), 0.86 ppb (MNG), 0.19 ppb (DN), 0.32 ppb (UF), and 0.94 ppb (DN-2-OH + DN-3-
Page | 37

OH) (USEPA 2004, DP Barcode: D285633). Terrestrial field dissipation results indicate that 

dinotefuran did not leach below the 0-15 cm soil layer (sandy loam) at the New York and 

California test sites, with two exceptions, and did not leach below the 15-30cm soil layer (sandy 

loam) at the Georgia test site. The transformation product MNG (the only degradate analyzed in 

this study) was not detected above the LOQ (0.01 mg/kg for dinotefuran and MNG) below the 0-

15 cm soil layer (MRID 45640118). Therefore, the data illustrate some leaching of parent residue 

to a depth of 15-30cm in the GA test site. Although soil samples were taken to a depth of 90 cm, 

it is generally difficult to discern clear leaching patterns from residue concentrations in soil 

samples.

In addition, dinotefuran is a mobile and persistent insecticide, there is potential for the compound 

to enter irrigation water leading to exposure to terrestrial plants apart from label prescribed rates. 

Exposure through systemic transport in plants to pollen/nectar and other edible tissue as well as 

drinking water, to terrestrial invertebrates is possible. Therefore, honey bees may be exposed via 

the oral route (edible portions in plants, drinking water) or contact route (spray from irrigation 

water). The extent of exposure to these organisms, however, is unclear, but toxicity is known to 

be high (acute oral 48-hr LD50 of 0.00076 μg a.i./bee; acute contact 48-hr LD50 0.024 μg a.i./bee; 

MRID 45639727); in addition, the acute contact LD50 translates to 0.19 ppm (i.e., 0.024 μg 

a.i./bee * 1 bee/0.128 g) or 187 ppb and the EEC associated with the interim LOC (0.05) is 

0.0094 ppm (9.4ppb), a concentration above which would be considered an LOC exceedance.

Atmospheric transport exposure

Fate properties, such as vapor pressure and Henry’s Law constant should be considered to 

characterize potential volatilization from dry and wet conditions. However, volatilization in air 

also depends on a variety of factors including soil properties (e.g., moisture content and organic 

matter content), farming practices (e.g., tillage and application rate and techniques), and 

meteorological factors (e.g., precipitation, temperature, humidity, and wind speed). If monitoring 

data provides evidence of a pesticide in the atmosphere, a tiered screening approach can be used 

to estimate the concentrations of applied pesticide in air, which can be compared with acute 

mammalian and avian inhalation toxicity data to evaluate potential effects on terrestrial 

organisms. Currently, EFED is evaluating some of the existing models in an effort to develop 

tiered screening and refined approaches to determine the rate of volatilization (flux) for semivolatile pesticides applications to bare soil and crop canopies and estimate the concentrations of 

applied pesticide in the atmosphere under varying environmental conditions.
Page | 38

Consumption of aquatic food items by piscivorous mammals and birds

KABAM (Kow (based) Aquatic BioAccumulation Model) is used to estimate potential 

bioaccumulation of hydrophobic organic pesticides in freshwater aquatic food webs and 

subsequent risks to mammals and birds via consumption of contaminated aquatic prey. KABAM 

should be used for pesticides having all of the following characteristics: the pesticide is a nonionic, organic chemical; the log Kow value is between 4 and 8; and, the pesticide has the potential 

to reach aquatic habitats. Dinotefuran meets two of the three criteria. It is a non-ionic organic 

chemical and has the potential to reach aquatic habitats; however, the log Kow value is -0.549. 

Therefore, KABAM will not be used to make estimates of exposure as bioaccumulation is not 

expected in freshwater aquatic food webs.

Figure 1. Conceptual model depicting stressors, exposure pathways, and potential effects 

to aquatic organisms from the use of dinotefuran. Dotted lines indicate exposure pathways 

that have a low likelihood of contributing to ecological risk.
Page | 39

Figure 2 Conceptual model depicting stressors, generic exposure pathways, and potential 

effects to terrestrial organisms (terrestrial plants, terrestrial invertebrates, and dietary 

routes of exposure for terrestrial vertebrates) from the use of dinotefuran. Dotted lines

indicate exposure pathways that have a low likelihood of contributing to ecological risk.

Additional Terrestrial Exposure Pathways

The Screening Tool for Inhalation Risk (STIR v.1.0, November 19, 2010) was used to calculate 

an upper bound estimate of exposure using dinotefuran’s vapor pressure (<1.275x10-8 mm Hg; 

<1.7 x 10-6 Pa at 30oC) and molecular weight (202.2 g/mol) for vapor phase exposure as well as 

the maximum application rate (0.54 lbs a.i./A, which is the maximum single as well as seasonal 

application rate to turfgrass) and method of application (ground spray applications; note: altering 

the method of application to aerial spray did not change the conclusions) for spray drift. STIR 

incorporates results from several toxicity studies including acute oral and inhalation rat toxicity 

endpoints obtained from the “six-pack” of core studies, which are a series of six guideline studies 

that are submitted to the Registration Division of the Office of Pesticide Programs for technical 

and formulated products of a pesticide (rat acute oral: ♀ LD50 = 2,000 mg/kg-bw, MRID 

45639823; rat inhalation (TGAI): LC50 >4.09 mg/L, MRID 45639902, although TEP endpoints 

on an a.i. basis were also modeled for comparison as well as the most sensitive acute oral avian 

toxicity endpoint (Japanese quail, using 193g as the body weight, LD50 > 2000 mg a.i./kg-bw, 

MRID 45639720). Based on the results of the STIR model, inhalation exposure alone was not 

determined to be a potential pathway of concern for avian or mammalian species on an acute 

basis. 

Inhalation Exposure
Page | 40

Inhalation exposure via spray drift and/or vapor-phase of the pesticide alone does not appear to 

be of concern. The analysis of the inhalation route in STIR does not consider that aggregation

with other exposure pathways such as dietary, dermal, or drinking water may contribute to a total 

exposure that has a potential for effects to non-target animals. However, the Agency does 

consider the relative importance of other routes of exposure in situations where data indicate that 

pesticide exposures through other routes may be potentially significant contributors to wildlife 

risk (USEPA, 2004). Detailed information about STIR v.1.0, as well as the tool, can be found on 

the EPA’s website at: http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial. 

Dermal Exposure

The dermal route of exposure for terrestrial wildlife can be divided into a few sub-routes. These 

include organisms exposed:

• In the treated field at the time of application or in the areas adjacent to the treated field 

and within the aerial drift plume that may come in direct contact with applied material. 

• While conducting daily activities within treated or drift-impacted areas whereby exposure 

may occur via contact with dislodgeable residues of the pesticide on treated vegetation. 

• To the pesticide deposited on soil particles either through contact with contaminated soil 

through portions of the body contacting the ground, dust bathing, or through incidental 

contact with fugitive dust emissions from treated or drift-impacted areas. 

• Via dermal contact with the pesticide that is dissolved in puddles water on the treated 

field or in areas impacted by drift and run-off. 

• To volatile compounds in the vapor phase integument via direct absorption. 

At the present time, the Agency does not have a method to quantify these levels of 

exposure, and data are limited to quantify the contribution of such exposures to the toxic burden 

an organism experiences. The Agency is actively working on a screening method to quantify 

exposure from direct impingement of applied foliar as well as bare ground sprays, granular 

applications, and from incidental contact with dislodgeable foliar pesticide residues from treated 

or drift-impacted vegetation. Given the application methods available for dinotefuran, this route 

of exposure for terrestrial wildlife is possible, but no quantification of exposure concentrations 

and attendant risks is possible until the completion of initial screening models.

Drinking Water Exposure

Drinking water for the purposes of terrestrial organism risk assessment is defined as that portion 

of an organism’s daily water intake that is not met by dietary or metabolic sources and must be 

consumed in liquid form. Typical drinking water sources for wildlife in pesticide use areas may 

include on-field puddles, irrigation equipment (e.g., drip irrigation in grape cultivation), dew 

deposited on treated plants, and off-field surface water exposures. 

The Screening Imbibition Program (SIP v.1.0, Released June 15, 2010) was used to calculate an 

upper bound estimate of exposure using dinotefuran’s high solubility in water (39,830 mg/L at 

20oC). Using TGAI dinotefuran data for the most sensitive acute (LD50>2000 mg a.i./kg-bw for 

the Japanese quail, using 193g as the body weight, MRID 45639720) and chronic (NOAEC of 
Page | 41

2150 mg a.i./kg-diet, mallard duck, MRID 45639723) avian toxicity endpoints and the most 

sensitive acute (♀LD50 = 2,000 mg/kg-bw, rat, MRID 45639823) and chronic (reproduction 

NOAEL = 3,000 mg/kg-diet or 241 mg/kg-bw/day, ♂ rat, MRID 45639913; as well as the 

maternal NOAEL = 52 mg/kg-bw/day, rabbit, using 3485g as the body weight, MRID 

45654208) mammalian toxicity endpoints. Drinking water exposure alone was determined to be 

a potential pathway of concern for avian and mammalian species on an acute and chronic basis 

(see Tables 15 and 16; note: the chronic mammalian results are based on the chronic rat, but the 

same conclusions are derived from the chronic rabbit data). However, this is likely a result of 

the high solubility limit and not necessarily expected based on available toxicity information. 

This pathway will be explored further with the development of SIP v.2.0 in the Ecological Risk 

Assessment for dinotefuran. Detailed information about the SIP v.1.0, as well as the tool, can be 

found on the EPA’s website at http://www.epa.gov/pesticides/science/models_pg.htm#terrestrial.

Table 15. Mammalian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 6850.7600 6850.7600

Adjusted toxicity value (mg/kg-bw) 1538.3211 185.3677

Ratio of exposure to toxicity 4.4534 36.9577

Conclusion*

Exposure through drinking 

water alone is a potential 

concern for mammals

Exposure through drinking 

water alone is a potential 

concern for mammals

Table 16. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 32262.3000 32262.3000

Adjusted toxicity value (mg/kg-bw) 1423.4785 106.6670

Ratio of exposure to acute toxicity 22.6644 302.4581

Conclusion*

Exposure through drinking 

water alone is a potential 

concern for birds

Exposure through drinking 

water alone is a potential 

concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. 

Therefore, when aggregated with other routes (i.e., diet, inhalation, dermal), pesticide exposure through 

drinking water may contribute to a total exposure that has potential for effects to non-target animals.
Page | 42

Figure 3. Conceptual model depicting stressors, drinking water and inhalation exposure 

pathways, and potential effects to terrestrial animals from the use of dinotefuran. Dotted lines

indicate exposure pathways that have a low likelihood of contributing to ecological risk.

7. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment will 

be estimated. The use, environmental fate, and ecological effects of dinotefuran will be 

characterized and integrated to assess the risks. Risk quotients (RQs) will be derived for 

dinotefuran by dividing estimated environmental concentrations (EEC) by the most sensitive 

endpoint from the relevant, available toxicity data for dinotefuran.

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket.
Page | 43

7.1. Stressors of Concern

The Agency does not routinely include, in its risk assessments, an evaluation of mixtures of 

active ingredients, either those mixtures of multiple active ingredients in product formulations or 

those in the applicator’s tank. In the case of the product formulations of multiple active 

ingredients (that is, a registered product containing more than one active ingredient), each active 

ingredient is subject to an individual risk assessment for regulatory decision regarding the active 

ingredient on a particular use site. If effects data are available for a formulated product 

containing more than one active ingredient, they may be used qualitatively or quantitatively in 

accordance with the Agency’s Overview Document and the Services’ Evaluation Memorandum 

(U.S., EPA 2004; USFWS/NMFS 2004). 

7.2. Measures of Exposure

In order to estimate risks of dinotefuran exposures in aquatic and terrestrial environments, all 

exposure modeling and resulting risk conclusions will be based on registered labels including 

maximum application rates and methods cited earlier for each use of dinotefuran. Measures of 

exposure are based on aquatic and terrestrial models that predict estimated environmental 

concentrations (EECs) of dinotefuran. The models used to predict aquatic EECs are the 

Pesticide Root Zone Model coupled with the Exposure Analysis Model System 

(PRZM/EXAMS). The model used to predict terrestrial EECs on food items is T-REX. The 

model used to derive EECs relevant to terrestrial and wetland plants is TerrPlant. These models 

are parameterized using relevant reviewed environmental fate data from registrant submissions 

and the literature; model input values will be consistent with the most recent version of the input 

parameter guidance (Version 2.1; EFED 2009). It should be noted that T-REX does not have 

capabilities to assess potential risk to terrestrial animals due to exposure to a systemic pesticide. 

Because dinotefuran is systemic, exposure to birds, mammals, and insects such as bees through 

consumption of translocated residues (applied via trunk injection, soil drench, or foliar 

spray/absorption) in plant materials (roots, leaves, stems, stalks, seeds, pollen, and nectar) is 

uncertain. 

PRZM (v3.12.2, May 2005) and EXAMS (v2.98.4.6, April 2005) are simulation models coupled 

with the input shell pe5.pl (November 2006). The models generate daily exposures and calculate 

1-in-10 year EECs of dinotefuran that may occur in surface water bodies adjacent to application 

sites receiving dinotefuran through runoff and spray drift. PRZM simulates pesticide 

application, movement, and transformation on an agricultural field and the resultant pesticide 

loadings to a receiving water body via runoff, erosion, and spray drift. EXAMS simulates the 

fate of the pesticide in the water body and estimates resulting concentrations. The standard 

scenarios used for ecological pesticide assessments assume application to a 10-hectare 

agricultural field that drains into an adjacent 1-hectare water body that is 2 meters deep (20,000 

m3 volume) with no outlet. PRZM/EXAMS is used to estimate screening-level exposure of 

aquatic organisms to dinotefuran. The measure of exposure for aquatic species is the 1-in-10 

year return peak or rolling mean concentration. The 1-in-10 year peak is used for estimating 

acute exposures of direct effects to aquatic organisms. The 1-in-10-year 60-day mean is used for 

assessing chronic exposure to fish and aquatic-phase amphibians. The 1-in-10-year 21-day mean 

is used for assessing chronic exposure to aquatic invertebrates.
Page | 44

In addition to modeling estimates, available monitoring data will be evaluated. Monitoring data 

will include those collected/reported by states as well as other federal departments/agencies (e.g., 

USGS National Water Quality Assessment (NAQWA; http://water.usgs.gov/nawqa)). 

Exposure estimates for terrestrial animals assumed to be in the target area or in an area exposed 

to spray drift are derived using the T-REX model (version 1.4.1, October 2008). This model 

incorporates the Kenaga nomograph, as modified by Fletcher et al. (1994), which is based on a 

large set of field residue data. The upper limit values from the nomograph represent the 95th

percentile of residue values from actual field measurements (Hoerger and Kenega 1972). The 

Fletcher et al. (1994) modifications to the Kenaga nomograph are based on measured field 

residues from 249 published research papers, including information on 118 species of plants, 121 

pesticides, and 17 chemical classes. EECs for terrestrial plants inhabiting dry and wetland areas 

are derived using TerrPlant (version 1.2.2, December 2006). This model uses estimates of 

pesticides in runoff and in spray drift to calculate EECs. EECs are based upon solubility, 

application rate and minimum incorporation depth in addition to type of formulation and method 

of application.

Two spray drift models, AGDisp and AgDRIFT are used to assess exposures of terrestrial plants 

to dinotefuran deposited in terrestrial habitats by spray drift. AGDISP (version 8.13; December 

2004) is used to simulate aerial applications. AgDrift (version 2.01; May 2001) is used to 

simulate spray blast applications to orchard crops.

7.3. Measures of Effect

Ecological effects data are used as measures of direct and indirect effects to biological receptors. 

Data are obtained from registrant-submitted studies and/or from literature studies identified by 

ECOTOX. The ECOTOX database provides more ecological effects data in an attempt to bridge 

existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential 

chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was 

created and is maintained by EPA, Office of Research and Development, and the National Health 

and Environmental Effects Research Laboratory's Mid-Continent Ecology Division.

Information on the potential effects of dinotefuran on non-target animals is also collected from 

the Ecological Incident Information System (EIIS; USEPA, 2007c). The EIIS is a database 

containing adverse effect (typically mortality) reports on non-target organisms where such 

effects have been associated with the use of pesticides. Incidents reported in the aggregate 

incident reports and the Avian Incident Monitoring System (AIMS) will also be searched. AIMS 

is a database administered by the American Bird Conservancy (partially funded by EPA). It 

contains publicly available data on reported avian incidents involving pesticides 

(http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm). Finally, the 

Incident Data System (IDS), a component of the PRISM database maintained by ITRMD, is also 

a source of incident information.

Where available, sub-lethal effects observed in both registrant-submitted and open literature 

studies will be evaluated qualitatively. Such effects may include behavioral changes (e.g., 
Page | 45

lethargy and changes in coloration). Quantitative assessments of risks, though, are limited to 

those endpoints that can be directly linked to the Agency’s assessment endpoints of impaired 

survival, growth and reproduction.

The assessment of risk for direct effects to non-target organisms makes the assumption that 

toxicity of dinotefuran to birds is similar to terrestrial-phase amphibians and reptiles. The same 

assumption is made for fish and aquatic-phase amphibians. 

The acute measures of effect used for animals in risk assessments are the LD50, LC50 and EC50. 

LD stands for "Lethal Dose", and LD50 is the amount of a material, given all at once, that is 

estimated to cause the death of 50% of the test organisms. LC stands for “Lethal Concentration” 

and LC50 is the concentration of a chemical that is estimated to kill 50% of the test organisms. 

EC stands for “Effective Concentration” and the EC50 is the concentration of a chemical that is 

estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic 

measures of exposure for listed and non-listed animals are the NOAEL/NOAEC and NOEC. 

NOAEL stands for “No Observed-Adverse-Effect-Level” and refers to the highest tested dose of 

a substance that has been reported to have no harmful (adverse) effects on test organisms. The 

NOAEC (i.e., “No-Observed-Adverse-Effect-Concentration”) is the highest test concentration at 

which none of the observed effects were statistically different from the control. The NOEC is 

the No-Observed-Effects-Concentration. For non-listed plants, only acute exposures are 

assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants); for listed plants either the 

NOAEC or EC05 is used. 

