2

dissipation rate of clofentezine on wildlife items, and used the refined half-life estimate to 

predict how rapidly terrestrial residues would decline to levels below the chronic toxicity 

NOAEC. 

The EPA reviewed Irvita’s revised assessment and agrees that the residue decline studies on fruit 

commodities offer a valid way to refine persistence of clofentezine residues on wildlife food 

items. Along these lines, EFED has conducted a very similar refined assessment in which 

decline of residues on terrestrial food items was estimated based on data from a residue decline 

study with grapes, and characterized how quickly the residues of terrestrial food items would be 

expected to drop below the chronic avian toxicity NOAEC (see Section VI.B.1 of the risk 

assessment). The results of this refined assessment are consistent with the one Irvita conducted, 

and yields similar conclusions.

The results of this risk assessment indicate that all outdoor uses of clofentezine can potentially 

lead to direct adverse effects to listed and non-listed birds and mammals. As birds serve as 

surrogates for reptiles and terrestrial-phase amphibians, risk to these taxa is also a possibility. 

Risk to terrestrial vertebrates is associated with sublethal effects on reproduction and growth that 

may occur with chronic exposure. Acute risk to terrestrial vertebrates is predicted to be minimal. 

Use of clofentezine is not expected to pose a risk to foraging (adult) bees; however, there is a 

potential for risk to non-listed and listed terrestrial arthropods because of adverse effects to 

reproduction and development. Use of clofentezine is not expected to cause direct or indirect 

adverse effects to non-listed or listed fish, aquatic invertebrates, or aquatic plants. Thus, a “no 

effect” determination is made for all listed aquatic organisms.

The chronic level of concern (LOC) was exceeded by dietary RQs for birds and by dose-based 

RQs (but not dietary-based RQs) for small and medium-sized mammals. Clofentezine is 

moderately persistent in the terrestrial environment and is expected to decline to below toxic 

levels approximately one to two weeks after application. The conclusion of chronic risk to 

mammals is uncertain. Although the chronic dose-based RQs slightly exceeded the LOC for 

small mammals (RQs 1.16-1.35), the predicted peak concentrations on short grass (62.4 mg 

a.i./kg) is less than the estimated dietary concentration in the chronic mammal study at which no 

adverse effects were observed (400 mg a.i./kg). 

A honey bee contact study found that clofentezine is practically nontoxic to adult bees. Based on 

available acute toxicity data with adult bees, no specific bee acute hazard statement is needed on 

product labels. Studies with beneficial beetles have found that clofentezine also has low acute 

toxicity to these species. However, data published in the open literature suggest concern about 

clofentezine toxicity to eggs and early life-stages of bees and other insects. The available 

toxicity data and risk assessment methods do not allow for a precise description of the chronic 

risk to terrestrial insects. A qualitative evaluation indicates that potential risk of clofentezine use 

to cause significant brood effects in bees is probably small, but the potential for it to cause 

adverse effects to listed species of terrestrial arthropods cannot be ruled out.

Several lines of evidence indicate that clofentezine has low toxicity to plants. Limit tests 

conducted with terrestrial plants found no significant phytotoxicity when plants were treated 

directly at the maximum application rate. A limit study testing the toxicity of a formulated 
3

product indicates that clofentezine is not toxic to green algae at the solubility limit of 

clofentezine. Also, clofentezine is routinely applied to a wide variety of plants in greenhouses, 

orchards, and tree farms without any reported problems with phytotoxicity or plant damage 

incidents. Finally, the only known toxic mode of action of clofentezine (toxicity to eggs and 

growth inhibition of early life-stages of invertebrates) is not relevant to plants. Therefore, EPA 

concludes that use of clofentezine will not pose risk to either terrestrial or aquatic plants, and is 

not expected to harm listed species of plants. Thus, a “no effect” determination is made for all 

listed plants.

The two major degradates of clofentezine are 2-chlorobenzonitrile from direct aqueous 

photolysis, and 2-chlorobenzoic acid (2-chlorobenzylidine)hydrazide (AE C593600) from abiotic 

hydrolysis. Because toxicity data on these degradation products were not available, acute 

toxicity to aquatic organisms was estimated based on structural-activity relationships (SAR) 

using the ECOSAR program. Toxicity estimates indicated that these degradation products are 

less toxic than parent. Therefore, the conclusion is that a risk assessment conducted based on 

exposure to the parent compound would be protective. 

The table below (Table 1) summarizes the risk conclusions for direct effects to listed species.
4

Table 1. Listed Species Risks Associated with Potential Direct Effects Due to the Applications of Clofentezine.

Listed Plant Taxon Potential Direct Effects

Terrestrial and semiaquatic plants –

monocots and dicots

No effect

Aquatic plants No effect

Listed Animal 

Taxon

Potential Direct Effects

Acute Notes Chronic Notes

Terrestrial 

invertebrates

Yes

(see 

note 

1)

1. Adverse effects to terrestrial 

invertebrates are expected to be 

limited to those that are exposed as 

eggs or larval stages. Terrestrial 

invertebrates exposed as adults are 

not expected to be affected.

ND

2. Based on results from the T-REX model, screening-level 

RQs exceed the chronic LOC for mammals of all size 

classes that eat any food items other than fruit, seeds, or 

pods. To reduce all of the RQs for chronic risk to listed 

mammals to less than the chronic LOC, the single 

application rate would need to be reduced to <0.19 lb 

a.i./A.

3. Chronic risk is uncertain because dietary-based RQs did 

not exceed the chronic LOC

4. Based on results from the T-REX model, screening-level 

RQs exceed the chronic LOC for birds that eat plants 

(short grass or broadleaf plants). To reduce all of the RQs 

for chronic risk to listed birds to less than the chronic 

LOC , the single application rate would need to be 

reduced to <0.125 lb a.i./A. These results are also 

applicable for reptiles and terrestrial phases of 

amphibians.

Mammals No 

effect

Yes

(see notes

2 and 3)

Birds No 

effect

Yes

(see note 

3)

Reptiles No 

effect

Yes

(see note 

4)

Amphibians No 

effect

Yes

(see note 

4)

Freshwater fish No 

effect No effect

Freshwater 

invertebrates

No 

effect No effect

Mollusks No 

data No data
5

Listed Plant Taxon Potential Direct Effects

Estuarine/marine fish No 

data No data

Estuarine/marine 

invertebrates

No 

effect No effect
6

Based on this screening-level assessment, there are potential risks of direct effects to listed birds, 

mammals, reptiles, terrestrial phases of amphibians, and terrestrial arthropods from the use of 

clofentezine on some of its registered use sites. Listed species of other taxa, such as terrestrial 

plants, may also be affected through indirect effects because of the potential direct effects on 

listed and non-listed species. Potential direct effects on listed birds, mammals, reptiles, 

terrestrial phases of amphibians, and terrestrial arthropods from the use of clofentezine may be 

associated with modification of Primary Constituent Elements (PCEs) of designated critical 

habitats, where such designations have been made. However, at this current stage of the 

Registration Review process, it is premature to make effects determinations for listed species 

until further scientific analysis and refinements are conducted, based on recommendations 

received from the National Academy of Sciences’ (NAS) National Research Council (NRC)

April 2013 report, available at http://www.nap.edu/catalog.php?record_id=18344. The NAS 

report outlines recommendations on specific scientific and technical issues related to the 

development of pesticide risk assessments that are compliant with the Endangered Species Act 

(ESA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

The EPA along with the U.S. Fish & Wildlife Service (USFWS), the National Marine Fisheries 

Service (NMFS) (collectively, the Services), and the U.S. Department of Agriculture (USDA), 

released a summary of their implementation plan for assessing risks of pesticides to listed species 

ahead of the stakeholder workshop held on November 15, 2013. This plan was developed in 

response to the NAS’ recommendations, including a common approach to risk assessment as a 

way of addressing scientific differences between EPA and the Services. During the workshop, 

the agencies received feedback from the public on the interim scientific approaches that were 

developed as part of the initial implementation of the NAS recommendations. These approaches 

will be jointly implemented and vetted as part of a phased iterative process. Once fully vetted, 

EPA will further refine the listed species effects determination portion of this risk assessment. 

To make effects determinations for individual listed species, useful refinements may include, but 

are not limited to, analyses of: 1) more detailed, species-specific ecological and biological data; 

2) more detailed and accurate information on clofentezine’s use patterns; and 3) sub-county level 

spatial proximity data for the co-occurrence of potential effects areas and listed species and any 

designated critical habitat. Examples of such refinements are described below.

EFED is currently developing tools that are expected to further refine the assessment and are 

designed to support effects determinations for individual federally listed species and their 

designated critical habitats (where applicable). Scientific information obtained from the 

Services, and other reliable sources is being collated by EFED to address all currently listed 

species. This information is being stored in an Office of Pesticide Programs (OPP) Pesticide 

Registration Information SysteM (PRISM) listed species knowledgebase. The listed species 

knowledgebase consists of an information repository that houses biological and behavioral 

information relevant to individual species (e.g., habitat, diet, and life history, including specific 

temporal and spatial associations) and a document repository that contains supporting documents 

(e.g., USFWS recovery plans) and electronic information (e.g., GIS data files). For terrestrial 

taxa, biological information relevant to the assessment (e.g., diet and body weight) will be used 

to parameterize exposure estimates using a method consistent with currently used methods in the 

T-REX and T-HERPS models. 
7

Refinements will also include more detailed analyses of the registered uses and specific use 

patterns that result in either “Likely to Adversely Affect” (LAA) or “Not Likely to Adversely 

Affect” (NLAA) determinations for federally listed species. The analyses may include more 

information on where, when, and how clofentezine is used on all use sites. Actual usage data

(when available) and national land-cover datasets that indicate potential use sites [e.g., National 

Land Cover Dataset (NLCD), Cropland Data Layer (CDL)] may be used to support a more 

refined analysis of where clofentezine is reasonably expected to be used. Similarly, refinements 

on the timing of applications and a more in-depth exploration of agronomic practices for

clofentezine may be included as part of the refinement.

The refinements based on individual species data; additional, detailed usage information, when 

available; and recommendations from the NRC report are expected to help to more accurately 

identify potential areas of effect and to better inform effects and habitat determinations for listed 

species and any designated critical habitats.

 
8

Ecological Risk Assessment in Support of the 

Registration Review of Clofentezine

Clofentezine

1,2,4,5-Tetrazine, 3,6-bis(2-chlorophenyl)-

CAS No. 74115-24-5

P.C. Code: 125501

Prepared by:

Nicholas Mastrota, Wildlife Biologist

Ronald Parker, Senior Environmental Engineer

Approved by:

Dana Spatz, Branch Chief

Office of Chemical Safety and 

Pollution Prevention
9

TABLE OF CONTENTS

I. Executive Summary................................................................................................................ 11

A. Purpose of this Assessment............................................................................................ 11

B. Summary of Effects and Risk Conclusions.................................................................... 11

II. Problem Formulation ....................................................................................................... 16

A. Introduction .................................................................................................................... 16

B. Nature of the Stressor..................................................................................................... 16

1. Pesticide Type, Class, and Mode of Action................................................................ 16

2. Physical and Chemical Properties .............................................................................. 17

C. Stressor Source and Distribution.................................................................................... 18

1. Pesticide Use............................................................................................................... 18

2. Pesticide Usage........................................................................................................... 20

D. Environmental Fate Summary........................................................................................ 22

1. Clofentezine................................................................................................................ 22

1. Degradation Products of Clofentezine........................................................................ 24

E. Ecological Effect Summary ........................................................................................... 25

1. Aquatic Effects........................................................................................................... 25

2. Terrestrial Effects....................................................................................................... 31

3. Toxicity of Degradation Products............................................................................... 34

F. Ecosystems Potentially at Risk .......................................................................................... 36

G. Assessment Endpoints.................................................................................................... 36

III. Analysis Plan and Conceptual Model ............................................................................. 38

A. Measures to Evaluate Risk Hypothesis.......................................................................... 38

B. Conceptual Model .......................................................................................................... 38

C. Risk Hypothesis.............................................................................................................. 39

D. Conceptual Diagram....................................................................................................... 39

IV. Exposure Analysis............................................................................................................. 41

A. Use Characterization ...................................................................................................... 41

B. Aquatic Fate and Exposure Characterization................................................................. 42

1. Fate Characterization.................................................................................................. 42

2. Model Input Parameters.............................................................................................. 42

3. Estimated Environmental Concentrations.................................................................. 43

4. Monitoring Data ......................................................................................................... 44

C. Terrestrial Exposure ....................................................................................................... 44

V.Risk Estimates for Non-Target Organisms .......................................................................... 46

A. Aquatic Organisms......................................................................................................... 46

1. Aquatic Animals......................................................................................................... 46

2. Aquatic Plants............................................................................................................. 49

B. Terrestrial Organisms..................................................................................................... 50

1. Terrestrial Wildlife ..................................................................................................... 50

2. Terrestrial Plants......................................................................................................... 52

3. Bees and Other Nontarget Terrestrial Arthropods...................................................... 52

VI. Risk Description and Characterization .......................................................................... 54

A. Risk to Aquatic Organisms ............................................................................................ 54

1. Aquatic Animals......................................................................................................... 54
10

2. Aquatic Plants............................................................................................................. 57

B. Risk to Terrestrial Organisms ........................................................................................ 58

1. Nontarget Terrestrial Vertebrates............................................................................... 58

2. Terrestrial Arthropods ................................................................................................ 61

3. Terrestrial Plants......................................................................................................... 62

C. Ecological Incidents....................................................................................................... 62

D. Uncertainties, Limitations, and Assumptions ................................................................ 63

1. Endocrine Disruption.................................................................................................. 63

2. Uncertainties Related to Data Limitations.................................................................. 64

3. Uncertainty in Risk Conclusions................................................................................ 65

VII. Risk Conclusions............................................................................................................... 66

VIII. References.......................................................................................................................... 69

APPENDIX A.............................................................................................................................. 71

APPENDIX B .............................................................................................................................. 74

APPENDIX C.............................................................................................................................. 75

APPENDIX D.............................................................................................................................. 76

APPENDIX E .............................................................................................................................. 83

APPENDIX F .............................................................................................................................. 85

APPENDIX G.............................................................................................................................. 87
11

I. Executive Summary

A. Purpose of this Assessment

The purpose of this document is to assess the ecological risks of the clofentezine (PC Code 

125501). Clofentezine is an agricultural pesticide used to control mites (i.e., an acaricide). It is 

used for mite control on fruit trees, nut trees, Christmas trees, and ornamental plants grown in 

greenhouses. This pesticide was first registered in the United States in 1989; thus, it has not 

been subjected to evaluation under reregistration. In 2007, the EFED completed a problem 

formulation for assessing the ecological risks of use of clofentezine (USEPA, 2007). 

This assessment evaluates risks that clofentezine’s registered uses may pose to federally listed 

endangered and threatened (listed) species, as well as to all other non-target plant and animal 

(“non-listed”) species. This risk assessment incorporates the available effects data, and most 

current modeling and risk methodologies, some of which may not have been available at the time 

when previous clofentezine risk assessments were conducted. 

B. Summary of Effects and Risk Conclusions

The results of this risk assessment indicate that all outdoor uses of clofentezine have the potential 

for direct adverse effects to listed and non-listed birds and mammals. As birds serve as 

surrogates for reptiles and terrestrial-phase amphibians, risk to these taxa is also a possibility. 

Risk to terrestrial vertebrates is associated with sublethal effects on reproduction and growth that 

may occur with chronic exposure. Chronic risk to mammals is uncertain and is expected to be 

limited. Acute risk to terrestrial vertebrates is predicted to be minimal. Use of clofentezine is not 

expected to pose a risk to foraging (adult) bees; however, there is a potential for risk to listed and 

non-listed terrestrial arthropods because of adverse effects to reproduction and development. 

Use of clofentezine is not expected to cause direct or indirect adverse effects to listed and nonlisted fish, aquatic invertebrates, terrestrial plants, or aquatic plants. Thus, a “no effect” 

determination is made for all listed aquatic organisms.

Based on the available data, suspended concentrate (SC) formulated products of clofentezine are 

slightly to practically non-toxic to freshwater fish and invertebrates on an acute-exposure basis. 

The limited solubility of the technical grade active ingredient (TGAI) prevented classification of 

the acute toxicity, but the TGAI was shown to be nontoxic at concentrations that are close to the 

aqueous solubility limit. Acute risk quotients (RQs) for fish and aquatic invertebrates were 

below the EPA’s LOCs for listed and non-listed species. Chronic toxicity tests did not find any 

adverse effects caused by chronic exposure to fish at concentrations up to the solubility limit.

Chronic exposure to aquatic invertebrates was found to inhibit reproduction; however, the noobservable-adverse-effects concentration (NOAEC) in these studies was greater than EECs, and 

thus the chronic RQs are all below EPA’s LOC.

For birds and mammals, clofentezine is practically nontoxic on an acute exposure basis. The 

lack of toxicity and the relatively low use rate resulted in acute risk quotients well below the 

EPA’s level of concern. However, chronic studies identified adverse effects to birds and 

mammals. Because the NOAEC of these studies were less than the EEC for some types of birds 

and mammals, the chronic RQs were above the EPA’s LOC (dietary-based RQs 0.08 – 2.08, 
12

dose-based chronic RQs 0.01 – 1.35). Specifically, chronic RQs exceeded the LOC for small 

birds that feed on plant foliage, and for mammals that feed on plant foliage or arthropods. Thus, 

all uses of clofentezine are predicted to pose chronic risk to birds, mammals, reptiles, and 

terrestrial amphibians, and may cause adverse effects to listed species of these taxa. Chronic risk 

to mammals is uncertain because the chronic LOC was exceeded only by dose-based RQs, and 

only for small to medium mammals feeding exclusively on short grass. The peak EECs for short 

grass were less than the dietary concentration that cause no chronic frank effects in a twogeneration rat study.

A honey bee contact study found that clofentezine is practically nontoxic to adult bees. Based on 

available acute toxicity data with adult bees, no specific bee acute hazard statement is currently 

needed on product labels. Studies with beneficial beetles have found that clofentezine also has 

low acute toxicity to these species. However, data published in open literature show that 

clofentezine causes toxicity to eggs and early life-stages of bees and other insects. The available 

toxicity data and risk assessment methods do not allow for a precise description of the chronic 

risk to terrestrial insects. A qualitative evaluation indicates that potential risk of clofentezine use 

to cause significant brood effects in bees is probably small, but the potential to cause adverse 

effects to listed species of terrestrial arthropods cannot be ruled out.

Because clofentezine is applied only once per year and residues are not very persistent in the 

environment, chronic effects to terrestrial animals are not expected to be on a scale that would 

significantly affect their populations. Therefore indirect effect to endangered animals from loss 

of ecological services, such as diminished seed dispersal of plants, are believed to be 

discountable.

Several lines of evidence indicate that clofentezine has low toxicity to plants. Limit tests 

conducted with terrestrial plants found no significant phytotoxicity when plants were treated 

directly at the maximum application rate. A limit study testing the toxicity of a formulated 

product of clofentezine to green algae also found no observable toxic effects when tested at the 

high concentration of 100 mg product/L, with the maximum active ingredient concentration 

assumed to be at the solubility limit (34.2 μg/L). Although other types of aquatic plants may be 

more sensitive, and testing with other species of aquatic plants would be needed to draw general 

conclusions for aquatic plants as a group, this test indicates that clofentezine is not toxic to green

algae at the solubility limit of clofentezine. Also, clofentezine is routinely applied to a wide 

variety of plants in greenhouses, orchards, and tree farms without any reported problems with 

phytotoxicity or plant damage incidents. Finally, the only known toxic mode of action of 

clofentezine (toxicity to eggs and growth inhibition of early life-stages of invertebrates) is not 

relevant to plants. Therefore, EPA concludes that use of clofentezine will not pose significant 

risk to either terrestrial or aquatic plants, and is not expected to harm listed species of plants. 

Thus, a “no effect” determination is made for all listed plants.

The two major degradates of clofentezine are 2-chlorobenzonitrile from direct aqueous 

photolysis, and 2-chlorobenzoic acid (2-chlorobenzylidine) hydrazide (AE C593600) from 

abiotic hydrolysis. Because toxicity data on these degradation products were not available, acute 

toxicity to aquatic organisms was estimated based on structural-activity relationships (SAR) 

using the ECOSAR program. Additional information on development and use of the ECOSAR 
13

model is available at: http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. Toxicity estimates 

indicated that the toxicity of the degradation products would be less than that of the parent. 

Therefore, the conclusion is that a risk assessment conducted based on exposure to the parent 

compound would be protective.

Conclusions about the potential for clofentezine to cause direct effects to threatened and 

endangered species of various taxa are summarized in Table 2. Because of limitations in 

available toxicity data and assumptions made in the exposure assessments, some uncertainty 

exists in the conclusions described here. (see Section VI.C.)
14

Table 2. Listed Species Risks Associated with Potential Direct Effects Due to the Applications of Clofentezine.

Listed Plant Taxon Potential Direct Effects

Terrestrial and semiaquatic plants –

monocots and dicots

No effect

Aquatic plants No effect

Listed Animal 

Taxon

Potential Direct Effects

Acute Notes Chronic Notes

Terrestrial 

invertebrates

Yes

(see 

note 

1)

1. Adverse effects to terrestrial 

invertebrates are expected to be 

limited to those that are exposed as 

eggs or larval stages. Terrestrial 

invertebrates exposed as adults are 

not expected to be affected.

ND

2. Based on results from the T-REX model, screening-level 

RQs exceed the chronic LOC for mammals of all size 

classes that eat any food items other than fruit, seeds, or 

pods. To reduce all of the RQs for chronic risk to listed 

mammals to less than the chronic LOC, the single 

application rate would need to be reduced to <0.19 lb a.i./A.

3. Chronic risk is uncertain because dietary-based RQs did 

not exceed the chronic LOC.

4. Based on results from the T-REX model, screening-level 

RQs exceed the chronic LOC for birds that eat plants (short 

grass or broadleaf plants). To reduce all of the RQs for 

chronic risk to listed birds to less than the chronic LOC, the 

single application rate would need to be reduced to <0.125

lb a.i./A. These results are also applicable for reptiles and 

terrestrial phases of amphibians.

Mammals No 

effect

Yes

(see notes

2 and 3)

Birds No 

effect

Yes

(see note

4)

Reptiles No 

effect

Yes

(see note

4)

Amphibians No 

effect

Yes

(see note

4)

Freshwater fish No 

effect No effect

Freshwater 

invertebrates

No 

effect No effect

Mollusks No 

data No data
15

Listed Plant Taxon Potential Direct Effects

Estuarine/marine fish No 

data No data

Estuarine/marine 

invertebrates

No 

effect No effect
16

II. Problem Formulation

A. Introduction

The problem formulation describes the stressor, the conceptual model used to estimate exposure, 

and the tools and methods used to assess the potential risk of clofentezine to nontarget 

organisms. The problem formulation for this assessment was originally provided on February 2, 

2007 in a memorandum entitled EFED Problem Formulation for Clofentezine Registration 

Review, which is part of the Clofentezine Registration Review Summary Document available in 

the Clofentezine Docket1. The problem formulation in this document represents the original 

problem formulation modified in response to public comments received on the original version. 

