## UNITED STATES ENVIRONMENTAL PROTECT I ON AGENCY

WAS HINGTON

. D.C. 20460

OFFICE OF CHEM I CAL SA F E T Y
AND POL L U TI ON P REVEN TI ON



### PC Code : 124871

DP Barcode: 422433

MEMORANDUM

SUBJECT: 

### Registration Review

- Problem Formulation f or the Eco l og i cal Ri s k Assessment
and D r inking Water Exposu r e Assessment to Be Conducted for Spirod icl ofen

Justin Housenger, Biologist

# ~~e fj/ 

# fJ o!

# /~g/;>'" Larry L iu, PhD, Chemist 

# t{;7**~** Environmen t a l Risk Branch 5 FROM :



### E nviro n menta l Fate and Effect s D i vision (7507P)

#

_



### THROUGH : 

### Mah Shamim

, PhD, Branch Chief

# AA4tl~ ol 

# I

).S/**/~** Enviro n mental Risk Branch 5 

# 1//Y::..::------

Environmental Fa t e and Effects Division (7507P)

TO: 

### Julia Stokes, Chemical Review Manager
Jill Bloom, Team Leader
Linda Arrington, Branch Chief
Ris k Management and Imp l ementa t ion Branch 5
Pestic i de Re

- Evalua t i o n Division (7508P)

Please, find attached t he Preliminary Problem Formulation for the Eco l ogical Risk Assessment
and Drinking Water E xposure Assessmen t for Registration Review to be conducted for

. Sp i rodiclofen

.

### 2



# Contents

1. Executive summary

................................ ................................ ................................ ................. 3
2. Introduction

................................ ................................ ................................ ............................. 8
3. Use Characterization

................................ ................................ ................................ ............... 9
4. Conclusions from Previous Risk Assessment s

................................ ................................ ....... 9

a. Ecological Risk Assessment

................................ ................................ .............................. 10
b. Drinking Water Exposure Assessments

................................ ................................ ............. 10

c. Clean Water Act Programs

................................ ................................ ................................ 11
5. Environmental Fate and Transport

................................ ................................ ........................ 11

a. Transformation Products

................................ ................................ ................................ .... 13
b. Transport and Mobility

................................ ................................ ................................ ...... 15

c. Field Dissipation

................................ ................................ ................................ ................ 16
d. Bioaccumulation

................................ ................................ ................................ ................ 16

6. Receptors

................................ ................................ ................................ ............................... 16

a. Effects to Aquatic Organisms

................................ ................................ ............................ 17
b. Effects to Terrestrial Organisms

................................ ................................ ........................ 22

c. Ecological Incidents

................................ ................................ ................................ ........... 31
7. Exposure Pathways of Concern

................................ ................................ ............................ 31
8. Analysis Plan

................................ ................................ ................................ ........................ 33

a. Stressors of Concern

................................ ................................ ................................ .......... 33
b. Measures of Exposure

................................ ................................ ................................ ........ 33

c. Measures of Effect

................................ ................................ ................................ ............. 33
9. Endangered Species Assessments

................................ ................................ ......................... 33
10. Endocrine Disruptor Screening Program

................................ ................................ ........... 34
11. Preliminary Identification of Data Gaps

................................ ................................ ............ 34

a. Environmental Fate

................................ ................................ ................................ ............ 34
b. Effects

................................ ................................ ................................ ................................ 37
12. References

................................ ................................ ................................ .......................... 51

### 3



# 1. Executive summary

The Environmental Fate and Effects Division (EFED) has completed the problem formulation for
the ecological risk, environmental fate, endangered species, and drinking water assessments to be conducted as part of the registration review of s pirodiclofen (BAJ 2740) . The problem formulation
describes the methods planned to be used during the completion of drinking water and ecological

r isk assessments in support of registration review and provide s an ove rview of the environmental fate, ecological effects , and potential risks associated with the use of s pirodiclofen as well as
uncertain ties unique to ris k assessment of s pirodiclofen . This document also identifies additional
studies that would be beneficial to the conduct of an ecological risk assessment to parent spirodiclofen and its degradation products

. Major environmental fate and ecological effects data
needs as well as uncertainties related to the assessment follow:

Environmental Fate Data Gaps

835.4200 Anaerobic Soil Metabolism

. No studies are available. EFED recommends that n ew studies be submitted.

835.4400 Anaerobic Aquatic Metabolism

. Only one water/sediment system is available. EFED recommends that the registrant select a n a dditional water/sediment system according to the 835.4400 guidance, and submit anaerobic metabolism data for that system . In the absence of data,
EFED will make conse rvative assumptions, based upon the overall behavior observed in the available study. A conservative 3x factor will also be added, since there is only one water/sediment system available.

850.6100 Environmental Chemistry Methods (ECM) and Independent Lab oratory Validation (ILV)

. Analytical methods for water for the parent compound and its major degradates (BAJ 2740

- enol, BAJ 2740

- dihydroxy, and BAJ 2740

- ketohydroxy) are needed. ECM/ILV studies are available for the analysis in soil, which are in review. The data gap will remain
unfulfilled until the available studies are reviewed.

Ecological Effects Data Gaps

850.2100 Avian acute oral toxicity test (with passerine species): Currently, there is only one acute oral study available for spirodiclofen whic h is conducted on the northern bobwhite quail

. An avian acute oral toxicity study with a passerine species is therefore a data gap. At the current maximum labeled rate of spirodiclofen (grapes, 0.53 lbs a.i/A, 1 application), the acute dose based RQ for small birds eating short grass already meets the endangered species LOC of 0.1. Therefore, an acute oral passerine study showing increased sensitivity to any degree would exceed the listed species LOC to a greater degree and would have the potential to ex ceed the acute restricted use
and acute non

- listed species LOCs. Please refer to Section 11 of this assessment for further
information.

### 4

850.1735. Whole Sediment Acute Toxicity Invertebrates, Freshwater 1
, 2 

### Currently, there is one chronic spiked water sed iment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius. Available data indicate that spirodiclofen has a high propensity to
bind to the sediment and is likely to affect the growth, development, and reproduct ion of arthropods via the inhibition of fatty acid biosynthesis. The available chronic sediment toxicity study

, however

, does not provide sediment or pore water concentrations, but only initial measured concentrations that were spiked into the overlying w ater. While it was stated by the registrant that this route of exposure offers the most realistic and conservative scenario (as midges would be exposed to parent spirodiclofen and its main degradate, BAJ 2770

- enol, in the sediment and pore

water ; see Sect ion 6 for more details), there were no analytical measurements in the pore water or sediment that provided an indication of what concentrations the organisms were actually exposed to. It was further contended by the registrant that parent spirodiclofen un dergoes a rapid
transformation in both the water column and sediment to the degradate BAJ 2740

- enol , which is shown in registrant submitted studies to be at least 2 orders of magnitude less toxic than parent spirodiclofen . In the available sediment toxici ty study with parent, however, there was 0% emergence in the three highest treatment concentrations (320, 560, and 1000 μg a.i/L) and below 50% emergence in the next two lowest concentrations (100 and 180 μg a.i/L). These results indicate that parent spir odiclofen can exhibit toxicity before its eventual transformation to BAJ
2740

- enol in the water column and/or sediment. EFED recommends a new study that provides analytical measurements for the sediment as well as pore water . As previously mentioned,

env ironmental fate data indicate parent spirodiclofen undergoes transformation to BAJ 2740

- enol relatively quickly and therefore a subchronic, 10

- day study is requested with the freshwater midge
Chironomus dilutus . While a protocol does not need to be submit ted, it is recommended that the spiked sediment system not be aged prior to initiation of the definitive test in order to capture any
toxic effects mediated by parent spirodiclofen.

850.1735. Whole Sediment Acute Toxicity Invertebrates, Freshwater 1
, 3



### . Cu rrently, there is
one chronic 28

- day spiked water sediment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius

. Per the discussion i n the preceding paragraph , a spiked sediment system for parent spirodiclofen wi th analytical measurements for sediment and
pore water is preferred for this study, rather than the spiked water system currently used in the
available study

. To examine the potential for differential sensitivities of aquatic insects and
benthic crustacea ns to spirodiclofen, a subchronic (10

- day) sediment study with the freshwater amphipod species Hyalella azteca is recommended

. As with the data gap discussed in the preceding paragraph, it is recommended that the spiked sediment system not be aged prior t o initiation of the definitive test in order to capture any toxic effects mediated by parent spirodiclofen

.

1 Also known as “Whole Sediment: Subchronic Freshwater Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecolo gical Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

2 A 10

- day study is requested as opposed to a chronic life cycle 60

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

3 A 10

- day study is requeste d as opposed to a chronic life cycle 42

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

### 5

850.17 40 . Whole Sediment Acute Toxicity Invertebrates, Marine 4
, 5 

### Currently, there is one chronic spiked water sediment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius. Per the preceding discussion

, a spiked sediment system for parent spirodiclofen with analytical measurements for sediment and pore water is preferred for this study,
rather than the s piked water system used in the available study. To examine the potential for differential sensitivities of aquatic insects and benthic crustaceans to spirodiclofen, a subchronic (10

- day) sediment study with the estuarine/marine amphipod species Leptocheir us plumulosus is
recommended to be requ ir ed. I t is recommended that the spiked sediment system not be aged prior to initiation of the definitive test in order to capture any toxic effects mediated by parent spirodiclofen.

850.1350: Mysid Chronic Toxicity Test

. A chronic life cycle toxicity test with the estuarine/marine invertebrate mysid shrimp was previously submitted and classified as unacceptable. The rationale was that the high solvent control mortality rate (56% of the solvent control group) confo unded the interpretation of the study. In the initial review of the study, it was stated that minimal exposure to the parent in the marine environment water column is expected as spirodiclofen has a very low solubility in water and partitions into the sed iment. Additionally, it was stated that a valid chronic study with the mysid shrimp with the BAJ

- 2740 enol degradate is available and exposure was more likely for this degradate. The Agency concluded that a repeat of the study with parent spirodiclofen w as not need ed.

More recently, a re

- examination of the chronic daphnia toxicity study calls into question the registrant’s earlier contention that parent spirodiclofen would not be available to elicit a toxic effect
in the water column. Available environme ntal fate data indicate that parent spirodiclofen has a hydrolysis half

- life at pH 7 of 30 days and an aerobic aquatic metabolism half

- life of 1

- 7 days. These data are corroborated by a chronic life cycle toxicity study with daphnia in which there were
si gnificant (p<0.05) decreases in mean length and mean dry weight at the highest treatment concentration (32.7 μg a.i/L) determined during the 21

- day study . Additionally, there was
determined to be a significant (p<0.05) decrease in the mean number of young per adult reproductive day in the two highest treatment concentrations (20.2 and 32.7 μg a.i/L). The primary degradate of parent spirodiclofen, BAJ

- 2740 enol did not exhibit similar effects at these concentrations (as its solubility is orders of magnitud e higher) and so these effects are attributed to parent spirodiclofen. As spirodiclofen has an insect growth regulator type mode of action via inhibition of fatty acid biosynthesis

, effects on growth and reproduction are anticipated in
freshwater and estu arine/marine invertebrates including crustaceans, which are closely related to
insects.

A new chronic mysid toxicity study is re commend ed s o the Agency can better understand what levels of parent spirodiclofen adversely impact estuarine/marine growth an d reproduction.

4 Also known as “Whole Sediment: Subchronic Marine Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

5 A 10

- day study is requested as opposed to a chronic life cycle 28

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

### 6

Special Study ( OECD TG 237 ) (Tier 1) : Honey Bee Larvae Acute Oral Toxicity (Tier I) 6 

### Acceptable acute contact and oral toxicity data are available for adult honey bee exposures to spirodiclofen; however, data are not available for larval toxicity. As the mode of action of spirodiclofen is documented be an insect growth regulator mediated by the inhibition of fatty acid biosynthesis, data are needed to characterize the toxicity of spirodiclofen to terrestrial invertebrates
in the larval s tage of the life cycle. An available semi

- field study conducted with the honey bee shows no significant effects to adult honey bees while brood development and colony strength are negatively impacted. These effects corroborate the premise that spirodicl ofen may have enhanced toxicity to larvae as compared to adult bees. No protocol needs to be submitted to the Agency
before the initiation of this study. Pending the results of this study, higher tiered ( e.g. semi

- field)
studies as well as residue stud ies may be required.

Special Study (Tier 1) : Honey Bee Larvae Chronic Oral Toxicity. Acceptable acute contact and oral toxicity data are available for adult honey bee exposures to spirodiclofen ; however, data are not available for larval toxicity. As the mode of action of spirodiclofen is documented be an insect growth regulator mediated by the inhibition of fatty acid biosynthesis, data are needed to characterize the toxicity of spirodiclofen to terrestrial invertebrates in the larval stage of the lif e cycle. An available semi

- field study conducted with the honey bee shows no significant effects to adult honey bees while brood development and colony strength are negatively impacted. These
effects corroborate the premise that spirodiclofen may have e nhanced toxicity to larvae as compared to adult bee s. EFED recommends that a protocol (following the OECD draft guidance document, November 25, 2013) be submitted for review and approval by the Agency prior to initiation of this study. Pending the result s of this study, higher tiered ( e.g. semi

- field) studies as well as residue studies may be required.

Special Study: Honey Bee Adult Chronic Oral Toxicity (Tier 1). Bees can be exposed to pesticides through multiple pathways including contact with spray s and dusts and through ingestion of residues in food/water ( e.g ., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed to residues in pollen and nectar either throug h direct contamination of these matrices by foliar sprays and/or dusts through translocation of residues via systemic transport of the active ingredient. Residues can in turn be brought back to bee colonies where in

- hive bees including young adult and dev eloping brood ( i.e ., eggs, larvae and pupae) may be exposed. EPA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended to facilitate screening for potential acute and chronic effects to individual adul t and larval bees. The
10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL)
and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Risk estimates
based on these data will be considered alon g with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level. EFED recommends that the registrant
submit a protocol and consult with the Agency prior to study initiation.

Special Study : Field Trial of Residu es in Pollen and Nectar (Tier 2) : Submission of studies for crops of concern that evaluate residue in plant parts ( e.g. pollen and nectar) may be of high

6 Depending on the desi gn of the “Honey Bee

– 21

- day repeated dose chronic larval toxicity,” study, a 72

- hour LD 50 value may be derived from this study. If that is possible, it would obviate the need for this study.

### 7

value depending on the results of the screening level risk assessment and the Tier I larval bee
toxi city study. If refinements to the screening level risk assessment for honey bees are needed, these studies will allow for a more refined exposure analysis when applications are made at bloom.

T his chemical is of low toxicity to adults, but applications a t bloom could contaminate pollen and nectar that adult foragers bring back to the colonies , resulting in potential expos ur e s to the brood. In order to evaluate this exposure pathway, these residue studies would assess spirodiclofen residues in pollen and nectar. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Special Study: Semi

- Field Testing for Pollinators (Tunnel or Colony Feeding Studies) (Tier 2). Screening level and refined Tier 1 risk assessments with the honey bee larvae may indicate the need to progress to higher tier toxicity testing under semi

- field conditions . In evaluating the effects of spirodiclofen on honey bees at the colony level, there are uncertainties relating to the grow th and reproduction of the colonies and measurement endpoints that relate to brood development and production. Semi

- field testing data can be used to address these uncertainties with either a tunnel or colony feeding study experiment design. EFED recomme nds that the registrant submit a protocol and consult with the Agency prior to study initiation.

850.3040: Field Testing for Pollinators (Tier 2 or 3) : Screening level and refined Tier 1 risk assessments with the honey bee larvae may indicate the need to progress to higher tier toxicity testing under field condition s

. In evaluat ing the effects of spirodiclofen on honey bees at the colony level , t he re are uncertainties relat ing to the growth and reproduction of the colonies and measurement endpoints that r elate to brood development and production. Field testing data can be used to address these uncertainties. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Uncertainties

Degradates of Spirodicl ofen

The absence of full environmental fate information about the degradates of parent spirodiclofen constitutes an uncertainty at this time. As will be discussed later, registrant

- submitted studies are
available to characterize the toxicity for certain transformation products of spirodiclofen with some having more complete data sets than others. The degradate BAJ

- 2740

- enol has several studies submitted for aquatic taxa while BAJ

- 2740

- ketohydroxy studies are available for birds. ECOSAR (v1.1) analysis w as used to supplement the toxicity database for these degradates. There is uncertainty inherent in all ECOSAR estimates because some ECOSAR classes hav e more data points than others (refer to section entitled “ Determination of Spirodiclofen Residues of Ec ological
Concern ”). Based on the analysis in that section, only parent spirodiclofen will be included in the expression of the toxic residues of ecological concern. Based on the analysis provided by HED, both parent spirodiclofen and three major degradat es (i.e., spirodiclofen

- enol, spirodiclofen

dihydroxy, spirodiclofen

- ketohydroxy , also known as BAJ 2740

- enol, BAJ 2740

- dihydroxy, and
BAJ 2740

- ketohydroxy, respectively ) will be included in the expression of the total toxic residues of drinking water.

### 8

E xtent of Toxicity to Larval and Juvenile Honey bees

Currently, there are data available that characterize the acute contact and acute oral toxicity of spirodiclofen to adult honey bees. As will be discussed in this assessment, spirodiclofen has an
insec t growth regulator type mode of action mediated by inhibiting the synthesis of lipids. Currently available non

- guideline studies conducted on non

- Apis terrestrial invertebrates corroborate the suggestion that larval and juvenile insects are more sensitive to spirodiclofen exposure than adults. Further toxicity data is needed to characterize this uncertainty.



# 2. Introduction

Spirodiclofen [CAS name: 3

- (2,4

- dichlorophenyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl 2,2

- dimethylbutanoate ; IUPAC name: 3

- (2,4

- dichloroph enyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl 2,2

- dimethylbutyrate ; CAS number 148477

- 71

- 8 ; PC Code 124871 ; and molecular formula
C 21 

### H 24 

### Cl 2 

### O 4 

### ], is an miticide/acaricide that inhibits lipid synthesis (IRAC 7 

### G roup 23). It is of the
tetronic and tetramic acid de rivative class of chemicals along with the active ingredients

sp i r otetramat and spiromesifen , all of which share the same mode of action

. It reportedly works by contact with mite eggs, and all nymphal stages

, and has insect growth regulator action by way of inhibiting lipid synthesis

. Furthermore, the European Food Safety Authority (EFSA) document

“ Peer Review of the Pesticide Risk Assessment of the Active Substance Spirodiclofen 8 

### ,” states that, “ spirodiclofen is an insecticide/acaricide with an insect gr owth regulator related mode of action. Hence it is expected that larval stages of insects and mites are particularly sensitive to spirodiclofen.”

EFED evaluated the systemicity of spirodiclofen relative to other members of the class, spiromesifen and sp irotetramat, in a memo entitled “Response to Registrant Submission on Systemic ity of Keto

- enols Spiromesifen.” (D385088, D384526, 04/04/11). In this memo, EFED and HED weighed registrant submitted data suggesting that spirotetramat is more readily
translo cated through plants due to its lower Log K OW 

### as well as its propensity to dissociate into a weak acid. Spirodiclofen is associated with a markedly higher Log K OW 

### than spirotetramat (5.83 for spirodiclofen vs 2.7 for spirotetramat) as well as a lower prop ensity to dissociate into a weak acid. Plant uptake studies of radiolabelled chemical showed no movement of spirodiclofen within the plant after 6 days post

- treatment whereas an extensive amount was found for spirotetramat. Despite this finding, a semi

- f ield study conducted with spirodiclofen on apples showed effects to brood development and colony strength and therefore it was determined that residues remaining on foliage after bloom would still pose risk to honey bee populations presumably to residues b eing
returned to the hive

.

EFED evaluated the most recent ecological risk assessments for spirodiclofen in association with the updated toxicity, exposure, and usage information to determine if sufficient data are available

7 Insecticide Resistance Action Committee ( http://www.irac

- online.org/ ).
Classification available at http://www.irac

- online.org/documents/moa

- classification/?ext=pdf (accessed September,
201 4)

8 Peer Review of the Pesticide Risk Assessment of the Active Substance Spirodiclofen. EFSA Scientific Report (2009) 339, 1

- 86. Available online at: http://www.efsa.europa.eu/en/efsa journal/doc/339r.pdf

### 9

and if further updates are need ed to support registration review. I n addition, EFED considered the latest Agency science policies and risk assessment methodologies. The structure of spirodiclofen

, as well as the chemical names and other identifiers can be found in the chemical identit y table
attached to this document which also includes the various degradation products of spirodiclofen ( Appendix A )

.



# 3. Use Characterization

There is one technical and one active Section 3 label for spirodiclofen. The sole end

- use product (Envidor® 2 SC) is a suspension concentrate product. The following are spirodiclofen’s uses : avocado, black sapote, canistel, mamey sapote, mango, papaya , sapodilla, star apple, citrus (crop group 10 that includes orange, grapefruit, lemon, lime, calomodin, citrus citron, citrus hybrids, kumquat, mandarin, pummelo, and Satsuma mandarin), grapes, hops, pome fruit (Crop Group 11)

, stone fruit (Crop Group 12 that includes apricot, cherry, nectarine, peach, plum, plumcot, and prune), tree nuts (Crop Group 14 includes almond, b eech nut, brazil nut, butternut, cashew, chestnut, chinquapin, filbert, hickory nut, macadamia nut, pecan, pistachio, and walnuts), and on Christmas tree plantations. According to the Screening Level Usage Analysis (SLUA) for spirodiclofen , dated August 2 5, 2014 , the top five crop uses for the chemical are oranges, grapes, grapefruit, almonds, and apples . The SLUA covers the years 200 3

- 20 10

. The spirodiclofen BEAD Chemical Profile (BCP) drafted by the Biological and Economic Analysis Division (11/06/2014 ) indicates that spirodiclofen usage in terms of pounds a.i applied rose steadily after registration in 2005 to peak in 2010 and declined in 2011 and 2012. Of the five highest crop uses for spirodiclofen, grapefruit represent the highest percent crop trea ted with 50% of the total acreage of grapefruit being applied with spirodiclofen.

