UN I T E D S T

A TES E N V I R ONM E NTAL PROTECTION AG EN C Y
WASHINGTON D

. C.

, 20460
OFF I CE OF CHEMICAL SAFETY AND PO LLUT ION PREVENT I ON

PC Cod e: 006329
DP B a r c od e: D423845
D a te : May 18

, 2015

MEMORANDUM

Subject :

T o:

From: Registration Review: P r ob l em Fo r mulation fo r the Env ir onmental Fate, Ecological Risk,
E ndangered Spec i es , a n d Drink i ng W ate r Assessmen t s for A cequinocy l

Meg Hathaway, Chemical Review Manager
Dana Friedman, Acting Team Leader/Cathryn Britton, Team Leader
Kevin Costello

, Branch Chief
Risk Management and Implementation Branch II

Pesticide Re

- Evaluation Division (7508P/ ,,4.. 

# /a_ S/J .1

/,SFreeborn Jewett, M.S., Biolog i st

# ~**~~ ft**  Michael L owit, Ph.D., Eco l ogist

## ~ 

# M

. s· I; ' I. Sujatha Sankula, Ph.D., Branc h Chief (

, · 

## <J-"--

## '/**_!./ '/~** **{** 

# c

Environmental Risk Branch I / \ : 

### = 5 l 

### \€ l "')
Environmental Fate and Effects Division (7507P)

12

1. Executive Summary:

The Environmental Fate and Effects Division (EFED) has completed the problem formulation for the environmental fate, ecological risk, endangered species, and drinking water exposure assessments to be
conducted as part of the Registration Review of the miticide acequinocyl . Functioning as the first stage of the risk assessment process for Registration Review, this problem formulation provides an overview of what is currently known about the environmental fate an d ecological effects associated with acequinocyl and its degradates. It also describes the preliminary ecological risk hypothesis and analysis plan for evaluating and characterizing drinking water exposure and risk to non

- target species and the
environment in support of the Registration Review of acequinocyl . This document also recommends
studies that should be included in a data call

- in (DCI) to address uncertainties surrounding the environmental fate and potential ecological effects of acequinocyl

.

Reco mmended Studies :
Ecological Effects

 Guideline 850.1025

- E stuarine/marine invertebrate acute toxicity using mollusk (TGAI)

 Guideline 850.2100: Avian acute oral toxicity

- with a passerine species (TGAI)

 Guideline 850.1400

- Freshwater fish early

- life stage ( TGAI)

 Guideline 850.1400

- Estuarine/marine fish early

- life stage (TGAI)

 Guideline 850.4400

- Aquatic vascular plant toxicity test ( TEP )

 Guideline 850.4500

- Estuarine/ m arine diatom toxicity test using Skeletonomea costatum ( TEP )

 Guideline 850.4500

- Freshwate r diatom toxicity test using Navicula pelliculosa ( TEP )

 Guideline 850.4550

- Blue g reen a lgae toxicity test using Anabaena flos

- aquae ( TEP )

 Non Guideline

- Whole sediment chronic invertebrates

- freshwater midge Chironomus dilut u s , freshwater amphipod Hyalell a azteca , and estuarine/marine amphipod Leptocheirus plumulosus 1 (TGAI) 2

 Non Guideline Tier I: Honeybee adult chronic oral exposure (TGAI)

 Non Guideline Tier I: Honeybee larval acute and chronic oral exposure (TGAI)

 Non

- Guideline Tier II: Re sidue in pollen and nectar (recommendation pending risks identified in Tier I studies) (TEP)

 Guideline 850.3040: Tier II semi

- field testing for pollinators (tunnel and feeding studies) ( recommendation pending risks identified in Tier I studies) (TEP)

 Guideline 850.3040: Tier III full

- field testing for pollinators ( recommendation pending risk identified in Tier II studies) (TEP)

1 EFED acknowledges that acequinocyl stability issues have been reported in estuarine/marine
invertebrate tests that resulted in a waiver for the chronic estuarine/marine invertebrate study (USEPA, 2010) . If chemical stability is an issue during the chronic testing with a marine/estuarine amphipod species

, consulting with EFED scientists about other testing options may be possible.

2 A s indicated i n 40 CFR Part 158, the registrant is required to submit a protocol for approval prior to initiating studies with each of the three invertebrate species.3

Fate

Although fate data are available, there are data gaps for all guideline requirements trigg ered for acequinocyl uses (except terrestrial field dissipation) because of the numerous issues with the available studies ( described in Section 11 ). In general, there is uncertainty for most of the studies about whether or not degradation rates were over estimated because there are unresolved questions about the potential contribution of non

- experimental related sources of degradation that may have occurred during the course of the studies . It would be ideal to collectively address the data gaps ( outlined in Table 7) for all of the fate studies; however, the ecological risk assessment and drinking water assessment (DWA) may proceed based on the available data by making conservative assumptions as in past risk assessments. Two approaches may be used to bou nd aquatic estimated environmental concentrations (EECs):

 In Approach 1 , acequinocyl will conservatively be assumed to be stable to all routes of degradation because of the uncertainties associated with the environmental fate data, mainly the lack of valid ation of the analytical methods and the lack of storage stability
data.

 In Approach 2 , it will be assumed that the half

- lives of acequinocyl and the degradation product 2

- dodecyl

- 3

- hydroxy

- 1, 4

- naphthale ne dione aka 2

- dodecyl

- 3

- hydroxy

- 1,4

- naphthoquinone or R1 (hereinafter R1 ) are accurate and total toxic residues (acequinocyl + R1) will be modeled to address toxicity concerns with R1. Uncertainties about degradation rates would need to be addressed for all studies in order to move away from conservative ass umptions such as those outlined above ( i.e., approach 1)

. A ddressing other issues such as testing on additional soils (e.g. aerobic soil metabolism) is expected to have little impact on the risk assessment unless issues with the existing
studies surroundi ng potential overestimation of degradation rates are addressed first; thereby, potentially allowing the risk assessment to move away from the assumption of stability ( upper bound EEC )

. Despite uncertainties in the fate data

, EECs based on both approaches led to the same conclusions in past risk assessments ; that is, the greatest risk to the aquatic environment from use of acequinocyl is direct effects on invertebrate species. On the other hand, r eliance on potentially conservative assumptions may lead

to overly conservative mitigation measures to protect endangered aquatic species.

2. Introduction

The purpose of this problem formulation is to provide an under standing of what is known about the environmental fate and ecological effects of acequinocyl

, consi dering its currently registered uses. This document will provide a plan for analyzing data relevant to acequinocyl and for conducting ecological risk, endangered species, and drinking water exposure assessments for its registered uses. T his problem
formula tion 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 acequinocyl

. Acequinocyl (CAS: 57960

- 19

- 7 ; PC Code: 006329 ; (2

- (acetyloxy)

- 3

- dodecyl

- 1,4

- nap h thalenedione) ) is a miticide belonging to the q uinoline class of chemicals

. Acequinocyl is registered for commercial use
under the name of Kanemite 15 SC (15.8% a.i.) (EPA reg. #66330

- 38) for the control of various mite species (USEPA, 2014 a )

. In the U.S.

, acequinocyl is labeled for use on tree nuts, pistachios, citrus, climbing vine fruits, pome fruits, fruiting vegetables, low growing berries, caneberries, cherries,4

succulent shelled beans, melons, cucumbers, okra , edible podded beans, succulent soybean, hops, and landscape ornamentals

. A cequin oc yl is applied by foliar spray application using ground equipment at a
maximum single application rate of 0. 3 lbs a.i./A with a maximum of two applications annually

.

3. Use Characterization

a. Mode of Action

Acequinocyl belongs to the quinoline class of chemicals. Upon application, acequinocyl hydrolyzes to hydroxy

- acequinocyl (R1) in the mite body and binds to the Qo center at complex III in mitochondria.
The net result is the blockage of cellular respiration and other adverse metabolic effects in mites

, although it is not clear at this point what proportion of the miticidal action is through the parent and which is through the metabolite R1

. Acequinocyl has no systemic activity but provides contact control of all life stages of mites.

b. Overview of Pesticide Use and Usage

The Biological and Economic Analysis Division (BEAD) provided a Screening Level Usage Analysis (SLUA) (USEPA, 2014 a ) to provide estimates of the actual usage o f acequinocyl on a gricultural crops

. The screening level usage profile (SLUA) produced by BEAD and located in the docket (USEPA, 2014 a )
and summarized in Table 1 , lists the use patterns for the current uses of acequinocyl . Primary uses in terms of average weight of applied product of acequinocyl are almonds, apples, oranges, and
strawberries

. These data represent annual data from 2004

- 2012.

Appendix 2 summarizes the application rates of acequinocyl for all labeled uses.

Table 1 : Estimates of the Actual U sage of Acequinocyl on Agricultural Crops.

Crop Average

Annual Lbs.
A.I. Percent Crop Treated

Average Maximum

Almonds 1,000 * <1 <2.5 Apples 1,000 <2.5 <2.5 Grapefruit <500 <2.5 <2.5
Grapes <500 <1 <2.5

Lemons <500 <2.5 <2.5
Oranges 1,000 <1 <2.5

Pears <500 <1 <2.5

Strawberries 10,000 5 10
Tangerines <500 <2.5 5

Walnuts <500 <1 <2.5 *All numbers rounded.5

4. Conclusions from Previous Risk Assessments

a. Ecological Risk Assessment

Acequinocyl was first assessed in 2003. Since then, the Agency has conducted multiple ecological risk assessments on acequin o cyl

. The most recent risk assessment was carried out in 2011 in Succulent Soybean, Low Growing Berry, Small Fruit Vine Climbing (except kiwifruit), S ucculent S helled B eans, C owpea F orage, Caneberry, Melon, Cucumber, and Cherry (D448205). A full list of previous acequinocyl
risk assessments is available in Appendix 1

. The direct risk concerns identified in past assessments are:

 Freshwater Invertebrates (Acute listed and non

- listed and Chronic listed and non

- listed )

 Estuarine/Marine I nvertebrates ( Acute listed and non

- listed and Chronic listed and non

- listed )

 Mammals (Chronic listed and non

- listed )

 Terrestrial Invertebrates (Assumed based on lack of acceptable endpoints)

 Birds (Chronic listed and n on

- listed )

b. Drinking Water Exposure Assessments

The most recent DWA was conducted in 2011 (DP389520). Two approaches were used to estimate drinking water concentrations (EDWCs) due to uncertainties associated with the available
environmental fate data. In Approach 1 , acequinocyl was assumed to be stable to all routes of degradation. In Approach 2

, it was assumed that the half

- lives of acequinocyl and the degradation product R1 were accurate and total toxic residues (acequinocyl + R1) were modeled to add ress toxicity concerns with both acequinocyl and R1.