B. Nature of the Stressor

1. Pesticide Type, Class, and Mode of Action

Clofentezine (3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine; CAS Registry Number 74115-24-5) is 

the primary chemical stressor to be considered in this registration review assessment. 

Clofentezine belongs to the tetrazine chemical family of pesticides. The structure of clofentezine 

is shown in Figure 1. The only other acaricide in this chemical family is diflovidazin (3-(2,6-

clorophenyl)-6-(2,6-diflurophenyl)-1,2,4,5-tetrazine; CAS Registry Number 162320-67-4), 

which is not a registered pesticide in the United States.

Figure 1. Chemical Structure of Clofentezine

Clofentezine is used as a selective mite growth regulator by acting as an ovicide. According to 

information provided by the registrant on the label for Clofentezine SC (EPA Reg. No. 66222-

53), clofentezine is active against eggs and early life stages of mites. Yoshida and Fuchs (1989) 

found that at low doses clofentezine interferes with the development of larval stages of Varroa

mites. The Insecticide Resistance Action Committee (IRAC) classifies the mode of action as 

Group 10, mite growth inhibitors, although the exact site of action is unknown or non-specified

(IRAC, 2012). Based on claims made on the product labels, clofentezine is not disruptive to

beneficial insects and mites even though it has good residual activity on European red mites, 

 1 http://www.regulations.gov/#!docketDetail;D=EPA-HQ-OPP-2006-0240-0003
17

McDaniel mites, Pacific spider mites, two-spotted spider mites, Eriophyes and yellow spider 

mites.

In addition to considering exposure to the parent, two degradation products are expected to be 

formed in the environment in significant quantities and therefore are considered as potential 

stressors. Degradation of clofentezine in soil and water via aqueous hydrolysis forms 2-

chlorobenzoic acid (2-chlorobenzylidine)hydrazide (AE C593600). Degradation of clofentezine 

in shallow water via aqueous photolysis forms 2-chlorobenzonitrile. 2-chlorobenzonitrile has 

also been observed to form on the fruit and foliage of plants (JMPR, 2007). However, QSAR 

analysis of these degradation products indicate that they both are significantly less toxic than the 

parent compound and therefore will not contribute substantially as stressors to nontarget 

organisms (see Section II.E.3.)

2. Physical and Chemical Properties

Clofentezine is a crystalline solid with low aqueous solubility and low volatility. The physical 

and chemical properties of the primary stressor, clofentezine, are shown in

Table 3. During the preparation of this assessment, the solubility of clofentezine was revised 

upward to 34.2 parts per billion (ppb) from the previously reported value of “less than 2.0 ppb” 

based on newly received data2

. The Koc value used in earlier EFED assessments was based on 

the 2.0 ppb solubility concentration and has therefore also been updated for use in this 

assessment. The Koc value (516.1 L/kg) was calculated using the USEPA EPI (Estimation 

Programs Interface) Suite program version 4.10.

Table 3. Physical and Chemical Properties of Clofentezine

Common Name Clofentezine

IUPAC and CAS Name: 3,6-bis-(2-chlorophenyl)-1,2,4,5-tetrazine

CAS Registry Number 74115-24-5

Company Code: NC 21314

SMILES Code Clc1ccccc1c1nnc(c2ccccc2Cl)nn1

Empirical Formula C14H8C12N4

Molecular Weight, Daltons 303.15

Physical State Crystalline Solid (magenta crystals)

Melting Point, ° C 179-182

Boiling Point, ° C Not applicable

Solubility in Water, mgL-1, 25° C, pH 7 34.2 μg/L

Solubility in Non-aqueous Solvents, 20° C Acetone, 0.5 g/100mL

Chloroform, 5 g/100mL

Benzene, 0.25 g/100mL

Ethanol, 0.1 g/100mL

Hexane, 0.1 g/100mL

Dissociation Constant Not applicable

Vapor Pressure, 25° C 9.75 x 10-10 mm Hg

Henry’s Law Constant 1.14 x 10-8 atm-m3mole-1

Log n-octanol/water Partition Coefficient (Log Kow) 3.1

 2 MRID 48210701Van Meter, D. (2010) Clofentezine: Determination of the Water Solubility of a Test Substance. 

Project Number: 11742/6149. Unpublished study prepared by Springborn Smithers Laboratories.
18

C. Stressor Source and Distribution

1. Pesticide Use

Clofentezine is a registered active ingredient of agricultural pesticide products used for control of 

mite pests, including spider mites and the European red mite. It is registered for use on fruit trees 

(apples, apricots, cherries, nectarines, peaches, pears, and persimmons), nut trees (almonds and

walnuts), grapes, Christmas trees, and ornamental plants. It is available in three formulated 

products:

• Apollo 42% Ovicide/Miticide (EPA Reg. No. 66222-65)

• Apollo SC Ovicide/Miticide (EPA Reg. No. 66222-47)

• Clofentezine SC Ovicide/Miticide (EPA Reg. No. 66222-53)

All clofentezine products are formulated as suspension concentrates. 

Clofentezine products are diluted with water and applied as a spray onto foliage. For all crops, 

only one treatment is permitted per growing season, and the maximum application rate is 0.26 lb 

ai/A. Treatment is recommended to occur at the first sign of mite activity, which is likely to 

occur early in the growing season. Spray is typically applied to foliage, although apple trees may 

be treated as delayed dormant spray, that is, shortly prior to the openings of the buds in the 

spring. Treatment may occur up to the pre-harvest interval, which varies from 10 days for 

peaches and nectarines (CA only) to 140 days for persimmons. Crop-specific details of 

application methods are given in Table 4.
19

Table 4. Use Site and Application Information for Clofentezine

Site Description Products1

AI Single 

Maximum 

Application 

Rate (lb/A)

Max. 

Apps/ 

Crop 

Cycle

PHI2

(days)

Application 

Methods Restrictions

Apples Apollo SC 0.26 1 45

Delayed dormant 

or foliar spray 

with low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Pears Apollo 42%, 

Apollo SC 0.26 1 21

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Stone Fruits: apricot, 

peach, and nectarine

Apollo 42% , 

Apollo SC 0.26 1 10-21a Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Cherry Apollo SC 0.26 1 21

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Grape Apollo 42% , 

Apollo SC 0.26 1 21

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Not in NY

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Cherry Apollo SC 0.26 1 21

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Persimmon Apollo 42%, 

Apollo SC 0.26 1 140

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Tree Nuts: Almonds 

and Walnuts

Apollo 42%, 

Apollo SC 0.26 1 14-30b

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Christmas Trees Apollo SC 0.26 1 N/A

Foliar spray with 

low or high 

volume sprayer

No aerial application

No chemigation

Not in CA

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Forestry trees grown in 

greenhouses

Clofentezine 

SC 0.26 1 N/A

Low or ultralow 

volume sprayer, or 

hand-held sprayer

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

Ornamental Plants: 

nonbearing trees, 

shrubs, vines and 

herbaceous plants

Clofentezine 

SC 0.26 1 N/A

Low or ultralow 

volume sprayer, or 

hand-held sprayer

No chemigation

Do not apply within 100 ft 

of freshwater or estuarine 

habitat

1 Apollo 42%: Apollo 42% Ovicide/Miticide (Reg. No. 66222-65); Apollo SC: Apollo SC Ovicide/Miticide (Reg. 

No. 66222-47); Clofentezine SC: Clofentezine SC Ovicide/Miticide (Reg. No. 66222-53)

2 PHI = Pre-harvest interval (number of days prior to harvest that the application may occur.)

a PHI of 10 days is for California only. 

b PHI of 14 days is for almonds grown in California only. 
20

2. Pesticide Usage

EPA’s Biological and Economic Analysis Division (BEAD) provided an analysis of nationallevel usage information using state-level usage data obtained from various public and proprietary 

sources (Appendix A). Table 5 provides recent estimates of the usage of clofentezine on various 

crops. Crops with the largest use of clofentezine are almonds, apples, cherries, peaches, and 

walnuts. Crops with low usage (< 500 lbs A.I.) include apricots, grapes, nectarines, pears, and 

plums. Clofentezine use is not restricted geographically and thus may be used nationwide. 

States with the greatest usage would be those that greatest production of non-citrus fruits and 

nuts, which include California, Georgia, Michigan, New York, South Carolina, and Washington.

Table 5. Screening Level Estimates of Agricultural Uses of Clofentezine (125501) (February 17, 

2012)

1,2

Crop Lbs. A.I. Percent Crop Treated

Average Maximum

Almonds 3,000 <2.5 5

Apples 1,000 <2.5 10

Apricots <500 <2.5 <2.5

Cherries 1,000 5 10

Grapes <500 <1 <2.5

Nectarines <500 5 10

Peaches 1,000 5 15

Pears <500 5 10

Plums/Prunes+ <500 <2.5 <2.5

Walnuts 2,000 5 10

1 All numbers rounded.

<500 Less than 500 pounds of active ingredient

<2.5 Less than 2.5 percent of crop treated

<1 Less than 1 percent of crop treated

+ Crops not known to be listed on active end use product registrations or as Section 18 emergency

exemptions when this report was run

2 SLUA data sources include: 

USDA-NASS (United States Department of Agriculture's National Agricultural Statistics Service) 

Private Pesticide Market Research

California DPR (Department of Pesticide Regulation)

Figure 2 below is a map of agricultural pesticide usage at the Crop Reporting District (CRD) 

level prepared by BEAD for use in the Environmental Fate and Effects Division documents. 

These maps are used to help visualize where the pesticide being considered is most likely to 

be used and can be helpful in scenario selection and placing the exposure assessment in 

context. CRDs are boundaries created by USDA NASS which are aggregates of counties 

(USDA, 2010). Pesticide usage is displayed as average pounds (for the years 2006-2010) per 

1,000 acres of farmland in a CRD to normalize for the variation in farmland between CRDs. 

Farmland acreage was obtained from USDA (2007). Usage is based on private market surveys 
21

of pesticide use in agriculture (Proprietary Data, 2006-2010). The survey data are limited to 

the states that represent the top 80-90% of acreage for the individual crops; therefore, use may 

be occurring in regions outside the scope of the survey. CRDs showing no usage of pesticides 

may be due to either the lack of pesticide use in the region or non-participation in the 

agricultural surveys. In addition, across the years, there may be variations in the specific crops 

included in the CRD survey. This may result in a lower annual average for the CRD. 

This map displays ratio data (i.e., average pounds per 1,000 acres of farmland) summarized at 

a very high-level. Readers are strongly cautioned against trying to over interpret the map 

without examination of the underlying data. The underlying data may explain some of the 

many reasons that a Crop Reporting District may have a high value for a particular active 

ingredient such as significant acreage (compared with the CRD as a whole) of a crop or crops 

with a high application rate and frequency of application.

Proprietary Data. 2006-2010

USDA, 2006-2010. NASS Crop Reporting Districts. Online: 

http://www.ers.usda.gov/briefing/arms/resourceregions/resourceregions.htm#nass.

USDA, 2007. Census of Agriculture. Online: http://www.agcensus.usda.gov/Publications/2007/index.asp.

Figure 2. Map of clofentezine usage by crop reporting district (2006-2010).
22

D. Environmental Fate Summary

1. Clofentezine

Abiotic hydrolysis and direct photolysis in water (clear shallow water) and microbial-mediated 

degradation are major routes of transformation for clofentezine in the environment. Abiotic 

hydrolysis is pH and temperature dependent. At 25°C, the hydrolytic half-lives of clofentezine 

are 10.4 days (pH 5), 1.4 days (pH 7) and 0.18 days (pH 9). The direct photolysis half-life is 8.8

days. Although clofentezine under laboratory conditions appears to be more persistent in aerobic 

soil (t1/2 = 4 weeks in clay, 6 weeks in loamy sand and 8 weeks in clay loam), abiotic hydrolysis 

and/or direct photolysis are likely to control the degradation of clofentezine in the environment. 

However, extensive mineralization (i.e., CO2 formation, up to 56% in aerobic soil after one year) 

was found in the aerobic soil metabolism studies. Thus, mineralization is an important route of 

degradation in the environment. The proportion of radioactivity becoming irreversibly bound to

soil increases with time to between approximately 30% and 50% of applied radioactivity 

depending on soil type. Levels of 'bound' radioactivity further increase after establishment of

anaerobic conditions.

Clofentezine mobility in soils is uncertain because of the lack of acceptable data to assess its 

mobility; however, the soil-TLC data suggests that clofentezine may have low-to-moderate 

mobility in soils. Results of a more recent batch-equilibrium adsorption/ desorption study (the 

currently accepted methodology) was deemed invalid because of rapid hydrolysis of 

clofentezine. Even though mobility in soil data suggest the potential of clofentezine to partition 

into the sediment phase, hydrolytic and photolytic processes in the water column are expected to 

decrease the amount of clofentezine available for sorption onto the sediment phase. EFED 

therefore used the USEPA EPI (Estimation Programs Interface) Suite3 program to estimate the 

Koc (516.1 L/kg). Clofentezine has low potential to volatilize from soil or water.

Two aquatic metabolism studies, one aerobic and one anaerobic, were completed in 2010 and 

reviewed by the Canadian Pesticide Management Regulatory Agency (PMRA), (Lentz, 2010a, 

2010b). Whole system aerobic and anaerobic aquatic half-lives were calculated for 

water/sediment samples collected from two rivers in the United Kingdom. PMRA-calculated, 

aerobic whole-system half-life values are 23.0 and 28.9 days for the Taunton River system and 

Weweantic River system, respectively. PMRA-calculated, anaerobic whole-system half-life 

values are 44.9 and 33.2 days for the Taunton River system and Weweantic River system, 

respectively. An additional aerobic aquatic study with two surface water/sediment ditch 

microcosms was also conducted in the United Kingdom. Aerobic whole-system half-life values 

were 18.2 and 18.9 days for the ditch water- sandy clay loam sediment study and ditch waterclay loam sediment study, respectively. Studies submitted on the environmental fate of 

clofentezine are summarized in Table 6.

 3 http://www.epa.gov/oppt/exposure/pubs/episuite.htm US EPA. [2012]. Estimation Programs Interface SuiteTM for 

Microsoft® Windows, v 4.10].
23

Table 6. Environmental Fate Data from Submitted Studies on Clofentezine

Environmental Fate Study Data Comments References 

835.2130 [Abiotic] 

Hydrolysis

Temperature: 25° C

Half-lives (days)

1.4 (pH 7)

pH and temperature 

dependent

MRID: 47192107

MRID: 00159135

835.2240 [Direct] Photolysis 

in Water

8.8 days Dark control corrected 

half-life

MRID: 00159136

MRID: 00159152

835.2410 Photolysis on Soil 31 days 86% of parent remained 

after 31 days

835.4100 Aerobic soil 

metabolism

835.4200 Anaerobic soil 

metabolism

Temperature: 25° C

Half-lives (days)

4 weeks (clay)

6 weeks (loamy sand)

8 weeks (clay loam)

Qualitative results only

Mineralization was high

Biotransformation slows 

down under anaerobic 

conditions; mineralization 

is much lower than under 

aerobic conditions

MRID: 40048101

MRID: 40048102

MRID: 41203701

835.4400 Anaerobic Aquatic 

Metabolism

Whole-system half-life 

values are 44.9 and 33.2 

days for two rivers in the 

United Kingdom

PMRA Reviewed Study

(2077909)

MRID: 48269302

835.4300 Aerobic Aquatic 

Metabolism

Whole-system half-life 

values are 23.0 and 28.9 

days for two rivers in the 

United Kingdom

Whole-system half-life 

values are 18.2 and 18.9 

days for two watersediment ditches in the 

United Kingdom

PMRA Reviewed Study

(2096105) MRID: 48269301

MRID: 47192116

835.1230 Mobility in Soil Koc: 516.1 (L/kg) Calculated Value EPI Suite Ver 4.10

850.1730 Fish 

Bioconcentration BCF: 230x (whole body)

During the depuration 

phase, 93% of 

accumulated clofentezine 

was eliminated, with

virtually completely 

elimination after 3 days. 

MRID 405522-01
24

1. Degradation Products of Clofentezine

The major degradates of clofentezine are 2-chlorobenzonitrile (CAS No. 873-32-5) from direct 

aqueous photolysis and 2-chlorobenzoic acid (2-chlorobenzylidine) hydrazide (AE C593600) 

from abiotic hydrolysis. The product 2-chlorobenzoic acid (2-chlorobenzylidine) hydrazide) has 

been identified as an abiotic hydrolysis product. The rate of abiotic hydrolysis is pH and 

temperature dependent. At 25° C, the half-lives of clofentezine decrease with increasing pH 

(10.4 day at pH 5, 1.4 day at pH 7, and 0.18 day at pH 9). The percentage, as percent of the 

applied radioactivity, of the hydrolysis product AE C593600 increases with increasing pH. At 

the conclusion of 30 days, it accounted 14-23% at pH 5, 38% at pH 7, and 45% at pH 9. The 

direct photolysis of clofentezine may involve the hydrolytic product as an intermediate. 

However, direct photolysis would only be significant in clear, shallow water but not in deep, 

turbid water. Except for CO2, only traces of other degradates were identified in aerobic soils. See 

Table 7 below. Degradate structures are shown in Appendix B.

Clofentezine is degraded in soils under aerobic conditions with a half-life of approximately 4, 6 

and 8 weeks in the clay, loamy sand and clay loam respectively. Degradation of the parent 

proceeds via hydrolytic cleavage of the tetrazine ring leading to the formation of 2-chlorobenzoic 

(2-chlorofenzylidine) hydrazide. Further degradation leads to the formation of several other 

minor metabolites including 2-chlorobenzamide and 2-chlorobenzoic acid with ultimate 

mineralization to CO2, substantial amounts of which (up to 50% of the applied compound) were 

evolved in the first 6 months from aerobic soils. The rate of mineralization to CO2 was 

drastically reduced under anaerobic conditions and is virtually absent in sterile soils indicating 

that the activity of soil microorganisms is involved in the degradation of the pesticide in aerobic 

soils.

On the surface of treated plants, clofentezine degrades primarily by photolysis, and the only 

major degradation product formed is 2-chlorobenzonitrile (JMPR 2007).

Table 7. Degradation Products of Clofentezine

Environmental Fate 

Process

Major Degradates Minor Degradates

Hydrolysis

MRID: 00159135

2-chlorobenzoic acid (2-

chlorobenzylidene)hydrazide (M1 or VII)

2-chlorobenzonitrile (M2 or V) 

2-chlorobenzamide (M5 or II)

Aerobic Aquatic

Metabolism

MRID: 47192116

2-chlorobenzoic-(2-chlorobenzylidene)-

hydrazide (compound III, AE C593600)

2,5-bis(2-chlorophenyl)-1,3,4-

oxadiazole (NC 12940, compound II)

N',N-bis(2-chlorobenzoyl)-hydrazine 

(NC 12898, compound IV)

2-chlorobenzoic acid (NC 233, 

compound V)

Anaerobic Aquatic

Metabolism

MRID: 48269302

PMRA: 2077909

2-cholorbenzoic acid

2-chlorobenzoic hydrazone

N',N-bis(2-chlorobenzoyl)-hydrazine 

(NC 12898, compound IV)

2-chlorobenzoic acid (NC 233, 

compound V)

Aerobic Soil Metabolism 2-chlorobenzoic (2-chlorofenzylidine) 2-chlorobenzamide
25

MRID: 00159138 hydrazide

2-chlorobenzoic acid

Direct Aqueous Photolysis

MRID: 00159136

2-chlorobenzonitrile

2-chlorobenzaldehyde

E. Ecological Effect Summary

1. Aquatic Effects

Table 8 contains the available acute toxicity data that the EPA used to assess the risks of 

clofentezine to aquatic animals and plants. Freshwater fish serve as a surrogate to assess 

potential risk to aquatic-phase amphibians as well as fish. Acute toxicity studies show that 

clofentezine is not acutely toxic to freshwater fish or invertebrates at aqueous concentrations up 

to the solubility limit. Because of the limited solubility of clofentezine, testing with the TGAI 

could not be conducted at much above the solubility limit. Testing at higher concentrations was

possible when tests were conducted with a typical end-use product (TEP), Apollo® 50 SC, 

which forms a colloidal suspension in water. Although nominal concentrations were very high, 

the dissolved component of clofentezine in these studies is believed to be near the solubility limit 

of 34.2 μg/L, while the remainder of the active ingredient would exist as suspended particles. 

(Measured concentrations of clofentezine reported in the study reports are believed to be 

unreliable because the test solution samples were not filtered or centrifuged before analysis.) 

While the findings of all three available acute toxicity tests with fish agree in showing that the 

LC50 is greater than the solubility limit of clofentezine, the TEP study conducted with the 

rainbow trout using Apollo 50 SC (MRID 40568202) was used as the definitive acute fish 

toxicity study in this risk assessment because it is the only one of the three studies that was 

classified as acceptable). This TEP study showed that the 96-hr LC50 is >24 mg product/L, 

classifying the product as no more than slightly toxic to fish. The limited solubility prevents 

classification of the acute toxicity of the active ingredient, but the TEP study shows that it does 

not cause mortality or sublethal effects at concentrations up to the solubility limit. 

Three acute toxicity tests are available with the water flea, a freshwater crustacean. Two studies 

conducted with the TGAI were classified as supplemental because the lab failed to test up to the 

solubility limit of clofentezine (both studies) and failed to filter or centrifuge samples before 

measuring the test concentrations (MRID 00105919). The TEP study conducted using Apollo 50 

SC (MRID 40568203) was used in this risk assessment as the definitive acute freshwater 

invertebrate toxicity study because it is the only one of the three studies that was classified as 

acceptable). This TEP study with the water flea showed that the 48-hr LC50 of the product is 

>100 mg product/L, classifying the product as practically nontoxic to freshwater invertebrates.

In acute aquatic tests conducted with Apollo® 50 SC, the mean measured concentration of the 

test concentrations far exceeds the solubility limit of clofentezine. Since there is no indication 

that the test concentrations were filtered before chemical analysis, the reported measured 

concentrations are believed to represents concentrations of undissolved suspended solids as well 

as the dissolved component of clofentezine. The concentration of dissolved clofentezine in these 
26

tests was assumed to be at equilibrium at near the solubility limit, and thus the LC50 values for 

the active ingredient were expressed as greater than the solubility limit (>34.2 μg a.i./L). 

A toxicity study Selenastrum capricornutum conducted with a formulated product, Apollo 50 

SC, found that clofentezine had no significant adverse effects on growth and reproduction of 

green algae at product concentrations as high as 100 mg product/L (MRID 47200501). This 

study was classified as supplemental because the test duration (92 hr) was shorter than the 

recommended duration (96-120 hr), and because the study report was missing some information 

on methodology, including the photoperiod, the age of the algal inoculum, test vessel fill 

volumes, and a description of the dilution water. Also, at the higher test concentrations, cell 

growth was greatly stimulated. According to the study authors, the stimulation presumably 

occurred because the parent compound was degrading into nitrogenous products which added 

nutrients to the growth medium, similar to fertilizer. As with the acute freshwater invertebrate 

tests, the concentration of clofentezine was not expected to exceed the solubility limit, and thus 

the reported endpoints which exceeded the solubility limit were adjusted to the solubility limit of

34.2 μg ai/L. Despite these shortcomings, this study was sufficient to show that clofentezine is 

not toxic to green algae up to the solubility limit of clofentezine.