Spirodiclofen can be applied via ground application or aerially for sit es that include avocado and Christmas trees. Ground airblast sprayers are permitted for the citrus an d hop uses. Application rates of spirodiclofen vary by use but range from 0.19 to 0.53 lbs a.i/A with all uses having only one application per crop season

. EFED will use application scenarios that result in maximum exposure scenarios for a given use for the risk assessment . Any absence of information on the
labels that specifies the maximum single application rate, the application interval, the annual maximum rate allowed (lbs a.i./year), or application method may result in conservative assumptions

.

It is noteworthy that the spirodiclofen label has language indicating that the chemical is toxic to honey bee larvae through direct contamination of pollen and nectar , and prohibits appl ication of spirodiclofen to blooming, pollen

- shedding, or nectar

- producin g parts of plants if bees forage on
the plants.



# 4. Conclusions from Previous Risk Assessments

This problem formulation updates conclusions from r ecent risk assessments

, includ ing the following:

### 10

 Use of Spirodiclofen on stone fruits, pome fruits, citrus, and tree nut crops (New
Chemical Assessment

– D300903, D293789, D284995, D309421, March 9, 2005)

 Use of Spirodiclofen on Christmas Trees and Hops (D346338 and D346339

– November, 2007)

 Proposed Rate Change of Spirodiclofen on Grapes (D358807

– December 2008)

 U se of Spirodiclofen on Tropical Fruit (D361072

– October 2009)

 Use of Spirodiclofen on Bushberry subgroup 13

- 07B (IR

- 4) (D373475

– August 2010)

 Use of Spirodiclofen on Tropical Fruits (IR

- 4) (D387358

– April, 2011) (this assessment covered additional trop ical fruits than those assessed in 2009)



## a. Ecological Risk Assessment

The Agency has conducted multiple ecological risk assessments on spirodiclofen that serve as a
basis for this preliminary problem formulation

, that are provided in the list above. The primary
risk of concern, as identified by the previous assessments, was for chronic risk to mammals. Previous risk findings are summarized in Table 1

.

Table 1 . Summary of Risk Concerns Identified for Spirodiclofen in Previous Assessments

Birds Mammals Te rr.

Plants Terr.
Inverts Fish BCF Aquatic
Inverts Aquatic

Plants Groundwater

Contamination Persistence Degrad at es of
Concern 6

No Yes 1 No 2 NA 7 No NA 3 No No No 4 Yes 5 BAJ 2740

- enol, BAJ
2740

- ketohydroxy,
BAJ 2740

- dihydroxy 1 Chronic RQs exceeded LOC for al l uses
2 Toxicity data for the most sensitive monocot from the seedling emergence study and most sensitive dicot from the vegetative vigor study were not available. Th ese data ha ve since been submitted and determined to be acceptable

. 3 Log K OW of 5.8

. BCF = 166 L/kg for edible tissue

. 62% of the recovered in edible tissue at Days 21 was identified as spirodiclofen enol. 66 % of residues in fish had depurated after Day 1 and 9 7 % after 13 days , indicating a strong potential for bioaccumulation

. 4 Based o n parent spirodiclofen’s low solubility (50 μg/L) and high K OC (values ranging from 51,000

– 101,000)
5 Spirodiclofen shows moderate persistence (weeks to months) under most testing conditions with the exception of
aerobic aquatic metabolism ( half

- life = 1

- 7 days)

. 6 These degradates were consider ed stressor s in previous drinking water assessments but not in the ecological risk

assessments

. T hese degradates were identified by the Health Effects Division (HED) Metabolite Assessment Review Committee (MARC) a s being spirodiclofen residues of toxicological concern for human health (Petition No. 2F6469. D285047)

. 7 Although RQs were not previously calculated for terrestrial invertebrates, impacts to honey bees have been previously indicated in spirodiclofen risk assessments.

“ Yes ” = at least one LOC has been exceeded in previous assessments; “ No ” = LOCs have not been exceeded in previous assessments ; “ NA ” = RQs have not been calculated previously.



## b. Drinking Water Exposure Assessments

The most recent Tier 1 drink ing water exposure assessment (DWA) was conducted in 2011 (USEPA 2011)

, for the proposed IR

- 4 new use on tropical fruits. This assessment referred to the

### 11

drinking water assessment conducted in 2005 ( USEPA 2005 ) for the initial registration of spirodiclofe n , and relied on a simulated the labeled application rate of 0.53 lbs a.i

. /A , which was
both the maximum s ingle application rate and the maximum application rate per crop season. Although the proposed application rate for grapes was higher, the Florida ci trus scenario resulted in the highest estimated acute drinking water concentration ( EDWC )

-- 23.9 μg/L as a peak
concentration in surface water using the Tier I PRZM/EXAMS model . Non

- cancer and cancer chronic EDWCs were 4.99 and 1.67 μg/L, respectively ( Tab le 2) . The Tier I SCI

- GROW model
used in generating ground water concentrations based on the highest proposed application rate (0.53 lbs a.i/A) resulted in an estimated concentration of 0.43 μg/L for both acute and chronic

exposures. T hese concentrations represent the total residues of parent spirodiclofen and the degradation products of BAJ 2740

- enol, BAJ 2740

- ketohydroxy, and BAJ 2740

- dihydroxy. As noted above, t hese degradate s , along with the parent, have been identified as the residues of toxicologic al concern for human health

.

Table 2 . Tier I EDWCs for human health drinking water risk assessment for spirodiclofen
, residues of toxicological concern

Stressor Acute EDWC
Surface Water
PRZM/EXAMS (ppb) Chronic EDWC

Surface Water
PRZM/EXAMS (ppb)* Acu te and Chronic
EDWC Ground Water
SCI

- GROW (ppb)* Non

- cancer Cancer

chronic Total residues (parent spirodiclofen,
BAJ

- 2740

- enol, BAJ 2740

- ketohydroxy, and BAJ 2740

- dihydroxy 23.9 4.99 1.67 0.43

* Results presented in ppb of total residues of spirodic lofen , as opposed to ppb of parent equivalent.



## c. Clean Water Act Programs

Spirodiclofen is not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. No Total Maximum Daily Load (TMDL) crit eria have been developed for spirodiclofen (at http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885



### ,
access ed 09/26 /2014)

. Aquatic benchmarks have not been established for spirodiclofen , based on
information available at http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benc hmark.htm (accessed 0 9/26 /2014) . Any data submitted or otherwise located as part of the registration review process may be used to update aquatic life benchmarks if applicable.



# 5. Environmental Fate and Transport

Spirodiclofen has a low solubility in wate r at pH 4 (50 ug/L) . Since spirodiclofen is unstable in aqueous solutions with pH > 4 , no water solubility data could be obtained with pH > 4. The low solubility of spirodiclofen is one of the indicators of a low potential for leaching. The vapor

pressu re (5.25 × 10

- 9 

### torr at 25°C) indicates spirodiclofen is relatively non

- volatile , and the Henry’s

L aw C onstant ( 2.4 × 10

- 8 

### atm

- m 3 

### /mol) indicates spirodiclofen is expected to be relatively non

-

### 12

volatile from water or moist soil surfaces. The log Kow is 5.83 at pH 4, indicating a strong potential for bioaccumulation. From the environmental fate data, there appears to be a differential rate of degradation of parent spirodiclofen in abiotic vs. biotic systems. This is evidenced by a relatively stable 31 day h ydrolysis half

- life (in an abiotic system) as compared to aquatic metabolism and acute and chronic toxicity studies where the rate of degradation was much faster.

T he structure and physicochemical properties of spirodiclofen relevant to the environment are summarized in Table 3

.

Table 3 . Basic Physical and Chemical Properties of Spirodiclofen.

Properties Values Source of
Information
Chemical Structure

Product Chemistry
Review
4/20/05

Molecular formula C 21 H 24 Cl 2 O 4 Product Chemistry
Review
4/20/05 Chemical Name 3

- (2,4

- dichlorophenyl)

- 2

- oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

- 4

- yl

2,2dimethylbutyrate Molecular Weight 411.3 g/mol
CAS Number 148477

- 71

- 8

SMILES String O=C1C(=C(C2(O1)CCCCC2)OC(=O)C(C)(C)CC)c1c(cc(cc1)Cl)Cl EPI Suite

Water Solubility 5 0 ug/L (pH 4 and 20°C) Product Chemistry
Review
4/20/05 Vapor Pressure 2.25xl 0

- 9 torr (20°C)
5.25xl 0

- 9 torr (25°C)

Henry's Law Constant 2.4x l0

- 8 atm

- m 3 /mol (20°C) Calculated
from VP and
WS

Log Kow ( n

octanol

– water partition coefficient) 5.83 at 20°C and pH 4 Product Chemistry
Review
4/20/05



### Laboratory studies have shown that spirodiclofen degrades through a combination of biotic and
abiotic reactions and is moderately persistent in the environment . Under acidic conditions the compound is relat ively stable, but is readily hydrolyzed under alkaline conditions with a half

- life of approximately 5 days at pH 9. Spirodiclofen has been shown to biodegrade with half

- lives ranging from 10 days to approximately about 2 months in soil under aerobic condi tions employing four soils from California, Florida and Germany. Photodegradation on soil surfaces was shown to be insignificant for spirodiclofen applied to a sandy loam from California when irradiated with a xenon arc lamp over the course of 15 days. H owever, in sterile pH 4 buffer solutions, the half

- life of spirodiclofen is 14 days when continuously irradiated with a xenon arc lamp for 12 days

### 13

(equivalent to environmental half

- life of 44 days in Arizona and 62 days in Canada) , which suggests the relat ively low potential for photolysis of spirodiclofen in sunlit surface waters.

Spirodiclofen initially degrades to BAJ 2740

- enol and, then, to several other metabolites. Although information regarding the degradation kinetics of these metabolites is incom plete, available data suggest that these compounds may be slightly more persistent than the parent compound and have greater mobility in soils than spirodiclofen

. T able 4 summarizes the major environmental fate studies conducted in the laboratory for spiro diclofen.

Table 4 . Summary of environmental fate and transport properties of spirodiclofen

Property Value Reference

Hydrolysis half

- life pH 4 pH 7 pH 9 63 days 31 days 5 days MRID 45697217

Aqueous photolysis half

- life 13.7 days (artificial light) 43.8 days (Phoenix, AZ

– estimated environmental photolysis half

- life ) 61.6 days ( Edmonton, Canada

– estimated environmental photolysis half

- life) MRID 45697218

Soil photolysis half

- life Stable MRID 45697230

Aerobic soil metabolism
half

- life (All studies conducted at 20 degrees Celsius) 63.9 days (Hesperia fine sandy loam from California) 16.8 days (Winder fine sand from Florida) 23.8 days (Loamy sand from Germany) 10.0 days (Silt from Germany) 24.4 days (Sandy loam from California) MRID 456 97204; 45697206; 45697228;

Aerobic aquatic half

- life 3.7

- 13.4 days in German total pond and lake

water/sediment system s MRID 45697205

Anaerobic aquatic half

- life 40.4 days (total sediment/water system from lake in CA) MRID 45697212

Adsorption co efficient

K oc 75,019 German Sandy loam 51,097 German silt loam 61,338 California loam 101,366 Texas clay loam Average K oc : 72,248 MRID 45697219

Bioconcentration factor (BCF) 699 (whole fish) 1,439 (non

- edible tissue) 166 (edible tissues) MRID 45697002



## a. Transformation Products

S pirodiclofen, applied at 0.0025 mg a.i./mL, had hydrolysis half

- lives of a pproximately 63, 31, and 5 days at pH 4, 7, and 9, respectively (MRID 45697217). The sole major degradation product

### 14

observed was BAJ 2740

- enol. Spirodiclofen undergoes an ester clearage of the side chain in hydrolysis to form the tetronic acid (BAJ 2510; BAJ 2740

- enol metabolite). No other major hydrolysis products were identified. Continuous irradiation of spirodiclofen, applied at 0.0025 mg

a .i./mL in sterilized pH 4 buffered solution for 12 days, resulted in a photodegradation half

- life of approximately 13.7 days. Under these conditions, 24 hours of irradiation using the xenon arc lamp source was reported to be equivalent to 3.2 days of natu ral sunlight for the month of June in Phoenix, Arizona (33.26 o 

### N), and 4.5 days in Edmonton, Alberta, Canada (53.33 o 

### N). Thus, the predicted environmental phototransformation half

- lives of spirodiclofen in Phoenix and Edmonton were 43.8 and 61.6 days, res pectively. BAJ 2740

- enol and BAJ 2740

- dioxoketone, were identified as the primary degradation products in the photolysis study (MRID 45697218). The parent compound undergoes a n enol cleavage to produce BAJ 2740

- enol (BAJ 2510), which in turn degrades t o BAJ 2740

- dioxoketone via a photolytic cyclization. The half

- life of spirodiclofen applied to a sandy loam soil from California following continuous irradiation with an artificial light source was greater than the dark control (MRID 45697230). Therefore, it was concluded that direct photolysis on soil surfaces is not an important environmental fate process for spirodiclofen.

Under aerobic conditions, spirodiclofen degraded in a sandy loam from Fresno, CA and a sand from Vero Beach, FL with half

- lives o f 63.9 and 16.8 days, respectively, while in loamy sand from Germany and silt soil from Germany, the half

- lives were 23.8 and 10.0 days, respectively. All of
the aerobic soil metabolism studies were conducted at 20 o 

### C (MRIDs 45697204, 45697208).
Carbon di oxide and five nonvolatile transformation products, including BAJ 2740

- enol, BAJ
2740

- lactide, BAJ 2740

- ketohydroxy, BAJ 2740

- dihydroxy, and 2

, 4

- dichlorobenzoic acid, were
identified as metabolites. The BAJ 2740

- enol and BAJ 2740

- ketohydroxy were major

tr ansformation products in all four soils. The dihydroxy was a major transformation product in the sandy loam, and 2

, 4

- dichlorobenzoic acid was a major product in the sand from Florida. A
transformat ion pathway was proposed ( Figure A.1 in A ppendix A ) where by ester cleavage of the side yields the enol (BAJ 2510, maximums of 17.5

- 51.9% of the applied), with subsequent oxidation of the dihydrofuranon ring yielding the ketohydroxy (maximums of 10.6

- 44.4%). The ketohydroxy can either be reduced to form the dihy droxy (maximums of 1.0

- 16.7%) or be rearranged to form the lactide (maximums of 0.4

- 3.0%), with the latter reaction influenced by pH.
2

, 4

- Dichlorobenzoic acid ( m aximums of 2.1

- 39.6%) could be formed from either the ketohydroxy, the dihydroxy or the lactid e, with ultimate formation of CO 2 

### (maximums of 22.5

- 93.1%) upon cleavage of the dihydrofuranon ring.

I n aquatic systems, spirodiclofen dissipated with half

- lives of about 1

- 7 days in natural water/sediment mesocosms under aerobic conditions (MRID 4569720 5) and approximately 40 days in mesocosms when maintained under anaerobic conditions (MRID 45697212). In each case, the major degradation product was BAJ 2740

- enol. All the major degradates detected in the fate
studies are summarized in Table A

- 1 (see Ap pendix A )

.

In addition to the investigation of the fate of parent compound in the studies summarized above,
additional studies were conducted to monitor the fate of three major degradates ( BAJ 2740

- enol

, BAJ 2740

- dihydroxy , and BAJ 2740

- 2,4

- dichlorobenzoi c acid ) in the laboratory

.

The transformation product BAJ 2740

- enol was studied in unfiltered and unsterilized Rhine River water (pH 7.4), at a concentration of 0.15 mg a.i./mL, under continuous irradiated using a UV

-

### 15

filtered xenon arc lamp for 24 hours a t 25 ± 1 o 

### C (MRID 456 9 7227). The enol metabolite appeared to be relatively nonpersistent because BAJ 2740

- enol degraded with a half

- life of 7.53 hours in the aqueous photolysis study

. Since 24 hours of natural sunlight (June) in Phoenix, Arizona (33.26 o



### N ) was reported to be equivalent to 7.38 hours of artificial light or 5.24 hours of artificial light for Edmonton, Alberta, Canada (53.33 o 

### N), the predicted environmental phototransformation half

lives of BAJ 2740

- enol in Phoenix and Edmonton were approxima tely 1 and 1.4 days, respectively.
BAJ 2740

- enol photodegrades to BAJ 2740

- dioxoketone via cyclization and loss of a chlorine

atom. One major degradate (BAJ 2740

- dioxoketone) was detected with the maximum
concentration of 26% at 24 hours. The relatively short half

- life could be attributed to photolysis
and metabolism because the river water was neither filtered not sterilized.

The transformation product BAJ 2740

- dihydroxy was studied in silt loam soil (pH 6.9

- 7.9, organic carbon 0.69%) from Germany at 20 o 

### C (MRID 45697226) . The half

- life was 49.9 days

. The temperature corrected half

- life at 25 o 

### C was 35.3 days. BAJ 2740

- diohydroxy was also studied in
two additional soils at 20 o 

### C . The half

- lives were 19.8 and 15 days in silt from Germany and silty clay loam from Spain, respectively (MRID 45697215). No major degradates were detected in all
three soils.

The transformation product BAJ 2740

- 2,4

- dichlorobenzoic acid was studied in three soils (MRID 45697224) . Half

- lives were 12.1, 13.9, and 4.4 days in s and from Florida, sa ndy loam from Italy, and silt from Germany, respectively. No major degradates were detected in all three soils.



## b. Transport and Mobility

Spirodiclofen is expected to be immobile in soil surfaces based on Koc values in the range of
51 ,000 to 101,000 measured in 4 soils (MRID 45697219). The degradation products BAJ 2740

- enol, BAJ 2740

- dihydroxy, and 2

, 4

- dichlorobenzoic acid were all shown to have much greater mobility than the parent compound. In adsorption/desorption studies using sa ndy loam, clay loam, sand, and silt soils, the transformation product BAJ 2470

- enol was very highly mobile (average Koc 18) , BAJ 2740

- dihydroxy (average Koc 71) was highly to very highly mobile, and 2,4

- dichlorobenzoic acid (average Koc 10) was very highl y mobile (MRIDs 45697213, 45697214

, and
45697223 ; US EPA. 2006 )

.

Due to the unstable nature of BAJ 2740

- ketohydroxy in the 0.01 CaCl 2 

### solution, batch equilibrium studies could not be conducted. However, the study author still reported an average Koc of 76 (MRID 45697225). Additionally, estimations of adsorption coefficients in soil using a HPLC
method determined that spirodiclofen could be classified as immobile, BAJ 2740

- ketohydroxy was classified as having low to slight mobility, BAJ 2740

- dihydroxy as having had moderate mobility,
BAJ 2740

- dioxoketone as having was slightly mobile, and BA J 2740

- enol and 2

, 4

- dichlorobenzoic acid as having were very highly mobility.

Based on its vapor pressure and Henry’s law constant, volatilization from water and soil surfaces is not expected to be an important environmental fate process for spirodiclofen.

### 16



## c. Field Dissipation

Spirodiclofen applied at a target application rate of 0.543 kg a.i./ha to fields located in California, Florida, Washington, and Canada dissipa ted rapidly with a calculated half

- life in the range of 3

- 5 days for each study (MRIDs 45697207, 45697208, 45697209, 45697210). Major transformation products detected were BAJ2740

- enol (all test sites), BAJ 2740

- ketohydroxy (Florida, Washington, and Ontar io test sites), 2,4

- dichlorobenzoic acid ( California, Washington, and Ontario test sites), and BAJ 2740

- dihydroxy (Florida test site). Spirodiclofen and its transformation products were not detected below the 0

- 15 cm depth, except for single detections
of BAJ 2740

- dihydroxy at the Florida test site and 2

, 4

- dichlorobenzoic acid at the California test site, each in the 15

- 30 cm soil depth.



## d. Bioaccumulation

Due to its e x tremely high oc tanol water partition coefficient (Log K ow 

### 5.83), spirodiclofen is
expect ed to bioaccumulate in fish. This prediction was supported by the results in the fish bioaccumulation study (MRI D 45697205). The maximum bioconcentration factors (BCF) for total
recovered radioactive residues were 699 for whole fish, 1, 439 for non

- edible tissue, and 1 66 for
edible tissues. These bioconcentration factors are lower than would be predicted based on spirodiclofen’s K OW 

### alone. I n the edible tissue, spirodiclofen was not detected. The transformation product spirodiclofen E nol (BAJ 2510) was 62.4% of the recovered (0.81 mg/kg);
4

- OHax

- Enol was 19. 2 % of the recovered (0.25 mg/kg), and 4

- OHeq

- Enol (which is an isomer of
4

- OHax

- Enol ) was 14.3% of the recovered (0.1 9 mg/kg) . In the non

- edible tissues, spirodiclofen was 0.3% of the recovered (0.04 mg/kg), 4

- OHax

- Enol was 36.0% of the recovered (4.46 mg/kg), Enol (BAJ 2510) was 27. 6 % of the recovered (3.4 2 mg/kg), and 4

- OHeq

- Enol was 22. 4 % of the recovered (2.77 mg/kg). Depuration was rapid. After 1 day of depuration, total r esidues in whole
fi sh tissues had decreased by 66% . After 13 days of depuration, total residues had decreased by
97%.



# 6. R eceptors

As described in the Agency's Overview Document (U.S EPA, 2004), the most sensitive endpoint for each taxonomic group will be used to calculate ri sk quotients (RQs). Assessment endpoints include direct toxic effects on the survival, reproduction, and growth of terrestrial and aquatic life as well as indirect effects such as reduction in prey base and/or modification of habitat. Acute and
chronic t oxicity data from studies submitted by pesticide registrants along with the available open literature are used to evaluate the potential direct effects of spirodiclofen to the aquatic and terrestrial receptors identified in this section. This includes toxi city data on the technical grade active ingredient, degradates, and when available, formulated products. The open literature studies are identified through EPA's ECOTOX database ( http://cfpub.epa.gov/ecotox/ ), w hich employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and
wildlife.