Some EDWCs exceed the solubility limit of acequinocyl (6.69 μg/L at 20°C); therefore, in those cases the
recommended EDWCs are equal to the solubility limit. The acute EDWC = 6.69 μg/L ( Approach 1 ) an d
5.5 9 μg/L ( Approach 2 )

. The a nnual mean (chronic) EDWC = 6.69 μg/L ( Approach 1 ) and 1.36 μg/L ( Approach 2 )

. The 30

- year annual mean EDWC = 6.69 μg/L ( Approach 1 ) and 0.27 μg/L ( Approach 2 ). The ground water concentration = 3.6 x 10

- 3 μg/L (acute and c hronic)

.

c. Clean Water Act Programs

Acequinocyl is not identified as a cause of impairment for any bodies listed as impaired under section 303(d) of the Clean Water Act (as of 11/2014). 1 A Total Maximum Daily Load (TMDL) has not been developed. 2 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’ s Registration Review Risk Assessment and Management Process 3 , in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

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

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollut

a nt_group_name=PESTICIDES

3 http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1

- sop.pdf6

5. Environmental Fate and Transport

Acequinocyl appears to undergo fairly rapid transformation in most aquatic and terrestrial environments. Acequinocyl undergoes rapid hydrolysis under neutral and alkaline pH conditions with a
half

- life of 1.26 hours to less than 2 days. However, it is more stable under acidic pH conditions (e.g., 75 days at pH 4). Photodegradation in water appears to occur even more quickly with half

- lives of less than 15 minutes in sterile lab and river water. In contrast, available data provides no evidence of photodegradation in soil. Aerobic biotransformation in soil was also rapid with half

- lives less than 2 days under laboratory conditions. Acequinocyl also dissipated quickly in aquatic metabolism studies (half

- lives < 1 day); however, hydrolysis may have contributed to the observed degradation. Under field conditions, acequinocyl applied to bare plots dissipated with half

- lives ranging from 2 h ou rs in California to 14 hours in New York. In contrast, magnitude of residue studies showed longer half

- lives (mean half

life of 20 days based on apples, pears, oranges, grapef ruit, lemon, and almonds; USEPA, 2004a).

Vapor pressure (1.69 x 10

- 6 Pa at 25 ° C) and Henry's Law Constant (9.59 x10

- 7 atm x m3/mol) indicate a low possibility of volatilization of acequinocyl from soil and water.

Acequinocyl is expected to exhibit l ow mobility in soil. The soil adsorption Kd for acequinocyl ranged from 678 ml/g in sandy loam soil to 1,620 ml/g in silty clay loam soil. One of the major degradation products, R1 , is slightly more mobile than acequinocyl under some conditions (Kd ranged from 27 ml/g in silt loam to 3,400 ml/g in sandy loam soil). In the field studies, acequinocyl and the observed degradates (R1 and AKM

- 18) were not detected below 0

- 15 cm soil depth.

Acequinocyl has a tendency to bioconcentrate based on the bioconcentrat ion factor (BCF) in fish (307 to 387) and high octanol/water partition coefficient (Log Pow ≥ 6.2). However, the depuration half

- life is less than 1 day. The p hysical, chemical, and environmental fate properties of acequinocyl are
summarized in Table 2

.

a. T ransformation Products

The major degradation products (formation > 10% of applied acequinocyl) most often detected in the laboratory and field studies were R1 (2

- dodecyl

- 3

- hydroxy

- 1, 4

- napthoquinone) and AKM

- 18 (2

- (1,2

- dioxotetradecyl) benzoic acid). AKM

- 08 (2

- (2

- oxo

- dodecyl)

- 3

- hydroxy

- 1,4

- naphthoquinone), o

- phthalic acid, and phenol were major degradates only in the aqueous photolysis study. CBAA (2

- carboxy

- α

- oxo

benzene acetic acid) was a major degradate only in the aerobic aquatic metabolism study. Fate data are
not avail able for the major degradation products with the exception of the batch equilibrium study for
R1. Appendix 3 summarizes the maximum formation of major acequinocyl degradation products

.

Table 2

. Physical, Chemical, and Environmental Fate Properties of Ace quinocyl

Parameter Value Reference Comments

Chemical Acequinocyl

Chemical Name 2

- (acetyloxy)

- 3

- dodecyl

- 1,4

- naphthalenedione
Empirical Formula C 24 H 32 O 4 MRID 45434901

CAS Number 57960

- 19

- 77

Parameter Value Reference Comments

Structure MRID 45434909

SMILES C(CCCCCCCCCCC)C1 =C(C(=O)(c2 c(cccc2)C1(=O)))OC(=O)C EPI Suite v 4.1 1

Selected Physical/Chemical Parameters

Molecular mass 384.5 MRID 45434901
Water Solubility ( 20°C) 6.69 μg/L MRID 45434906

Log Pow ≥6.2
Vapor pressure (25°C) 1.69 x 10

- 6 Pa MRID 45434905
Henry’s law constant 9.59 x10

- 7 atm·m 3 /mol Calculated

Persistence 2

Hydrolysis (t 1⁄2 ) 19 days (pH 1.2) 75 days (pH 4) 1.6 days (pH 7) 1.26 hours (pH 9) MRID 45434908 Supplemental

Aqueous Photolysis (t 1⁄2 ) 14 minutes (buffer solution, pH 5)
12 minutes (st erile river water, pH 7.8) MRID 45434909 Supplemental

Soil Photolysis (t 1⁄2 ) Stable* MRID 45434910 Supplemental *Rate of degradation was

the same in irradiated samples (t 1⁄2 = 2.0 days) and dark controls (t 1⁄2 = 1.9 days)
Aerobic Soil Metabolism (t 1⁄2 ) < 2 days (visual) MRID 45434911 Supplemental
Aerobic Aquatic Metabolism (t 1⁄2 ) 8.5 and 9.8 hours (total system) MRID 45434914 Supplemental Degradation likely driven

by hydrolysis given that the system pH ~ 8.
Anaerobic Aquatic Metabolism (t 1⁄2 ) < 1 day (visual, total system) MRID 45434913 Supplemental

Mobility

Kd 678

- 1620 mL/g (acequinocyl)

27

- 3400 mL/g (R1) MRID 45531902 Supplemental
MRID 45434907 Supplemental
Field Dissipation
Terrestrial Field Dissipation (t 1⁄2 ) 2

- 14 hours MRID 45651601
Accepta ble8

Parameter Value Reference Comments

Bioaccumulation
Bioaccumulation in Common Carp (Depuration t 1⁄2) (BCF) < 1 day* (whole fish)
307

- 387 (whole fish) * 80% depuration after 1 day

1 http://www.epa.gov/opptintr/expo sure/pubs/episuite.htm

2 Half

- lives based on acequinocyl + R1 residues may be recalculated at the time of risk assessment using the most

up

- to

- date guidance (acequinocyl + R1 residue half

- lives are present ed in DP285811+, USEPA, 2004a).

6. Receptors

Consist ent with the process described in the Overview Document (USEPA, 2004 a ), the risk assessment for acequinocyl relies on a surrogate species approach. Toxicological data generated from surrogate test species, which are intended to be representative of broad taxonomic groups, will be used to extrapolate the potential effects on a variety of species (receptors) included under these taxonomic groupings. Table 3 and Table 4 provide a summary of the aquatic and terrestrial taxonomic groups, respectively, and the m ost sensitive surrogate species tested to characterize the potential acute and chronic effects of acequinocyl. Appendix 4 provides a full listing of the aquatic animal and plant toxicity endpoints for acequinocyl, as well as expanded explanations about the validity of the endpoints for risk

assessments. Table 5 provides information for the degradate R1. Empirically

- measured toxicity data were not provided for major degradates AKM 18, AKM

- 08, o

- Phthalic acid, Phenol, and CBAA. Estimates
of the toxicities of these degradates are available in Table 6 . Based on available ecotoxicity information, acequinocyl is very highly toxic to freshwater aquatic invertebrates. Acequinocyl is highly toxic to estuarine/marine fish and invertebrates, moderately toxic to freshwa ter fish, and slightly toxic to rats via inhalation. Acequinocyl is practically nontoxic to rats (acute oral exposure), birds, and honeybees (adult contact).

a. Effects to Aquatic Organisms

Aquatic invertebrates are the most sensitive taxa to acequinocyl e xposure. Chronic t oxicity data are available for freshwater invertebrates , but are not available for estuarine/marine invertebrates. A waiver request was granted for assessing chronic exposure to estuarine/marine invertebrates under chronic, flow

- through c onditions due to the fact that under experimental conditions, acequinocyl was not sufficiently stable to ensure desired exposure concentrations (USEPA 2010). This wa i ver applies to chronic studies, as stability was not as prevalent of an issue in acute stu dies. As a result, f or the purposes of risk assessment, an estimated chronic toxicity value for estuarine/marine invertebrates will be estimated by taking an acute to chronic ratio (ACR) for water flea endpoints ( MRIDs 46372101;
454349 22) (2.4μg/L/0.98μg/L =2.45) and applying it to the most sensitive acute endpoint for an
estuari ne/marine invertebrate species, which is mysid shrimp (MRID 45434917 ) (0.94 μg/L/2.45=0.38 μg/L).

Several studies presented in Table 3 were classified as supplemental because of low % recovery of the
chemical. Unless specified otherwise in the “MRID & status” column of Table 3, these studies may be used quantitatively in risk assessments , as the low % recovery was consistent across all aquatic studies and degradation is presumed to r esult in conversion to major degradate R1 . The R1 degradate is assumed to be of equal toxicity to acequinocyl to aquatic taxa , based on available aquatic toxicity data and results of ECOSAR toxicity modeling shown in Table 5 and Table 6

.9

Part of the regis tration rev iew process involves reviewing previously submitted studies to ensure that the study classifications reflect current guideline requirements. T hree studies were submitted that tested the acute toxicity of acequinocyl TEP to bluegill sunfish ( Lep omis macrochirus ) (MRID 45428605)

, rainbow trout ( Oncorhynchus mykiss ) (MRID 45530601) and sheepshead minnows ( Cyprinodon variegatus ) (MRID 45428606)

. These studies were initially classified as acceptable , but will be downgraded based on the presence of a precipitate that was not centrifuged or filtered prior to analysis

. The study measuring acute toxicity to rainbow trout ( Oncorhynchus mykiss ) (MRID 45530601) will be downgraded to invalid because a dose response was observed

, but endpoints could not be det ermined
because of uncertainty related to the bioavailability of the exposure concentrations . The studies measuring acute toxicity to sheepshead minnows ( Cyprinodon variegatus ) (MRID 45428606) and bluegill sunfish ( Lepomis macrochirus ) (MRID 45428605) will be downgraded to supplemental because no effects were observed at any concentrations, and exposure concentrations are assumed to be the limit of solubility (6.69 ppb). DER s for these studies will be modified to reflect these classification change s

.