Data are not available on the toxicity of clofentezine to vascular aquatic plants. However, based 

on the mode of action of this pesticide (i.e., as an acaricide), the lack of phytotoxicity observed 

in terrestrial vascular plants, the lack of reported plant damage incidents or warnings about 

phytotoxicity to sensitive plants, adverse effects to aquatic vascular plants are not expected.

Table 8. Most Sensitive Acute Toxicity Values for Clofentezine to Aquatic Animals and Plants

Taxonomic Group, 

Study Type Surrogate Species Toxicity CitationMRID

Acceptability

Classification

Fish

Freshwater fish,

Acute study with 

TGAI

Rainbow Trout 

(Oncorhynchus mykiss)

96-hr LC50 > 14.6 μg ai/L

(No mortality or adverse 

effects were observed; 

highest test level was close 

to the solubility limit)

MRID 

40568201 Supplemental1

Freshwater fish,

Acute study with 

Apollo 50 SC 

(50% AI)

Rainbow Trout 

(Oncorhynchus mykiss)

96-hr LC50 >

24 mg product/L

96-hr LC50 > 34.2 μg ai/L2

MRID 

40912101 Acceptable

Bluegill Sunfish

(Lepomis macrochirus)

96-hr LC50 >

10.1 mg product/L

96-hr LC50 > 34.2 μg ai/L2

MRID 

00159120 Supplemental

Aquatic Invertebrates

Freshwater 

invertebrates with 

TGAI,

Acute

Water flea

(Daphnia magna) 48-hr LC50 > 1.15 μg ai/L MRID

40568203 Supplemental3

Water flea

(Daphnia magna) 48-hr LC50 > 0.80 μg ai/L MRID00105919 Supplemental4

Freshwater 

invertebrate,

Acute study with 

Apollo 50 SC 

(50% AI)

Water flea

(Daphnia magna)

48-hr LC50 >

100 mg product/L

48-hr LC50 > 34.2 μg ai/L2

MRID

40568202

Acceptable 

(for TEP)

Aquatic Plants
27

Taxonomic Group, 

Study Type Surrogate Species Toxicity CitationMRID

Acceptability

Classification

Algae, study with 

Apollo 50 SC 

(50% AI)

Green algae

(Selenastrum 

capricornutum)

Formulation :

96-hr IC50 > 100 mg/L

NOAEC: 100 mg/L

LOAEC: >100 mg/L

Active Ingredient:

96-hr IC50 > 34.2 μg/L2

NOAEC: 34.2 μg/L2

LOAEC: >34.2 μg/L2

MRID

47200501 Acceptable

1. This study was classified as supplemental because the study failed to establish the NOAEC and did not test 

to either 100 mg a.i./L or the solubility limit of clofentezine. 

2. Results for the active ingredient that were calculated based on reported measured concentration are not 

reported here because the analytical analysis is believed to have measured undissolved solids suspended in

the suspension concentrate formulation as well as the dissolved component. Instead, endpoints with 

reported active ingredient concentrations greater than the solubility limit were adjusted to greater than the 

solubility limit (>34.2 μg a.i./L).

3. This study was classified as supplemental because the study failed to establish the NOAEC and did not test 

to either 100 mg a.i./L or the solubility limit of clofentezine.

4. This study was classified as supplemental because the test was conducted at a nominal concentration well 

above the solubility limit of clofentezine, and centrifuging or filtering of undissolved test material was not 

used prior to measurement of the concentration of test material.

Table 9 contains available data on the chronic toxicity of clofentezine to fish and aquatic 

invertebrates. Two studies have been conducted on the effects of clofentezine on the early life 

stage of freshwater fish. The first study conducted with the rainbow trout (MRID 42735201) 

found no adverse effects when the active ingredient was tested at concentrations up to 6 μg ai/L. 

(Testing was conducted at 6 μg ai/L based on a solubility study conducted in 1985 which 

erroneously reported the solubility of clofentezine as less than 2 μg/L; however, this study was 

later found to be invalid and a new solubility study yielded a solubility limit of 34.2 μg/L.) This 

study was classified as supplemental because the concentration of the solvent use (acetone) was 

not reported, and a solvent control group was not included in the study. A second study was 

conducted with the fathead minnow and using the formulated product Apollo® 50 SC (MRID 

47192101). This study was conducted using a flow-through system, and results are presented 

based on the time-weighted average of measured concentrations of the active ingredient. Since 

clofentezine forms a colloidal suspension in this formulated product, the study was able to test 

higher concentrations than in the TGAI study. This study found no adverse effects on growth, 

hatching success, or time to hatch at test concentrations as high as 979 μg ai/L, establishing a 

NOAEC at this level.

Four aquatic invertebrate life-cycle studies have been submitted for clofentezine. Deficiencies in 

all of these studies resulted in all being classified as supplemental. However, the study 

submitted which tested the toxicity of the TGAI to Daphnia magna (MRID 42523901) is 

adequate as a limit test because it demonstrates that clofentezine would not cause chronic 

toxicity to this species at concentrations expected in natural water. This test found no chronic 

effects were caused by a single test concentration of 26.2 μg ai/L, which is close to the solubility 

limit of clofentezine at pH 7 (34.2 μg/L). Another life-cycle test was recently submitted which 

tested the chronic toxicity of the TGAI to the mysid (Americamysis bahia), a saltwater 
28

crustacean (MRID 48342701). This study indicates that the mysid is more sensitive to 

clofentezine than Daphnia magna. Female reproduction was significantly impaired at 

concentrations as low as 3.6 μg a.i./L, whereas growth and survival were not adversely affected 

at any test concentration. These results suggest that the toxic mode of action in the target 

organisms, i.e., toxicity to eggs and early growth stages, may also result in similar toxicity to 

some aquatic invertebrates. 

In addition to the TGAI studies, two submitted life-cycle studies and one open literature study 

provides information on the chronic toxicity to the water flea (Daphnia magna) of Apollo 50 SC,

a suspension containing 43.5% clofentezine. Both of these studies were conducted according to 

the OECD test guideline for testing reproduction with Daphnia sp. (Guideline No. 211), which 

differs from the comparable EPA test guideline (850.1300), and one study (MRID 47192117) 

had numerous guideline deviations. Thus, both of the submitted life-cycle studies were 

classified as supplemental. Both of these studies found that reproduction was a more sensitive 

chronic endpoint than growth or survival. One study (MRID 47192117) was deficient because

solubility challenges made the exposure concentrations uncertain, measured concentrations in 

aged samples were highly variable, and the study failed to establish an NOAEC for reproduction. 

This study found that all test concentrations significantly reduced the number of offspring 

produced per female. Percent reductions (relative to the control) ranged from 8.25% at 0.10 mg 

product/L to 17.5% at 15 mg product/L. A second study (MRID 47192102) had a similar setup to 

the first except that the test vessels contained sediment, the test was conducted under static 

conditions rather than under static-renewal conditions, and the test material was applied to 

overlying water at either Day 0 or at Day 6. Reproduction was again the most sensitive endpoint. 

When the test material was applied on Day 0, significant reductions in offspring produced per 

female were observed at all test levels. Percent reductions ranged from 14.6% at 0.275 mg 

product/L to 19.2% at 2.65 mg product/L. As the results of this study were similar to the results 

of the study without sediment, the presence of sediment did not appear to substantially affect the 

reproductive toxicity of clofentezine to Daphnia magna. The study without sediment (MRID 

47192117) tested lower test concentrations than did the study with sediment, and thereby

established the lower LOAEC for reproductive toxicity of 100 μg product/L, or 44 μg a.i./L. 

None of the studies established a NOAEC. 

For chronic risk assessment, the reproductive LOAEC of 44 μg a.i./L for Daphnia magna

(MRID 47192117) was selected as the endpoint to assess chronic risk to freshwater invertebrates, 

and the NOAEC of 1.7 μg/L (MRID 48342701) was selected to assess chronic risk to saltwater 

invertebrates.

Table 9. Chronic Toxicity of Clofentezine to Aquatic Animals

Taxonomic Group, 

Study Type Surrogate Species Toxicity CitationMRID

Acceptability 

Classification

Fish

Freshwater Fish,

Early Life-Stage

Rainbow Trout 

(Oncorhynchus mykiss)

NOAEC: 6 μg ai/L

LOAEC: >6 μg ai/L

MRID 

42735201 Supplemental1

Freshwater fish,

Early Life-Stage with 

Apollo 50 SC 

(50% AI)

Fathead Minnow

(Pimephales promelas)

NOAEC: 979 μg ai/L

LOAEC: >979 μg ai/L

MRID 

47192101 Acceptable
29

Taxonomic Group, 

Study Type Surrogate Species Toxicity CitationMRID

Acceptability 

Classification

Freshwater Invertebrates

Freshwater 

invertebrates,

Life-Cycle with 

TGAI (99.8% purity)

Water flea

(Daphnia magna)

NOAEC: 26.2 μg ai/L

LOAEC: >26.2 μg ai/L

MRID

42523901 Supplemental2

Freshwater 

invertebrates,

Life-Cycle study with 

Apollo 50 SC 

(50% AI)

Water flea

(Daphnia magna)

Survival

NOAEC: 15 mg product/L

 (6.5 mg ai/L)

LOAEC: >15 mg/L

 (>6.5 mg ai/L)

Reproduction

NOAEC: <100 μg product/L

 (<44 μg ai/L)

LOAEC: 100 μg product/L

 (44 μg ai/L)

(Reduced number of 

offspring per female ; 8.25% 

reduction at lowest test level)

Growth

NOAEC: 100 μg product/L

 (44 μg ai/L)

LOAEC: 350 μg product/L

 (150 μg ai/L)

(Reduced length)

MRID

47192117 Supplemental2

Freshwater 

invertebrates,

Reproduction study 

with Apollo 50 SC 

(50% AI)

Water flea

(Daphnia magna)

Reproduction

NOAEC: 0.12 mg product/L

 (0.06 mg ai/L)

LOAEC: 1.2 mg/L

 (0.60 mg ai/L)

(Reduced number of 

offspring)

Eco Ref # 

12662

Barber and 

Barrett 

(1993)

Qualitative

Freshwater 

invertebrates,

Life-Cycle study, 

water with sediment 

system with Apollo 

50 SC 

(50% AI)

Water flea

(Daphnia magna)

Survival

NOAEC: 2.50 mg product/L 

 (1.04 mg ai/L)

LOAEC: >2.50 mg product/L

 (>1.04 mg ai/L)

Reproduction

NOAEC: 

 < 0.275 mg product/L

 (<0.114mg ai/L)

LOAEC: 

 0.275 mg product/L

 (0.114 mg ai/L)

(Reduced number of 

offspring when exposed to < 

24-hr old neonates)

Growth

NOAEC:

 2.50 mg/L 

MRID

47192102 Supplemental3
30

Taxonomic Group, 

Study Type Surrogate Species Toxicity CitationMRID

Acceptability 

Classification

 (1.04 mg ai/L)

LOAEC: 

 >2.50 mg/L 

 (>1.04 mg ai/L)

Saltwater Invertebrates

Estuarine/marine 

invertebrates,

Life-Cycle

Mysid shrimp 

(Americamysis bahia)

Survival

NOAEC: 29 μg ai/L

LOAEC: >29 μg ai/L

Reproduction

NOAEC: 1.7 μg ai/L

LOAEC: 3.6 μg ai/L

(Reduced number of 

offspring per female)

MRID

48342701 Supplemental4

1. This study was classified as supplemental because a solvent control was not included in the study design, 

the solvent concentration was not reported, and the study report lacked reporting of sublethal effects.

2. This study was classified as supplemental because the study did not identify the NOAEC and LOAEC for 

clofentezine, the amount of disolved AI in the test solutions was uncertain, and the control mortality was 

excessive (12.5%).

3. This study was classified as supplemental because it was conducted according to the protocol of OECD 

Guideline 202, which deviates significantly from the OSPP Guideline for freshwater invertebrate life-cycle 

testing, 850.1300. Furthermore, the study failed to establish an NOAEC for reproductive effects.

4. This study was classified as supplemental because the diluter system delivered inconsistent concentrations 

of active ingredient during the study. Results are based on time-weighted average concentrations.

Barber and Barrett (1993) conducted a study to test their hypothesis that the chronic toxicity to 

Daphnia magna exhibited by clofentezine products formulated as suspension concentrate is the 

consequence of particles in the formulated product causing physical interference with filter 

feeding rather than the result of intrinsic toxicity of the active ingredient. They tested the 

reproductive response of Daphnia magna when exposed to three concentrations of Apollo 50 SC 

(50% clofentezine), concentrations of inert polyvinyl toluene (PVT) latex beads that were 

equivalent to the Apollo 50 SC concentrations in terms of particle concentrations, and a 

formulated blank (Apollo 50 SC formulation without the active ingredient) at a rate equivalent to 

the highest test concentration. The concentrations of Apollo 50 SC tested were 0.12, 1.2, and 12 

mg/L, which is equivalent to 0.060, 0.60, and 6.0 mg ai/L. The result showed reproduction 

performance was not significantly affected (relative to the control) by the formulated blank, but 

was significantly reduced by both the Apollo 50 SC and the PVT bead treatments. The NOAEC

for Apollo 50 SC treatment was 0.12 mg product/L (0.06 mg ai/L). The reproductive response of 

Daphnia magna in this study was less sensitive to Apollo 50 SC in this study than a life-cycle 

study submitted to the EPA (MRID 47192117) in that the NOAEC and LOAEC were greater, 

although the dose-response of the number of offspring per female were similar in both studies. 

For example, MRID 47192117 found an 8.25% reduction in this endpoint at a concentration of 

0.044 mg ai/L, and this study found a 9.8% reduction at the slightly higher concentration of 

0.060 mg ai/L.

Barber and Barrett (1993) found that exposure of Daphnia magna to supposedly inert PVT latex 

beads also caused reductions in reproductive performance. The reduction in number of offspring 
31

produced per adult was generally similar in test solutions of Apollo 50 SC and mixtures of water 

and latex beads with identical particular concentrations (Table 10). The reproductive response

was similar between comparable treatments with the exception that the reduction in offspring 

production was somewhat greater in the latex bead mixture than the Apollo 50 SC at the highest 

particular concentration (3.7 x 109 L-1). According to the study authors, this similarity in the 

reproductive responses “suggests that the effect of Apollo 50 SC was not due to any intrinsic 

toxicity of the formulation, but rather a consequence of its particular concentration.” This may 

explain why reproductive toxicity was observed in daphnids exposed to the SC formulated 

product, but not when exposed to technical grade clofentezine.

Table 10. Comparison of reproductive response of Daphnia magna exposed to Apollo 50 SC 

and PVT latex beads with identical particle concentrations (from Barber and Barrett, 1993)

Particle 

Concentration

(particles/L)

Product 

Concentration

(mg/L)

AI Concentration

(mg ai/L)

Number of Offspring per 

Adult

Percent Change in No. 

Offspring/Adult

Apollo 50 

SC

Latex 

beads

Apollo 50 

SC

Latex 

beads

Formulated blank 0 0 35.8 35.8 -- --

3.7 x 107 0.12 0.06 32.3 33.8 -9.8 -5.8

3.7 x 108 1.2 0.60 31.4 31.9 -12.6 -10.9

3.7 x 109 12 6.0 29.7 23.0 -17.1 -35.9

2. Terrestrial Effects

Table 11 presents the acute toxicity data that the Agency used to assess the risk of clofentezine to 

terrestrial animals and plants. Birds act as surrogates for reptiles and terrestrial-phase 

amphibians when data on those species are not available. Acute oral and subacute dietary studies 

with the northern bobwhite and mallard all showed that clofentezine has low acute toxicity to 

birds. These studies classify clofentezine as practically nontoxic to birds. Acute toxicity studies 

with mammals show that clofentezine is practically nontoxic to mammals on an acute basis. 

Studies on dermal and inhalation toxicity in mammals found no mortality at the doses tested, 

indicating low acute toxicity through these exposure routes (Toxicity Category III or IV). 

An acute contact test with adult honey bees determined the LD50 to be >1500 mg a.i./L. This 

study was classified as supplemental because exposure was expressed as the concentration of the 

solution sprayed onto the bee, rather than the amount of active ingredient applied per bee, per the 

EPA test guideline. Nevertheless, this study is sufficient to show that use of clofentezine 

products is expected to pose minimal hazard to adult bees from acute contact exposure. Also, an 

available acute oral toxicity honeybee study determined the acute oral toxicity of clofentezine to 

be >20 μg/bee. Based on the classification scheme used by the EPA for the acute contact 

studies, this toxicity level would classify clofentezine as practically nontoxic to bees.

Yoshida and Fuchs (1989, Eco Ref. No. 154863) provides additional information on the 

developmental toxicity of clofentezine to the honey bee. In one test, the authors exposed the 

bees in the 5th instar (L5) stage with topical applications of 10μl clofentezine solutions, with test 

concentrations ranging from 0.05 to 500 μg/bee. Failure of the larvae to seal the cell was used as 
32

a measure of mortality. Elevated levels of mortality were observed at treatment concentrations 

of 50 μg a.i./bee and greater. High levels of abnormal pupa development (over 40%) were

observed at concentrations of 25 μg a.i./bee and greater. This test established an NOAEL of 5 

μg a.i./bee for toxicity from acute contact exposure. In a second bee larvae feeding study, pollen 

mixtures, containing 1.0 to 1000 mg a.i./kg clofentezine were fed to larvae bees of nucleus 

colonies. Bee larvae were in various stages of development from L1 to L5, and were grouped 

into three groups (L1 and L2, L3 and L4, and L5) to measure effects with exposure to various 

developmental stages. In all developmental groups, abnormal bee pupas were observed in 

groups fed pollen with a clofentezine concentration of 1000 mg a.i./kg. Results on mortality 

were uncertain because no statistical analyses were conducted, but mortality of bees exposed at 

the L1 level appeared to be elevated at clofentezine concentrations of 10 mg a.i./kg and greater. 

Based on mortality, the NOAEL for the feeding study was 1.0 mg a.i./kg pollen.

One submitted report (MRID 471921-22) and two papers published in the open literature 

(Samsoe-Peterson, 1993, Olszak, 1999) provide further information on the toxicity of 

clofentezine to terrestrial beetles (Order Coleoptera). MRID 471921-22 found no significant 

adverse effects on egg survival, larvae survival, or pupae emergence in the ladybird beetle 

(Coccinella septempunctata) when they were exposed to 100 and 200 g a.i./ha, which 

corresponds to 0.089 and 0.18 lb a.i./A, respectively. The spray volumes used were 500 and 

1000 L/ha, which are equivalent to 54 and 110 gal/A, respectively. Olszak (1999) studied the 

toxicity of clofentezine and 29 other pesticides to another ladybird beetle, Adalia bipunctata. An 

immersion study using 0.027% (270 ppm) concentration of clofentezine caused relatively low 

levels of mortality (0-15%) of various developmental stages from L1 to adult. Clofentezine 

exposure caused greater effects on reproduction. When eggs were immersed, percent hatch 

ranged from 76.9 % for 1-day-old eggs to 45.0% for 3-day-old eggs. When females were 

immersed, egg production was approximately 300 eggs/female, compared to approximately 650 

eggs/female in the control. Beetles were also reared on leaves which had been treated with a 

0.027% clofentezine solution and allowed to age for 2 hours to 21 days. Exposure of the second 

instar resulted in 0% to 47% mortality, and exposure to the forth instar resulted in 0% to 37% 

mortality. Samsoe-Peterson (1993) studied the effects of Apollo 50 SC on the survival and 

reproduction of the rove beetle, Aleochara bilineata. The beetles were sprayed with a 

concentration of clofentezine of 0.02% at a rate of 6 μl/cm2, which the authors claim is 

equivalent to exposure to spray at the maximum application rate. The exposure resulted in no 

mortality of adults and no significant reduction in egg production, but caused a 28% reduction in 

percent hatching of eggs relative to the control. Together these papers show that clofentezine is 

not toxic to adult beetles, but is toxic to eggs and early life-stages.

One study is available on the phytotoxicity of clofentezine. In a Tier 1 vegetative vigor study 

with the formulated product Apollo 50 SC, application of clofentezine at the maximum 

application rate of 0.26 lb a.i./A resulted in no observable adverse effects to 4 dicot species and 2 

monocot species (MRID 47192103). This indicates that foliar exposure to clofentezine is not 

toxic to emerged plants at environmentally-relevant concentrations. Toxicity related to effects 

on seed germination and plant emergence is unknown.
33

Table 11. Acute Toxicity of Clofentezine to Terrestrial Species

Taxonomic 

Group,

Study Type

Surrogate Species Toxicity 

(expressed as AI)

Citation

MRID

Acceptability 

Classification

Birds1

Birds1, Acute Oral

Bobwhite quail

(Colinus virginianus) LD50 > 7500 mg a.i./kg-bw MRID00105913 Acceptable

Mallard 

(Anas platyrhynchos) LD50 > 3000 mg/kg-bw MRID00105914 Acceptable

Birds1, Subacute 

Dietary

Bobwhite quail

(Colinus virginianus) LC50 > 19,900 mg/kg-diet MRID 00159117 Acceptable

Mallard 

(Anas platyrhynchos) LC50 > 20,700 mg/kg-diet MRID00159118 Acceptable

Mammals

Mammals, Acute 

Oral

Laboratory rat

(Rattus norvegicus) LD50 > 3230 mg a.i./kg-bw MRID 00159071 Acceptable(Minimal)

Mammals, Acute 

Oral, with 80% 

wettable powder 

formulation

Laboratory rat

(Rattus norvegicus) LD50 > 4000 mg a.i./kg-bw MRID 00105904 Acceptable

(Minimal)

Mammals, Acute 

Oral, with 50% 

wettable powder 

formulation

Laboratory rat

(Rattus norvegicus)

LD50 > 5000 mg/kg-bw

LD50 > 2500 mg a.i./kg-bw MRID 00105903 Acceptable

(Guideline)

Mammals, Acute 

Inhalation, 80% 

wettable powder 

formulation

Laboratory rat

(Rattus norvegicus)

LC50 > 11.35 mg/kg-bw

LC50 > 9.08 mg a.i./kg-bw MRID 00159072 Acceptable

(Minimal)

Mammals, Acute 

Dermal, Apollo 

SC formulation 

(42% a.i.)

Rabbit

LC50 > 20,050 mg/Kg-bw

LC50 > 16,040 mg a.i./Kgbw

MRID 00105905 Acceptable

(Minimal)

Beneficial Insects

Bee, acute contact Honey bee 

(Apis mellifera)

LD50 (contact) 

 > 1500 mg a.i./L MRID 00159121 Supplemental2

Bee, acute oral Honey bee 

(Apis mellifera) LD50 (oral) > 20 μg/bee MRID 00159121 Supplemental

(Nonguideline)

Beneficial insect, 

with Apollo® 50 

SC (51.7% a.i.)

