UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON. D.C. 20460 

OFFICE OF CHEMICAL SAFETY 

AND POLLUTION PREVENTION 

PC Code: 124871 

DP Barcode: 422433 

MEMORANDUM 

SUBJECT: Registration Review - Problem Formulation for the Ecological Risk Assessment 

and Drinking Water Exposure Assessment to Be Conducted for Spirodiclofen 

Justin Housenger, Biologist ~~e fj/ fJ o! /~g/;>'" FROM: 

Larry 

Environmen

Liu, PhD, 

tal Risk 

Chemist 

Branch 5 

t{;7 ~ 

Environmental Fate and Effects Division (7507P) # _ 

THROUGH: Mah Shamim, PhD, Branch Chief AA4tl~ ol I ).S/ /~ Environmental Risk Branch 5 1//Y::..::------

Environmental Fate and Effects Division (7507P) 

TO: Julia Stokes, Chemical Review Manager 

Jill Bloom, Team Leader 

Linda Arrington, Branch Chief 

Risk Management and Implementation Branch 5 

Pesticide Re-Evaluation Division (7508P) 

Please, find attached the Preliminary Problem Formulation for the Ecological Risk Assessment 

and Drinking Water Exposure Assessment for Registration Review to be conducted for . 

Spirodiclofen. 
2

Contents

1. Executive summary................................................................................................................. 3

2. Introduction............................................................................................................................. 8

3. Use Characterization............................................................................................................... 9

4. Conclusions from Previous Risk Assessments....................................................................... 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 spirodiclofen (BAJ 2740). The problem formulation 

describes the methods planned to be used during the completion of drinking water and ecological 

risk assessments in support of registration review and provides an overview of the environmental 

fate, ecological effects, and potential risks associated with the use of spirodiclofen as well as

uncertainties unique to risk assessment of spirodiclofen. 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 new 

studies be submitted.

835.4400 Anaerobic Aquatic Metabolism. Only one water/sediment system is available. EFED 

recommends that the registrant select an additional 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 conservative 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 Laboratory 

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 which 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 exceed 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, Freshwater1,2 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 sediment 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 the 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 

50% emergence in the next two lowest concentrations (100 and 180 μg a.i/L). These results 

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 protocol 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 Invertebrates, Freshwater1,3. 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 insects 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 sediment system not be aged prior to 

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 Ecological 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 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
5

850.1740. Whole Sediment Acute Toxicity Invertebrates, Marine4,5 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 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. 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.

850.1350: 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) 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 

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 daphnia 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 solubility 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 anticipated 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.

 

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 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) 

studies 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 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 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. 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 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 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 nectar 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 brought 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 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 data 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 Study: 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 

 

6 Depending on the design of the “Honey Bee – 21-day repeated dose chronic larval toxicity,” study, a 72-hour LD50

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 

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 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 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 experiment 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 larvae may indicate the need to progress to higher tier toxicity 

testing under field conditions. 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 

measurement endpoints that relate 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 Spirodiclofen

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 was used to supplement the toxicity database for these degradates. There is 

uncertainty inherent in all ECOSAR estimates because some ECOSAR classes have more data 

points than others (refer to section entitled “Determination of Spirodiclofen Residues of Ecological 

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 degradates (i.e., spirodiclofen-enol, spirodiclofendihydroxy, 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

Extent 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 

insect 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-dichlorophenyl)-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 

C21H24Cl2O4], is an miticide/acaricide that inhibits lipid synthesis (IRAC7 Group 23). It is of the 

tetronic and tetramic acid derivative class of chemicals along with the active ingredients 

spirotetramat 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 Spirodiclofen8,” states 

that, “spirodiclofen is an insecticide/acaricide with an insect growth 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 spirotetramat, in a memo entitled “Response to Registrant Submission on 

Systemicity 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 

translocated through plants due to its lower Log KOW as well as its propensity to dissociate into a 

weak acid. Spirodiclofen is associated with a markedly higher Log KOW than spirotetramat (5.83 

for spirodiclofen vs 2.7 for spirotetramat) as well as a lower propensity 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-field 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 being 

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, 

2014)

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/efsajournal/doc/339r.pdf
9

and if further updates are needed to support registration review. In 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 identity 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, beech 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 25, 2014, the top five crop uses for the chemical are oranges, grapes, 

grapefruit, almonds, and apples. The SLUA covers the years 2003-2010. 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 treated with 50% of the total acreage 

of grapefruit being applied with spirodiclofen.

Spirodiclofen can be applied via ground application or aerially for sites that include avocado and 

Christmas trees. Ground airblast sprayers are permitted for the citrus and 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 application of 

spirodiclofen to blooming, pollen-shedding, or nectar-producing parts of plants if bees forage on 

the plants. 

4. Conclusions from Previous Risk Assessments

This problem formulation updates conclusions from recent risk assessments, including 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)

 Use 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 tropical 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 Terr.

Plants

Terr.

Inverts Fish BCF Aquatic Inverts

Aquatic 

Plants

Groundwater 

Contamination Persistence Degradates of Concern6

No Yes1 No2 NA7 No NA3 No No No4 Yes5

BAJ 2740-

enol, BAJ 

2740-

ketohydroxy, 

BAJ 2740-

dihydroxy

1 Chronic RQs exceeded LOC for all 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. These data have since been submitted and determined to be acceptable . 