### 1 7



## a. Effects to Aquatic Organisms

A summary of the available ecotoxicity information and the incident information for spirodiclofe n is provided below. Table 5 provides a summary of the taxonomic groups and the surrogate species tested to help understand potential acute and chronic ecological effects of spirodiclofen

. In addition, the table provides a preliminary overview of the pote ntial acute toxicity of spirodiclofen by providing the acute toxicity classifications.

Spirodiclofen did not elicit a 50% mortality response in the freshwater and estuarine/marine fish
and invertebrate acute toxicity tests conducted up to the limit of s olubility ( 50 μg/L ). There were no mortalities or clinical signs of toxicity observed in any of the acute toxicity tests with the exception of one mortality each in the second lowest and second highest (mean measured 13 and 25 μg a.i/L treatment c oncentra tions, respectively). The pH level of the acute toxicity studies ranged from 6.0

– 8.0 and therefore methanol that was acidified with a low percent (2.5%) glacial acetic acid was used a solvent. The solvent was not reported to have an impact on the healt h of the test organisms in any study and was used to increase the analytical recovery of the test
substance. Also of note is an acute freshwater fish toxicity study with the bluegill sunfish tested with a formulation of spirodiclofen (22.2% purity). The formulation increased the solubility limit of spirodiclofen, although the study did not achieve a definitive LC 50 

### due to a lack of a 50% mortality response. The LC 50 

### was determined to be >58.3 mg a.i/L.

On a chronic exposure basis

, an early life stage st udy with the rainbow trout conducted under a
flow

- through system determined effects on length and weight at the highest treatment concentration (3.81 μg a.i/L). There were no significant effects on survival, percent hatched, or time to swim up nor were th ere any clinical signs of toxicity observed.

In a chronic life cycle study with freshwater invertebrates ( Daphnia magna ) conducted under a
flow

- through system , there was a significant (p<0.05) reduction in the mean number of young per reproductive day a t the two highest treatment concentrations (20.2 and 32.7 μ g a.i/L). Additionally, there were significant (p<0.05) effects on mean length and dry weight at the highest
treatment concentration. There are no chronic estuarine/marine fish or invertebrate st udies available for technical spirodiclofen.

A chronic, 28

- day study with the freshwater midge ( Chironomus riparius ) is available and conducted using a spiked water system. Percent emergence and mean developmental rate were
examined. The results ind icated that l ess than 50% emergence occurred at treatment
concentrations 100 μg a.i/L and above (initial nominal concentrations). T his initial nominal concentration was above the reported solubility limit of spirodiclofen . M ean measured
concentrations we re not reported and there were no reports of particulates or precipitates forming. There was 0% emergence in the three highest treatment concentrations (320, 560, and 1000 μg a.i/L, nominal). The mean developmental rate was not significantly impacted up to 180 μg a.i/L (nominal) beyond which there was 0% emergence. The review of the study noted that the analytical results indic a ted spirodiclofen rapidly bound to the sediment and/or underwent degradation. This statement corroborates o the r environmental f ate information that indicates spirodiclofen rapidly binds to the sediment (51

– 92% bound on Day 1 of the study) and then rapidly degrades (DT 50 

### or time to reach 50% degradation <12 days) to the BAJ 2740

- enol

### 18

degradate within the sedi ment layer. This deg radation was even faster in the overlying water where
the DT 50 

### of parent spirodicl ofen is less than one day.

Available vascular and non

- vascular aquatic plant studies indicate that TGAI and formulated spirodiclofen do not cause significant phytotoxic e ffects up to limit of solubility. These findings
are based on the results of tests on one vascular and one non

- vascular aquatic plant species.

T 

### able 5 . Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for Spirodiclofen

Taxonomic
Gr oup Study Type

- Test
Material Surrogate Species Toxicity Value 2 Acute Toxicity
Classification Source

(Classification)

Freshwater fish 1 Acute

-

TGAI Rainbow trout

( Oncorhynchus mykiss ) LC 50 = >35 μg/L

(N/A; N/A) Very highly

toxic 3 456 97001

(Acceptable)

Acute

- formulation Bluegill sunfish

( Lepomis
macrochirus ) LC 50 >58.3 mg/L

(N/A; N/A) Slightly toxic 45697009 (Acceptable)

Chronic (Early Life

Stage)

- TGAI Rainbow trout

( Oncorhynchus mykiss ) 97

- d NOAEC =

3.81 μg/L;
LOAEC = 1.95 μg/L (length and weig ht) -- 45697109 (Acceptable)

Freshwater
invertebrates Acute

-

TGAI Water Flea

( Daphnia magna ) 48

- hr EC 50 = >45.5

μg/L (N/A; N/A) Very highly

toxic 3 45697026

(Acceptable)

Acute

- formulation 48

- hr EC 50 >7.97 mg/L (N/A; N/A) Moderately

toxic 45697013

(S upplemental)

Chronic

- TGAI Water Flea

( Daphnia magna ) 21

- d NO A EC = 11

μ g/L ; LO A EC =
20 μ g/L (young per adult per reproductive day) -- 45697101 (Acceptable)

Estuarine/marine
fish Acute

-

TGAI Sheepshead Minnow

( Cyprinodon variegat u s ) 96

- hr LC 50 >35.2

μ g/L (N/A; N/A) Very highly

toxic 3 45697027

(Acceptable)

Estuarine/marine
invertebrates Acute

-

TGAI Eastern Oyster

( Crassostrea virginica ) 96

- hr LC 50 >43

μg/L (N/A; N/A) Very highly

toxic 3 45697019

(Acceptable)

Saltwater mysid ( Americamysis bahia ) 96

- hr LC 50 : >37

μg/L (N/A; N/A) Very highly

toxic 3 45697018

(Acceptable)

Sediment

Dwelling
Invertebrates Chronic

Spiked

water system

- TGAI Freshwater midge

( Chironomus riparius ) 28

- day NOAEC =

32 μg/L; LOAEC = 100 μg/L (emergence) -- 45697117 (Acceptable)

Aquatic plants and algae Vascular

-

TGAI Duckweed

( Lemna gibba ) 14

- day EC 50 =

>63.8 μ g /L

14

- d NOAEC = 63.8 μ g /L -- 45697028 (Acceptable)

### 19

Taxonomic
Gr oup Study Type

- Test
Material Surrogate Species Toxicity Value 2 Acute Toxicity
Classification Source

(Classification)

Non

vascular 2

- TGAI Freshwater Green

Algae ( Pseudokirchneriella subcapitata) 96

- hour EC 50 ( cell

density) > 60

μ g/L

96

- hr NOAEC =
60 μ g/L -- 45697005 (Acceptable)

Non

vascular 2

- formulation Freshwater Green

Algae ( Pseudokirchneriella subcapitata) 96

- hour EC 50 ( cell

density) >4.18

mg /L

NOAEC (growth
rate and cell density) = 2.26

mg / L -- 45697011 (Acceptable)

1 Freshwater fish may be surrogates for aquatic

- phase amphibians.

2 Concentrations expressed in terms of active ingredient ; (95% confidence intervals; slope) if available

3 Although the acute toxicity classification is “very hig hly toxic,” these studies did not elicit a 50% mortality response up to the limit of solubility. The classification is based on the standard EPA classification system for endpoint less than 0.1 mg a.i /L.



### Table 6 shows the results of available degradate toxicity studies of spirodiclofen

. Data are available only for BAJ

- 2740

- enol, which is considered to be the primary degradate of spirodiclofen in both aquatic and soil degradation pathways. In a freshwater fish study conducted at a single
concentratio n ( mean measured, 73 mg a.i/L), BAJ

- 2740

- enol exposure caused two mortalities in the exposure group and therefore did not elicit a 50% lethal effect. There were no clinical signs of toxicity noted in the study. Conversely, an acute toxicity study with Da phnia magna exposed
to BAJ 2740

- enol caused 0, 33, 43, 40, 37, and 43% mortality in the mean measured 3.2, 10, 18, 32, 56, and 100 mg a.i/L concentrations, respectively . Clinical signs of toxicity included some
individuals in all but the lowest treatment concentration ; some individuals were observed in an abnormal position at the bottom of the test chamber or had very little movement overall

.

A chronic freshwater fish early life stage test with the rainbow trout with BAJ

- 2740

- enol yielded

no treatment r elated effects on egg hatchability, survival, and fry growth up to and including the highest treatment concentration of 115 μg a.i/L. Similarly, a chronic fish full life cycle test with an estuarine/marine fish species (sheep s head minnow) yielded no treat ment related effects up to and including the highest treatment concentration (190 μg a.i/L). There were no clinical signs of toxicity were observed in either study. In a chronic life cycle test with a freshwater invertebrate, test organisms were exposed to BAJ

- 2740

- enol concentrations up to 56 μg a.i/L (nominal). Effects at this highest treatment concentration included significant (p<0.05) reductions in adult body length, number of neonates per adult, number of neonates per reproduction day

, and an
incr ease in adult mortality. There were no other clinical signs of toxi city observed in the study. In a chronic life cycle test with an estuarine/marine invertebrate, test organisms were exposed to
BAJ 2740

- enol concentrations of up to 11 mg a.i/L (mean meas ured). There was no effect on survival and growth (assessed by length and body weight for males and females) at any treatment concentration. There was a significant (p<0.05) reduction in reproductive success (defined as number of offspring p er female per reproductive day ) in the two highest treatment concentrations.

### 20

A 28

- day sediment toxicity test with the freshwater midge ( Chironomus riparius ) was conducted
with BAJ

- 2740

- enol in a spiked water system. There was 0% emergence in the three highest

treat ment concentrations (10, 32, and 100 mg a.i/L, nominal). As a result, the study could not provide mean developmental rate data.

In the initial review of the sediment toxicity study conducted on parent spirodiclofen , there were
several noted deficiencie s. First, the system used was spiked water and not spiked sediment. Additionally, sediment concentrations of parent spirodiclofen were not measured nor were the degradation products. Furthermore, it was determined via analytical measurements of the

over lying water that recoveries of parent spirodiclofen were 15% or nominal after Day 7 and less than 3% by the time of test termination at 28 days. As a result, it was not known from the provided
information at which concentrations that organisms in the sedi ment were exposed to, particularly in the first 7 days of the study. The registrant provided a response to these deficiencies and the call for a new spiked sediment system study with the following rationale as to why the spiked water study was more approp riate:

 Rapid decline of parent spirodiclofen occurs in the overlying water starting at Day 0

, driven by the high K OC 

### of the chemical and its propensity to bind to the sediment

.

 Rapid degradation of parent spirodiclofen to BAJ 2740

- enol in the sediment la yer indicates that midges were also exposed to BAJ 2740

- enol in the sediment layer throughout the 28

- day duration of the study

.

 The lower K OC 

### of BAJ 2740

- enol as compared to parent spirodiclofen (18 vs. 83261)
indicates BAJ 2740

- enol moves in and out of t he sediment layer and into the water phase throughout the course of the study.

 Parent spirodiclofen had a very low solubility (50 μg/L) as compared to BAJ 2740

- enol (6 g/L)

.

The registrant concluded that the water phase exposure at the water / sediment inte rface to the more toxic parent compound is greater in the spiked water system and would represent a worst case exposure scenario since the midges are exposed to both parent spirodiclofen and BAJ 2740

- enol in the sediment and the water column throughout the course of the study.

The Agency believes that because these sediment toxicity studies do not provide analytical measurements for sediment and pore water concentrations, the concentrations to which the test organisms were actually exposed are uncertain

. Additionally, it is evident from the available study with parent spirodiclofen that a toxic effect is elicited before the transformation to BAJ 2740

- enol ; there was 0% emergence of organisms in the three highest treatment concentrations (320, 560, and
10 00 μg a.i/L)

, and less than 50% emergence in the next two lowest concentrations (100 and 180 μg a.i/L). While the environmental fate data supports the contention that parent spirodiclofen transforms relatively quickly to BAJ 2740

- enol to some extent

, this study suggests that th e transformation occurs at a slow enough rate that allows the parent compound to elicit a toxic effect on the freshwater midge.

To better understand at which concentrations that the freshwater midge is impacted by parent spirodicl ofen, a new 10

- day study spiked sediment study with the freshwater midge Chironomus
dilutus that provide s analytical measurements of parent spirodiclofen in the sediment and pore

### 21

water is recommended . As environmental fate data indicate that parent spirod iclofen transforms relatively rapidly to BAJ 2740

- enol (aquatic metabolism half

- life of 1

- 7 days), a subchronic, 10

- day study is requested (OPPTS 850.1735). A protocol does not need to be submitted, but since EFED is interested in the impacts of spirodicl ofen in the sediment and pore water, it is requested that the test be initiated without prolonged aging or equilibrating spirodiclofen in the sediment

.

As noted above, 28

- day spiked water system studies with the parent and BAJ 2740

- enol are
available and as other water column toxicity studies indicate, BAJ 2740

- enol is several order s of magnitude less toxic than parent spirodiclofen. While data are available on one species ( Chironomus riparius ), additional sediment tests with freshwater and estuarine/mar ine benthic crustaceans ( i.e. Hyalella azteca and Leptocheirus plumulosus , respectively) would better characterize the effects of spirodiclofen across a broader taxonomic range as compared to the
standard water column tests.

A non

- vascular aquatic plant s tudy conducted with BAJ 2740

- enol yielded definitive endpoints to
be used for non

- listed species risk estimation but as there were significant (p<0.05) effects at all treatment concentrations for all endpoints assessed, a definit ive NOAEC could not be deri ved.

T he lowest treatment concentration ( 3.13 mg a.i/L ) resulted in reductions of 9.6 and 9.7% in biomass and cell density relative to the control

. As noted above, past modeling of p arent spirodiclofen resulted in a peak surface water EEC of 4.12 μg a.i/ L. As degradation of parent is expected in the aquatic media and would obviously result in concentrations less than that of parent (hydrolysis data indicate 52% maximum formation at pH 7, so a conservative estimate of 2.06 μg a.i/L)

, the separation of exp osure and effect level of BAJ 2740

- enol on freshwater green algae is expected to be several orders of magnitude. Despite a definitive NOAEC not being achieved, by assuming the LOAEC was the NOAEC (which would underestimate the toxicity), there would be

at least three orders of magnitude of separation in a conservative estimate of exposure and a potentially under conservative estimate of toxicity. It is noted that there is obviously inherent uncertainty in this statement as the relative toxicity cannot be precisely defined.

Table 6 . Summary of Endpoints from Aquatic Toxicity Studies for the Spirodiclofen Degradate BAJ

- 2740

- enol

Taxonomic Group (study type) Surrogate Species 1 Toxicity Value 1 Acute Toxicity
Classification Source

(Classification)

Freshwate r fish 2 (acute toxicity) Rainbow trout

( Oncorhynchus mykiss ) 96

- hr LC 50 = >73 mg/L

(N/A; N/A) Slightly toxic 45697015 (Acceptable)
Freshwater fish (chronic early life stage) 97

- d NOAEC = 115 μg/L; LOAEC = >115 μg/L -- 45697125 (Acceptable)

Freshwate r invertebrate (acute toxicity)
Water Flea

( Daphnia magna ) 48

- hr EC 50 = >100 mg/L

(N/A; N/A) Practically

non

- toxic 45697014

(Acceptable)

Freshwater
invertebrates (chronic life cycle) 21

- d NO A EC = 32 m g/L ; LO A EC = 56 μ g a.i. /L (mortality, adult body le ngth, time to first brood, number of young per adult, and number of young per reproductive day -- 45697126 (Acceptable)

### 22

Taxonomic Group (study type) Surrogate Species 1 Toxicity Value 1 Acute Toxicity
Classification Source

(Classification)

Estuarine/marine fish (chronic fish full life cycle) Sheepshead minnow

( Cyprinodon variegatus ) 11

- d NOAEC = 190 μg/L;

LOAEC = >190 μg/ L -- 45697102 (Acceptable)

Estuarine/marine
invertebrate (chronic life cycle) Saltwater mysid

( Americamysis
bahia ) 28

- d NOAEC = 3.0 mg/L;

LOAEC = 5.8 mg/L (reproductive success) -- 45697103 (Acceptable)

Freshwater sediment dwelling
invertebrate (Whole s ediment, chronic, spiked water system) Freshwater midge

( Chironomus riparius ) 28

- day NOAEC = 3.2 mg/L;

LOAEC = 10 mg/L (development rate and emergence) -- 45697022 (Acceptable)

Aquatic Plant (Algal toxicity) Freshwater Green

Algae ( Pseudokirchneriella

su bcapitata) 96

- hr EC 50 (cell density) = 66.3

mg/L

96

- hr NOAEC (cell density, growth rate, biomass) = <3.13

m g a.i/L -- 45697016 (Acceptable)

1 Concentrations expressed in terms of active ingredient

. 2 Freshwater fish may be surrogates for aquatic

- phase amphibians.



## b. Effects to Terrestrial Organisms

Terrestrial studies indicated a general lack of toxicity for birds (acute oral, sub

- acute dietary ) and mammals (acute oral ) with acute studies reaching non

- definitive endpoints. There were no
mortalities or c linical si g ns of toxicity that were observed in an acute oral toxicity study and two
sub

- acute dietary toxicity studies. In one avian reproduction study with the northern bobwhite quail, spirodiclofen exposure in the diet did not cause any reductions in g rowth or reproductive
parameter s even at the highest dose (691 ppm, mean measured). Additionally, there were no clinical signs of toxicity observed. Similarly, in the companion reproductive study conducted with the mallard duck, there were no significant (p>0.05) reductions in any growth or reproductive
parameter s even at the highest dose (734 ppm, mean measured) with no clinical signs of toxicity
observed.

An acute oral toxicity study with the Norway rat indicated that parent spirodiclofen was practical ly

non

- toxic, with no mortality or clinical signs of toxicity being observed. In a two

- generation reproduction study, spirodiclofen did not cause treatment

- related clinical signs of toxicity or mortality in parental male or female rats of either generatio n at all treatment groups. Mean body weights were significantly (p<0.01 or <0.05) decreased by 6

- 8% throughout the study in high

- dose F0 males. F1 males in the highest treatment group weighed 17

- 23% (p<0.01) less than controls throughout the study. Ev aluation of reproductive performance and function showed no treatment

related effects on the fertility index, gestation index, total number of pups born, number of stillbirths, post implantation loss or number of live litters produced in either generation, mean gestation interval, estrous cycle length, the number of females with prolonged or abnormal cycles, day of vaginal patency in F1 females, percent motile sperm or percent abnormal sperm in both generations, or testicular spermatid and e pididymal sperm count in high

- dose F0 males. The

### 23

NOAEL for this study based on parental body weight effects is 70 ppm (5.2

- 6.4 mg/kg bw/day for
males and 5.5

- 7.0 mg/kg bw/day for females).

A combination seedling emergence /vegetative vigor study is available for terrest rial plants. Ten plant species (4 monocot and 6 dicot species) were exposed to a single concentration of formulated spirodiclofen. For the seedling emergence component, ryegrass was the most sensitive monocot species based on effects on dry weight and he ight ; a most sensitive dicot species could not be determined due to lack of toxicity. For the vegetative vigor component, a most sensitive monocot species could not be determined due to lack of effects

, and turnip was identified as the most
sensitive dico t species based on effects to dry weight and height. F ollow

- up Tier II stud ies w ere conducted for ryegrass ( seedling emergence ) and turnip ( vegetative vigor ) . These studies definitive endpoints for use in terrestrial plant risk estimation.

A combination acute toxicity study to honey bees demonstrated that spirodiclofen was practically
nontoxic to adults on an acute contact and acute oral basis

, with a single mortality occurring at the highest treatment concentration in each component. This finding is ge nerally expected of an insect growth regulator type chemical such as spirodiclofen where the mode of action would be expected to have greater activity on larv al and juvenile bees. Similarly, a combination acute contact and acute oral study conducted with formulated spirodiclofen observed one mortality in each of the acute contact and acute oral components of the test.

In a 27

- day toxicity study, honey bees ( Apis mellifera ) were exposed to formulated spirodiclofen at 0 (control) and 0.13 lbs a.i/A applicat ion rates on apple tree foliage in tunnel cages. T he maximum single application rate for apples is approximately two

- fold higher than the assessed

rate. Bees were confined to the control and treatment plots to prevent bees from collecting nectar
from othe r sources. The colonies consisted of 3000

- 4000 worker bees with a queen. The apple trees were approximately 2 m. in height and approximately 50% of the blossoms were in bloom at the time of application. During the study, the temperature ranged from 18 t o 28°C, relative humidity ranged from 26 to 97%, and there was one precipitation event at 5 days post exposure. There were 40 trees in the control and in the treated group.

Six days after application the bee hives were removed from the tunnels and reloc ated to an
untreated area . T he bees were allowed to forage on natural food sources, and the development of
the colonies was further assessed. Treatment with formulated spirodiclofen did not affect adult
bees , based on lack of effects to mortality, foragi ng activity, nectar and pollen storage and egg

laying . C olony strength did appear to be influenced by the treatment as control/treatment densities at days 19 and 27, were 1890/1190 and 2940/980, respectively. Additionally, p upal abundance (brood developm ent) was adversely affected by treatment as control/treatment abundance at days

- 1, 4, 7, 12, 19 and 27, was 1855/1400, 1575/630, 1050/315, 490/140, 1400/490, and 2450/525, respectively. Larval abundance (brood development) also appeared adversely affec ted by
treatment as control/treatment abundance at days

- 1, 4, 7, 12, 19 and 27 was 350/420, 245/70, 210/35, 525/210, 595/315 and 560/350, respectively. These results would suggest that parent spirodiclofen under semi field conditions does not impact adult bees but does have effects on brood and larval development and abundance. These results corroborate the fact that spirodiclofen has insect growth regulator type activity.