Table 3 : Most Sensitive Aquatic Toxicity Endpoints for Acequinocyl

Taxa Study Type % ai Species Toxicity Value & Category MRID &
Status Endpoints

Affected

Freshwater
Fish Acute

850.1075 97.1 Bluegill Sunfish Lepomis macrochirus LC50>1.1 mg ai/L

NOAEC= 1.1 mg ai/L

Moderately toxic 45434918 Supplemental

Endpoints are
valid for risk

assessment. None

Freshwater
Invertebrates Acute

850.1010 98.3 Water Flea Daphnia magna LC50= 2.7 μ g ai/L

NOAEC= 0.66 μ g ai/L

Very highly t oxic 46372101 Acceptable Mortality and

sublethal
effects (lethargy)
Chronic
850.1300 98.3 Water Flea Daphnia magna NOAEC= 0.98 μg ai/L

LOAEC= 1.8 μg ai/L 45434922 Supplemental

Endpoints
valid for risk

assessment Number of

young, length and dry weight

Estuarine/
Marine Fish Acute

850.1075 9 7.1 Sheepshead
minnow Cyprinodon variegatus LC50> 0.19 mg ai/L

NOAEC= 0.19 mg ai/L

Highly Toxic 45434921 Supplemental

Endpoints
valid to quantitatively
assess risk. None

Estuarine/
Marine Invertebrates Acute

850.1035 97.1 Mysid shrimp Americamysis b ahia LC50=0.94 μg ai/L

NOAEC= 0.27 μg ai/L

Highly Toxic 45434917 Supplemental

Endpoints
valid to quantitatively
assess risk. Lethargic

swimming, loss of equilibrium10 Taxa Study Type % ai Species Toxicity Value & Category MRID &
Status Endpoints

Affected
Chronic
850.1350 NA Mysid Shrimp Americamysis bahia NOAEC: 0.38 μ g ai /L

(Estimated us ing Acute to Chronic Ratio (ACR) ) NA NA

Aquatic Plants Non Vascular

850.4400 97.1 Green Algae
Pseudokirchneriella subcapitata 72

- hour EC50 =0.96 mg

a.i./L

NOAEC = 0.0017 mg ai/L 45435008 Supplemental

Endpoints can
be used to quantitatively
assess risk t o

non

- vascular aquatic plants

. Study was
conducted for
72 hour s, shorter than
the
recommended
96

- 120 hour

, yet the toxicity endpoint is
several orders of magnitude
above the
limit of solubility for this chemical,

so a new study would be unlikely to change risk
conclusions. N one

a. Effects to Terrestrial Organisms

Table 4 : Most Sensitive Terrestrial Toxi city Endpoints for Acequinocyl

Taxa Study Type % ai Species Toxicity Value & Category MRID &
Status Endpoints

Affected

Mammals Acute oral

870.1100 96.8 Rat Rattus norvegicus LD50> 5000 mg/kg

- bw

(Males and Females)

Practically nontoxic 45435011 Acceptable None11 Taxa Study Type % ai Species Toxicity Value & Category MRID &
Status Endpoints

Affected
Chronic
870.3800 97.1 Rat Rattus norvegicus Parental

NOAEL (m)= 100 mg/kg

- diet LOAEL (m)= 800 mg/kg

diet

Offspring NOAEL= 100 mg/kg

diet
LO AEL= 800 mg/kg

- diet 45531909 Acceptable None

Acute Inhalation 96.5 Rat Rattus norvegicus LC50> 0.84 mg/L

Males and Females

Slightly Toxic 45435013 Acceptable Mortality

Birds Acute Oral

850.2100 98.4 Mallard Duck Anas platyrhynchos LD50> 2000 mg ai/k g

bw NOAEL= 2000 mg ai/kg

bw

Practically nontoxic 48660601 Acceptable None

Acute Dietary
850.2200 15.6 Northern Bobwhite Quail Colinus virginianus LC50> 5970 mg ai/kg

diet
NOAEC= 5970 mg ai/kg
diet

Practically nontoxic 46622701 Acceptable None

Chroni c 850.2300 97.1 Mallard Duck Anas platyrhynchos NOAEC= 100 mg/kg

diet LOAEC= 500 mg/kg

- diet 45435005 Acceptable Female body

Weight gain

Terrestrial
Invertebrates Adult Acute

Contact
850.3020 97.1 H oneyb ee Apis mellifera 48

- hr LD50> 100 μg

ai/bee

NOAEL= 100 μg ai/bee

Practically Nontoxic 45435007 Acceptable None

Adult A cute Oral 15.4 H oneyb ee Apis mellifera 72

- hr LD50> 315 μg

ai/bee NOAEL= 43.8 μg ai/bee 45428608 Supplemental

Acceptable for
use in risk

assessment None

Terrestrial
Plants Seedling

Emer gence Monocot
850.4100 15.3 Oat ( Avena sativa )
Onion ( Allium

cepa )
Corn ( Zea mays ) EC25>0.9 lb ai/a

NOAEC= 0.9 lb ai/a No effect for all species 45428609 Acceptable None12 Taxa Study Type % ai Species Toxicity Value & Category MRID &
Status Endpoints

Affected Ryegrass ( Lolium

perenne ) Seedling Emergence
Dicot
850.4100 15.3 Carrot ( Daucus

ca rota ) Rapeseed ( Brassica

napus ) Sugarbeet ( Beta vulgaris)
Tomato ( Solanum Lycopersicum ) Cabbage ( Brassica oleracea ) Soybean (Glycine

max ) EC25= 0.7 lb ai/a

NOAEC = 0.3 lb ai/a

Most sensitive species : Carrot 45428609 Acceptable Shoot Height

Vegetative
V igor
Monocot
850.4150 15.3 Oat ( Avena sativa )
Onion ( Allium

cepa )
Corn ( Zea mays ) Ryegrass ( Lolium

perenne ) EC25> 0.9 lbs ai/a

NOAEC= 0.9 lbs ai/a No effect for all species 45428610 Acceptable None

Vegetative Vigor
Dicot
850.4150 15.3 Carrot ( Daucus

ca rota ) Rapeseed ( Brassica

napus ) Sugarbeet ( Beta vulgaris )
Tomato ( Solanum Lycopersicum ) Cabbage ( Brassica oleracea ) Soybean (Glycine

max ) EC25> 0.9 lbs ai/a

NOAEC= 0.3 lbs ai/a

Most sensitive species : Beets, cabbage 45428610 Acceptable Shoot Height

b. De gradate toxicity

Two s tudies were submitted that compared the acute toxicity of acequinocyl and R1 to the most sensitive aquatic species, the water flea ( Daphina magna ) (LC 50 acequinocyl= 2.7 μ g ai/L; LC50 R1= 2.4

μ g ai/L)

. The results of these studies ( T able 5 ) indicate that acute exposure of acequinocyl and the R1 degradate are of equal toxicity to aquatic freshwater invertebrates

. A study carried out with the common carp ( Cyprinus carpio ) (MRID 46370502) did not observe toxicity effects for acequinocyl or R1 up to a maximum concentration of 1.1 mg ai/L

. Toxicity data were not available for major degradates AKM 18, AKM 08, o

- Phthalic acid, Phenol, CBAA. A full list of the major degradates and their chemical properties is available in Appendix 3

.13

Table 5: Toxicity Endpoints of Acequinocyl and the Major Acequinocyl Degradate H

- Acequin o cyl (R1)

Taxa Study Type Compound Species Toxicity Value & Category MRID &

Status

Freshwater
Invertebrate Acute

850.1010 Acequinocyl

97.0% Water Flea

Daphnia magna LC50= 2 .7 μ g

ai/L

NOAEC= 0.66 μ g ai/L

Very highly
Toxic 46372101

Acceptable

Freshwater
Invertebrate Acute

850.1010 R1

96.9% Water Flea

Daphnia magna LC50= 2.4 μ g

ai/L

NOAEC= 1.7 μ g ai/L

Very Highly
Toxic 46372101

Acceptable

Freshwater
Invertebrate Acute

850 .1010 Mixture

composed of equal parts: Acequinocyl
97.0%

+ R1 96.9% Water Flea

Daphnia magna LC50= 5.2 μ g

ai/L

NOAEC= 1.5 μ g ai/L

Very Highly
Toxic 46372101

Acceptable

Freshwater
Fish Acute

850. 1075 R1

99.3% Common Carp

Cyprinus carpio LC50>2.3 m g

ai/L

NOAEC= 2.3 m g ai/L

Moderately
Toxic 46370502

Supplemental

Non guideline test species and was
conducted as
a limit test. Endpoint can
be used to quantitatively
assess risk.

ECOSAR was used to predict toxicity of the major degradates (>10% formation) R1, AKM 18, AKM 08, o

Phthalic acid, Phenol, and CBAA

. ECOSAR uses quantitative structure activity relationships (QSAR) to predict effects of acute exposure to aquatic species. Reliability of the predictive capacity o f ECOSAR modeling is determined base d on how closely the modeling program can estimate the toxicity of the parent compound.

S imilarities between empirically

- derived toxicity values for the parent or the R1 degradate and the toxicity values predicted by ECOSAR indicated that predicted toxic ity values provided meaningful indications of acute and chronic exposure toxicity of acequinocyl degradates to the most sensitive14

aquatic taxa, Daphnia magna, as well as exposure to green algae. Based on a similar comparison of
ECOSAR

- predicted toxicity va lues of acequinocyl to freshwater and estuarine/marine fish with the predicted values generated by ECOSAR, there was no confidence in these predicted values . The ECOSAR output for daphnia and green algae are available in Table 6.15 Table 6 : Acute and Chroni c V alues ( μ g ai/L) P redicted t hrough ECOSAR M odeling

Exposure (Acute/ Chronic) Taxa Parent Degradate Acequinocyl Toxicity (from studies) Acequinocyl

(Predicted) R1

(From studies) R1

(predicted) 

### AKM 18 AKM 08 o
- Phthalic
acid Phenol CBAA

Acute Daphnia

magna LC 50 2.7 8 2.4 12 540 59 4,858,623 9,295 365,026

Chronic Daphnia

magna NOAEC 0.98 9

-- 3 149 45 1 373,177 1,770 43,360

Acute Green Algae 960 34

-- 34 1889 15 2,538,352 44,824 1,028,138

1 Estimated by ECOSAR program using Acut e to Chronic toxicity ratio16

ECOSAR modeling does not provide evidence that major degradates R1 and AKM 08 are more or less
toxic than acequinocyl , as the predicted toxicities of these degradates are similar to the measured toxicity endpoints of acequinoc yl

. In the case of R1, this was verified empirically, as discussed above. The degradates AKM

- 18, o

- Phthalic acid

, phenol and CBBA are predicted to be several orders of magnitude
less toxic t han acequinocyl.

c. Ecological Incidents

The Ecological Incident In formation System or EIIS maintained by the Environmental Fate and Effects Division, and the Avian Incident Monitoring System (AIMS) maintained by the American Bird Conservancy, were searched on February 26 , 201 5 and no ecological incidents were recorded re sulting
from the use of acequinocyl

. In addition to the incidents recorded in EIIS and AIMS, additional incidents are reported to the Agency in aggregated form. Pesticide registrants report certain types of incidents to the Agency as aggregate
counts of i ncidents occurring per product per quarter. Ecological incidents reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W

- B), ‘minor plant’ (P

- B), and ‘other non

target’ (ONT) incidents. ‘Other non

- target’ incidents include reports of adverse effects to insects and
other terrestrial invertebrates. For acequinocyl

, there have been no reported incident summaries as of January 8 , 201 5

.

