UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE O 

OFFICE OF CHEMCICAL SAFETY AND 

POLLUTION PREVENTION 

Environmental Fate and Ecological Risk Assessment 

Problem Formulation 

In Support of Registration Review of Cyclanilide 

http://pubchem.ncbi.nlm.nih.gov/image/structurefly.cgi?cid=86133&width=400&height=400

February 2, 2010 

Completed By: Reviewed By: 

Mohammed Ruhman, Agronomist Mah T. Shamim, Ph.D 

Justin Housenger, Biologist Branch Chief, Environmental Risk Branch 5 

Environmental Risk Branch 5 Environmental Fate and Effects Division 

Environmental Fate and Effects Division 
2 

Table of Contents

1. Purpose ........................................................................................................................ 3 

2. Problem Formulation .................................................................................................. 3 

2.1 Nature of Regulatory Action ..................................................................................... 3 

2.2 Previous Risk Assessments ....................................................................................... 3 

3. Stressor Source and Distribution ................................................................................ 4 

3.1 Mechanism of Action ................................................................................................ 5 

3.2 Overview of Pesticide Usage .................................................................................... 5 

3.3 Environmental Fate and Transport ............................................................................ 7 

4. Ecological Effects ..................................................................................................... 11 

4.1 Aquatic and Terrestrial Effects ............................................................................... 11 

4.2 Incident Database Review ....................................................................................... 15 

4.3 Ecosystems Potentially at Risk ............................................................................... 15 

4.4 Assessment Endpoints ............................................................................................ 16 

4.5 Conceptual Model ................................................................................................... 16 

5. Analysis Plan ............................................................................................................ 19 

5.1 Stressors of Concern ............................................................................................... 20 

5.2 Measures of Exposure ............................................................................................. 20 

5.3 Measures of Effect .................................................................................................. 20 

5.4 Integration of Exposure and Effects ....................................................................... 23 

5.5 Endangered Species Assessments ........................................................................... 23 

5.6 Monitoring Data ...................................................................................................... 24 

5.7 Clean Water Act ...................................................................................................... 24 

5.8 Endocrine Disrupter Screening Program ................................................................ 24 

5.9 Uncertainty and Preliminary Identification of Data Gaps ...................................... 25 

List of Tables 

Table 1. Summary of use information for Cyclanilide, based on LUIS Report EFED 

spread sheet dated 03/26/2010 and evaluation of all labels (note: assumed entries based 

on label language and crop growth characteristics) ............................................................ 5 

Table 2 Summary of physicochemical properties of cyclanilide ........................................ 7 

Table 3. Summary of Fate Properties of Cyclanilide ......................................................... 9 

Table 4. Test Species Evaluated for Assessing Potential Acute and Chronic Ecological 

Effects of Cyclanilide. ...................................................................................................... 13 

Table 5. Measures of Ecological Effects and Exposure for Cyclanilide ......................... 21 

 Table 6. Ecological Effects Data Requirements for Cyclanilide ..................................... 28 

List of Figures 

Figure 1. Cotton acreage data compared to estimated usage data for cyclanilide .............. 7 

Figure 2. Structures for parent cyclanilide and main degradate ...................................... 11 

Figure 3. A conceptual model for cyclanilide effects on aquatic organisms. .................. 18 

Figure 4. A conceptual model of cyclanilide effects on terrestrial organisms ................. 19 
3 

1. Purpose 

The purpose of this problem formulation is to provide the foundation for the ecological 

risk assessment being conducted for the registered uses of cyclanilide. As such, it 

articulates the purpose and objectives of the risk assessment, evaluates the nature of the 

problem, and provides a plan for analyzing the data and characterizing there ecological 

risk (EPA, 1998). Additionally, this problem formulation is intended to identify data 

gaps, uncertainties, and potential assumptions needed to address those uncertainties in 

characterizing the ecological risk associated with the registered uses of cyclanilide. 

Cyclanilide is a plant growth regulator that inhibits the activity of auxin. The chemical 

was initially registered in 1997 and currently has uses on cotton as a growth regulator and 

harvest aid, and on cut flowers, ornamentals, and non-bearing nursery trees as a plant 

growth regulator. It is available as a suspension concentrate and can be applied, in liquid

form, either as a ground or aerial spray. 

2. Problem Formulation 

2.1 Nature of Regulatory Action 

The Food Quality Protection Act of 1996 mandated the EPA to implement a new 

program, i.e., registration review (http://www.epa.gov/oppsrrd1/registration_review/). All 

pesticides distributed or sold in the United States generally must be registered by EPA. 

The decision to register a pesticide is based on the consideration of scientific data and 

other factors showing that it will not cause unreasonable risks to human health, workers, 

or the environment when used as directed on product labeling. The registration review 

program is intended to ensure that, as the ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet the statutory standard of no 

unreasonable adverse effects to human health and the environment. Changes in science, 

public policy, and pesticide use practices will occur over time. Through the new 

registration review program, the Agency periodically reevaluates pesticides to make sure 

that as change occurs, products in the marketplace can be used safely. 

As part of the implementation of the new Registration Review program pursuant to 

Section 3(g) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the 

Agency is beginning its evaluation to determine whether cyclanilide continues to meet 

the FIFRA standard for registration. This problem formulation for the environmental fate 

and ecological risk assessment chapter in support of the registration review is intended 

for the initial docket opening the public phase of the review process. 

2.2 Previous Risk Assessments 

Cyclanilide has been registered since 1997, and has been subject to two main risk

assessments. Previous assessments serve as the basis for this problem formulation and a 

summary of the two assessments are included hereunder:
4 

(1) EFED's chapter for the first registration of this chemical (dated November 1996)1

. 