### 24

Table 7 . Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studie s for Spirodiclofen

Taxonomic Group Study Type Surrogate Species Toxicity Value

2,3 Acute

Toxicity
Classification Source

(Classification)

Birds 1 Acute Oral Bobwhite quail ( Colinus virginianus ) LD 50 > 2000 mg/kg

- bw

(N/A; N/A) Practically

non

- toxic 4569 7004

(Acceptable)

Sub

- acute dietary LC 50 > 5000 mg/kg

- diet (N/A; N/A) Practically

non

- toxic 45697003

(Acceptable)

Chronic NOAEC = 691 ppm LOAEC = >691 ppm -- 45697104 ( Acceptable )

Mammals Acute Oral Laboratory rat ( Rattus norvegicus ) 14

- day LD 50 >2000

mg/kg bw (N/A; N/A) Practically

non

- toxic 45696616

(Acceptable)

Chronic NOAEL (decreased body weight and body weight gain in F 1 pups) = 70 ppm
LOAEL = 350 -- 45696802 (Acceptable)

Insects Acute

contact/oral
combination study

- TGAI Honey bee

( A pis mellifera ) (Adult honey bees) Contact LD 50 > 196

μg/bee (N/A; N/A)
Oral LD 50 > 200 μg/bee (N/A; N/A) Practically

non

- toxic 45697017

(Acceptable)

Acute
contact/oral
combination study

- formulation Contact LD 50 > 100 μg/bee (N/A; N/A)
Oral LD 50 > 100 μg/bee (N/A; N/A) Practically

non

- toxic 45697010

(Acceptable)

Acute

- TGAI Earthworm

( Eisenia fetida ) 14

- day LC 50 >1000

mg/kg dw soil -- 45697008 (Acceptable)

Acute

- formulation 14

- day LC 50 >1000 mg/kg dw soil -- 45697106 (Acceptable)

Terrestrial plants Seedling

Emergence/ Vegetative Vigor (Tier I) Seedling

Emergence Dicot

– None EC 25 > 0.36 lbs a.i/A

NOAEC = 0. 36 lbs
a.i/A

-- 45696925 (Acceptable) Seedling Emergence
Monocot

– Ryegrass EC 25 (dry weight,

height) <0.36 lbs a.i/A
NOAEC (dry weigh t, height) = <0.36 lbs
a.i/A

Vegetative Vigor
Dicot

- Turnip EC 25 <0.52 lbs a.i/A

NOAEC = 0. 52 lbs
a.i/A

Vegetative Vigor
Monocot

- None EC 25 >0.52 lbs a.i/A

NOAEC = 0.52 lbs
a.i/A Endpoint: N/A

### 25

Taxonomic Group Study Type Surrogate Species Toxicity Value

2,3 Acute

Toxicity
Classification Source

(Classification)

Seedling Emergence/ Vegetative Vigor (Tier II) Seedling

Emergence
Monocot

– Ryegrass EC 25 ( survival): 0.25 lbs

a.i/A
NOAEC = 0.14 lbs
a.i/A

-- 45697028 (Acceptable)

Vegetative Vigor
Dicot

- Turnip EC 25 > 0.55 lbs a.i/A

NOAEC (dry weight) =
0.27 lbs a.i/A

1 Birds represent surrogates for terres trial

- phase amphibians and reptiles.

2 Concentrations expressed in terms of active ingredient.

3 An N/A under endpoint means that there was not a most sensitive species tested.



### There are studies available with the degradation products of spirodiclofen ( Tab le 8) . In an acute oral toxicity study with the bobwhite quail exposed to BAJ 2740

- enol, there were no mortalities
observed even at the highest dose of 2000 mg a.i/kg

- bw. Seven of ten birds had diarrhea on Day 2, with no observances noted after Day 4 in the 1000 mg a.i/kg

- bw group. In the 20 0 0 mg a.i/kg

bw group, all birds were observed with diarrhea at Day 2 with no observances after Day 4. In
another acute oral toxicity study with the bobwhite quail exposed to BAJ 2740 4

- hydroxy

- enol,
there were no mor talities observed even at the highest dose of 2000 mg a.i/kg bw. Similar incidences and timing of observances of diarrhea occurred in this study as with the previously mentioned study conducted with BAJ

- 2740

- enol.

Table 8. Summary of Endpoints from Terre strial Toxicity Studies for the Degradation Products of Spirodiclofen

Taxonomic Group (study type) Degradate Surrogate Species Toxicity Value

(all units in terms
of measured active ingredient) 2,3 Acute

Toxicity
Classification Source

(Classification)

Bird s (Acute oral toxicity) 1 BAJ 2740

-

enol Bobwhite

quail ( Colinus virginianus ) LD50 > 2000

mg/kg

- bw (N/A; N/A) Practically non

toxic 45697111

(Acceptable)

BAJ 2740 4

- hydroxy

- enol LD50 > 2000 mg/kg

- bw (N/A; N/A) Practically non

toxic 45697112

(Acceptabl e)

Mammals (Acute oral toxicity) BAJ 2740

-

ketohydroxy Norway rat

( Rattus norvegicus ) 14

- day LD50 >2000

mg/kg

- bw Practically non

toxic 45696814

(Acceptable)

BAJ 2740

- enol 14

- day LD50 >300 mg/kg

- bw <500 mg/kg bw4 Moderately

toxic 45696815

(Acceptable)

Terrestrial
invertebrates (subchronic toxicity) BAJ 2740

-

enol Earthworm

( Eisenia fetida ) 14

- day LC50 >1000

mg/kg dw soil -- 45697007 (Acceptable)

BAJ 2740

- ketohydroxy 14

- day LC50 >1000 mg/kg dw soil -- 45697106 (Acceptable)

1 Birds represent surrogat es for terrestrial

- phase amphibians and reptiles. 2Range of numbers within parentheses refers to the 95% confidence limit of the point estimate value 3An N/A under endpoint means that there was not a most sensitive species tested.



### There are several non

- gu ideline beneficial insect studies available for spirodiclofen . They include laboratory acute contact toxicity tests , extended laboratory tests that include developmental and

### 26

reproductive endpoints, and field studies conducted in agricultural sites like ap ple orchards

. The field studies in particular assess the efficacy of spirodiclofen on the target pests while also examining the detrimental effects to beneficial insects that serve as predators for these pests. Notably, the semi

- field study conducted wit h honey bees found that while adults were not significantly impacted, bee brood development and colony strength were negatively impacted that corroborates the fact that spirodiclofen is an insect growth regulator

- type chemical. These results
are summarize d below in Table 9

.

Table 9

. Summary of Studies Conducted on Non

- target Terrestrial Invertebrates with formulated Spirodiclofen Study type ( test material ) Test Species Results synopsis MRID (Classification)

Semi

- field study Honey bee

( Apis mellifera ) Treatment did not affect adult bees (no effects to mortality, foraging activity, nectar and pollen storage, and egg

laying )

.

Bee brood development and colony strength appeared to be influenced by treatment as well as population density.

It is noted th at the application rate assessed in this study (0.13 lbs a.i/A) is approximately half the maximum single application rate allowed for apples. 45697105 (Acceptable)

Non

- target arthropod toxicity in the field Parasitic wasp

( Trichogramma

cacoeciae ) 8

- d E C 50 >648.6 g product/hectare 45697109 (Acceptable)

Parasitic wasp ( Aphidus rhopalosiphi ) 11

- d EC 50 >236.6 g product/hectare; 11

- day NOAEC (mortality) = 131.8 g product/hectare 45697110 (Acceptable)

Predacious mite ( Typhlodromus pyri ) 32

- d NOAEC (develo pment and mortality) = 23.6 g product/hectare 45697113 (Acceptable)

Non

- target arthropod toxicity in the field Predacious mite

( Typhlodromus pyri ) Treated plots had clear reduction in number of spider mites that serve as prey for predatory mites. 456971 14 (Acceptable)

28

- d NOAEC (based on mite population) = 439 g product/hectare 45697116 (Acceptable)

Non

- target arthropod toxicity Lacewing

( Chrysoperla carnea ) No remarkable effects 45697115 (Acceptable)

Non

- target arthropod life cycle toxicity Predac ious mite

( Typhlodromus pyri ) 14

- d NOAEC (based on reproduction) = <12.7 g product/hectare 45697120 (Acceptable)

Non

- target arthropod toxicity Predacious mite

( Typhlodromus pyri ) 17

- d NOAEC (mortality) = <259 g product/hectare 45697121 (Acceptable)

Non

- t arget arthropod

to xicity in the field Predacious mite

( Typhlodromus pyri ) Treatment of the plots at 654.5 g product/hectare reduced mite abundance 55% as compared to the control group 45697112 (Acceptable)

Non

- target arthropod toxicity Wolf spider ( Pardo sa

spp.) 14

- d NOAEC (mortality) = 654.5 g product/hectare 45697123 (Acceptable)
Carabid beetle ( Poecilus cupreus ) 14

- d NOAEC (mortality) = 654 g product/hectare 45697124 (Acceptable)

### 27

Determination of Spirodiclofen Residues of Ecological Concern

As des cribed in Section 5a, spirodiclofen degrades by various routes in the environment . Five different degradation products were formed in the fate studies at concentration s of 10% or greater
than the applied parent spirodiclofen ( Appendix A ). Figure A.1 in t he appendix shows the registrant

- proposed degradation pathway for spirodiclofen under aerobic soil conditions

. When available, registrant submitted toxicity data for degradates were consulted. Additionally, t he ECOSAR (v1. 1 ) module of E PI S UITE (v.4. 1 ) wa s employed to estimate the toxicity of these degradates of spirodiclofen alongside the available registrant submitted data

. E COSAR uses structure activity relationships to predict the toxicity of compounds that share similar structural
moieties. In cases where multiple estimates of toxicit y for a particular taxa are pre dicted for a degradate, the most sensitive estimate was tabulated

.

For each ECOSAR class ( i.e. grouping of estimates based on moieties detected in the structure)

, varying numbers of data points are associated in building the structure activity relationship that informs the estimate of toxicity for a given ECOSAR class.

Table 10 shows the ECOSAR classes for each degradate for which toxicity es t imates were predicted. These results are c ompared alongside registrant submitted data that are available for spirodiclofen as well as the degradate s

.

Table 10. Registrant submitted data compared to ECOSAR predicted toxicity (μg a.i./L) of spirodiclofen and its degradates

. 4

Compound ( ECOSAR
class ) Toxicity Endpoint (μg a.i/L)

Acute
FW
Fish
LC 50 Acute

FW
Invert
EC 50 Chronic

FW Fish
NOAEC Chronic

FW
Invert
NOAEC Acute

E/M
Fish
LC 50 Acute
E/M
Invert
LC 50 Chronic
E/M
Fish
NOAEC Chronic

E/M
Invert
NOAEC Algae

EC 50

Spirodiclofen (registrant)

– TGAI 3 >35 >45.5 3.81 11 >35 >37 >60

Spirodiclofen (ECOSAR)

– TGAI 190 1 252 1 6 51 1 224 1 28 1 68 0.38 55 1

BAJ 2740

- enol

- (BAJ 2510)
BAJ 27040

- enol (registrant) >73000 >100000 115 32000 190 3000 66300

Esters 4540 1769 913

BAJ 2740

- ketohydroxy

Esters 905 1380 37 411 1153 273 278 56 372 Benzyl alcohols 284 283 47 2 98 2 376
Ketone alcohols 642 474 30 2 43 2 285

BAJ 2740

- dihydroxy

Esters 1609 1 2569 1 72 864 2105 1 614 470 297 740 Benzyl alcohols 675 651 102 2 202 2 734

BAJ 2740

- dioxoketone Neutral organics 1111 795 144 151 1420 185 742 7 90 1
DCB

- acid
Neutral organics

- acid 287000 176000 30000 21000 363000 154000 65000 10000 179000

### 28 1 ECOSAR i ndicates that chemical may not be soluble enough to measure this predicted effect

2 ECOSAR i ndicates that this value w as estimated using an acute

- to

- chronic ratio (ACR)

3 Data in this row refer to registrant submitted studies for spirodiclofen deemed suitable for risk estimation. These values are included in the table for comparison purposes against the ECOSAR predicted e ndpoints for parent spirodiclofen one row below.

4 Results are from the ECOSAR class denoted unless specified as being derived from registrant submitted studies



### Table 10 indicates that when comparing registrant submitted data for the taxa available, the
de gradates of spirodiclofen are generally less toxic than parent although there is uncertainty in that

statement with some degradates more than others

. There is uncertainty in this statement comparisons are being made between an endpoint that is greater tha n the absolute value of a non

definitive value. What follows is an analysis of the estimates for each degradate:

BAJ

- 2740

- enol

There are seven registrant submitted studies available to characterize the toxicity of BAJ 2740

- enol to freshwater fish (acute and chronic)

, freshwater and estuarine/marine invertebrates (acute and chronic for each of freshwater and estuarine/marine)

, freshwater green algae , and freshwater sediment dwelling invertebrates

. It is noted that ECOSAR does not provide estimates of tox icity
for sediment

- dwelling invertebrates The comparison of endpoints indicates BAJ 2740

- enol to be at least 3 orders of magnitude less toxic than parent spirodiclofen on an acute basis although
relative toxicity cannot be precisely defined for acute toxi city due to the presence of non

- definitive endpoints ( e.g. >35 μg a.i/L) . Chronic toxicity data for freshwater fish and invertebrates indicate that parent spirodiclofen is approximately two orders of magnitude more toxic than BAJ 2740

- enol . As there were no acute toxicity studies available for acute risk to estuarine/marine fish and
invertebrates for BAJ 2740

- enol, the results of ECOSAR were compared to that of those endpoints in parent spirodiclofen toxicity studies that simi l arly indicated BAJ 2740

- enol is approximately 2 orders of magnitude less toxic than parent. As in the case of acute freshwater fish and invertebrates, relative toxicity cannot be precisely defined due to the presence of non

- definitive endpoints for the parent spirodiclofen estuarine /marine fish and invertebrate studies.

Environmental fate data show that BAJ 2740

- enol forms at concentrations that are generally above 10% of the applied residues and depending on the degradation pathway, can form at concentrations as high as 80

- 90% of the applied residues . BAJ 2740

- enol was the only major degradate found in the hydrolysis pathway where the rates of formation increased as the pH increased . This is consistent with parent spirodiclofen‘s in stab ility at pH values higher than pH 4, sugges ting that this instability is a result of degradation to BAJ 2740

- enol. Nearly 50% of the app lied was found
as BAJ

- 2740

- enol at pH 7 at the end of the study duration ( 30 days ). The aerobic aquatic metabolism degradation pathway was an even bigger contri butor of BAJ 2740

- enol formation with
concentrations ranging from 86

- 95% as quickly as 14 days depending on the study . The soil metabolism studies generally show that BAJ 2740

- enol form s at lower rates in soil than in aquati c systems

, but can still form a t concentrations ranging from 17

– 52% depending on the type of soil.
EPISUITE estimates indicate BAJ 2740

- enol has a higher solubility and lower K OC 

### than parent spirodiclofen

, which would make it more available for a runoff event into aquatic systems. T his prediction is supported by the adsorption/desorption stud y (MRID 45697219). The average Koc
for BAJ

- 270

- enol is 18 ( classified as mobile) in sandy loam, clay loam, sand, and silt soils.

### 29

BAJ 2740

- enol can form or enter into aquatic systems via spray d rift or runoff events. The
formation of the degradate in water is offset by relatively low application rates (maximum single application rate of 0.53 lbs a.i/A) and the lower acute toxicity of BAJ 2740

- enol relative to the
parent

, suggest ing that BAJ 2740

- enol is not of significant ecotoxicological concern. BAJ 2740

- enol was fairly persistent in the aquatic metabolism studies (with up to 78% residues remaining at study termination of 112 days), but of lower chronic toxicity than the parent spirodiclofen

, suggesting that the degradate also is not of significant concern on a chronic basis

.

BAJ 2740

- ketohydroxy

There are no registrant submitted aquatic toxicity studies available for BAJ 2740

- ketohy d roxy (only one study each of avian acute oral toxicity a nd earthworm subchronic toxicity). ECOSAR estimates of the toxicity of BAJ 2740

- ketohydroxy indicate that this degradate is generally at least one order of magnitude less toxic than parent spirodiclofen on an acute and chronic basis for taxa
where estimat es are available. Available environmental fate data however, show that BAJ 2740

- ketohydroxy do es not form at sig nificant levels in the hydrolysis, aqueous photolysis, and aquatic metabolism studies. The primary route of degradation for BAJ 2740

- ketohydro xy is via the aerobic soil metabolism pathway with the maximum concentrations ranging from 11

– 44% depending on the soil. This suggests that BAJ 2740

- ketohydroxy will only be available in aquatic systems following runoff events as the environmental fate properties of BAJ 2740

- ketohydroxy
indicate a higher solubility (1.7 mg/L) than parent spirodiclofen as well as a lower Log K OC 

### (3.3), as estimated by EPISUITE

. Due to the unstable nature of BAJ 2740

- ketohydroxy in the 0.01 CaCl 2 

### solution, batch equilibri um studies could not be conducted. However, the study author still reported an average Koc of 76 (MRID 45697225). Additionally, estimations of adsorption coefficients in soil using a HPLC method determined that spirodiclofen could be classified as
immobi le and BAJ 2740

- ketohydroxy was classified as having low to slight mobility

. Spray drift events have minimal potential to form BAJ 2740

- ketohydroxy as there was no formation observed
in environmental fate studies conducted in the aquatic media. The two te rrestrial toxicity studies with this degradate indicated a lack of toxic effects. Given the relatively low maximum application rate of parent spirodiclofe n (0.53 lbs a.i/A), the low likelihood of BAJ

- 2740

- ketohydroxy enter ing aquatic systems except in run off

, and ECOSAR estimates generally indicating less toxicity than parent spirodiclofen for aquatic organisms, BAJ 2740

- ketohydroxy is not considered to be of significant ecotoxicol o gical concern as compared to parent spirodiclofen both on an acute and
chro nic basis

.

BAJ

- 2740

- dihydroxy

There are no registrant submitted studies for BAJ

- 2740

- dihydroxy. ECOSAR estimates of the toxicity of BAJ 2740

- dihydroxy indicate that this degradate is generally at least one order of magnitude less toxic than parent s pirodiclofen on an acute and chronic basis for taxa where
estimates are available. BAJ 2740

- dihydroxy is similar in its formation profile to BAJ 2740

- ketohydroxy in that it only forms as a major degradate via the aerobic soil metabolism pathway. However, whereas BAJ 2704

- ketohydroxy formed at up to 44% of the applied residues, the
maximum concentration for BAJ 2740

- dihydroxy was 16% (marginally exceeding what is considered to be a major degradate) in one soil and 5, 4, 3, and 1% in four other soils. As BA J
2740

- dihydroxy is expected to form in lower rates than BAJ 2740

- ketohyroxy, this degradate is

### 30

not anticipated to be of significant ecotoxicological concern as compared to parent spirodiclofen

on both an acute and chronic basis

.

BAJ 2740

- dioxoketone

T here are no registrant submitted studies available for BAJ 2740

- dioxoketone. ECOSAR estimates indicate that this degradate is at least one order of magnitude less toxic than parent spirodiclofen on an acute and chronic basis for all taxa for which estimat es are available.
Environmental fate data indicate that this degradate form s only by the aqueous photolysis pathway and in marginally major (maximum 11%) percentages of applied residues. Since BAJ 2740

- dioxoketone would form only following spray drift ev ents (as no formation was observed in soil degradation studies) , and is estimated to be at least an order of magnitude less toxic than parent spirodiclofen, this degradate is not anticipated to be of significant ecotoxicological concern on both an acute an d chronic basis

.

DCB

- acid

There are no registrant submitted studies available for dichlorobenzoic acid (DCB

- acid). ECOSAR estimates indicate that this degradate is at least four orders of magnitude less toxic than parent spirodiclofen on both an acute a nd chronic basis for all taxa for which estimates are available. Environmental fate data indicate that this degradate forms at a maximum of 40% of the applied residues in the submitted aerobic soil metabolism studies. It can also form via the soil photol ysis pathway. Additionally, according to the registrant

- postulated degradation pathway for spirodiclofen in soil under aerobic conditions ( Figure A.1 ), DCB

- acid is the second to last degradate in the pathway, eventually transforming to carbon dioxide. BA J 2740

- ketohydroxy and
BAJ 2740

- dihydroxy residues eventually can transform to DCB

- acid. DCB

- acid would only have the potential to impact aquatic taxa following a runoff or soil erosion event as its formation was not observed in hydrolysis, aquatic metabo lism, or aqueous photolysis studies. Given the separation of several orders of magnitude between expected DCB

- acid concentrations and the ECOSAR estimated toxicity endpoints, DCB

- acid is not anticipated to be of significant ecological

concern on both an a cute and chronic basis

.

Conclusions: Stressor(s) of Concern

In summary, available empirical and ECOSAR acute and chronic deg radate data for freshwater
fish and invertebrates, estuarine/marine fish and invertebrates and freshwater green algae generally
sh ow decreased toxicity to these taxa as compared to parent spirodiclofen

. Transformation to BAJ
2740

- enol is expected to take place quickly in aquatic system s via the aquatic metabolism and/or hydrolysis pathways. ECOSAR data suggest that BAJ 2740

- ketohyd roxy, BAJ 2740

- dihydroxy,
and BAJ 2740

- dioxoketone are more toxic than BAJ 2740

- enol but less toxic than the parent on
both an acute and chronic basis

. E nvironmental fate data indicate these three degradates will not form in concentrations as high as BAJ 2740

- enol, especially BAJ

- 2740

- dihydroxy and BAJ 2740

- dioxoketone. ECOSAR estimates f or DCB

- acid indicate that it is much less toxic than the parent on both an acute and chronic basis for taxa where estimates are available. In consideration of
these fac tors

, spirodiclofen alone will be considered the stressor of concern for the registration
review risk assessment.

### 31



## c. Ecological Incidents

The ecological incident information system (EIIS) is an EFED

- maintained database that houses ecological incidents that have been reported to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects observed in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemic al residue analysis or other analyses conducted during incident investigation. EIIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure. The OPP

- maintained Incident Database System (IDS) and the Aggrega te Incident Database provide incident counts at the chemical and product level but do not provide the narrative information contained in EIIS. The
Avian Incident Monitoring System (AIMS) is a database administered by the American Bird Conservancy that con tains publicly available data on reported avian incidents involving pesticides. Many of the incidents listed in this database are also in the EIIS. Searches of the incident databases were conducted in September, 2014.