3 Log KOW 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 97% after 13 days, indicating a strong 

potential for bioaccumulation.

4 Based on parent spirodiclofen’s low solubility (50 μg/L) and high KOC (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 considered stressors in previous drinking water assessments but not in the ecological risk

assessments. These degradates were identified by the Health Effects Division (HED) Metabolite Assessment

Review Committee (MARC) as 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 drinking 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 

spirodiclofen, and relied on a simulated the labeled application rate of 0.53 lbs a.i./A, which was 

both the maximum single application rate and the maximum application rate per crop season. 

Although the proposed application rate for grapes was higher, the Florida citrus 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 (Table 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. These 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, these degradates, along with the parent, have been identified as the residues of 

toxicological 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)*

Acute 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 spirodiclofen, 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) criteria 

have been developed for spirodiclofen (at 

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

accessed 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_benchmark.htm

(accessed 09/26/2014). 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 water 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 

pressure (5.25 × 10-9torr at 25°C) indicates spirodiclofen is relatively non-volatile, and the Henry’s 

Law Constant (2.4 × 10-8atm-m3/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 hydrolysis 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. 

The 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 C21H24Cl2O4 Product 

Chemistry 

Review 

4/20/05

Chemical Name 3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl2,2dimethylbutyrate

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 50 ug/L (pH 4 and 20°C) Product 

Chemistry 

Review 

4/20/05

Vapor Pressure 2.25xl 0-9torr (20°C) 

5.25xl 0-9torr (25°C)

Henry's Law Constant 2.4x l0-8atm-m3/mol (20°C) Calculated 

from VP and 

WS

Log Kow (noctanol–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 relatively 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 conditions 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. However, 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 relatively 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 incomplete, 

available data suggest that these compounds may be slightly more persistent than the parent 

compound and have greater mobility in soils than spirodiclofen. Table 4 summarizes the major 

environmental fate studies conducted in the laboratory for spirodiclofen. 

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 45697204; 

45697206; 45697228; 

Aerobic aquatic half-life 3.7-13.4 days in German total pond and lake 

water/sediment systems

MRID 45697205

Anaerobic aquatic half-life 40.4 days (total sediment/water system from lake in 

CA)

MRID 45697212

Adsorption coefficient

Koc

75,019 German Sandy loam

51,097 German silt loam

61,338 California loam

101,366 Texas clay loam

Average Koc: 72,248

MRID 45697219

Bioconcentration factor 

(BCF)

699 (whole fish)

1,439 (non-edible tissue)

166 (edible tissues)

MRID 45697002

a. Transformation Products

Spirodiclofen, applied at 0.0025 mg a.i./mL, had hydrolysis half-lives of approximately 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 natural sunlight for the month of June in 

Phoenix, Arizona (33.26o N), and 4.5 days in Edmonton, Alberta, Canada (53.33o N). Thus, the 

predicted environmental phototransformation half-lives of spirodiclofen in Phoenix and Edmonton 

were 43.8 and 61.6 days, respectively. BAJ 2740-enol and BAJ 2740-dioxoketone, were identified 

as the primary degradation products in the photolysis study (MRID 45697218). The parent 

compound undergoes an enol cleavage to produce BAJ 2740-enol (BAJ 2510), which in turn 

degrades to 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 of 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 20oC (MRIDs 45697204, 45697208). 

Carbon dioxide 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 

transformation 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 

transformation pathway was proposed (Figure A.1 in Appendix A) whereby 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 dihydroxy (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 (maximums of 2.1-39.6%) could be formed from either the ketohydroxy, 

the dihydroxy or the lactide, with ultimate formation of CO2 (maximums of 22.5-93.1%) upon 

cleavage of the dihydrofuranon ring. 

In aquatic systems, spirodiclofen dissipated with half-lives of about 1-7 days in natural 

water/sediment mesocosms under aerobic conditions (MRID 45697205) 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 Appendix 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-dichlorobenzoic 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 at 25 ± 1oC (MRID 45697227). 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 (33.26o

N) was reported to be equivalent to 7.38 hours of artificial light or 5.24 hours of artificial light for 

Edmonton, Alberta, Canada (53.33o N), the predicted environmental phototransformation halflives of BAJ 2740-enol in Phoenix and Edmonton were approximately 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 20oC (MRID 45697226). The half-life was 49.9 days. The 

temperature corrected half-life at 25oC was 35.3 days. BAJ 2740-diohydroxy was also studied in 

two additional soils at 20oC. 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 sand from Florida, sandy 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 sandy 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 highly mobile (MRIDs 45697213, 45697214, and 

45697223; USEPA. 2006). 

Due to the unstable nature of BAJ 2740-ketohydroxy in the 0.01 CaCl2 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 BAJ 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 dissipated 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 Ontario 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 extremely high octanol water partition coefficient (Log Kow 5.83), spirodiclofen is 

expected to bioaccumulate in fish. This prediction was supported by the results in the fish 

bioaccumulation study (MRID 45697205). The maximum bioconcentration factors (BCF) for total 

recovered radioactive residues were 699 for whole fish, 1,439 for non-edible tissue, and 166 for 

edible tissues. These bioconcentration factors are lower than would be predicted based on 

spirodiclofen’s KOW alone. In the edible tissue, spirodiclofen was not detected. The 

transformation product spirodiclofen Enol (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 (0.19 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 (3.42 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 residues in whole 

fish tissues had decreased by 66%. After 13 days of depuration, total residues had decreased by 

97%. 