7. Exposure Pathways of Concern

EFED's environmental exposure models estimate the potential exposure of plants and animals to pesticide residues in aquatic and terrestrial environments based on registered labels including maximum acequinocyl application rates and intervals . Some of the aquatic models can also be utilized to estimate pesticide res idues in drinking water for use in the dietary exposure models. A more detailed description of aquatic and terrestrial models can be found at the following website: http://www.epa.gov/pesti cides/science/models_db.htm

.

The Screening Imbibition Program (SIP v.1.0) is used during the problem formulation phase of Registration Review to provide an upper

- bound estimate of exposure of birds and mammals to pesticides through drinking water alone. SIP does not aggregate the drinking water exposure route with other exposure routes ( i.e., dietary, inhalation, dermal). D ue to the lack of an observed toxicological effect at all levels, the risk from acequinocyl exposure from drinking water alone is pre sumed to be low. SIP readout for acequinocyl is available in Appendix 5

The Screening Tool for Inhalation Risk (STIR v.1.0) is used during the problem formulation phase of Registration Review to assess the potential for exposure to birds and mammals throu gh inhalation. The exposure pathways that are assessed by this tool include both droplet inhalation and vapor phase inhalation. STIR is intended to determine if exposure is likely and not whether or not the potential for risk exists. If STIR predicts that exposure is likely, additional inhalation data may be necessary to adequately assess risk due to the inhalation exposure pathway. The STIR model predicted that exposure if not likely significant

. STIR inputs and outputs for acequinocyl are available in App endix 6.17

8. Analysis Plan

a. Stressors of Concern

In order to estimate risks of acequinocyl exposures in aquatic and terrestrial environments, all exposure modeling and resulting risk conclusions will be based on registered labels including maximum applicati on rates and methods for each use of acequinocyl . EFED's environmental exposure models estimate the potential exposure of plants and animals to pesticide residues in aquatic and terrestrial
environments.

i. Ecological Risk Assessment

The stressors of concer n for terrestrial taxa are acequinocyl and R1 . B ased on empirically

- derived toxicity endpoints and predicted toxicity from ECOSAR, acequinocyl and R1 are predicted to be of equal toxicity. The stressors of concern for aquatic taxa are acequinocyl, R1, and the degradate AKM

- 08 which forms primarily during aqueous photolysis

. Based on chemical similarities, empirically

- derived toxicity endpoints, and the results of ECOSAR modeling results for aquatic taxa

, these chemicals are presumed
to be equally toxic to aquatic taxa. As in past risk assessments, conservative assumptions may be made for modeling aquatic EECs due to uncertainties about the available fate data. T wo approaches may be
used to address the uncertainty by bounding EECs

. Approach 1 will assume parent compound stability,

w hile Approach 2 (total toxic residues of acequinocyl + R1) will assume that the half

- lives of acequinocyl
and the R1 degradate were accurate. A pproach 2 will assume equal toxicity for acequinocyl and R1

. Approach 2 will not cap ture exposure to AKM

- 08 which is proposed as a degradation product of R1 and is assumed to be equally as toxic as R1 and acequinocyl. Approach 2 may be updated to include AKM

- 08 if it is determined that the available fate data are sufficient to address AK M

- 08 formation and decline. However, Approach 1 will account for any uncertainty in the formation of AKM

- 08 or any minor degradates which have similar structure to acequinocyl 4 and may have similar toxicity to acequinocyl
and R1.

ii. Drinking Water

The last DWA was conducted in 2011 (DP389520). A new DWA will be conducted in registration review for all registered uses of acequinocyl. The DWA will include exposure estimates based on acequinocyl and the hydroxylated degradate, that is, R1 (residue of concern recommended by the Metabolism Assessment Review Committee (MARC) of the Health Effec ts Division (HED) (USEPA, 2004c ) in surface and ground waters.

As in previous DWAs, two approaches may be used to calculate EDWCs due to uncertainties associated
with the a vailable environmental fate data. In Approach 1 , acequinocyl will be conservatively assumed to be stable to all routes of degradation. In Approach 2 , it will be assumed that the half

- lives of acequinocyl and the degradation product R1 were accurate and t he total toxic residues (acequinocyl + R1) will be modeled to address toxicity concerns with both acequinocyl and R1.

Surface water and ground water concentrations will be modeled using the most up

- to

- date models and guidance at the time of the risk asse ssment. The DWA will also include a summary of available surface and ground water monitoring data.

4 Minor degradates with structures similar to acequinocyl formed in some of the available fate studies (e.g., aqueous photolysis and aerobic aquatic metabolism)18 b. Measures of Exposure

EFED will use standard available models to evaluate potential exposures to aquatic and terrestrial organisms as described at http://www.epa.gov/pesticides/science/models_db.htm

.

i. Available Monitoring Data

EFED will consider available monitoring data from federal and state agencies or other sources. The Agency welcomes submission of monitoring data.

c. Measures of Effect

Ecot oxicity data presented in Table s 3

- 4 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior
to conduct ing the risk assessment will also be considered. The open literature studies will be identified using EPA’s ECOTOXicology database ( ECOTOX 5 ) , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrest rial plants, and wildlife.

9. Endangered Species Assessment

Consistent with EPA’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses of p esticides in accordance with the Joint Interim Approaches developed to implement the recommendations of the April 2013 National Academy of Sciences (NAS) report, Assessing Risks to Endangered and Threatened Species from Pesticides

. The NAS report outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to acequinocyl in connection with the development of its final registration review decision for acequinocyl

. In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries (the Services), and
USDA released a white paper containing a summary of their joint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developed jointly by the agencies in response to the NAS recommend ations, and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between the EPA and the Services. Details of the joint Interim Approaches are contained in the November 1, 2013 white paper

, Interim Approaches for National

- Level Pesticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report.

Given that the agencies are continuing to develop and work toward implementation of the Interim Approaches to assess the potential risks of pesticides to listed species and their designated critical habitat, this ecological problem formulation supporting the Preliminary Work Plan for acequinoc yl does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted during registration review. While the agencies continue to develop a common method for ESA analysi s, the planned risk assessment for the registration review of acequinocyl will describe the level of ESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types of species where the potential for effects exists, once the scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to

5 http://cfpub.epa.gov/ecotox/19

complete risk assessments for listed spe cies and their designated critical habitats, these methods will be applied to subsequent analyses of acequinocyl as part of completing this registration review.

10. Endocrine Disruptors Screening Program

Acequinocyl was not included in either the first or sec ond group of chemicals issued an order to conduc t Tier I EDSP testing, for more information on the EDSP program, visit http://www.epa.gov/endo/

.

11. Preliminary Identification of D ata Gaps

a. Fate

Table 7 lists the status of the fate and transport data requirements for acequinocyl. Although fate data are available, there are data gaps for all guideline requirements triggered for acequinocyl uses (except terrestrial field dissipation) because of the numerous issues with the available studies. These issues need to be addressed to upgrade the status of these studies. A common issue identified in most of the submitted fate studies is the necessity to determine whether the analytical methods were appropriate to accurately asse ss the rate of degradation of acequinocyl and to identify its major transformation products. Validation of all analytical methods used is required to address this issue. Another common deficiency is the lack of storage stability data to determine if the degradation of [ 14 C] acequinocyl and its transformation products occurred during storage before the analysis of samples. Storage stability data reflecting storage conditions for each study are required to address this issue. Although some data have
been submitted to address these issues (e.g., method validation), they are insufficient to upgrade any of
the studies.

It would be ideal to collectively address the data gaps for all of the fate studies; however, the ecological
risk assessment and DWA may proce ed based on the available data by making conservative assumptions as in past risk assessments. Two approaches may be used to bound aquatic EECs . In Approach 1

, acequinocyl will conservatively be assumed to be stable to all routes of degradation because of the uncertainties associated with the environmental fate data, mainly the lack of validation of the analytical methods and the lack of storage stability data. In Approach 2 , it will be assumed that the half

- lives of acequinocyl and the degradation prod uct R1 are accurate and total toxic residues (acequinocyl + R1) will be modeled to address toxicity concerns with R1.

Uncertainties about degradation rates would need to be addressed for all studies in order to move away from conservative assumptions suc h as those outlined above. Addressing other issues such as testing on additional soils (e.g. aerobic soil metabolism) is expected to have little impact on the risk assessment unless issues with the existing studies surrounding potential overestimation of degradation rates are addressed first; thereby, potentially allowing the risk assessment to move away from the assumption of stability. Despite uncertainties in the fate data, EECs based on both approaches led to the same conclusions in past risk assessme nts; that is, the greatest risk to the aquatic environment from use of acequinocyl is direct effects on aquatic invertebrate species. On the other hand, r eliance on potentially conservative assumptions may lead to overly conservative mitigation measures t o protect endangered aquatic species.20

Table 7

. Environmental Fate Data and Data Gaps for Acequinocyl

OCSPP
Guideline Data Requirement MRID Classification Data Gap? Comments

835.2120 Hydrolysis 45434908 Supplemental Yes It would be ideal to collecti vely address the data gaps for all of the fate studies; however , the ecological risk assessment and

DWA may proceed based on the available data by making conservative assumptions as in past risk assessments.

A detailed discussion about data gaps and a ss umptions that will be
made in the absence of additional
data are described above. 835.2240 Aqueous Photolysis 45434909 Supplemental Yes

835.2410 Soil Photolysis 45434910 Supplemental Yes

835.4100 Aerobic Soil

Metabolism 45434911

45434912 Suppl emental

Invalid Yes

835.4200 Anaerobic Soil

Metabolism - - Yes

835.4300 Aerobic Aquatic

Metabolism 45434914 Supplemental Yes

835.4400 Anaerobic Aquatic

Metabolism 45434913 Supplemental Yes

835.1230
835.1240 Leaching

Adsorption/ Desorption 45531902

45434907 Supplemental

Supplemental Yes

835.6100 Terrestrial Field

Dissipation 45651601 Acceptable No

850.1730 Accumulation in Fish 45434923 Supplemental Yes

b. Effects

Table s 8

- 9 identify ecological effect studies by MRID that offer data for each gui deline requirement. In the case that studies providing valid toxicity endpoints are not available, these will be recommended below. Rationale for additional data requests are presented in the table, and in the case that OCSPP test guidelines are not availa ble for the data requirement, rationale for the additional data request is present
in the comments

.
Table 8 : Data Gap Table of Aquatic Effect Data for Acequinocyl and Major Degradates
OCSPP Guideline Data requirement MRID Classification Data Gap? Comments

850.1010 Freshwater

Invertebrate Acute Toxicity 46372101 Acceptable No

850.10 3 5 Mysid

850.1025 Oyster Estuarine/Marine

Invertebrate

O yster Acute Toxicity 45434917

45434916 Supplemental

Supplemental Yes Guideline requirement for mysid shrimp is fulfilled. Study recorded high rate of degradation of the chemical throughout the experiment, however this recovery % is consistent with all aquatic
studies.21

OCSPP Guideline Data requirement MRID Classification Data Gap? Comments

Guideline requirement for mollusk
remains unfulfilled. Poor performance of controls in the

ea stern oyster study (MRID 45434916) means that this study is only valid for qualitative use

. 850.1300 Freshwater

Invertebrate Life Cycle 45434922 Supplemental No The supplemental study is considered scientifically sound for use in the risk assessment, as the low recovery % was outside guideline recommendations but was consistent with other aquatic
studies.