A search of EIIS , the IDS, and AIMS returned no reported wildlife incidents involving spirodiclofen

.

A search of the Aggregate Incident Database returned one relevant incident, involving the sole formulated product of spirodiclofen (Envidor ® 2 SC). The inciden t (Package and Sequence
Num ber: 022684

- 00032) was categorized as a minor plant damage incident. No further information was provided in the report.



# 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of spirodiclofen indicate that direct spray, spray
dr ift, and runoff (mainly in events accompanied by erosion), represent potential transport
mechanisms of spirodiclofen to aquatic and terrestrial organisms. Leaching to groundwater and atmospheric deposition are not important pathways for the chemical.

Oth er Exposure Pathways t o Terrestrial Species

Drinking Water Exposure

The S creening I mbibition P rogram (SIP v.l.0), Released June 15, 2010) was used to calculate an upper bound estimate of exposure using spirodiclofen’s solubility (0.05 5 mg/L), the most se nsitive acute and chronic avian toxicity endpoints (northern bobwhite quail LD 50 

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

- bw and northern bobwhite quail NOAEC of 691 ppm, respectively) and the most sensitive acute and chronic mammalian toxicity endpoints (Norway rat LD 50 

### of > 2 0 00 mg a.i/kg

- bw and Norway rat
NOAEL 70 ppm , respectively). Drinking water exposure alone was not determined to be a potential pathway of concern for both avian and mammalian species on both an acute and chronic
basis.

### 32

Although drinking water exposure al one does not appear to be of concern, when aggregated with other exposure pathways (dietary food sources, dermal, inhalation)

, drinking water may contribute to a total exposure that has a potential for effects on non

- target animals. Because there is a high degree of conservatism in the SIP 1.0 exposure estimate, there is a limited expectation that use scenarios not triggering a SIP 2.0 concern would contribute significantly to aggregate risks from water plus diet when a refined water exposure model is incor porated in the actual quantitative risk assessment. Detailed information about SIP v.l.0 as well as he tool can be found
on the EPA's website at http://www.epa.gov/pesticid es/science/models/pg.htm#terrestrial

.

Inhalation Exposure

The S creening T ool for I nhalation R isk (STIR v.l.0, November 19, 2010) was used to calculate an upper bound estimate of exposure using spirodiclofen’s vapor pressure ( 2.3 X 10

- 9 

### torr ) and
molecul ar weight for vapor phase exposure as well as the maximum application rate and method of application for spray drift. STIR incorporates results from several toxicity studies including acute oral and inhalation rat toxicity endpoints obtained from the "six pack," of core studies for technical and formulated products ( rat oral LD 50 

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

- bw and inhalation LC 50 

### = >5.03 mg/L) as well as the most sensitive acute oral avian toxicity endpoint (mallard duck oral

LD 50 

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

- bw). Based on the results of the STIR model, inhalation exposure alone was not determined to be a potential pathway of concern for avian and mammalian species on an
acute basis.

Inhalation exposure via spray drift and/or vapor

- phase of spirodiclofen alone does not appear to be of concern. The analysis of the inhalation route in STIR does not consider that aggregation with other exposure pathways such as dietary, dermal, or drinking water may contribute to a total exposure that has a potential for effects to non

- target anim als. However, the Agency does consider the relative importance of other routes of exposure may be potentially significant contributors to wildlife risk (US EPA, 2004). Detailed information about STIR v.l.0, as well as the tool, can be
found on the EPA's website at: http://www.epa.gov/pesticides/science/models/pg.htm#terrestrial

Dermal exposure

Potential exists for spirodiclofen dermal exposure to terrestrial wildlife. At the present time, the Agency does not have a method to quantify levels of dermal exposure from chemical applications, but is actively working on a screening tool to account for this route of exposure.

Exposure resulting from bioaccumulation

The potent ial for bioaccumulation of spirodiclofen will also be examined in the risk assessment. Spirodiclofen shows a significant potential to bioconcentrate, as expected from its extremely high
octanol/water partition coefficient ( log K OW 

### = 5. 83 ). Residues bioc oncentrated in bluegill sunfish
with maximum bioconcentration factors of 160 L/kg for the edible tissue, and 699 L/kg for whole fish. However, depuration was relatively rapid ( 70% of residues had depurated after Day 1 and 98% after 13 days )

. B ioaccumulat ion will be a ssessed using the results from bioaccumulation in fish studies, as well as the K OW 

### (based) A quatic B io A ccumulation M odel, version 1.0, 2009 (KABAM)

.

### 33



# 8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

Please see the section enti tled “ Determination of Spirodiclofen Residues of Ecological Concern ”
in Section 6 of this assessment for a detailed rationale for identifying the spirodiclofen parent as
the stressor of concern for the registration review ecological risk assessment

.

ii. Drink ing Water

Data from fate studies for spirodiclofen recommended to be required by this problem formulation
will be considered for a determination of residues of concern , and an updated drinking water assessment may be needed as part of the Registration Re view process. If a new drinking water assessment is needed, EFED will include the recently revised percentage crop area (PCA) factors as well as the newly

- developed PRZM

- GW and SWCC models to determine EDWCs in groundwater and surface water , respectively

.



## b. Measures of Exposure

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

.

The Agency is aware of monitoring conducted by federal and state agencies and this source of exposure data will be considered in the assessment to the extent that data on spirodiclofen are availabl e.



## c. Measures of Effect

Toxicity data presented in Section 3 of this problem formulation will be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literatur e prior to conduct of the risk assessment will also be considered. The open literature studies are identified using EPA’s ECOTOXicology database ( ECOTOX) (USEPA, 2007 c ), which employs a literature search engine for locating chemical toxicity data for aqua tic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insight into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.



# 9. Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and/ or endangered (listed) species from registered

### 34

uses of spirodiclofen in registration review

. The process for evaluating potential risks to listed species is further described at ht tp://www.epa.gov/oppfead1/endanger/litstatus/riskasses.htm

.



# 10. Endocrine Disruptor Screening Program

Spirodiclofen was not included in the first group of 67 chemicals issued an order to conduct Tier
1 EDSP testing. For additional information the EDSP pro gram, visit http://www.epa.gov/endo/

.


# 11. Preliminary Identification of Data Gaps

a. Environmental Fate

Table s 1 1 and 12 identif y environmental fate studies by MRID for spirodiclofen and its degradation products and

, the ir study classifications . The tables also show where additional data are needed to support risk assessment.

835.4 2 00 Anaerobic Soil Metabolism: N o studies are available. New studies should be
submitted.

835.4 4 00 Anaerobic Aquatic Metabolism: Only one w ater/ sediment system is available

. Additional water/ sediment system should be selected according to the 835.4400 guidance, and submitted. In the absence of data, EFED will make conservative assumptions, based upon the
overall behavior observed in the ava ilable study. A conservative 3x factor will also be added, since there is only one study ( water/ sediment system) available.

850.6100 Environmental Chemistry Methods (ECM) and Independent Laboratory Validation (ILV): Analytical methods for water for the p arent compound and its major degradates are needed. ECM/ILV studies are available for the analysis in soil, which are in review. The data requirement will remain unfulfilled until the available studies are reviewed.

Table 1 1 . Submitted Environmental Fat e Data for Spirodiclofen

OCSPP
Guideline Data

Requirement Submitted Studies

(MRID) Study

Classification Are data

needed to
conduct
risk

assessment
? Notes

835.2120 Hydrolysis 45697217 Acceptable No

-- - 835.2240 Aqueous

photolysis 45697218
45697201 Suppl emental

Supplemental No

-- -

835.2410 Soil photolysis 4 5697230 Acceptable No

---

### 35

OCSPP
Guideline Data

Requirement Submitted Studies

(MRID) Study

Classification Are data

needed to
conduct
risk

assessment
? Notes

835.4100 Aerobic soil

metabolism 45697204/
45697228
45697206
45697215
45697224/
45697310
45697226 Acceptable

Supplemental Supplemental Supplemental

Supplemental No

---

83 5.4200 Anaerobic soil

metabolism - - Yes No studies are
available. New studies
are needed

835.4300 Aerobic aquatic

metabolism 45697205 Acceptable No Pond and lake systems
were included in the study.

835.4400 Anaerobic

aquatic
metabolism 456 97212 Accepta ble Yes Only one water/sediment system
was included in the study. A n a dditional water/sediment system
is needed.

835.1230
835.1240 Adsorption/

desorption and leaching 45697219
45697229
45697307
46040405
46040406
46040407
45697222
46040406
45697202
456972 16 Supplemental

Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental Supplemental No

-- -

835.1410 Volatility

–

laboratory Waived Waived No The vapor pressure and Henry’s Law Constant for spirodiclofen a re relatively low.

835.6100 Terrestrial field

dissipation 45697207/45697303

45697208/45697303
45697209/45697303
45697210/4569730 3 Acceptable Acceptable Acceptable Acceptable No

---

835.6200 Aquatic field

dissipation Waived Waived No

---

835.8100 Volatil ity

- field 45697321 Unacceptable No The vapor pressure and Henry’s Law Constant for spirodiclofen are relatively low.

850.1730 Fish

bioconcentration 45697002 Acceptable No

---

### 36

OCSPP
Guideline Data

Requirement Submitted Studies

(MRID) Study

Classification Are data

needed to
conduct
risk

assessment
? Notes

850.6100 Analytical

method in soil (ECM/ILV) 456972

- 11/

- 21

(for spirodiclofen and its degradates
BAJ 2470

- eno l

, - ketohydrox y , - dihydroxy, and
DCB

- acid) In review No Not yet determined;
studies are in review.

Analytical
method in water (ECM/ILV) 45697220 (ECM for

parent compound only )

456972 03 (ECM for degradate BAJ
2470

- enol only ) In review

(these studies are unlikely to be acceptable
because not all parent and its major degradates were analyzed) Yes A new ECM study and the corresponding ILV study are needed.
These studies should include the analysis of the parent compound

a nd its major degradates ( BAJ 2470

- enol,

- ketohydroxy,

- dihydroxy, and DCB

acid)
Shaded and bolded cells indicate that additional data are required for the corresponding data requirement.

### 37

Table 1 2 . Submitted Environmental Fate Data for the Spirodiclofen D egradates

OCSPP
Guideline Data

Requirement Submitted Studies

(MRID and test
substance ) Study

Classifications Are data

needed to
conduct risk
assessment? Notes

835.2240 Aqueous

photolysis 45697 227

(spirodiclofen enol) Supplemental No

---

835.4100 Aerob ic soil

metabolism 45697215

(spirodiclofen dihydroxy)
45697224 (spirodiclofen DCB acid)
45697226 (spirodiclofen dihydroxy) Supplemental

Supplemental Supplemental No

---

835.1230
835.1240 Adsorption/

desorption and leaching 45697213

(spirodiclofen enol)
4 5697214 (spirodiclofen dihydroxy)
45697223 (spirodiclofen DCB acid)
45697225 (spirodiclofen ketohydroxy) Supplemental

Supplemental

Supplemental

Unacceptable (unstable in
CaCl 2 ) No

-- -



## b. Effects

Table s 14

- 17 identify ecological effects studies by MRID that offer data for each guideline requirement for parent spirodiclofen and the degradation products in the aquatic medi a and
terrestrial environment , respectively, as well as study classifications and whether or not further data are needed in order to sup port risk assessment.

Currently, there is only one acute oral study available for spirodiclofen which is conducted on the mallard duck. The study was tested up to concentrations of 2000 mg a.i/kg

- bw with no mortalities or clinical signs of toxicity o bserved in the study. Similarly, in two available acute dietary studies with the mallard duck and northern bobwhite quail, birds were exposed to concentrations of spirodiclofen in the diet up to 5000 mg a.i/kg

- diet. As in the acute oral study, there were no treatment related mortalities or clinical signs of toxicity observed.

At the current maximum labeled rate of spirodiclofen ( grapes, 0.53 lbs a.i/A, 1 application ), the acute dose based RQ for small birds eating short grass already meets the endangered species LOC of 0.1. Therefore, an acute oral passerine study showing increased sensitivity to any degree would already be exceeding the listed species LOC and would have the potential to exceed the acute
restricted use and acute non

- listed species LOCs. An avian acute oral toxicity study with a passerine species is therefore a data gap.

### 38

As discussed earlier in this assessment, spirodiclofen has an insect growth regulator type mode of action that is mediated by the inhibition of lipid synthesis. Spirodi clofen is in a chemical class that is shared by spiromesifen and spirotetramat. It was investig ated as to whether chemicals in this
class had data that would corroborate the data available for spirodiclofen and potentially provide insight as to whether an additional toxicity study with a passerine species would add substantial
value to the risk assessment.

T he chemicals recognized to be part of the tetronic and tetramic acid derivatives class by the Insecticide Resistance Action Committee (IRAC) are liste d in Table 1 3

, which compiles detailed information about insecticide mode of action. The endpoints tabulated below represent supplemental and acceptable studies suitable for quantitative risk assessment.

Other ecological effects studies that have been de termined to be data needs to support risk
assessment for spirodiclofen are as follows:

850.2100 Avian acute oral toxicity test (with passerine species): Currently, there is only one acute oral study available for spirodiclofen which is conducted on the m allard duck. An avian acute oral toxicity study with a passerine species is therefore a data gap. At the current maximum labeled rate of spirodiclofen (grapes, 0.53 lbs a.i/A, 1 application), the acute dose based RQ for small birds eating short grass alr eady meets the endangered species LOC of 0.1. Therefore, an acute oral passerine study showing increased sensitivity to any degree would already be exceeding the listed species LOC and would have the potential to exceed the acute restricted use and acute

non

- listed species LOCs.

Available data from other chemicals within this subclass of insecticides (Table 13 ) shows that
this group of chemicals is generally not toxic to northern bobwhite quail and mallard duck on an acute oral and subacute dietary exp osure basis. There were no mortalities that occurred in all studies tabulated below except where otherwise noted in a footnote. It was noted however in one acute oral study with spiromesifen and one acute oral study with spirotetramat that there were
obs ervations of diarrhea in at least one treatment group. These observations did not persist throughout the study. Additionally, in two sub

- acute dietary toxicity studies conducted with spirotetramat, there were observation of reduced feed consumption at on e or more treatment groups that coincided with effects on body weight. In one study, complete food avoidance was noted in the two highest treatment groups. It was also noted in both studies with these observations
that once the birds were taken off chemi cal exposure in the recovery period, that feeding and body weight gain returned to normal levels.

An examination of terrestrial EECs as generated from T

- REX (version 1.5.2.) indicates at the maximum single application rate of 0.53 for spirodiclofen tha t the highest dose and dietary

- based EECs will be 145 mg/kg

- bw and 127 ppm, respectively. While no clinical signs of toxicity were observed in the spirodiclofen acute oral toxicity studies, the maximum dose

- based EECs reside a factor of approximately 3.5 fold away from levels w here clinical signs of toxicity (diarrhea) were observed in studies for chemicals related to spirodiclofen. Similarly, while no clinical signs of toxicity were observed in sub acute dietary studies with spirodiclofen, the maximum di etary

- bas ed EECs reside a factor of approximately 3 fold away from levels where clinical signs of toxicity

### 39

(reduced body weight gain, observation of reduced food consumption, observations of food avoidance) were observed in studies with chemicals related t o spirodiclofen.

Table 1 3 . Available avian acute data from the tetronic and tetramic acid derivatives class
of insecticides.

Chemical Acute oral

(passerine) mg a.i/kg

bw Acute

oral (quail)

mg a.i/kg

bw MRID or

source Acute

oral (Mallard)

mg a.i/kg

- bw Sub

acute dietary (quail) a.i/kg

diet MRID or

source Sub

acute dietary (mallard) a.i/kg

diet MRID or

source

Spirodiclofen >2000 45697004 >5000 45697003 >5000 45697118

Spirotetrama t >2000 2,3 Barfknecht (2003) >4998 4 Barfknecht (2004) >6050 5 Stoughton (20 05) Spiromesifen >2000 1 45819723 >4767 45819721 >5278 45819722

1 Observations of diarrhea at all treatment groups (500, 1000, and 2000 mg a.i/kg

- bw) during the first 2 days of

treatment.

2 Observations of diarrhea at the low and middle treatment groups ( 500 and 1000 mg a.i/kg

- bw) that ceased on Day 3 (low group) and Day 10 (middle group)

3 One female and one male each died at the highest treatment group (1000 mg a.i/kg

- bw). Observations of reduced activity, fluffed feathers, apathy, and drooping of the ey elid.

4 Signific ant effects of reduced body weight gain at the two highest treatment groups (2550 and 5000 mg a.i/kg

- diet)
coincided with food avoidance observations at these two treatment levels. Chicks were determined to have
consumed 30

- 50% less than th e amount of the control groups. These effects were compensated as soon as the birds were taken off chemical exposure.

5 Observations of reduced feed consumption at all treatment groups (344, 708, 1436, 2843, and 6050 mg a.i/kg

- diet) that coincided with Day 5 body weight being significantly reduced from control. Food consumption was determined to have returned to normal levels following chemical exposure after Day 5.



### 850.1735. Whole Sediment Acute Toxicity Invertebrates, Freshwater 9
, 10 

### Currently, there is one chronic spiked water sediment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius. Available data indicate that spirodiclofen has a high propensity to bind to the sediment and is likely to affect the growth , development, and reproduction of arthropods via the inhibition of fatty acid biosynthesis. The available chronic sediment toxicity study, however, does not provide sediment or pore water concentrations, but only initial measured
concentrations that were spiked into the overlying water. While it was stated by the registrant that this route of exposure offers the most realistic and conservative scenario (as midges would be exposed to parent spirodiclofen and its main degradate, BAJ 2770

- enol, in the sedim ent and pore
water; see Section 6 for more details), there were no analytical measurements in the pore water or sediment that provided an indication of what concentrations the organisms were actually exposed to. It was further contended by the registrant that parent spirodiclofen undergoes a rapid transformation in both the water column and sediment to the degradate BAJ 2740

- enol, which is shown in registrant submitted studies to be at least 2 orders of magnitude less toxic than parent spirodiclofen. In t he available sediment toxicity study with parent, however, there was 0% emergence in the three highest treatment concentrations (320, 560, and 1000 μg a.i/L) and below

9 Also known as “Whole Sediment: Subchronic Freshwater Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

10 A 10

- day study is requ ested as opposed to a chronic life cycle 60

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

### 40

50% emergence in the next two lowest concentrations (100 and 180 μg a.i/L). These resul ts indicate that parent spirodiclofen can exhibit toxicity before its eventual transformation to BAJ
2740

- enol in the water column and/or sediment. EFED recommends a new study that provides analytical measurements for the sediment as well as pore water. As previously mentioned, environmental fate data indicate parent spirodiclofen undergoes transformation to BAJ 2740

- enol relatively quickly and therefore a subchronic, 10

- day study is requested with the freshwater midge
Chironomus dilutus . While a protoco l does not need to be submitted, it is recommended that the spiked sediment system not be aged prior to initiation of the definitive test in order to capture any toxic effects mediated by parent spirodiclofen.

850.1735. Whole Sediment Acute Toxicity Inver tebrates, Freshwater 1, 11



### . Currently, there is
one chronic 28

- day spiked water sediment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius

. Per the discussion in the preceding paragraph, a spiked sediment system for parent spirodiclofen with analytical measurements for sediment and pore water is preferred for this study, rather than the spiked water system currently used in the available study. To examine the potential for differential sensitivities of aquatic i nsects and benthic crustaceans to spirodiclofen, a subchronic (10

- day) sediment study with the freshwater amphipod species Hyalella azteca is recommended. As with the data gap discussed in the preceding paragraph, it is recommended that the spiked sedimen t system not be aged prior to initiation of the definitive test in order to capture any toxic effects mediated by parent spirodiclofen

.

850.1740. Whole Sediment Acute Toxicity Invertebrates, Marine 12
, 13 

### Currently, there is one chronic spiked water sediment study available for parent spirodiclofen conducted on the freshwater midge, Chironomus riparius. Per the preceding discussion, a spiked sediment system for parent spirodiclofen with analytical measurements for sediment and pore water is preferred for th is study, rather than the spiked water system used in the available study. To examine the potential for differential sensitivities of aquatic insects and benthic crustaceans to spirodiclofen, a subchronic (10

- day) sediment study with the estuarine/marine amphipod species Leptocheirus plumulosus is recommended to be required. I t is recommended that the spiked sediment system not be aged prior to initiation of the definitive test in order to capture any toxic effects mediated by parent spirodiclofen.

850.1 350: Mysid Chronic Toxicity Test

. A chronic life cycle toxicity test with the estuarine/marine invertebrate mysid shrimp was previously submitted and classified as unacceptable. The rationale was that the high solvent control mortality rate (56% of the s olvent control group) confounded the interpretation of the study. In the initial review of the study, it was stated that minimal exposure to the parent in the marine environment water column is expected as spirodiclofen has a very low solubility in water and partitions into the sediment. Additionally, it was stated that a valid chronic study with the mysid shrimp with the BAJ

- 2740 enol degradate is

11 A 10

- day study is requested as opposed to a chronic life cycle 42

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

12 Also known as “Whole Sediment: Subchronic Marine Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

13 A 10

- day study is requested as opposed to a chronic life cycle 28

- day study as parent spirodiclofen is shown to degrade to the enol degradate in 1

- 7 days

### 41

available and exposure was more likely for this degradate. The Agency concluded that a repeat of the study with parent spirodiclofen was not needed.

