# 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 ana lyzing data relevant to dinotefuran and fo r 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 (FIF RA), 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 speci es 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 mar ketplace 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 determin e 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 we ll 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)

**•** O PPTS Guidance 835.4400 Anaerobic Aquatic Metabolism

Effects Data Gaps (see Table s 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

- GL N 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

- vasc ular 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

- furylm ethyl) 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 Barco de: 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, sq uash, 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 h ighlighted 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 hea d 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, 20 04 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

- 11 1 

### ) 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 br oadcast 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 dinotefura n did not trigger acute risks to non

- target non

listed 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 es tuarine/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 p attern, 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 exceedance s 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: D 332829 ) 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 l abel for leafy brassica does not result in exposures exceeding LOCs. A previous assessment was cited (USEP A 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 Agricultu re 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 PA 3 

### 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 registra nt]; and, Scorpion 35SL Insecticide with 35% dinotefuran a.i., EPA Reg. No. 10163

- 317, respectively [Gowan as registrant]) on commercial pome fruit and stone fruit 4 

### orchards to control the brown marmorated stink bug ( Halyomorpha halys) from April 15 to Oct ober 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 pl ants (listed and non

- listed) were not expected from the pro posed 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 w as 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 c rops 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 inver tebrates 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 nectar

producing 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 (increas ing use rates) 3328 29 2006 Leafy Brassica Sweet potato

w hitefl y 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, autom obiles, 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

c ontrol a brown marmorated s tink b ug (BMSB) infestation in pome fruit and stone fruit in Virginia, Delaware, North Carolina, West Virginia, Pennsylvania, New J ersey and Maryland (see DP Barc ode: 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 b y 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

a nnual 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 t reated 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.

Ta ble 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

- OH 3 100% 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 r esidues 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 sub

class formulated as granules, emulsifiable concentrate, ready

- to

- use solution, and as a

### Page | 8 pressurized liquid . Agricultural use sites include cucurbits, grapes, pine apple, 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 pre mises, 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 runo ff, soil erosion, and off

- target spray drift. Due to the low adsorption potential of dinotefuran and its degradate MNG (K oc 

### ’s <45; but DN

- Phosphate K oc 

### 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 a nd 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 met hod, 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. Acetylch oline (ACh) is the endogenous agonist and excitatory neurotransmitter of the cholinergic nervous system. Therefore, d inotefuran acts on the autonomic nervous system by binding to the postsynaptic nicotinic acetylcholine receptor. Although the cholinesteras e 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 @20 o 

### 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 grub s, 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 agricult ural 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 highe st 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 wi th 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 m ealybug 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 l b 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 Kiw ifruit, hard y Maypop Schisandra berry Cultivars, Vari eties and/or hybrids of these Foliar : (0.045 to 0

. 1 35 lb ai/ A) @ 14 days interval Or Soil: ( 0.225 to 0 .33 8 1b ai/A) @ 14 days interval Foliar : ( 0 .2 70 lb ai/ A)

Soil: ( 0 .33 8 l b 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 Bluebe rry Lowbush Clo udb e rry Cranberry Lingonberr y M untries Part rid ge berry Cu l tivar s , v ari eties and/or h ybrids of t hese F oliar : (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 (Chi nese Preserv ing Melon ) Citron Melon Crenshaw Melon Crookneck Squash Cucu mber Edible Gourd Gherkin Golden Pershaw Melon Honey Balls Honeydew Me lon Hubbard Squash Mango Melon Momordica spp. Muskmelon Persian Melon P i neapple Melon Pumpkin S anta Claus Melon Scallop Squash Snake Melon Spaghetti Squash St raightne ck 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 0.26 8 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 0.53 6 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

O verall 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) Arracac ha ArrowRoot Artichoke

, Chinese Artichok e, J erusalem Canna, edible Cassa v a, bitter and sweet Chayote (root) Chufa Foliar: 0.045 to 0.068 lb ai/ A @ 14 days interval Or Soil: 0.293 to 0.33 8 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) Ginge r Leren Potato Swee t P otato T anier 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

O verall 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, interio r plant scapes, 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 l b ai/A) Foliar: 0.360 l b 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 E astern Hemlock

(F orest/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 Use s

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 PROCESS ING 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/MARK ETING/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 OUTD OOR, 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 (K ow 

### = 0.283; log K ow 

### =
- 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 

### a tm • M 3 

### /mol) suggest that this compound is not expected to volatilize substantially from water or soils in the environment. The e nvironmental fate and
p hysico

- chemical properties of d inotefuran 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 (20 o C) 39,830 mg/L for parent MRID# 45640112

Vapor pressure (30 o C) <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 m 3 /mol Calculated Octanol/Water Partition, K ow 0.283 @25 o C MRID # 45639702 log K OW - 0.549 MRID # 45639702 Dissociation constant (pKa) 12.6 @20 o C (estimated) MRID # 45639702 Melting point 107.5 o C MRID # 45639702 pH 5.6 @25 o C MRID # 45654201 Density 1.40 g/cm 3 @20 o C 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 route s 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. M ajor 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 h ydrogen succinate (BCDN succinate). DN is a minor photodegradation product (<10% applied radioactivity). D inotefuran is moderately persistent in soil under both aerobic (half

- life = 16

- 100 days) and anaerobic (half

life = 62 days) conditions. D inotefura n degrades to form 1

- methyl

- 2

- nitroguanidine ( MNG ), which subsequently degrades to form nitroguanidine (NG). I t is very highly mobile (K oc 

### = 6

- 45) in soil. Because dinotefuran has low sorption coefficients i n soil , it ha s a high potential to leach and runoff from the application site. T he 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 m etabolism is expected to dominate the dissipation processes. Dinotefuran wa s 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 dinotef uran 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 ) Photo degradation in W ater Half

- life 1.8 days MRID# 45640105 (s)

Photo degradation in Soil Half

- life Stable MRID# 45640109 (u)

Aerobic Soil M etabolism 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 s oil 15.9 days

, Silt Loam soil MRID# 45640111 (s) M RID# 45640112 (s) MRID#’s 46751101(a) MRID#45640112(a) MRID# 46711201 (s)

Anaerobic Soil M etabolism Half

- life 65 days MRID# 45891616 (s)

Aerobic Aquatic metabolism Half

- life 79.3 days
76 .0 days MRID # 45640117 (s)