7.4. Integration of Exposure and Effects

Risk characterization is the integration of exposure and ecological effects characterization to 

determine the potential ecological risk from the use of dinotefuran and the likelihood of direct 

and indirect effects to non-target organisms in aquatic and terrestrial habitats. The exposure and 

toxicity effects data are integrated in order to evaluate the risks of adverse ecological effects on 

non-target species. For the assessment of dinotefuran risks, the risk quotient (RQ) method is 

used to compare exposure and measured toxicity values. EECs are divided by acute and chronic 

toxicity values. The resulting RQs are then compared to the Agency’s Levels of Concern (LOC) 

(USEPA, 2004). These criteria are used to indicate when dinotefuran’s use, as directed on the 

labels, has the potential to cause adverse direct or indirect effects to non-target organisms. In 

addition, incident data from EIIS, incident data system reports, and AIMS will be considered as 

part of the risk characterization.
Page | 46

7.5. Deterministic and Probabilistic Assessment Methods

The quantitative assessment of risk will primarily depend on the deterministic point-estimate

based approach described in a subsequent risk assessment. Depending on the risk manager’s 

need for additional information regarding risk, an effort will be made to further describe risk 

using probabilistic tools that the Agency has developed. These tools have been reviewed by 

FIFRA Scientific Advisory Panels (http://www.epa.gov/scipoly/sap/index.htm) and have been 

deemed as appropriate means of refining assessments where deterministic approaches have 

identified risks.

7.6. Endangered Species Assessment

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the 

Agency will evaluate risks to Federally-listed threatened and/or endangered (listed) species from 

registered uses of dinotefuran. Risk assessments will be conducted in accordance with the 

Overview Document (USEPA, 2004), provisions of the ESA, and the Services’ Endangered 

Species Consultation Handbook (USFWS/NMFS, 1998).

The assessment of effects associated with the registration of dinotefuran is based on an action 

area. The action area is considered to be the area directly or indirectly affected by the federal 

action, as indicated by the exceedance of Agency Levels of Concern (LOCs) used to evaluate 

direct or indirect effects. The Agency’s approach to defining the action area under the provisions 

of the Overview Document (USEPA, 2004) considers the results of the risk assessment process 

to establish boundaries for that action area with the understanding that exposures below the 

Agency’s defined LOCs constitute a no-effect threshold. For the purposes of endangered species 

risk assessment, attention will be focused on the footprint of the action (i.e., the area where 

dinotefuran application occurs), plus all areas where offsite transport (i.e., spray drift, runoff, 

etc.) may result in potential exposure that exceeds the Agency’s LOCs. Specific measures of 

ecological effect that define the action area for listed species include any direct and indirect 

effects and/or potential modification of its critical habitat, including reduction in survival, 

growth, and reproduction as well as the full suite of sub-lethal effects available in the effects 

literature. Therefore, the action area extends to a point where environmental exposures are 

below any measured lethal or sub-lethal effect threshold for any biological entity at the whole 

organism, organ, tissue, and cellular level of organization. In situations where it is not possible 

to determine the threshold for an observed effect, the action area will be assumed to encompass 

the entire United States.
Page | 47

7.7. Drinking Water Assessment

The most recent dinotefuran EFED drinking water assessment was carried out for a Section 18 to 

control a brown marmorated stink bug (BMSB) infestation in pome fruit and stone fruit in 

Virginia, Delaware, North Carolina, West Virginia, Pennsylvania, New Jersey and Maryland. 

See DP Bar Code: D389034, May 26, 2011. Screening-level Estimated Drinking Water 

Concentrations (EDWCs) simulated with the EFED FIRST model for the proposed new uses 

were approximately 20% higher than the EDWCs calculated previously by EFED. That 

assessment included total (cumulative) concentrations for parent dinotefuran and the same four 

degradates of toxicological concern that were included in the previous drinking water 

assessment. This was a tier 1 exposure assessment which assumed that peak concentrations for 

the parent and all four degradates occur simultaneously and that the entire drinking water 

watershed is treated at the same time with dinotefuran. Estimated surface water concentrations 

were higher than groundwater concentrations which were estimated based on the EFED 

SCIGROW model.

EFED will carry out a screening level exposure assessment for parent dinotefuran plus each 

degradate of toxic concern using the EFED FIRST model for the human health assessment. 

Under this tier 1 method, it is assumed that the peak concentrations for the parent and all toxic 

degradates occur simultaneously. If the resultant concentrations exceed EFED and/or HED levels 

of concern (LOC), a tier 2 exposure assessment using the formation/decline method in the linked 

EPA PRZM and EXAMS models will be carried out.

Concentrations of the residue in surface waters will be estimated using PRZM/EXAMS (see 

description above). The PRZM model simulates pesticide movement and transformation on and 

across the agricultural field resulting from crop applications. The EXAMS model simulates 

pesticide loading via runoff, erosion, and spray drift assuming a standard watershed of 172.8 ha 

that drains into an adjacent standard drinking water index reservoir of 5.26 ha and an average 

depth of 2.74 m. Percent Cropped Areas (PCA) that account for the maximum area within a 

watershed that may be planted with the modeled crop will be applied to adjust predicted 

concentrations by PRZM/EXAMS. Ground water estimates of dinotefuran concentrations will 

be established using SCI-GROW. The SCI-GROW model was developed by fitting a linear 

model to ground water concentrations with the Relative Index of Leaching Potential (RILP) as 

the independent variable. Ground water concentrations were taken from 90-day average high 

concentrations from Prospective Ground Water studies. The RILP is a function of aerobic soil 

metabolism and the soil-water partition coefficient. The drinking water assessment will also 

include available surface and ground water monitoring data.
Page | 48

7.8. 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 the registration review decision, 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/.

7.9. Preliminary Identification of Data Gaps

Available studies submitted to fulfill environmental fate and ecological effects guideline 

requirements, as well as outstanding data gaps for dinotefuran, are presented here.

7.9.1. Fate Data Gaps

The environmental fate data requirements for dinotefuran are partially fulfilled, and some data 

gaps still remain (Table 17). 
Page | 49

Table 17. Status of Available Environmental Fate Data and Remaining 

Data Gaps

Guideline Description MRID Classification Data 

Gap?

835.2120 Hydrolysis @ 50o

C 45640101 Supplemental

Hydrolysis @ 25oC 45640102 Acceptable

Hydrolysis @ 40oC 45640102 Supplemental No

MNG Hydrolysis in Water 45640103 Supplemental

DN Phosphate Hydrolysis in Water 45640104 Supplemental

835.2240 Photodegradation in Water 45640105 Supplemental

Photodegradation in Water 45640106 Unacceptable No

MNG Photodegradation in Water 45640107 Supplemental

DN Phosphate Photodegradation in 

Water

45640108 Supplemental

835.2410 Photodegradation in Soil 45640109

D316645

Supplemental No

835.2370 Photodegradation in Air 45640110 Supplemental No

835.4100

835.4200

Aerobic Soil Metabolism 45640111 Supplemental

Aerobic Soil Metabolism 46751101, 

45640112

Acceptable No

MNG Aerobic Soil Metabolism 46711202 Supplemental

Anaerobic Soil Metabolism 45891616 Supplemental No

N/A MNG Rate of Mineralization 46751103 Supplemental No

835.4300

835.4400

Aerobic Aquatic Metabolism 45640117 Supplemental No

Anaerobic Aquatic Metabolism N/A --- Yes

835.1230

835.1240

Leaching

Adsorption/Desorption

45640114

45640115

Acceptable

Supplemental

DN-Phosphate Leaching

Adsorption/Desorption

45640113 Supplemental No

MNG Leaching

Adsorption/Desorption

45640116 Supplemental

835.6100 Terrestrial Field Dissipation 45640118

45640124

45891610

45891615

Acceptable No

835.6200 Aquatic Field Dissipation N/A --- No

835.6300 Forestry Dissipation N/A --- No1

850.1730 Bioaccumulation in Fish (BCF) N/A --- No

1

Although the trigger for the forestry dissipation study is met (dinotefuran is registered 

for use in forests), EFED does not believe that a forestry dissipation study would add any 

additional useful information about major routes of dissipation above what is already 

known from the terrestrial field dissipation studies. 

N/A: Not available
Page | 50

7.9.2. Effects Data Gaps

Although many submissions have been made to provide data on the effects of dinotefuran to 

aquatic and terrestrial organisms, data gaps still exist and are included in Tables 18 to 20, below. 

For some neonicotinoids, recent assessments have identified the need for additional data to 

assess pollinator risks (e.g., residue studies of pollen and nectar, larval bee toxicity, lab feeding 

studies, field studies). Similar data requests are proposed for dinotefuran as well.

Although EFED has not historically assessed risk to nontarget insects or terrestrial invertebrates 

using the risk quotient method in ecological risk assessments, potential effects of dinotefuran on 

terrestrial invertebrates, using the honeybee (Apis mellifera) as a surrogate species will be 

evaluated pending developments in the Agency’s risk assessment process with respect to this

taxa. 

In an attempt to address protection of pollinators, EPA (or, the Agency) is anticipating data and 

assessment needs using bees as a surrogate for all beneficial terrestrial invertebrates. In moving 

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

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

Workshop on Pesticide Risk Assessment for Pollinators and the FIFRA Science Advisory Panel 

and is working with its federal and state partners, industry, and academia to determine 

appropriate assessment methodology. For compounds such as dinotefuran, which is (1) known 

to be acutely toxic to bees and (2) known to have exposure routes to bees, the Agency is 

requiring toxicity and exposure studies to allow for evaluation of risks to pollinators. The 

registrant should consult with the Agency on the conduct of these studies. 

The Agency will consider pollinator field studies (semi-field and full-field) as data gaps. 

However, requirement of these higher tier data will be based, in part, upon receipt and review of 

lower tier pollinator studies (i.e., residues in plant parts; the pollinator larval toxicity test; and/or, 

the pollinator laboratory chronic feeding study). The Agency will consider the recommendations 

of the SETAC workshop on Pesticide Risk Assessment for Pollinators and the FIFRA Scientific 

Advisory Panel. Furthermore, given that the California Department of Pesticide Regulation 

(CDPR) has already issued a data call-in for some honey bee studies for dinotefuran, it is 

possible that the Agency may be able to make use of that data for the purposes of the national 

ecological risk assessment; the registrant should consult with the Agency prior to assuming that 

the data received by CDPR will satisfy Agency data requirements.

Additional data gaps are noted and described below. Appendix C lists additional data needs for 

studies which were deemed either acceptable or supplemental, but potentially upgradeable, as 

well as an inquiry regarding one potential non-guideline study. Appendix D includes data call-in 

(DCI) justification tables for pollinator non-guideline studies and the pollinator field test.
Page | 51

Table 18. Available Ecological Effects Data for Terrestrial Animals Exposed to 

Dinotefuran and Remaining Data Gaps

Guideline Description MRID/

Accession Classification Data Gap? Comments

850.2100 Avian oral toxicity 45639720

(TGAI)

Supplemental Yesa a Acceptable avian oral 

toxicity data was submitted for 

the Northern bobwhite quail; 

and supplemental data have 

been submitted for the 

Japanese quail. However, 

avian acute oral toxicity data 

are not available for 

passerines, which are required 

under 40 CFR Part 158. 

Additional justification is 

provided in the succeeding 

text.

b Additional information from 

the residues on alfalfa study is 

requested: 

1) Foliar residue 

measurement data

2) Purity of test 

compound

c Several issues with the field 

testing for pollinators study 

prevent use in risk assessment. 

Therefore, this higher tier

(semi- or full-field) study is

recommended in addition to 

receipt and review of lower 

tier studies (foliage residue 

toxicity, 850.3030 –i.e., given 

the requested information 

above; and, non-guideline 

studies: larval toxicity, 

residues in pollen and nectar / 

field residue analysis study;

and, chronic feeding study).

47353601

(TGAI)

Acceptable

850.2200 Avian dietary toxicity 45639721

(TGAI)

Supplemental No

45639722

(TGAI)

Acceptable

850.2300 Avian reproduction 45639724

(TGAI)

Supplemental No

45639723

(TGAI) Acceptable

850.3020 Honeybee acute 

contact toxicity

45639725

(TGAI)

Acceptable No

45639726

(TEP, 

21.4% a.i.)

Acceptable

45639727

(TEP, 

21.4% a.i.)1

Acceptable

NonguidelineHoneybee acute oral 

toxicity

45639725

(TGAI)

Supplemental2 No

45639726

(TEP, 

21.4% a.i.)

Supplemental2

45639727

(TEP, 

21.4% a.i.)1

Supplemental2

850.3030 Honeybee toxicity of 

residues on foliage 

(alfalfa)

45639728

(TEP, %a.i. 

not reported)

Acceptable Nob

NonguidelineParasitoid wasp 

survival and 

reproduction

45640121

(TEP, 

21.09% a.i.)

Supplemental3 No

NonguidelinePredacious bug 

survival and 

reproduction

45640122

(TEP, 

21.09% a.i.)

Supplemental3 No

NonguidelinePredaceous mite 

survival and 

reproduction

45640120

(TEP, 

21.09% a.i.)

Supplemental3 No
Page | 52

Table 18. Available Ecological Effects Data for Terrestrial Animals Exposed to 

Dinotefuran and Remaining Data Gaps

Guideline Description MRID/

Accession Classification Data Gap? Comments

850.3040 Field testing for 

pollinators

48120501

(TEP, 

70% a.i.)

Supplemental4

(qualitative use 

only; not 

upgradable)

Yesc

NonguidelinePollinator larval 

toxicity study

Not 

submitted Not applicable Yesc

NonguidelinePollinator chronic 

feeding study

Not 

submitted Not applicable Yesc

Nonguideline

Residues in pollen and 

nectar / Field residue 

analysis

Not 

submitted Not applicable Yesc

1 No negative control was utilized

2 The study is a non-guideline study and does not fulfill an OPP guideline requirement. 3

The test species is not a US EPA-recommended species for toxicity testing with terrestrial invertebrates; SEP 

guidelines do not exist for this species. 4 Poor study design (e.g., evidence for cross contamination between control and treatment plots). Toxicity endpoints 

are not to be used in risk assessment.

*Range-finding test
Page | 53

Table 19. Available Ecological Effects Data for Aquatic Animals Exposed to Dinotefuran 

and Remaining Data Gaps

Guideline Description MRID/ 

Accession Classification Data Gap? Comments

850.1075

Freshwater fish –

Acute toxicity

45639714

(TGAI) Acceptable

No

a Additional information from 

the freshwater invertebrate 

study is requested: 

1) Purity of test 

compound 

(metabolite)

b Dinotefuran may enter the 

estuarine/marine environment 

due to its use and mobility 

patterns. It is also expected to 

be persistent in water under 

some conditions. As such, an 

estuarine/marine fish early life 

stage test is considered a 

requirement under 40 CFR 

Part 158. However, given nondefinitive acute effect 

concentration for saltwater (as 

well as freshwater) fish and 

chronic effect concentration 

for freshwater fish, the request 

for a chronic saltwater fish 

early life stage study and a 

fish life cycle test is not 

recommended. 

c

An estuarine/marine 

invertebrate life cycle test is 

recommended because 

dinotefuran may enter this 

environment due to its use and 

mobility patterns (i.e. parent 

Koc range is 42-45 in US soils 

[ loam, sandy loam, and clay 

loam], which is classified as 

mobile according to FAO

2000). It is also expected to 

be persistent in water under 

some conditions. As such, this 

study is considered a 

requirement under 40 CFR 

Part 158. In addition, an acute 

mysid study showed mortality 

and sublethal effects.

However, freshwater 

invertebrate data are 

45639715

(TGAI) Acceptable

45639716

(TGAI) Supplemental1

850.1075

Estuarine/marine fish –

Acute toxicity 45639717

(TGAI) Supplemental3 No

850.1010

Freshwater 

invertebrates –

Acute toxicity

45639709

(TGAI) Acceptable

45639710 No

(metabolite DNphosphate)2, aAcceptable

850.1025

850.1035

Estuarine/marine

invertebrates –

Acute toxicity 

45639711

(TGAI) Acceptable

No

45639713

(TGAI) Acceptable

850.1400 Freshwater fish –

early life stage test

45639719

(TGAI) Acceptable4 No

850.1400 Estuarine/marine fish –

early life stage test Not submitted Not applicable Nob

850.1300

Freshwater 

invertebrate –

life cycle test

45639718

(TGAI) Acceptable No

850.1350

Estuarine/marine 

invertebrates –

life cycle test

Not submitted Not applicable Yesc

850.1500 Fish Life Cycle Not submitted Not applicable Nob

850.1710

850.1730

850.1850

Aquatic organisms 

bioavailability, 

biomagnifications, 

toxicity (i.e. BCF and 

food chain transfer 

studies)

Not submitted Not applicable Nod

850.1735

Freshwater 

invertebrate – Acute 

whole sediment

Not submitted Not applicable Noe

850.1740

Estuarine/marine 

invertebrate – Acute 

whole sediment

Not submitted Not applicable Noe
Page | 54

Table 19. Available Ecological Effects Data for Aquatic Animals Exposed to Dinotefuran 

and Remaining Data Gaps

Guideline Description MRID/ 

Accession Classification Data Gap? Comments

OtherA

Freshwater and 

estuarine/marine 

invertebrate – Chronic 

whole sediment

Not submitted Not applicable Noe

insufficient for ACR 

estimation of the 

estuarine/marine chronic 

endpoint.

d

The study is not required 

under CFR Part 158 as the log 

Kow < 3 for parent dinotefuran 

(i.e., log Kow = -0.549).

e

This data is not required

under CFR Part 158 on the 

basis of the fate properties of 

the parent compound. The Kd

≥50, the log Kow is ≥3, and a 

Koc is ≥1000 requirements are 

not met. However, sensitivity 

to dinotefuran is expected for 

these organisms based on data 

from other neonicotinoids (see 

body of text for details under 

Sediment exposure description 

in the Conceptual Diagram 

section of this problem 

formulation).

AThree species required using the following study guidance: 1) EPA 600/R-99/064 Test Method 100.4: Hyalella 

azteca 42-d Test for Measuring the Effects of Sediment Associated Contaminants on Survival, Growth, and 

Reproduction; 2) EPA 600/R-99/064 Test Method 100.5: Life-cycle Test for Measuring the Effects of Sedimentassociated Contaminants on Chironomus dilutus or C. tentans in USEPA 2000 Methods for Measuring the Toxicity 

and Bioaccumulation of Sediment-associated Contaminants with Freshwater Invertebrates; 3) Leptocheirus 

plumulosus in USEPA 2001 Method for Assessing the Chronic Toxicity of Marine and Estuarine Sedimentassociated Contaminants with the Amphipod Leptocheirus plumulosus EPA 600/R-01/020. 

1 The common carp is not a recommended species

2 The purity of the test compound was not reported

3 Mean fish weight of 0.35g, determined from control fish at test termination, was less than the required initial weight 

range of 0.5 to 5g

4 Study was previously classified invalid on account of low recoveries of test concentrations and highly variable 

analytical results; however, as no endpoints were affected at the lowest, measured dinotefuran concentration (that is, 

6.36 mg a.i./L) and the limit testing on guideline 72-4 is allowable, the study was reclassified to acceptable in 2006 

(USEPA, DP Barcodes D331699 & D316645)
Page | 55

Table 20. Available Ecological Effects Data for Plants Exposed to Dinotefuran and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

850.4100

Terrestrial Plant 

toxicity: Tier I

seedling emergence

45639729

(TEP, 

20.39% a.i.)