More recently, a re

- examination of the chronic daphnia toxicity study calls into question the registrant’s earlier contention that parent spirodiclofen would not be available to elicit a toxic effect
in the water column. Available environmental fate data indicate that parent spirodiclofen has a hydrolysis half

- life at pH 7 of 30 days and an aerobic aquatic metabolism half

- life of 1

- 7 days. These data are corroborated by a chronic life cycle toxicity study with dap hnia in which there were significant (p<0.05) decreases in mean length and mean dry weight at the highest treatment concentration (32.7 μg a.i/L) determined during the 21

- day study. Additionally, there was determined to be a significant (p<0.05) decrease in the mean number of young per adult reproductive day in the two highest treatment concentrations (20.2 and 32.7 μg a.i/L). The primary degradate of parent spirodiclofen, BAJ

- 2740 enol did not exhibit similar effects at these concentrations (as its solub ility is orders of magnitude higher) and so these effects are attributed to parent spirodiclofen. As spirodiclofen has an insect growth regulator type mode of action via inhibition of fatty acid biosynthesis, effects on growth and reproduction are anticip ated in freshwater and estuarine/marine invertebrates including crustaceans, which are closely related to
insects.

A new chronic mysid toxicity study is recommended so the Agency can better understand what levels of parent spirodiclofen adversely impact estuarine/marine growth and reproduction.

Special Study ( OECD TG 237 ) (Tier 1) : Honey Bee Larvae Acute Oral Toxicity (Tier I) 14 

### Acceptable acute contact and oral toxicity data are available for adult honey bee exposures to spirodiclofen; however, data a re not available for larval toxicity. As the mode of action of spirodiclofen is documented be an insect growth regulator mediated by the inhibition of fatty acid biosynthesis, data are needed to characterize the toxicity of spirodiclofen to terrestrial in vertebrates in the larval stage of the life cycle. An available semi

- field study conducted with the honey bee shows no significant effects to adult honey bees while brood development and colony strength are negatively impacted. These effects corroborate the premise that spirodiclofen may have enhanced toxicity to larvae as compared to adult bees. No protocol needs to be submitted to the Agency before the initiation of this study. Pending the results of this study, higher tiered ( e.g. semi

- field)
stud ies as well as residue studies may be required.

Special Study (Tier 1) : Honey Bee Larvae Chronic Oral Toxicity. Acceptable acute contact and oral toxicity data are available for adult honey bee exposures to spirodiclofen; however, data
are not availabl e for larval toxicity. As the mode of action of spirodiclofen is documented be an insect growth regulator mediated by the inhibition of fatty acid biosynthesis, data are needed to characterize the toxicity of spirodiclofen to terrestrial invertebrates in the larval stage of the life cycle. An available semi

- field study conducted with the honey bee shows no significant effects to adult honey bees while brood development and colony strength are negatively impacted. These
effects corroborate the premise th at spirodiclofen may have enhanced toxicity to larvae as compared to adult bee s. EFED recommends that a protocol (following the OECD draft guidance

14 Depending on the design of the “Honey Bee

– 21

- day repeated dose chronic larval toxicity,” study, a 72

- hour

LD 50 valu e may be derived from this study. If that is possible, it would obviate the need for this study.

### 42

document, November 25, 2013) be submitted for review and approval by the Agency prior to
initiation of this study. Pending the results of this study, higher tiered ( e.g. semi

- field) studies as well as residue studies may be required.

Special Study: Honey Bee Adult Chronic Oral Toxicity (Tier 1). Bees can be exposed to pesticides through multiple pathways i ncluding contact with sprays and dusts and through ingestion of residues in food/water ( e.g ., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and nectar can be repeatedly exposed to residues in poll en and nectar either through direct contamination of these matrices by foliar sprays and/or dusts through translocation of residues via systemic transport of the active ingredient. Residues can in turn be brought back to bee colonies where in

- hive bees in cluding young adult and developing brood ( i.e ., eggs, larvae and pupae) may be exposed. EPA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended to facilitate screening for potential acute and chronic effects to individual adult and larval bees. The
10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL)
and lowest

- observed adverse effect level (LOAEL) for assessing chronic effects. Risk estimates
based on these d ata will be considered along with other lines of evidence to determine whether higher

- tier studies are needed at the whole colony level. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Special S tudy : Field Trial of Residues in Pollen and Nectar (Tier 2): Submission of studies for crops of concern that evaluate residue in plant parts ( e.g. pollen and nectar) may be of high value depending on the results of the screening level risk assessment and the Tier I larval bee toxicity study. If refinements to the screening level risk assessment for honey bees are needed, these studies will allow for a more refined exposure analysis when applications are made at bloom. This chemical is of low toxicity to adults, but applications at bloom could contaminate pollen and nectar that adult foragers bring back to the colonies, resulting in potential exposures to the brood. In order to evaluate this exposure pathway, these residue studies would assess spirodiclo fen residues in pollen and nectar. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Special Study: Semi

- Field Testing for Pollinators (Tunnel or Colony Feeding Studies) (Tier 2). Screening lev el and refined Tier 1 risk assessments with the honey bee larvae may indicate the need to progress to higher tier toxicity testing under semi

- field conditions . In evaluating the effects of spirodiclofen on honey bees at the colony level, there are uncerta inties relating to the growth and reproduction of the colonies and measurement endpoints that relate to brood development and production. Semi

- field testing data can be used to address these uncertainties with either a tunnel or colony feeding study exper iment design. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

850.3040: Field Testing for Pollinators (Tier 2 or 3) : Screening level and refined Tier 1 risk assessments with the honey bee larva e may indicate the need to progress to higher tier toxicity testing under field condition s . In evaluating the effects of spirodiclofen on honey bees at the colony level, there are uncertainties relating to the growth and reproduction of the colonies and

m easurement endpoints that relate to brood development and production. Field testing data can

### 43

be used to address these uncertainties. EFED recommends that the registrant submit a protocol and consult with the Agency prior to study initiation.

Table 1 4

. Submitted Aquatic Ecological Effects Data for Spirodiclofen

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to
conduct risk
assessment? Justification and Assumptions

EPA will Make in Absence of

Data

850.1 010 Freshwater

invertebrate acute toxicity 45697026 Acceptable

No --

45696924 Acceptable

45697013 Acceptable

850.1025
850.1035
850.1045
850.1055 Saltwater

invertebrate acute toxicity 45697018 Acceptable

No --

45697019 Acceptable

850.1 075 Freshwater fish

acute toxicity 45696926 Acceptable

No --

45697009 Acceptable

45697006 Acceptable

45697001 Acceptable

850.1075 Saltwater fish

acute toxicity 45697027 Acceptable No --

850.1300 Freshwater

invertebrate life cycle 456 97101 Acceptable No --

850.1350 Saltwater

invertebrates life cycle 45697023 Unacceptable Yes A previous chronic mysid study was found to be unacceptable due to high solvent control mortality. It was previously determined a new study would not be need ed since the chemical degraded to the enol degradate that showed reduced toxicity as compared to parent. A re

- evaluation of the
data determined that because growth and reproductive effects were seen in the chronic daphnia study, that parent spirodiclofen was exhibiting toxic effects before degradation to the enol product. As invertebrates are expected to
be the driver of the risk
assessment for a chemical like spirodiclofen, a new study is
recommended.

850.1400 Freshwater fish

early

- life stage 4569710 9 Acceptable No



### --

850.1500 Fish life cycle

saltwater fish 45697102 Acceptable No

--

### 44

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to
conduct risk
assessment? Justification and Assumptions

EPA will Make in Absence of

Data

Non

guideline 28

- day chronic

spiked water
sediment test

– Freshwater 45697117 Acceptable No

--

850.1735 Whole

sediment Acute Toxicity Invertebrates,
Freshwater 15 No data available Yes Spirodiclofen is shown in the
environmental fate data to have a high propensity to bind to
sediment. Additionally, in a chronic spiked water sediment test, spirodiclofen had significant effects on percent emergence at the three highest treatment concentrations. N ew subchronic
10

- day spiked sediment studies
with min i mal or no aging time that provide analytical
measurements for both sediment and pore water in t wo species ( Chironomus dilut u s and Hyalella

azteca ) are needed for risk

assess ment

.

15 Also known as “Whole Sediment: Subchronic Freshwater Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessme nt Guidance for Benthic Invertebrates.” April 2014.

### 45

OCSPP
Guideline Data

Requirement Submitted

Studies (MRID) Study

Classifications Are data

needed to
conduct risk
assessment? Justification and Assumptions

EPA will Make in Absence of

Data

850. 1740 Whole

sediment: Acute Toxicity
Invertebrates

, Marine 16 No data available Yes Spirodiclofen is shown in the
environmental fate data to have a high propensity to bind to sediment. Additionally, in a chronic spiked water sediment test, spirodi clofen had significant effects on percent emergence at the three highest treatment
concentrations. A subchronic 10

- day spiked sediment system study
is recommended for the estuarine/marine amphipod Leptocheirus plumulosus with minimal, if any aging time in order to capture the effects of
parent spirodiclofen before it undergoes transformation. Analytical measurements of parent spirodiclofen for the sediment and pore water are

re commend ed.

850.4400 Aquatic plant

Toxicity Test using Lemna

spp. 45697028 Acce ptable No

--

850.4500 Algal toxicity 45697005 Acceptable No

-- 45697011 Acceptable No



### Table 1 5 . Aquatic Ecological Effects Data for the Degradation P roducts of Spirodiclofen

OCSPP
Guideline Data Requirement

(Degradation produ ct) Submitted Studies (MRID) Study

Classifications Are data needed for

risk assessment ?

850.1010 Freshwater invertebrate acute

toxicity 45697014 Acceptable No

850.1075 Freshwater fish acute toxicity 45697015 Acceptable No

850. 1300 Freshwater invertebra te

life cycle (BAJ 2740

- enol) 45697126 Acceptable No

850. 1350 Saltwater invertebrates

life cycle (BAJ 2740

- enol) 45697103 Acceptable No

850.1400 Chronic early life stage

–

freshwater fish (BAJ 2740

- enol) 45697125 Acceptable No

16 Also known as “Whole Sediment: Subchronic Marine Invertebrates,” as per EFED Guidance Document Entitled “Toxicity Testing and Ecological Risk Assessment Guidance for Benthic Invertebrates.” April 2014.

### 46

OCSPP
Guideline Data Requirement

(Degradation produ ct) Submitted Studies (MRID) Study

Classifications Are data needed for

risk assessment ?

850.4500 Algal toxicity (BAJ 2740

- enol) 45697016 Acceptable No

Non

guideline 28

- day chronic spiked water

sediment test

– Freshwater 45697022 Acceptable No



### Table 1 6 . Submitted Terrestrial Ecological Effects Data for Spirodiclofen

OCSPP
Guideline Data

Requirement Submitted

Stud ies (MRID) Study

Classifications Are data

needed for
risk

assessment ? Justification and

Assumptions EPA will
Make in Absence of
Data

850.2100 Avian oral toxicity

45697004 Acceptable Yes An acute oral toxicity study with a passerine species is need ed for risk
assessment because any increased sensitivity relative to earlier testing
would indicate an acute risk concern for listed and

non

- listed bird s pecies

. 850.2200 Avian dietary

toxicity 45697003 Acceptable No --

45697118 Acceptable

850.2300 Avia n

reproduction 45697104 Acceptable
No --

45697107 Acceptable

850.3020 Honey bee acute

contact and oral toxicity 45697017 Acceptable No --

45697010

850.3030 Honey Bee

toxicity of residues on foliage No data available No Data only conditionally required if active ingredients indicates an

acute LD 50 of < 11μg
a.i/bee as determined in the acute contact toxicity study.

850.6200 Earthworm

Subchronic Toxicity 45697008 Acceptable No --

45697106

Special Study Honey bee adult

chronic oral
toxici ty No data available Yes

Special Study Honey bee larvae

chronic oral toxicity Yes

### 47

OCSPP
Guideline Data

Requirement Submitted

Stud ies (MRID) Study

Classifications Are data

needed for
risk

assessment ? Justification and

Assumptions EPA will
Make in Absence of
Data

Special Study (Tier 2) Field trial of

residues in pollen
and nectar Yes

850.3040 (Tier 2 or 3) Field Testing for

Pollinators Yes

Non

- guideline Semi

- field study

w ith the Honey
bee 45697105 Acceptable No --

850.4100 /4150 S eedling

E mergenc e / Vegetative Vigor 45696925

45697028 Acceptable No --

Non

- guideline Toxicity to egg

parasitoid ( Trichogramma cacoeciae) 45697109 Acceptable No --

Parasitic Wasp ( Aphidius rhop alosiphi ) Toxicity test 45697110 Acceptable No

--

Predatory mite ( Typhlodromus pyri )

– Acute
contact and reproductive test 45697113 Acceptable No

--

Predatory mite ( Typhlodromus pyri ) field study 45697114 Acceptable No

--

Lacewing ( Chrysoperla

carnea ) toxicity

test 45697115 Acceptable No

--

Predatory mite ( Typhlodromus pyri )

– Field Study (Non

- target effects) 45697116 Acceptable No

--

Predatory mite ( Typhlodromus pyri )

– Life cycle

test 45697120 Acceptable No

--

Predatory mite ( Typhlodromus

pyr i )

– Life cycle

test 45697121 Acceptable No

--

### 48

OCSPP
Guideline Data

Requirement Submitted

Stud ies (MRID) Study

Classifications Are data

needed for
risk

assessment ? Justification and

Assumptions EPA will
Make in Absence of
Data

Predatory mite ( Typhlodromus pyri ) field study 45697122 Acceptable No

--

Wolf spider ( Pardosa spp. ) toxicity test 45697123 Acceptable No

--

Carabid beetle ( Poecilus cupreus ) toxicity 45697124 Acceptable No



### --

Shaded and bolded cells indicate that additional data are re commend ed for the corresponding data requirement.



### Table 17 . Aquatic Ecological Effects Data for the Degradation P roducts of Spirodiclofen

OCSPP
Guideline Data Requirement

(Degradation pr oduct) Submitted Studies (MRID) Study

Classifications Are data needed for risk

assessment ?

850. 2100 Avian oral toxicity

(BAJ 2740 4

- hydroxy enol) 45697112 Acceptable No

850. 2100 Avian oral toxicity (BAJ

2740

- enol) 45697111 Acceptable No

850 .6200 Earth worm Subchronic

Toxicity (BAJ 2740

- ketohydroxy) 45697106 Acceptable No

Earthworm Subchronic Toxicity (BAJ 2740

- enol) 45697007 Acceptable No



### Special Study: Honey Bee Adult Chronic Oral Toxicity (Tier 1)

Rationale for Requiring the Data


### Bees can be ex posed to pesticides through multiple pathways including contact with sprays and dusts and through ingestion of residues in food/water ( e.g ., pollen/nectar and water used to maintain colony temperature). Worker bees foraging on flowers for pollen and necta r can be repeatedly exposed to residues in pollen and nectar either through direct contamination of these matrices by foliar sprays and/or dusts through translocation of residues via systemic transport of the active ingredient. Residues can in turn be bro ught back to bee colonies where
in

- hive bees including young adult and developing brood ( i.e ., eggs, larvae and pupae) may be exposed. EPA guidance on assessing the risk of pesticides to bees identifies a suite of laboratory

- based studies intended that ser ve as the foundation for screening chemical for potential acute and chronic effects to individual adult and larval bees. The 10

- day toxicity study with young adult bees provides no

- observed adverse effect level (NOAEL) and lowest

observed adverse effect l evel (LOAEL) for assessing chronic effects. Data obtained from this study will be used in estimating chronic risk to individual adult bees. Risk estimates based on

### 49

these data will be considered along with other lines of evidence to determine whether highe r

tier studies are needed at the whole colony level. The registrant should provide a protocol and consult with the Agency prior to study initiation. Practical Utility of the Data


### How will the data be used? Chronic toxicity data for honey bees will be use d to identify potential risks to terrestrial invertebrates resulting from chronic exposure in the adult stage to spirodiclofen

. The data will
reduce uncertainties associated with the current risk assessment for terrestrial invertebrates and will improve t he Agency’s understanding of the potential chronic effects of spirodiclofen on terrestrial invertebrate species at the adult stage. If chronic adult toxicity data are not submitted for honey bees, then risk to terrestrial invertebrates from chronic exposu re will be presumed under the assumption that prolonged exposures may take place at the adult stage of the life cycle. Special Study: Honey Bee Larvae Acute Oral Toxicity Study (Tier 1) (OECD TG237) and Honey
Bee Larvae Chronic Oral Toxicity Study (Tier 1 ) Rationale for Requiring the Data 

### Acceptable acute contact and oral toxicity data are available for adult honey bee exposures to spirodiclofen ; however, data are not available for larval toxicity. As the mode of action of spirodiclofen is reported to h ave insect growth regulator type activity mediated by inhibition of lipid biosynthesis, d ata is needed to characterize the toxicity of spirodiclofen to terrestrial invertebrates in this stage of the life cycle. Available non

- guideline acute contact toxic ity studies to other non

Apis terrestrial invertebrates corroborate enhanced toxicity to larvae as compared to adults. The
studies being requested will aid in evaluating this concern for honey bees which serve as a surrogate
for terrestrial invertebrates. A protocol for the honey bee larvae acute oral toxicity (OECD TG237) does not need to be submitted as this guideline is well characterized. However, a protocol (following the OECD draft guidance document, June 25, 2013) must be submitted for review and approval by the Agency prior to initiation of this study. Pending the results of this study, higher tiered ( e.g

. , semi

- field) studies as well as residue studies may be required. Practical Utility of the Data

How will the data be used? 

### Larval toxicity da ta for honey bees will be used to identify potential risks to terrestrial invertebrates resulting from exposure in the larval stage to spirodiclofen

. The data will reduce uncertainties
associated with the current risk assessment for terrestrial invertebra tes and will improve the Agency’s understanding of the potential effects of spirodiclofen on terrestrial invertebrate species at the larval stage

. If larval toxicity data are not submitted for honey bees , then risk to terrestrial
invertebrates from acute contact exposure will be presumed under the assumption that exposures may take place at the larval stage of the life cycle. Special Study: Field Trial of Residues in Pollen and Nectar (Tier 2) Rationale for Requiring the Data 

### Applications at bloom ma y result in exposure to honey bee brood

. Given the low toxicity to adults, potential contamination of pollen and nectar from applications at bloom may allow adult foragers to bring contaminated pollen and nectar back to the hives, which would then
result in exposure to the brood. If Tier I screening for risks to honey bees, which is based on conservative estimates and assumptions of exposure, yields risk of concern, then the Agency
will consider the need for studies that analyze residues in multiple crops based on certain
selective criteria in order to refine the exposure . The protocol will depend on application type

### 50

and crop. The registrant should consult the Agency on the design of the protocol prior to the initiation of the study. Practical Utility of the Data
How will the data be used? The data will be used to assess exposure and risk of spirodiclofen to non

- target listed and non

listed terrestrial in vertebrate species, including bee pollinators. These data would allow the Agency to refine the screen ing level risk assessment for pollinating bees

. Exposure data is an integral part of determining the potential for risk to pollinating bees through direct exposure
from their food sources. Special Study: Semi

- Field Testing for Pollinators (Tunnel or Col ony Feeding Studies) (Tier 2) The decision to move to more refined effects testing and to transition from laboratory

- based studies with individual bees ( i.e, Tier 1) to colony

- based studies (i.e. Tier 2 or Tier 3) depends
on whether Tier 1 LOCs are exceed ed, the availability of data, and the nature of the uncertainties that warrant further testing. The Tier 2 studies are typically considered “semi

field,” studies where small colonies are enclosed in tunnels, along with pesticide

- treated crops.
Tier 2 stu dies may also include feeding studies in which whole colonies are tested; however,
the colonies are not confined to enclosures. The design of the Tier 2 tunnel study should be flexible in addressing the specific risks identified in the Tier 1 risk assessm ent for either foliar application, seed or soil treatments, or other exposure routes of concern with reasonable
modifications. The registrant should consult the Agency on the design of the protocol prior to the initiation of the study. Practical Utility of the Data
How will the data be used?
Semi

- field studies provide a means of recording of a number of measurement endpoints including adult and larval survival, larval/pupa development, quee n fecundity, ad worker bee
behavior to estimate various attribute s regarding the whole colony.

### 51



# 12. References

Food and Agriculture Organization of the United Nations. 2000. FAO PESTICIDE DISPOSAL
SERIES 8. Assessing Soil Contamination: A Reference Manual. Appendix 2. Parameters of pesticides that inf

luence processes in the soil. Editorial Group, FAO Information Division: Rome, 2000. http://www.fao.org/DOCREP/003/X2570E/X2570E00.htm

.

Barfknecht, R

. 2003. Acute Oral Toxicity for Bobwh ite Quail ( Colinus virginianus ) for the Test Item BYI 08330 (techn.) Report/Doc number: BAR/LD 047.

Barfknecht, R

. 2004. BYI 08330 techn. a.s.: 5

- Day Dietary LC 50 

### Bobwhite Quail ( Colinus virginianus ) Report/Doc number: BAR/LC017, M

- 084796

- 01

- 2.

Stou ghton, T. 2006

. Technical BYI 08330: A Subacute Dietary LC50 with Mallards. Project Number: EBFNX012, M/274385/01/1. Unpublished study prepared by Bayer CropScience LP. 52 p.

EFSA. 2009. Conclusion on Pesticide Peer Review. Peer Review of the Pesticide Risk Assessment
of the Active Substance Spirodiclofen . (Question No EFSA

- Q

- 2009

- 669). EFSA Scientific Report (2009) 339, 1

- 86.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs . United States Environme ntal Protection Agency (USEPA). Environmental Fate and Effects Division. Office of Pesticide Programs. Available at http://www.epa.gov/espp/consultation/ecorisk

- overview.pdf (access ed 02/19/2014)

.

USEPA. 2005 a . Estimated Drinking Water Concentrations of combined residues of spirodiclofen and its degradates (spirodiclofen

- enol, spirodiclofen

- ketohydroxy, and spirodiclofen

dihydroxy) in surface water and groundwater. Memorandum fro m Faruque Kahn and Larry Liu (EFED) to Rita Kumar and Daniel Kenny (RD) and Mary Clock

- Rust and Tom Bloem (HED) dated January 4, 2005 (DP Barcode D311291).

USEPA. 2005 b . Environmental Fate and Ecological Risk Assessment of Spirodiclofen.
Memorandum f

rom Michael Rexrode, Larry Liu, and Faruque Kahn (EFED) to Rita Kumar and Meredith Laws (RD) Dated March 9, 2005 (DP Barcode D300903, D293789, D284995, and D309421).