Batch Equilibrium L oam 1.01 42 Texture Kd Koc

Sandy Loam 0.71 45 C lay L oam 1.22 42 L oamy S and 0.12 6 Si lt L oam 0.22 22 MRID# 45640114 (a)

Terrestrial Field Dissipation CA (SL) t 1/2 = 65.2 days MNG (degradate) was detected in 0

- 15 cm soil at 31.5% @ 45 days after 2nd application. GA (SL) t 1/2 = 19.4 days MNG was detected in 0

- 15 cm soil at 5.3% max. mean concentration after 7 and 30 days after the 2 nd application. NY (SL) t 1/2 = 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 (K OW = 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 half

life, 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 2 nd application; study termination at 170 days after 2 nd 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

- OH 1 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. M GN is stable to abioti c hydrolysis at pH 4, 7, and 9 . It rapidly photodegrades (t 1/2 

### = 2.4 days) in water. MGN is moderately persistent (t 1/2 

### = 66.9 to 166 days) in soil and persistent (t 1/2 

### = 459 days) in aquatic environments. It has low soil:water portioning coefficients (K d 

### < 1; K oc 

### <31), suggesting a potential for l eaching 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 N H 2

N C H 3

N O 2

O N H

N H N H C H 3

H 3 P O 4

O N H

O N H C H 3

N H N H N H 2 C H 3

Cl H

O H N NH

HN OH COOH

COOH 2

N H N O

N H C H 3 C O O H

C O O H

### Page | 21 Table 7

. Physicochemical and Environmental Fate Pro perties for Dinotefuran Degradation Product

- MGN

Parameter 

### Value Reference/ Comments Selected Physical Chemical Parameters Water Solubility (20 o C) 11,480 mg/L MRID# 45640112 MRID# 45639702, 45639706, 45639707 (USEPA Pesticide Fact Sheet, 2004)

Hydrolysis Half

- life pH 4

- 9 (50 o C) 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 t 1/2 459.3 days MRID # 45640117 (USEPA Pesticide Fact Sheet, 2004) Mobility in Soils L oam 0.75 31 Texture K d K OC

S andy L oam 0.12 8 C lay L oam 0.70 24 L oamy S and 0.16 8 Si lt 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

- phosphate 5 

### are shown in Table 8 . Potential routes of dissipa tion include photodegradation, microbial

- mediated metabolism, leaching, and runoff. N

phosphate is stable to abiotic hydrolysis at pH 4, 7, and 9). Photodegradation is slow (t 1/2 

### = 53.4 to stable days) in water at pH 5, 7, and 9. It is moderately persistent (t 1/2 

### = 114 days) in soil and aquatic environments. DN

- phosphate h as low soil:water portioning coefficients (K d 

### < 3; Koc 58

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

### : 7

- 72; K oc 

### : 270

- 2502) were found in clay textured soils. These data suggest the extent leaching or

ru noff 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), photod egradation 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

- (tetrahy dro

- 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 (20 o C) 619,400 mg/L MRID# 45640112

MRID# 45639702, 45639706, 45639707 (USEPA Pesticide Fact Sheet, 2004)

Hydrolysis Half

- life DN

- Phosphate pH 4

- 9 (50 o C) 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 t 1/2 114 days MRID# 45640117 (USEPA Pesticide Fact Sheet, 2004) Mobility in Soils DN

- Phosphate L oam 2.08 87 Texture K d K OC

S a ndy L oam 2.07 58 C lay L oam 72.54 2502 S andy L oam 2.93 413 C lay 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 (t 1/2 

### = 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 (20 o C) 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. T oxicological 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 M etabolism A ssessment R eview C ommittee (MARC, USEPA 2 004 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 t oxicity and potential expos ure 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 t he available toxicity data for dinotefuran will be used to quantify risk.

A cute 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 E COTOX 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.go v/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 LC 50 

### 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 LD 50 

### 0.075 **μ** g a.i./ bee ( 0.0628

- 0.0896 **μ** g 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 ter restrial habitats is provided later in this document . A description of ecologica l 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 LC 50 

### > 99 mg a.i./L), as well as freshwater invertebrate s ( D. magna 48

- hour LC 50 

### > 968.3 mg a.i./L; MRID 45639709)

### Page | 24 and saltwater mollusks (eastern oyster 96

- hr EC 50 

### > 141 mg a.i./L ; MRID 45639711 ) ; no sublethal effects were noted in these studies . The degradate of dinotefuran (DN phosphate) is also considered practi c ally non

- toxic to the freshwater invertebrate ( D. magna 48

- hour LC 50 

### > 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 estu arine/marine invertebrates (mysid shrimp LC 50 

### = 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 > 6.3 6 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 est uarine/marine invertebrates. Based on the available data the estuarine/marine invertebrates (mysid, LC 50 

### = 0.79 mg a.i./L) are significantly more sensitive to dinotefuran than freshwater invertebrates ( Daphnia , LC 50 

### >110.6 mg a.i./L) on an acute exposure b asis. 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 need ed to address this uncertainty.

Table 10

. Acute effect concentrations (LC 50 /EC 50 ) for aquatic animals following exposure to dinotefuran Species Measurement Endpoint Time LC 50 /EC 50 MRID / OPPTS GLN# Waterflea Daphnia magna Mortality/Immobility (Test substance: DN phosphate, metabolite of dinotefuran) 48 hr LC 50 > 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 non

toxic 1 )

850.1010

Mysid Americamysis bahia Mortality (TGAI: 99.2%) 96 hr LC 50 : 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 toxic 1 )

850.1035

1 Based on EC 50 (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 T oxicity testing on aquatic vascular plant s ( L. gibba ; MRID 45639731) showed no treatment related effects yielding 7

- day EC 50 

### 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 EC 50 

### and NOAEC values of > 98.7/ ≥98.7 mg a.i./L and > 100.4 / ≥100.4 mg a.i./L, r espectively. 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 EC 50 

### for cell density, biomass, and gr owth rate endpoints, however, is >97.6 mg a.i./L (the highest conc entration tested).