Acceptable No

a Additional information 

from the aquatic plant 

growth study is 

requested: 

1) Purity of test 

compound 

(metabolite)

b No endpoints were 

affected in the Tier I 

seedling emergence 

study; observed 

reductions relative to 

control across all species 

tested were <25%.

c No endpoints were 

affected in the Tier I 

vegetative vigor study; 

observed reductions 

relative to control across 

all species tested were 

850.4225

Terrestrial Plant 

toxicity: Tier II

seedling emergence

N/A N/A Nob

850.4150

Terrestrial Plant 

toxicity: Tier I 

vegetative vigor

45639730

(TEP, 

20.39% a.i.)

Acceptable No

850.4250

Terrestrial Plant 

toxicity: Tier II 

vegetative vigor

N/A N/A Noc

850.5400 Aquatic Plant Growth: 

non-vascular plant 

45639732

(TGAI)

Acceptable

(green algae)

Yesd

(but not 

critical)

45639733

(metabolite 

MNG)1, a

Supplemental2

(green algae)

45639734

(metabolite DNphosphate)1, a

Supplemental2

(green algae)
Page | 56

Table 20. Available Ecological Effects Data for Plants Exposed to Dinotefuran and 

Remaining Data Gaps

Guideline Description MRID Classification Data 

Gap? Comments

850.4400 Aquatic Plant Growth: 

vascular plants

45639731

(TGAI) Supplemental3 No

<25%.

d Species of algae that 

were not tested and for 

which data were not 

submitted include 

freshwater diatom, 

Navicula pelliculosa; 

marine diatom, 

Selenastrum costatum; 

freshwater blue-green 

alga/cyanobacterium, 

Anabaena flos-aquae. 

The freshwater green 

algae (S. capricornutum 

or R. subcapitata) that 

was used in the three 

cited submitted studies 

does not alone cover the 

spectrum of possible 

effects to non-vascular 

plants. Additional studies 

on representative species 

are recommended on the 

basis of OPPTS 

Guidance 850.5400.

However, the data are 

not critical; in the 

absence of additional 

data, the submitted green 

algae study may 

justifiably be used as a 

surrogate for the 

remaining taxa. 

1 The purity of the test compound was not reported

2 As there is no requirement for testing with a degradate, the study is classified as supplemental. 3 The study is scientifically sound, but does not satisfy guideline requirements for a tier II acute toxicity study with 

aquatic vascular plants because the test concentrations that plants were exposed to were not analytically determined

and replicate data were only provided for frond number.

Ecotox Studies – DATA GAPS

OPPTS 850.2100 Avian Acute Oral Toxicity Test

Acceptable avian oral toxicity data was submitted for the Northern bobwhite quail; and 

supplemental data for the Japanese quail (a non-guideline species) were submitted. However, 
Page | 57

avian acute oral toxicity data are not available for passerines, which are required under 40 CFR 

Part 158 (July 1, 2010). The Part 158 data requirements specify that acute avian oral toxicity 

data be submitted for either a mallard duck or bobwhite quail and a passerine species. Though all 

four, submitted acute avian studies (oral, MRID 45639720 and 47353601, as well as dietary, 

MRID 45639721 and 45639722) indicated low toxicity (no endpoints were affected and 

sublethal effects, somnolence up to 3 hours after gavage in the 2000 mg a.i./kg-bw level, were 

noted only in the acute oral Japanese quail study) to the parent dinotefuran, the passerine test 

species may indicate greater sensitivity. For LOC exceedances to take place, acute toxicity 

endpoints (LD50/LC50) for passerines (approximate body weight of 20g) would need to be on the 

order of 1300 mg a.i./kg-bw or 1200 mg a.i./kg-diet, respectively (assuming a single application 

rate of 0.54 lbs a.i./A and default half-life of 35 days; using T-REX 1.4.1). Given that little is 

known about the relative toxicities of upland game birds and waterfowl to passerines, the 

probability of achieving this value is uncertain. However, given that the 14-day NOAEL for the 

Japanese quail acute oral study (1000 mg a.i./kg-bw) was on the order of the potential level at 

which LOC exceedances might be observed (i.e., at LD50 of 1300 mg a.i./kg-bw), a request for a 

passerine study is warranted.

Furthermore, passerines are the most common birds (in terms of numbers and number of species) 

in the United States. Many utilize agricultural fields, forests, residential areas and surrounding 

areas, and, therefore, have the potential to be exposed to pesticides used in agricultural, forest, 

and residential settings. It is likely that, for the requested use patterns, passerines are more likely 

to be exposed to dinotefuran than upland game species and waterfowl. Passerines are smaller 

and have a higher energy requirement than larger-sized birds. As such, passerines may be more 

sensitive than other birds. A sample protocol is required prior to submission of the study. If oral 

acute toxicity data are not submitted for passerines, EFED will assume acute risk for passerine 

species.

OPPTS 850.3040 Field Testing for Pollinators

The Agency will consider field studies (semi-field and/or full-field) as data gaps. However, 

requirement of these [higher tier] data will be based, in part, on receipt and review of lower tier 

pollinator studies (i.e., the honey bee foliage residue toxicity test, the pollinator larval toxicity 

study; and/or the pollinator chronic feeding study). In requiring these data, the Agency will also 

consider the [anticipated] recommendations of the SETAC workshop on Pesticide Risk 

Assessment for Pollinators. 

Dinotefuran is highly toxic to bees on an acute oral and contact basis and when applied as a 

foliar spray at a rate of 0.13 lbs a.i./A it will remain toxic to bees on foliage for more than 24 

hours after application (MRID 45639728). Test crop(s) for pollinator study(ies) should be one on 

which bees will actively forage for both nectar and pollen (e.g., cotton, melon, alfalfa). As is 

typical for all effects studies, EFED expects the study design will include maximum dinotefuran 

application rates, at minimum intervals, and maximum number of applications. EFED does not 

know how much dinotefuran can be expected to be translocated to the nectar and pollen when 

applied as a foliar, soil, or tree injection application to plants before nectar or pollen production. 

Though the currently reviewed field study had detected residues in pollen and nectar of flowers 

after foliar application to cotton, the study design was such that toxicity endpoints could not be 
Page | 58

reliably determined. If dinotefuran is being translocated to the nectar and pollen, there is 

uncertainty as to whether there is any adverse effect to foragers or to the hive over time. 

Therefore, several issues with the submitted field testing for pollinators study (MRID 48120501) 

prevent use in risk assessment. 

Therefore, a new honey bee field study that provides relevant and reliable toxicity information 

on the performance of the colonies after exposure to dinotefuran is recommended. Additional 

semi-or full-field studies may be requested pending review of lower tier studies (foliage residue 

toxicity, 850.3030 –i.e., given the requested information [see information needs for this study in 

Appendix C]; and, non-guideline studies: larval toxicity; chronic feeding study; and, residues in 

pollen and nectar/field residue analysis). A study protocol for the field test (semi-field or fullfield) should be submitted for Agency review prior to study initiation.

Non-Guideline Pollinator Larval Toxicity Study

Dinotefuran is highly toxic to bees on an acute contact and oral exposure basis; however, 

because these studies are conducted with young adult honeybees, there is uncertainty regarding 

the potential effects of dinotefuran on larval bees. Therefore, EFED recommends that the 

registrant conduct a larval toxicity study. The registrant should consult with the Agency prior to 

initiation of this study. Because the California Department of Pesticide Regulation has already 

issued a data call-in that included dinotefuran (in addition to other neonicotinoid chemicals 

clothianidin, thiamethoxam, and imidacloprid), and that data call-in required, among other data, 

larval toxicity data, it is possible that the Agency may be able to make use of that data for the 

purposes of the national ecological risk assessment. The registrant should consult with the 

Agency prior to assuming that the CDPR data will satisfy Agency data requirements.

Non-Guideline Lab Pollinator Chronic Feeding Study

A chronic adult laboratory feeding study should be conducted to determine if chronic, repeated 

exposure leads to mortality or sublethal effects. This study would provide an endpoint for 

comparison with acute oral data and a comparison of effects from acute to sustained exposure 

over longer periods of time. The registrant should consult with the Agency prior to initiation of 

this study.

Non-Guideline: Residues in Pollen and Nectar / Field Residue Analysis of Edible Parts of 

Trees/Plants (including, but not limited to residues in whole flowers [such as pollen and nectar 

{from flowers and, if present, extrafloral nectaries}], whole plant tissue [such as leaves and 

stems], sap/resins, and guttation water, if appropriate)

Submission of a residues in plant parts study that quantifies potential exposure levels after tree 

injection and other application types would be of high value. Risks may be further quantified 

and refined if a residues in plant parts study in treated trees and plants is submitted that evaluates 

concentrations of dinotefuran in edible/transportable-to-hive parts of treated trees and plants, 

including but not limited to residues in leaves, sap/resins, guttation water, as well as blooming, 

pollen-shedding, and nectar producing parts (i.e., flowers and, if present, extrafloral nectaries) of 

plants. The reason for asking for multiple test species and plant part residues stems from open 

literature data available for imidacloprid, another systemic neonicotinoid. The studies reveal that 
Page | 59

imidacloprid will move into the plant parts at different concentrations based on the type of plant 

(i.e., corn pollen will have different concentrations of imidacloprid compared to sunflower 

pollen, Bonmatin et al. 2005) and the part of the plant (i.e., pollen will have different 

concentrations of imidacloprid compared to nectar, Stork 1999). In addition, given that there is 

no information on rate of degradation of dinotefuran inside the plant, concentrations of 

degradates of dinotefuran in these plant parts would also be of high value. Therefore, the EFED 

concludes that information on parent dinotefuran and dinotefuran degradate concentrations, in 

various plant parts for different crops is essential to understanding the potential exposure levels

of dinotefuran and degradates to terrestrial non-target invertebrates. A study protocol should be 

submitted for Agency review prior to study initiation. The EFED will consider a semi-field, fullfield, or greenhouse-based protocol lasting at least two years with multiple sampling time-steps.

The protocol will likely depend on application type and crop (e.g., tree injection uses may be 

more amenable to greenhouse-based protocols).

Additionally, dinotefuran is a systemic compound and there is uncertainty as to the extent that 

residues may be translocated to edible/transportable-to-hive parts of plants. Therefore, EFED 

recommends residue studies of leaves, sap/resins, guttation water as well as blooming, pollenshedding, and nectar producing parts (i.e., flowers and, if present, extrafloral nectaries) on 

pollinator-attractive crops on which the compound is registered for use. The registrant should 

consult with the Agency prior to initiation of these studies. The California Department of 

Pesticide Regulation has already issued a data call-in for pollinator data which included

dinotefuran (in addition to other neonicotinoid chemicals clothianidin, thiamethoxam, and 

imidacloprid). It is possible that the Agency may be able to make use of that data for the 

purposes of the national ecological risk assessment. The registrant should consult with the 

Agency prior to assuming that the CDPR data will satisfy Agency data requirements.

OPPTS 850.1350 Estuarine/marine Invertebrate Life Cycle Test (Mysid Chronic Toxicity Test)

Since estuarine/marine chronic toxicity studies were not submitted for this compound there is an 

uncertainty regarding chronic risk to estuarine/marine fish and invertebrates. However, given 

that dinotefuran technical is highly toxic (i.e., <1 mg a.i./L) to mysid shrimp (with a 96-hr LC50

of 0.79 mg a.i./L) on an acute basis (MRID 45639713), given its use dinotefuran may enter the 

estuarine/marine environment, the hydrolysis half-life (MRID 45640101) of dinotefuran 

indicates that the parent is persistent and stable in water at pH 4-9 (at 25oC), due to its mobility 

patterns (i.e. parent Koc range is 42-45 in US soils [loam, sandy loam, and clay loam per soil 

mobility study MRID 45640114], which is classified as mobile according to FAO 2000), a mysid 

chronic toxicity study is required under 40 CFR §158. Furthermore, acute and chronic endpoints

on freshwater invertebrates are non-definitive and, therefore, insufficient for estimating the 

mysid chronic endpoint using the acute to chronic ratio, further justifying the need for the 

chronic mysid study.

850.5400 Aquatic Plant Growth: non-vascular plants

Species of algae that were not tested and for which data were not submitted include freshwater 

diatom, Navicula pelliculosa; marine diatom, Selenastrum costatum; freshwater blue-green 

alga/cyanobacterium, Anabaena flos-aquae. The freshwater green algae (S. capricornutum or R. 

subcapitata) that was used in the three cited submitted studies under this guideline does not 

alone cover the spectrum of possible effects to non-vascular plants -- although additional studies 
Page | 60

would have to indicate sensitivity to parent dinotefuran of three orders of magnitude greater than 

the current green algae study (cell density: 96-hr EC50 > 97.6 mg a.i./L; 96-hr NOAEC: 25 mg 

a.i./L from MRID 45639732) to exceed the plant LOC of 1 – that is, assuming a single 

application rate of 0.54 lbs a.i./A applied once via aerial spray (turfgrasses GENEEC output7

from USEPA 2004, DP Barcode D285633)-- OPPTS 850.5400 draft guidance indicates that this 

test is to be performed once for each of the recommended algal species or selected alternates. 

Furthermore, the application rate may increase for existing uses or be higher than the modeled 

application rate for new uses. 

In addition, acetamiprid (also a neonicotinoid insecticide, PC Code: 099050) received a full suite 

of non-vascular plant studies, which showed comparable sensitivities to the compound across the 

four species for a new chemical risk assessment (USEPA 2002). The EFED generally uses 

multiple non-vascular plant species to make a risk estimate; additional studies on representative 

species are recommended. However, in the absence of the additional studies the available green 

algae study results will be used as a surrogate for the remaining non-vascular plants and any 

additional information from other neonicotinoid chemicals will be used for characterization.

Therefore, although this is a data gap, an aquatic plant growth non-vascular plant study is not 

anticipated as being needed in support of registration review

References

Bonmatin, J.M., P.A. Marchand, R. Charvet, I. Moineau, E.R. Bengsch, and M.E. Colin. 2005. Quantification of 

Imidacloprid Uptake in Maize Crops. J. Agric. Food Chem. 53: 5336-5341. MRID 47523411

Durkin. P.R. 2009. Administrative Materials: Dinotefuran Human Health and Ecological Risk Assessment. Vol 5. 

USDA Forest Service, Southern Region. Contract No. AG-3187-C-06-0010. Submitted by Mitsui 

Chemicals, Inc. c/o Landis International, Inc. April 24, 2009. MRID 47814402

FAO. 2000. Appendix 2. Parameters of pesticides that influence processes in the soil. In FAO Information Division 

Editorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil Contamination. A Reference Manual. 

Rome: Food & Agriculture Organization of the United Nations (FAO). Available at 

http://www.fao.org/DOCREP/003/X2570E/X2570E06.htm (Accessed July 10, 2009).

Fletcher, J.S., J.E. Nellesson and T. G. Pfleeger. 1994. Literature review and evaluation of the EPA food-chain 

(Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Environ. Tox. And Chem. 

13(9):1383-1391.

Hoerger, F. and E.E. Kenaga. 1972. Pesticide residues on plants: correlation of representative data as a basis for 

estimation of their magnitude in the environment. IN: F. Coulston and F. Corte, eds., Environmental 

Quality and Safety: Chemistry, Toxicology and Technology. Vol 1. George Theime Publishers, Stuttgart, 

Germany. pp. 9-28.

OECD. 2007. Guidance document on the honey bee (Apis melliferaL.) brood test under semi-field conditions. 

Series on Testing and Assessment No. 75. ENV/JM/MONO(2007)22.

 7 Peak concentration EEC = 30.58 μg/L
Page | 61

Stork, A. 1999. Residues of 14C-NTN 33893 (Imidacloprid) in Blossoms of Sunflower (Helianthus annuus) after 

Seed Dressing. Unpublished report no. MR-550/99, Bayer CropScience AG, Metabolism/Environmental 

Fate, Monheim, Germany.

USEPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and 

Development, Washington, D.C. EPA/630/R-95/002F. April 1998. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

USEPA 2002. EFED New Chemical review for Acetamiprid. Washington, DC. OPP/EFED. February 28, 2002. (PC 

Code 099050).

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. 

Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of 

Pesticide Programs, Washington DC. January 23, 2004.

U.S. EPA. 2004. Dinotefuran Fact Sheet. http://www.epa.gov/opprd001/factsheets/dinotefuran.pdf

USEPA 2004. Dinotefuran. Report of the Metabolism Assessment Review Committee. Office of Prevention, 

Pesticides, and Toxic Substances. OPP/EFED. Washington, DC. January 20, 2004. TXR No. 0052304. DP 

Barcode D293759.

USEPA 2004. FIFRA Section 3. Environmental Risk Assessment for the New Use Registration of Dinotefuran on 

Cotton, Potato, Head and Stem Brassica, Fruiting Vegetables, Cucurbits, Grapes, Ornamental Plants and 

Flower Beds, Lawn, Shrubs and Additional Residential Uses. DP Barcode: D304957. August 9, 2004. 

Washington, DC, OPPTS/OPP/EFED.

USEPA 2004. Revised Section 3 Environmental Risk Assessment for the Registration of Dinotefuran on Leafy 

Vegetable, Turfgrasses, Ornamentals and Residential Use. DP Barcode D285633. June 30, 2004. 

Washington, DC. OPPTS/OPP/EFED.

USDA 2005. Imidacloprid- Human Health and Ecological Risk Assessment – Final Report. USDA Forest Service. 

Forest Health Protection. December 28, 2005. GSA Contract No. 10F-0082K. USDA Forest Service BPA: 

WO-01-3187-0150. USDA Purchase Order No.: 43-1387-4-3131. Task No. 24.

USEPA 2006. FIFRA Section 3 Environmental Risk Assessement for Increasing the Use Rates for the Registration 

of Dinotefuran on Head and Stem Brassica, Cucurbits, Fruiting Vegetables, Grapes, Leafy Vegetables, and 

Potatoes. DP Barcode D324854. October 16, 2006. Washington, DC, OPPTS/OPP/EFED.

USEPA 2006. Request for Use of Dinotefuran in Texas on Leafy Brassica to Control Whitefly. DP Barcode 

D332829. October 31, 2006.Washington, DC, OPPTS/OPP/EFED.

USEPA 2008. Request for Use of Dinotefuran in Texas on Rice to Control Rice Stink Bug. DP Barcode D355010. 

October 28, 2008. Washington, DC, OPPTS/OPP/EFED.

USEPA, 2008. EFED Problem Formulation for the Registration Review of Imidacloprid. DP Barcode: D353978, PC 

Code: 129099. November 13, 2008. Washington, DC. OCSPP/EFED/ERB5

USEPA 2009. Incremental Environmental Risk Assessment for the IR-4 Petition for the Registration of Dinotefuran 

Use on Leafy Brassica Greens (Subgroup 5B). DP Barcode D358860. June 15, 2009. Washington, DC. 