6. Receptors

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 risk 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 toxicity 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 toxicity 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/), which employs a 

literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and 

wildlife. 
17

a. Effects to Aquatic Organisms

A summary of the available ecotoxicity information and the incident information for spirodiclofen

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 potential 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 solubility (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 concentrations, 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 health 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 LC50 due to a lack of a 50% 

mortality response. The LC50 was determined to be >58.3 mg a.i/L.

On a chronic exposure basis, an early life stage study 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 there 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 at the two highest treatment concentrations (20.2 and 32.7 μg 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 studies 

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 indicated that less than 50% emergence occurred at treatment 

concentrations 100 μg a.i/L and above (initial nominal concentrations). This initial nominal 

concentration was above the reported solubility limit of spirodiclofen. Mean measured 

concentrations were 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 indicated spirodiclofen rapidly bound to the sediment and/or underwent 

degradation. This statement corroborates other environmental fate information that indicates 

spirodiclofen rapidly binds to the sediment (51 – 92% bound on Day 1 of the study) and then 

rapidly degrades (DT50 or time to reach 50% degradation <12 days) to the BAJ 2740-enol 
18

degradate within the sediment layer. This degradation was even faster in the overlying water where 

the DT50 of parent spirodiclofen is less than one day. 

Available vascular and non-vascular aquatic plant studies indicate that TGAI and formulated 

spirodiclofen do not cause significant phytotoxic effects up to limit of solubility. These findings 

are based on the results of tests on one vascular and one non-vascular aquatic plant species.

Table 5. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Spirodiclofen

Taxonomic 

Group

Study Type

- Test 

Material

Surrogate Species Toxicity Value 2

Acute 

Toxicity 

Classification

Source 

(Classification)

Freshwater fish1

Acute -

TGAI

Rainbow trout

(Oncorhynchus 

mykiss)

LC50 = >35 μg/L

(N/A; N/A)

Very highly 

toxic3

45697001

(Acceptable)

Acute -

formulation

Bluegill sunfish 

(Lepomis 

macrochirus)

LC50 >58.3 mg/L

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

Chronic 

(Early LifeStage) -

TGAI

Rainbow trout

(Oncorhynchus 

mykiss)

97-d NOAEC = 

3.81 μg/L; 

LOAEC = 1.95 

μg/L (length and 

weight)

--

45697109

(Acceptable)

Freshwater 

invertebrates

Acute -

TGAI Water Flea 

(Daphnia magna)

48-hr EC50 = >45.5 

μg/L

(N/A; N/A)

Very highly 

toxic3

45697026

(Acceptable)

Acute -

formulation

48-hr EC50 >7.97 

mg/L (N/A; N/A)

Moderately 

toxic

45697013

(Supplemental)

Chronic -

TGAI

Water Flea 

(Daphnia magna)

21-d NOAEC = 11 

μg/L; LOAEC = 

20 μg/L (young 

per adult per 

reproductive day)

--

45697101

(Acceptable)

Estuarine/marine 

fish

Acute -

TGAI

Sheepshead Minnow 

(Cyprinodon 

variegatus)

96-hr LC50 >35.2 

μg/L 

(N/A; N/A)

Very highly 

toxic3

45697027

(Acceptable)

Estuarine/marine 

invertebrates

Acute -

TGAI

Eastern Oyster 

(Crassostrea 

virginica)

96-hr LC50 >43 

μg/L

(N/A; N/A)

Very highly 

toxic3

45697019

(Acceptable)

Saltwater mysid

(Americamysis bahia)

96-hr LC50: >37 

μg/L

(N/A; N/A)

Very highly 

toxic3

45697018

(Acceptable)

SedimentDwelling 

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 EC50 = 

>63.8 μg/L 

14-d NOAEC = 

63.8 μg/L

--

45697028

(Acceptable)
19

Taxonomic 

Group

Study Type

- Test 

Material

Surrogate Species Toxicity Value 2

Acute 

Toxicity 

Classification

Source 

(Classification)

Nonvascular2

-

TGAI

Freshwater Green 

Algae 

(Pseudokirchneriella 

subcapitata)

96-hour EC50 (cell 

density) > 60

μg/L 

96-hr NOAEC = 

60 μg/L

--

45697005

(Acceptable)

Nonvascular2 

-

formulation

Freshwater Green 

Algae 

(Pseudokirchneriella 

subcapitata)

96-hour EC50 (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

3Although the acute toxicity classification is “very highly 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 

concentration (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 Daphnia 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 related 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 (sheepshead minnow) yielded no treatment 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 

increase in adult mortality. There were no other clinical signs of toxicity 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 measured). 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 per 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 

treatment 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 deficiencies. 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 

overlying 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 sediment 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 appropriate:

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

driven by the high KOC of the chemical and its propensity to bind to the sediment.

 Rapid degradation of parent spirodiclofen to BAJ 2740-enol in the sediment layer indicates 

that midges were also exposed to BAJ 2740-enol in the sediment layer throughout the 28-

day duration of the study. 