### Page | 26 Table 11

. Effect concentrations (EC 50 /NOAEC) for aquatic plants following exposure to dinotefuran Species Measurement Endpoint Time EC 50 /NOAEC MRID / OPPTS GLN# Vascular
Duckweed Lemna gibba Dry weight, growth rate, biomass (TGAI: 99.2 7

- day All endpoints: EC 50 >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 (Supplemental 1 )

850.4400

Non

- vascular Green Algae Pseudokirchneriella subcapitata (a.k.a . Selenastrum capricornutum ) Cell density, biomass, growth rate (TGAI: 97.26%) 96 hr EC 50 > 97.6 mg a.i./L EC 05 : 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

concent rations, respectively. Shape of cells was unaffected. 45639732 (Acceptable)

850.5400

Green Algae Pseudokirchneriella subcapitata (a.k.a . Selenastrum capricornutum ) Metabolite MNG 96 hr EC 50 > 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 (Supplemental 2 )

850.5400

Green Algae Pseudokirchneriella subcapitata (a.k.a . Selenastrum capricornutum ) Metabolite DN (DN

- Phosphate) 96 hr EC 50 > 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 (Supplemental 2 )

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 (LD 50 

### > 2,000 mg a.i./kg

- bw; MRID 45639720) and bobw hite quail (LD 50 

### > 2,250 mg a.i./kg

- bw; MRID 47353601) on an acute oral basis and to mallard duck (LC 50 

### > 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 (LC 50 

### > 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 high est 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 stu dies. 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 perc entages of number of hatchlings/eggs laid, eggs set, and 14

- day old survivors.

Dinotefuran is slightly to practically nontoxic on an acute basis to mammal s (laboratory rat) (female LD 50 

### = 2000 mg/kg

- bw; MRID 45639823). Chronic studies indicated e ffects 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 ut e rus and estrous cyclicity in F o 

### and F 1 

### females, slight increases in abnormal sperm morphology in F o 

### and F 1 

### males, and slight decreases in testicular sperm count in F o 

### males and sperm mortality in F 1 

### 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 s tomach). 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 s tudies may be utilized in risk description of a future risk assessm ent

. 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 LD 50 

### = 0.047 **μ** g ai /bee) and on an acute oral basis (48

- hr LD 50 

### = 0.023 **μ** g 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 LD 50 

### = 0.061 **μ** g a.i ./bee and 0.024 **μ** g 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 LD 50 

### = 0.032 **μ** g a.i./bee and 0.0076 **μ** g a.i./bee, respectively). The RT 25 

### (or

### Page | 28 residual time to cause 25% mortality) derived from the exposure to residues on alfalfa study (MRID 4 5639728) with the formulation MTI

- 446 20% WG indicated that bees were most sensitive to the 8 hour aged residue (RT 25 

### = 4.8 hours) and least sensitive to treatment when exposed to 48 hour aged residue (RT 25 

### = 90 hours). When translocated from pollen and ne ctar 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 implicatio ns 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 LC 50 

### 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 app lication 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 4 7814402 ). For further details on the toxicity studies see Appendix B

.

### Page | 29 Table 12 . Acute effect concentrations (LD 50 /LC 50 ) for terrestrial organisms following exposure to dinotefuran.

Species Measurement Endpoint Time LD 50 /LC 50 MRID / OPPTS GLN#
Birds Japanese quail Coturnix japonica Oral Toxicity (TGAI: 97.26%) 14 day LD 50 > 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 non

toxic 3 )

850.2100

Mammals
Rat Rattus norvegicus Oral Toxicity (TGAI: 99.1%) 14 day ♂ LD 50 = 2,804 mg/kg

- bw ♀ LD 50 = 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) LC 50 > 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) LC 50 > 2.34 mg form/L LC 50 > 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) LC 50 > 2.02 mg form/L LC 50 > 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 LD 50 = 0.0076 **μ** g 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 (Supplemental 2 ;

highly toxic 1 )

850.3020

### Page | 30 concurrent dimethoate test had 13% mortality in the solvent control. At 4 hours, there were stumbli ng and/or knockdown bees observed in every treatment and control group, except for the 0.00056 **μ** g 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 LD 50 = 0.024 **μ** g 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 **μ** g a.i./bee
groups. 45639727 (Acceptab le / Highly toxic 1 )

850.3020

1 Based on acute contact LD 50 ( **μ** g 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 LD 50 (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 effect s: 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) a ffected/Sublethal effects: Decreased uterine weights, microscopic alteration in uterus and vagina of F o ♀; decreased numbers of primordial follicles in F 1 ♀, altered estrous cyclicity in F
o ♀; slight increases in abnormal sperm morphology in F

o and F 1 ♂, and slight decreases in testicular sperm count in F o ♂ and sperm mortality in F 1 ♂. 45639913 (definitive test) 45639914 (range

finding 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 tox icity 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). Ot her 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 EC 25 

### 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 inciden t databases : 1) the Ecological Incident Information System v. 2.1.1 (EIIS) maintained by EFED ; 2 ) the Avian Incident Monitoring Sy stem (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 effec t; this is the case for all three incident databases searched. The absence of documented incidents does not necessarily mean that such incidents did
not o ccur.

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

- w ay 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 onl y 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 report ing 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 non

target 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 di scovering 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 t he 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 un cultivated 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 u ses 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 chara cteristics (USEPA, 1998). For dinotefuran , the ecological entities may include the following: birds, mammals, terrestrial

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

- phase

am phibians, 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 e cological 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 complet e, 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 . R isk 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

- tar get organisms include f ederally

- 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 tran sport 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 att ribute 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:
t 1/2 

### range approximately 16

- 10 0 days for aerobic soil metabolism and 76

- 79 days for aerobic aquatic metabolism ), no K d 

### value is ≥50 L/kg, no available log K ow 

### is ≥3, and no K oc 

### ≥1, 000 L/kg OC, which imp lies that, on the bas is 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 K d 

### is 72.5 and K oc 

### is 2,502 which are outlier s 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 EC 50 

### >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, EC 50 

### : 0.069 mg/L, 96

- hr LC 50 

### : 0.0105 mg/L, 10

- day growth NOAEC: 0.00067 mg/L) and the amphipod crustacean ( Hyalella azteca , MRID 42256303, 96

- hr EC 50 

### : 0.055 mg/L, 96

- hr LC 50 

### : 0.526 mg/L) are of comparable sensitivity to imidacloprid as is the saltwater mysid ( Mysidopsis bahia

, MRID 42055319, LC 50 

### : 0.037 mg/L; MRID 42055322, NOAEL >0.0006 mg/L and LOAEC: 0.0013 mg/L ). Furthermore, these organi sms are more sensitive to imidacloprid relative to the water flea