850.1350 Estuarine/Marine

Invertebrate Life Cycle None NA No Waiver request was granted to exempt the registrant from this guideline requirement beca use of solubility issues with acequinocyl. This endpoint will be estimated using an Acute to Chronic Ratio (ACR).

850.1075 Freshwater Fish

Acute Toxicity 45868502 /

45434920 (same study)

Trout

45434918 Bluegill Supplemental

Supplemental No The supp lemental study is considered scientifically sound for quantitative use in the risk

asse ssment as the low chemical recovery % was outside guideline
recommendations but was consistent with other aquatic
studies.

850.1075 Estuarine/Marine

F ish Acute Toxicity 45434921 Supplemental No The supplemental study is considered scientifically sound for use in the risk assessment, as this
limit test measured no effect at
levels that were several orders of magnitude above the limit of solubility. The chemical recovery % was outside guideline
recommendations but was consistent with other aquatic
studies.

850.1400 Freshwater Fish

Early

- Life Stage 45428607 Supplemental Yes Only two replicate s per test
concentration were included

. As a result, the study may only be used to qualitatively assess risk of chronic exposure to freshwater fish. Study22

OCSPP Guideline Data requirement MRID Classification Data Gap? Comments

must be repeated with the recommended four replicates. In the absence of these data, chronic
freshwater fish toxicity data for surrogate pesticides

– starting with data for closely related pesticides and proceeding to data for less related pesticides

– may be used to characterize the chronic toxicity of acequinocyl to freshwater fish

. 850.1400 Estuarine/Marine

Fish Early

- Life Stage None NA Yes In absence of data , chronic toxicity to estuarine/marine fish may be
characterized using data for surrogate pesticides

– starting with data for closely related pesticides and proceeding to data for less related pesticides

.

EFED acknowledges that previous
chronic studies with estuarine/marin e studies have encountered difficulties maintaining concentrations due to low solubility in salt water. If this problem continues to occur, this test can be conducted using TEP, as this is reported to have a higher solubility
in salt water.

850.4400 Aqua tic Vascular

Plant Toxicity Test using Lemna spp. None NA Yes 40 CFR Part 158 requires the submission of aquatic vascular plant toxicity data. Risk to this taxa will be presumed until data are submitted.

850.4500 Green Algae

Toxicity Pseudokirchneriell a subcapitata 45428611

TGAI
45435008
TEP Supplemental No Both studies with green algae were conducted for less than the
recommended 96 hours a nd as a result, are classified as supplemental. The toxicological endpoints derived from these studies for green algae are far above the limit of solubility of this 850.4500 Marine diatom

Skeletonema

costatum None NA Yes23

OCSPP Guideline Data requirement MRID Classification Data Gap? Comments

850.4500 Freshwater diatom

Navicula pelliculosa None NA Yes chemical, so the submission of a new study on green algae would not impact the risk conclusion and is therefore not requested at this time.

40 CFR Part 158 requires the submission of toxicity data for nonvascular aquatic plant species Green Algae Pseudokirchneriella subcapitata, Marine diatom Skeletonema costatum,
Freshwater diatom Navicula pelliculosa, and Blue Green Algae/Cyanobacterium Anabaena flos

- aquae . Risk to this taxa will be presumed until va lid studies are
submitted for each taxa except green algae

. 850.4550 Blue Green Algae /

Cyanobacterium Anabaena flos

aquae None NA Yes

Non Guideline Whole sediment:

chronic
invertebrates

freshwater and estuarine/marine None NA Yes Chronic sediment invertebrate toxicity data are required under 40 CFR Part 158
and further clarified in Guidance for Benthic Invertebrates (USEPA, 2014 ) if:
i. T he half

- life of the pesticide in sediment if > 10 days in either the aerobic soil or aquatic metabolism studies and if any of the following exist:

A. The soil partition coefficient (Kd) is ≥ 50

B. The log Kow is ≥ 3.
C. The Koc is ≥ 1,000.

T he average half

- li fe of acequinocyl and major degradate R1 reported in the
aerobic soil metabolism is 42 days ; and the log Kow and Koc of acequinocyl are 6.69 and 1027

- 97 0 mL/g, respectively. Exposure duration for benthic invertebrates to acequinocyl and R1 is
considered more relevant because available data suggest that the toxicity of the two compounds is equal for aquatic invertebrates.

Therefore, chronic sediment test s with the midge Chironomus dilutus

, freshwater amphipod Hyalella azteca

,24

OCSPP Guideline Data requirement MRID Classification Data Gap? Comments

and estuarine/marine amphipod Leptocheirus plumulosus are needed.

In the absence of these data, sediment

dwelling invertebrate chronic toxicity data for surrogate pesticides

– sta rting with data for closely related pesticides and proceeding to data for less related pesticides

– may be used to characterize the chronic toxicity of acequinocyl to sediment

- dwelling invertebrates.

As indicated in 40 CFR Part 158, the registrant is requ ired to submit a protocol for approval prior to initiating the study

.

Table 9 : Data Gap Table of Terrestrial Effects Data for Acequinocyl
OCSPP Guideline Data requirement Submitted
Studies (MRID) Study

Classifications Data

Gap? Comments

850.2100 Avian Acute Oral

Toxicity (Upland game or waterfowl species) 45660601 Acceptable No

--

850.2100 Avian Acute Oral

Toxicity (Passerine species) None NA Yes Measures of effect from a non

passerine species could potentially
underestimate acequinocyl toxicity to pas serine species, consequently,
additional information on acequinocyl toxicity to a passerine species is needed to reduce the uncertainty created by this analysis.

850.2200 Avian Dietary

Toxicity 46622701

45435003 Acceptable

Acceptable No

--

850.2300 Avian

Reproduction 45435005

45435006 Acceptable

Acceptable No

--

850.3020 Tier I

- Honeyb ee

Acute Adult Contact Toxicity 45435007 Acceptable No

--

Non

Guideline (OECD 213) Tier I

- Honeybee

A cute A dult O ral Toxicity 45428608 Supplemental No The supplemental st udy is considered scientifically sound for
use in the risk assessment.

Non

Guideline Tier I

- Honeybee

A dult C hronic O ral

E xposure None NA Yes This study estimates the exposure to adult bees resulting from visits to
contaminated flowers over an25

OCSPP Guideline Data requirement Submitted
Studies (MRID) Study

Classifications Data

Gap? Comments

extended per iod of time or through consumption of contaminated food
in the hive.

Non

Guideline Tier I

- Honeybee

Larval Acute and
C hronic O ral

E xposure None NA Yes These studies help characterize the effect of repeated exposure of the brood to pesticides that may e nter the hive and be stored in food sources such as pollen, honey, royal or brood jelly.

850.3030 Tier II

- Honey b ee

Toxicity of Residue s on Foliage None NA No The acute contact 48

- hr LD50 was above 100 μg ai/bee . This study is only triggered if contact to xicity is less than 11 μg ai/bee

. Non

Guideline Tier II

- Nectar and

Pollen Residue Study for Insect
Pollinators (none) NA Yes If risks are identified from Tier I risk estimation for honeybees, then Tier II risk estimations may need to be
called in to ide ntify more targeted routes of exposure. Exposure of acequinocyl through translocation to nectar and pollen could be a route of exposure to insect pollinators.

Non

Guideline (OECD 75) Tier II

- Semi

- Field

Testing for Honeybees None NA Yes If risks are iden tified from Tier I risk estimation for honeybees, then Tier II risk estimations may need to be
called in to identify more targeted risk mitigation options . Typical ly
semi

- field studies are usually
conducted under conditions that represent the worst

- case ex posure scenario of proposed uses to the entire colony.

850.3040 Tier III

- Field

Testing for
Pollinators None NA Yes If risks are identified from Tier II risk estimation for honeybees, then Tier III field studies may need to be
called in to identify more targeted risk mitigation options

. 850.4100 Seedling

Emergence and Seedling Growth 45428609 Acceptable No

--

850.4150 Vegetative Vigor 45428610 Acceptable No

Justifications for non

- guideline data requirements are below:26

Study Title: Tier I

- Polli nator Chronic Oral Toxicity, Adult Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants an d subsequently brought back to the hive. Therefore, potential chronic effects to adult honeybees and other pollinators from oral exposure to some pesticides could exist. Currently available toxicity studies do not address possible lethal and sublethal
ef fects of chronic oral exposure on adult terrestrial invertebrates and will assist in determining whether the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for pollen and nectar to be contaminated with pestici de residues, and subsequently brought back to the hive, it is important to determine the chronic oral toxicity of this compound to adult honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological t esting for invertebrates with the honeybee. The guidance discusses Tier I laboratory

- based chronic oral toxicity studies of individual adult honeybees as a critical component of the screening

- level risk assessment process for examining potential risks fro m specific routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Study design elemen ts for the chronic 10

- day oral toxicity test with honeybees are similar to the OECD Test Guideline 213 acute oral toxicity test http://w ww.oecd

- ilibrary.org/environment/test

- no

- 213

- honeybees

- acute

- oral

- toxicity

test_9789264070165

- en

. Practical Utility of the Data
How will the data be used? The Tier I chronic oral toxicity d ata on adult bees serve as a foundation for the screening

- leve l assessment of potential risk to non

- target organisms including federally listed threatened or endangered species and

non

- listed terrestrial invertebrate insects, including pollinators, from chronic oral exposures to pesticides.
The data will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect polli nators and to determine whether adult toxicity differs substantially from other life stages evaluated in other Tier I tests. If chronic oral effects data for adults are not available, risks to terrestrial insects from chronic oral exposure will be assumed

. How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target sp ecies or is likely to adversely affect listed threatened or endangered species and/or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the E SA, and could result in use restrictions.