Ladybird Beetle 

(Coccinella 

septempunctata)

LC50 > 200 g a.i./ha

NOAEC: 200 g a.i./HA MRID 47192122 Supplemental

(Nonguideline)

Terrestrial Plants

Terrestrial Plants, 

Tier 1 Vegetative 

Vigor with Apollo 

50 SC (49.8% a.i.)

Dicots

(carrot, cucumber,

pea, and canola)

IC25: >0.26 lb a.i./A

NOAEL: 0.26 lb a.i./A

LOAEL: >0.26 lb a.i./A MRID 47192103 Supplemental3

Monocots

(chufa and oat)

IC25: >0.26 lb a.i./A

NOAEL: 0.26 lb a.i./A

LOAEL: >0.26 lb a.i./A

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

2. This study was classified as supplemental because the acute contact LD50 was expressed as a concentration 

(mg/L) rather than the amount of a.i. per bee.

3. This study was classified as supplemental because it tested only six species (4 dicots and 2 monocots) and did 

not measure survival or plant height.
34

Table 12 provides results of chronic toxicity tests conducted with birds and mammals. The 

northern bobwhite was the most sensitive bird species. A dietary concentration of 90 mg a.i./kg 

significantly reduced embryo viability, establishing the NOAEC at 30 mg a.i./L. For mammals, 

a rat 2-generation reproduction test established the chronic NOAEL at 20 mg/kg day. Daily 

dietary doses up to 20 mg a.i./ kg-BW day resulted in no frank effects on survival, reproduction, 

or development in the F1 and F2 generations. For adult male and nonlactating female rats, this 

daily dose is approximately equivalent to a dietary concentration of 400 mg/kg-diet.

Table 12. Chronic Toxicity of Clofentezine to Terrestrial Species 

Taxonomic 

Group,

Study Type

Surrogate Species Toxicity 

(expressed as AI)

Citation

MRID

Acceptability 

Classification

Birds1, 

Reproduction

Northern bobwhite

(Colinus virginianus)

NOAEC: 30 mg a.i./kg-diet

LOAEC: 90 mg a.i./kg-diet

(reduced embryo viability)

MRID

42776101 Acceptable

Mallard 

(Anas platyrhynchos)

NOAEC: 270 mg a.i./kg-diet

LOAEC: >270 mg a.i./kgdiet

MRID

42776102 Acceptable

Mammals, 2-

Generation 

Reproduction

Laboratory rat

(Rattus norvegicus)

Frank effects

NOAEC: 20 mg/kg-BW day

LOAEC: >20 mg/kg-BW 

day

(no effects on survival, 

reproduction, or 

development)

Other effects

NOAEC: 20 mg/kg-BW day

LOAEC: >20 mg/kg-BW day

(minimal entrilobular 

hepatocyte hypertrophy in 

males)

MRID 00147844 Acceptable

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

3. Toxicity of Degradation Products

The two major degradates of clofentezine are 2-chlorobenzonitrile and 2-chlorobenzoic acid (2-

chlorobenzylidine)hydrazide (AE C593600). Photolysis of clofentezine forms 2-

chlorobenzonitrile in soil and shallow water, and on plant surfaces. Hydrolysis of clofentezine 

forms 2-chlorobenzoic acid (2-chlorobenzylidene) hydrazide (AE C593600) in soil and water. 

Transformation of clofentezine into both of these products involves cleavage of the triazine ring 

in the center of the molecule. As this substantially changes the shape of the molecule, these

products would not likely retain the ovicidal activity of the parent compound. However, they

may have toxicity through other mechanisms.

Because no studies on the toxicity of AE C593600 are available, the ECOSAR (ver. 1.0) 

program was used to estimate toxicity of this compound to aquatic organisms based on 

quantitative structural-activity relationships (QSAR). Table 13 presents the estimated acute and 

chronic toxicity threshold values based on relationships with hydrazines and amides, and based 
35

on relationships with all uncharged compounds (neutral organics). The predicted toxicity of this 

degradation product is less than that of the parent compound with the exception of the 

predictions for toxicity to algae based on hydrazines. Except for green algae, conversion of the 

some of the parent compound to the degradation product would decrease the overall hazard to 

nontarget organisms, compared to if the applied active ingredient remained as the parent 

compound. Thus, because the terrestrial and aquatic risk assessments assumed 100% of the 

applied active ingredient remained as the parent compound, the risk assessments are protective. 

Any conversion of the parent compound to the degradation product would only reduce risk, with 

the possible exception of risk to algae if the ECOSAR predictions based on hydrazines are 

correct.

Table 13. Predicted Toxicity of the Degradation Product AE C593600 to Aquatic Organisms 

Based on Quantitative –Structural Relationships.

Organism Duration Endpoint Predicted Toxicity (μg/L)

Hydrazines Amides Neutral Organics

Acute Toxicity

Fish 96-hr LC50 344 3,320 16,800

Daphnid 48-hr LC50 7,230 2,970 11,400

Green Algae 72-96 hr EC50 0.0549 274 8,470

Chronic Toxicity

Fish chronic NOAEC 26 20 1,540

Daphnid chronic NOAEC 65 39 1,330

Green Algae chronic NOAEC 0.0137 490 3,910

ECOSAR appears to predict AE C593600 may have very high toxicity to green algae based on 

the toxicity of hydrazine (N2H4). Hydrazine, without a carboxyl group or any other functional 

groups attached, is highly toxic to green algae (144-hr EC50 0.041 μg/L); however, 

semicarbazides which are substituted with various functional group have been found to be 

generally much more toxic to green algae by 5 to7 orders of magnitude (EC50 range from 2.5 to 

190 mg/L) (Clements 1996). Also, as indicated by the predicted results in Table 13, amides are 

generally much less toxic to algae. Because AE C593600 is hydrazide, making it an amide as 

well as a hydrazine, and because it has two chloro-phenyl functional groups attached, we do not 

believe that the predictions of high toxicity to green algae based on simple hydrazine are 

appropriate for predicting the toxicity of this compound. We expect the toxicity of AE C593600

to be closer to the SAR prediction made based on amides, 490 μg/L. Thus, we do not expect AE 

C593600 to be more toxic to algae than the parent, and formation of this degradation product is 

not expected to pose a risk to aquatic plants above what is predicted by the current aquatic risk 

assessment.

ECOSAR (ver. 1.0) was also used to estimate toxicity of 2-chlorobenzonitrile to aquatic 

organisms. By comparing this compound to similar neutral organics, ECOSAR predicts 

relatively low acute and chronic toxicity for all evaluated aquatic animals and plants (Table 14). 

Toxicity of this degradation product is therefore expected to be much less than that of the parent.

As a check of the predictive ability of ECOSAR for compounds related to clofentezine, 

ECOSAR was used to predict the aquatic toxicity of clofentezine itself, and these predictions 

were compared to the measured toxicity values. ECOSAR predictions of clofentezine were 

based on all uncharged compounds (neutral organics). All predicted acute and chronic toxicity 

thresholds were well above the solubility limit of clofentezine (34.2 μg/L). The predictions 
36

therefore agreed with the acute toxicity measurements for fish and aquatic invertebrates, and the 

measured toxicity for green algae, in predicting no observable toxicity at concentrations up to the 

solubility limit. ECOSAR failed to predict the chronic toxicity related to reproductive and 

developmental endpoints observed in freshwater and saltwater invertebrates. This is likely 

because related chemicals with this specific ovicide mode of action were not present in the set of 

chemicals used to develop ECOSAR.

Table 14. Predicted Toxicity of the Degradation Product 2-Chlorobenzonitrile to Aquatic 

Organisms Based on Quantitative –Structural Relationships.

Organism Duration Endpoint Predicted Toxicity (mg/L)

Neutral Organics

Acute Toxicity

Freshwater Fish 96-hr LC50 73.0

Saltwater Fish 96-hr LC50 100

Daphnid 48-hr LC50 42.3

Mysid 96-hr LC50 63.8

Green Algae 96 hr EC50 21.7

Chronic Toxicity

Freshwater Fish 30-days NOAEC 7.70

Saltwater Fish chronic NOAEC 11.8

Daphnid chronic NOAEC 5.05

Mysid chronic NOAEC 5.22

Green Algae chronic NOAEC 8.57

F. Ecosystems Potentially at Risk

Ecosystems potentially at risk from the use of clofentezine include the orchards, vineyards, 

nurseries, and tree farms to which it is directly applied, and nearby terrestrial and aquatic 

ecosystems. Ecological receptors are both terrestrial and aquatic nontarget organisms that 

inhabit or move through these ecosystems. Terrestrial ecosystems which may be at risk are those 

that may be exposed by direct application of the pesticide and those in adjacent areas which may 

be exposed from spray drift. Terrestrial animals and plants that live in or feed in exposed 

habitats may be at risk. Aquatic ecosystems that may be exposed include ponds, streams, 

wetlands, and other water bodies receiving runoff and/or spray drift from applications to 

agricultural sites. As clofentezine is used in coastal locations, aquatic ecosystems potentially at 

risk include salt marshes and estuaries. Aquatic organisms potentially at risk include fish, 

aquatic invertebrates, and plants living in the water column and sediment.

G. Assessment Endpoints

Assessment endpoints include reduced survival of individuals or reproduction within populations 

and/or adverse effects to communities. Organisms potentially exposed include terrestrial and 

aquatic plants and animals. Potential effects are determined through testing of surrogate 

representatives within those taxonomic groups, or from other related taxonomic groups. 

Assessment endpoints and toxicity data used to evaluate the assessment endpoints are identified 

in Table 15.
37

Table 15. Summary of Assessment Endpoints and Measures of Effects for Screening Level Risk 

Assessment of Clofentezine

Assessment Endpoint Measurement Endpoint

1. Survival, reproduction, and growth of birds (Birds also 

serve as surrogates for reptiles and terrestrial phase 

amphibians in that birds are generally more sensitive than 

species from these other taxonomic groups.)

•Acute oral LD50 values, subacute 5-d dietary LC50 values 

•Avian reproduction study NOAEC 

2. Survival, reproduction, and growth of mammals •Acute oral mammalian LD50 values 

•Mammal 2-generation reproduction study NOAEC or NOAEL 

3. Survival and reproduction of freshwater fish and 

invertebrates (Fish also serve as surrogates for aquatic 

phase amphibians because fish are generally more sensitive 

than amphibians)

•Freshwater fish 96-h LC50 and early life-stage NOAEC 

•Freshwater invertebrate 48-h EC50 and life cycle NOAEC 

4. Survival and reproduction of estuarine/marine fish and 

invertebrates

•Estuarine/marine fish 96-h LC50 and early life-stage NOAEC*

•Estuarine/marine invertebrate 96-h LC50 (clofentezine) and life 

cycle NOAEC*

*Currently, no acute or reproduction study using clofentezine has 

been submitted. Without these data, freshwater data could be used 

as surrogate for these tests. 

5. Perpetuation of non-target terrestrial plants (crops and 

non-crop species)

•Monocot and dicot seedling emergence EC25 and NOAEC, or EC05

(clofentezine TEP) * 

•Monocot and dicot vegetative vigor EC25 and NOAEC, or EC05

(clofentezine TEP) *

* Currently, no terrestrial plant study using clofentezine TEP has 

been submitted. Without terrestrial plant data, assumptions of 

sensitivity would be made based on mode of action and other 

available information.

6. Survival of beneficial insect populations (Terrestrial 

invertebrates are represented by the honey bee)

•Honey bee acute contact LD50*

* Various effects levels on toxicity to eggs and larval stages from 

studies published in the open literature are also considered in 

characterizing risk to beneficial insects.

7. Maintenance and growth of aquatic plants from 

standing crop or biomass

•Aquatic plant growth and biomass 96-h EC50 *

•Aquatic plant growth and biomass 96-h NOAEC or EC05 *

*Currently, no aquatic plant study using clofentezine has been 

submitted. Without aquatic plant data, assumptions of sensitivity 

would be made based on mode of action and other available

information.

LD50 : Lethal dose to 50% of test population

LC50 : Lethal concentration to 50% of the test population

EC50 : median effect concentration is the concentration that results in a specific effect (e.g., immobility, emergence) to 50% of the exposed test 

population

EC05 and EC25 : the concentration that results in a specific effect to 5% and 25%, respectively, of the exposed test population.

NOAEC = No observed adverse effect concentration
38

III. Analysis Plan and Conceptual Model

A. Measures to Evaluate Risk Hypothesis

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

exposure modeling and resulting risk conclusions were made based on the maximum application 

rate, which is 0.26 lb a.i./A for all uses. As only one application may be made per season, no 

more than one ‘season’ of crop production in a year is expected, and clofentezine is not highly 

persistent in the environment, there is no need to model repeated application. Tier II aquatic 

estimated environmental concentrations (EEC) were generated with the USEPA Pesticide Root 

Zone Model (PRZM) and Exposure Analysis Modeling System (EXAMS) models using the 

EXPRESS shell, (http://www.epa.gov/ceampubl/swater/express). The model used to produce 

terrestrial EECs on food items is T-REX (version 1.5). The model used to derive EECs relevant 

to terrestrial and wetland plants is TerrPlant (ver. 1.2.2). These models are parameterized using 

relevant reviewed registrant-submitted environmental fate data. For more information on EPA 

models, http://www.epa.gov/pesticides/science/models_db.htm.

In the preliminary risk assessment, acute and chronic EECs are compared to acute and chronic 

toxicity endpoint to estimate risk to nontarget animals and plants, and to determine if the risk 

exceed the EPA’s levels of concern. Toxicity levels are based on the most sensitive toxicity 

endpoints from surrogate test species. Acute endpoints are based on mortality, and chronic 

endpoints are based on adverse effects on growth, reproduction, or survival. Measures of effect 

are obtained from a suite of studies conducted with a limited number of surrogate species. 

B. Conceptual Model

Spraying of agricultural and ornamental plants will release clofentezine into the terrestrial 

environment. Most of the clofentezine spray will settle on plants and soil at the target site, while 

some will drift off site and contaminate nearby terrestrial and aquatic habitats. That which 

settles on the target site may remain on treated plants, percolate into the soil, or runoff with 

surface water. Terrestrial animals will be exposed when they feed on contaminated food on 

treated sites and on sites contaminated by spray drift. Spray drift, surface runoff, and movement 

of soil particles with sorbed residues will cause in contamination of aquatic habitats, exposing 

aquatic animals and plants. Little of the applied residues are likely to volatilize, and thus longrange atmospheric transport is unlikely. In soil, water, and sediment, hydrolysis and photolysis 

of the parent clofentezine will form 2-chlorobenzoic acid (2-chlorobenzylidine) hydrazide and/or 

2-chlorobenzonitrile, thereby exposing terrestrial and aquatic organisms to these degradation

products.

Clofentezine is not expected to bioaccumulate in fish in appreciable amounts. A 

bioconcentration study with the bluegill sunfish measured a low whole-body BCF of 230x and 

depuration is virtually complete after 3 days (MRID 405522-01). Furthermore, the log Kow of 

clofentezine is only moderate (3.1), and the compound degrades rapidly in the environment 

through photolysis and hydrolysis (half-lives less than 7 days). Therefore, exposure of 

clofentezine to piscivorous wildlife through consumption of fish is expected to be a very minor 

route of exposure and will not be investigated in this risk assessment.
39

EPA’s Screening Imbibition Program (SIP) was used to conduct a screen-level assessment for 

risk to terrestrial wildlife from drinking of water contaminated with clofentezine. This screening 

tool determines preliminary risk quotients (RQs) for birds and mammals assuming they are 

drinking from a water source in which the clofentezine concentration was equal to the solubility 

limit. This program found that acute and chronic RQs from this route of exposure will be no 

more than 0.001, indicating that drinking water is not s significant route of exposure for 

terrestrial wildlife. This finding was expected based on the low solubility of clofentezine (34.2

μg/L). Therefore, drinking water was not included as a route of exposure in the conceptual 

model for clofentezine.

EPA’s Screening Tool for Inhalation Risk (STIR, version 1.0) was used to screen for the 

potential of risk to birds and mammals from inhalation of clofentezine from foliar application. 

STIR calculates risk based on a theoretical upper bound estimate of inhalation exposure based on 

the maximum application rate, vapor pressure, and molecular weight. Based on the results of the 

STIR model, inhalation is not a significant route of exposure for terrestrial wildlife. This finding 

was expected based on the low vapor pressure of clofentezine (9.75 x 10-10 mmHg). Therefore,

inhalation was not included as a route of exposure in the conceptual model for clofentezine.

C. Risk Hypothesis

The Agency will employ the following risk hypothesis when assessing ecological risks of the use 

of clofentezine:

Clofentezine, when used in accordance with current labels, may result in contamination 

of ecosystems and adverse effects upon the survival, growth, and reproduction of nontarget terrestrial and aquatic organisms, including organisms that are federally-listed as 

threatened and endangered species.

D. Conceptual Diagram

The potential exposure pathways and effects of clofentezine are depicted for aquatic 

environments in Figure 3 and for terrestrial environments in Figure 4.
40

Figure 3. Conceptual model depicting stressors, exposure pathways, and potential effects to 

aquatic animals and plants from the use of clofentezine. 
41

Figure 4. Conceptual model depicting stressors, exposure pathways, and potential effects to 

terrestrial animals and plants from the use of clofentezine. 

IV. Exposure Analysis

A. Use Characterization

Registered uses of clofentezine are described in detailed in section I.C of this document. 

Clofentezine is used for mite control in orchards of various non-citrus tree crops fruit trees 

(including apples, apricots, cherries, nectarines, peaches, pears, and persimmons), nut trees 

(almonds and walnuts), and grapes. Clofentezine is also used on Christmas tree farms. All of 

these outdoor uses are evaluated in this ecological risk assessment. Indoor use of clofentezine on 

ornamental plants in greenhouses is not expected to release significant contaminants into the 

environment and is therefore not considered in this assessment. Information on the usage of 

clofentezine in the United States is provided in Appendix A.
42

B. Aquatic Fate and Exposure Characterization

1. Fate Characterization

Abiotic hydrolysis and direct photolysis in water (clear shallow water) and microbial-mediated 

degradation are major routes of transformation for clofentezine in the environment. Abiotic 

hydrolysis is pH and temperature dependent. At 25°C, the hydrolytic half-lives of clofentezine 

are 10.4 days (pH 5), 1.4 days (pH 7) and 0.18 days (pH 9). The direct photolysis half-life is 8.8

days. Although clofentezine under laboratory conditions appears to be more persistent in aerobic 

soil (t1/2 = 4 weeks in clay, 6 weeks in loamy sand and 8 weeks in clay loam), abiotic hydrolysis 

and/or direct photolysis are likely to control the degradation of clofentezine in the environment. 

However, extensive mineralization (i.e., CO2 formation, up to 56% in aerobic soil after one year) 

was found in the aerobic soil metabolism studies. Thus, mineralization can also be included as a 

route of transformation in the environment. The proportion of radioactivity becoming 

irreversibly bound to soil increases with time to between approximately 30% and 50% of applied 

radioactivity depending on soil type. Levels of 'bound' radioactivity further increase after 

establishment of anaerobic conditions.

The USEPA EPI (Estimation Programs Interface) Suite program was used to estimate the Koc

for clofentezine and its potential mobility in soils. Based on the predicted value of 516.1 L/kg, 

clofentezine is not expected to be very mobile in the environment. The low aqueous solubility of 

clofentezine (34.2 μg/L) also limits its transport in ground and surface water. Clofentezine has 

low potential to volatilize from soil or water.

Whole system aerobic and anaerobic aquatic half-lives were calculated for water/sediment 

samples collected from two rivers in the United Kingdom. Whole-system half-life values are 

23.0 and 28.9 days for the Taunton River system and Weweantic River system, respectively. 

PMRA-calculated, whole-system half-life values are 44.9 and 33.2 days for the Taunton River 

system and Weweantic River system, respectively. 

2. Model Input Parameters

The physical/chemical and environmental fate properties for clofentezine used as the input 

parameters in modeling to estimate potential aquatic environmental concentrations are 

summarized in Table 16, which also take into account the required 100-foot buffers, as stated on 

product labels.

Table 16. Input Parameters Used in PRZM/EXAMS Modeling to Estimate Aquatic 

Concentrations of Clofentezine

Input Parameter (Symbol; Unit) Value for Clofentezine

Molecular Weight 303.15

Vapor Pressure (torr) 9.75 x 10-10, mm Hg

1.31 x 10-7 , Pa
43

Henry’s constant (25 oC) 1.14 x 10-8 atm-m3

mole-1

Solubility in Water (mg/L at 25 oC) 0.0342

Hydrolysis Half-life (t1/2 at pH 7) 1.4 days

Aquatic Photolysis Half-life (days; t1/2 at pH 7) 8.8 days

Aerobic Soil Metabolism [upper 90th percentile confidence 

bound on the mean half-life value (t1/2; 28, 42 and 56 days)] 57.2 days

Aerobic Aquatic Metabolism Half-life (t1/2; days) [Entire 

water/sediment system; upper 90th percentile confidence bound 

on the mean half-life value (t1/2; 28.9, 23.0,18.2,18.9)] 

25.8 days

Anaerobic Aquatic Metabolism Half-life (t1/2; days) [Entire 

water/sediment system; upper 90th percentile confidence bound 

on the mean half-life value (t1/2; 44.9 and 33.2)]

57.1 days

Average Organic Carbon-Water Partitioning Coefficient (Koc;

mL/g) (EPI Suite Program Version 4.10)

516.1

PRZM Scenarios and Application Dates

North Carolina Apple: Oct 11

New York Grape: Oct 1

Calif. Almond: Sept 30

Oregon Christmas Trees: Dec 17

Spray Drift Fraction (100 foot buffer) (From GENEEC2) 7.37

3. Estimated Environmental Concentrations

Potential aquatic exposures were estimated using the Tier II models Pesticide Root Zone Model 

(PRZM v3.12.2, May 12, 2005) and Exposure Analysis Modeling System (EXAMS v2.98.04.06, 

April 25, 2005) coupled with the input shell pe5.pl (Nov. 16, 2006). PRZM simulates fate and 

transport of pesticides on the agricultural field and EXAMS simulates the fate and resulting daily 

concentrations of pesticides that reach an adjacent water body through runoff, erosion, and spray 

drift. Simulations are based on crop-specific scenarios developed to represent environmental 

conditions at sites at high runoff-vulnerability for pesticide transport to surface waters from a 

particular crop. Exposure is estimated using a standard pond scenario based on a10-ha field 

bordering a 1-ha water body, 2-m deep (20,000 m3

) with no outlet. Using appropriate scenarios

linked with local meteorological data, the model is run for 30 years with the reported EECs 

representing the values that are expected once every ten years, based on the thirty years of daily 

values generated during the simulation. Additional information about model assumptions and 

uncertainties, input guidance, and scenario metadata are available at the EPA’s water modeling 

website, http://www.epa.gov/oppefed1/models/water/.