 The lower KOC of BAJ 2740-enol as compared to parent spirodiclofen (18 vs. 83261) 

indicates BAJ 2740-enol moves in and out of the 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 interface 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 

1000 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 the

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 

spirodiclofen, a new 10-day study spiked sediment study with the freshwater midge Chironomus 

dilutus that provides analytical measurements of parent spirodiclofen in the sediment and pore 
21

water is recommended. As environmental fate data indicate that parent spirodiclofen 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 spirodiclofen 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 orders of 

magnitude less toxic than parent spirodiclofen. While data are available on one species 

(Chironomus riparius), additional sediment tests with freshwater and estuarine/marine 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 study 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 definitive NOAEC could not be derived. 

The 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 parent 

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 exposure 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 Species1 Toxicity Value1 AcuteToxicity 

Classification

Source

(Classification)

Freshwater fish2

(acute toxicity) Rainbow trout

(Oncorhynchus 

mykiss)

96-hr LC50 = >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)

Freshwater 

invertebrate (acute 

toxicity)

Water Flea 

(Daphnia magna)

48-hr EC50 = >100 mg/L

(N/A; N/A)

Practically 

non-toxic

45697014

(Acceptable)

Freshwater 

invertebrates 

(chronic life cycle) 

21-d NOAEC = 32 mg/L; 

LOAEC = 56 μg a.i./L

(mortality, adult body length, 

time to first brood, number of 

young per adult, and number of 

young per reproductive day

--

45697126

(Acceptable)
22

Taxonomic 

Group (study 

type)

Surrogate Species1 Toxicity Value1 AcuteToxicity 

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 sediment, 

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 

subcapitata)

96-hr EC50 (cell density) = 66.3 

mg/L

96-hr NOAEC (cell density, 

growth rate, biomass) = <3.13 

mg 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 clinical signs 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 growth or reproductive 

parameters 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 

parameters 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 practically 

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 generation 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. Evaluation of reproductive performance and function showed no treatmentrelated 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 epididymal 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 terrestrial 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 height; 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 dicot species based on effects to dry weight and height. Follow-up Tier II studies were

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 generally expected of an insect 

growth regulator type chemical such as spirodiclofen where the mode of action would be expected 

to have greater activity on larval 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 application rates on apple tree foliage in tunnel cages. The 

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 other 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 to 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 relocated to an 

untreated area. The 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, foraging activity, nectar and pollen storage and egglaying. Colony 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, pupal abundance 

(brood development) 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 affected 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 Studies for 

Spirodiclofen

Taxonomic 

Group Study Type Surrogate Species

Toxicity Value

2,3

Acute 

Toxicity 

Classification

Source

(Classification)

Birds1

Acute Oral

Bobwhite quail

(Colinus 

virginianus)

LD50 > 2000 mg/kg-bw 

(N/A; N/A)

Practically 

non- toxic

45697004

(Acceptable)

Sub-acute 

dietary

LC50 > 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 LD50 >2000 

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

Practically 

non-toxic

45696616

(Acceptable)

Chronic

NOAEL (decreased 

body weight and body 

weight gain in F1 pups) 

= 70 ppm

LOAEL = 350

--

45696802

(Acceptable)

Insects

Acute 

contact/oral 

combination 

study - TGAI

Honey bee 

(Apis mellifera)

(Adult honey 

bees)

Contact LD50 > 196

μg/bee (N/A; N/A)

Oral LD50 > 200 μg/bee

(N/A; N/A)

Practically 

non-toxic

45697017

(Acceptable)

Acute 

contact/oral 

combination 

study -

formulation

Contact LD50 > 100

μg/bee (N/A; N/A)

Oral LD50 > 100 μg/bee

(N/A; N/A)

Practically 

non-toxic

45697010

(Acceptable)

Acute - TGAI

Earthworm 

(Eisenia fetida)

14-day LC50 >1000 

mg/kg dw soil --

45697008

(Acceptable)

Acute -

formulation

14-day LC50 >1000 

mg/kg dw soil --

45697106

(Acceptable)

Terrestrial 

plants

Seedling 

Emergence/

Vegetative 

Vigor (Tier I)

Seedling 

Emergence Dicot 

– None

EC25 > 0.36 lbs a.i/A

NOAEC = 0.36 lbs 

a.i/A

--

45696925

(Acceptable)

Seedling 

Emergence 

Monocot –

Ryegrass

EC25 (dry weight, 

height) <0.36 lbs a.i/A 

NOAEC (dry weight, 

height) = <0.36 lbs 

a.i/A

Vegetative Vigor 

Dicot - Turnip

EC25 <0.52 lbs a.i/A 

NOAEC = 0.52 lbs 

a.i/A

Vegetative Vigor 

Monocot - None

EC25 >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

EC25 (survival): 0.25 lbs 

a.i/A

NOAEC = 0.14 lbs 

a.i/A --

45697028

(Acceptable)

Vegetative Vigor 

Dicot - Turnip

EC25 > 0.55 lbs a.i/A 

NOAEC (dry weight) = 

0.27 lbs a.i/A

1 Birds represent surrogates for terrestrial-phase amphibians and reptiles.

2 Concentrations expressed in terms of active ingredient.

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

There are studies available with the degradation products of spirodiclofen (Table 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 2000 mg a.i/kgbw 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 mortalities 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 Terrestrial 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)

Birds (Acute oral 

toxicity)1

BAJ 2740-

enol

Bobwhite 

quail

(Colinus 

virginianus)

LD50 > 2000 

mg/kg-bw (N/A; 

N/A)

Practically nontoxic45697111

(Acceptable)

BAJ 2740 4-

hydroxy-enol

LD50 > 2000 

mg/kg-bw (N/A; 

N/A)

Practically nontoxic45697112

(Acceptable)

Mammals (Acute 

oral toxicity)

BAJ 2740-

ketohydroxy Norway rat 

(Rattus 

norvegicus)

14-day LD50 >2000 

mg/kg-bw

Practically nontoxic45696814

(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 surrogates 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-guideline 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 apple 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 with 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 summarized 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 egglaying). 