Study Title: Tier I

- Pollinator Acute Oral Toxicity, Larvae Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide

re sidues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be exposed. Therefore, potential adverse effects to developing bees and other insect pollinators could result from exp osure to pesticide residues. Available toxicity studies do not address possible effects on brood (larvae and pupae) survival/development. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine the acute oral toxicity of this compound to bee brood.27

The Office of Pesticide Programs has made available a guidance regarding ecological testing for terrestrial invertebrates using the honeybee as a surro gate test species. The guidance discusses Tier I laboratory

based acute toxicity studies of individual honeybee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidance can be
found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional guidance on larval honeybee toxicity tes t design can be found in OECD Test Guideline 237 http://www.oecd

- ilibrary.org/environment/test

- no

- 237

- honey

- b ee

- apis

- mellifera

- larval

- toxicity

- test

- single

exposure_9789264203723

- en

. Practical Utility of the Data
How will the data be used? The Tier I acute oral toxicity d ata on honeybee larvae serve as a foundation for the screening

- level assessment of potent ial risk to non

- target organisms such as federally listed threatened or endangered and

non

- listed terrestrial invertebrate insects, including pollinators, and/or modify their designated critical habitat from acute oral exposures to pesticides. The data wi ll be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential effects on terrestrial species and whether there is a differential sensitivity of larval bees relativ e to adult bees. If acute oral effects data for larvae are not available, risks to terrestrial insects from acute oral exposure will be assumed How could the data impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered species and/or modify their designated cri tical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

Study Title: Tier I

- Pollinator Chronic Oral Toxicity, Larva e Rationale for Requiring the Data Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive where larvae and pupae may be exposed. Therefore, potential effects to developing bees could result from chronic oral exposure to pesticide residues. Available toxicity studies do not address possible chronic effects on brood (larvae and pupae) sur vival. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to
determine chronic larval/pupal toxicity and whether adult emergence is adversely affected. Thi s study will provide information on whether honeybee larvae differ in sensitivity from adult bees following chronic

exposure.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance discusses Tier 1 laboratory

- based chronic oral toxicity studies of individual honeybee larvae as a critical component of the screening

- level risk assessment process for examining potential risks from specific routes of exposure. The guidanc e can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance

. Additional information on larval honeybee toxicity repeat exposu re test design can be found in the oECD draft guidance http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_November_2013. p df

.28 Practical Utility of the Data
How will the data be used? The Tier I chronic oral toxicity d ata on bee larvae serve as a foundation for the screening

- level assessment of potential risk to non

- target organisms including federally listed threatened or endangered and non

- listed terrestrial invertebrate insects, including pollinators, from chronic oral exposures to pesticides. The data
will be used to reduce uncertainties associated with the risk assessment for terrestrial invertebrates and will impro ve EPA’s understanding of the potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, particularly insect pollinators. These data will also assist in determining whether early life stages of the bee differ in th eir sensitivity to pesticides relative to adults. If chronic oral effects data for larvae are not available, risks to terrestrial insects from chronic oral exposure will be
assumed. How could the data impact the Agency’s future decision

- making?
The data w ill inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect listed threatened or endangered spec ies and/or modify their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.

Study Title: Tier II S emi

- Field Toxicity Testing (tunnel/enclosure studies) Rationale for Requiring the Data Tier II studies are conditional on the outcome of the screening

- level assessment where acute and/or chronic
risk levels of concern have been exceeded for terrestrial i nvertebrates. Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive and may adversel y affect developing brood (egg, larvae, and pupae) and adult bees . Screening

- level (Tier I) studies of individual bees do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nect ar to be contaminated with pesticide residues, and subsequently brought back to the hive, it is important to determine whether bee colonies may be negatively affected under relatively controlled exposure conditions of a semi

- field study. In addition to pro viding effects data, these studies can provide data on exposure as pesticide residues in pollen/nectar of treated plants.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional in formation on honeybee colony studies under semi

- field conditions can be found in the OECD Guidance 75 http://www.oecd.org/officialdoc uments/publicdisplaydocumentpdf/?cote=env/jm/mono%28

. Practical Utility of the Data
How will the data be used? Tier II colony

- level data will be used to assess potential risk to non

- target organisms including listed and

non

- listed t errestrial social invertebrate species and to determine whether effects observed in the screening

- level (Tier I) laboratory

- based studies of individual bees are evident in colony

- level studies under
semi

- field conditions. The Tier II semi

- field test of wh ole colonies is a relatively controlled study, i.e ., bees are confined to a specific area, that is designed to represent potential field

- level exposure and account for hive dynamics, which are not achievable from other pollinator studies. This study will be used to determine whether adverse effects to insect pollinators at the whole colony level, may result for the use of pesticides and will help to refine risk estimates derived in the screening

- level risk assessment for beneficial terrestrial29

invertebrate s. Measured residues in pollen/nectar can also be used to refine risk estimates derived from
model

- based or default values in the screening

- level assessment.

How could the data impact the Agency’s future decision

- making?
The data will inform the determin ation required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to presume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

Study Title: Tier II Semi

- Field Toxi city Testing (feeding studies) Rationale for Requiring the Data Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to the hive, and may adversely affect developing brood (egg, larvae, and pupae) and adult bees . Tier II feeding studies are conditional on the outcome of the screening

- level assessment where acute and/or
chronic risk levels of concern have been exceeded for terrestrial invertebrates based on Tier I studies of individual bees. Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of test material and represent a means of ensuring exposure to the test material through spiked pollen and/or sugar solutions fed to the colony while still allowing the be es to forage freely. Since bee colonies are not confined to enclosures, colonies can be exposed for longer duration periods without subjecting the bees to stress that typically results from Tier II tunnel studies. Available toxicity studies of individual bees (Tier 1) conducted to support screening

- level assessments do not address possible effects and/or exposure to pesticide residues at the colony

- level. Because of the potential for pollen and nectar to be contaminated with pesticide residues, and subse quently brought back to the hive, it is important to determine whether bee colonies may be negatively affected where bees are free foraging and have the option to collect/consume alternative forage items beyond the spiked food. Since multiple dose levels c an be more readily tested, feeding studies can help to define dose

- response relationships at the whole colony level.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guid ance describes the tiered testing process and can be found at: http://www2.epa.gov/pollinator

- protection/pollinator

- risk

- assessment

- guidance . Additional informa tion on honeybee colony feeding studies can be found in the EPPO Guidance 170 at: http://www.nationalbeeunit.com/index.cfm?pageId=187

. Practical Utility of the Data
How will the data b e used? Tier II colony feeding data will be used to assess potential risk to non

- target organisms including listed and

non

- listed terrestrial social invertebrate species. The colony feeding study is designed to represent potential field

- level exposure and account for hive dynamics using longer duration exposure periods than are possible in Tier II tunnel studies. The study will be used to determine whether potential adverse effects to insect pollinators at the whole colony level when bees are able to fora ge naturally beyond the spiked food. Results from the feeding study will help to refine the screening

- level risk assessment for beneficial terrestrial invertebrates that were based on Tier I studies on individual bees. Since feeding studies can help
to d efine a dose

- response relationship at the colony level, the studies can provide a means of determining exposure thresholds below which the likelihood of adverse effects on colonies may be low.

How could the data impact the Agency’s future decision

- making ?30

Tier II colony

- level data will be used to refine screening

- level risk estimates derived using Tier I laboratory

based data on individual bees. The Tier II data will inform the determination required under FIFRA or the ESA as to whether continued registr ation of a pesticide is likely to result in unreasonable adverse effects to

non

- target species or is likely to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA may need to pre sume risk which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in significant use restrictions.

Study Title: Residues in Pollen and Nectar Rationale for Requiring the Data
Terrestrial invertebrates are likely to be impacted if exposed to pesticide residues in various use settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and subsequently brought back to hive where all life stages may be exposed. For some pesti cides, the quantification of pollinator

relevant residues in treated flowering plants is needed, since pollinators will be exposed to residues from either current or prior season applications (due to the potential for residues to accumulate in plants and

t rees). Residues in edible/transportable

- to

- hive parts of treated trees and plants, including (where appropriate), but not limited to, guttation water, sap/resins, whole plant tissue ( e.g., leaves, stems), as well as blooming, pollen

- shedding, and nectar p roducing parts ( i.e. , flowers and, if present, extra

- floral nectaries) of plants may inform the potential for risk. Studies should be designed to provide residue data for crops and application methods of concern.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for invertebrates with the honeybee. The guidance can be found at: http://www2.epa.gov/pollinator

protection/po llinator

- risk

- assessment

- guidance

. Practical Utility of the Data
How will the data be used?
Measured residue d ata will be used to refine conservative estimates of pesticide exposure and reduce uncertainties associated with the Tier I exposure assessme nt by providing direct measurements of pesticide concentrations resulting from actual use settings. Measured residues may provide a more realistic understanding of exposure through contact or ingestion with which to calculate risk quotients for individual bees as well as to characterize exposure to the colony. If measured residue data are not available, risk
estimates for terrestrial insects will be based on model

- generated or default values used to support the screening

- level assessment.

How could the d ata impact the Agency’s future decision

- making? The data will inform the determination required under FIFRA or the ESA as to whether continued registration of a pesticide is likely to result in unreasonable adverse effects to non

- target species or is likel y to adversely affect federally listed threatened or endangered species or their designated critical habitat. Without these data, EPA will have to rely on conservative estimates of exposure which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in use restrictions.3132

12. Bibliography

USEPA. 2004a. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. Environmental Protection Agency, Office of Prevention, Pesti cides and Toxic Substances, Office of Pesticide Programs, Washington DC. January 23, 2004.

USEPA 2004b. Section 3 Request for Uses of Acequinocyl (PC code 006329) on Pome Fruit, Citrus, Almonds, Pistachios, Strawberries, and Outdoor Ornamentals. February 3, 2004. DP 285811, 286428, 289153, 290010, 287269, 290009, 291174

USEPA, 2004c. Acequinocyl. Report of the Metabolism Assessment Review Committee (MARC). Meeting Date: December 17, 2003. Memo date d January 7, 2004. TRX 0052294

USEPA, 2010. Review of study of stability of acequinocyl in solvent and seawater and decision regarding data requirement for mysid reproduction study. U.S. Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Wash ington DC. August 10, 2010. D368576.

USEPA, 2011. Acequinocyl: Drinking Water Assessment to Support Proposed New IR

- 4 Uses (Succulent Soybean Vegetable, Low Growing Berry, Small Fruit Vine Climbing

- Except Fuzzy Kiwifruit, Succulent Shelled Beans, Cowpea Forage, Caneberry, Melon, Cucumber, and Cherry).
DP389520.

USEPA. 2014a. Acequinocyl (006329): Screening Level Usage Analysis (SLUA). Biological and Economic Analysis Division, Office of Pestici de Programs. November 10, 2014.