 

Tier II aquatic EECs for registered outdoor uses on crops are listed in Table 17. The use rate and 

application method is similar for all uses, but different scenarios were used for fruit trees, grapes, 

nut trees, and Christmas trees to best represent these use sites. The complete output from the 

PRZM/EXAMS runs conducted is provided in Appendix C. 

Table 17. Tier II Surface Water Estimated Environmental Concentrations (EECs) for Registered 

Uses of Clofentezine 
44

Crop/Use Site Model Scenario Peak

μg/L (ppb)

21-day μg/L 

(ppb)

60-day

μg/L (ppb)

Fruit Trees

(1 ground application @ 0.26 lb a.i./A)

North Carolina Apples

(NC1App-P) 3.34 0.406 0.145

Grapes

(1 ground application @ 0.26 lb a.i./A)

New York Grapes

(NY2Gra-P) 1.02 0.170 0.0742

Almonds and Walnuts 

(1 ground application @ 0.26 lb a.i./A)

California Walnuts

(CA1Wal-P) 0.454 0.0705 0.0265

Christmas Trees 

(1 ground application @ 0.26 lb a.i./A)

Oregon Christmas Trees

OR1Xma-P 0.964 0.123 0.0430

4. Monitoring Data

There were no reported detections of clofentezine residues in ground water at the time that the 

Pesticides in Ground Water Data Base was published, in 1992 (USEPA, 1992). This may be 

because very few ground-water samples have been analyzed for clofentezine residues in the 

United States and because it has limited usage areas and crops. Clofentezine were not included 

in the suite of analyses conducted in the USEPA's National Survey of Pesticides in Drinking 

Water Wells (USEPA, 1990). Clofentezine also was not included in the USGS NAQWA 

program. No surface water monitoring was located.

The California Department of Pesticide Regulation (CDPR) surface water database 

(http://www.cdpr.ca.gov/docs/emon/surfwtr/surfcont.htm), USGS NAWQA surface and ground 

water database (http://infotrek.er.usgs.gov/apex/f?p=136:1:0::NO:::), Pesticide Data Program 

(http://www.ams.usda.gov/AMSv1.0/ams.fetchTemplateData.do?template=TemplateG&navID=

&rightNav1=&topNav=&leftNav=ScienceandLaboratories&page=PDPDownloadData/Reports&

resultType=&acct=pestcddataprg), and the USGS/EPA Reservoir Data Program were evaluated 

for available monitoring data. No detects were seen for clofentezine in any of these databases; 

however, it is important to note that these sources did not appear to be looking for clofentezine in 

water bodies. As a result, no detects does not necessarily mean that clofentezine is not found in 

surface and ground water sources.

C. Terrestrial Exposure

Terrestrial exposure estimates for avian and mammalian risk assessments were derived using the 

T-REX model (version 1.5, 3/22/2012). All terrestrial EECs for clofentezine are based on a 

single foliar application at the maximum rate of 0.26 lb a.i./A. Input parameters used in this 

modeling are given in Table 18. The default value of 35 days was used as the foliar half-life 

because the distribution of chemical-specific half-lives for clofentezine is uncertain. As only one 

application was modeled, the peak EEC which are used to calculate acute and chronic risk 

quotients occurs immediately application. Therefore, the selection of the foliar half-life has no 

effect on the calculated terrestrial EECs or RQs. Because clofentezine degrades fairly rapidly 

through photolysis, and the foliar half-life may be considerably less than the default value of 35 
45

days, the persistence of foliar residues may be less than predicted by the T-REX model. 

Implications of this potentially more rapid dissipation from terrestrial food will be explored in 

the Risk Description and Characterization section (Section VI).

Table 18. Input Parameters for T-REX Modeling for All Uses of Clofentezine

Input Parameters Value Source

Single Application Rate

(lb a.i./A) All Uses: 0.26 EPA Reg. No.

Foliar Half-life 35 days Default value1

Number of Applications 

(Interval between 

Applications, days)

All Uses: 1 EPA Reg. No. 66222-47, 66222-

53, 66222-65

Avian Oral LD50 7500 mg/kg-bw (bobwhite) MRID 00105913

Avian Dietary LC50 19,900 mg/kg-bw (bobwhite) MRID 00159117

Avian NOAEC 30 mg/kg-diet (bobwhite) MRID 42776101

Mammal LD50 3200 mg/kg-bw (rat) MRID 00159071

Mammal NOAEC 50 mg/kg-diet (rat) MRID 44399146 1 The foliar half-life did not influence the prediction of the terrestrial EECs for clofentezine because only one 

application of clofentezine is allowed per season, and thus the peak concentration occurs immediately after this 

single application before any dissipation occurs.

Terrestrial EECs for dietary-based calculations are given in Table 19, and terrestrial EECs for 

dose-based calculations are given in Table 20. Complete output from the T-Rex Model is 

provided in Appendix D.

Table 19. Dietary-Based Clofentezine EEC Values 

Dietary Item Dietary-Based EEC (mg/kg)

Short Grass 62.40

Tall Grass 28.60

Broadleaf Plants 35.10

Fruits, Pods, and Seeds 3.90

Arthropods 24.44
46

Table 20. Avian and Mammalian Dose-Based Clofentezine Upper Bound EEC Values

Application Rate 

(crop)

Size Class 

(g)

Avian Dose-Based EECs (mg/kg-bw)

Dietary Item

Short Grass Tall Grass Broadleaf 

Plants

Fruits & 

Pods Arthropods Seeds

Avian

One application @ 

0.26 lb a.i./A (all 

uses)

20 71.07 32.57 39.98 4.44 27.83 0.99

100 40.53 18.57 22.80 2.53 15.87 0.56

1000 18.14 8.32 10.21 1.13 7.11 0.25

Mammalian

One application @ 

0.26 lb a.i./A (all 

uses)

15 59.46 27.27 33.47 3.72 23.30 0.83

35 41.12 18.85 23.13 2.57 16.10 0.57

1000 9.53 4.37 5.36 0.60 3.73 0.13

V. Risk Estimates for Non-Target Organisms

A. Aquatic Organisms

1. Aquatic Animals

Table 21 provides RQs for risk to fish from acute and chronic exposures associated with uses of 

clofentezine. Because of the very low solubility of clofentezine, all of the acute and chronic 

toxicity endpoints are nondefinitive, in that the tests were only able to show that the LC50 value 

is greater than the highest test concentration, or in the case of tests with the TEP, are greater than 

the solubility limit of clofentezine (34.2 μg/L). Because the toxicity values are expressed as 

“greater than” inequalities, the RQs calculated from them are expressed as “less than” 

inequalities, indicating the upper bound of the RQ. For fish, acute risk quotients were shown to 

be less than EPA’s LOC for risk to nonendangered species (0.5) and the LOC for potential 

adverse effects to endangered species (0.05) for all use sites except fruit trees. For use on fruit 

trees, the RQ for fish was only shown to be less than 0.10, and therefore was not demonstrated to 

be less than the LOC for endangered species. However, since no treatment-related mortality or 

adverse effects observed in the acute toxicity test with the TGAI at close to the solubility limit 

(MRID 40568201), or with the TEP at nominal concentrations exceeding the solubility limit 

(MRIDs 40912101 and 00159120), the EPA concludes that acute exposure from all uses of 

clofentezine, including on fruit trees, will not result in adverse effects to listed species of fish 

(see Section VI.A.1 for more discussion). For risk from chronic exposure, RQs for all use sites

were less than 1, and therefore the RQ did not exceed the LOC for chronic risk (1) for all uses.

For fish, toxicity testing with the rainbow trout found no mortality or adverse effects at exposure 

at or near the solubility limit (MRID 00159120). Therefore, the EPA concludes that clofentezine 

will not cause adverse acute effects at concentrations that would occur in natural waters. 

Therefore, a “no effect” conclusion is made for fish for all uses, including use on fruit trees.
47

Since acute and chronic toxicity tests with saltwater fish are not available, the conclusions for 

freshwater fish are assumed for saltwater fish as well, although these conclusions are uncertain. 

In summary, the EPA concludes that all registered uses of clofentezine pose minimal risk to 

freshwater and saltwater fish, and are not expected to harm threatened or endangered species of 

fish.

Table 21. Acute and Chronic Risk Quotients for Fish

Crop

(Application 

method)

Exposure 

Type Habitat Type Toxicity(μg a.i./L)

EEC

(μg a.i./L) RQ

Fruit Trees

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 3.34 <0.10

Saltwater N/A 3.34 N/A1

Chronic

Freshwater >34.2 0.145 <0.01

Saltwater N/A 0.145 N/A1

Grapes

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 1.02 <0.03

Saltwater N/A 1.02 N/A1

Chronic

Freshwater >34.2 0.0742 <0.01

Saltwater N/A 0.0742 N/A1

Almonds and 

Walnuts 

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 0.454 <0.01

Saltwater N/A 0.454 N/A1

Chronic

Freshwater >34.2 0.0265 <0.01

Saltwater N/A 0.0265 N/A1

Christmas Trees 

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 0.964 <0.03

Saltwater N/A 0.964 N/A1

Chronic

Freshwater >34.2 0.0430 <0.01

Saltwater N/A 0.0430 N/A1

1 No toxicity data are available for saltwater fish; however, based on the very low toxicity observed in freshwater 

fish, the RQ for saltwater fish is also expected to be well below 0.01. 

Table 22 provides RQs for risk to aquatic invertebrates from acute and chronic exposures 

associated with uses of clofentezine. Because of the very low solubility of clofentezine, all of 

the acute toxicity endpoints for aquatic invertebrates are nondefinitive. As for fish, the acute 

toxicity tests were only able to show that the EC50 value is greater than the highest test 

concentration or the solubility limit of clofentezine (34.2 μg/L). Because the toxicity values are 

expressed as “greater than” inequalities, the RQs calculated from them are again expressed as 

“less than” inequalities. Acute toxicity tests using the TGAI were supplemental and were 

conducted at levels less than the solubility limit. The acceptable acute toxicity test using the

formulated product (MRID 40568202) was therefore used for RQ calculations. Since the 

nominal test concentrations in this test were much greater than the solubility limit of 

clofentezine, the concentration of dissolved clofentezine is assumed to have been close to the 

solubility limit of 34.2 μg a.i./L. As for fish, acute risk quotients were found to be less than 

EPA’s LOC for risk to nonendangered species (0.5) and the LOC for potential adverse effects to 

endangered species (0.05) for all use sites except fruit trees. For use on fruit trees, the RQ was 

only shown to be less than 0.10 and therefore does not preclude possible adverse effects to 
48

endangered species. For risk from chronic exposure, RQs for all use sites were less than 1, and 

therefore the RQ did not exceed the LOC for chronic risk (1) for any use.

In the acceptable acute toxicity study with daphnid (MRID 40568202), no more than 3 out of 30 

(10%) of daphnids were immobilized at any test concentration, which equals the number that 

were immobilized in the negative control. At the highest test concentration (nominal 

concentration of 100 mg a.i./L), there were 2 daphnids immobilized, less than in the control. 

Because the number of immobilized daphnids in the treatments did not exceed the number in the 

control, they are assumed to be incidental and not treatment related. Other than immobilization, 

no sublethal effects were observed at any test concentration. Because exposure to daphnids at 

the solubility limit did not result in any significant adverse effects (i.e., effects greater than in the 

control), the EPA concludes that all uses of clofentezine, including use on fruit trees, will cause 

no acute toxic effects to threatened and endangered species of aquatic invertebrates.

Chronic studies with clofentezine found that it does negatively affect the reproduction of 

freshwater and saltwater invertebrates, but only at concentrations above the chronic EECs 

predicted for registered uses. Because the chronic NOAEC for both freshwater and saltwater 

crustaceans are greater than the chronic EECs, all of the chronic RQs are less than 1.0, and 

therefore does not exceed the EPA’s chronic LOC.

In summary, the EPA concludes that all registered uses of clofentezine pose minimal risk to 

freshwater and saltwater invertebrates, and are not expected to cause any adverse effects to 

threatened or endangered species of invertebrates.

Table 22. Acute and Chronic Risk Quotients for Aquatic Invertebrates

Crop

(Application 

method)

Exposure 

Type Habitat Type Toxicity(μg a.i./L)

EEC

(μg a.i./L) RQ

Fruit Trees

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 3.34 <0.10

Saltwater N/A 3.34 N/A1

Chronic

Freshwater 44 0.406 0.012

Saltwater 1.7 0.406 0.24

Grapes

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 1.02 <0.03

Saltwater N/A 1.02 N/A1

Chronic

Freshwater 44 0.170 <0.012

Saltwater 1.7 0.170 0.10

Almonds and 

Walnuts 

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 0.454 <0.01

Saltwater N/A 0.454 N/A1

Chronic

Freshwater 44 0.0705 <0.012

Saltwater 1.7 0.0705 0.04

Christmas Trees 

(1 ground 

application @ 

0.26 lb a.i./A)

Acute

Freshwater >34.2 0.964 <0.03

Saltwater N/A 0.964 N/A1

Chronic

Freshwater 44 0.123 <0.012

Saltwater 1.7 0.123 0.07
49

1 No toxicity data are available for saltwater invertebrates; however, based on the very low toxicity observed in 

freshwater invertebrate, the RQ for saltwater invertebrate is also expected to be well below 0.01.

2 The RQ is uncertain because it is based on the LOAEL rather than the NOAEL.

2. Aquatic Plants

An algal toxicity test with the TEP (MRID 47200501) found no observable adverse effects to 

green algae at nominal concentrations up to 100 mg product/L. The test concentrations of 

dissolved clofentezine in this study are unknown because the samples used for chemical analysis 

were not filtered before analysis. However, the dissolved concentrations in the test solutions are 

expected to be close to the solubility limit, and thus the study demonstrated that clofentezine 

does not adversely affect the growth of green algae up to the aqueous solubility limit of 34.2 μg 

a.i./L. Based on this, the RQs for both endangered and nonendangered species of nonvascular 

aquatic plants are well below the LOC of 1 for all uses of clofentezine (Table 23).

Lack of data on the toxicity of clofentezine to vascular aquatic plants prevents quantitative 

assessment of risk to vascular aquatic plants. Vascular plants would need to be over 9.7 times 

more sensitive than the tested nonvascular aquatic plant (green algae) for the RQ to exceed the 

LOC. Since clofentezine does not have a known mechanism of action that is relevant to toxicity 

to plants, exhibited low phytotoxicity in a study of terrestrial vascular plants, has no reported 

problems with plant safety, and is expected to occur in natural water at only very low 

concentrations, use of clofentezine is not expected to pose significant risk to vascular aquatic 

plants.

Table 23. Risk Quotients for Aquatic Plants

Crop

(Application method) Plant Type Toxicity(μg a.i./L)

EEC

(μg a.i./L)

RQ

NonEndangered Endangered

Fruit Trees

(1 ground application @ 

0.26 lb a.i./A)

Vascular N/A 3.34 N/A N/A

Non-vascular IC50: >34.2

NOAEC: >34.2 3.34 <0.10 <0.10

Grapes

(1 ground application @ 

0.26 lb a.i./A)

Vascular N/A 1.02 N/A N/A

Non-vascular IC50: >34.2

NOAEC: >34.2 1.02 <0.03 <0.03

Almonds and Walnuts 

(1 ground application @ 

0.26 lb a.i./A)

Vascular N/A 0.454 N/A N/A

Non-vascular IC50: >34.2

NOAEC: >34.2 0.454 <0.01 <0.01

Christmas Trees 

(1 ground application @ 

0.26 lb a.i./A)

Vascular N/A 0.964 N/A N/A

Non-vascular IC50: >34.2

NOAEC: >34.2 0.964 <0.03 <0.03
50

B. Terrestrial Organisms

1. Terrestrial Wildlife

Table 24 provides acute and chronic risk quotients (RQs) for birds based on dietary toxicity 

studies, and Table 25 provides additional acute RQs based on single-dose oral toxicity studies. 

Since all uses of clofentezine are restricted to one application with a maximum application rate 

of 0.26 lb a.i./A, the RQs presented in these tables are applicable for all registered outdoor uses 

of clofentezine (indoor greenhouse uses are not expected to pose risk to nontarget wildlife). As

birds are used as surrogate species for assessing risk to reptiles and terrestrial-phase amphibians, 

inferences based on these RQs are applied to those groups of organisms as well. The very low 

acute toxicity of clofentezine resulted in all of the acute RQs being very low. All acute RQs are 

well below EPA’s levels of concern (LOCs) for general risk to birds (0.5) and risk of adverse 

effects to threatened and endangered species of birds (0.1). Thus, EPA concludes that all of the 

registered uses of clofentezine pose minimal acute risk to birds, reptiles, and terrestrial-phase 

amphibians.

Toxicity data show that sublethal effects caused by chronic exposure to clofentezine occur at 

much lower exposure levels than those which may cause mortality. Thus, chronic RQs are 

higher than acute RQs, although they are somewhat limited by the relatively low maximum 

application rate and the restriction of use to one application per growing season. Dietary-based 

chronic RQs are based on the observation of reduced embryo viability in the bobwhite quail at 90 

mg ai/kg/diet, yielding a chronic NOAEL of 30 mg ai/kg-diet (MRID 42776101). Chronic RQs 

exceed the EPA’s level of concern for chronic effects to birds (1.0) for birds that feed on short 

grass and broadleaf plants (Table 24). This screening-level assessment indicates that all 

registered outdoor uses of clofentezine pose a chronic risk to birds, reptiles, and terrestrialphases of amphibians, including threatened and endangered species of birds, reptiles, and 

terrestrial-phases of amphibians.

Table 24. Acute and Chronic Dietary-Based RQs for Birds

Application Rate 

(crop) Exposure

Avian Dietary-Based RQs

Short Grass Tall Grass Broadleaf 

Plants

Fruits, 

Pods, & 

Seeds

Arthropods

One application @ 

0.26 lb a.i./A (all 

uses)

Acute <0.01 <0.01 <0.01 <0.01 <0.01

Chronic 2.08 0.95 1.17 0.13 0.81
51

Table 25. Acute Dose-Based RQs for Birds

Application Rate 

(crop)

Size Class 

(g)

Avian Dose-Based RQs

Short Grass Tall Grass Broadleaf 

Plants

Fruits & 

Pods Seeds Arthropods

One application @ 

0.26 lb a.i./A (all 

uses)

20 0.03 0.02 0.02 <0.01 <0.01 0.01

100 0.01 0.01 0.01 <0.01 <0.01 0.01

1000 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01

Table 26 provides acute and chronic risk quotients (RQs) for mammals based on dietary toxicity 

studies, and Table 27 provides additional acute RQs based on single-dose oral toxicity studies. 

The RQs presented in these tables are applicable for all registered outdoor uses of clofentezine. 

The very low acute toxicity of clofentezine resulted in all of the acute RQs being very low. All 

acute RQs are well below EPA’s levels of concern (LOCs) for risk to mammals (0.5) and risk of 

adverse effects to threatened and endangered species of mammals (0.1). Thus, EPA concludes 

that all of the registered uses of clofentezine pose minimal acute risk to mammals.

Chronic RQs are based a chronic NOAEL of 20 mg a.i./kg-BW day (MRID 00147844). Chronic 

dietary-based RQs for mammals do not exceed the EPA’s level of concern for chronic effects 

(1.0) for any dietary category (Table 26). Most of the chronic dose-based RQs also are below 

the chronic LOC for mammals, except for small to medium mammals that feed on short grass, 

for which the chronic RQs slightly exceed one (Table 27). The Agency therefore concludes that 

all registered outdoor uses of clofentezine potentially could pose a chronic risk to small 

herbivorous mammals, including threatened and endangered mammals, although this conclusion 

is uncertain. Uncertainties of the potential chronic risk to mammals are discussed in Section 

IV.B.

Table 26. Acute and Chronic Dietary-Based RQs for Mammals

Application Rate 

(crop) Exposure

Mammalian Dietary-Based RQs

Short Grass Tall Grass Broadleaf 

Plants

Fruits, 

Pods, & 

Seeds

Arthropods

One application @ 

0.26 lb a.i./A (all 

uses)

Acute <0.01 <0.01 <0.01 <0.01 <0.01

Chronic 0.16 0.07 0.09 0.01 0.06
52

Table 27. Acute and Chronic Dose-Based RQs for Mammals

Application Rate 

(crop)

Size Class 

(g)

Mammalian Dose-Based RQs

Short Grass Tall Grass Broadleaf 

Plants

Fruits & 

Pods Seeds Arthropods

Acute

One application @ 

0.26 lb a.i./A (all 

uses)

20 0.01 <0.01 <0.01 <0.01 <0.01 <0.01

100 0.01 <0.01 <0.01 <0.01 <0.01 <0.01

1000 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01

Chronic

One application @ 

0.26 lb a.i./A (all 

uses)

15 1.35 0.62 0.76 0.08 0.01 0.06

35 1.16 0.53 0.65 0.07 0.45 0.02

1000 0.62 0.28 0.35 0.04 0.24 0.01

2. Terrestrial Plants

In a vegetative vigor study, four dicotyledonous plants and two monocotyledonous plants were 

exposed to Apollo 50 SC (49.8% a.i.) at a rate of 0.26 lb a.i./A (MRID 47192103). This limit 

test measured inhibition of plant wet weight and phytotoxic effects. Compared to the control, the 

plants exposed to 0.26 lb a.i./A did not show any significant reduction in biomass, as measured 

by plant wet weight, and did not show any signs of phytotoxicity. The application rate used in 

this study was equal to the maximum application rate for all registered crops. The EEC for 

nontarget terrestrial plants living outside the treatment site would be less than this application 

rate. As the EEC has been demonstrated to be less than the IC25 and NOAEL, the RQs for both 

endangered terrestrial plants (EEC/NOAEL) and nonendangered terrestrial plants (EEC/IC25) 

would be less than 1.0. The risk to emerged nontarget plants, including endangered species, is

thus less than the EPA’s level of concern.

No data are available on the effects of clofentezine on the germination and emergence of 

nontarget plants. Therefore, risk from inhibition of the germination and emergence of seeds is 

not known. However, considering that the vegetative vigor test found that clofentezine does not 

have any phytotoxicity activity at the maximum use rate, and clofentezine is recommended for 

use on a wide variety of woody and herbaceous plants in greenhouse use without any reported 

phytotoxicity, the EPA assumes that use of clofentezine will not pose any risk significant risk to 

nontarget plants.