OPPTS/OPP/EFED.

USEPA 2011. Guidance for the Development of Conceptual Models for Problem Formulation Developed for 

Registration Review. Office of Chemical Safety and Pollution Prevention/OPP/EFED. Washington, DC. 

March 11, 2011
Page | 62

USEPA 2011. FIFRA Section 3 New Use, Environmental Risk Assessment for the Registration of Dinotefuran for 

Forestry Uses (Christmas Trees, Trees in Plantations, Reforestation Nurseries, Forests, and Woodland 

Areas). DP Barcode D378125. May 3, 2011. Washington, DC. OPPTS/OPP/EFED.

USEPA 2011. Section 18 Request for Use of Dinotefuran in VA, WV, DE, MD, NC, PA, and NJ on Stone Fruit and 

Pome Fruit to Control Brown Marmorated Stink Bug. DP Barcodes D388997(VA), D390375 (VA), 

D390381 (WV), D390380 (WV), D390376 (DE), D389144 (DE), D390383 (MD), D390382 (MD), 

D390379 (NC), D390378 (NC), D390377 (PA), D389436 (PA), D390903 (NJ), D390904 (NJ). June 16, 

2011. Washington, DC. OPPTS/OPP/EFED.

USEPA 2011. BEAD Chemical Profile for Registration Review: Dinotefuran (044312). OCSPP/BEAD. 

Washington, DC. July 20, 2011.

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. Endangered 

Species Consultation Handbook: Procedures for Conducting Consultation and Conference Activities Under 

Section 7 of the Endangered Species Act. Final Draft. March 1998.
Page | 63

Appendix A. Nomenclature and structures of dinotefuran and its transformation products

Table A1. Nomenclature

Applicant's Code IUPAC Chemical CAS Name CAS No.

Dinotefuran/MTI-446 (RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl) 

guanidine

N-methyl-N’-nitro-N”-[(tertrahydro-3-furanyl) methyl] 

guanidine.

165252-70-0

(PC Code 

044312)

DN-Phosphate 1-Methyl-3-(tetrahydro-3-furylmethyl) guanidinium 

dihydrogen phosphate

NA NA

MNG 1-Methyl-2-nitroguanidine N-methyl-N’-nitro-guanidine 4245-76-5

UF 1-methyl-3-(tetrahydro-3-furylmethyl)urea NA NA

DN-2-OH + DN-3-OH Bis[1-(3-hydroxytetrahydro-3-furylmethyl)-3-

methylguanidinium] terephthalate

NA NA

Mg-HCl 1-methylguanidinium chloride NA NA

BCDN succinate 3-(methylamino)-9-oxa-2-aza-4-

azoniabicyclo[4.3.0]non-3-ene hydrogen succinate

NA NA

Table A2. Nomenclature and structures of dinotefuran and its transformation products (extracted 

from Section 18 of October 28, 2008 DP Barcode D355010)

Dinotefuran [MTI-446] – Parent Compound

IUPAC Name: (EZ)-(RS)-1-Methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine.

CAS Name: N-Methyl-N′-nitro-N′′-[(tetrahydro-3-furanyl)methyl]guanidine.

CAS Number: 165252-70-0.

SMILES String: CNC(=NN(=O)=O)NCC1COCC1 (ISIS v2.3/Universal SMILES).

No EPI Suite, v3.12 SMILES String found as of 9/29/06.

O C

H2

N

H

C

N

N

H

NO2

CH3
Page | 64

1-Methyl-2-nitroguanidine [N-Methyl-N’-nitro-guanidine; MNG]

IUPAC Name: 1-Methyl-2-nitroguanidine.

CAS Name: N-methyl-N’-nitro-guanidine.

CAS Number: 4245-76-5.

SMILES String: NC(=NN(=O)=O)NC (ISIS v2.3/Universal SMILES).

N(=O)(=O)NC(=N)NC EPI Suite, v3.12 SMILES String found as of 

07/02/08.

4245-76-5

Nitroguanidine [NG]

IUPAC Name: Nitroguanidine.

CAS Name: Not reported.

CAS Number: Not reported.

1-Methyl-3-(tetrahydro-3-furylmethyl)urea [UF]

IUPAC Name: 1-Methyl-3-(tetrahydro-3-furylmethyl)urea.

CAS Name: Not reported.

CAS Number: Not reported.

N

H

H2N

N

CH3

NO2

H2N NH2

N

NO2

O N

H

O

N

H

CH3
Page | 65

1-Methyl-3-(tetrahydro-3-furylmethyl)guanidinium dihydrogen phosphate [DN phosphate] (a salt 

of DN)

IUPAC Name: Not reported.

CAS Name: Not reported.

CAS Number: Not reported.

3-(Methylamino)-9-oxa-2-aza-4-azoniabicyclo[4.3.0]non-3-ene hydrogen succinate [BCDN 

Succinate]

IUPAC Name: 3-(Methylamino)-9-oxa-2-aza-4-azoniabicyclo[4.3.0]non-3-ene hydrogen 

succinate.

CAS Name: Not reported.

CAS Number: Not reported.

1-Methylguanidinium chloride [MG Hydrogen chloride]

IUPAC Name: 1-Methylguanidinium chloride.

CAS Name: Not reported.

CAS Number: Not reported.

O N

H

NH

N

H

CH3

H3PO4

HN N

O

HN

CH3

COOH

COOH

NH

N

H

H2N

CH3

ClH
Page | 66

Guanidine [G]

IUPAC Name: Guanidine.

CAS Name: Not reported.

CAS Number: Not reported.

N-Methylurea [MU]

IUPAC Name: N-Methylurea.

CAS Name: Not reported.

CAS Number: Not reported.

Bis[1-(3-hydroxytetrahydro-3-furylmethyl)-3-methylguanidinium] terephthalate [DN-3-OH]

IUPAC Name: Bis[1-(3-hydroxytetrahydro-3-furylmethyl)-3-methylguanidinium] 

terephthalate.

CAS Name: Not reported.

CAS Number: Not reported.

NH

NH2 NH2

O

H

NH N 2

O

H

N NH

HN

OH

COOH

COOH

2
Page | 67

Appendix B. Environmental Toxicity Summary

The toxicity endpoints for available studies are summarized below. Values in bold indicate 

definitive endpoints and, of these, some were used as inputs for risk quotient calculations for the 

tree injection screening assessment. Earlier assessments cited an acute contact honey bee study 

48-hour LD50 of 0.047 μg a.i./bee (MRID 45639725) as the most sensitive terrestrial invertebrate 

endpoint. Since then, an even more sensitive endpoint (48-hour LD50 of 0.0076 μg a.i./bee) 

obtained from an acute oral honey bee study (MRID 45639727) was considered. The field study 

of foraging honey bees after exposure to dinotefuran applied to cotton fields in Georgia (MRID 

48120501) is supplemental and is only intended for qualitative purposes. 

Terrestrial Toxicity Summary (Acute/ Chronic)

Terrestrial Invertebrates

Dinotefuran technical, MTI-446, (MRID 45639725) is highly toxic to bees on an acute contact

basis (48-hr LD50 = 0.047 μg ai /bee) and on an acute oral basis (48-hr LD50 = 0.023 μg ai/bee). 

Similarly, the dinotefuran formulation, MTI-446 20%WG (MRID 45639726, with control; 

MRID 45639727, without negative but with solvent control) is also highly toxic to bees on an 

acute contact (48-hr LD50 = 0.061 μg a.i./bee and 0.024 μg a.i./bee, respectively) and on an acute 

oral basis (48-hour LD50 = 0.032 μg a.i./bee and 0.0076 μg a.i./bee, respectively). The RT25 (or

residual time to cause 25% mortality) derived from the exposure to residues on alfalfa study 

(MRID 45639728) with the formulation MTI-446 20% WG indicated that bees were most 

sensitive to the 8 hour aged residue (RT25 = 4.8 hours) and least sensitive to treatment when 

exposed to 48 hour aged residue (RT25 = 90 hours). In addition, exposure to dinotefuran 

formulation MTI-446 20% SG applications (of varying exposure periods) led to survivorship and 

reproductive effects on non-Apis terrestrial invertebrates including parasitoid wasp (MRID 

45640121), predaceous bug (MRID 45640122), and predatory mite (an arachnid, MRID 

45640120) indicating LC50 values of 6.89x10-5 lbs a.i./A, 1.19x10-5 lbs a.i./A, and 0.027 lbs 

a.i./A, respectively. It is important to note that the lowest non-definitive chronic endpoint 

NOAEC (<1.21 x 10-6 lbs a.i./A) reported for the predaceous bug study implies that we do not 

know, at this time, how much lower the application would need to be to elicit no response in 

terrestrial invertebrates. For additional comparative analyses including a comparison of 

dinotefuran and imidacloprid toxicities to insects refer to USDA Forest Service risk assessment 

(Durkin 2009; MRID 47814402).
Page | 68

Table B1. Acute effect (mortality) concentrations (LD50/ LC50) for terrestrial invertebrates following 

exposure to Dinotefuran (Technical MTI-446, Formulation MTI-446 20% WG, Formulation MTI446 20% SG) and Dinotefuran (Formulation MTI-446 20% SG) residues on alfalfa. 

Species %a.i. Study Parameters LD50/LC50; NOAEL/NOAEC MRID Classification 

/Category

Technical MTI-446

Honey bee

Apis mellifera

99.5 48-hour, acute 

contact toxicity

Worker bees, 1-7 

days old

3 reps; 10 bees/rep

Solvent: 0.1% triton 

x-100

Nominal 

concentrations: 0 

(negative, solvent 

control), 0.0063, 

0.0125, 0.025, 0.05, 

0.1, and 0.2 μg 

a.i./bee

48-hour LD50: 0.047 μg a.i./bee 

(95% CI: 0.039-0.057 μg a.i./bee)

48-hour NOAEL: 0.0063 μg 

a.i./bee

Probit slope: 2.60

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 0, 

10, 16.7, 46.7, 76.7, and 100% 

mortality was observed in the test 

treatments, respectively. Negative 

conrol mortality was 3.3%; solvent 

control mortality was 0%. After 24 

hours, symptoms of ataxia were 

observed in the 0.1 μg a.i./bee 

group.

45639725 Acceptable / 

Highly toxic1

Honey bee

Apis mellifera

99.5 48-hour, acute oral

toxicity

Worker bees, 1-7 

days old

3 reps; 10 bees/rep

Solvent: 0.1% triton 

x-100

Nominal 

concentrations: 0 

(negative, solvent 

control), 0.00315, 

0.0063, 0.0125, 

0.025, 0.05, and 0.1 

μg a.i./bee

Mean-measured 

concentrations: 0, 

0.003, 0.006, 0.012, 

0.023, 0.046, 0.09 μg 

a.i./bee

48-hour LD50: 0.023 μg a.i./bee 

(95% CI: 0.019-0.027 μg a.i./bee)

48-hour NOAEL: 0.003 μg a.i./bee

Probit slope: 3.75

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 

30, 26.7, 56.7, 86.7, and 100% 

mortality was observed in the test 

treatments, respectively. Negative 

control mortality was 13.3%; 

solvent control mortality was 

16.7%.

*An important note is that the control 

mortality exceeded 10% (an OECD 

requirement), but not the 20% guideline 

limit set for an acute contact study (OPPTS 

850.3020).

45639725 Supplemental2 / 

Highly toxic1

Formulation MTI-446 20%WG

Honey bee

Apis mellifera

21.4 48-hour, acute contact

toxicity

48-hour LD50: 0.061μg a.i./bee 

(95% CI: 0.05 – 0.073 μg 

a.i./bee)

45639726 Acceptable / 

Highly toxic1
Page | 69

Worker bees, 1-7 

days old

3 reps; 10 bees/rep

Solvent: Triton x-100 

(wetting agent), 1 g/L

Nominal 

concentrations: 0 

(negative, solvent 

control), 0.0125, 

0.025, 0.05, 0.1, 0.2, 

and 0.4 μg a.i./bee

48-hour NOAEL: 0.0125 μg 

a.i./bee

Probit slope: 3.48

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 

0, 6.7, 36.7, 73.3, 100, and 

100% mortality was observed in 

the test treatments, respectively. 

Negative conrol mortality was 

0%; solvent control mortality 

was 0%. After 4 hours, 

symptoms of ataxia were 

observed in the 0.2 and 0.4 μg 

a.i./bee groups.

Honey bee

Apis mellifera

21.4 48-hour, acute oral

toxicity

Worker bees, 1-7 

days old

3 reps; 10 bees/rep

Solvent: Triton x-100 

(wetting agent), 1 g/L 

Nominal 

concentrations: 0 

(negative, solvent 

control), 0.0063, 

0.0125, 0.025, 0.05, 

0.1, and 0.2 μg 

a.i./bee

Mean-measured 

concentrations: 0, 

0.005, 0.011, 0.021, 

0.046, 0.088, 0.173 

μg a.i./bee

48-hour LD50: 0.032 μg a.i./bee 

(95% CI: 0.025 – 0.041 μg 

a.i./bee)

48-hour NOAEL: 0.005 μg 

a.i./bee

Probit slope: 2.26

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 

6.7, 16.7, 43.3, 53.3, 90, and 

100% mortality was observed in 

the test treatments, respectively. 

Negative control mortality was 

3.3%; solvent control mortality 

was 6.7%.

45639726 Supplemental2 / 

Highly toxic1

Formulation MTI-446 20%WG - no negative control

Honey bee

Apis mellifera

21.4 48-hour, acute contact

toxicity

Adult worker bees, 

age not specified

3 reps; 10 bees/rep

Solvent: Triton x-100 

(wetting agent), 1 g/L

Nominal 

concentrations: 0 

(solvent control), 

0.0014, 0.0032, 

48-hour LD50: 0.024 μg a.i./bee 

(95% CI: 0.018 – 0.031 μg 

a.i./bee)

48-hour NOAEL: 0.0032 μg 

a.i./bee

Probit slope: 2.0

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 

3, 3, 7, 43, 63, and 87% 

mortality was observed in the 

45639727 Acceptable / 

Highly toxic1
Page | 70

0.0072, 0.016, 0.036, 

0.08μg a.i./bee

*No negative (water) 

control was used

test treatments, respectively. 

Solvent control mortality was 

0%. At 4 hours, there were 

stumbling and knockdown bees 

in the 0.036 and 0.08 μg a.i./bee 

groups.

Honey bee

Apis mellifera

21.4 48-hour, acute oral

toxicity

Adult worker bees, 

age not specified

3 reps; 10 bees/rep

Solvent: Triton x-100 

(wetting agent), 1 g/L 

Nominal 

concentrations: 0 

(solvent control), 

0.00056, 0.0013, 

0.0028, 0.0064, 

0.014, and 0.032 μg 

a.i./bee

Mean-measured 

concentrations: 0 

(solvent control), 

0.00056, 0.0013, 

0.0028, 0.0061, 

0.013, and 0.029 μg 

a.i./bee

*No negative (water) 

control was used

48-hour LD50: 0.0076 μg 

a.i./bee (95% CI: 0.004 – 0.012 

μg a.i./bee)

48-hour NOAEL: 0.0013 μg 

a.i./bee

Probit slope: 3.0

Endpoint(s) affected: Mortality.

(Sub)lethal effects: By 48 hours, 

13, 3, 17, 43, 97, and 90% 

mortality was observed in the 

test treatments, respectively. 

Solvent control mortality was 

20%. However, a concurrent 

dimethoate test had 13% 

mortality in the solvent control. 

At 4 hours, there were stumbling 

and/or knockdown bees 

observed in every treatment and 

control group, except for the 

0.00056 μg a.i./bee

*An important note is that the control 

mortality exceeded 10% (an OECD 

requirement), but not the 20% guideline 

limit set for an acute contact study 

(OPPTS 850.3020).

45639727 Supplemental2 / 

Highly toxic1

Formulation MTI-446 20%WG - residues on alfalfa *(OPPTS 850.3030; honey bee toxicity of residues on foliage)

Honey bee

Apis mellifera

Not 

reported

72-hour, toxicity to 

residues on alfalfa 

(foliar spray 

application)

1-7 days old

6 reps; 25 bees/rep

Solvent: water

(i.e., negative 

control)

Single nominal 

application rate: 150 

g a.i./ha (60.75 g 

a.i./A or 0.1338 lbs 

a.i./A†

)

3-hour aged residue ♠

RT25 = 6.7 (3.3-14) hour

Probit slope = 2.37 ± 0.431

8-hour aged residue

RT25 = 4.8 (2.4-9.6) hour

Probit slope = 2.66 ± 0.436

24-hour aged residue

RT25 = 24 (14-44) hour

Probit slope = 4.63 ± 1.54

48-hour aged residue

RT25 = 90 (75-110) hour

Probit slope = 6.36 ± 3.78

Endpoints considered: Mortality, 

45639728 Acceptable
Page | 71

Bees exposed to 

residues on leaves 

collected at 3, 8, 24, 

and 48 hours posttreatment

*Foliar residues of MTI446 were not measured

behavior, toxicological response 

(at 3, 24, 48, 72, and a single obs. 

at 100 hours post-exposure for 48 

hour group)

Endpoint(s) affected: Mortality.

(Sub)lethal effects: After 24 and 

48 hours of exposure to 3, 8, and 

24 hour aged residue, there was 

significant mortality relative to 

the controls for each residue 

group. After 72 hours, mortality 

was 95, 98, and 97% for bees 

exposed to 3, 8, and 24 hour 

residues. There appeared to be no 

significant effect on mortality to 

bees exposed to 48 hour aged 

residue, regardless of exposure 

period. By 72 hours, negative 

control mortality was 7, 12, 73, 

and 12% in the 3-, 8-, 24-, and 

48-hour post-treatment groups, 

respectively. The positive control 

(dimethoate) was only reported 

for the 3-hour residue group and 

had significant mortality in the 

24 and 48 hour exposure periods 

relative to controls and 64% 

mortality after 72 hours of 

exposure.

Hyperactivity observed in bees 

exposed to 3 and 8 hour posttreatment residues. Ataxia in 

some bees exposed to 3, 8, 24, 

and 48 hour post-treatment 

residues and in controls of the 3 

and 8 hour groups. 

Formulation MTI-446 20% SG – Also, nonguideline studies

Parasitoid 

wasp

Aphidius 

rhopalosiphi

(Hymenoptera, 

Braconidae)

21.09 13-day, survival 

(exposure phase: 2 

day exposure; 11 day 

obs) and separate 

repro study 

(fecundity phase: 1 

day exposure; 10 day 

obs)

1-2 days old

Nominal 

applications: 0 

(negative control), 2, 

13-d LC50: 77.2 mg a.i./ha

(6.89x10-5 lbs a.i./A)

(95% CI: 59.4 – 102.6 mg a.i./ha; 

5.30 x 10-5 – 9.16x10-5 lbs a.i./A)

NOAEC: 7 mg a.i./ha

(6.25x10-6 lbs a.i./A)

Endpoints considered: Mortality 

and reproductive effects 

(parasitism)

Endpoint(s) affected: Mortality, 

parasitism success.