Bee brood development and colony 

strength appeared to be influenced by 

treatment as well as population density.

It is noted that 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 EC50 >648.6 g product/hectare 45697109 

(Acceptable)

Parasitic wasp 

(Aphidus 

rhopalosiphi)

11-d EC50 >236.6 g product/hectare; 11-

day NOAEC (mortality) = 131.8 g 

product/hectare

45697110 

(Acceptable)

Predacious mite 

(Typhlodromus pyri)

32-d NOAEC (development 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.

45697114 

(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

Predacious 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-target arthropod 

toxicity 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 (Pardosa

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 described in Section 5a, spirodiclofen degrades by various routes in the environment. Five

different degradation products were formed in the fate studies at concentrations of 10% or greater 

than the applied parent spirodiclofen (Appendix A). Figure A.1 in the appendix shows the 

registrant-proposed degradation pathway for spirodiclofen under aerobic soil conditions. When 

available, registrant submitted toxicity data for degradates were consulted. Additionally, the 

ECOSAR (v1.1) module of EPISUITE (v.4.1) was employed to estimate the toxicity of these 

degradates of spirodiclofen alongside the available registrant submitted data. ECOSAR uses 

structure activity relationships to predict the toxicity of compounds that share similar structural 

moieties. In cases where multiple estimates of toxicity for a particular taxa are predicted 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 estimates were 

predicted. These results are compared alongside registrant submitted data that are available for 

spirodiclofen as well as the degradates.

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 

LC50

Acute 

FW 

Invert 

EC50

Chronic 

FW Fish 

NOAEC

Chronic 

FW 

Invert 

NOAEC

Acute 

E/M 

Fish 

LC50

Acute 

E/M 

Invert 

LC50

Chronic 

E/M 

Fish 

NOAEC

Chronic 

E/M 

Invert 

NOAEC

Algae 

EC50

Spirodiclofen 

(registrant) –

TGAI3

>35 >45.5 3.81 11 >35 >37 >60

Spirodiclofen 

(ECOSAR) –

TGAI

1901 2521 6 511 2241 281 68 0.38 551

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 284 283 472 982 376

Ketone alcohols 642 474 302 432 285

BAJ 2740-dihydroxy

Esters 16091 25691 72 864 21051 614 470 297 740

Benzyl alcohols 675 651 1022 2022 734

BAJ 2740-dioxoketone

Neutral organics 1111 795 144 151 1420 185 742 7 901

DCB-acid

Neutral 

organics-acid 287000 176000 30000 21000 363000 154000 65000 10000 179000
28

1ECOSAR indicates that chemical may not be soluble enough to measure this predicted effect

2ECOSAR indicates that this value was estimated using an acute-to-chronic ratio (ACR)

3Data 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 endpoints for parent 

spirodiclofen one row below.

4Results 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 

degradates 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 than the absolute value of a nondefinitive 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 toxicity 

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 toxicity 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 similarly 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 instability at pH values higher than pH 4, suggesting that 

this instability is a result of degradation to BAJ 2740-enol. Nearly 50% of the applied 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 contributor 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 forms at lower rates in soil than in aquatic 

systems, but can still form at concentrations ranging from 17 – 52% depending on the type of soil. 

EPISUITE estimates indicate BAJ 2740-enol has a higher solubility and lower KOC than parent 

spirodiclofen, which would make it more available for a runoff event into aquatic systems. This 

prediction is supported by the adsorption/desorption study (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 drift 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, suggesting 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-ketohydroxy 

(only one study each of avian acute oral toxicity and 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 estimates are available. Available environmental fate data however, show that BAJ 2740-

ketohydroxy does not form at significant levels in the hydrolysis, aqueous photolysis, and aquatic 

metabolism studies. The primary route of degradation for BAJ 2740-ketohydroxy 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 KOC (3.3), 

as estimated by EPISUITE. Due to the unstable nature of BAJ 2740-ketohydroxy in the 0.01 CaCl2

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 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 terrestrial toxicity studies 

with this degradate indicated a lack of toxic effects. Given the relatively low maximum application 

rate of parent spirodiclofen (0.53 lbs a.i/A), the low likelihood of BAJ-2740-ketohydroxy entering

aquatic systems except in runoff, and ECOSAR estimates generally indicating less toxicity than 

parent spirodiclofen for aquatic organisms, BAJ 2740-ketohydroxy is not considered to be of 

significant ecotoxicological concern as compared to parent spirodiclofen both on an acute and 

chronic 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 spirodiclofen 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 BAJ 

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

There 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 estimates are available. 

Environmental fate data indicate that this degradate forms 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 events (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 and 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 and 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 

photolysis 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. BAJ 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 metabolism, 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 acute and chronic basis.