3. Bees and Other Nontarget Terrestrial Arthropods

Multiple lines of evidence indicate that use of clofentezine pose little risk to bees. An acute 

contact test with adult honey bees determined the LD50 to be >1500 mg a.i./L. Based on 

recommended dilution rates provided on the product labels, concentrations of clofentezine in 

tank mixtures would not be greater than approximately 600 mg a.i./L. The 48-hr mortality 

measured for bees exposed at a spray concentration of 1500 mg a.i./L was 3.3%, which was less 

than the mortality observed in the vehicle control. Thus this study indicates that direct 

application of clofentezine products to adult bees would cause little or no mortality. An acute 
53

oral toxicity honeybee study (MRID 00159121) found that the acute oral toxicity of clofentezine 

was >20 μg a.i./bee. While the EPA does not have a bee toxicity classification scheme for acute 

oral exposure, if the scheme for acute contact toxicity for adult honey bees were applied, 

clofentezine would be classified as practically nontoxic to bees. Yoshida and Fuchs (1989)

found that acute contact of larval honey bees (5th instar) caused elevated mortality with 

exposures of 50 μg a.i./bee or greater, and caused increased occurrence of abnormal 

development at concentrations of 25 μg a.i./bee and greater. The LOAEL of 25 μg a.i./bee was 

associated with abnormal development of 42.3% of the pupa. By assuming all of the abnormal 

pupa would die, this LOAEL may be used as a conservative estimate of the LD50 for exposed bee 

larvae. Again, if this conservative estimate of the LD50 for bee larvae were compared to the 

scheme based on the acute contact LD50 for adult honey bees, clofentezine would be classified as 

practically nontoxic to bees.

Yoshida and Fuchs (1989) derived an NOAEL for developmental toxicity resulting from topical 

exposure of clofentezine of 5 μg a.i./bee. By converting this NOAEL to a dose expressed as the 

amount per body weight, this NOAEL can be compared directly to the terrestrial EEC for 

arthropods to assess the potential for risk to bees. Assuming a honey bee weight of 0.128 g

(USEPA, 2012), the NOAEL is equivalent to a dose of 39 mg a.i./kg-bw. The maximum EEC 

for arthropods is 24.4 mg/kg (Table 19). Therefore, this evaluation indicates that topical 

exposure of clofentezine to the honey bee will be below levels that would cause toxic effects. 

This conclusion is uncertain, however, because the published study lacked replication, requiring 

effects levels to be estimated through visual inspection, and did not evaluate growth 

measurements such as size or weight.

In a pollen feeding study (Yoshida and Fuchs, 1989), instances of abnormal development were

observed when bee larvae were fed pollen with a clofentezine concentration of 1000 mg a.i./kgpollen, but no instance of abnormal development was observed with exposure concentrations of 

100 mg a.i./kg-pollen or less. The same study found that the percentage of L1 and L2 larvae that 

sealed their cells appeared to decrease with clofentezine concentrations in pollen of 10 mg a.i./kg 

and greater. Compared to the control, the percentage of sealed cells decreased 6.9% and 9.1% 

when exposed to 10 and 100 mg a.i./kg. No decrease in sealed cells was evident in larvae 

exposed at the L3 through L5 stages with exposure concentrations up to 1000 mg a.i./kg. This is 

consistent with the known mode of action of clofentezine to mites, the target arthropods, which 

is toxicity to eggs and early developmental stages. Unfortunately this study was conducted 

without replication, and thus the statistical significance of observed trends could not be 

determined.

To characterize potential risk to the honey bee, EFED compared the effect concentrations 

observed in the pollen feeding study of Yoshida and Fuchs (1989) with terrestrial EECs for 

plants treated directly with the maximum application rate (Table 19). The terrestrial EECs for 

plants range from 3.9 mg/kg (for fruits and pods) to 62.4 mg/kg (for short grass). Thus, plant 

EECs are below the NOAEL for observed abnormal development of bee larvae (100 mg/kg), but 

were within the range in which a small percentage of observed adverse effects in bee larvae 

(<10% decrease of sealed cells). This suggests that if honey bees were to forage the flowers of 

plants directly treated with clofentezine soon after application, and bring contaminated pollen 

back to the hive for feeding to larval bees, there is potential for risk to bees of the earliest 
54

development stages. While not evaluated in this study, exposure in the hive could possibly also 

cause toxicity to the eggs of bees, as was observed in a study with the ladybird beetle (Olszak 

1999). However, as clofentezine may be applied only once per growing season, and residues on 

foliage are not expected to be highly persistent (estimated half-life is 15.7 days), the overall 

effect on reproduction of the hive is expected to be minor and transient.

Being an acaricide, some toxicity to nontarget arthropods is expected. Studies with beneficial 

insects have found clofentezine to have very little toxicity to adult insects at environmentally 

relevant concentrations. Studies indicating that clofentezine is practically nontoxic to adult bees 

have already been discussed (see above). A nonguideline study submitted by the registrant 

(MRID 47192122) found no adverse effects to a ladybird beetle (Coccinella septempunctata) 

when they were exposed to clofentezine spray at application rates of 0.089 and 0.18 lb a.i./A. 

Samsoe-Peterson (1993) observed no mortality in adult rove beetles (Aleochara bilineata) when 

sprayed with a solution of clofentezine at a concentration and spray rate equivalent to the 

maximum application rate. However, studies have found that environmentally-relevant 

exposures to clofentezine can cause adverse effects on survival and development of the early 

life-stages of insects, including honey bees (Yoshida and Fuchs, 1989), coccinellid beetles 

(Olszak, 1999), and rove beetles (Samsoe-Peterson, 1993). Because of this, these data indicate

that use of clofentezine may pose a risk to non listed and threatened and endangered arthropods 

that forage in treated orchards and tree farms. Overall, though, the toxicity and risk of 

clofentezine to nontarget arthropods appear to be less than that of most insecticides (SamsoePeterson, 1993; Olszak, 1999). 

In conclusion, toxicity data on the effects of clofentezine to adult and immature bees do not 

warrant placement of any label statement to clofentezine products for the protection of bees. Use 

of clofentezine is not expected to harm adult nontarget arthropods which may be exposed in 

treated sites during or after application. However, there is a potential for risk to nontarget 

arthropods from potential reproduction impairment and toxicity to early life-stages. Direct 

adverse effects to threatened and endangered arthropods are therefore possible.

VI. Risk Description and Characterization

The results of this screening-level risk assessment indicate that the foliar uses of clofentezine 

have the potential for direct adverse effects to listed or non-listed birds (and, thus, reptiles and 

terrestrial-phase amphibians), mammals, and terrestrial arthropods. Therefore, the risk 

hypothesis from the Problem Formulation is supported based on expected direct effects to these 

species. Because direct adverse effects to these taxa considered in this assessment are expected, 

indirect effects to listed species are also expected through potential alterations to food source. 

A. Risk to Aquatic Organisms

1. Aquatic Animals
55

Aquatic exposure to clofentezine is limited by several factors: the relatively low application rate, 

the low mobility in water, the low solubility in water, and the relatively rapid degradation of the 

parent by hydrolysis and photolysis. Clofentezine has also been found to not be toxic to fish and 

aquatic invertebrates at concentrations up to the solubility limit. This was sufficient to show that 

the acute RQ was less than the endangered species LOC of 0.05 for all uses except the use on 

fruit trees, for which the acute RQ was only shown to be less than 0.10. Aquatic TGAI toxicity 

tests with fish and daphnids were conducted up to concentrations near saturation of clofentezine. 

In the TEP studies, reliable measurements of dissolved active ingredient in the test solutions are 

not available, but since nominal test concentrations made with the suspended concentrate product 

far exceeded the solubility limit of clofentezine, the dissolved concentration of clofentezine in 

these test solutions are also assumed to have been close to the solubility limit. Both the TGAI 

and TEP studies found clofentezine caused no significant mortality (i.e., not greater than in the 

control). Additionally, no sublethal effects were observed for either fish or daphnids at the 

highest test concentration. Therefore, despite failing to show that the RQ for use on fruit trees is

less than the LOC of 0.05 (i.e., failing to demonstrate a 20x margin between the acute EEC and 

acute toxicity level), EPA believes that the lack of observed adverse effects at the solubility limit 

of clofentezine is enough evidence to conclude that all uses of clofentezine will not result in any 

adverse effects to fish or aquatic invertebrates, including endangered species. For chronic risk, 

all fish and aquatic invertebrate RQs were less than 1 for all uses, indicating chronic risk does 

not exceed the EPA’s level of concern. 

Clofentezine is applied as products formulated as suspension concentrates. Suspension 

concentrates are composed of small colloidal particles which remain suspended in the 

formulation and tank mixture when applied. When applied to plants, the solid particles are 

expected to move little from the use site, with primarily the residues that dissolve in water being 

transported to natural waters. However, spray drift may deposit onto bodies of water, thereby 

transporting the entire formulated product, including the colloidal solid particles as well as the 

dissolved component of clofentezine. To evaluate the potential for risk from this route of 

exposure, the AgDRIFT model (v. 2.01) was used to estimate maximum initial water 

concentrations in a body of water receiving spray drift deposition. Since a 100-ft buffer zone is 

required between application areas and natural water, the water body was assumed to be a 100 ft 

from the edge of the application area. To be conservative, fine to very fine spray droplets were 

assumed, and a small water body was assumed with a width of 10 ft and a water depth of 0.5 ft. 

The water concentrations estimated by this model were then compared to the toxicity endpoints 

obtained from the aquatic toxicity tests with the TEP.

Using the maximum product application rate of 8 oz/A (0.5 lb a.i./A), AgDRIFT predicts an 

initial water concentration of 8.70 μg product/L if the application was made with a ground boom, 

or 0.218 μg product/L if it is done an air blast application is made. TEP testing with Apollo 50 

SC found that product concentrations up to 24 mg/L did not cause mortality to fish (MRID 

40912101), and product concentrations up to 100 mg/L did not cause immobility in daphnids 

above the level observed in the control (MRID 40568202). These test concentrations are over 3 

orders of magnitude greater than the predicted initial product concentrations in the water body 

receiving spray drift. Therefore, spray drift of the product clearly will not yield water 

concentrations that would approach toxic levels, and thus would not result in any adverse acute 

effects to fish or aquatic invertebrates.
56

Chronic tests with a formulated product of clofentezine found toxic effects to the reproduction of 

aquatic organisms, but only at concentrations above those predicted to occur from registered uses

of clofentezine. A fish early life stage study with Apollo 50 SC did not find observable sublethal 

effects at a concentration of 979 μg/L, which is much higher than the predicted chronic EECs. 

All chronic RQs for fish were less than 0.01. Clofentezine showed greater toxicity to aquatic 

invertebrates in life-cycle studies. The most sensitive endpoint in these studies was fecundity 

(the number offspring produced per female). Reproductive effects were observed at 

concentrations as low as 44 μg/L in the waterflea (a saltwater crustacean) and as low as 3.6 μg/L 

in the mysid (a saltwater crustacean). 

The mode of action of clofentezine to the target species, mites, is toxicity to eggs and early life 

stages. It thus appears that clofentezine may exhibit the same mode of action in aquatic 

arthropods as well. However, a Daphnia magna reproductive toxicity study of Barber and 

Barrett (1983) suggests an alternative explanation of chronic toxicity to aquatic invertebrates. 

This study measured the reproductive response of Daphnia magna when exposed to three 

concentrations of Apollo 50 SC (50% clofentezine) and three concentrations of inert polyvinyl 

toluene (PVT) latex beads. Apollo 50 SC is a suspension concentrate formulation, meaning that 

it consists of small particles of solid clofentezine that remain suspended in the product and 

applied tank mixture. The test concentrations of latex beads had equivalent particle 

concentrations as did the Apollo 50 SC. The result of the study showed reproduction 

performance was significantly reduced when exposed to both the Apollo 50 SC and the PVT 

bead treatments. The percent reduction in number of offspring produced per female was similar,

regardless if the test was conducted with the clofentezine product or with the latex beads. The 

study authors thus concluded that the effect of Apollo 50 SC was not due to any intrinsic toxicity 

of the formulation, but rather a consequence of its particular concentration. They suggest that 

the ingestion of both the clofentezine particles and the latex beads by the waterflea while filter 

feeding reduced the organism’s feeding efficiency, which resulted in the organisms having 

reduced reproductive output. 

Regardless of the cause of the chronic toxicity, the lowest NOAEC obtained in the aquatic 

reproductive test (1.7 μg a.i./L for the mysid) was higher than the highest chronic EEC for 

aquatic invertebrates (0.49 μg a.i./L for use on fruit trees). The highest chronic RQ was 

therefore less than the EPA’s chronic LOC (1).

Some uncertainty exists for chronic risk to freshwater invertebrates because one study with the 

waterflea (Daphnia magna) failed to identify an NOAEC, finding significant reduction in 

fecundity at the lowest test concentration of 44 μg a.i./L (MRID 47192117). This test level is 

approximately 100 times greater than the maximum chronic EEC (0.49 μg a.i./L). The percent 

reduction in number of offsprings per female observed at 44 μg a.i./L was relatively small, 

8.25%, and thus, even less reduction on offspring production is expected at the maximum 

chronic EEC (0.49 μg a.i./L). Furthermore, two other chronic studies with Daphnia magna

which did obtain NOAECs found no significant chronic effects at test concentrations well above 

the chronic EEC. A study submitted by the registrant (MRID 42523901) obtained an NOAEC of 

26.2 μg a.i./L, and a published literature study Barber and Barrett (1993) obtained an NOAEC of 

60 μg a.i./L. These NOAECs are near to or above the solubility limit of clofentezine and well 
57

above even the highest predicted peak EEC (4.34 μg a.i./L). Finally, the comparison of results of 

MRID 47192117 with the mysid life-cycle study (MRID 48342701) indicates that the mysid is 

the more sensitive species of the two. While a test concentration of 44 μg a.i./L resulted in only 

an 8.25% reduction in fecundity in the waterflea study, a lower test concentration of 29 μg a.i./L 

resulted in a 23.7 % reduction in fecundity in the mysid study. Since a lower concentration 

resulted in greater impairment of reproduction, the mysid appears to be more sensitive than the 

waterflea. Thus, the risk conclusions of low chronic risk based on the mysid study should be 

protective freshwater invertebrates as well. 

In conclusion, the lack of a fully acceptable study with a freshwater invertebrate and the 

nondefinitive results obtained in two of the supplemental studies increases uncertainty in the risk 

assessment for freshwater invertebrates, the weight of the evidence indicate that chronic 

exposure levels will likely remain below levels that could otherwise pose chronic effects such as 

reproduction impairment. 

2. Aquatic Plants

Risk of clofentezine to aquatic plant is uncertain because toxicity data are available for only one 

species, green algae. An algal toxicity test with the TEP (MRID 47200501) found no observable 

adverse effects to green algae at nominal concentrations up to 100 mg product/L. This 

concentration is far greater than would be expected to occur in natural water from deposition of 

spray drift. Thus, contamination from spray drift of the formulated product would not pose a 

significant risk to green algae. While this study failed to measure the concentrations of dissolved 

test material (since the samples were not filtered prior to analysis), the amount of suspended 

clofentezine added to the test solutions far exceeded the solubility of clofentezine, and thus the 

concentration of clofentezine in the test solutions would likely be close to the solubility limit. 

Thus, the study demonstrated that clofentezine does not adversely affect the growth of green 

algae up to the aqueous solubility limit of 34.2 μg a.i./L. The highest predicted peak EEC was 

3.34 μg a.i./L for fruit trees. Thus, there is at least a 10-fold margin of safety between the 

expected peak exposure levels and the threshold of toxic effects for green algae. As clofentezine 

is applied only once per year and residues in water degrade fairly rapidly by hydrolysis, water 

concentrations are expected to decline fairly rapidly from the peak, creating an even greater 

margin of safety. While some uncertainty exists in the risk assessment because of the lack of 

testing of species other types of green algae and diatoms, the EPA believes that the available 

information is sufficient to conclude that use of clofentezine will not cause significant adverse 

effects to nonvascular aquatic plants.

Lack of data on the toxicity of clofentezine to vascular aquatic plants, and classes of nonvascular 

aquatic plants other than green algae, prevents quantitative assessment of risk to vascular aquatic 

plants. However, since clofentezine does not have a known mechanism of action that is relevant 

to toxicity to plants, exhibited low phytotoxicity in a study of terrestrial vascular plants, has no 

reported incidents or issues concerning plant safety, there is no reason to suspect that 

clofentezine would be toxic to these other classes of aquatic plants. Considering the low 

solubility of clofentezine, and the low predicted concentrations in natural waters, registered uses

of clofentezine is not expected to pose significant risk to any aquatic plants, and will not likely 

harm threatened or endangered species of aquatic plants.
58

B. Risk to Terrestrial Organisms

1. Nontarget Terrestrial Vertebrates

Acute toxicity studies with both birds and mammals indicate that clofentezine has low toxicity to 

terrestrial vertebrates. In addition, the relatively low use rate of clofentezine (0.26 lb a.i./A) 

limits exposure to terrestrial animals. These two factors combine to create very low acute RQs 

for terrestrial vertebrates, with RQ values below 0.01 for all uses. Additionally, no incidents 

have been reported that attribute wildlife mortality to exposure to clofentezine.

However, chronic exposure to clofentezine is more toxic to terrestrial vertebrates. For birds, 

adverse effects on reproduction were observed at dietary concentrations as low as 90 mg ai/kgdiet, with a NOAEL established at 30 mg ai/L. Maximum EECs of clofentezine on foliage (short 

grass and broadleaf plants), assuming exposure immediately after application, are predicted to 

exceed the chronic NOAEC, making the RQs greater than the chronic LOC of 1. Clofentezine 

appears to have somewhat less chronic toxicity to mammals. For mammals, dietary-based 

chronic RQs do not exceed the chronic LOC for mammals of any dietary class. When calculated 

based on the expected daily dose of active ingredient per unit body weight, however, chronic 

RQs for mammals slightly exceeded 1 for mammals of small (15 g) and moderate (35) weight 

classes that feed on short grass. Together these results indicate potential chronic risk to birds, and 

potential but uncertain chronic risk to some small mammals.

While the screening-level risk assessment indicates potential chronic risk to terrestrial 

vertebrates, several factors would limit the extent of this risk. First, the terrestrial maximum 

EECs fall close to the threshold for concluding potential chronic risk. While a few EECs exceed 

the NOAEC, none of the EECs exceed the LOAEC. Maximum dietary-based EECs that do 

exceed the NOAEC do so by no more than about a factor of 2. Second, clofentezine is not very 

persistent in the terrestrial environment. The photolysis half-life is less than 7 days, and thus 

residues on foliage and fruit exposed to the sun are expected to dissipate fairly quickly. This 

would mean that the length of exposure to chronically toxic residues through consumption of 

contaminated plants would be fairly short. Finally, only one application of clofentezine is 

permitted per growing season. This limit reduces the amount and duration of exposure, 

compared to pesticides with multiple applications.

In the screening-level risk assessment, RQs are calculated based on the peak EEC (i.e., those 

immediately after application before any degradation takes place. This would represent the 

exposure of an animal feeding in a treated orchard immediately after treatment. The persistence 

of the residues on the food items being consumed would influence the risk of reproductive and 

developmental effects occurring in that animal. If the residues quickly drop below potentially 

toxic levels, then the exposure to the animal in the field would not necessarily result in the same 

reproductive or developmental impairment that was observed in chronic laboratory studies, 

where the animal is exposed to a set dietary concentration for a long duration, such as 21 weeks 

in the avian reproduction study. While it is possible that the shorter-term exposure would 

produce the same reproductive effects as the long-term exposure, this is less certain than for a 

more persistent chemical, for which the duration of exposure in the wild would more closely 

match the duration of exposure in the avian reproduction tests.
59

To evaluate the duration that residues on wildlife food items would remain above potentially 

toxic levels, a half-life for residue decline on those items must be estimated. The dietary-based 

risk assessment indicates that birds feeding on plant foliage (short grass or broadleaf plants) may 

be at risk. Unfortunately data were not available to measure a half-life for foliar residues. 

Instead, we used a study which measured the decline of residues on grapes after treatment with 

clofentezine (MRID 45080701). A review of this study by the Health Effects Division found it 

to be scientifically acceptable. While the absolute concentration of residues on grapes may be 

quite different than on leaves, the decline of residues is expected to be similar. Thus the half-life

of residues in this study is expected to be a reasonable estimate of the foliar half-life.

Table 28 gives residue concentrations measured on grapes between 0 and 21 days after a single 

application of Apollo at the application rate of 4.0 oz product/A (0.125 lb a.i./A). From these 

values, a first-order decline rate (k) was estimated to be 0.0441, and the half-life (T1/2) was 

estimated to be 15.7 days. This indicates that clofentezine residues are moderately persistent on 

foliage. Assuming the same rate of decline for residues on foliage, the foliar EECs are expected 

to decline over time as depicted in Figure 5. For reference, the avian NOAEC value is also 

depicted as a horizontal line. Residues on short grass are expected to remain above the avian 

chronic NOAEC for approximately 16-17 days after application, whereas residues on broadleaf 

plants are expected to remain above the avian chronic NOAEC for approximately 5 days. 

Residues on tall grass and arthropods (not shown) are not expected to exceed the NOAEC at any 

time. In the laboratory which determined the NOAEL, birds were exposed to clofentezine for 10 

to 20 weeks while laying eggs. Thus, their duration of exposure was much longer durations of 

exposure expected for wild birds feeding in treated orchards. While it is possible that the same 

effects could occur after the much shorter exposure period expected in the field (i.e., the 16 to 17 

days when the EEC is expected to exceed the NOAEC), it is also possible that these shorter 

exposure durations would not cause the same reproductive effects. .

Table 28. Measured Concentration of Clofentezine After an Application of Apollo at 4 oz/acre 

(from MRID 45080701)

Days Post-Application Concentration of Clofentezine on Grapes (ppm)

0 0.79

1 0.41

3 0.75

7 0.45

14 0.34

21 0.29
60

Figure 5. Expected decline of maximum clofentizine residues on foliage, in relation to the avian 

NOAEC value.

Also, the screening level risk assessment used upper bound values predicted by the T-REX

model to represent the maximum residue concentrations expected on wildlife food items. These 

values represent the highest concentrations expected to be found on a treated field immediately 

after application (Fletcher et al., 1994). While it is possible that a particular animal may feed in 

the area of the field with the maximum residues, the concentration that would be encountered by 

a typical bird would be better represented by the values T-REX predicts for mean residue 

concentrations (Table 29). These values represent the mean of all concentrations expected in 

various places on a treated field immediately after application. As evident from Table 29, none 

of the mean concentrations exceed the NOAEC for birds (30 mg/kg). Of course, these residues 

would decline further as time after application increases. Thus, an animal feeding in an area of 

the treated field with average residue concentrations is not expected to have any adverse effects 

to reproduction or development via dietary exposures.

Table 29. Dietary-Based Clofentezine EEC Values Based on Predicted Mean Concentrations

Dietary Item Dietary-Based EEC (mg/kg)

Short Grass 22.10

Tall Grass 9.36

Broadleaf Plants 11.70

Fruits, Pods, and Seeds 1.82

Arthropods 16.90

For mammals, the chronic risk conclusion is more uncertain than for birds. Even the peak EEC 

for immediately after application (62.4 mg a.i./kg) is below the mammalian chronic NOAEL for 

reproductive effects (400 mg ai/kg), thus making the dietary RQ below the LOC of 1 (RQ = 

0.16). It is only when the NOAEL is converted to a daily dose (assuming 100 mg/kg-diet is 

equivalent to 5 mg a.i./kg-bw) and compared to the expected daily doses that the LOC exceeded, 

0.00

10.00

20.00

30.00

40.00

50.00

60.00

70.00

0 5 10 15 20 25 30

Predicted Concentration (ppm)

Days

Short Grass

Broadleaf Plants

Tall Grass

Avian NOAEC
61

and then only slightly and only for small to medium mammals consuming short grass (RQ 1.35 

for 35-g mammal and 1.16 for 35-g mammal). The disagreement of these two risk assessment 

approaches add uncertainty to the risk conclusion for mammals. Furthermore, since no frank 

effects were observed at any test level in the 2-generation rat reproduction study, it is possible 

that the actual NOAEL is somewhat higher than the one used to calculate the RQs. Therefore, it 

is possible the chronic RQs for mammals might be less than the LOC if the actual NOAEL was 

known..