### Page | 35 ( Daphnia magna

, MRID 42055317, 48

- hr EC 50 

### : 85 mg/L; MRID 42055321, 21

- day immobilization NOAEC: 1.3 mg/L). Given a similar response to dinotefuran, whereby greater sensitivity of the saltwa ter mysid shrimp ( LC 50 

### = 0.79 mg a.i./L; MRID 45639713 ) is observed relative to the daphnia (48

- hour LC 50 

### > 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 o bserved for chemicals in the same class (neo nicotinoids) 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 confirmato ry 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 LC 50 = 0.069 mg/L 48

- hr NOAEC = 0.001 mg/L [MRID 42256304]

Chronic: Invalid study [MRID 42256304] Acute: 48

- hr EC 50 : 0.035 mg/L NOAEC: 0.013 mg/L [MRID 44714918] Acute: 48

- Hr EC 50 = 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 EC 50 = 0.055 mg/L 96

- hr LC 50 = 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]

Saltwa ter mysid ( Mysidopsis bahia ) 850.1035 (A) 850.1350 (C) Acute: LC 50 = 0.79 mg/L [MRID 45639713]

Chronic data not available Acute: LC 50 = 0.037 mg/L [MRID 42055319]

Chronic: NOAEL> 0.0006 mg/L LOAEC = 0.0013 mg/L [MRID 42055322] Acute: 96

- hr LC 50 : 6.9 mg/L NOAEC: <2.0 mg/L [MRID 44714922]

Chronic data not available Acute: 96

- Hr LC 50 = 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 LC 50 >968.3 mg/L [MRID 45639709]

Chronic: 21

- day NOAEC > 95.3 mg/L [MRID 45639718] Acute: 48

- hr EC 50 = 85 mg/L [MRID 42055317]

Chronic: 21

- day immobilization NOAEC = 1.3 mg/L LOAEC = 3.6 mg/L [MRID 42055321] Acute: 48

- hr EC 50 : >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 EC 50 > 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 qualita tive 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 sta ble to hydrolysis at 25 o 

### C and pH 4

- 9; and

, persistent in soil (t 1/2 

### range is approximately 16

- 10 0 days for aerobic soil metabolism [MRID 456401 11, 45640112, 46751101, 46711201 ] , which is greater than 2 weeks as prescribed in USEPA 2011 guidance , and the t 1 /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 Ba rcode: 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 l oam) 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 irri gation water leading to exposure to terrestrial plants apart from label prescribed rates

. E xposure through systemic transport in plants to pollen/nectar and other edible tissue as well as drinking water , to terrestrial invertebrates is poss ible. 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 e xposure to these organisms, however, is unclear, but toxicity is known to be high (acute oral 48

- hr LD 50 

### of 0.00076 **μ** g a.i./bee; acute contact 48

- hr LD 50 

### 0.024 **μ** g a.i./bee; MRID 45639727) ; in addition, the acute contact LD 50 

### translates to 0.19 ppm ( i.e. , 0 .024 **μ** g 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 provide s evidence of a pestic ide 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 tox icity 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 approach es to determin e the rate of volatilization (flux) for semi

volatile pesticides applications to bare soil and crop canopies and estimate the concentrations of applied pesticide in the atmosphere under varying environment al conditions.

### Page | 38 Consumption of aquatic food items by piscivorous mammals and birds KABAM ( K ow 

### (based) A quatic B io A ccumulation M odel) is used to estimate potential bioaccumul ation 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 i s a non

ionic, organic chemical; the log K ow 

### 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 ha bitats; however, the log K ow 

### 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, an d 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 con tributing to ecological risk.

Additional Terrestrial Exposure Pathways

The S creening T ool for I nhalation R isk (STIR v .1.0, November 19, 2010) was used to calculate an upper bou nd estimate of exposure using din otefuran’s vapor pressure ( <1.275x10 - 8 

### mm Hg; <1.7 x 10 - 6 

### Pa at 30 o 

### C ) 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 in halation 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 pestici de (rat acute oral: ♀ LD 50 

### = 2,000 mg/kg

- bw , MRID 45639823; rat inhalation (TGAI): LC 50 

### >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, LD 50 

### > 2000 mg a.i./kg

- bw, MRID 45639720 ). Based on the results of the STIR model, i nhalation exposure alone was not determined to be a potential pathway of concern for avian or mammalian species on an a cute basis. Inhalation Exposure

### Page | 40 I nhalation exposure via spray drift and/or vapor

- phase of the pesticide alone does not appear to be of concern . The ana lysis of the inhalation route in STIR do es not consider that aggregat ion with other exposure pathways such as d ietary, 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 area s 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 volat ile 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 or ganism 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 res idues 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 t he 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 wat er exposures.

The S creening I mbibition P rogram (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 2 0 o 

### C) . Using TGAI dinotefuran data for the most sensitive acute ( LD 50 

### >200 0 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 ( ♀LD 50 

### = 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 conclusion s 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 t he 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 ecologic al 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 f ate, 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 dinotefu ran

. 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 . Stresso rs 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 th e 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 Memo randum (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). Th e 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 submiss ions 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 d ue 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 mater ials (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 ca lculate 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 fiel d 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 pesticid e 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

m 3 

### 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 u sed 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. Monitor ing 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 95 th 

### 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. AGD ISP (version 8.13; December 2004) is used to simulate aerial applications. AgDrift (versi on 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 s tudies 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.

In formation on the potential effects of dinotefuran on non

- target animals is also collected from the Ecological Incident Information System (EIIS; USEPA, 2007 c ). The EIIS is a database containing adverse effect (typically mortality) reports on non

- target or ganisms 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 C onservancy (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 Agenc y’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 LD 50 

### , LC 50 

### and EC 50


### . LD stands for "Lethal D ose", and LD 50 

### 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 LC 50 

### is the concentration of a chemical that is estimated to kill 50% of the test or ganisms. EC stands for “Effective Concentration” and the EC 50 

### 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

- Effec t

- 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. , EC 25 

### for terrestrial plants and EC 50 

### for aquatic plants); for listed plants either the NOAEC or EC 05 

### is used.

7.4 . Integration of Exposure and Effects

Risk characterization is the integration of exposure and ecological effects characterization to determi ne 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 risk s 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 Agenc y 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 d eterministic 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 i n 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) us ed 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 thre shold. 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 measure s of ecological effect that define the action area for listed species include a ny 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 de termine 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

c ontrol a brown marmorated s tink b ug (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 Concen trations (EDWCs) simulated with the EFED FIRST model for the proposed new uses were approximately 20% higher than the EDWCs calculated previously by EFED. T hat 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 d rinking 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 p arent 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. P ercent Cropped Areas (PCA) t hat 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 S CI