USEPA. 2005 c . Environmental Fate and Ecological Risk Assessment of Spirodiclofen: Resp onse to RD on Mammalian Risk. Memorandum from Michael Rexrode (EFED) to Rita Kumar and Meredith Laws (RD) dated May 23, 2005.

USEPA. 2005 d . EFED’s Response to Sherry Movassaghi’s (Bayer Crop Science) Request to Modify the Recommended Bee Precautionary Labeling Statement for the Spirodiclofen End

Use Product, Envidor 2 SC. Memorandum from Gabe Patrick (EFED) to Rita Kumar and Meredith Laws (RD) dated June 16, 2005. (DP Barcode D317315).

USEPA. 200 6

. Standard Soil Mobility Classification Guidance

. Memorandum from D onald Brady dated April 21, 2006

.

### 52

USEPA. 2010. Guidance for Reporting on the Environmental Fate and Transport of the Stressors of Concern in Problem Formulations for Registration Review, Registration Review Risk Assessments, Listed Spec ies Litigation Assessments, New Chemical Risk Assessments, and Other Relevant Risk Assessments. Memorandum from Donald Brady dated January 25, 2010 ( http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_spec ies_reregistration_workgroup/esa_reporting_fate.htm ).

USEPA. 2011. Drinking Water Assessment for the Proposed IR

- 4 Use of the Spirodiclofen Product ENVIDOR® as a Miticide on Tropical Fruits. Memorandum from Larry Liu (EFED) to Laura Nollen and Barbara Madden (RD), dated April, 2011. (DP Barcode: D386204).

### 53



## Appendi x A . Nomenclature and Structures for Spirodiclofen and Its Major Degradates

For a figure of the proposed degradation pathway under aerobic soil conditions, see Figure A.1 at the end of this appendix.

Table A

- 1

. Spirodiclofen and Its Major Environmental Degradates

Common Name/ Synonym Chemical Name Chemical Structure Study Type Ref.
(MRID) Maximum

% Applied (day) Final %AR

(study length, day)

P arent 

### Spirodiclofen

(BAJ 2740 

# ) Chemical Name: 3

- (2,4

- Dichlorophenyl)

- 2

-

oxo

- 1

- oxaspiro[4.5]dec

- 3

- en

4

- yl 2,2

- dimethylbutyrate

CAS No. 148477

- 71

- 8

Molecular Weig ht: 411.3 g/mol

SMILES: O=C1C(=C(C2(O1)CCCCC2)OC(=O)C(C)( C)CC)c1c(cc(cc1)Cl)Cl

Molecular Formula:
C 21 H 24 Cl 2 O 4 Spirodiclofen Transformation Products

### 54

Common Name/ Synonym Chemical Name Chemical Structure Study Type Ref.
(MRID) Maximum

% Applied (day) Final %AR

(study length, day)


### BAJ 2740

- enol ( BAJ 2510 ) Chemical Name: 3

- (2,4

- Dichlorophenyl)

- 4

-

hydroxy

- 1

- oxaspiro[4.5]dec

3

- en

- 2

- one

CAS No. 148476

- 22

- 6

Molecular Weight: 313.2 g/mol

SMILES: c1cc(c(cc1Cl)Cl)C2=C(C3(CCCCC3)OC2=O )O

Molecular Formula:

C 15 H 14 Cl 2 O 3 Hydrolysis

45697217 29 (pH 4; Days 30) 52 (pH 7; Days 30) 101 (pH 9; Days 30) 29 (pH 4; Days

3 0) 52 (pH 7; Days 30) 101 (pH 9; Days 30) Soil photolysis
45297230 Not detected Not detected (Days 15)

Aerobic soil 45697204

45697228 17 (Days 6;

CA soil) 38 (Days 9; FL soil) 19 (Days 2; Germany BBA 2.2 soil) 52 (Days 2; Germany Hoefchen soil) Not detected

(Days 360; CA soil) 1 (Days 120; FL soil) 0.4 (Days 120; Germany BBA 2.2 soil)
Not detected (Days 120; Germany Hoefchen soil)
45 697206 43 (Days 13;

CA soil) 0.3 (Days 119;

CA soil) Aerobic aquatic 45697205 86 (Days 100; German pond system) 95 (Days 14;
German lake system) 78 (Days 1 12 ;

German pond system)
30 (Days 1 12 ; German lake system) Anaerobic aquatic 45697212 94 (Days 56;
CA lake system) 85 (Days 365;

CA lake system)

Terrestrial dissipation 45697207 0.02

- 0.130 ppm in 0

- 15 cm till Days 10 ( Florida ) Not detected

(Days 547)

Terrestrial dissipation 45697208 0.02

- 0.14 ppm
in 0

- 15 cm till Days 1y ( California ) Not detected

(Days 372)

### 55

Common Name/ Synonym Chemical Name Chemical Structure Study Type Ref.
(MRID) Maximum

% Applied (day) Final %AR

(study length, day)

Terrestrial dissipation 45697209 0.02

- 0.10 ppm
in 0

- 15 cm till Days 14 ( Washington ) No t detected

(Days 542)

Terrestrial dissipation
45697210 0.05

- 0.12 ppm
in 0

- 15 cm till Days 7 ( Ontario,
Canada ) Not detected

(Days 125)

Fish
bioaccumulation 45697002 62% of the
recovered in
edible tissue - -



### BAJ 2740

- ketohydroxy Chemical Name: 3

- (2,4

- Dichlorophenyl)

- 3

-

hydroxy

- 1

- oxaspiro[4.5]decane

- 2,4

- dione

CAS No. Not available

Molecular Weight: 329.2 g/mol

SMILES: c1cc(c(cc1Cl)Cl)C2(C(=O)C3(CCCCC3)OC 2=O)O

Molecular Formula:

C 15 H 14 Cl 2 O 4 Aerobic soil 4 5697204 28 ( Days 20;
California ) 44 (Days 30; Florida) 21 (Days 9; Germany) 11 (Days 3; Germany) 2 ( Days 360)

11 (Days 120) 1 (Days 120)
Not detected (Days 120)

4 5697206 8 ( Days 130;

California ) 0.2 ( Days 119)

Terrestrial dissipation 45697207 0.01 ppm in 0

- 15 cm (D ay 1;
Florida ) Not detected

(Days 547)

Terrestrial dissipation 45697208 0.006 ppm in
0

- 15 cm (Days 3; California ) Not detected

(Days 372)

Terrestrial dissipation 45697209 0.024 ppm in
0

- 15 cm ( Day 1; Washington ) Not detected

(Days 542)

Terrest rial dissipation 45697210 0.01

- 0.03 ppm
in 0

- 15 (Days
3

- 17; Ontario,
Canada ) Not detected

(Days 125)

### 56

Common Name/ Synonym Chemical Name Chemical Structure Study Type Ref.
(MRID) Maximum

% Applied (day) Final %AR

(study length, day)


### BAJ 2740

- dihydroxy Chemical Name: 3

- (2,4

- Dichlorophenyl)

- 3,4

-

hydroxy

- 1

- oxaspiro[4.5]decan

- 2

- one \

CAS No. not available

Molecular Weight: 331.2 g/mol

SMILES: c1cc(c(cc1Cl)Cl)C2(C(C3(CCCCC3)OC2=O )O)O

Molecular Formula:

C 15 H 16 Cl 2 O 4 Aerobic soil 4 5697204

4 5697206 16 ( Days 20;

California ) 5 (Days 30; Florida) 3 (Days 20; Germany) 1 (Days 3; Germany)

4 ( Days 28;
California ) 1 1 ( Days 360)

5 (Days 120)
Not detected (Days 120)
Not detected (Days 120)

2 ( Days 119)

Terrestrial dissipation 45697207 0.01 (Days 273; Florida ) Not detected

(Days 547)
Terrestrial dissipation 45697208 Not detected ( California ) Not detected

(Day s 372)
Terrestrial dissipation 45697209 Not detected ( Washington ) Not detected

(Days 542)
Terrestrial dissipation 45697210 Not detected ( Ontario,
Canada ) Not detected

(Days 125)



### BAJ 2740

- di oxoketone Chemical Name: 6'

- Chlorospiro[cyclohexane

1,2'( 3'H)

- furo[2,3

- b]benzofuran]

- 3'

- one

CAS No. not available

Molecular Weight: 276.7 g/mol

SMILES: c1cc2c(cc1Cl)oc3c2C(=O)C4(O3)CCCCC4

Molecular Formula:

C15H13ClO3 Aq photolysis 45697218 11 (Days 10) 9 (Days 12)



### DCB

- acid Chemical Na me: 2,4

- Dichlorobenzoic acid

CAS No. 50

- 84

- 0 Soil photolysis 45697230 14 (Days 15) 14 (Days 15)
Aerobic soil 4 5697204 2 ( Days 30;
California )
40 (Days 120; Florida) Not detected

( Days 360) 40 (Days 120) 2 (Days 120)

### 57

Common Name/ Synonym Chemical Name Chemical Structure Study Type Ref.
(MRID) Maximum

% Applied (day) Final %AR

(study length, day)
Molecular Weight: 191.01

SMILES: c1cc(c(cc1Cl)Cl)C(=O)O

Molecular Formula: C 7 H 4 Cl 2 O 2 3 (Days 13; Germany) 5 (Days 3; Germany) Not detected

(Days 120)

Terrestrial dissipation 45697207 Not detected ( Florida ) Not detected

(Days 547)
Terrestrial dissipation 4569720 8 Not detected ( California ) Not detected

(Days 372)
Terrestrial dissipation 45697209 Not detected ( Washington ) Not detected

(Days 542)
Terrestrial dissipation 45697210 Not detected ( Ontario,
Canada ) Not detected

(Days 125)

### 58

Figure A. 1. R egistrant

- p ostulated degradation pathway for s pirodiclofen under aerobic
conditions

### 59



# Appendix B. Spirodiclofen Fate and Ecological Effects Bibliography

1 24871 Spirodiclofen Fate Chemistry Bibliography

161

- 1 Hydrolysis

MRID Citation Reference

45697217 Babczinski, P. (2000) Hydrolysis of (Dihydrofuranone

- 3

- (Carbon 14)) BAJ 2740 in Sterile Aqueous Buffer Solutions: Lab Project Number:
M1110818

- 0: 109787: MR

- 489/99. Unpublished study prepared by Bayer AG. 85 p.



## 161

- 2 Photode gradation

- water

MRID Citation Reference

45697201 Hellpointner, E. (1998) Determination of the Quantum Yield and Assessment of the Environmental Half

- Life of the Direct Photodegradation of BAJ 2740 in Water: Lab Project Number: M1430843

- 3: 108547: 4378. Unpublished study prepared by Bayer Corporation. 32 p.

45697218 Stupp, H. (2001) Photolysis of BAJ 2740 in Aqueous Buffer Solution at pH 4 Under Controlled Conditions: Lab Project Number: M1121076

- 8: 110030. Unpublished study prepared by Bayer AG . 59 p.

45697227 Babczinski, P. (2000) Photolysis of BAJ 2740

- Enol (BAJ 2510) in Natural Water: Lab Project Number: M 112 1023

- 0: 110866: MR

- 294/2000. Unpublished study prepared by Bayer AG. 62 p.



## 161

- 3 Photodegradation

- soil

MRID Citation Reference

45697230 Hellpointner, E. (2000) Photolysis of (Dihydrofuranon

- 3

- (Carbon 14)) BAJ2740 on Soil Surfaces: Lab Project Number: M 113 0866

- 5: 110871: MR

708/99. Unpublished study prepared by Bayer AG. 60 p.



## 162

- 1 Aerobic soil meta bolism

### 60

MRID Citation Reference

45697204 Oi, M.; Bornatsch, W. (1999) Aerobic Degradation and Metabolism of BAJ 2740 in Soil: Lab Project Number: M1250817

- 4: 109581. Unpublished study prepared by Bayer AG. 128 p.

45697206 Oi, M. (1999) Aerobic Metabolism of (Cyclohexyl

- l

- (Carbon 14)) BAJ 2740 in Soil: Lab Project Number: M1250895

- 0: 109583: MR060/99. Unpublished study prepared by Bayer AG. 38 p.

45697215 Burhenne, J. (1999) Degradation of (Oxolan

- 3

- (Carbon 14)) BAJ 2740

- Dihydroxy in Two Soils Under Aerobic Conditions: Lab Project Number:
1250004

- 2: 109760. Unpublished study prepared by University of Kassel. 53

p.

45697224 Burhenne, J. (1999) Aerobic Degradation of (phenyl

- UL

- (Carbon 14)) 2,4

- Dichlorobenzoic Acid on Soil: Lab Project Number: 125001

- 9: 110863. Unpublished study prepared by University of Kassel. 49 p.

45697226 Scholz, K. (2000) Degradation of (Carbon 14) BAJ2740

- Dihydroxy in a Soil Under Aerobic Conditions: Lab Project Number: M1250996

- 2: 110865. Unpublished study prepared b y Bayer AG. 31 p.

45697228

45697310 Schad, T. (2000) Calculation of Half

- Lives of BAJ2740 and its Main
Metabolites BAJ2740

- Enol and BAJ2740

- Ketohydroxy Generated by Aerobic Soil Degradation: Lab Project Number: P668 00 6763: 110867: MR

- 405/00. Unpub lished study prepared by Bayer AG. 29 p.

Babczinski, P. (2002) Collection of Additional Soil Data Supporting Diverse Metabolism Studies on BAJ2740 and Related Metabolites: Lab Project
Number: M9991193

- 1: MR

- 126/02. Unpublished study prepared by Bayer AG. 10 p.



## 162

- 3 Anaerobic aquatic metab.

MRID Citation Reference

45697212 Wujcik, C.; Desmarteau, D.; Arthur, E. (1999) Anaerobic Aquatic Metabolism of (Dihydrofuranone

- 3

- (Carbon 14)) BAJ 2740 in a Fresno, California Water and Sedim ent System: Lab Project Number: BJ042401: 109728. Unpublished study prepared by Bayer Corporation. 110 p.

46865401 Mislankar, S. (2000) Anaerobic Aquatic Metabolism of [Dihydrofuranone

- 3

- (Carbon 14)] BAJ 2740 in a Fresno, California Water and Sediment Sy stem. Project Number: 109728/1, BJ042401. Unpublished study prepared by Bayer Corp. 110 p.



## 162

- 4 Aerobic aquatic metab.

### 61

MRID Citation Reference

45697205 Riegner, K. (1999) Aerobic Aquatic Degradation and Metabolism of BAJ 2740
in the Wate r

- Sediment System: Lab Project Number: M 151 0865

- 6: 109582: 4431. Unpublished study prepared by Bayer AG. 87 p.



## 163

- 1 Leach/adsorp/desorption

MRID Citation Reference

45697213 Oi, M. (1999) Adsorption/Desorption of BAJ 2510 (Enol

- BAJ 274 0) in Soil: Lab Project Number: 109758: M 131 0874

- 4: 4350. Unpublished study prepared by Bayer AG. 55 p.

45697214 Burhenne, J. (1999) Adsorption/Desorption of [Oxolan

- 3

- (Carbon

- 14)] BAJ
2740

- Dihydroxy on Soils: Lab Project Number: 109759: 1310012

- 8. Un published study prepared by University of Kassel. 40 p.

45697216 Babezinski, P. (2000) Aged Soil Column Leaching of BAJ 2740: Lab Project
Number: M1210862

- 0: 109786. Unpublished study prepared by Bayer AG. 86

p.

45697219 Shepherd, J.; Arthur, E. (200 2) Mobility Determination of BAJ2740 by Soil
Thin

- Layer Chromatography in Four Soils: Lab Project Number: BJ182101: 110343. Unpublished study prepared by Bayer Corporation. 54 p.

45697222 Aga, D.; Desmarteau, D. (2001) Estimation of the Adsorption Coeff icient (Koc) of BAJ 2740 Dioxoketone on Soil using High Performance Liquid Chromatography (HPLC): Lab Project Number: BJ184001: 110768. Unpublished study prepared by Bayer Corporation. 23 p.

45697223 Burhenne, J. (1999) Adsorption/Desorption of 2,4

- Dich lorobenzoic Acid on Soils: Lab Project Number: 1310011

- 7: 110862. Unpublished study prepared by University of Kassel. 43 p.

45697225 Hein, W. (2000) Adsorption/Desorption of (oxolan

- 3

- (Carbon 14)) KTS 9301

- 4A (Ketohydroxy

- BAJ2740) on Four Different Soils: Lab Project Number: BAY38: 110864. Unpublished study prepared by Staatliche Lehr

- und Forschungsanstalt fur Landwirtschaft. 28 p.

45697229 Gilges, M.; Babczinski, P.; Gilges, M. (2001) Leaching Behaviour of BAJ2740 in Four Soils: Amended Repo rt: Lab Project Number: M 1211000

- 5: 110868: MR 455/00. Unpublished study prepared by Bayer AG. 61 p.

45697307 Sabbagh, G.; Fisher, J. (2002) Estimating BAJ 2740 Soil Adsorption Value for Surface and Ground Water Modeling: Lab Project Number: 110984.
U npublished study prepared by Bayer Corporation. 24 p.



## 163

- 3 Volatility

– field

### 62

MRID Citation Reference

45697321 Pangilinan, N.; Jantzen, T. (1998) Determination of the Volatilization Behavior of BAJ 2740 (SC240) in a Field Trial: Lab Project Number: M1180963

- 8: 108900. Unpublished study prepared by Bayer AG. 47 p.



## 164

- 1 Terrestrial field dissipation

MRID Citation Reference

45697207 South, N.; Davis, M. (1998) BAJ 2740 Terrestrial Field Dissipation Study on Florida So il, 1998: Lab Project Number: AG90016: F98623

- 001: BJ022101. Unpublished study prepared by Battelle Memorial Institute, A & L Great Lakes Laboratories, Inc., Bayer Corporation and EPL, Bio

- Analytical Services, Inc. 188 p.

45697208 South, N.; Davis, M. ( 2001) BAJ 2740 Terrestrial Field Dissipation Study on California Soil, 1998: Lab Project Number: BJ022101: 109650: AG990016. Unpublished study prepared by Battelle Memorial Institute, A & L Great Lakes Laboratories, Inc., Bayer Corporation and Bayer Resear ch Farm. 181 p.

45697209 South, N.; Davis, M. (2001) BAJ 2740 Terrestrial Field Dissipation Study on Washington Soil, 1998: Lab Project Number: 109652: BJ022103: AG990018. Unpublished study prepared by Battelle Memorial Institute, A & L Great Lakes
Labo ratories Inc., Bayer Corporation and Qualls Agricultural Laboratories,Inc. 185 p.

45697210 Davis, M.; South, N. (2001) Terrestrial Field Dissipation of BAJ 2740 in Ontario Soil, 1999: Lab Project Number: AG990020: F99578

- 001: BJ022104. Unpublished study prepared by Battelle Memorial Institute, A & L Great Lakes Laboratories, Inc., Bayer Corporation and Vaughn Agricultural Research Services, Ltd. 158 p.



## 165

- 4 Bioaccumulation in fish

MRID Citation Reference

45697002 Dorgerloh, M.; Kos ter, J.; Riegner, K. (2000) (Carbon 14)

-- BAJ 2740

-- Bioconcentration in Bluegill (Lepomis macrochirus) under Flow

- Through Conditions: Lab Project Number: 109694: E 244 1065

- 2: DOM 96017. Unpublished study prepared by Bayer AG. 112 p.



## Nonguideline S tudies

### 63

MRID Citation Reference

42967211

45967221 South, N. (2001) Laboratory Validation of Analytical Method for the Determination of BAJ 2740 and its Relevant Metabolites in Soil: Lab Project Number: AF000003: BJ112101: 109669. Unpublish ed study prepared by Battelle Memorial Institute. 151 p. {OPPTS 850.7100}

South, N. (2001) Laboratory Validation of Analytical Method for the Determination of BAJ 2740 and its Relevant Metabolites in Soil: Lab Project
Number: AF000003: BJ112101: 109669

4 5697220 Mattern, G.; Lam, C. (2001) Determination of BAJ 2740 in Water by HPLC: Lab Project Number: 110615: BJ881601. Unpublished study prepared by Bayer Corporation. 14 p.

45697203 Sommer, H. (1999) Method for Determination of BAJ 2510 in Test Water fr om Aquatic Toxicity Tests by HPLC: Lab Project Number: P60497051: 109488: 00593. Unpublished study prepared by Bayer AG. 13 p. {OPPTS 860.1400}

45697303 Wood, S. (2002) Analysis for BAJ 2740 Dioxoketone in Soils from BAJ 2740 Soil Dissipation Studies in Florida, Washington, California, and Ontario: Lab Project Number: 110972: BJ192101: BJ022102. Unpublished study prepared by Bayer Corporation. 29 p.



# 107091 Spirodiclofen Eco Effects Bibliography

71

- 1 Avian Single Dose Oral Toxicity

MRID Citatio n Reference

45697004 Barfknecht, R. (1999) BAJ 2740

-- Acute Oral Toxicity for Bobwhite Quail (Colinus virginianus): Lab Project Number: 109696: BAR/LD 018: E 292 1326

- 5. Unpublished study prepared by Bayer AG. 35 p.

45697111 Barfknecht, R. (2000) BAJ 2740 Enol: Acute Oral Toxicity for Bobwhite Quail (Colinus virginianus): Lab Project Number: 110637: E 292 1853

- 0: BAR/LD033. Unpublished study prepared by Bayer Ag Institute for Environmental Biology. 33

p.

45697112 Barfknecht, R. (2000) BAJ 2740 4

- Hydroxy

- enol: Acute Oral Toxicity for Bobwhite Quail (Colinus virginianus): Lab Project Number: 110638: E 292
1854

- 1: BAR/LD034. Unpublished study prepared by Bayer Ag. 34 p.