USEPA, 2014b. Toxicity Testin g and Ecological Risk Assessment Guidance for Benthic Invertebrates. USEPA Office of Chemical Safety and Pollution Prevention, Office of Pesticide Programs. April 9,
2014.33

Appendix 1 : Previous Actions and Assessed Uses for Acequinocyl
Crop Application Rat e (lb ai/A) Number of Applications (Application Interval in Days) Action/DP Barcode/Date

Single Lbs a.i./A Seasonal/

Annual Lbs a.i./A Succulent Soybean, Low Growing Berry, Small Fruit Vine Climbing (except kiwifruit), succulent shelled beans, cowpea forage, Caneberry, Melon, Cucumber, and Cherry 0.3 0.6 2 (14

- 21) IR

- 4 New Uses D389520, D390259 10/25/2011

Tier II Drinking Water

Assessment

D448205 9/7/2011 Fruiting Vegetables, Okra, Edible podded beans, Hop 0.3 0.6 2 (21) IR

- 4 New Uses Registration / Drinking Water Assessment
D368579, D368426, D417967, D417966 4/29/2010 Citrus, Tree Nuts, Grapes, Pome Fruits,
Strawberries 0.3 0.6 2 (21)

Outdoor Ornamental 0.125 0.25 2 (14)
Citrus, Tree Nuts, Grapes,

Pome Fruits 0.3 0.6 2 (21) Section 3

New Uses D337381, D330467,

D330471 8/15/2007 Non

- food outdoor uses (various ornamentals) 0.125 0.6 5 (14)

Food Crops (citrus, tree nuts, grapes, pome fruits, strawberries) 0.3 0.6 2 (21) Tier II Drinking Water

Assessment

DP337221 6/27/2007 Outdoor Residential Ornamentals (including roses) 0.125 0.625 5 (14)

Pome Frui ts
Citrus
Almonds
Pistachios
Strawberries 0.3 0.6 2 (21) Section 3

New Uses D285811, D286428, D289153, D290010, D287269, D290009,

D291174 2/3/ 20 04 Outdoor Ornamentals 0.125 0.250 2 (14)

Greenh ouse, Shade House Ornamental, Floral, Foliage, Nursery Crops 0.125 lbs/100 gallons
formulation N/A N/A Section 3

New Uses

D291707 8/7/ 20 0334

Appendix 2 : Application Rates of Acequinocyl on Agricultural Crops (Based on Kanemite 15 SC Label)

. Use Max s ingl e a pp

r ate ( l bs./A) Max # a pps per

year Max a pp r ate per

year ( lbs ai /A) Minimum

r etreatment
i nterval ( d ays)

Tree Nuts and Pistachios 31 fl oz/A 1 2 0.6 21

Citrus 31 fl oz/A 2 0.6 21
Small

- Vine subgroup 13

- 07F (Except Kiwi) 31 fl oz/A 2 0.6 21

Pome Frui ts 31 fl oz/A 2 0.6 21

Low

- Growing Berries

Subgroup 13

- 07G 31 fl oz/A 2 0.6 21

Fruiting Vegetables (Except cucurbits) 31 fl oz/A 2 0.6 21

Melon Crop Group 9A and
Cucumber 31 fl oz/A 2 0.6 21

Succulent Shelled Bean 31 fl oz/A 2 0.6 14 Caneberry Crop S ubgroup 13

- 07A 31 fl oz/A 2 0.6 21

Cherry 31 fl oz/A 2 0.6 14
Okra 31 fl oz/A 2 0.6 21
Edible Potted Beans 31 fl oz/A 2 0.6 21 Succulent Soy Vegetable 31 fl oz/A 2 0.6 21 Hops 31 fl oz/A 2 0.6 21 Landscape Ornamentals 12.8 fl oz/A 2 2 0.25 14

1 Label states that Kanemite contains 1.25 lb ai/gal

2 Inferred based on maximum single and annual application rates.35

Appendix 3

. Summary of Acequinocyl Major Degradates and Maximum Percent Formation Observed in the Laboratory and Field Studies

Degradate Ma ximum Degradate Concentration (% of applied) and Time to Max Concentration

Hydrolysis 1 Aqueous

Photolysis Soil

Photolysis 4 Aerobic Soil

Metabolism Aerobic

Aquatic
Metabolism 5 Anaerobic

Aquatic
Metabolism 5 Terrestrial Field

Dissipation

R1 (2

- dodecyl

- 3

- hy droxy

1,4

- naphthalenedione )

pH 7: 54.7% (96 hr) -- 2

-- Silt loam soil; phenyl

- U

14 C
label: 33.8% (2 days) Total system:

12.2% (0 days) Total system:

41.0

- 41.1% (3, 7, and 14 days) NY: 37.8% (3 hr

after 2 nd application)

GA: 37.8% 7

CA: 26.4% 7

AKM 18 [2

- (1,2

- dioxotetradecyl)benzoic acid]

pH 9: 10.9% (3 hr) -- -- 4

-- Total system: 19.5% (1 day) Total system:

23.2% (269 days) NY: 16.5% 7,8

AKM

- 08 [2

- (2

- oxo

- dodecyl)

- 3

- hydroxy

- 1,4

- naphthoquinone]

-- Buffer solution: 12.9% (2 hr)

-- -- -- -- --36

Degradate Ma ximum Degradate Concentration (% of applied) and Time to Max Concentration

Hydrolysis 1 Aqueous

Photolysis Soil

Photolysis 4 Aerobic Soil

Metabolism Aerobic

Aquatic
Metabolism 5 Anaerobic

Aquatic
Metabolism 5 Terrestrial Field

Dissipation

o

- Phthalic acid

-- Buffer solution: 12.7% (24 hr) 3

River water: 11.9% (24 hr) 3 -- -- -- -- --

Phenol

-- River water: 10% (24 hr) 3

-- -- -- -- --

CBAA (2

- car boxy

- α

- oxo

benzene acetic acid)

-- -- -- -- Water layer: 11.3% (2 days) 6 -- --

1 “Unknown 1” was described as polar radioactive material consisting of one or more compounds. It was observed at pH 1.2, 4, 7, and 9 and represented a maximum of 41.6% of the applied radioactivity (pH 9, 0.75 hours).

2 Although a maximum of 11.61% formed in the irradi ated sample, formation can be predominately attributed to hydrolysis (9.07% formation in the dark control).

3 There is uncertainty about the % formation. Detected in the aqueous eluate fraction which was only analyzed for the irradiat ed samples at 24 hour s. Aqueous eluate fraction was 40.53% (buffer solution) and 43.90% (river water) for the irradiated samples and < 5.08% (buffer solution) and < 5.19% (river water) for the dark samples at 24 hours. Unknown if present in dark samples but must be less the ca. 5% of applied radioactivity in those samples. Only a portion of the aqueous eluate fraction was analyzed (60% of the buf fer solution and 87% of the river water fraction applied to the column) due to loss during purification.

4 AKM

- 18 and compound A (u nidentified) formed greater than 10% in the irradiated samples; however, an equal or greater amount formed in the dark contro ls indicating that formation was not due to photolysis. Likewise, radioactive material designated as polar compounds was observed greater than 10% of the applied radioactivity (26.2% irradiated samples and 23.4% dark controls). However, it is uncertain if the irradiated polar peak represented photolytic degradation b ecause the polar peaks may have represented more than one compound and those compounds may or may not have been present in both irradiated samples and dark controls.

5 Degradates retaining the naphthoquinone structure formed less than 10% of applied acequinocyl.

6 Sediment layer was not analyzed.

7 Formed immediately afte r application.

8 Formation based on a single replicate. The second replicate ha d a concentration below the LOD and the third replicate was not analyzed due to a lab error

.37 Appendix 4 : Complete List of Toxicity Endpoints for Acequinocyl

Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected

Mammals Acute oral

870.1100 96.8 Rat Rattus norvegicus LD50> 5000 mg/kg

- bw

(Males and Females)

Practically nontoxic 45435011 Acceptable None

Chronic
Two
Generation Reproductive
Stu dy
870.3800 97.1 Rat Rattus norvegicus Male NOAEC = 100

mg/kg

- diet
Male LOAEC = 800 mg/kg

- diet
Female NOAEC> 1500 mg/kg

- diet 45531909 Acceptable None

Acute Inhalation
870.1300 96.5 Rat Rattus norvegicus LC50> 0.84 mg/L

Males and Females

Slightly Toxic 45435013 Acceptable Mortality

Birds Acute Oral

850.2100 97.1 Japanese Quail
Coturnix coturnix japonica 8

- Day LD50> 2000

mg/kg

- bw
8

- day NOAEL= 2000 mg/kg

- bw

Practically nontoxic 45435002 Supplemental

Japanese quail

not a recommended species. May be used for quantitative assessment of
risk. No Effect

Acute Oral
850.2100 98.4 Mallard Duck Anas platyrhynchos LD50> 2000 mg ai/kg

bw NOAEL= 2000 mg ai/kg

bw

Practically nontoxic 48660601 Acceptable None

Acute Oral
850.2100 15.6 Northern Bobwhite Quail
Coli nus virginianus 8

- Day LC50> 2000

mg/kg

- bw
8

- Day NOAEL= 2000 mg/kg

- bw

Practically nontoxic 45530602 Acceptable No Effect

Acute Dietary
850.2200 97.1 Japanese Quail
Coturnix coturnix japonica 8

- Day LC50> 4952

mg/ k g

- diet NOAEC= 926 mg/kg

diet

Slightly t oxic 45435004 Supplemental

Japanese Quail

not recommended test species

. May be used for quantitative Subacute

toxicity= NOAEC based on weight loss38 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected
assessment of
risk. Acute Dietary
850.2200 15.6 Northern Bobwhite Quail Colinus virginianus LC50> 5970 mg ai/kg

diet
NOAEC= 5970 mg ai/kg
diet

Practically nontoxic 46622701 Acceptable None

Acute Dietary
850.2200 97.1 Mallard Duck Anas platyrhynchos LC50> 5000 mg/kg

- diet

NOAEC= 488 mg/kg
diet

Practically nontoxic 45435003 Acceptable Body Weight

Gain

Chro nic (reproduction)
850.2300 97.1 Northern Bobwhite Quail Colinus virginianus NOAEC= 2515 mg/kg

ai

- diet

LOAEC> 2515 mg/kg ai

diet 45435006 Acceptable None

Chronic (reproduction)
850.2300 97.1 Mallard Duck Anas platyrhynchos NOAEC= 100 mg/kg

diet

LOAEC= 500 mg/kg

- diet 45435005 Acceptable Female body

Weight gain

no mortality

Freshwater
Fish Acute

850.1075 97.1 Rainbow Trout Oncorhynchus mykiss LC50> 33 mg ai/L

NOAEC= 33 mg ai/L

Slightly Toxic 45434920 and
45868502

- Supplemental Recurring solubility i ssues led to questions about the

exposure concentrations. As this study
tested well
above the solubility limit (>1000x) and saw no effect,
this is satisfactory to fulfill guideline requirements for an acute study. Endpoints are
valid for None39 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected quantitative risk assessment
Acute
850.1075 15.4 Rainbow Trout Oncorhynchus mykiss 45530601 Invalid (formerly Acceptable) 2 Mortality

Acute
850.1075 97.1 Bluegill Sunfish Lepomis macrochirus LC50> 1.1 mg ai/L

NOAEC= 1.1 mg ai/L

Moderately toxic 45434918 Suppleme ntal

Conducted as a
limit test . No effect was
observed at
concentrations far greater than solubility
limit. As a result, endpoints are
valid to quantitatively
assess risk

. None

Acute
850.1075 15.8 Bluegill Sunfish Lepomis macrochirus 45428605 Suppleme ntal (Formerly Acceptable ) 2 None

Acute
850.1075 97.1 Zebrafish Brachydanio rerio LC50> 1.1 mg ai/L

NOAEC= 1.1 mg ai/L 45434919 Suppleme ntal

Not an acceptable species. Endpoints may only be used
for quantitative risk analysis

. None

Chronic
850.1400 15.8 Rainbow Trout Oncorhynchus mykiss NOAEC= 0.52 mg ai/L

( 1 Centrifuged NOAEC= 0.07 mg ai/L) LOAEC= 1.1 mg ai/L 45428607 Supplemental

Only two replicate s per
test
concentration. Endpoints are may only be
used to qualitatively Post Hatch

Survival40 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected
characterize
risk

.