In conclusion, the screening level risk assessment indicate that exposure to clofentezine may 

cause adverse reproductive and developmental effects to wildlife that feed on the treated field 

during a time when it is reproducing. However, this risk appears to be limited for the following 

reasons:

• Maximum EECs fell between the avian NOAEC and LOAEC, and thus the studies did 

not confirm that adverse effects would occur at the EEC.

• Dose-based EECs for mammals are only slightly above the highest dose tested in the 

chronic mammal toxicity study. It is possible that the EEC would not be above the 

NOAEL if higher doses were tested. 

• Dietary-based risk assessment predicted risk only for animals which feed on short grass 

or broadleaf plants, but not other food items

• While maximum expected dietary concentrations exceed the NOAEC for birds, mean 

residue concentrations do not.

• For mammals, chronic risk is predicted by dose-based RQs only for short grass, but not 

by any dietary-based RQs.

2. Terrestrial Arthropods

As with any acaricide or insecticide, clofentezine will pose some risk to nontarget terrestrial 

arthropods. However, the risks posed by clofentezine appear to be quite limited compared to 

other acaricide or insecticide. The toxicity of clofentezine is specific to eggs and early larval 

stages, with very little toxicity to adult arthropods. Therefore, use of clofentezine is not expected 

to pose a risk to adult insects who feed on treated orchards, including worker bees and other 

insect pollinators such as butterflies and moths. Studies have shown that exposure to 

clofentezine at environmentally relevant exposure levels does reduce fecundity and reduces 

survival of early life stages of beetles (Olszak, 1999; Samsoe-Peterson, 1993) and the honey bee 

(Yoshida and Fuchs, 1989). Yoshida and Fuchs (1989) found that clofentezine has less 

reproductive toxicity to bees than to Verroa mite, indicating that the toxicity is somewhat 

selective to mites.

Clofentezine may be applied only once per year, and clofentezine is not highly persistent in the 

environment. Therefore, any adverse effects that may result to the reproduction of nontarget 

arthropods are expected to be transient and not have significant population- or ecosystem-level 

effects. However, some impairment of the reproduction of nontarget insects and arachnids is 
62

possible. Since the toxicity of clofentezine is specific to eggs and early life stages, listed species 

of terrestrial arthropods may be adversely affected, including those which would lay their eggs 

on trees or other vegetative plants in treated orchards and vineyards, and pollinators which would 

collects nectar or pollen from flowers of treated plants during periods of reproduction.

3. Terrestrial Plants

A tier 1 vegetative vigor study found that exposure of four dicotyledonous plants and two 

monocotyledonous plants to Apollo 50 SC at a maximum application rate of 0.26 lb a.i./A caused 

no observable adverse effects (MRID 47192103). Exposure by spray drift to nontarget terrestrial 

plants living outside the treatment site would be equal to or less than this application rate. 

Therefore, spray drift from all uses of clofentezine are not expected to adversely affect the

vegetative vigor of nontarget plants. The fact that no incidents of phytotoxicity damage have

been reported for clofentezine is consistent with the conclusion that foliar exposure to 

clofentezine is not expected to be harmful to plants.

No data are available on the effects of clofentezine on the germination and emergence of 

nontarget plants. Therefore, risk from inhibition of the germination and emergence of seeds is 

not known. However, the following lines of evidence suggest that clofentezine is not phytotoxic 

to plants:

• The mode of action of clofentezine is not relevant to toxicity of plants.

• A vegetative vigor study found no observable phytotoxicity at the maximum application 

rate.

• Clofentezine is recommended for use on a wide variety of woody and herbaceous plants 

in greenhouse use without any reported phytotoxicity.

Furthermore, clofentezine is applied only by ground equipment and has low mobility in soil, 

factors that limit exposure to nontarget plants via spray drift and runoff, respectively. Therefore, 

the EPA assumes that use of clofentezine is not expected to pose any risk to nontarget plants, 

including listed species of terrestrial plants.

C. Ecological Incidents

A preliminary review of the Ecological Incident Information System (EIIS, version 2.1) in May 

2012 did not identify any ecological incident of adverse field effects to nontarget plants or 

animals which was attributed to use of clofentezine. Also, review of the Avian Monitoring 

Information System (AIMS), which is maintained by the American Bird Conservancy, did not 

identify any ecological incident associated with the use of clofentezine. 

In addition to the incidents recorded in EIIS and AIMS, the Agency maintains a database which 

stores counts of minor incidents that pesticide registrants record in quarterly aggregated incident 

reports. Ecological incidents recorded in these aggregated reports include those categorized as 

‘minor fish and wildlife’ (W-B), ‘minor plant’ (P-B), and ‘other non-target’ (ONT) incidents, 

which includes reports of adverse effects to bees and other invertebrates. A review of this 
63

database in February 2014 did not identify any minor incident associated with use of 

clofentezine.

D. Uncertainties, Limitations, and Assumptions

1. Endocrine Disruption

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the Preliminary Problem Formulation for Registration Review (DP 

Barcode D336262), EPA reviewed these data and selected the most sensitive endpoints for 

relevant risk assessment scenarios from the existing hazard database. However, as required by 

FFDCA section 408(p), clofentezine is subject to the endocrine screening part of the Endocrine 

Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Clofentezine is 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for clofentezine. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

http://www.epa.gov/endo/.
64

2. Uncertainties Related to Data Limitations

In the absence of available data to describe the adsorption-desorption of clofentezine in the soil, 

EPI Suite was used to estimate the Koc of 516.1 L/kg. Although there are uncertainties 

associated with the estimated Koc, it predicts moderate mobility in soil and aquatic 

environments. 

Numerous limitations in the available toxicity data set contributed to uncertainty in this risk 

assessment. Chronic toxicity studies with fish were limited to early life-stage studies. These 

studies measured toxic effects of clofentezine to eggs and larval stages, but did not evaluate 

potential impacts on the fecundity of adult female fish exposed to the compound. For aquatic 

invertebrates, several life-cycle studies were available, but they all suffered deficiencies that 

caused them to be classified as supplemental. In addition, two of the studies failed to test at 

levels low enough to establish a NOAEC. Because they failed to establish the chronic NOAEC, 

the lowest LOAEC value (44 μg/L from MRID 47192117) was used to assess risk to freshwater 

invertebrates. The study of chronic effects to the saltwater invertebrates (MRID 48342701) did 

produce a NOAEC, but the results were uncertain because the diluter system in the study failed 

to deliver consistent concentrations of test solution in the exposure chambers. Finally, toxicity 

data were not available for some aquatic species, including estuarine mollusks (e.g., the oyster), 

sediment-dwelling arthropods, aquatic vascular plants, diatoms, and blue-green algae. These 

species may be more sensitive than the species which were tested, and thus the risk assessment 

may have underestimated risk to aquatic invertebrates and plants.

(Barber and Barrett, 1993) provides data suggesting that reproductive impairment observed in 

chronic studies with daphnids exposed to Apollo SC, a suspension concentrate formulation of 

clofentezine, may be the result of physical stress caused by ingestion of small solid particles 

while filter-feeding, rather than by inherent toxicity of clofentezine. The chronic endpoint used 

in the freshwater invertebrate risk assessment was based on a life-cycle toxicity study conducted 

with Apollo 50 SC (MRID 47192102), and thus the observed toxicity may have been caused by 

exposure to suspended particles. Crustaceans living in the wild exposed to clofentezine from 

runoff from treated areas would be exposed mainly to dissolved clofentezine, without the high 

concentration of suspended particles present in the laboratory study. Thus, the study may have 

overestimated chronic risk to freshwater invertebrates in the wild.

The lack of complete phytotoxicity data for clofentezine also creates uncertainty in the risk 

assessment for terrestrial plants. Only one vegetative vigor study has been submitted (MRID 

47192103). That study was classified as supplemental because it tested only 6 plant species, 

whereas the guideline requires 10 species. No seedling emergence data have been submitted, 

therefore it was not possible to assess the risk of impairment of the germination or emergence of 

plants. Nevertheless, the risk assessment concluded that significant adverse effects to nontarget 

plants from use of clofentezine are unlikely (see Section VI.B.3.)

The lack of toxicity data on the two major degradation products that are expected to form in the 

environment also contributes to uncertainty in this risk assessment. Risk could be 

underestimated if either of these degradates are significantly more toxic to nontarget organisms 

than the parent compound. QSAR analysis using the ECOSAR program does not predict 
65

significant toxicity for these degradates with the possible exception of toxicity of AE C593600 

to aquatic plants (Section II.E.3). ECOSAR results provided contradictory predictions for the 

toxicity of AE C593600 to green algae based on comparisons with different chemical classes 

(Table 12), and further evaluation led to the conclusion that this compound is not likely to be 

very toxic to aquatic plants. However, risk could have been underestimated if AE C593600 is 

actually very toxic to aquatic plants (as suggested by one of the ECOSAR predictions), or if 

either of the major degradate compounds is more toxic to any taxa of organisms than the QSAR 

analysis predicted.

3. Uncertainty in Risk Conclusions

The conclusion of “no effects” for threatened and endangered fish is not highly certain because 

the nondefinitive endpoint obtained for acute toxicity to fish was not sufficient to demonstrate 

that RQ is less than the LOC for endangered species (0.05) for use on fruit trees. Measurement 

of the acute LC50 for fish was limited by the solubility of clofentezine and thus only was shown 

to be greater than 34.2 μg/L. The LC50 would need to be greater than 66.8 μg/L for the acute RQ 

to be less than the 0.05. A conclusion of “no effects” was made based on the lack of toxic effects 

observed at the solubility limit of 34.2 μg/L, which is approximately 10 times greater than the 

peak EEC. Nevertheless, this conclusion would have been more certain if all of the acute RQs 

for fish were found to be less than the LOC of 0.05.

Finally, the conclusion that use of clofentezine will pose chronic risk to terrestrial wildlife is 

uncertain because chronic RQs were only slightly greater than the LOC when considering the 

peak EEC, but would not exceed the LOC when considering the mean EEC. In some cases peak 

terrestrial EECs on wildlife food items exceeded the NOAEC for chronic effects, but in no case 

did they exceed the LOAEC. Chronic RQs were calculated based on the maximum EEC 

predicted by the T-REX model. If RQs were calculated based on mean EECs, which predict 

average residues expected throughout a treated field, the RQs would not exceed the LOC. Also, 

as clofentezine may be applied only once per season, and terrestrial residues are expected to 

dissipate fairly rapidly, even the maximum EECs would be expected to remain at potentially 

toxic level for no more than 17 days for residues on short grass, or 4 days for residues on 

broadleaf plants (Fig. 5). In the chronic toxicity studies, test animals were exposed to 

clofentezine for much longer durations than this (for example, approximately 22 weeks in the 

avian reproduction study). Thus, it is uncertain that the relatively short exposure that is expected 

to animals in the wild would produce as much chronic toxicity as observed in the laboratory 

studies.

The risk assessment determined that risk exceeds the EPA’s LOC only for chronic effects to 

terrestrial animals. Because clofentezine may only be applied one time per year, the chronic 

terrestrial RQs cannot be reduced by limiting the number of allowable applications or increasing 

the minimal application interval. Only reducing the single application rate would reduce these 

chronic RQs. For protecting birds, the maximum single application rate would need to be 

reduced to <0.125 lb a.i./A to reduce the chronic RQ to less than the chronic LOC (1). For 

protecting mammals, the single application rate would need to be reduced to <0.19 lb a.i./A, to 

reduce the RQ to less than the LOC.
66

VII. Risk Conclusions

The results of this screening-level risk assessment indicate that all outdoor uses of clofentezine 

have the potential for direct adverse effects to listed and non-listed birds and mammals. As birds 

serve as surrogates to reptiles and terrestrial-phase amphibians, risk to these taxa is also possible. 

Risk to terrestrial vertebrates is associated with sublethal effects on reproduction and growth that 

may occur with chronic exposure. However, the risk of chronic effects to mammals is uncertain 

because dietary-based RQs do not exceed the LOC. Use of clofentezine is not expected to pose a 

risk to foraging bees, but because of potential adverse effects to reproduction and development, 

potentially may harm nonlisted and listed species of terrestrial arthropods. Use of clofentezine is 

not expected to cause direct or indirect adverse effects to fish, aquatic invertebrates, terrestrial 

plants, or aquatic plants.

Based on the available data, suspended concentrate (SC) formulated products of clofentezine are 

slightly to practically non-toxic to freshwater fish and invertebrates on an acute-exposure basis. 

The limited solubility of the technical grade active ingredient (TGAI) prevented classification of 

the acute toxicity, but the TGAI was shown to be nontoxic at concentrations that are close to the 

limit of its solubility in water. Acute RQs for fish and aquatic invertebrates were below the 

EPA’s LOC for listed and nonlisted species. Chronic toxicity tests did not find any adverse 

effects caused by chronic exposure to fish at concentrations up to the solubility limit. Chronic 

exposure to aquatic invertebrates was found to inhibit reproduction; however, the NOAEC in 

these studies were greater than expected environmental concentrations (EECs), and thus the 

chronic RQs are all below EPA’s LOC.

For terrestrial birds and mammals, clofentezine is practically nontoxic on an acute exposure 

basis. The lack of toxicity and the relatively low use rate resulted in acute risk quotients well 

below the EPA’s level of concern. However, chronic studies identified adverse sublethal effects 

to birds and mammals. Because the NOAEL of these studies were less than the EEC for some 

types of birds and mammals, the chronic RQs were above the EPA’s LOC (dietary-based RQs 

0.08 – 2.08, dose-based chronic RQs 0.01 – 1.35). Thus, all uses of clofentezine are predicted to 

pose chronic risk to birds, mammals, reptiles, and terrestrial amphibians, and may cause adverse 

effects listed species of these taxa. The chronic risk to terrestrial animals is uncertain because 

the two chronic risk assessment approaches gave different conclusions. Since the peak dietary 

EECs for all dietary items were less than the exposure level which caused no frank effects in a

mammal 2-generation rat study (MRID 00147844), the dietary-based risk assessment approach

concludes that the chronic risk is below the level of concern. However, when the daily oral dose 

is converted to an approximate dietary concentration (based on the assumption of the dietary 

concentration for an adult rat (mg/kg-diet) is approximately equivalent to 20 times the daily dose 

expressed as mg/kg-BW per day), the chronic RQ slightly exceeds the chronic LOC for small to 

medium mammals that feed on short grass (RQs 1.16 to 1.35). Another source of uncertainty is 

that the two-generation rat reproduction study did not test to high enough levels to generate frank 

effects on growth, survival, or reproduction. Therefore, the NOAEL was set at the highest test 

dose of 20 mg ai/kg-BW day (assumed to be equivalent to 400 kg a.i./kg-diet). If the pesticide 

would have been tested at higher levels, it is possible that somewhat higher exposure levels 

might also fail to produce frank effects, yielding a higher NOAEC. If the actual NOAEC is 540 

mg ai.i/kg-diet or greater, then none of the chronic RQs would not exceed the LOC.
67

A honey bee contact study found that clofentezine is practically nontoxic to adult bees. Based on 

available acute toxicity data, no specific bee acute hazard statement is currently needed on 

product labels. Studies with beneficial beetles have found that clofentezine also has low acute 

toxicity to these species. However, as with mites (the target species), clofentezine has been 

found to cause toxicity to eggs and early life-stages of bees and other insects. While the 

available toxicity data and risk assessment methods do not allow for a precise description of the

chronic risk to terrestrial insects, a qualitative evaluation indicates that potential risk of 

clofentezine use to cause significant brood effects in bees is small. However, because of 

potential reproductive effects, the EPA believes that all uses of clofentezine have the potential to 

cause adverse effects to nonlisted and listed species of terrestrial arthropods.

Because clofentezine is applied only once per year and residues are not very persistent in the 

environment, chronic effects to terrestrial animals are not expected to be on a scale that would 

significantly affect their populations. Therefore indirect effects to endangered organisms from 

loss of ecological services, such as diminished seed dispersal of plants, are believed to be 

discountable.

Several lines of evidence indicate that clofentezine has low toxicity to plants. Toxicity to plants 

is not expected by the mode of action of this pesticide (toxicity to eggs and growth inhibition of 

early life-stages of invertebrates). Limit tests conducted with terrestrial plants found no 

significant phytotoxicity when plants were treated directly at the maximum application rate. A 

limit study testing the toxicity of a formulated product of clofentezine to green algae also found 

no observable toxic effects when tested at the high concentration of 100 mg product/L. Although 

other types of aquatic plants may be more sensitive, and testing with other species of aquatic 

plants would be needed to draw general conclusions for aquatic plants as a group, this test 

indicates that clofentezine is not toxic to green algae at the solubility limit of clofentezine. Also, 

clofentezine is routinely applied to a wide variety of plants in greenhouses, orchards, and tree 

farms without any reported problems with phytotoxicity or plant damage incidents. Therefore, 

EPA concludes that use of clofentezine will not pose significant risk to either terrestrial or 

aquatic plants, and is not expected to harm listed species of plants.

Conclusions on the potential for clofentezine to cause direct and indirect effects to federally 

listed threatened and endangered species of various taxa are summarized in Table 30. 

Conclusions for direct effects to listed species are also summarized in Table 1 of the Executive 

Summary.

Table 30. Non-listed and Listed Species Risks Associated with Potential Direct or Indirect 

Effects Due to the Applications of Clofentezine 

LISTED TAXON

DIRECT EFFECTS INDIRECT 

EFFECTS1

Non-listed Listed

Terrestrial and semi-aquatic plants 

– monocots No No No

Terrestrial and semi-aquatic plants 

– dicots No No No
68

LISTED TAXON

DIRECT EFFECTS INDIRECT 

EFFECTS1

Non-listed Listed

Birds Yes Yes Yes

Terrestrial phase amphibians Yes Yes Yes

Reptiles Yes Yes Yes

Mammals Yes Yes Yes

Terrestrial Invertebrates Yes Yes Yes

Aquatic plants No No No

Freshwater fish No No No

Aquatic phase amphibians No No No

Freshwater crustaceans No No No

Mollusks2 No No No

Marine/estuarine fish2 No No No

Marine/estuarine crustaceans2 No No No

1 Indirect effects may include general habitat modification, host plant loss, and food supply disruption.

2 Quantitative data are not available for saltwater invertebrates, therefore RQs were not calculated. Risk conclusions 

were based on risk quotients calculated for freshwater invertebrates.
69

VIII. References

Barber, I. and K. Barrett. 1993. The effect of a pesticide suspension concentrate formulation on 

Daphnia magna Straus reproduction. Sci. Total Environ., 134 (Suppl. 2): 853-858.

BEAD, 2012. Usage/Use Report Package in Support of Registration Review for Clofentezine. 

Memorandum from Biological and Economic Analysis Branch to Pesticide ReEvaluation Division. March 01, 2012.

Clements, R.G., J.V. Nabholz, and M. Zeeman. 1996. Estimating toxicity of industrial chemicals 

to aquatic organisms using structure-activity relationships. Ed.: R.G. Clements. 

IRAC. 2012. IRAC MoA Classification Scheme. Version 7.2. IRAC International MoA Working 

Group. 23 pp. Available online at:

http://www.irac-online.org/content/uploads/MoA-classification.pdf

JMPR, 2007. Pesticide Residues in Food 2007, Evaluations Part 1 – Residues. Joint Meeting of 

the FOA Panel of Experts on Pesticide Residues in Food and the Environment and the 

WHO Core Assessment Group, Geneva, Switzerland, 18-27 2007. FAO Plant Production 

and Protection Paper 192. World Health Organization and Food and Agriculture 

Organization of the United Nations. Rome, 2008. Available online at:

http://www.fao.org/ag/AGP/AGPP/Pesticid/JMPR/Download/2007_eva/Evaluation.pdf

Lentz, Nancy R. 2010a. [14C] Clofentezine – Aerobic Aquatic Sediment Metabolism, 

Springborn Smithers Laboratories, Wareham, Massachusetts, Sponsored by Irvita Plant 

Protection N.V. c/o Makhteshim–Agan of North America Inc. 4515 Falls of Neuse Rd., 

Suite 300, Raleigh, NC, USA, 27609. Study No. 11742.614746J, 135 p. PMRA 2060524

Lentz, Nancy R. 2010b. [14C]Clofentezine – Anaerobic Aquatic Sediment Metabolism, 

Springborn Smithers Laboratories, Wareham, Massachusetts, Sponsored by Irvita Plant 

Protection N.V. c/o Makhteshim–Agan of North America Inc. 4515 Falls of Neuse Rd., 

Suite 300, Raleigh, NC, USA, 27609. Study No. 11742.6148, 134 p. PMRA 2060525.

Olszak, R.W. 1999. Influence of some pesticides on mortality and fecundity of the 

aphidophagous coccinellid Adalia bipunctata L (Col., Coccinellidae). J. Appl. Ent. 

123:41-45.

Samsoe-Petersen, L. 1993. Effects of 45 Insecticides, Acaricides and Molluscicides on the Rove 

Beetle Aleochara bilineata (Col.: Staphylinidae) in the Laboratory. Entomophaga 38(3): 

371-382.

USEPA, 1990. National Survey of Pesticides in Drinking Water Wells. Report Number: USEPA 

570/9-90-015, USEPA Office of Water, Washington, DC.

USEPA, 1992. Pesticides in Ground Water Data Base. Report Number(s): PB-89-164230/XAB; 

EPA-540/9-89/036, Environmental Protection Agency, Washington, DC (USA). Office 

of Pesticide Programs
70

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

USEPA, 2012. EFED Problem Formulation for Clofentezine Registration Review. 

Memorandum from the Environmental Fate and Effects Division to the Registration 

Division, Office of Pesticide Programs, Office of Chemical Safety and Pollution 

Prevention. February 2, 2007.

USEPA, 2012. OCSPP 850.3020: Honey Bee Acute Contact Toxicity. Ecological Effects Test 

Guideline. Office of Chemical Safety and Pollution Prevention. EPA 712-C-019. January 

2012.

Yoshida, T. and S. Fuchs. 1989. Blocking reproduction in Verroa jacobsoni Oud. by feeding 

clofentezine with pollen to its host Apis mellifera L. J. Appl. Ent. 108:519-526.
71

APPENDIX A

Clofentezine (125501)

Screening Level Usage Analysis (SLUA)

Date: February 17, 2012 

What is a Screening Level Usage Analysis (SLUA)?

• Available estimates of pesticide usage data for a particular active ingredient that is 

used on agricultural crops in the United States.