Conclusions: Stressor(s) of Concern

In summary, available empirical and ECOSAR acute and chronic degradate data for freshwater 

fish and invertebrates, estuarine/marine fish and invertebrates and freshwater green algae generally 

show decreased toxicity to these taxa as compared to parent spirodiclofen. Transformation to BAJ 

2740-enol is expected to take place quickly in aquatic systems via the aquatic metabolism and/or 

hydrolysis pathways. ECOSAR data suggest that BAJ 2740-ketohydroxy, 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. Environmental 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 for 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 factors, 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 chemical 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 Aggregate 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 contains 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 incident (Package and Sequence 

Number: 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 

drift, 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.

Other Exposure Pathways to Terrestrial Species

Drinking Water Exposure

The Screening Imbibition Program (SIP v.l.0), Released June 15, 2010) was used to calculate an 

upper bound estimate of exposure using spirodiclofen’s solubility (0.055 mg/L), the most sensitive 

acute and chronic avian toxicity endpoints (northern bobwhite quail LD50 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 LD50 of >2000 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 alone 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 incorporated 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/pesticides/science/models/pg.htm#terrestrial.

Inhalation Exposure

The Screening Tool for Inhalation Risk (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 10-9torr) and 

molecular 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 LD50 = >2000 mg a.i/kg-bw and inhalation LC50 = 

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

LD50 = >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 animals. 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 potential 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 KOW = 5.83). Residues bioconcentrated 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). Bioaccumulation will be assessed using the results from bioaccumulation in 

fish studies, as well as the KOW (based) Aquatic BioAccumulation Model, version 1.0, 2009 

(KABAM).
33

8. Analysis Plan

a. Stressors of Concern

i. Ecological Risk Assessment

Please see the section entitled “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. Drinking 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 Review 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 

available. 

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 literature 

prior to conduct of the risk assessment will also be considered. The open literature studies are 

identified using EPA’s ECOTOXicology database (ECOTOX) (USEPA, 2007c), which employs 

a literature search engine for locating chemical toxicity data for aquatic 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 http://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 program, visit http://www.epa.gov/endo/.

11. Preliminary Identification of Data Gaps 

a. Environmental Fate

Tables 11 and 12 identify environmental fate studies by MRID for spirodiclofen and its 

degradation products and, their study classifications. The tables also show where additional data 

are needed to support risk assessment.

835.4200 Anaerobic Soil Metabolism: No studies are available. New studies should be 

submitted.

835.4400 Anaerobic Aquatic Metabolism: Only one water/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 available 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 parent 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 11. Submitted Environmental Fate 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

Supplemental

Supplemental

No ---

835.2410 Soil photolysis 45697230 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 ---

835.4200 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

45697212 Acceptable Yes Only one 

water/sediment system 

was included in the 

study. An additional 

water/sediment system 

is needed.

835.1230

835.1240

Adsorption/ 

desorption and 

leaching

45697219

45697229

45697307

46040405

46040406

46040407

45697222

46040406

45697202

45697216

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 are 

relatively low.

835.6100 Terrestrial field 

dissipation

45697207/45697303

45697208/45697303

45697209/45697303

45697210/45697303

Acceptable

Acceptable

Acceptable

Acceptable

No ---

835.6200 Aquatic field 

dissipation

Waived Waived No ---

835.8100 Volatility - 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-enol, -

ketohydroxy, -

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)

45697203 (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 

and its major degradates

(BAJ 2470-enol, -

ketohydroxy, -

dihydroxy, and DCBacid)

Shaded and bolded cells indicate that additional data are required for the corresponding data requirement.
37

Table 12. Submitted Environmental Fate Data for the Spirodiclofen Degradates

OCSPP 

Guideline

Data 

Requirement

Submitted Studies 

(MRID and test 

substance)

Study 

Classifications

Are data 

needed to 

conduct risk 

assessment?

Notes

835.2240 Aqueous 

photolysis

45697227

(spirodiclofen enol)

Supplemental No ---

835.4100 Aerobic 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)

45697214 

(spirodiclofen 

dihydroxy)

45697223 

(spirodiclofen DCB 

acid)

45697225 

(spirodiclofen 

ketohydroxy)

Supplemental

Supplemental

Supplemental

Unacceptable

(unstable in 

CaCl2)

No ---

b. Effects

Tables 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 media and 

terrestrial environment, respectively, as well as study classifications and whether or not further 

data are needed in order to support 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 observed 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. Spirodiclofen is in a chemical class that 

is shared by spiromesifen and spirotetramat. It was investigated 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.

The chemicals recognized to be part of the tetronic and tetramic acid derivatives class by the 

Insecticide Resistance Action Committee (IRAC) are listed in Table 13, 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 determined 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 mallard 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 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. 

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 exposure 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 

observations 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 one 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 chemical 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 that 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 where 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 dietary-based 

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 to spirodiclofen.

Table 13. Available avian acute data from the tetronic and tetramic acid derivatives class 

of insecticides.

Chemical

Acute oral 

(passerine) 

mg a.i/kgbw

Acute 

oral 

(quail) 

mg 

a.i/kgbw

MRID or 

source

Acute 

oral 

(Mallard) 

mg 

a.i/kg-bw

Sub

acute 

dietary 

(quail)

a.i/kgdiet

MRID or 

source

Sub 

acute 

dietary 

(mallard) 

a.i/kgdiet

MRID or 

source

Spirodiclofen >2000 45697004 >5000 45697003 >5000 45697118

Spirotetramat >20002,3 Barfknecht 

(2003) >49984 Barfknecht (2004) >60505 Stoughton (2005)

Spiromesifen >20001 45819723 >4767 45819721 >5278 45819722

1Observations of diarrhea at all treatment groups (500, 1000, and 2000 mg a.i/kg-bw) during the first 2 days of 

treatment.