### 64



## 71

- 2 Avian Dietary Toxicity

MRID Citation Reference

45697 003 Barfknecht, R. (1999) BAJ 2740 techn.: 5

- Day Dietary LC50 for Bobwhite Quail (Colinus virginianus): Lab Project Number: 109695: E 295 1325

- 7: BAR/LC 003. Unpublished study prepared by Bayer AG. 32 p.

45697104 Barfknecht, R. (2000) Amendment Number 1: BAJ 2740 Techn. ai.: Effects of a Subchronic Dietary Exposure to the Northern Bobwhite Quail Including Effects on Reproduction and Behavior: Lab Project Number: 110344: E 298 1327

- 2: BAR/REP002. Unpublished study prepared by Bayer AG Crop Protection. 11 6

p.

45697118 Barfknecht, R. (1998) BAJ 2740 techn: 5

- Day Dietary LC50 to Mallard Duck (Anas platyrhynchos): Amendment No. 1: Lab Project Number: E 297 1324

- 8: 110769: BAR/LC002. Unpublished study prepared by Bayer AG. 35 p.



## 71

- 4 Avian Reproduc tion

MRID Citation Reference

45697104 Barfknecht, R. (2000) Amendment Number 1: BAJ 2740 Techn. ai.: Effects of a Subchronic Dietary Exposure to the Northern Bobwhite Quail Including Effects on Reproduction and Behavior: Lab Project Number: 11034 4: E 298 1327

- 2: BAR/REP002. Unpublished study prepared by Bayer AG Crop Protection. 116

p.

45697107 Bowers, L. (2001) Effect of Technical BAJ 2740 on Mallard Reproduction: Lab Project Number: BJ740801: 110591. Unpublished study prepared by Bayer Corpor ation. 112 p.



## 72

- 1 850.1075 Acute Toxicity to Freshwater Fish

MRID Citation Reference

4569692
6 Dorgerloh, M. (1999) BAJ 2740

-- Acute Toxicity (96 Hours) to Bluegill (Lepomis macrochirus) under Flow

- Through Conditions (Limit Test): Lab Project Number: E 253 1320

- 6: 109687: DOM 98002. Unpublished study prepared by Bayer AG. 46 p.

4569700
1 Dorgerloh, M. (1999) BAJ 2740

-- Acute Toxicity (96 hours) to Rainbow Trout (Oncorhynchus mykiss) under Flow

- Through Conditions (Limit Test): Lab Project Number: 109688: E 251 1319

- 2: DOM 98001. Unpublished study prepared by Bayer AG. 46 p.

4569700
6 Dorgerloh, M. (1999) BAJ 2740 SC 240

-- Acute Toxicity (96 hours) to Rainbow Trout (Oncorhynchus mykiss) in a Static Test (Limit Test): Lab Project N umber: 109699: E 250 1330

- 4: DOM 98006. Unpublished study prepared by Bayer AG. 45 p.

### 65

4569700
9 Dorgeloh, M. (1999) BAJ 2740 SC 240

-- Acute Toxicity (96 hours) to Bluegill (Lepomis macrochirus) in a Static Test (Limit Test): Lab Project
Number: E 252 132 9

- 4: 109702: DOM 98007. Unpublished study prepared by Bayer AG. 45 p.

4569701
5 Peither, A. (1999) Acute Toxicity of BAJ 2740

- Enol to Rainbow Trout (Oncorhynchus mykiss) in a 96

- Hour Static Test: Lab Project Number: 743084: 109709. Unpublished study pre pared by RCC Ltd. 39 p. {OPPTS 850.1075}



## 72

- 2 Acute Toxicity to Freshwater Invertebrates

MRID Citation Reference

45696924 Heimbach, F. (1998) Acute Toxicity of BAJ 2740 (tech.) to Water Fleas (Daphnia magna) under Flow

- Through Test Co nditions: Lab Project Number: E
320 1331

- 3: 108744: HBF/DM 191. Unpublished study prepared by Bayer AG. 47 p.

45697013 Heimbach, F. (1998) Acute Toxicity of BAJ 2740 SC 240 to Water Fleas (Daphnia magna): Lab Project Number: 109707: E 320 1415

- 6: HBF/DM 200. Unpublished study prepared by Bayer AG. 40 p.

45697014 Heimbach, F. (2000) Acute Toxicity of BAJ 2740

- Enol to Water Fleas (Daphnia magna): Lab Project Number: E 320 1715

- 9: 109708: HBF/DM 217. Unpublished study prepared by Bayer AG. 34 p.

456970 26 Hall, A.; Lam, C. (2000) Acute Toxicity of BAJ 2740 Technical to the Waterflea (Daphnia magna) Under Static

- Renewal Conditions: Lab Project Number: BJ820701: 109892. Unpublished study prepared by Bayer Corp. 31 p.



## 72

- 3 Acute Toxicity to Est uarine/Marine Organisms

MRID Citation Reference

45697018 Drottar, K.; Krueger, H. (2000) BAJ 2740: A 96 Hour Flow

- Through Acute Toxicity Test with the Saltwater Mysid (Mysidopsis bahia): Lab Project Number:
149A

- 116: BJ833101: 109743. Unpublished study prepared by Wildlife International, Ltd. 42 p. {OPPTS 850.1035}

45697019 Drottar, K.; Krueger, H. (2000) BAJ 2740: A 96 Hour Shell Deposition Test with the Eastern Oyster (Crassostrea virginica): Lab Project Number: 149A

- 119: BJ881501: 109744. Un published study prepared by Wildlife International, Ltd. 43 p. {OPPTS 850.1025}

45697027 Hall, A.; Lam, C. (2000) Acute Toxicity of BAJ 2740 (Technical) to the Sheepshead Minnow (Cyprinodon variegatus) Under Flow

- Through Conditions: Lab Project Number: BJ812801: 109894. Unpublished study prepared by Bayer Corp. 31 p.



## 72

- 4 Fish Early Life Stage/Aquatic Invertebrate Life Cycle Study

### 66

MRID Citation Reference

45697012 Heimbach, F. (1998) Influence of (Carbon 14)

- BAJ 2740 (Technical) on the Reproduction of Water Fleas under Flow

- Through Test Conditions: Lab Project
Number: 109706: E 321 1332

- 5: HBF/RDM 63. Unpublished study prepared by Bayer AG. 79 p.

45697023 Drottar, K.; Kendall, T.; Krueger, H. (2000) BAJ 2740: A Flow

- Through Life

Cycle Toxicity Test with the Saltwater Mysid (Mysidopsis bahia): Lab Project
Number: 149A

- 118A: BJ843101: 109788. Unpublished study prepared by Wildlife International, Ltd. 66 p. {OPPTS 850.1350U

45697101 Hall, A.; Lam, C. (2001) Chronic Toxicity of BAJ 2740 Technical to the Waterflea (Daphnia magna) Under Flow

- Through Conditions: Lab Project Number: 110095: BJ820702. Unpublished study prepared by Bayer Corporation. 52 p.

45697103 Lima, W. (2001) BAJ 2510 (Metabolite of BAJ 2740)

-- Life

- Cycle Toxicity Test with Mysids (Mysidopsis bahia): Lab Project Number: 110199: BJ843102: 13507.6137. Unpublished study prepared by Springborn Laboratories, Inc. 69 p.

45697109 Dorgerloh, M. (2000) (Carbon 14)

- BAJ 2740

-- Early Life Stage Toxicity to Rainbow Trout (Oncorhync hus mykiss) Under Flow

- Through Conditions

-- Amendment No. 1: Lab Project Number: E 284 1198

- 3: 110632: DOM 98022. Unpublished study prepared by Bayer Ag Crop Protection

- Development. 74 p.

45697125 Dorgerloh, M. (2001) BAJ 2740

- enol

-- Early Life Stage Toxi city to Rainbow Trout (Oncorhynchus mykiss) Under Flow

- Through Conditions: Lab Project Number:
E 284 1779

- 8: 110794: DOM 20026. Unpublished study prepared by Bayer AG. 87 p.

45697126 Hendel, B. (2000) Influence of BAJ 2740

- enol on the Reproduction Rate of Water Fleas: Lab Project Number: E 321 1811

- 7: 110850: HDB/RDM 65. Unpublished study prepared by Bayer AG Institute for Environmental Biology. 63 p.



## 72

- 5 Life cycle fish

MRID Citation Reference

45697102 Dionne, E. (2001) BAJ 2510

-- Chronic T oxicity to the Sheepshead Minnow (Cyprinodon variegatus) During a Full Life

- Cycle Exposure: Lab Project Number: 13507.6128: BJ852801: 110096. Unpublished study prepared by Springborn Laboratories, Inc. 507 p.



## 122

- 1 Seed Germination/Seedline Emerge nce and Vegetable Vigor

MRID Citation Reference

45696925 Bowers, L.; Dollinger, M. (2000) Tier 1 Seedling Emergence and Vegetative Vigor Nontarget Phytotoxicity Study Using BAJ 2740 240 SC: Lab Project

### 67 Number: 109597: BJ451601: BJ451602. Unpublis hed study prepared by Bayer Corp. 89 p.



## 122

- 2 Aquatic plant growth

MRID Citation Reference

45697005 Anderson, J. (1998) Influence of BAJ 2740 (techn.) on the Growth of the Green Alga, Pseudokirchneriella subcapitata (formerly Selenastru m capricornutum): Lab Project Number: E 323 1342

- 8: 109698: AJO/166597. Unpublished study prepared by Bayer AG. 43 p.

45697011 Dorgeloh, M. (1999) BAJ 2740 SC 240

-- Influence on the Growth of the Green Alga, Selenastrum capricornutum: Lab Project Number: 109705: E 323 1343

- 9: DOM 98045. Unpublished study prepared by Bayer AG. 38 p.

45697016 Seyfried, B. (2000) Toxicity of BAJ 2740

- Enol to Pseudokirchneriella Subcapitata (formerly Selenastrum Capricornutum) in a 96

- Hour Algal Growth
Inhibition Test: Lab Project Number: 743106: 109710: 743117. Unpublished study prepared by RCC Ltd. 51 p. {OPPTS 850.5400}

45697028 Hancock, G.; Lam, C. (2001) Toxicity of BAJ 2740 (Technical) to Duckweed (Lemna gibba G3): Lab Project Number: BJ881601: 110009. Unpublished study prepared by Bayer Corp. 39 p.



## 123

- 1 Seed germination/seedling emergence and vegetative vigor

MRID Citation Reference

45697025 Bowers, L. (2001) Tier 2 Seedling Emergence and Vegetative Vigor Nontarget Phytotoxicity Study Using BAJ 2740 S C240: Lab Project Number: 109853: BJ451603: BJ451604. Unpublished study prepared by Bayer Corp. 77 p.



## 141

- 1 Honey bee acute contact

MRID Citation Reference

45697010 Weyman, G. (1998) BAJ 2740 SC 240

-- Acute Contact and Oral Toxicity to th e Honey Bee, Apis mellifera: Lab Project Number: 262/99

- D2145: 109703: 262/99. Unpublished study prepared by Covance. 28 p.

45697017 Kleiner, R. (1998) Testing Toxicity to Honeybee

-- Apis mellifera L. (Laboratory): BAJ 2740: Lab Project Number: 97 10 48 069: 109711. Unpublished study prepared by BioChem Agrar. 26 p.



## 141

- 5 Field test for pollinators

### 68

MRID Citation Reference

45697105 Maus, C.; Doering, J. (2001) Evaluation of the Effects of BAJ 2740 SC 240 on the Development of Bee Colonies and the Behavior and Mortality of Honey Bees (Apis mellifera) in Orchards Under Semi Field Conditions (Location Laacher Hof): Lab Project Number: 110345: MAUS/AM 011: E 319 2058

- 8. Unpublished study prepared by Bayer AG Crop Protection. 37 p.



## 850.3040 Field testing for pollinators

MRID Citation Reference

48749301 Schur, A. (2006) Assessment of Side Effects of Spirodiclofen SC 240 on the Honey Bee (Apis mellifera L.) in the Field: Final Report. Project Number: 20051112/01/BFEU, G05N003B, G05N004B. U npublished study prepared by GAB Biotechnologie Gmbh. 315p.



## 143

- 2 Toxicity to Predators and Parasites in Fruit and Nut Crops

MRID Citation Reference

45697114 Gossmann, A. (2000) Effects of BAJ 2740 SC 240 on Predatory Mites Typhlodromus pyri Sc heuten (Acari, Phytoseiidae) in Orchards, Field Experiment: Lab Project Number: 3351064: 110641. Unpublished study prepared by IBACON GmbH. 35 p.

45697120 Neumann, P. (2000) Effects of BAJ 2740 SC 240 on the Life Cycle of the Predaceous Mite Typhlodromu s pyri under Extended Laboratory Conditions: Amendment 1: Lab Project Number: E 287 1582

- 4: 110789: NNP/TP004. Unpublished study prepared by Bayer AG Agricultural Centre Institute for Environmental Biology. 33 p.

45697121 Schmuck, R. (1998) Effects of B AJ 2740 SC 240 on the Life Cycle of the Predaceous Mite Typhlodromus pyri, Under Laboratory Conditions: Lab Project
Number: E 387 1354

- 1: 110790: TP 02. Unpublished study prepared by Bayer AG Crop Protection Institute for Environmental Biology. 24 p.

456 97122 Aldershof, S. (2000) Evaluating Effects of a Single BAJ 2740 SC 240 Application on the Predatory Mite Fauna (Acari: Phytoseiidae) in the Field (Apple Orchards): Lab Project Number: B017AFF: 110791. Unpublished study prepared by MITOX. 36 p.

456971 23 Bruhnke, C. (2000) BAJ 2740 SC 240 Laboratory Test on Paradosa spp. (Araneae, Lycosidae): Lab Project Number: IPA 71801: 110792: 000323BL. Unpublished study prepared by Laboratorium Fur Angewandte Biologie. 35 p.



## Non

- Guideline Study

### 69

MRID Citation Reference

45696922 Christenson, W.; Freyberger, A.; Sangha, G.; et al. (2002) The Development and Integration of a Toxicological Mode of Action (MOA) into the Hazard (and Risk) Assessment for a Proposed Agrochemical (BAJ 2740) with Endocrine Disrup ting Properties Including Evidence of a Carcinogenic Potential: Lab Project Number: 111009. Unpublished study prepared by Bayer Corp. 125 p.

45697007 Heimbach, F. (2000) Acute Toxicity of BAJ 2740

- Enol to Earthworms (Eisenia fetida): Lab Project Number: 109700: E 310 1652

- 8: HBF/RG 322. Unpublished study prepared by Bayer AG. 19 p.

45697008 Heimbach, F. (1998) Acute Toxicity of BAJ 2740 (tech.) to Earthworms (Eisenia fetida): Lab Project Number: E 310 1317

- 6: 109701: HBF/RG 271. Unpublished study prep ared by Bayer AG. 18 p.

45697020 Kendall, T.; Nixon, W. (2000) Analytical Method Verification and Determination of the Solubility of BAJ 2740 in Freshwater: Lab Project Number: 149C

- 110: BJ881301: 109745. Unpublished study prepared by Wildlife Internati onal, Ltd. 34 p.

45697021 Kendall, T.; Nixon, W. (2000) Analytical Method Verification and Determination of the Solubility of BAJ 2740 in Saltwater: Lab Project Number: 149C

- 111: BJ881302: 109746. Unpublished study prepared by Wildlife International, Lt d. 34 p.

45697022 Heimbach, F. (2000) Influence of BAJ 2740

- Enol on Dependent and Emergence of Larvae of Chironomus riparius in a Water

- Sediment System: Lab Project Number: 109776: E 416 1741

- 4: HBF/CH 38. Unpublished study prepared by Bayer AG. 46 p.

45697024 Fuhrman, V. (2000) BAJ 2740: Validation of an HPLC Method, and Determination of Homogeneity and Animal Room Stability in Avian Feed in Support of an Avian Reproduction Test: Lab Project Number: 99052: BJ111901: 109794. Unpublished study prepared by Genesis Laboratories, Inc. 32 p. {OPPTS 850.2300}

45697106 Meisner, P. (2000) Acute Toxicity of BAJ 2740 Ketohydroxy to Earthworms (Eisenia fetida): Lab Project Number: 110346: E 310 1885

- 6: MPE/RG 348/00. Unpublished study prepared by Bayer AG Crop Protection. 20 p.

45697108 Schuld, M. (2000) BAJ 2740 SC 240 Toxicity to the Egg Parasitoid, Trichogramma cacoeciae Marchal (Hymenoptera, Calcidoidae) in the Laboratory: Lab Project Number: 20001048/01

- NLTC: 110631. Unpublished study prepared by Arbeit sgemeinschaft, GAB Biotechnologie GmbH & IFU Umweltanalytik GmbH. 30 p.

45697110 Mead

- Briggs, M. (1998) Laboratory Tests to Determine the Effect of BAJ 2740 SC 240 on the Parasitic Wasp Aphidius rhopalosiphi: Lab Project
Number: BAY

- 98

- 1: 110633. Unpubl ished study prepared by Agrochemical Evaluation Unit, School of Biological Sciences, the University of Southampton. 21 p.

45697113 Kleiner, R. (2000) BAJ 2740 SC 240 Toxicity to the Predatory Mite Typhlodromus pyri (Scheuten) Under Extended Laboratory C onditions: Lab Project Number: 110640: 99 10 48 114. Unpublished study prepared by BioChem agrar. 26 p.

### 70

45697115 Moll, M. (1998) Effects of BAJ 2740 SC 240 on the Lacewing Chrysoperla carnea Steph. (Neuroptera, Chrysopidae) in the Laboratory: Lab Projec t Number: 3352046: 110765. Unpublished study prepared by Institut fur Biologische Analytik und Consulting IBACON GmbH. 32 p.

45697116 Oberwalder, C. (1998) A Field Study to Evaluate the Effects of BAJ 2740 SC 240 Containing 240g/L a.i. Against the Preda tory Mite, Typhlodromus pyri in Vines (One Location in Germany): Lab Project Number: 98110/G1

- NFTP: 110766: G98007E. Unpublished study prepared by Arbeitgemeinschaft GAB Biotechnologie GmbH and IFU Umweltanalytik GmbH. 36 p.

45697117 Heimbach, F. (1999) Amendment No. 1 of August 21, 2000 Influence of BAJ 2740 (tech.) on Development and Emergence of Larvae Chironomus riparius
in a Water

- Sediment System: Lab Project Number: HBF/CH 34: 110767: E
416 1538

- 8. Unpublished study prepared by Bayer AG Institute f or Environmental Biology. 51 p.

45697119 Meisner, P. (2001) Acute Toxicity of Spirodiclofen SC 240 to Earthworms, Eisenia fetida: Lab Project Number: E 310 2041

- 1: 110788: MPE/RG 363/01. Unpublished study prepared by Bayer AG Crop Protection Institute f or Environmental Biology. 21 p.

45697124 Schmuck, R. (1998) Acute Effects of a Spray Application of BAJ 2740 SC 240 on Carabid Beetles, Poecilus cupreus, Under Laboratory Conditions: Lab Project Number: E 371 1311

- 7: 110793: SXR/LA PC034. Unpublished s tudy prepared by Bayer AG Institute for Environmental Biology. 24 p.

45697127 Sabbagh, G. (2002) Ecotoxicology Aquatic Exposure Assessment for BAJ 2740: Lab Project Number: 111033. Unpublished study prepared by Bayer Corporation Agriculture Division. 46 p.

45697203 Sommer, H. (1999) Method for Determination of BAJ 2510 in Test Water from Aquatic Toxicity Tests by HPLC: Lab Project Number: P60497051: 109488: 00593. Unpublished study prepared by Bayer AG. 13 p. {OPPTS 860.1400}

### 71



## Appendix C . SIP Outp ut

Table 1. Inputs

Parameter Value

Chemical name Spirodiclofen Solubility (in water at 25 o C; mg/L) 0.05

Mammalian LD 50 (mg/kg

- bw) 2000 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Mammalian NOAEL (mg/kg

- bw) 350 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg

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

Mineau scal ing factor 1.15

Mallard NOAEC (mg/kg

- diet) 731 Bobwhite quail NOAEC (mg/kg

- diet) 691 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) 0.0086 0.0086 Adjusted toxicity value (mg/kg

- bw) 1538.3211 269.2062 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 concern for mammals

Table 3. Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg

- bw) 0.0405 0.0405 Adjusted toxicity value (mg/kg

- bw) 1038.4508 36.2668 Ratio of exposure to acute toxicity 0.0000 0.0011

Conclusion* Drinking water exposure alone is NOT a potential concern for birds Drinking water exposure alone is NOT a potential concern for birds

### 72



## Appendix D. STIR Output



# Input

Application and Chemical Information

Enter Chemical Name Spirodiclofen

Enter Chemical Use Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) ground Enter Chemical Molecular Weigh t (g/mole) 411.3 Enter Chemical Vapor Pressure (mmHg) 2.30E

- 09 Enter Application Rate (lb a.i./acre) 0.53

Toxicity Properties

Bird

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

Enter Tested Bir d Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD 50 (mg/kg bw) 2000

Enter Lowest Rat Inhalation LC 50 (mg/L) 5.03 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35



# Output
Results Avian (0.020 kg )

Maxi mum Vapor Concentration in Air at Saturation (mg/m 3 ) 5.09E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 6.40E

- 06

Adjusted Inhalation LD 50 2.02E+01
Ratio of Vapor Dose to Adjusted Inhalation LD 50 3.17E

- 07 Exposure not Likely Significant

Maxim um Post

- treatment Spray Inhalation Dose (mg/kg) 5.60E

- 02 Ratio of Droplet Inhalation Dose to Adjusted Inhalation
LD 50 2.77E

- 03 Exposure not Likely Significant



### Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation ( mg/m 3 ) 5.09E

- 05

Maximum 1

- hour Vapor Inhalation Dose (mg/kg) 8.04E

- 06

Adjusted Inhalation LD 50 2.99E+02
Ratio of Vapor Dose to Adjusted Inhalation LD 50 2.69E

- 08 Exposure not Likely Significant

Maximum Post

- treatment Spray Inhalation Dose (mg/kg ) 7.04E

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

- 04 Exposure not Likely Significant