• Pesticide usage data obtained from various sources. The data are then merged, 

averaged, and rounded so that the presented information is not proprietary, business 

confidential, or trade secret. 

What does it contain?

• Pesticide usage data for a single active ingredient only.

• Agricultural use sites (crops) that the pesticide is reported to be used on.

• Available pesticide usage information from U.S. states that produce 80% or more of a 

crop, in most cases, or less than 80%, in rare cases, depending on the scope of the 

survey and available resources.

• Annual percent of crop treated (average & maximum) for each agricultural crop.

• Average annual pounds of the pesticide applied for each agricultural crop (i.e., for the 

states surveyed, not for the entire United States).

What assumptions can I make about the reported data?

• Average pounds of active ingredient applied - Values are calculated by merging 

pesticide usage data sources together; averaging across all observations, then 

rounding. Note: If the estimated value is less than 500, then that value is labeled 

<500. Estimated values between 500 & <1,000,000 are rounded to 1 significant 

digit. Estimated values of 1,000,000 or greater are rounded to 2 significant digits.)

• Average percent of crop treated - Values are calculated by merging data sources 

together; averaging by year, averaging across all years, & rounding to the nearest 

multiple of 5. Note: If the estimated value is less than 2.5, then the value is labeled 

<2.5. If the estimated value is less than 1, then the value is labeled <1.

• Maximum percent of crop treated - Value is the single maximum value reported 

across all data sources, across all years, & rounded up to the nearest multiple of 5. 

Note: If the estimated value is less than 2.5, then the value is labeled <2.5.

What are the data sources used?

• USDA-NASS (United States Department of Agriculture’s National Agricultural 

Statistics Service) – pesticide usage data from 2003 to 2010.

• Private pesticide market research – pesticide usage data from 2003 to 2010.

• California Department of Pesticide Regulation (DPR) Pesticide Use Reporting

(PUR) data for 2003 to 2010.

What are the limitations to the data?

• Additional registered uses may exist but are not included because the available 

surveys do not report usage (e.g., small acreage crops).

• Lack of reported usage data for the pesticide on a crop does not imply zero usage.
72

• Usage data on a particular site may be noted in data sources, but not quantified. In 

these instances, the site would not be reported in the SLUA.

• Non-agricultural use sites (e.g., turf, post-harvest, mosquito control, etc.) are not 

reported in the SLUA. A separate request must be made to receive these estimates.

• Some sites show some use, even though they are not on the label. This usage could 

be due to various factors, including, but not limited to Section 18 requests, existing 

stocks of the chemical, data collection errors, and experimental use permits (EUPs). 
73

 

February 17, 2012 

Screening Level Estimates of Agricultural Uses of Clofentezine (125501)

Sorted Alphabetically

Crop

Lbs. A.I.

Percent Crop Treated

Average Maximum

1 Almonds 3,000 <2.5 5

2 Apples 1,000 <2.5 10

3 Apricots <500 <2.5 <2.5

4 Cherries 1,000 5 10

5 Grapes <500 <1 <2.5

6 Nectarines <500 5 10

7 Peaches 1,000 5 15

8 Pears <500 5 10

9 Plums/Prunes+ <500 <2.5 <2.5

10 Walnuts 2,000 5 10

All numbers rounded.

<500 Less than 500 pounds of active ingredient

<2.5 Less than 2.5 percent of crop treated

<1 Less than 1 percent of crop treated

** California data only. No information available about use of this chemical on this crop in 

other states.

+ Crops not known to be listed on active end use product registrations or as Section 18 

emergency

exemptions when this report was run

SLUA data sources include: 

USDA-NASS (United States Department of Agriculture's National Agricultural Statistics Service) 

Private Pesticide Market Research

California DPR (Department of Pesticide Regulation)

These results reflect amalgamated data developed by the Agency and are releasable to the public.
74

APPENDIX B

Structures of Clofentezine Degradates
75

APPENDIX C

PRZM/EXAMS Aquatic EECs Output File

Upper 10th Percentile Limnetic EECs in Farm Pond

Chemical - Clofentezine

 Scenarios Instantaneous 96-Hour 21-Day 60-Day 90-Day Annual

RUN ID: NC1App-P

RUN ID: MI1Che-P

RUN ID: NY2Gra-P

RUN ID: PA1App-P

RUN ID: OR1Xma-P

RUN ID: GA1Pch-P

RUN ID: OR1App-P

RUN ID: CA1Wal-P

RUN ID: CA1Gra-P

RUN ID: CA1Orc-P

3.34

1.04

1.02

0.996

0.964

0.832

0.726

0.454

0.170

0.139

1.48

0.460

0.453

0.477

0.377

0.363

0.413

0.210

0.745E-01

0.642E-01

0.406

0.156

0.170

0.128

0.123

0.929E-01

0.155

0.705E-01

0.214E-01

0.173E-01

0.145

0.605E-01

0.742E-01

0.558E-01

0.430E-01

0.361E-01

0.723E-01

0.265E-01

0.862E-02

0.709E-02

0.967E-01

0.423E-01

0.514E-01

0.400E-01

0.287E-01

0.241E-01

0.490E-01

0.218E-01

0.756E-02

0.475E-02

0.239E-01

0.105E-01

0.130E-01

0.988E-02

0.902E-02

0.594E-02

0.122E-01

0.594E-02

0.204E-02

0.190E-02

Express v. 1.03.02 (2007-07-20) - Exams 2.98.04.06 with PRZM 3.12.2[48]
76

APPENDIX D

Output from T-Rex Model Run for Clofentezine

Acute and Chronic RQs are based 

on the Upper Bound 

Kenaga Residues.
77

Chemical Name:

Clofentezine The maximum single day residue 

estimation is used for 

 Use All

both the acute and 

reproduction RQs. Formulation 0

Application Rate 0.26 lbs a.i./acre

RQs reported as "0.00" in the RQ 

tables below should be noted as

Half-life 15.7 days 

<0.01 in your assessment. This is 

due to rounding and significant

Application Interval 0 days figure issues in Excel.

Maximum # Apps./Year 1

Length of Simulation 1 year

Variable application 

rates? no

Endpoints

Avian

Bobwhite 

quail 

LD50 

(mg/kg-bw) 3000.00

Bobwhite 

quail 

LC50 

(mg/kg-diet) 19900.00

Mallard 

duck 

NOAEL(mg/k

g-bw) 0.00

Bobwhite 

quail 

NOAEC 

(mg/kg-diet) 30.00

Mammals

LD50 (mg/kg-bw) 3230.00

LC50 (mg/kg-diet) 0.00

NOAEL (mg/kg-bw) 2.50

NOAEC (mg/kg-diet) 50.00
78

Dietary-based EECs 

(ppm)

Kenaga

Values

Short Grass 62.40

Tall Grass 28.60

Broadleaf plants 35.10

Fruits/pods/seeds 3.90

Arthropods 24.44

Avian 

Results

Avian Body Ingestion (Fdry)

Ingestio

n (Fwet) % body wgt FI

Class Weight (g) (g bw/day) (g/day) consumed

(kgdiet/day)

Small 20

5 23

114

2.28E-02

Mid 100

13 65

65

6.49E-02

Large 1000

58 291

29

2.91E-01

20 5 5 25 5.06E-03

Granivores 100 13 14 14 1.44E-02

1000 58 65 6 6.46E-02

Avian Body Adjusted LD50

Weight (g) (mg/kg-bw)

20 2161.29

100 2751.43

1000 3886.50
79

Dose-based 

EECs 

(mg/kg-bw)

Avian Classes and Body Weights (grams)

small mid large

20 100 1000

Short Grass 71.07 40.53 18.14

Tall Grass 32.57 18.57 8.32

Broadleaf 

plants 39.98 22.80 10.21

Fruits/pods 4.44 2.53 1.13

Arthropods 27.83 15.87 7.11

Seeds 0.99 0.56 0.25

Dose-based 

RQs 

(Dosebased 

EEC/adjust

ed LD50)

Avian Acute RQs

Size Class (grams)

20 100 1000

Short Grass 0.03 0.01 0.00

Tall Grass 0.02 0.01 0.00

Broadleaf 

plants 0.02 0.01 0.00

Fruits/pods 0.00 0.00 0.00

Arthropods 0.01 0.01 0.00

Seeds 0.00 0.00 0.00
80

Dietary-

based RQs 

(Dietary-

based 

EEC/LC50 

or NOAEC)

RQs

Acute Chronic

Short Grass 0.00 2.08

Tall Grass 0.00 0.95

Broadleaf 

plants 0.00 1.17

Fruits/pods/

seeds 0.00 0.13

Arthropods 0.00 0.81

Note: To 

provide risk 

management 

with the 

maximum 

possible 

information,

it is 

recommende

d that both 

the dose-

based and 

concentration-

based 

RQs be 

calculated 

when data are 

available
81

Clofentezine All

Upper bound Kenaga 

Residues

Mammalian 

Results

Mammalian Body 

Ingestion 

(Fdry)

Ingestion 

(Fwet)

% body 

wgt FI

Class Weight

(g 

bwt/day) (g/day) consumed

(kgdiet/day)

15 3 14 95 1.43E-02

Herbivores/ 35 5 23 66 2.31E-02

insectivores 1000 31 153 15 1.53E-01

15 3 3 21 3.18E-03

Grainvores 35 5 5 15 5.13E-03

1000 31 34 3 3.40E-02

Mammalian Body Adjusted Adjusted

Class Weight LD50 NOAEL

15 7098.99 5.49

Herbivores/ 35 5743.84 4.45

insectivores 1000 2484.39 1.92

15 7098.99 5.49

Granivores 35 5743.84 4.45

1000 2484.39 1.92

Dose-Based EECs 

(mg/kg-bw)

Mammalian Classes and Body weight

(grams)

15 35 1000

Short Grass 59.49 41.12 9.53

Tall Grass 27.27 18.85 4.37

Broadleaf plants 33.47 23.13 5.36

Fruits/pods 3.72 2.57 0.60

Arthropods 23.30 16.10 3.73

Seeds 0.83 0.57 0.13

Dose-based RQs 

(Dose-based 

EEC/LD50 or 

NOAEL)

Small mammal Medium mammal Large mammal

15 grams 35 grams 1000 grams

Acute Chronic Acute Chronic Acute Chronic

Short Grass 0.01 10.83 0.01 9.25 0.00 4.96

Tall Grass 0.00 4.96 0.00 4.24 0.00 2.27

Broadleaf plants 0.00 6.09 0.00 5.20 0.00 2.79

Fruits/pods 0.00 0.68 0.00 0.58 0.00 0.31

Arthropods 0.00 4.24 0.00 3.62 0.00 1.94

Seeds 0.00 0.15 0.00 0.13 0.00 0.07
82

Dietary-based 

RQs (Dietarybased EEC/LC50 

or NOAEC)

Mammal RQs

Acute Chronic

Short Grass #DIV/0! 1.25

Tall Grass #DIV/0! 0.57

Broadleaf plants #DIV/0! 0.70

Fruits/pods/seeds #DIV/0! 0.08

Arthropods #DIV/0! 0.49

Note: To provide 

risk management 

with the maximum 

possible 

information,

it is recommended 

that both the dosebased and 

concentrationbased 

RQs be calculated 

when data are 

available
83

APPENDIX E

Output from the Screening Imbibition Program (SIP) for Clofentezine

Table 1. Inputs

Parameter Value

Chemical name Clofentezine

Solubility (in water at 25oC; mg/L) 0.002

Mammalian LD50 (mg/kg-bw) 3230

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian 

species

Mammalian NOAEL (mg/kg-bw) 20

Mammalian test species laboratory rat

Body weight (g) of "other" mammalian 

species

Avian LD50 (mg/kg-bw) 3000

Avian test species mallard duck

Body weight (g) of "other" avian species

Mineau scaling factor 1.15

Mallard NOAEC (mg/kg-diet) 270

Bobwhite quail NOAEC (mg/kg-diet) 30

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) 0.0003 0.0003

Adjusted toxicity value (mg/kg-bw) 2484.3886 15.3832

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
84

Table 3. Avian Results

Parameter Acute Chronic

Upper bound exposure (mg/kg-bw) 0.0016 0.0016

Adjusted toxicity value (mg/kg-bw) 1557.6762 3.1889

Ratio of exposure to acute toxicity 0.0000 0.0005

Conclusion*

Drinking water exposure 

alone is NOT a potential 

concern for birds

Drinking water exposure 

alone is NOT a potential 

concern for birds

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

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

drinking water may contribute to a total exposure that has potential for effects to non-target animals.
85

APPENDIX F

Output from the Screening Tool for Inhalation Risk (STIR) for Clofentezine

Welcome to the EFED 

Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining 

the potential

significance of the inhalation exposure route to birds and mammals in a risk 

assessment.

Input

Application and Chemical Information

Enter Chemical Name Clofentezine

Enter Chemical Use all

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) 303.15

Enter Chemical Vapor Pressure (mmHg) 9.75E-10

Enter Application Rate (lb a.i./acre)

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 3000

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 1.58

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 3200

Enter Lowest Rat Inhalation LC50 (mg/L) 9.08

Duration of Rat Inhalation Study (hrs) 6

Enter Rat Weight (kg) 0.35
86

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.59E-05

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.00E-06

Adjusted Inhalation LD50 5.13E+01

Ratio of Vapor Dose to Adjusted Inhalation LD50 3.90E-08 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 0.00E+00

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 0.00E+00 Exposure not Likely Significant

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.59E-05

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.51E-06

Adjusted Inhalation LD50 8.11E+02

Ratio of Vapor Dose to Adjusted Inhalation LD50 3.10E-09 Exposure not Likely Significant

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 0.00E+00

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 0.00E+00 Exposure not Likely Significant
87

APPENDIX G

Results of ECOTOX Literature Search for Clofentezine

Open literature studies with toxicity data on clofentezine were 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.

Accepted for EcoTox and OPP

Bostanian, N. J., Vincent, C., Pitre, D., and Simard, L. G. (1989). Chemical Control of Key and Secondary 

Arthropod Pests of Quebec Apple Orchards. Appl. Agric. Res. 4(3): 179-184.

EcoReference No.: 89749

Chemical of Concern: ACYP,AZ,BFT,CHX,CTZ,CYH,CYP,DM,FNV,FVL,HTX,OTQ,TDC; Habitat: T; 

Effect Codes: POP; Code: LITE EVAL CODED (AZ,BFT,CTZ,CYH,CYP,DM,FNV,FVL,HTX,TDC), 

NO EFED CHEM (ACYP,CHX,OTQ) 

Easterbrook, M. A. (1984). Effects of Pesticides on the Apple Rust Mite Aculus schlechtendali (Nal.) (Eriophyidae). 

J. Hortic. Sci. 59(1): 51-55.

EcoReference No.: 71031

Chemical of Concern: 

AMZ,CBL,CHX,CPY,CTZ,DCF,DFZ,ES,FPP,FRM,MZB,PHSL,PIRM,PPG,SFR,TDF,TFR; Habitat: T; 

Effect Codes: POP; Code: LITE EVAL CODED 

(AMZ,CBL,CTZ,DCF,DFZ,FPP,FRM,MZB,PIRM,PPG,SFR,TDF,TFR), NO EFED CHEM (CHX,PHSL), 

TARGET (CPY,ES) 

Fouche, C., Verdegaal, P., Duncan, R., and Cutter, D. (1998). Evaluation of Acaricides for Control of Spider Mites 

on Almonds and Impact on Two Beneficial Arthropods, 1997. Arthropod Manag. Tests 23: 59-(1D).

EcoReference No.: 150672

Chemical of Concern: ABM,CFP,CTZ,EXZ,HTX,NMO,PPG,PRB; Habitat: T; Effect Codes: POP; Code:

LITE EVAL CODED (CTZ), NO EFED CHEM (EXZ), OK (ABM,CFP,HTX,NMO,PPG,PRB) 

Goodwin, S. (1984). Laboratory Evaluation of Pesticides on an Australian Strain of the Chilean Predatory Mite, 

Phytoseiulus persimilis Athias-Henriot. In: D.A.Griffiths and C.E.Bowman (Eds.), Acarology VI, Vol. 2, 

Ellis Horwood, Chichester, UK 2: 647-654.

EcoReference No.: 94828

Chemical of Concern: 

AZ,BMY,BTN,CHX,CPY,CTZ,Captan,DCF,DIE,DMT,DZ,ES,FBOX,FNV,FO,IPD,MDT,MLN,MZB,OT

Q,OXC,PIM,PMR,PPG,SFR,TCF,TDF,TFR,VCZ; Habitat: T; Effect Codes: MOR,REP; Code: LITE 

EVAL CODED 

(AZ,BMY,CPY,CTZ,Captan,DCF,DMT,DZ,ES,FBOX,FNV,IPD,MDT,MLN,MZB,PIM,PMR,PPG,SFR,T

CF,TDF,TFR,VCZ), NO EFED CHEM (BTN,CHX,DIE,OTQ,OXC) 

Olszak, R. W. (1999). Influence of Some Pesticides on Mortality and Fecundity of the Aphidophagous Coccinellid 

Adalia bipunctata L. (Col., Coccinellidae). Z. Angew. Entomol. 123(1): 41-45.

EcoReference No.: 64265

Chemical of Concern: 

ACYP,AMZ,CTZ,DFC,DOD,EFV,ES,FBOX,FO,FPP,FRM,FUZ,HTX,IPD,MEM,MZB,PHSL,PPG,TFR,

TFZ,VCZ; Habitat: T; Effect Codes: MOR,REP; Code: LITE EVAL CODED 

(DOD,EFV,ES,FRM,FUZ,IPD,MEM,MZB,VCZ,CTZ), NO EFED CHEM (ACYP,DFC,PHSL), NO 

ENDPOINT (HTX,TFZ), TAR

Samsoe-Petersen, L. (1993). Effects of 45 Insecticides, Acaricides and Molluscicides on the Rove Beetle Aleochara 
88

bilineata (Col.: Staphylinidae) in the Laboratory. Entomophaga 38(3): 371-382.

EcoReference No.: 63489

Chemical of Concern: 

ACP,AMZ,AZ,BPZ,CBL,CPY,CTZ,CYF,CYP,CYR,DFZ,DM,DMT,DZ,FNT,FPP,FVL,FYC,HTX,KSP,L

CYT,MAL,MCB,MTM,MVP,OML,OTQ,PIM,PMR,PPHD,PSM,THO; Habitat: T; Effect Codes: 

MOR,REP; Code: LITE EVAL CODED 

(CBL,CPY,CTZ,CYF,CYP,CYR,DFZ,DMT,DZ,FPP,FVL,FYC,HTX,KSP,LCYT,MAL,MCB,MTM,MVP

,OML,PIM,PMR,PSM), NO EFED CHEM (BPZ,OTQ,PPHD,THO), NO PUBL AS 

(ACP,AMZ,AZ,DM,FNT), TARGET (AMZ,AZ,DM,FNT) 

Urbaneja, A., Pascual-Ruiz, S., Pina, T., Abad-Moyano, R., Vanaclocha, P., Monton, H., Dembilio, O., Castenera, 

P., and Jacas, J. A. (2008). Efficacy of Five Selected Acaricides Against Tetranychus urticae (Acari: 

Tetranychidae) and Their Side Effects on Relevant Natural Enemies Occurring in Citrus Orchards. Pest 

Manag. Sci. 64(8): 834-842.

EcoReference No.: 154868

Chemical of Concern: ALSV,CTZ,FBOX,FZQ,MOIL,TFY; Habitat: T; Effect Codes: MOR,POP,REP; 

Code: LITE EVAL CODED (ALSV,CTZ,FBOX,FZQ,MOIL,TFY), NO EFED CHEM (TFY) 

Yoshida, T. and Fuchs, S. (1989). Blocking Reproduction in Varroa jacobsoni Oud. by Feeding Clofentezin with 

Pollen to Its Host Apis mellifera L. J. Appl. Entomol.: 519-526.

EcoReference No.: 154863

Chemical of Concern: CTZ; Habitat: T; Effect Codes: GRO,MOR,REP; Code: LITE EVAL CODED 

(CTZ) 

Papers not Accepted for ECOTOX

Hull, L. A. and Krawczyk, G. (1998). Tufted Apple Bud Moth Control Tactics for Apple, 1997. Arthropod Manag. 

Tests 23: 22-26 (15A).

EcoReference No.: 150741

Chemical of Concern: ABM,ALSV,CTZ,IMC,MFZ,MOIL,MOM,MP,PYX,SS,TUZ; Habitat: T; Effect 

Codes: POP; Code: NO EFED CHEM (SS), NO MIXTURE (ABM,CTZ,IMC,MFZ,MOM,MP,TUZ), 

TARGET (ALSV,MOIL,PYX,TUZ) 

Longhurst, C., Bacci, L., Buendia, J., Hatton, C. J., Petitprez, J., and Tsakonas, P. (1992). Fenazaquin, a Novel 

Acaricide for the Management of Spider Mites in a Variety of Crops. In: Br.Crop Prot.Counc., Brighton 

Crop Prot.Conf.: Pests and Diseases, Vol.1-3, Int.Conf., Nov.23-26, 1992, Brighton, England, UK, Br.Crop 

Prot.Counc.(BCPC), Farnham, England, UK: 51-58.

EcoReference No.: 106270

Chemical of Concern: BFT,CTZ,DCF,FBOX,FPP,FZQ,HTX,PPG; Habitat: T; Effect Codes: PHY,POP; 

Code: NO CONTROL (BFT,CTZ), NO ENDPOINT (FBOX,HTX,PPG), OK (DCF,FPP,FZQ) 

Maciesiak, A. and Olszak, R. W. (1999). Effectiveness of Acaricide Mixtures in the Control of Phytophagous Mites 

on Apple Trees. J. Fruit Ornam. Plant Res. 7(2): 91-96.

EcoReference No.: 97506

Chemical of Concern: AMZ,CTE,CTZ,HTX,PPG; Habitat: T; Effect Codes: POP; Code: LITE EVAL 

CODED (PPG), NO MIXTURE (AMZ,CTZ), TARGET (HTX) 

Somerville, L., Challis, I. R., and Needham, D. (1989). Relevance of Kinetic and Metabolic Data to the 

Interpretation of Toxicological Findings. Food Addit. Contam. 6(1): 33-39.

EcoReference No.: 150077

Chemical of Concern: CTZ; Habitat: T; Effect Codes: ACC; Code: NO CONTROL (CTZ), NO 

ENDPOINT (CTZ) 

Van Leeuwen, T., Stillatus, V., and Tirry, L. U. C. (2004). Genetic Analysis and Cross-Resistance Spectrum of a 

Laboratory-Selected Chlorfenapyr Resistant Strain of Two-Spotted Spider Mite (Acari: Tetranychidae). 
89

Exp. Appl. Acarol. 32(4): 249-261.

EcoReference No.: 75967

Chemical of Concern: AMZ,BFT,CFP,CTZ,DMT,PPB,SDF; Habitat: T; Effect Codes: MOR; Code: NO 

CONTROL (AMZ,BFT,CFP,CTZ,DMT,SDF), NO MIXTURE (PPB)