45640121 Supplemental3
Page | 72

7, 20, 70, and 200 

mg a.i./ha 

(1.79x10-6, 6.25x10-

6

, 1.79x10-5, 6.25 x 

10-5

, and 0.0002 lbs 

a.i./A)

*Only the underlined 

concentrations were used 

for the parasitism effect 

component (i.e., fecundity 

phase), in which aphids 

(Rhopalosiphum padi) 

were fed to ♀ wasps only; 

note: ♂ & ♀ wasps were 

used in presumed equal 

numbers in the mortality 

component (i.e., exposure 

phase)

Note: test substance was 

sprayed on the top and 

bottom glass plates of the 

test units with a calibrated 

track sprayer; 2 treated 

glass plates were placed in 

ventilated glass cages

(Sub)lethal effects: Corrected 

mortality (using SchneiderOrelli’s fomula4

) was -7, -2, 9, 

50, and 74% in the test 

treatments, respectively. 

Significant mortality obs in the 

two highest concentrations. 

Negative control mortality was 

10%.

Percent reduction in parasitism 

success (#of aphid mummies per 

♀) was -1 and 67% for the two 

concentrations tested (7 and 20 

mg a.i./ha). Significant reduction 

in parasitism obs in 20 mg a.i./ha 

group. Control parasitization 

success was 8.4 aphid mummies 

per ♀ per 22 hour parasitization 

period.

Predaceous 

bug 

Orius 

laevigatus

(Hemiptera, 

Anthocoridae)

21.09 21 day (9 day 

exposure; 12 day 

obs), survival (9 

days) and 

reproduction (12 

days) study

Nymphs, 5-6 days 

old

Nominal 

applications: 0 

(negative control), 

1.36, 2.72, 5, 8.8, 

and 13.6 mg a.i./ha 

(1.21x10-6

, 2.43x10-

6

, 4.46x10-6, 7.86x10-

6

, and 1.21x10-5 lbs 

a.i./A)

*Only the underlined 

concentrations were used 

for the reproductive effect 

component (i.e., fecundity 

phase), in which only ♀ 

bugs were present; note: ♂ 

& ♀ bugs were used in the 

mortality component (i.e., 

exposure phase)

Note: The test substance 

was sprayed on all inner 

parts of the test units with 

a calibrated lab track 

sprayer. 

21-d LC50: 13.3 mg a.i./ha

(1.19x10-5 lbs a.i./A)

(95% CI: 7.0 - 25.1 mg a.i./ha;

6.25x10-6 – 2.24x10-5 lbs a.i./A)

NOAEC <1.36 mg a.i./ha

(1.21x10-6 lbs a.i./A)

Probit slope: 2.11

LOAEC: 8.8 mg a.i./ha

Endpoints considered: Mortality 

and reproductive effects 

(oviposition, egg hatch success)

Endpoint(s) affected: Mortality.

(Sub)lethal effects: Corrected 

mortality (using SchneiderOrelli’s fomula4

) was 15, 1, 13, 

43, and 49% in the test 

treatments, respectively. 

Significant mortality obs in the 

lowest and two highest 

concentrations. Negative control 

mortality was 16%.

Percent reduction in mean #of 

eggs produced per day per ♀ was 

4 and -2% and percent inhibition 

for egg hatch were 0 and -1% for 

the two concentrations tested 

(2.72 and 5 mg a.i./ha). 

Fecundity was not significantly 

45640122 Supplemental3
Page | 73

affected by treatment. 

Reproductive success was 6.9 

eggs per ♀ per day and average 

egg hatch success was 92%.

Predaceous 

mite

Typhlodromus 

pyri

(Acari: 

Phytoseiidae)

21.09 14 day (7 day 

exposure; 7 day obs), 

survival (7 days) and 

reproduction (7 days) 

study

Protonymphs, 1 day 

old

Nominal 

applications: 15, 20,

30, 40, and 60 g 

a.i./ha (0.013, 0.018, 

0.027, 0.036, and 

0.053 lbs a.i./A)

*Only the underlined 

concentrations were used 

for the reproductive effect 

component (i.e., fecundity 

phase); note: ♂ & ♀ mites 

were used both in the 

reproductive effect 

component and in the 

mortality component (i.e., 

exposure phase)

Note: The test substance 

was sprayed on inner parts 

of glass cage and petri 

dishes with a calibrated 

lab track sprayer.

14-d LC50: 30.1 g a.i./ha

(0.027 lbs a.i./A)

(95% CI: 26.7- 34.2 g a.i./ha;

0.024 – 0.030 lbs a.i./A)

NOAEC <15 g a.i./ha

(0.013 lbs a.i./A)

Endpoints considered: Mortality 

and reproductive effects (# of 

eggs and oviposition)

Endpoint(s) affected: Mortality, 

fecundity.

(Sub)lethal effects: Corrected 

mortality (using SchneiderOrelli’s fomula5

) was 39, 32, 79, 

47, and 96% in the test 

treatments, respectively. 

Significant mortality obs in all 

test concentrations. Negative 

control mortality was 10%.

Percent reduction in mean #of 

eggs produced per day per ♀ was 

41 and 51% for the two 

concentrations tested (15 and 20 

g a.i./ha). Fecundity was 

significantly reduced in the 20 g 

a.i./ha treatment. Reproductive 

success was 9 eggs per ♀ per 

day.

45640120 Supplemental3

1 Based on acute contact LD50 (μg a.i./bee) <2 highly toxic; 2-10.99 moderately toxic; ≥11 practically non-toxic 2 The study is a non-guideline study and does not fulfill an OPP guideline requirement. . 3

The test species is not a US EPA-recommended species for toxicity testing with terrestrial invertebrates; SEP guidelines 

do not exist for this species.

4 Schneider-Orelli’s formula: Corrected % = (%mortality in treated - %mortality in control) / (100-%mortality in control) 

*100

† The application is below (constitutes 25% of) the maximum seasonal application rate (0.54 lbs a.i./A/yr) for the 

proposed label (Reg. No. 86203-11) applications (foliar, airblast, broadcast spray; soil applications; chemigation; basal 

trunk spray).

♠ RT25 = residual time to cause 25% mortality; bees were most sensitive to the 8 hour aged residue and least sensitive to 

treatment when exposed to 48 hour aged residue. Bee mortality on 48 hour aged residues did not differ from bees exposed 

to control leaves after 48 hours.
Page | 74

Honey Bee Field Study

Classification and Conclusions

The submitted field study of foraging honey bees (Apis mellifera) after exposure to dinotefuran 

70 SG (70% a.i.) applied to cotton fields in Georgia, USA (MRID 48120501) was deemed 

supplemental (for qualitative use only and not upgradable). It is very important to note that on 

account of a poor study design, inadequate raw data reporting8

, and multiple additional 

considerations the toxicity determinations cannot be used for risk assessment purposes.

However, information regarding residue detections may be informative assuming freezer 

stability (MRID 48120502) was conducted at -20 o

C (as reported in the field study), or at an 

alternative, representative temperature. Therefore, solely on the basis of the residue data, the 

field study may still be utilized to address long-term exposure of honey bees to dinotefuran.

Although bees were exposed to dinotefuran, the dinotefuran residue levels detected in treatment 

plot samples of nectar, honey, beeswax, and pollen, did not, for the most part, differ greatly from 

those detected in the control samples, which is indicative of cross contamination in the control 

plot blossoms and hives (of all three trials in pollen and/or nectar samples) and likely foraging of 

treatment groups on control plots and of control groups on treated plots. For example, only trial 1 

samples of nectar in flowers for days 7 and 17 indicated a clear distinction between no residue 

detected in controls and detected levels (0.012-0.021 ppm) in both treatment plots; and, in trial 3 

day 26 flower nectar samples where no residues were detected in the control, but were detected 

in the two treatments as 0.013 ppm and <LOQ (0.004 ppm). As a result of the crosscontamination, this study is inconclusive in terms of the toxicity of dinotefuran applications on 

cotton to honey bee hives. In addition, the lack of quantitative data rather than simply 

presence/absence on overwintering parameters such as egg abundance, larval abundance, pupal 

abundance renders the study inconclusive in terms of assessing overwintering success. The data 

suggest that all colonies (control and treatment) for all three trials were healthy (w/ >4 frames of 

adults) by approximately 200 days after exposure (i.e., Spring colony assessment performed in 

February for all three trials), with presence of queen, larvae, and eggs. However, the numbers on 

these hive attributes are not included. Instead, the quantitative data for this time step indicates 

that all colonies had adults present in all 10 frames of each colony; this was the case for all three 

trials. Also, an estimate of the number of capped brood was only provided for trial 1, but the 

difference between control and treatment groups did not appear to be significant. In addition, 

presence of queens may not be an indicator of overwintering success as new queens were added 

to hives when queen loss occurred during the study. While re-queening hives is a common 

management practice, it is not particularly desirable for field studies as it prevents a test from 

quantifying the colony's ability to supersede naturally. 

The data on toxic effects in this study cannot be used for risk assessment purposes on account of 

poor study design. Similarly, residue values below the LOQ (i.e., a <LOQ value that was 

calculated by integration for samples where residue values were <0.010mg/kg) cannot be used 

quantitatively in the risk assessment; therefore, the residue analysis is of limited value other than 

characterizing qualitatively the presence/absence of dinotefuran residues over time. In addition, 

there are two major metabolites, MNG and DN, for which no residue data are provided in this 

study. The presence/absence data for residues, particularly in nectar, are important, however, 

 8 Statistical verification of the adult bee mortality was not possible as the raw data counts were not provided by the 

study author.
Page | 75

because they suggest that residues could potentially be present in extra floral nectaries once 

flowers have been shed, and dinotefuran (or, total) residues will be present in stored food inside 

hives for long periods of time (i.e., at least 85 days after application). Therefore, honeybee 

adults and brood will likely be exposed to low levels of dinotefuran for relatively long periods of 

time, but the toxicity of these levels of residues remains an uncertainty.

Field Study: Exposure

Concentrations of dinotefuran residues appear to be higher in flower nectar compared to flower 

pollen. Residues were detected in nectar samples from treated flowers up to 27 days after 

application in trial 1 and up to 26 days after application in trials 2 and 3. These time points 

represent the latest time points that residues were collected from flowers in treated plots. The 

fact that residues were still present in these flower nectar samples, including one sample that had 

quantifiable residues of 0.013 ppm (LOQ = 0.004 ppm) after 26 days (trial 3), indicates that 

residues could potentially be found in nectar from extra floral nectaries in cotton plants as well as 

the flowers. These nectaries, which are not part of the blossom, may continue to produce nectar 

even after bloom that bees will use as a sugar source. Therefore, continual chronic exposure is 

likely to occur. 

Given detections of dinotefuran in hive nectar (plot 1) at day 34, may suggest that nectar was 

collected by bees from either available flowers or extrafloral nectaries (which are present, but 

may or may not be active, continuously – even when flowers fall off). Though dinotefuran 

detections were not made on the extrafloral nectaries of cotton plants, the presence of 

dinotefuran in flower nectar (e.g., up to day 27 post-application for plot 1 samples) lends strong 

support for dinotefuran concentrations in extrafloral nectaries given the common phloem source 

and dinotefuran’s systemic properties, which would have implications for long-term exposure 

post-bloom.

Furthermore, trial 2 shows that dinotefuran residues can be detected in stored honey inside hives 

at least 85 days after application, which also suggests the occurrence of long-term chronic 

exposure inside the hive, which has implications for overwintering success as well.

Terrestrial Animals (birds/mammals)

Dinotefuran was tested on various species of birds (Japanese quail, northern bobwhite quail, and 

mallard duck for acute oral and dietary studies; and, bobwhite quail and mallard duck for chronic 

reproduction studies). The parent compound is practically nontoxic to Japanese quail (LD50 > 

2,000 mg a.i./kg-bw; MRID 45639720) and bobwhite quail (LD50 > 2,250 mg a.i./kg-bw; MRID 

47353601) on an acute oral basis and to mallard duck (LC50 > 5,000 mg a.i./kg-diet; whereby the 

mean test item intake is 997.9 mg a.i./kg-diet; MRID 45639722) and Japanese quail (LC50 > 

5,000 mg a.i./kg-diet; whereby the mean test item intake is 1301 mg a.i./kg-diet; MRID 

45639721) on a subacute dietary basis. However, sublethal effects (somnolence up to 3 hours 

after administration of the test compound) were observed in the highest test concentration (2,000 

mg a.i./kg-bw) of the acute oral Japanese quail study leading to a NOAEL determination of 

1,000 mg a.i./kg-bw. Although there appeared to be no significant treatment-related effects on 

bobwhite quail (MRID 45639724) reproductive parameters, chronic testing on mallard duck

(NOAEC = 2,150 mg a.i./kg-diet; MRID 45639723) showed significant reductions in the 

percentages of number of hatchlings/eggs laid, eggs set, and 14-day old survivors.
Page | 76

Dinotefuran is slightly to practically nontoxic on an acute basis to surrogate wild mammal 

species (laboratory rat) (female LD50 = 2000 mg/kg-bw; MRID 45639823). Chronic studies 

indicated effects on rats and rabbits. A 2-generation reproduction study for MTI-446 technical on 

the rat indicated a reproductive NOAEL of 3,000 mg/kg-diet (MRID 45639913) based on 

decreased uterine weights and microscopic alterations in the utrus and estrous cyclicity in Fo and 

F1 females, slight increases in abnormal sperm morphology in Fo and F1 males, and slight 

decreases in testicular sperm count in Fo males and sperm mortality in F1 males. The 

developmental toxicity NOAEL for MTI-446 technical on rabbits is ≥ 300 mg/kg-bw/day, while 

the maternal toxicity NOAEL is 52 mg/kg-bw/day based on decreased body weight gain, 

decreased food consumption, and gross necropsy findings (pale discoloration of the liver and 

gray white plaques in the stomach). The rabbit study is included here to illustrate that sublethal 

effects as a result of chronic exposure to dinotefuran occur in multiple mammalian species; the 

endpoint is utilized in additional calculations at a later section in the risk assessment. The 

degradates MNG and DN were not tested on birds or surrogate mammals.

Table B2. Acute effect (mortality) concentrations (LD50/ LC50) for terrestrial animals 

(birds/mammals) following exposure to Dinotefuran (Technical MTI-446). 

Species %a.i. Study 

Parameters

LD50/LC50; NOAEL/NOAEC MRID Classification 

/Category

Birds

Japanese

quail

Coturnix 

japonica

97.26 14-day, acute 

oral study 

(gavage)

8-wks old

Nominal 

concentrations: 

vehicle control 

(H2O), 200, 

1000, 2000 mg 

a.i./kg-bw

14-day LD50 >2000 mg a.i./kg-bw

14-day NOAEL: 1000 mg a.i./kgbw

Endpoint(s) affected: None.

(Sub)lethal effects: No mortality 

observed. All ♂ & ♀ birds showed 

somnolence up to 3 hours after 

gavage in 2000 mg a.i./kg-bw 

level which was the basis for a 

NOAEL of 1000 mg a.i./kg-bw; 

otherwise, none

45639720 Supplemental 

/Practically nontoxic1

Northern 

Bobwhite 

quail

Colinus 

virginianus

94.7±1.04 14-day, acute 

oral study

(gavage)

(limit test)

25-wks old

Nominal 

concentrations: 

0 and 2250 mg 

a.i./kg-bw

14-day LD50 >2250 mg a.i./kg-bw

14-day NOAEL ≥ 2250mg a.i./kgbw

Endpoint(s) affected: None.

(Sub)lethal effects: None.

47353601 Acceptable 

/Practically nontoxic1

Japanese

quail

97.26 8-day (5-day 

exposure; 3-

8-day LC50 >5000 mg a.i./kg-diet 45639721 Supplemental 

/Practically non-
Page | 77

Coturnix 

japonica

day obs), acute 

dietary study

(limit test)

16-days old

Nominal 

concentrations: 

0 and 5000 mg 

a.i./kg-diet

Meanmeasured 

concentrations:

0 and 4936 mg 

a.i./kg-diet; 

mean test item 

intake = 1301 

mg a.i./kg-diet

8-day NOAEC ≥5000 mg a.i./kgdiet

Endpoint(s) affected: None.

Sublethal effects: None.

toxic

2

Mallard duck

Anas 

platyrhynchos

99.2 8-day (5-day 

exposure; 3-

day obs), acute 

dietary study

(limit test)

16-days old

Nominal 

concentrations: 

0 and 5000 mg 

a.i./kg-diet

Meanmeasured 

concentrations:

0 and 4732 mg 

a.i./kg-diet; 

mean test item 

intake = 997.9 

mg a.i./kg-diet

8-day LC50 >5000 mg a.i./kg-diet

8-day NOAEC ≥ 5000 mg a.i./kgdiet

Endpoint(s) affected: None.

Sublethal effects: None.

45639722 Acceptable 

/Practically nontoxic2

Mammals

Laboratory 

rat

Rattus 

norvegicus

99.1 14-day acute 

oral toxicity

♂ LD50 = 2,804 mg/kg-bw

♀ LD50 = 2,000 mg/kg-bw

Endpoint(s) affected: Morbidity.

45639823 Acceptable

(Tox. Category III)

1 Acute Oral (avian/mammal): Based on LD50 (mg/kg) <10 very highly toxic; 10-50 highly toxic; 51-500 moderately 

toxic; 501-2000 slightly toxic; >2000 practically nontoxic 2 Acute Dietary (avian): Based on LC50 (mg/kg) <50 very highly toxic; 50-500 highly toxic; 501-1000 moderately toxic; 

1001-5000 slightly toxic; >5000 practically nontoxic

*Values in bold indicate definitive endpoint and/or one which is used in risk quotient calculation.
Page | 78

Table B3. Chronic effect concentrations (NOAEC/LOAEC) for terrestrial animals (birds/mammals) 

following exposure to Dinotefuran (Technical MTI-446). 

Species %a.i. Study Parameters NOAEC/LOAEC MRID Classification 

/Category

Birds

Northern 

bobwhite quail

Colinus 

virginianus

99.3 1-generation (21 wks) 

reproductive study

(dietary)

21-wks old at initiation

Mean-measured 

concentrations:

0, 764, 2150, and 5270 

mg a.i./kg-diet

21-wk NOAEC ≥ 5270 

mg a.i./kg-diet

21-wk LOAEC > 5270 

mg a.i./kg-diet

Endpoint(s) affected: 

None.

(Sub)lethal effects:

Two incidental 

mortalities, one each in 

control and 5270 mg 

a.i./kg-diet level. 