- 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 Pros pective 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 Scre ening 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 carcinogenicit y, 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, s exual 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 taxonomi c 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 i s 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 o f 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

- i ns 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 call

ins, 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 li sts, 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 a nd 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 @ 50 o C 4 5640101 Supplemental

Hydrolysis @ 25 o C 4 5640102 Acceptable

Hydrolysis @ 40 o C 4 5640102 Supplemental No

MNG Hydrolysis in Water 4 5640103 Supplemental DN Phosphate Hydrolysis in Water 4 5640104 Supplemental

835.2240 P hotodegradation in Water 4 5640105 Supplemental Photodegradation in Water 4 5640106 Unacceptable No

MNG Photodegradation in Water 4 5640107 Supplemental DN Phosphate Photodegradation in Water 4 5640108 Supplemental

835.2410 Photodegradation in Soil 4 5640109 D316645 Supplemental No

835.2370 Photodegradation in Air 4 5640110 Supplemental No

835.4100

835.4200 Aerobic Soil Metabolism 4 5640111 Supplemental

Aerobic Soil Metabolism 46751101, 4 5640112 Acceptable No

MNG Aerobic Soil Metabolism 46711202 Supplemental

Anaerobic Soil Metabolism 45891616 Supplemental No

N/A MNG Rate of Mineralization 46751103 Supplemental No

835.43 00

835.4400 A erobic Aquatic Metabolism 45640117 Supplemental No

Anaerobic Aquatic Metabolism N/A

--- Yes

835.1230 835.1240 Leaching Adsorption/Desorption 4 5640114 4 5640115 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

835.63 00 Forestry Dissipation N/A

--- No 1

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 an d 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 meth od in ecological risk assessments, potential effects of dinotefura n 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 p artners, industry, and academia to determine appropriate assessment methodology. For compounds such as dinotefuran, which is (1) known
to be acute ly 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 feedi ng 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 alrea dy 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 Ag ency prior to ass uming 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 upgrade able , 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 Yes a 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 pollin ators study prevent use in risk assessment. Therefore, th is 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

4563972 2

(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

Non

guideline Honeybee acute oral toxicity 45639725 (TGAI) Supplemental 2 No

45639726

(TEP, 21.4% a.i.) Supplemental 2

45639727

(TEP, 21.4% a.i.) 1 Supplemental 2

850.3030 Honeybee toxicity of residues on foliage (alfalfa) 45639728 (TEP, %a.i. not reported) Acceptable No b

Non

guideline Parasitoid wasp survival and reproduction 45640121 (TEP, 21.09% a.i.) Supplemental 3 No

Non

guideline Predacious bug survival and reproduction 45640122 (TEP, 21.09% a.i.) Supplemental 3 No

Non

guideline Predaceous mite survival and reproduction 45640120 (TEP, 21.09% a.i.) Supplemental 3 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.) Supplemental 4 (qualitative use only; not upgradable) Yes c

Non

guideline Pollinator larval toxicity study Not submitted Not applicable Yes c

Non

guideline Pollinator chronic feeding study Not submitted Not applicable Yes c

Non

guideline Residues in pollen and
nectar / Field residue analysis Not submitted Not applicable Yes c

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 exis t 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 D inotefuran 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 non

definitive acute effect concentration for saltwater (as well as freshwater) fish and chronic effect c oncentration 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

re commended because dinotefuran may enter this environme nt due to its use and mobility patterns ( i.e. parent K oc 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) Supplemental 1

850.1075 Estuarine/marine fish

– Acute toxicity 45639717 (TGAI) Supplemental 3 No

850.1010 Freshwater invertebrates

– Acute toxicity 45639709 (TGAI) Acceptable

No 45639710 (metabolite DN

phosphate) 2, a Acceptable

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) Acceptable 4 No

850.1400 Estuarine/marine fish

– early life stage test N ot submitted Not applicable No b

850.1300 Freshwater invertebrate

– life cycle test 45639718 (TGAI) Acceptable No

850.1350 Estuarine/marine invertebrates

– life cycle test Not submitted Not applicable Yes c

850.1500 Fish Life Cycle Not submitted Not applicable No b

850.1710 850.1730 850.1850 Aquatic organisms bioavailability, biomagnifications, toxicity ( i.e. BCF and

food chain transfer studies) Not submitted Not applicable No d

850.1735 Freshwater invertebrate

– Acute

whole sediment Not submitted Not applicable No e

850.1740 Estuarine/marine invertebrate

– Acute

whole sediment Not submitted Not applicable No e

### 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

Other A Freshwater and estuarine/marine invertebrate

– Chronic whole sediment Not submitted Not applicable No e insufficient for ACR estimation of the estuarine/marine chronic endp oint.

d The study is not required under CFR Part 158 as the log K ow < 3 for parent dinotefuran ( i.e. , log K ow =
- 0.549).

e This data is not required under CFR Part 158 on the basis of the fate properties of the parent compound

. T he K d ≥ 50, the log K ow is ≥ 3, and a K oc 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).

A Three 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 Sediment

associated 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 Sedim ent

associated 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 te rmination, was less than the required initial weight

r ange 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 lowe st, 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 Ter restrial 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 <2 5%.

c No endpoints were affected in the Tier I vegetative vigor study; observed reductions relative to control across all species tested were 850.4225 Ter restrial Plant toxicity: Tier II seedling emergence N/A N/A No b

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 No c

850.5400 Aquatic Plant Growth:

non

- vascular plant 45639732 (TGAI) Acceptable (green algae)

Yes d (but not critical) 45639733 (metabolite

MNG) 1, a Supplemental 2 (green algae)

45639734 (metabolite DN

phosphate) 1, a Supplemental 2 (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) Supplemental 3 No <25%.

d Species of algae that were not tested and for which data were not submitted include freshwater diatom, Navicul a 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 co ver 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 al gae 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 suppl emen tal.
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 w ere 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 r e quired 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 (LD 50 

### /LC 50 

### ) for passerines (approximate body weight of 20g) would need to be on the

or der 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 w aterfowl 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 observ ed ( i.e. , at LD 50 

### of 1300 mg a.i./kg

- bw) , a request for a passerine study is warranted.