2Observations 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)

3One 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 eyelid.

4Significant 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 the amount of the control groups. These effects were compensated as soon as the birds 

were taken off chemical exposure.

5Observations 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, Freshwater9,10 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 sediment 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 the 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 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
40

50% emergence in the next two lowest concentrations (100 and 180 μg a.i/L). These results 

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 protocol 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 Invertebrates, Freshwater1,11. 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 insects 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 sediment 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, Marine12,13 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 this 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. 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.

850.1350: 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) 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 daphnia 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 solubility 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 anticipated 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 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 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) 

studies 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 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 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. 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 

LD50 value 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 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 nectar 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 brought 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 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 data 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 Study: 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 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 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 experiment 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 larvae may indicate the need to progress to higher tier toxicity 

testing under field conditions. 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 

measurement 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 14. 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

850.1010

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

850.1075 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 

45697101 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 needed 

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 45697109 Acceptable No --

850.1500 Fish life cyclesaltwater 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

Nonguideline 28-day chronic 

spiked water 

sediment test –

Freshwater 

45697117 Acceptable No --

850.1735

Whole 

sediment Acute 

Toxicity 

Invertebrates, 

Freshwater15

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. New subchronic 

10-day spiked sediment studies 

with minimal or no aging time 

that provide analytical 

measurements for both sediment 

and pore water in two species 

(Chironomus dilutus and Hyalella 

azteca) are needed for risk 

assessment.

 

15 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.
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, 

Marine16

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. 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 

recommended.

850.4400

Aquatic plant 

Toxicity Test 

using Lemna 

spp.

45697028 Acceptable No --

850.4500 Algal toxicity

45697005 Acceptable No

--

45697011 Acceptable No

Table 15. Aquatic Ecological Effects Data for the Degradation Products of Spirodiclofen

OCSPP

Guideline

Data Requirement

(Degradation product)

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 invertebrate 

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 product)

Submitted 

Studies (MRID)

Study 

Classifications

Are data needed for 

risk assessment?

850.4500 Algal toxicity (BAJ 2740-enol) 45697016 Acceptable No

Nonguideline28-day chronic spiked water 

sediment test – Freshwater 45697022 Acceptable No

Table 16. Submitted Terrestrial Ecological Effects Data for Spirodiclofen

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(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 needed for risk 

assessment because any 

increased sensitivity 

relative to earlier testing 

would indicate an acute 

risk concern for listed and 

non-listed bird species.

850.2200 Avian dietary 

toxicity 

45697003 Acceptable

No

--

45697118 Acceptable

850.2300 Avian 

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 LD50 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 

toxicity 

No data available

Yes

Special Study

Honey bee larvae 

chronic oral 

toxicity

Yes
47

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(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 

with the Honey 

bee

45697105 Acceptable No

--

850.4100/4150

Seedling 

Emergence / 

Vegetative Vigor

45696925

45697028 Acceptable No

--

Non-guideline

Toxicity to egg 

parasitoid 

(Trichogramma 

cacoeciae)

45697109 Acceptable No

--

Parasitic Wasp 

(Aphidius 

rhopalosiphi) 

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 

pyri) – Life cycle 

test

45697121 Acceptable No --
48

OCSPP 

Guideline

Data 

Requirement

Submitted 

Studies 

(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 recommended for the corresponding data requirement.

Table 17. Aquatic Ecological Effects Data for the Degradation Products of Spirodiclofen

OCSPP

Guideline

Data Requirement

(Degradation product)

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

Earthworm 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 exposed 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 nectar 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 brought 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 serve 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 lowestobserved adverse effect level (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 highertier 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 used 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 the 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 exposure 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 have insect growth regulator type activity mediated by inhibition of lipid 

biosynthesis, data is needed to characterize the toxicity of spirodiclofen to terrestrial invertebrates 

in this stage of the life cycle. Available non-guideline acute contact toxicity studies to other nonApis 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 data 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 invertebrates 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 may 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 nonlisted terrestrial invertebrate species, including bee pollinators. These data would allow the 

Agency to refine the screening 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 Colony 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 exceeded, the availability of data, and the nature of the 

uncertainties that warrant further testing. The Tier 2 studies are typically considered “semifield,” studies where small colonies are enclosed in tunnels, along with pesticide-treated crops. 

Tier 2 studies 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 assessment 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, queen fecundity, ad worker bee 

behavior to estimate various attributes 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 influence 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 Bobwhite 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 LC50 Bobwhite Quail (Colinus 

virginianus) Report/Doc number: BAR/LC017, M-084796-01-2.

Stoughton, 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 Environmental Protection Agency (USEPA). Environmental Fate 

and Effects Division. Office of Pesticide Programs. Available at 

http://www.epa.gov/espp/consultation/ecorisk-overview.pdf (accessed 02/19/2014).

USEPA. 2005a. Estimated Drinking Water Concentrations of combined residues of spirodiclofen 

and its degradates (spirodiclofen-enol, spirodiclofen-ketohydroxy, and spirodiclofendihydroxy) in surface water and groundwater. Memorandum from 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. 2005b. Environmental Fate and Ecological Risk Assessment of Spirodiclofen. 