Incidental injuries due to 

pen-wear; slight (not 

considered treatment 

related), but statistically 

significant reduction in 

food consumption at 5270 

mg a.i./kg-diet level and 

percentage of viable 3-

week embryos at 764 mg 

a.i./kg-diet level

45639724 Supplemental

Mallard duck

Anas 

platyrhynchos

99.3 1-generation (20 wks) 

reproductive study

(dietary)

21-wks old at initiation

Mean-measured 

concentrations:

0, 764, 2150, and 5270 

mg a.i./kg-diet

20-wk NOAEC: 2150 

mg a.i./kg-diet

20-wk LOAEC: 5270 mg 

a.i./kg-diet

Endpoint(s) affected: 

number of hatchlings/eggs 

laid and set, 14-day old 

survivors/eggs set

(Sub)lethal effects: One 

incidental mortality in 

control. Incidental injuries 

due to pen-wear. 

Reproductive effects 

resulted in endpoint 

determination. 

45639723 Acceptable

Mammals

Laboratory 

rat

Rattus 

norvegicus

98.9 2-generation repro. 

study

(dietary)

Dietary concentrations: 

0, 300, 1000, 3000, and 

Repro. NOAEL = 3,000 

mg/kg-diet 

(241-269 mg/kg-bw/day ♂;

267-292.6 mg/kg-bw/day ♀)

Repro. LOAEL = 10,000 

45639913 

(definitive test);

45639914 (rangefinding test)

Acceptable
Page | 79

10000 mg/kg

Pre-mating doses:

Fo males

0, 24.1, 79.9, 241, 

822.1 mg/kg-bw/day

Fo females

0, 26.8, 90.1, 267.9, 

907 mg/kg-bw/day

F1 males

0, 27.2, 90.5, 269, 

934.7 mg/kg-bw/day

F1 females

0, 29.6, 96.5, 292.6, 

1004.8 mg/kg-bw/day

mg/kg-diet

(822.1-934.7 mg/kg-bw/day ♂;

907-1004.8 mg/kg-bw/day ♀)

Endpoint(s) 

affected/Sublethal effects: 

Decreased uterine 

weights, microscopic 

alteration in uterus and 

vagina of Fo ♀; decreased 

numbers of primordial 

follicles in F1 ♀, altered 

estrous cyclicity in Fo ♀; 

slight increases in 

abnormal sperm 

morphology in Fo and F1

♂, and slight decreases in 

testicular sperm count in 

Fo ♂ and sperm mortality 

in F1 ♂.

Laboratory rat

Rattus 

norvegicus

92.9 Prenatal development

(gavage)

Dose levels:

0, 100, 300, 1000 

mg/kg-bw/day on 

gestation days 6-15 

(inclusive)

Dev. NOAEL ≥ 1,000 

mg/kg-bw/day

Dev. LOAEL Not 

established

Endpoint(s) affected: 

None. No statistically 

significant effects on 

developmental endpoints. 

Sublethal effects:

Maternal toxicity was 

evident at a dose of 1000 

mg/kg-bw/day. After

initiation, decreases in 

body wt gain (5.5, 40, and 

56% of controls) and 

decreased food 

consumption (88, 87, and 

90% of controls) at 

gestation days (6-7, 7-8, 

and 9-10).

45654207 

(definitive test)

45639910 (range 

finding test)

Acceptable

Rabbit 92.9 Prenatal development

(gavage)

Dose levels:

0, 52, 125, 300 mg/kgbw/day on gestation 

days 6-18 (inclusive)

Dev. NOAEL ≥ 300 

mg/kg-bw/day

Dev. LOAEL Not 

established

Maternal NOAEL = 52 

mg/kg-bw/day

Maternal LOAEL = 125 

mg/kg-bw/day

Endpoint(s) affected: 

45654208 

(definitive test)

45639911 (range 

finding test)

45639912 (range 

finding test)

Acceptable
Page | 80

None. No statistically 

significant effects on 

developmental endpoints

Sublethal effects: 

Maternal toxicity was 

evident at doses of 125 

and 300 mg/kg-bw/day. 

Decreased bw gain (80% 

of controls) in ♀ in the 

125 mg/kg-bw/day group 

at gestation days 6-18 and 

transient decrease in food 

consumption (84-90% of 

controls) after initiation 

(gestation days 6-10). 

Other findings include: 

liver discoloration, 

stomach plaque, transient 

neurological signs

*Values in bold indicate definitive endpoint and/or one which is used in risk quotient calculation.

Aquatic Animals

The data submitted by the registrant show that dinotefuran (technical MTI-446) is practically 

nontoxic on an acute basis to freshwater and estuarine/marine fish (96-hour LC50 > 99 mg a.i./L), 

as well as freshwater invertebrate (D. magna 48-hour LC50 > 968.3 mg a.i./L; MRID 45639709) 

and saltwater invertebrate (eastern oyster 96-hr EC50 > 141 mg a.i./L; MRID 45639711). The 

degradate of dinotefuran (DN phosphate) is also considered practially non-toxic to the freshwater 

invertebrate (D. magna 48-hour LC50 > 110.6 mg a.i./L; MRID 45639710); however, on the 

basis of 10% immobility in the highest concentration tested a NOAEC of 10 mg a.i./L was 

determined. However, on an acute basis dinotefuran appears to be highly toxic to the 

estuarine/marine invertebrates (mysid shrimp LC50 = 0.79 mg a.i./L; MRID 45639713). Chronic 

toxicity testing on freshwater fish (rainbow trout; MRID 45639719) and invertebrates (D. 

magna; MRID 45639718) showed no treatment related effects and NOAECs of > 6.36 mg a.i./L 

and > 95.3 mg a.i./L, respectively. Since estuarine/marine chronic toxicity studies were not 

submitted for this compound there is uncertainty regarding chronic risk to estuarine/marine fish, 

but a major uncertainty regarding chronic risk to estuarine/marine invertebrates. Based on the 

available data the estuarine/marine invertebrates (mysid, LC50 = 0.79 mg a.i./L) are significantly 

more sensitive to dinotefuran than freshwater invertebrates (daphnia, LC50 >110.6 mg a.i./L) on 

an acute exposure basis. Given that the acute and chronic endpoints for the freshwater 

invertebrate are non-definitive, estimates for the chronic saltwater invertebrates on the basis of 

an acute-to-chronic ratio would not be reliable. Therefore, a chronic mysid study is needed to 

address this uncertainty.
Page | 81

Table B4. Acute effect concentrations (LC50/EC50) for aquatic animals and plants following exposure 

to Dinotefuran (Technical MTI-446; unless otherwise stated). 

Species %a.i. Study Parameters LD50/LC50/EC50;

NOAEL/NOAEC

MRID Classification 

/Category

Freshwater fish

Rainbow Trout

Oncorhynchus 

mykiss

97.26 96-hour acute toxicity

(limit test)

Static

Nominal 

concentrations: 0, 100 

mg a.i./L

Mean-measured 

concentrations: 0, 

99.5 mg a.i./L

96-hr LC50 > 99.5 mg 

a.i./L

96-hr NOAEC ≥ 99.5 mg 

a.i./L

Endpoints considered: 

mortality, intoxication

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639714 Acceptable / 

Practically nontoxic1

Bluegill sunfish 

Lepomis 

macrochirus

97.26 96-hour acute toxicity

(limit test)

Static

Nominal 

concentrations: 0, 100 

mg a.i./L

Mean-measured 

concentrations: 0, 

99.3 mg a.i./L

96-hr LC50 > 99.3 mg 

a.i./L

96-hr NOAEC ≥ 99.3 mg 

a.i./L

Endpoints considered: 

mortality, intoxication

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639715 Acceptable / 

Practically nontoxic1

Carp

Cyprinus carpio

97.26 96-hour acute toxicity

(limit test)

Static

Nominal 

concentrations: 0, 100 

mg a.i./L

Mean-measured 

concentrations: 0, 

99.1 mg a.i./L

96-hr LC50 > 99.1 mg 

a.i./L

96-hr NOAEC ≥ 99.1 mg 

a.i./L

Endpoints considered: 

mortality, intoxication

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639716 Supplemental†

/Practically nontoxic1

Freshwater invertebrate

Waterflea

Daphnia magna

97.26 48-hour acute toxicity

(limit test)

Static

48-hr LC50 > 968.3 mg 

a.i./L

48-hr NOAEC ≥ 968.3 

mg a.i./L

45639709 Acceptable 

/Practically nontoxic1
Page | 82

Nominal 

concentrations: 0, 

1000 mg a.i./L

Mean-measured 

concentrations: 0, 

968.3 mg a.i./L

Endpoints considered: 

immobility

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

Waterflea

Daphnia 

magna

Not 

reported 

Metabolite 

(DN 

Phosphate)

48-hour acute toxicity

Static

Nominal 

concentrations: 0, 1, 

10, and 100 mg a.i./L

Mean-measured 

concentrations: <5.04 

(<LOQ, control), and 

110.6 mg a.i./L (for 

the highest treatment 

group)

48-hr LC50 > 110.6 mg 

a.i./L

48-hr NOAEC: 10 mg 

a.i./L

48-hr LOAEC: 110.6 mg 

a.i./L

Endpoints considered: 

mortality/immobility

Endpoint(s) affected: 

After 48 hours, there was 

10% immobility in the 

110.6 mg a.i./L treatment 

group which was the 

basis for a NOAEC of 10 

mg a.i./L. The control 

and other treatment 

groups had 0% 

immobility.

(Sub)lethal effects:

None.

45639710 Acceptable / 

Practically nontoxic1

Saltwater fish

Sheepshead 

minnow

Cyprinodon 

variegatus

99.2 96-hour acute toxicity

(limit test)

Flow-through

Nominal 

concentrations: 0, 120 

mg a.i./L

Mean-measured 

concentrations: 0, 109 

mg a.i./L

96-hr LC50 > 109 mg 

a.i./L

96-hr NOAEC ≥ 109 mg 

a.i./L

Endpoints considered: 

mortality, intoxication

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639717 Supplemental♠

/Practically nontoxic1

Saltwater invertebrate

Eastern oyster

Crassostrea 

virginica

99.6 96-hour acute toxicity

Flow-through

Nominal 

concentrations: 0, 16, 

96-hr EC50 > 141 mg 

a.i./L

96-hr NOAEC ≥ 141 mg 

a.i./L

45639711 Acceptable 

/Practically nontoxic1
Page | 83

26, 43, 72, and 120 

mg a.i./L

Mean-measured 

concentrations: 0, 15, 

24, 47, 75 and 141 mg 

a.i./L

Endpoints considered: 

shell deposition 

Endpoint(s) affected: 

None. After 96 hours of 

exposure, mean shell 

growth was 2.2 mm for 

negative control, 2.26, 

2.43, 1.96, 1.71, and 2.22 

for the test 

concentrations, 

respectively.

(Sub)lethal effects:

None.

Mysid shrimp

Americamysis 

bahia

99.2 96-hour acute toxicity

Flow-through

Nominal 

concentrations: 0, 

0.063, 0.13, 0.25, 

0.50, 1.0 and 2.0 mg 

a.i./L

Mean-measured 

concentrations: 0, 

0.065, 0.13, 0.25, 

0.49, 1.0, and 2.0 mg 

a.i./L

96-hr LC50: 0.79 mg 

a.i./L (95% C.I.: 0.49-

1.0 mg a.i./L)

96-hr NOAEC: 0.49 mg 

a.i./L

96-hr LOAEC: 1.0 mg 

a.i./L

Endpoints considered: 

Mortality, sublethal 

effects

Endpoint(s) affected: 

Mortality, sublethal 

effects

(Sub)lethal effects: At 96 

hours, mortality was 5% 

in the contol and 5, 5, 0, 

5, 75, and 100% for the 

test concentrations, 

respectively. Erratic 

swimming and loss of 

equilibrium were 

observed in surviving 

mysids from the 1.0 and 

2.0 mg a.i./L treatment 

levels during the test. 

Lethargic mysids were 

observed in the 1.0 mg 

a.i./L treatment level.

45639713 Acceptable / 

Highly toxic1

1

Based on EC50 (mg/L): < 0.1 very highly toxic; 0.1-1 highly toxic; >1-10 moderately toxic; >10-100 slightly toxic; >100 

practically nontoxic

† The common carp is not a recommended species

♠ Mean fish weight of 0.35g, determined from control fish at test termination, was less than the required initial weight range 

of 0.5 to 5g

*Values in bold indicate definitive endpoint and/or one which is used in risk quotient calculation.
Page | 84

Table B5. Chronic effect concentrations (NOAEC/LOAEC) for aquatic animals following exposure to 

Dinotefuran (Technical MTI-446). 

Species %a.i. Study Parameters NOAEC/LOAEC MRID Classification 

/Category

Freshwater fish

Rainbow 

Trout

Oncorhynchus 

mykiss

98.9 Early life stage

(94 days: 34-day

hatching period; 60-day 

post hatch period)

(limit test)

Flow-through

Nominal 

concentrations: 0 and 

10 mg a.i./L

Mean-measured 

concentrations: 0 and 

10.4 mg a.i./L

94-d NOAEC > 6.36 mg 

a.i./L

94-d LOAEC ≥ 6.36 mg 

a.i./L

Endpoints considered: 

Fertilization / hatching 

success, time to hatch, 

time to swim up, posthatch survival, terminal 

length, wet or dry weights

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639719 Acceptable1

Freshwater invertebrate

Waterflea

Daphnia 

magna 

97.26 21-day chronic toxicity

Static renewal

Nominal 

concentrations: 0, 6.25, 

12.5, 25, 50, and 100 

mg a.i./L

Mean-measured 

concentrations (for 

highest concentration 

only): 95.3 mg a.i./L

21-d LC50/EC50 > 95.3 

mg a.i./L

21-d NOAEC > 95.3 mg 

a.i./L

21-d LOAEC ≥ 95.3 mg 

a.i./L

Endpoints considered: 

Mortality, reproductive 

effects (number of 

offspring per surviving 

adult), terminal length.

Endpoint(s) affected: 

None.

(Sub)lethal effects:

None.

45639718 Acceptable

Saltwater fish – NA

Saltwater invertebrate - NA 1

Study was previously classified invalid on account of low recoveries of test concentrations and highly variable analytical 

results; however, as no endpoints were affected at the lowest, measured dinotefuran concentration (that is, 6.36 mg a.i./L) 

and the limit testing on guideline 72-4 is allowable, the study was reclassified to acceptable in 2006 (USEPA, DP Barcodes 

D331699 & D316645)
Page | 85

Plants

Terrestrial plant testing (Tier I seedling emergence, MRID 45639729, and vegetative vigor, 

MRID 45639730) on ten species indicated no effects as a result of a single application of 

LX1414-01 MTI-446 20% SG (dinotefuran) Lot # 01i-6252 at a rate of 0.54 lbs a.i./A. For some 

plants, considered endpoints exhibited reductions relative to the controls which were < 25% (see 

Table 9), which indicates that further testing (i.e., Tier II) is not required. The 14-day EC25 and 

NOAEL for both studies were >0.54 lbs a.i./A and ≥ 0.54 lbs a.i./A, respectively.

Acute toxicity testing on aquatic vascular plant (L. gibba; MRID 45639731) showed no 

treatment related effects yielding 7-day EC50 annd NOAEC of > 110 mg a.i./L and ≥ 110 mg 

a.i./L, respectively. Non-vascular plant (P. subcapitata) acute toxicity testing on two degradates 

MNG (MRID 45639733) and DN (DN-phosphate; MRID 45639734) also showed no treatment 

related effects and thus 96-hour EC50 and NOAEC values of > 98.7/ ≥98.7 mg a.i./L and > 100.4 

/ ≥100.4 mg a.i./L, respectively. However, testing with the TGAI (MTI-446) indicated a 

significant effect on cell density for P. subcapitata at the two highest test concentrations yielding 

a 96-hour NOAEC of 25 mg a.i./L; the EC50 for cell density, biomass, and growth rate endpoints, 

however, is >97.6 mg a.i./L (the highest concentration tested).

Table B6. Effect concentrations (EC25/NOAEC) for terrestrial plants following exposure to 

Dinotefuran (TEP: MTI – 446 20%SG).

Species %a.i. Study Parameters EC25 / NOAEL MRID Classification 

/Category

Seedling 

emergence

20.39 Tier I, 14-day test; 

utilized overhead track 

sprayer

Single application rate:

600 g a.i./ha (i.e., 

0.5352 lbs a.i./A)

Dicots: bean, cabbage, 

lettuce, radish, 

soybean, tomato

Monocots: corn, onion, 

ryegrass, wheat

14-d EC25 > 0.54 lbs a.i./A

14-d NOAEL ≥ 0.54 lbs 

a.i./A

Endpoints considered: 

Emergence, survival, dry 

weight, plant height.

Endpoint(s) affected: None. 

No single monocot or dicot 

was most sensitive than the 

rest; there were no 

significant effects of 

treatment on any species or 

endpoint; however, 

observed reductions 

(relative to the control) for 

the considered endpoints 

across species were ≤ 14%.

(Sub)lethal effects:

None. By 2 weeks, no 

treatment related signs of

toxicity were observed.

45639729 Acceptable

Vegetative 

vigor

20.39 Tier I, 14-day test; 

utilized overhead track 

14-d EC25 > 0.54 lbs a.i./A

14-d NOAEL ≥ 0.54 lbs 

45639730 Acceptable
Page | 86

sprayer

Single application rate:

600 g a.i./ha (i.e., 

0.5352 lbs a.i./A)

Dicots: bean, cabbage, 

lettuce, radish, 

soybean, tomato

Monocots: corn, onion, 

ryegrass, wheat

a.i./A

Endpoints considered: 

Dry weight, plant height.

Endpoint(s) affected: None. 

No single monocot or dicot 

was most sensitive than the 

rest; however, by 14 days 

soybean dry weight 

exhibited a significant 

reduction (7%) relative to 

the control, which yields a 

NOAEL of <0.54 lbs a.i./A; 

but other reductions include 

lettuce plant ht (8%), onion 

dry wt (4%) and plant ht 

(10%), radish dry wt (3%) 

and plant ht (10%).

(Sub)lethal effects:

None. By 2 weeks, no 

treatment related signs of 

toxicity were observed.

Table B7. Effect concentrations (EC50/NOAEC) for aquatic plants following exposure to Dinotefuran 

(Technical MTI-446, unless otherwise stated). 

Species %a.i. Study Parameters EC50; NOAEC MRID Classification 

/Category

Vascular

Duckweed 

Lemna gibba

99.2 7-day acute toxicity

Static renewal

Nominal 

concentrations: 11, 

20, 35, 62, and 110 

mg a.i./L

Mean-measured 

concentrations: N/A, 

but a mean-measured 

test concentration 

averaged 101% of 

nominal 100 mg 

a.i./L

All endpoints:

7-d EC50 >110 mg a.i./L

7-d NOAEC ≥ 110 mg 

a.i./L

Endpoints considered: 

dry weight, growth rate, 

biomass

Endpoints affected: 

None. 