Furthermore , p asserines are the most common birds (in terms of numbers and number of species) in the United States. Many utilize agricultural fields, forests, residen tial 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 dinotef uran 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 f ield studies (semi

- field and/or full

- field) a s 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 foli ar 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). T est 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 exp ected 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 af

ter 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, s everal 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 inform ation needs for this study in Appendix C ] ; and, non

- gui deline 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 full

field) should be submitted f or 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, lar val 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 . T he registrant should consult with the Agency prior to assuming that the C DPR 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 a n endpoint for

com parison with acute oral data and a comparison of effects from acute to sustained exposure over longer periods of time. T he registrant should consult with the Agency prior to initiation of this study

.

Non

- Guideline: Residues in Pollen and Nectar / Field Re sidue Analysis of Edible Parts of Trees/Plants ( including, but not limited to residues in w hole flowers [ such as pollen and nectar {from flowers and, if present, extrafloral nectaries }]

, w hole plant tissue [ such as l eaves 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 , B onmatin 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, concent rations 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 und erstanding 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, full

field, 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, poll en

shedding, 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 initia tion of these studies. T he 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). I t is possible that the Agency ma y be able to make use of that data for the purposes of the national ecological risk assessment . T he registrant should consult with the Agency prior to assuming that the C DPR 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 d inotefuran technical is highly toxic ( i.e. , <1 mg a.i./L) to mysid shrimp (with a 96

- hr LC 50 

### 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 25 o 

### C)

, due to its mobility patterns ( i.e. parent K oc 

### range is 42

- 45 in US soils [ loam, sandy loam, and clay loam per soil mobility study MRID 45640114 ], which is cla ssified 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 en dpoint 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, Navicul a 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 guidel ine does not alone cover the spectrum of possible effects to non

- vascular plants

-- a lthough 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 EC 50 

### > 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 output 7 

### from USEPA 2004, DP Barcode D 285633)

-- 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 applic ation 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 ri sk assessment (USEPA 2002). The EFED generally uses multiple non

- vascular plant species to make a risk estimate; a dditional 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. Col in. 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, Southe rn 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 E ditorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil Contamination. A Reference Manual

. Rome: Food & Agriculture Organization of the United Nations (FAO). Available at http://ww w.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: correl ation 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 Res earch 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 Acetamipri d. 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 Subs tances, 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. Dinote furan. 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: D3049 57. 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. Washin gton, 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 Pur chase 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, a nd 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 C ode: 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 201 1. 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 Chem ical 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 C onducting 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 A 1. Nomenclature
Applicant's Code IUPAC Chemical CAS Name CAS No.

Dinotefuran/MTI

- 446 (RS)

- 1

- methyl

- 2

- nitro

- 3

- (tetrahydro

- 3

- furylmethy l) guanidine N

- methyl

- N’

- nitro

- N”

- [(tertra

hydro

- 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



### Ta ble A 2

. 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 H 2 N H C

N N H

N O 2 C H 3

### 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 N H 2

N C H 3

N O 2

N H 2 N H 2

N N O 2

O N H

O N H C H 3

### 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

N H N H C H 3

H 3 P O 4

N H N O

N H C H 3 C O O H

C O O H



### N H N H N H 2 

### C H 3



### Cl H

### 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 NH 2 NH 2

O H N NH 2

O H N NH

HN OH COOH

COOH 2

### Page | 67 Appendix B

. Environmental Toxicity Summary

The toxicity endpoints for ava ilable 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 LD 50 

### of 0.047 **μ** g a.i ./bee (MRID 45639725) as the most sensitive terrestrial invertebrate endpoint. Since then, an even more sensitive endpoint (48

- hour LD 50 

### of 0.0076 **μ** g a.i./bee) obtained from an acute oral honey bee study (MRID 45639727) was considered . The field study of f oraging 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 Inverteb rates Dinotefuran technical, MTI

- 446, (MRID 45639725) is hi ghly toxic to bees on an acute contact basis ( 48

- hr LD 50 

### = 0.047 **μ** g ai /bee) and on an acute oral basis ( 48

- hr LD 50 

### = 0.023 **μ** g ai/bee). Similarly, the dinotefuran formulation, MTI

- 446 20%WG (MRID 4 5639726, with control; MRID 45639727, without negative but with solvent control) is also highly toxic to bees on an
acute contact ( 48

- hr LD 50 

### = 0.061 **μ** g a.i./bee and 0.024 **μ** g a.i./bee, respectively) and on an acute oral basis (48

- hour LD 50 

### = 0.032 **μ** g a.i./bee and 0.0076 **μ** g a.i./bee, respectively) . The RT 25 

### (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 (RT 25 

### = 4.8 hours) and least sensitive to treatment when exposed to 48 hour aged residue (RT 25 

### = 90 hours)

. In addition, exposure to dinotefuran formulation MTI

- 446 20% SG applications (of varying exposure periods) led to survivorship an d reproductive effects on non

- Apis terrestrial invertebrates including p arasitoid wasp (MRID 45640121 ), predaceous bug (MRID 45640122 ), and predatory mite ( an arachnid, MRID 45640120) indicating LC 50 

### 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 app lication 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 4 7814402).

### Page | 68 Table B1

. Acute effect (mortality) concentrations (LD 50 

### / LC 50 

### ) for terrestrial invertebrates following exposure to Dinotefuran (Technical MTI

- 446, Formulation MTI

- 446 20% WG, Formulation MTI

446 20% SG) and Dinotefuran (F ormulation MTI

- 446 20% SG) residues on alfalfa.

Species %a.i. Study Parameters LD 50 /LC 50 ; 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 **μ** g a.i./bee 48

- hour LD 50 : 0.047 **μ** g a.i./bee (95% CI: 0.039

- 0.057 **μ** g a.i./bee)

48

- hour NOAEL: 0.0063 **μ** g a.i./bee Probit s lope: 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 **μ** g a.i./bee
grou p. 45639725 Acceptable / Highly toxic 1

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
**μ** g a.i./bee

Mean

- measured concentrations: 0, 0.003, 0.006, 0.012, 0.023, 0.046, 0.09 **μ** g a.i./bee 48

- hour LD 50 : 0.023 **μ** g a.i./bee (95% CI: 0.019

- 0.027 **μ** g a.i./bee)

48

- hour NOAEL: 0.003 **μ** g 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 1 3.3%; 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 Supplemental 2 / Highly toxic 1

Formulation MTI

- 446 20%WG Honey bee Apis mellifera 21.4 48

- hour, acute contact toxicity 48

- hour LD 50 : 0.061 **μ** g a.i./bee (95% CI: 0.05

– 0.073 **μ** g a.i./bee) 45639726 Acceptable / Highly toxic 1

### 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 **μ** g a.i./bee 48

- hour NOAEL: 0.0125 **μ** g a.i./bee Probit slope: 3.48

Endpoint(s) affected: Morta lity.