Memorandum from 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. 2005c. Environmental Fate and Ecological Risk Assessment of Spirodiclofen: Response to 

RD on Mammalian Risk. Memorandum from Michael Rexrode (EFED) to Rita Kumar and 

Meredith Laws (RD) dated May 23, 2005.

USEPA. 2005d. EFED’s Response to Sherry Movassaghi’s (Bayer Crop Science) Request to 

Modify the Recommended Bee Precautionary Labeling Statement for the Spirodiclofen EndUse Product, Envidor 2 SC. Memorandum from Gabe Patrick (EFED) to Rita Kumar and 

Meredith Laws (RD) dated June 16, 2005. (DP Barcode D317315). 

USEPA. 2006. Standard Soil Mobility Classification Guidance. Memorandum from Donald 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 Species 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

Appendix 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)

Parent

Spirodiclofen 

(BAJ 2740)

Chemical Name: 3-(2,4-Dichlorophenyl)-2-

oxo-1-oxaspiro[4.5]dec-3-en4-yl 2,2-dimethylbutyrate 

CAS No. 148477-71-8

Molecular Weight: 411.3 g/mol

SMILES: 

O=C1C(=C(C2(O1)CCCCC2)OC(=O)C(C)(

C)CC)c1c(cc(cc1)Cl)Cl

Molecular Formula: 

C21H24Cl 2O4

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]dec3-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: 

C15H14Cl 2O3

Hydrolysis

45697217

29 (pH 4; 

Days 30) 

52 (pH 7; 

Days 30) 

101 (pH 9; 

Days 30)

29 (pH 4; Days 

30) 

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) 

45697206 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 112; 

German pond 

system)

30 (Days 112; 

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)

Not 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: 

C15H14Cl 2O4

Aerobic soil 45697204 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)

45697206 8 (Days 130; 

California)

0.2 (Days 119)

Terrestrial 

dissipation 45697207

0.01 ppm in 0-

15 cm

(Day 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)

Terrestrial 

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: 

C15H16Cl 2O4

Aerobic soil 45697204

45697206

16 (Days 20; 

California)

5 (Days 30; 

Florida)

3 (Days 20; 

Germany)

1 (Days 3; 

Germany)

4 (Days 28; 

California)

11 (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 

(Days 372)

Terrestrial 

dissipation 45697209 Not detected (Washington)

Not detected 

(Days 542)

Terrestrial 

dissipation 45697210

Not detected 

(Ontario, 

Canada)

Not detected 

(Days 125)

BAJ 2740-

dioxoketone

Chemical Name: 6'-Chlorospiro[cyclohexane1,2'(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 Name: 2,4-Dichlorobenzoic acid

CAS No. 50-84-0

Soil photolysis 45697230 14 (Days 15) 14 (Days 15)

Aerobic soil 45697204 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: C7H4Cl2O2

3 (Days 13; 

Germany)

5 (Days 3; 

Germany)

Not detected 

(Days 120)

Terrestrial 

dissipation 45697207 Not detected (Florida)

Not detected 

(Days 547)

Terrestrial 

dissipation 45697208

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. Registrant-postulated degradation pathway for spirodiclofen under aerobic 

conditions
59

Appendix B. Spirodiclofen Fate and Ecological Effects Bibliography

124871 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 Photodegradation-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: MR708/99. Unpublished study prepared by Bayer AG. 60 p. 

162-1 Aerobic soil metabolism
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 by 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. 

Unpublished 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 Sediment 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 System. 

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 Water-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 2740) 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. 

Unpublished 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. (2002) 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 Coefficient (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-Dichlorobenzoic 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 Report: 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. 

Unpublished 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 Soil, 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 Research 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 

Laboratories 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.; Koster, 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 Studies
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. Unpublished 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

45697220 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 from 

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 Citation 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

45697003 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. 116 

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 Reproduction

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: 110344: 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 

Corporation. 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 Number: 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 1329-4: 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 prepared 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 Conditions: 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. 

45697026 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 Estuarine/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. Unpublished 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 LifeCycle 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 (Oncorhynchus 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 Toxicity 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 Toxicity 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 Emergence 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. Unpublished 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 Selenastrum 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 SC240: 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 the 

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. Unpublished 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 Scheuten (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 Typhlodromus 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 BAJ 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. 

45697122 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. 

45697123 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 

Disrupting 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 prepared 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 International, 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, Ltd. 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 Arbeitsgemeinschaft, 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. Unpublished 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 Conditions: 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 Project 

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 Predatory 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 for 

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 for 

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 study 

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 Output

Table 1. Inputs

Parameter Value

Chemical name Spirodiclofen

Solubility (in water at 25oC; mg/L) 0.05

Mammalian LD50 (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 LD50 (mg/kg-bw) 2000

Avian test species mallard duck

Body weight (g) of "other" avian species

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 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 Weight (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 LD50 (mg/kg bw) 2000

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 2000

Enter Lowest Rat Inhalation LC50 (mg/L) 5.03

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 5.09E-05

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.40E-06

Adjusted Inhalation LD50 2.02E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 3.17E-07 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 5.60E-02

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 2.77E-03 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 5.09E-05

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 8.04E-06

Adjusted Inhalation LD50 2.99E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 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 

LD50 2.35E-04 Exposure not Likely Significant