(Sub)lethal effects: 

Compared to the control, 

frond dry wt decreased by 

21.5, 2.9, 12.9, 2.3, and 

4.3%, biomass decreased 

by 11.2, 3, 17.5, 12.5, and 

8.4%, growth rate 

decreased by 4.8, 2.3, 6.9, 

4.7, and 3.2%.

45639731 Supplemental1

Non-vascular

Green Algae 

Pseudokirchneriella 

97.26 96-hour acute 

toxicity

Cell density

96-hr EC50 > 97.6 mg 

45639732 Acceptable
Page | 87

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Static 

Nominal 

concentrations: 0, 

6.25, 12.5, 25, 50, 

and 100 mg a.i./L

Mean-measured 

concentrations (for 

highest concentration 

only): 97.6 mg a.i./L

a.i./L

96-hr EC05: 21 mg a.i./L 

(95% C.I. 24-190 mg 

a.i./L)

96-hr NOAEC: 25 mg 

a.i./L

Probit slope: 0.535 ± 

0.325

AUG curve (biomass) & 

growth rate

96-hr EC50 >97.6 mg 

a.i./L

NOAEC ≥ 97.6 mg a.i./L

Endpoints considered: 

Cell density, AUG curve 

(biomass), growth rate

Endpoint(s) affected: Cell 

density.

(Sub)lethal effects:

Cell density significantly 

reduced in the two 

highest test 

concentrations, thus the 

determination of NOAEC 

of 25 mg a.i./L. The 96-hr 

%inhibition of growth 

rate was 1.5, 0, 0.5, 1.6, 

and 2.0%; of AUG curve 

was 12, -3.2, -1.1, 5.9, 

and 3.6% for test 

concentrations, 

respectively. Shape of 

cells was unaffected. 

Green Algae 

Pseudokirchneriella 

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Not 

reported

Metabolite

MNG

96-hour acute 

toxicity (limit test)

Static

Nominal 

concentrations: 0, 

1.0, 10, and 100 mg 

a.i./L

Mean-measured 

concentration (for 

highest concentration 

only): 98.7 mg a.i./L

All endpoints:

96-hr EC50 > 98.7 mg 

a.i./L

96-hr NOAEC ≥ 98.7 mg 

a.i./L

Endpoints considered: 

cell density, growth rate, 

AUG curve (biomass)

Endpoints affected: 

None. 

(Sub)lethal effects: 

Compared to the control, 

96-hr %inhibition for cell 

density was 34, -8, and 

23%, for growth rate was 

20, -1.7, and 8.3%, for 

45639733 Supplemental2
Page | 88

biomass was 30, -9.8, and 

14%

Green Algae 

Pseudokirchneriella 

subcapitata 

(a.k.a. Selenastrum 

capricornutum)

Not 

reported

Metabolite 

DN (DNPhosphate)

96-hour acute 

toxicity (limit test)

Static

Nominal 

concentrations: 0, 

1.0, 10, and 100 mg 

a.i./L

Mean-measured 

concentration (for 

highest concentration 

only): 100.4 mg 

a.i./L

All endpoints:

96-hr EC50 > 100.4 mg 

a.i./L

96-hr NOAEC ≥ 100.4 

mg a.i./L

Endpoints considered: 

cell density, growth rate, 

AUG curve (biomass)

Endpoints affected: 

None. 

(Sub)lethal effects: 

Compared to the control, 

96-hr %inhibition for cell 

density was 31, -6, and 

1%, for growth rate was 

7, 0, and 2%, for biomass 

was 15, 2, and 4%

45639734 Supplemental2

Freshwater Diatom 

Navicula pelliculosa

NA NA NA NA NA

Marine Diatom 

Selenastrum costatum

NA NA NA NA NA

Freshwater Alga 

Anabaena flosaquae

NA NA NA NA NA

1 The study is scientifically sound, but does not satisfy guideline requirements for a tier II acute toxicity study with aquatic 

vascular plants because the test concentrations that plants were exposed to were not analytically determined and replicate 

data were only provided for frond number 2 As there is no requirement for testing with a degradate, the study is classified as supplemental.

*Values in bold indicate definitive endpoint and/or one which is used in risk quotient calculation.
Page | 89

Appendix C. Data Requests from Various Studies (also a non-guideline study inquiry)

Fate

860.1340 Laboratory Validation Methods (MRID#48120503). This study was deemed 

supplemental because no independent laboratory validation was provided. The study is 

upgradable with submittal of an independent laboratory validation. The study was part of a threestudy data package for which review was completed on May 9, 2011 (DP Barcode: D380085). 

The study was a Laboratory Validation of Methods For The Analysis of Dinotefuran in Cotton 

Nectar, Honey, Beeswax and Pollen Obtained From Hives of Bees Foraging In Cotton. It was in 

support of a honeybee field study (MRID 48120501): Field evaluation of Foraging Honey Bees 

(Apis mellifera) and Hives After Exposure to Dinotefuran Applied to Cotton.

860.1380 Evaluation of the Freezer Storage Stability (MRID# 48120502). This study was 

deemed unacceptable because no details on the freezer storage conditions (temperature, etc.)

were provided in the study. The study is upgradable with submittal of the missing information. 

The study was part of a three-study data package for which review was completed on May 9, 

2011 (DP Barcode: D380085). The study was an Evaluation of the Freezer Storage Stability of 

Dinotefuran in Cotton Nectar, Honey, Beeswax and Pollen. It was in support of a honeybee field 

study (MRID 48120501): Field evaluation of Foraging Honey Bees (Apis mellifera) and Hives 

After Exposure to Dinotefuran Applied to Cotton.

See the following memo for the above two studies: USEPA 2011. Review of Dinotefuran Field Evaluation 

of Foraging Honey Bees. OCSPP/EFED. Washington, DC. May 9, 2011. DP Barcode: D380085. 

Effects

The following study is a special study that was submitted for imidacloprid.

Non-guideline Aquatic Invertebrate Decomposition Study

The study objective is to assess the potential impacts on invertebrates through consumption of 

contaminated leaf-litter from forestry uses of dinotefuran. Given the risk conclusions from the 

recent new use assessment on forestry uses (USEPA 2011, DP Barcode D378125) and, in 

particular, tree injection applications there are potential risks to saltwater invertebrates, terrestrial 

invertebrates, birds, and mammals. However, given the uncertainty in the tree injection analysis 

in particular for aquatic invertebrates, further clarification and data are needed. The registrant 

should provide a draft protocol to the Agency prior to study initiation.

The Data Evaluation Record (DER) states that plant residues were not chemically analyzed but 

there may be a possibility that the raw data was just not submitted for the following study.

850.3030 Honeybee toxicity of residues on foliage (MRID 45639728 alfalfa)

The submitted study testing honeybee toxicity to residues of formulation MTI-446 20% WG on 

alfalfa was deemed acceptable; however, a couple of things were not reported in the study that 

would benefit the evaluation of honeybee exposure to residues on foliage post foliar spray 

application. Specifically, the additional information requested from the residues on alfalfa study 

includes the following: 1) foliar residue measurement data; and, 2) purity of test compound.
Page | 90

OPPTS 850.3030 draft guidance indicates that the latter should be included in the study report; 

additional reporting should not be limited to what is listed in the guidance document. Therefore, 

at this time, the raw data is requested by EFED.

All that is needed in the following study is the purity of the test compound.

850.5400 Aquatic Plant Growth: non-vascular plant (metabolite studies: MRIDs 45639733, 

45639734)

The submitted studies testing freshwater green algae Pseudokirchneriella subcapitata 

(a.k.a. Selenastrum capricornutum) were both deemed supplemental on account of testing with 

metabolites (MNG and DN-phosphate); however, neither study reported the purity of the test 

compound, which is needed to better characterize exposure to these metabolites. 
Page | 91

Appendix D. Data Call-In (DCI) Justification Tables

Study Title: Pollinator Larval Toxicity Study

Guideline Number: Non-guideline

Test Substance: Dinotefuran

Rationale for Requiring the Data

Environmental fate and toxicological data indicate that dinotefuran is a persistent, mobile, and 

systemic insecticide and is highly toxic to adult honey bees on an acute exposure basis. Because of 

the potential for pollen and nectar to be contaminated with dinotefuran it is important to determine 

the toxicity of this compound to pollinator larvae. The registrant should consult the Agency on the 

design of the protocol prior to the initiation of the study.

Practical Utility of the Data

How will the data be used?

To assess risk to non-target listed and non-listed terrestrial invertebrate species. This study would 

allow the Agency to refine the screening level risk assessment for beneficial terrestrial 

invertebrates. The effects data will be used to determine the potential for risk to beneficial 

terrestrial invertebrates through direct effects on larval bees. 

How could the data impact the Agency’s future decision-making?

EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action 

it authorizes or takes “...is not likely to jeopardize the continued existence of any endangered or 

threatened species or result in the destruction or adverse modification of critical habitat” and “to 

use the best scientific data available” in carrying out this obligation. The data EPA intends to call 

in are necessary to inform the determination required by ESA as to whether continued registration 

of a pesticide is or is not likely to jeopardize the species or its critical habitat. The lack of these 

data will limit the flexibility that the Agency and registrants have in coming into compliance with 

ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of 

these data may result in assumed risk and potential mitigation of dinotefuran formulations under 

FIFRA.

Study Title: Pollinator Laboratory Chronic Feeding Study

Guideline Number: Non-guideline

Test Substance: Dinotefuran

Rationale for Requiring the Data

Environmental fate and toxicological data indicate that dinotefuran is a persistent, mobile, and 

systemic insecticide and is highly toxic to adult honey bees on an acute exposure basis. Because of 

the potential for pollen and nectar to be contaminated with dinotefuran it is important to determine 

the toxicity of this compound to adult pollinators on a chronic basis. It is possible for dinotefuran

to cause sublethal effects, which may affect the ability of the pollinator to forage for food, 

communicate, and rear young. The registrant should consult the Agency on the design of the 

protocol prior to the initiation of the study.

Practical Utility of the Data

How will the data be used?

To assess risk to non-target listed and non-listed terrestrial invertebrate species. This study would 

allow the Agency to refine the screening level risk assessment for beneficial terrestrial 
Page | 92

invertebrates. The effects data will be used to determine the potential for risk to beneficial 

terrestrial invertebrates through direct effects on bees over time. 

How could the data impact the Agency’s future decision-making?

EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action 

it authorizes or takes “...is not likely to jeopardize the continued existence of any endangered or 

threatened species or result in the destruction or adverse modification of critical habitat” and “to 

use the best scientific data available” in carrying out this obligation. The data EPA intends to call 

in are necessary to inform the determination required by ESA as to whether continued registration 

of a pesticide is or is not likely to jeopardize the species or its critical habitat. The lack of these 

data will limit the flexibility that the Agency and registrants have in coming into compliance with 

ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of 

these data may result in assumed risk and potential mitigation of dinotefuran formulations under 

FIFRA.

Study Title: Residues in Pollen and Nectar / Field Residue Analysis Study

Guideline Number: Non-guideline

Test Substance: Dinotefuran and degradates of concern

Rationale for Requiring the Data

Environmental fate and toxicological data indicate that dinotefuran is a persistent, mobile, and 

systemic insecticide that is highly toxic to adult honey bees on an acute exposure basis and has 

also shown sublethal effects. The systemic nature of the compound necessitates the quantification 

of pollinator-relevant residues in treated flowering plants, since pollinators will be exposed to 

residues from either current or prior season applications (due to the potential for residues to 

accumulate in plants and trees). Residues in edible/transportable-to-hive parts of treated trees and 

plants, including (where appropriate), but not limited to, guttation water, sap/resins, whole plant 

tissue (e.g., leaves, stems), as well as blooming, pollen-shedding, and nectar producing parts (i.e., 

flowers and, if present, extrafloral nectaries) of plants may inform the potential for risk.

The Agency will consider multiple crops based on certain selective criteria, including, but not 

limited to, the estimated usage, the application method, and whether the crop is attractive to 

pollinators. Furthermore, the Agency will consider a semi-field, full-field, or greenhouse-based

protocol lasting at least two years with multiple sampling time-steps. The protocol will depend on 

application type and crop. The registrant should consult the Agency on the design of the protocol 

prior to the initiation of the study.

Practical Utility of the Data

How will the data be used?

To assess risk to non-target listed and non-listed terrestrial invertebrate species. These data would 

allow the Agency to refine the screening level risk assessment for beneficial terrestrial 

invertebrates. Exposure data is an integral part of determining the potential for risk to beneficial

terrestrial invertebrates through direct exposure from their food sources.

How could the data impact the Agency’s future decision-making?

EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action 

it authorizes or takes “...is not likely to jeopardize the continued existence of any endangered or 

threatened species or result in the destruction or adverse modification of critical habitat” and “to 

use the best scientific data available” in carrying out this obligation. The data EPA intends to call 
Page | 93

in are necessary to inform the determination required by ESA as to whether continued registration 

of a pesticide is or is not likely to jeopardize the species or its critical habitat. The lack of these 

data will limit the flexibility that the Agency and registrants have in coming into compliance with 

ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of these 

data may result in an uncertain assumed risk and potential mitigation of dinotefuran formulations 

under FIFRA.

Study Title: Field Test For Pollinators

Guideline Number: 850.3040 (141-5) 

Test substance: Dinotefuran

Rationale for Requiring the Data

Given the potential for exposure to pollinators to toxic levels of dinotefuran translocated in 

treated crops, the Agency has indicated the need for pollinator field testing. This exposure to 

honey bees and other non-target terrestrial invertebrates could be manifested through the presence 

of dinotefuran from various routes of exposure, including, but not limited to, nectar and pollen. In 

order to have a better understanding of dinotefuran exposure routes and potential impact on 

pollinators, more information is needed from carefully designed field studies. The registrant 

should consult the Agency on the design of the protocol prior to the initiation of the study.

Practical Utility of the Data

How will the data be used? 

To assess risk to non-target listed and non-listed terrestrial invertebrate species. This study would 

allow the Agency to refine the screening level risk assessment for beneficial terrestrial 

invertebrates. The effects data would be used to determine the potential for risk to beneficial 

terrestrial invertebrates from specific routes of exposure. 

How could the data impact the Agency’s future decision-making?

EPA is required by section 7(a)(2) of the Endangered Species Act (ESA) to ensure that any action 

it authorizes or takes “...is not likely to jeopardize the continued existence of any endangered or 

threatened species or result in the destruction or adverse modification of critical habitat” and “to 

use the best scientific data available” in carrying out this obligation. The data EPA intends to call 

in are necessary to inform the determination required by ESA as to whether continued registration 

of a pesticide is or is not likely to jeopardize the species or its critical habitat. The lack of these 

data will limit the flexibility that the Agency and registrants have in coming into compliance with 

ESA and could result in use restrictions that are unnecessarily severe. In addition, the lack of 

these data may result in assumed risk and potential mitigation of dinotefuran formulations under 

FIFRA.
Page | 94

Appendix E. Environmental Fate Study Bibliography

161-1 Hydrolysis

MRID Citation Reference

45640101 Sydney, P. (1998) MTI-446: Determination of Hydrolysis as a Function of 

pH: Final Report: Lab Project Number: MTO/098: 95/MTO098/1216. 

Unpublished study prepared by Huntingdon Life Sciences. 47 p. 

45640102 Ishii, M. (2000) Hydrolysis Study of MTI-446: Lab Project Number: 

GH9901. Unpublished study prepared by Japan Analytical Chemistry 

Consultants Co., Ltd. 111 p. 

45640103 Mamouni, A. (2001) (Carbon-14)-MNG: Hydrolysis at Three Different pH 

Values: Lab Project Number: 731215. Unpublished study prepared by 

RCC Ltd. 45 p. {OPPTS 835.2110} 

45640104 Mamouni, A. (2001) (Carbon-14)-DN Phosphate: Hydrolysis at Three 

Different pH Values: Lab Project Number: 731237. Unpublished study 

prepared by RCC Ltd. 31 p. {OPPTS 835.2110} 

161-2 Photodegradation-water

MRID Citation Reference

45640105 van der Gaauw, A. (2002) Aqueous Photolysis of (Carbon-14)-MTI-446 

Under Laboratory Conditions and Determination of Quantum Yield: Lab 

Project Number: 729011. Unpublished study prepared by RCC Ltd. 104 p. 

{OPPTS 835.2210} 

45640106 Ishii, M. (2000) Aqueous Photodegradation of MTI-446: Lab Project 

Number: GP9901. Unpublished study prepared by Japan Analytical 

Chemistry Consultants Co., Ltd. 197 p. 

45640107 Burgener, A. (2001) Aqueous Photolysis of (Carbon-14)-MNG Under 

Laboratory Conditions and Determination of Quantum Yield: Lab Project 

Number: 731248. Unpublished study prepared by RCC Ltd. 69 p. {OPPTS 

835.2210} 

45640108 Burgener, A. (2001) Aqueous Photolysis of 14C-DN Phosphate under 

Laboratory Conditions. Unpublished Study Performed by the RCC Ltd., 

Environmental Chemistry & Pharmanalytics Division, Itingen, Switzerland; 

Sponsored and Submitted by Mitsui Chemicals, Inc., Agrochemical 

Division, Tokyo, Japan. RCC Study Number: 729077. Experimental Start 

Date December 19, 2000, and Completion Date February 28, 2001. Final 

Report Issued April 17, 2001.

161-3 Photodegradation-soil
Page | 95

MRID Citation Reference

45640109 Shah, J.; Hatzenbeler, C. (2001) Photodegradation of (Carbon-14)-MTI446 on Soil: Lab Project Number: 012788-1. Unpublished study prepared 

by Ricerca, LLC. 99 p. 

46711202 Volkl, S. (2004) (Carbon 14)-MNG: Degradation in Three Soils Incubated 

Under Aerobic Conditions. Project Number: 844180. Unpublished study 

prepared by RCC Umweltchemie Ag. 104 p.

Photodegradation-air

MRID Citation Reference

45640110 van der Gaauw, A. (2000) Estimation of the Degradation of MTI-446 by 

Photo-Oxidation in Air: Lab Project Number: 731160. Unpublished study 

prepared by RCC Ltd. 18 p. 

Aerobic soil metabolism

MRID Citation Reference

45640111 Lentz, N. (2001) Aerobic Degradation of MTI-446 in Soil—Preliminary 

Study: Lab Project Number: 012561-1. Unpublished study prepared by 

Ricerca, Inc. 73 p. 

45640112 Lentz, N. (2001) Aerobic Soil Metabolism of MTI-446: Lab Project 

Number: 013184-1. Unpublished study prepared by Ricerca, LLC. 80 p. 