(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 t he 0.2 and 0.4 **μ** g 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 **μ** g a.i./bee

Mean

- measured concentrations: 0, 0.005, 0.011, 0.021, 0.046, 0.088, 0.173
**μ** g a.i./bee 48

- hour LD 50 : 0.032 **μ** g a.i./bee (95% CI: 0.025

– 0.041 **μ** g a.i./bee)

48

- hour NOAEL: 0.005 **μ** g 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 Supplemental 2 / Highly toxic 1

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 LD 50 : 0.024 **μ** g a.i./bee (95% CI: 0.018

– 0.031 **μ** g a.i ./bee)

48

- hour NOAEL: 0.0032 **μ** g 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 toxic 1

### Page | 70 0.0072, 0.016, 0.036, 0.08 **μ** g a.i./bee

*No negative (water) control was used test treatments, respectively. Solvent control mortality was 0%. At 4 ho urs, there were stumbling and knockdown bees in the 0.036 and 0.08 **μ** g 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 **μ** g a.i./bee

Mean

- measured concentrations: 0 (solvent control), 0.00056, 0.0013, 0.0028, 0.0061, 0.013, and 0.029 **μ** g a.i./bee

*No negative (water) control was used 48

- hour LD 50 : 0.0076 **μ** g a.i./bee (95% CI: 0.004

– 0.012
**μ** g a.i./bee)

48

- hour NOAEL: 0.0013 **μ** g 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/o r knockdown bees observed in every treatment and control group, except for the 0.00056 **μ** g 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 8 50.3020). 45639727 Supplemental 2 / Highly toxic 1

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

♠ RT 25 = 6.7 (3.3

- 14) hour Probit slope = 2.37 ± 0.431

8

- hour aged residue RT 25 = 4.8 (2.4

- 9.6) hour Probit slope = 2.66 ± 0.436

24

- hour aged residue RT 25 = 24 (14

- 44) hour Pr obit slope = 4.63 ± 1.54

48

- hour aged residue RT 25 = 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 pos t

treatment

*Foliar residues of MTI

446 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 b ees 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

- , an d 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

ex posure.

Hyperactivity observed in bees exposed to 3 and 8 hour post

treatment 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 LC 50 : 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 Supplemental 3

### 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 Schneider

Orelli’s fomula 4 ) was

- 7,

- 2, 9, 50, and 74% in the test treatments, resp ectively. 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). Significan t 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)

*On ly 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 LC 50 : 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 Schneider

Orelli’s fomula 4 ) 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 Supplemental 3

### 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: Th e test substance was sprayed on inner parts of glass cage and petri dishes with a calibrated lab track sprayer. 14

- d LC 50 : 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 Schneider

Orelli’s fomula 5 ) 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 Supplemental 3

1 Based on acute contact LD 50 ( **μ** g 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

- Or elli’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. 862 03

- 11) applications (foliar, airblast, broadcast spray; soil applications; chemigation; basal trunk spray).

♠ RT 25 = 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 r aw data reporting 8 

### , and mul tiple 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 conducte d 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 c ontamination 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 flower s 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 d etected in the two treatments as 0.013 ppm and <LOQ (0.004 ppm). As a result of the cross

contamination, this study is inconclusive in terms of the toxicity of dinotefuran applications on cotton to honey bee hives. In addition, the lack of quantitative da ta 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 treatmen t) 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 dur ing 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 ri sk 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 provi ded in this study. The presence/absence data for residues, particularly in nectar, are important, however,

8 S tatistical 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) re sidues 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 t oxicity 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 nec tar 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 e xposure 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 implicati ons 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 (LD 50 

### > 2,000 mg a.i. /kg

- bw ; MRID 45639720 ) and bobwhite quail (LD 5 0 

### > 2,25 0 mg a.i. /kg

- bw ; MRID 47353601 ) on an acute oral basis and to mallard duck (LC 50 

### > 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 t he 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 (N OAEC = 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 mamma l species (laboratory rat) (female LD 50 

### = 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 F o 

### and F 1 

### females, slight increases in abnormal sperm morphology in F o 

### and F 1 

### males, and slight decreases in testicular sperm count in F o 

### males a nd sperm mortality in F 1 

### 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 necrops y findin gs (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 u tilized in additional calculations at a later section in the risk assessment. T he degradates MNG and DN were not tested on birds or surrogate mammals.

Table B2

. Acute effect (mortality) concentrations (LD 50 

### / LC 50 

### ) for terrestrial animals (birds/mammals) following exposure to Dinotefuran (Technical MTI

- 446). Species %a.i. Study Parameters LD 50 /LC 50 ; 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 (H 2 O), 200, 1000, 2000 mg a.i./kg

- bw 14

- day LD 50 >2000 mg a.i./kg

- bw

14

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

bw

Endpoint(s) affected: None.

(Sub)lethal effects : No mortality ob served. 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 non

toxic 1

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 LD 50 >2250 mg a.i./kg

- bw

14

- day NOAEL ≥ 2250mg a.i./kg

bw

Endpoint(s) affected: None.

(Sub)lethal effects : None. 47353601 Acceptable /Practically non

toxic 1

Japanese quail 97.26 8

- day (5

- day exposure; 3

- 8

- day LC 50 >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

Mean

measured 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./kg

diet

Endpoint(s) affected: None.

Sublethal effects : None. toxi c 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

Mean

measured concentrations: 0 and 4732 mg a.i./kg

- diet; mean test item intake = 997.9 mg a.i./kg

- diet 8

- day LC 50 >5000 mg a.i./kg

- diet

8

- day NOAEC ≥ 5000 mg a.i./kg

diet

Endpoint(s) affected: None.