Freshwater
Invertebrates Acute

850.1010 98.3 Water Flea Daphnia

magna LC50= 2.7 μ g ai/L

NOAEC= 0.66 μ g ai/L

Very highly Toxic 46372101 Acceptable Mortality and

sublethal
effects (lethargy)

Acute
850.1 010 15.4 Midge Chironomus riparius LC50 >13.23 mg a.i./L

*Endpoint reported in study did not correct for % a.i. The endpoint
reflected above reflects
the corrected
concentration. An addendum will be
issued to correct this in
the DER. Slightly Toxic 45782303 Supplemental

Concentrations

no t analyzed at
all
concentrations

- Endpoints

m ay be used to quantitatively
assess risk to midges from exposure in water column. Mortality

Chronic
850.1300 98.3 Water Flea Daphnia

magna NOAEC= 0.98 μg ai/L

LOAEC= 1.8 μg ai/L 454349 2 2 Supplemental

Quick
d egradation of
technical
meant low recovery rate (37

- 41%)

. Endpoints valid
for quantitative

assessment or risk

. Number of

young, length and dry weight

Estuarine/
Marine Fish Acute

850.1075 97.1 Sheepshead
minnow Cyprinodon variegatus LC50> 0.19 mg ai/L

NO AEC= 0.19 mg ai/L (Toxicity endpoints of centrifuged samples
with mean measured concentrations)

Highly Toxic 45434921 Supplemental

Limit test

Precipitate centrifuged
and counted in toxicity endpoints
calculation. No effect was
observed at
concentrati ons far exceeding the solubility None41 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected
limit of this
chemical. Therefore,
these endpoints are
valid for quantitative risk

assessment

. Acute
850.1075 15.8 Sheepshead
minnow Cyprinodon variegatus LC50> 68 mg ai/L

NOAEC=68 mg ai/L Slightly Toxic 45428606
S upplemental (Formerly Acceptable ) 2 None

Estuarine/
Marine Invertebrates Acute

850.1035 97.1 Mysid shrimp Mysidopsis bahia 96

- hour LC50=0.94 μg

ai/L NOAEC= 0.27 μg ai/L

Highly Toxic 45434917 Supplemental

Environmental conditions (pH, salinity, vessel size, temperature)
all outside
recommended
levels. Mean
measured
concentration were only 7.8

- 16% of
nominal. Endpoints are valid for quantitative risk

assessment. Lethargic

swimming, loss of equilibrium

Acute
850.1025 97.1 Eastern Oyster
Crassostrea vi rginica 96 Hour EC50 = 0.59 μg

ai/L NOAEC <0.11 μg ai/L 45434916 Supplemental

Shell deposition was
lower than
minimum 2.0

mm meaning there was uncertainty with the control quality.
Results of this study can be Shell

Depo sition42 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected
used to qualitatively
assess risk

. Chronic
850.1350 NA Mysid Shrimp Mysidopsis bahia NOAEC = 0.38 μ g/L

(Estimated using Acute/Chronic ratio) Acequinocyl is extremely
unstable in

seawater (MRID 47914901). As a result, a waiver request was granted
for studies assessing chronic

exp osure to
estuarine /marine
invertebrates
under flow

through
conditions (MRID 47256201).
For the purposes of
risk
assessment, chronic effect endpoints will
be estimated by taking the

acute to chronic ratio of endpoints
observed in
freshwater
invertebrates. 2

Aquatic Plants Non Vascular

850.4400 15 Green Algae
Pseudokirchneriella subcapitata 72

- hour EC50= 0.96 mg

ai/ L NOAEC= 0.0017 mg ai/L LOAEC=0.0055 mg ai/L 45428611 Supplemental

72 hour study
shorter than
the
recommended
96 hour

. Endpoints may Cell Density43 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected
be used for quantitative risk

assessment. Non Vascular
850.4400 97.1 Green Algae
Pseudokirchneriella subcapitata 72

- hour EC50>78.0 mg

ai/ L NOAEC ≥ 78.0 mg ai/L 45435008 Supplemental

72 hour study
shorter than
the
recommended
96 hour

. Endpoints valid for quantitative
use in risk

assessment none

Terrestrial
Invertebrates Adult A cute

Contact
850.3020 97.1 Honeybee Apis mellifera 48

- Hour LD50> 100 μg

ai/bee

NOAEL= 100 μg ai/bee

Practically Nontoxic 45435007 Acceptable None

Adult A cute Oral
Non

- Gu ideline 15.4 Honeybee Apis mellifera 72

- Hour LD50> 315 μg

ai/bee NOAEL= 43.8 μg ai/bee 45428608 Supplemental

study uses TEP.

E ndpoints can
be used for quantitative

assess ment of
risk to honeybees. None

Adult A cute
C ontact
850.3020 15.4 Honeybee Apis

m ellifera 72

- Hour LD50> 350 μg

ai/bee NOAEL= 175 μg ai/bee

Practically nontoxic 45428608 Acceptable None

Earthworm
Subchronic
850.6200 97.1 Earthworm Eisenia fetida LC50> 1000 mg ai/kg

NOAEC= 500 mg ai/kg

LOAEC= 1000 mg ai/kg 45435009 Supplemental

Non Guideline study Reductions in

body weight gain

Acute Toxicity Earthworm

– 850.6200 15.6 Earthworm Eisenia fetida LC50> 156 mg ai/kg

NOAEC= 156 mg ai/kg LOAEC >156 mg ai/kg 45782304 Supplemental

Non Guideline study Weight loss

Terrestrial
Plants Seedli ng

Emergence
Monocot 15.3 Oat Avena sativa,
Onion Allium cepa,
Corn Zea mays, Most Sensitive

Monocot: None
EC25> 0.9 lb ai/a 45428609 Acceptable None44 Taxa Study Type % a i Species Toxicity Value & Category MRID & Status Endpoints
Affected

850.4100 Ryegrass Lolium

perenne NOAEC= 0.9 lb ai/a

Seedling Emergence
Dicot
850.4100 15.3 Carrot Daucu s carota, Rapeseed Brassica

napus, Beets Beta vulgaris,
Tomato Lycopersicon esculentum, Cabbage Brassica Oleracea Soybean Glycine

max Most sensitive dicot:

Carrot EC25= 0.7 lb ai/a

NOAEC = 0.3 lb ai/a 45428609 Acceptable Shoot Height

Vegetative Vigor
Monocot
850.4150 15 .3 Oats Avena sativa,
Onion Allium cepa,
Corn Zea mays, Ryegrass Lolium

perenne Most Sensitive Species:

None
EC25> 0.9 lbs ai/a NOAEC= 0.9 lbs ai/a 45428610 Acceptable None

Vegetative Vigor
Dicot
850.4150 15 .3 Carrot Daucus

caro ta, Rapeseed Brassica

napus, Beets Beta vulgaris Cabbage Brassica Oleracea
Tomato Lycopersicon esculentum, Soybean Glycine

max Most Sensitive Species:

Beets and Cabbage

EC25> 0.9 lbs ai/a

NOAEC= 0.3 lbs ai/a 45428610 Acceptable Shoot Height

1 Centrifuge d samples yielded measured active ingredient concentrations of 13

- 19% of the uncentrifuged. For the purposes of risk assessment, the NOAEC will be 0.52 mg ai/L X 0.13 mg ai/L= 0.07 mg ai/L, and this adjusted value
will be used to calculate Risk Quotients.

2 For the purposes of risk assessment, an estimated chronic toxicity value for estuarine/marine invertebrates was assumed by taking the acute to chronic ratio (ACR) observed in freshwater invertebrate studies (MRIDs 46372101; 45434922) (2.4μg/L/0.98μg/L=2 .45) and applying it to the most sensitive estuarine marine acute endpoint (MRID 45434917) (0.94 μg/L/2.45=0.38 μg/L)

.



### Appendix 5

- SIP Inputs and Outputs45

Inputs

Parameter Value

Chemical name
Solubility (in water at 25 o C; mg/L) 0.00669

Mammalian LD 50 (mg/kg

- bw) 5000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 100 Mammalian test species laboratory rat Body weight (g) of "other" mammalian speci es

Avian LD 50 (mg/kg

- bw) 2000
Avian test species mallard duck Body weight (g) of "other" avian species Mineau scaling factor 1.15

Mallard NOAEC (mg/kg

- diet) 100 Bobwhite quail NOAEC (mg/kg

- diet) 2515 NOAEC (mg/kg

- diet ) for other bird species Body weight (g) of other avian species NOAEC (mg/kg

- diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results

Parameter Acute Chronic Upper bound exposure (mg/ kg

- bw) 0.0012 0.0012 Adjusted toxicity value (mg/kg

- bw) 3845.8028 76.9161 Ratio of exposure to toxicity 0.0000 0.0000

Conclusion* Drinking water exposure alone is NOT a potential concern for
mammals Drinking water exposure alone is NOT a potential conce rn for
mammals

Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.0054 0.0054 Adjusted toxicity value (mg/kg

- bw) 1038.4508 4.9613 Ratio of exposure to acute toxicity 0.0000 0.0011

Conclusion* Drinking water ex posure alone is NOT a potential concern for

birds Drinking water exposure alone is NOT a potential concern for

birds

Appendix 6

- STIR inputs and outputs for acequinocyl46



## Input

Application and Chemical Information

Enter Chemical Name Ace quinocyl
Enter Chemical Use Miticide Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weight (g/mole) 335 Enter Chemical Vapor Pressure (mmHg) 1.26E

- 08 Enter Applicatio n Rate (lb a.i./acre) 0.3

Toxicity Properties

Bird

Enter Lowest Bird Oral LD 50 (mg/kg bw) 2000 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 1.58
Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 5000

Enter Lowest Rat Inhalation LC 50 (mg/L) 0.84 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35



## Output
Results Avian (0.020 kg )
Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 2.27E

- 04

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 2.86E

- 05
Adjusted Inhalation LD 50 1.35E+00
Ratio of Vapor Dose to Adjusted Inhalation LD 50 2.11E

- 05 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.17E

- 02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.35E

- 02 Exposure not Likely Significant



### Results Mammalian (0.015 kg )
Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 2.27E

- 04

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 3 .59E

- 05
Adjusted Inhalation LD 50 5.00E+01
Ratio of Vapor Dose to Adjusted Inhalation LD 50 7.18E

- 07 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg) 3.98E

- 02
Ratio of Droplet Inhalation Dose to Adjusted Inhala tion LD 50 7.97E

- 04 Exposure not Likely Significant