46711201 Volkl, S. (2003) (Carbon 14)-MTI-446: Metabolism in One Soil Incubated 

Under Aerobic Conditions. Project Number: 843175. Unpublished study 

prepared by RCC Umweltchemie Ag. 95 p.

46751101 Lentz, N. (2006) Aerobic Soil Metabolism of MTI-446. Project Number: 

013184/1/1. Unpublished study prepared by Ricerca Biosciences, LLC. 22 

p.

Anaerobic soil metabolism

MRID Citation Reference

45891616 Volkl, S. (2003) Anaerobic Soil Degradation and Metabolism: (Carbon 14)-

MTI-446: Lab Project Number: 841703. Unpublished study prepared by 

RCC Ltd. 121 p. 

Aerobic aquatic metab.
Page | 96

MRID Citation Reference

45640117 Volkel, W. (2000) (Carbon-14)-MTI-446 Degradation and Metabolism in 

Aquatic Systems: Lab Project Number: 709604. Unpublished study 

prepared by RCC Ltd. 139 p. 

Leach/adsorp/desorption

MRID Citation Reference

45640113 Volkel, W. (2001) Adsorption/Desorption of (Carbon-14)-DN Phosphate on 

Soils: Lab Project Number: 729066. Unpublished study prepared by RCC 

Ltd. 76 p. 

45640114 Volkel, W. (2001) Adsorption/Desorption of (Carbon-14)-MTI-446 on Soils: 

Lab Project Number: 728998. Unpublished study prepared by RCC Ltd. 

102 p. 

45640115 Ishii, M. (2000) Soil Adsorption of MTI-446: Lab Project Number: GA9901. 

Unpublished study prepared by Japan Analytical Chemistry Consultants 

Co., Ltd. 50 p. 

45640116 Volkel, W. (2001) Adsorption/Desorption of (Carbon-14)-MNG on Soils: 

Lab Project Number: 729055. Unpublished study prepared by RCC Ltd. 

72 p. 

Terrestrial field dissipation

MRID Citation Reference

45640118 Hummel, R. (2002) Terrestrial Field Dissipation of Residues Following 

Application of MTI-446 to Bare Soil in California, Georgia, and New York: 

Lab Project Number: 41421A007. Unpublished study prepared by RCC 

Ltd. 227 p. 

45891610 Hummel, R. (2003) Terrestrial Field Dissipation of Residues Following 

Application of MTI-446 to Bare Soil in California, Georgia, and New York: 

Amended Final Report: Lab Project Number: 41421A007: 795284: 641-

01-414-01-21E-31. Unpublished study prepared by Landis International, 

Inc. and RCC LTD. 19 p. 

45640108 Burgener, A. (2001) Aqueous Photolysis of 14C-DN Phosphate under 

Laboratory Conditions. Unpublished Study Performed by the RCC Ltd., 

Environmental Chemistry & Pharmanalytics Division, Itingen, Switzerland; 

Sponsored and Submitted by Mitsui Chemicals, Inc., Agrochemical 

Division, Tokyo, Japan. RCC Study Number: 729077. Experimental Start 

Date December 19, 2000, and Completion Date February 28, 2001. Final 

Report Issued April 17, 2001.
Page | 97

Confined rotational crop

MRID Citation Reference

45639822 Hattermann, D. (2002) Confined Accumulation of (Carbon-14) MTI-446 in 

Rotational Crops in California: Lab Project Number: 41429C008: 820901: 

1651-01-414-01-29C-34. Unpublished study prepared by Landis 

International, Inc. 98 p. {OPPTS 860.1850} 

201-1 Droplet size spectrum

MRID Citation Reference

45639708 Hewitt, A. (2002) Atomization Droplet Size Spectra for MTI-446 

Insecticide: Lab Project Number: L02-001. Unpublished study prepared by 

Stewart Agricultural Research Services, Inc. 20 p. {OPPTS 840.1100} 

Non Guideline Selections

45639712 Kendall, T.; Nixon, W. (2001) Analytical Method Verification for the 

Determination of MTI-446 Technical in Saltwater: Lab Project Number: 

236C-102. Unpublished study prepared by Wildlife International, Ltd. 28 p. 

{OPPTS 850.1035} 

45639813 MacGregor, J.; Van Hoven, R.; Nixon, W. (2002) Independent Laboratory 

Validation of Methods for the Analysis of MTI-446 and Its Metabolite MNG 

in Soil: Lab Project Number: 236C-106: 836100: 739923. Unpublished 

study prepared by Wildlife International Ltd. 134 p. {OPPTS 860.1340} 

45640119 Wais, A. (2001) Validation of the Residue Analytical Method for MTI-446 

in Soil: Lab Project Number: 739923. Unpublished study prepared by RCC 

Ltd. 77 p. 

45640123 Wolf, S. (2001) Development and Validation of a Residue Analytical 

Method for the MTI-446 Metabolite MNG in Soil: Lab Project Number: 

836100. Unpublished study prepared by RCC Ltd. 47 p. 

45640124 Wais, A. (2002) MTI-446: Storage Stability in Soil: Interim Report: Lab 

Project Number: 827572. Unpublished study prepared by RCC Ltd. 31 p. 

{OPPTS 860.1380} 

45891615 Wais, A. (2002) Storage Stability in Soil: MTI-446: Lab Project Number: 

827572. Unpublished study prepared by RCC Ltd. 31 p. 

46403802 Cassidy, P. (2004) Independent Laboratory Validation: Residue Analytical 

Method, MTU 250/024447 for MTI-446, and Degradates, DN and UF, 

“Validation of bovine tissues (liver, kidney, muscle and fat), milk and 

cream and hen eggs”. Project Number: 017472/1. Unpublished study 

prepared by Ricerca Biosciences, LLC. 74 p.

46413801 Cassidy, P. (2004) LC-MS/MS Validation of Residues of MTI-446, and 
Page | 98

Degradates, DN and UF, From Lactating Goat Metabolism Study. Project 

Number: 017471/1, 017471/0. Unpublished study prepared by Ricerca 

Biosciences, LLC. 75 p.

46751103 Praveen-Kumar and R. Brumme (1999) Mineralization of Guanidine 

Derivatives in Soils. Published in Nutrient Cycling in Agroecosystems 53: 

133-138, 1999. Study Performed by Institute of Soil Science and Forest 

Nutrition, Goettingen, Germany; and Submitted by Mitsui Chemicals, Inc., 

c/o Landis International, Inc. Valdosta, Georgia.
Page | 99

Appendix F. Ecological Effects Study Bibliography

71-1 850.2100 Avian Single Dose Oral Toxicity

MRID Citation Reference

45639720 Burri, R. (2000) MTI-446 Technical: Acute Oral Toxicity Test in the 

Japanese Quail: Lab Project Number: 746425. Unpublished study 

prepared by RCC, Ltd. 46 p. 

47353601 Gallagher, S.; Beavers, J. (2007) MTI-446 Technical: An Acute Oral 

Toxicity Study with the Northern Bobwhite. Project Number: 236/127A. 

Unpublished study prepared by Wildlife International, Ltd. 34 p.

71-2 Avian Dietary Toxicity

MRID Citation Reference

45639721 Burri, R. (2000) MTI-446 Technical: Avian Dietary Toxicity Test in the 

Japanese Quail: Lab Project Number: 746436. Unpublished study 

prepared by RCC, Ltd. 47 p. {OPPTS 850.2200} 

45639722 Burri, R. (2000) MTI-446 Technical: Avian Dietary Toxicity Test in the 

Mallard Duck: Lab Project Number: 793754: 904994. Unpublished study 

prepared by RCC, Ltd. 46 p. {OPPTS 850.2200} 

71-4 Avian Reproduction

MRID Citation Reference

45639723 Mitchell, L.; Martin, K.; Beavers, J.; et. al. (2002) MTI-446 Technical: A 

Reproduction Study with the Mallard: Final Report: Lab Project Number: 

236-115. Unpublished study prepared by Wildlife International, Ltd. 157 p. 

45639724 Mitchell, L.; Martin, K.; Beavers, J.; et al. (2002) MTI-446 Technical: A 

Reproduction Study with the Northern Bobwhite: Final Report: Lab Project 

Number: 236-114. Unpublished study prepared by Wildlife International, 

Ltd. 159 p. 

72-1 Acute Toxicity to Freshwater Fish

MRID Citation Reference
Page | 100

45639714 Peither, A. (1999) Acute Toxicity of MTI 446 to Rainbow Trout 

(Oncorhynchus mykiss) in a 96-Hour Static Test: Lab Project Number: 

740924. Unpublished study prepared by RCC, Ltd. 33 p. {OPPTS 

850.1075} 

45639715 Peither, A. (2000) Acute Toxicity of MTI-446 to Bluegill Sunfish (Lepomis 

macrochirus) in a 96-Hour Static Test: Lab Project Number: 740946: 

740957. Unpublished study prepared by RCC, Ltd. 33 p. {OPPTS 

850.1075} 

45639716 Peither, A. (2000) Acute Toxicity of MTI-446 to Common Carp (Cyprinus 

carpio) in a 96-Hour Static Test: Lab Project Number: 741003: 741014. 

Unpublished study prepared by RCC, Ltd. 33 p. {OPPTS 850.1075} 

72-2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

45639709 Peither, A. (2000) Acute Toxicity of MTI-446 to Daphnia Magna in a 48-

Hour Immobilization Test: Lab Project Number: 740968: MTI-446: 740970. 

Unpublished study prepared by RCC Ltd. 32 p. {OPPTS 850.1010} 

45639710 Kelly, C.; Murphy, C.; Allan, J. (2002) DN Phosphate Determination of 

Acute Toxicity to Daphnia (48 h, Static): Lab Project Number: 20122: 

800141. Unpublished study prepared by Inveresk Research. 24 p. 

{OPPTS 850.1010} 

72-3 Acute Toxicity to Estuarine/Marine Organisms

MRID Citation Reference

45639711 Drottar, K.; Kendall, T.; Krueger, H. (2001) MTI-446 Technical: A 96-Hour 

Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): 

Final Report: Lab Project Number: 236A-106A. Unpublished study 

prepared by Wildlife International, Ltd. 38 p. {OPPTS 850.1025} 

45639713 Blankinship, A.; Drottar, K.; Kendall, T.; et al. (2001) MTI 446-Technical: A 

96-Hour Flow-Through Acute Toxicity Test with the Saltwater Mysid 

(Mysidopsis bahia): Final Report: Lab Project Number: 236A-104A. 

Unpublished study prepared by Wildlife International, Ltd. 38 p. {OPPTS 

850.1035} 

45639717 Blankinship, A.; Drottar, K.; Kendall, T.; et al. (2001) MTI-446 Technical: A 

96 Hour Flow-Through Acute Toxicity Test with the Sheepshead Minnow 

(Cyprinodon variegatus): Final Report: Lab Project Number: 236A-105. 

Unpublished study prepared by Wildlife International, Ltd. 39 p. {OPPTS 

850.1075} 

72-4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study
Page | 101

MRID Citation Reference

45639718 Peither, A. (2000) Influence of MTI-446 on Survival and Reproduction of 

Daphnia magna in a Semistatic Test over Three Weeks: Lab Project 

Number: 752106: 752117. Unpublished study prepared by RCC, Ltd. 40 p. 

{OPPTS 850.1300} 

45639719 Peither, A. (2001) Toxic Effects of MTI-446 to Rainbow Trout 

(Oncorhynchus mykiss) in an Early-Life Stage Toxicity Test: Lab Project 

Number: 794338: 794340. Unpublished study prepared by RCC, Ltd. 54 p. 

{OPPTS 850.1400} 

122-1 Seed Germination/Seedline Emergence and Vegetable Vigor

MRID Citation Reference

45639729 Porch, J.; Martin, K.; Krueger, H. (2001) MTI-446 20% SG: A Toxicity Test 

to Determine the Effects of the Test Substance on Seedling Emergence of 

Ten Species of Plants: Final Report: Lab Project Number: 236-116. 

Unpublished study prepared by Wildlife International, Ltd. 54 p. {OPPTS 

850.4100} 

45639730 Porch, J.; Brignole, A.; Krueger, H.; et al. (2001) MTI-446 20% SG: A 

Toxicity Test to Determine the Effects of the Test Substance on 

Vegetative Vigor of Ten Species of Plants: Final Report: Lab Project 

Number: 236-117. Unpublished study prepared by Wildlife International, 

Ltd. 74 p. {OPPTS 850.4150} 

122-2 Aquatic plant growth

MRID Citation Reference

45639731 Batscher, R. (2002) Toxicity of MTI-446 to the Aquatic Higher Plant 

Lemna Gibba in a 7-Day Semistatic Growth Inhibition Test: Lab Project 

Number: 827752. Unpublished study prepared by RCC, Ltd. 55 p. 

{OPPTS 850.4400} 

45639732 Seyfried, B. (2000) Toxicity of MTI-446 to Pseudokirchneriella subcapitata 

(Formerly Selenastrum capricornutum) in a 96-Hour Algal Growth 

Inhibition Test: Lab Project Number: 740981: 740992. Unpublished study 

prepared by RCC, Ltd. 37 p. {OPPTS 850.5400} 

45639733 Kelly, C.; Ferguson, K. (2002) MNG Alga, Growth Inhibition Test (96 h): 

Lab Project Number: 19918: 800199. Unpublished study prepared by 

Inveresk Research. 29 p. {OPPTS 850.5400} 

45639734 Kelly, C.; Ferguson, K. (2002) DN Phosphate Alga, Growth Inhibition Test 

(96 h): Lab Project Number: 19849: 800183: 8169. Unpublished study 

prepared by Inveresk Research. 28 p. {OPPTS 850.5400} 
Page | 102

141-1 Honey bee acute contact

MRID Citation Reference

45639725 Harnish, W. (2000) Acute Contact and Oral Toxicity of MTI-446, Active to 

Honey Bees: Lab Project Number: 41421F001. Unpublished study 

prepared by Landis International, Inc. 68 p. {OPPTS 850.3020} 

45639726 Harnish, W. (2000) Acute Contact and Oral Toxicity of MTI-446, 20% WG 

to Honey Bees: Lab Project Number: 41421F002. Unpublished study 

prepared by Landis International, Inc. 62 p. {OPPTS 850.3020} 

45639727 Thompson, H. (1998) A Formulation Containing MTI-446: Acute Contact 

and Oral Toxicity to Honey Bees (Apis mellifera): Lab Project Number: 

FP2400. Unpublished study prepared by Central Science Laboratory, 

National Bee Unit. 47 p. 

141-2 Honey bee residue on foliage

MRID Citation Reference

45639728 Hummel, R. (2001) Evaluation of Toxicity of Residues of MTI-446 on 

Alfalfa to Honey Bees (Apis mellifera): Lab Project Number: 43421F001. 

Unpublished study prepared by Landis International, Inc. 46 p. {OPPTS 

850.3030} 

850.3040 (formerly 141-5) Field testing for pollinators

MRID Citation Reference

47688101 Hummel, R. (2009) Field Evaluation of Foraging Honey Bees (Apis 

mellifera) and Hives after Exposure to Dinotefuran Applied to Cotton. 

Project Number: 43421F008. Unpublished study prepared by Landis 

International, Inc. 44 p.

48120501 Hummel, R. (2010) Field Evaluation of Foraging Honey Bees (Apis 

mellifera) and Hives After Exposure to Dinotefuran Applied to Cotton. 

Project Number: 43421F008. Unpublished study prepared by Landis 

International, Inc. 173 p.

143-1 Toxicity to Predator and Parasite Insects

MRID Citation Reference
Page | 103

45640120 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Predaceous Mite Typhlodromus pyri Scheuten (Acari:Phytoseiidae): Lab 

Project Number: RCC011TPL: 756268. Unpublished study prepared by 

MITOX Stichting Bevordering Duurzame Plaagbestrijding. 27 p. 

45640121 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Parasitoid Wasp Aphidius rhopalosiphi (DeStephani-Perez) 

(Hymenoptera: Braconidae): Lab Project Number: RCC012ARL: 756270. 

Unpublished study prepared by MITOX Stichting Bevordering Duurzame 

Plaagbestrijding. 24 p. 

45640122 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Predacious Bug Orius laevigatus (Fleber) (Hemiptera, Anthocoridae): Lab 

Project Number: 756281: RCC013OLL. Unpublished study prepared by 

MITOX Stichting Bevordering Duurzame Plaagbestrijding. 25 p. 

143-3 Chronic Effects to Predator and Parasite Insects

MRID Citation Reference

45640120 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Predaceous Mite Typhlodromus pyri Scheuten (Acari:Phytoseiidae): Lab 

Project Number: RCC011TPL: 756268. Unpublished study prepared by 

MITOX Stichting Bevordering Duurzame Plaagbestrijding. 27 p. 

45640121 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Parasitoid Wasp Aphidius rhopalosiphi (DeStephani-Perez) 

(Hymenoptera: Braconidae): Lab Project Number: RCC012ARL: 756270. 

Unpublished study prepared by MITOX Stichting Bevordering Duurzame 

Plaagbestrijding. 24 p. 

45640122 Aldershof, S. (2000) A Laboratory Dose-Response Study to Evaluate the 

Effects of MTI-446 20% SG on Survival and Reproduction of the 

Predacious Bug Orius laevigatus (Fleber) (Hemiptera, Anthocoridae): Lab 

Project Number: 756281: RCC013OLL. Unpublished study prepared by 

MITOX Stichting Bevordering Duurzame Plaagbestrijding. 25 p. 

Non Guideline Selections

45639712 Kendall, T.; Nixon, W. (2001) Analytical Method Verification for the 

Determination of MTI-446 Technical in Saltwater: Lab Project Number: 

236C-102. Unpublished study prepared by Wildlife International, Ltd. 28 p. 

{OPPTS 850.1035} 

47264701 Snell, E.; Sexton, W.; Weiner, D. (2006) Evaluation of the Efficacy of TC 
Page | 104

249 Dinotefuran Dust 0.25% When Applied to Black Widow Spiders 

(Latrodectus hesperus) in Glass Petri Dish Arenas. Project Number: 

WHITBWTC249DINOPANEL06. Unpublished study prepared by Snell 

Scientifics, LLC. 25 p.

47518702 Snell, E. (2008) Evaluation of Whitmire TC 267 When Applied as Direct 

Spray onto Brown Recluse Spiders (Loxosceles reclusa). Project Number: 

WHITTO267BRDIRECT08. Unpublished study prepared by Snell 

Scientifics, LLC. 20 p.

47518703 Sims, S. (2008) The Effects of a Direct Contact Spray from a Dinotefuran 

Aerosol Formulation on Workers of the Black Carpenter Ant, Camponotus 

pennsylvanicus (DeGeer) and the Field Ant, Formica subsericea Say 

(Hymenoptera: Formicidae). Project Number: 1221. Unpublished study 

prepared by Whitmire Micro-Gen Research Laboratories, Inc. 7 p.