Sublethal effects : None. 45639722 Acceptable /Practically non

toxic 2

Mammals Laboratory rat Rattus norvegicus 99.1 14

- day acute oral toxicity ♂ LD 50 = 2,804 mg/kg

- bw ♀ LD 50 = 2,000 mg/kg

- bw

Endpoint(s) affected: Morbidity. 45639823 Acceptable (Tox. Category III)

1 Acute Oral (avian/mammal): Based on LD 50 (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 LC 50 (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
percen tage 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 (range

finding test) Acceptable

### Page | 79 10000 mg/kg

Pre

- mating doses: F o males 0, 24.1, 79.9, 241, 822.1 mg/kg

- bw/day

F o females 0, 26.8, 90.1, 267.9, 907 mg/kg

- bw/day

F 1 males 0, 27.2, 90.5, 269, 934.7 mg/kg

- bw/day

F 1 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 ut erine weights, microscopic alteration in uterus and vagina of F o ♀; decreased numbers of primordial follicles in F 1 ♀, altered estrous cyclicity in F o ♀; slight increases in abnormal sperm morphology in F o and F 1 ♂, and slight decreases in testicular spe rm count in F o ♂ and sperm mortality in F 1 ♂.

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 Pre natal development (gavage)

Dose levels: 0, 52, 125, 300 mg/kg

bw/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 LC 50 

### > 99 mg a.i./L),

as w ell as freshwater invertebrate ( D. magna 48

- hour LC 50 

### > 968.3 mg a.i./L; MRID 45639709) and saltwater invertebrate (eastern oyster 96

- hr EC 50 

### > 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 LC 50 

### > 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 LC 50 

### = 0.79 mg a.i./L; MRID 45639713 ). Chronic toxicity testing on fr eshwater 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 submitt ed 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, LC 50 

### = 0.79 mg a.i./L) are significantly more sensitive to dinotefuran than freshwater invertebrates (daphnia, LC 50 

### >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 f or 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 concentra tions (LC 50 

### /EC 50 

### ) for aquatic animals and plants following exposure to Dinotefuran (Technical MTI

- 446; unless otherwise stated). Species %a.i. Study Parameters LD 50 /LC 50 /EC 50 ; 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 LC 50 > 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 non

toxic 1

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 LC 50 > 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 non

toxic 1

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 LC 50 > 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 non

toxic 1

Freshwater invertebrate Waterflea Daphnia magna 97.26 48

- hour acute toxicity (limit test)

Static 48

- hr LC 50 > 968.3 mg a.i./L

48

- hr NOAEC ≥ 968.3 mg a.i./L 45639709 Acceptable /Practically non

toxic 1

### 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 LC 50 > 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 non

toxic 1

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 LC 50 > 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 non

toxic 1

Saltwater invertebrate Eastern oyster Crassostrea virginica 99.6 96

- hour acute toxicity

Flow

- through

Nominal concentrations: 0, 16, 96

- hr EC 50 > 141 mg a.i./L

96

- hr NOAEC ≥ 141 mg a.i./L 45639711 Acceptable /Practically non

toxic 1

### 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

c oncentrations, 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 LC 50 : 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 ob served 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 toxic 1

1 Based on EC 50 (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 tha n 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, post

hatch survival, terminal length, wet or dry weights

Endpoint(s) affected: None.

(Sub)lethal effects : None. 45639719 Acceptable 1

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 LC 50 /EC 50 > 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 l imit 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 EC 25 

### 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 EC 50 

### 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 EC 50 

### 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 EC 50 

### for cell density, biomass, and growth rat e endpoints, however, is >97.6 mg a.i./L (the highest concentration tested).

Table B6

. Effect concentrations (EC 25 

### /NOAEC) for terrestrial plants following exposure to Dinotefuran (TEP: MTI

– 446 20%SG). Species %a.i. Study Paramet ers EC 25 / 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 EC 25 > 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 EC 25 > 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)leth al effects : None. By 2 weeks, no treatment related signs of toxicity were observed.



### Table B7

. Effect concentrations (EC 50 

### /NOAEC) for aquatic plants following exposure to Dinotefuran (Technical MTI

- 446, unless otherwise stated). Species %a.i. Study Parameters EC 50 ; 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 EC 50 >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 Supplemental 1

Non

- vascular Green Algae Pseudokirchneriella 97.26 96

- hour acute toxicity Cell density 96

- hr EC 50 > 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 EC 05 : 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 EC 50 >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 concentrati ons, 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 EC 50 > 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 con trol, 96

- hr %inhibition for cell density was 34,

- 8, and 23%, for growth rate was 20,

- 1.7, and 8.3%, for 45639733 Supplemental 2

### Page | 88 biomass was 30,

- 9.8, and 14% Green Algae Pseudokirchneriella subcapitata (a.k.a . Selenastrum capricornutum ) Not reported

Metabolite DN (DN

Phosphate) 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 EC 50 > 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 Supplemental 2

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 aquati c vascular plants because the test concentrations that plants were exposed to w ere 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 supplemen tal. *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
upg radable with submittal of an independent laboratory validation. 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 a Laboratory Validation of Methods For The Analysis of Dinot efuran 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 wit h 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, Hone y, 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 Invertebra te 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 particul ar 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 fro m 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 stu dies: 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, n either study reported the purity of the test compound, which is needed to better characterize exposure to these me tabolites.

### 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 comp ound 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 terrestria l invertebrate species. This study would allow the Agency to refine the screening level risk assessment for beneficial terrestrial invertebrates

. The effects data w ill 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 th e 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 ne cessary 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 registrant s 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 compo und 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 w ill be used to determine the potential for risk to beneficial terrestrial invertebrates through direct e ffects 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 e xistence 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 in form 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 an d 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
sy stemic 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 pl ants 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, a nd 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, t he Agency will consider a semi

- field, full

- field, or greenhouse

- based protocol lasting at least two years with multiple sampling time

- steps. The p rotocol 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 beneficia l 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 t akes “...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. Th e 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 route s 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

s hould 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 a vailable” 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 a nd 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 Pro ject 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. {O PPTS 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 Determinati on 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 Februa ry 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)

- MTI

446 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 Aerob ic 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 prepar ed 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 M ethod 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 p repared 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 F orest 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 Invertebrat es

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 Internat ional, 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/Seedl ine 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 Inter national, 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 Wildli fe 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, Growt h 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 Toxici ty 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 B ees (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 Lan dis 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

- Respo nse 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 B ug 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) An alytical 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 b y 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, LL C. 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.