This registration was for the cyclanilide formulated with ethephon as an emulsifiable 

concentrate for use as a cotton defoliant either aerially or by ground equipment. Risk 

to terrestrial and semi-aquatic plants was not completely assessed due to lack of 

acceptable data for the vegetative vigor tests and for phytotoxic symptoms from 

seedling emergence testing. 

(2) EFED chapter covering the proposed new use of cyclanilide to ornamentals, cut 

flower crops and non-bearing fruit trees (EFED, (DP# 323619, October 2006). 

Previous risk assessments concluded Level of Concern (LOC) exceedances as follows: 

- Terrestrial plants (dicots only) for listed and non-listed species 

- Acute LOC is exceeded for listed birds that feed on insects and for small-tointermediate sized listed mammals that feed on short grass for dose-based acute RQs 

- Chronic LOC for listed and non-listed mammals is exceeded for both dose and 

dietary-based RQs 

In the 2006 assessment, potential risk to listed and non-listed terrestrial plants could not 

be characterized quantitatively from exposure due to drift because vegetative vigor data 

was classified as invalid (MRID 43868323). However, a second study was submitted by 

the registrant and is currently in review. This study (MRID 44518602) and how it 

impacts the risk to terrestrial plants will be further discussed in this problem formulation. 

3. Stressor Source and Distribution 

Based on review of fate and transport data for cyclanilide, the stressor is considered to be 

parent plus main degradate 2, 4-dichloroaniline. The source of the stressor is application 

of cyclanilide to cotton fields and to nursery stock of some fruit trees and ornamentals. 

The chemical is a plant growth regulator formulated as emulsifiable concentrate and as 

liquid to be foliar applied, in liquid form, by ground and/or aerial equipment. Cyclanilide 

is stable to hydrolysis and photo degradation in water or on soils is not an important. 

Biotic laboratory studies suggest that the chemical degradates rather slowly in the soil 

system (half-life of 95 days) and expected to be highly persistent in anaerobic aquatic 

water/sediment systems. The degradation profile of cyclanilide in aerobic soil systems 

suggests formation of a major degradate, 2, 4-dichloroaniline metabolite. Metabolite 2, 4-

dichloroaniline contain its parent’s moiety and appears to be persistence in at least one of

the two soil systems examined. Cyclanilide parent shows similar persistence in the field 

with half-lives ranging from 35 to 114 days. 

 

1

 EFED’s Registration chapter for cyclanilide use on cotton (DP Bar codes: D223580, D223583, D225001, 

D226430, D226431, and D2230465). 
5 

Cyclanilide may partition into the air from dry or wet soil service based on reported 

vapor pressure (6.3 x 10-8 torr at 50  ̊C). Additionally, adsorption/desorption data suggest 

that cyclanilide and its metabolite are mobile and expected to reach both surface and 

ground water by run-off. 

3.1 Mechanism of Action 

Cyclanilide is an auxin inhibitor that enhances lateral branching. Auxin is a plant 

hormone that influences the way buds break during growth. Cyclanilide is formulated 

alone to regulate growth in selected fruit and ornamental trees. In this case, actively 

growing plants shoots, developing leaves produce auxin, which inhibits later buds in leaf 

axils from developing into lateral shoot. Auxin, will in turn, tend to grow the plant 

upwards rather than branching laterally. As a result, nursery plants (fruit trees or 

ornamentals) often need to be mechanically pruned. Cyclanilide can be used as an 

alternative to pruning, by forcing the plant to branch laterally. When applied to actively 

growing foliage, cyclanilide appears to induce a transient inhibition of auxin activity 

without otherwise damaging the growing shoot tip. As a result, lateral buds tend to 

develop as lateral shoots.2

 Because of this mechanism of action, cyclanilide is most 

effective in plant species that exhibit strong apical dominance, that is, plants in which the 

main (upwardly growing) stem grows more rapidly than side stems. 

Additionally, cyclanilide is formulated with two other active ingredients where the use 

purpose and mode of action is modified as follows: 

(1) With mepiqual-Cl: The formulation is used during cotton growth (the squaring 

period) to regulate cotton plant growth and manage the vegetative vigor; and 

(2) With ethephon: The formulation is applied at the end of the cotton season, before 

boll-opening, to promote boll opening, defoliation and inhibition of terminal foliar 

re-growth (i.e., bring cotton to maturity for harvest). 

3.2 Overview of Pesticide Usage 

A summary of currently labeled agricultural use patterns for cyclanilide is shown in 

Table 1

1Table 1. Summary of use information for Cyclanilide, based on LUIS Report EFED 

spread sheet dated 03/26/2010 and evaluation of all labels (note: assumed entries based 

on label language and crop growth characteristics) 

Use Pattern 

Single 

Rates (lb 

a.i./A) 

Number of 

Applications 

Maximum 

Yearly Rate 

(lb a.i./A) 

Application 

Interval (days) 

Application Method 

& Timing of 1st Application 

Selected Pome & Stone Fruits Nursery 

Stock: (Apple, Pear, Cherry & Plum)* 0.1133 3 0.3400 14 

(Assumed) 

Ground Spray; early 

Spring (both Assumed) 

 

2 Elfving D.C., Visser D.B. 2003. Managing Growth, Fruiting and Fruit Quality in Washington 

with Bioregulators. The Compact Fruit Tree. 36(3): 79-80. 
6 

Use Pattern 

Single 

Rates (lb 

a.i./A) 

Number of 

Applications 

Maximum 

Yearly Rate 

(lb a.i./A) 

Application 

Interval (days) 

Application Method 

& Timing of 1st Application 

Selected Ornamentals Nursery Stock 

(Shade trees, Woody shrubs, 

Herbaceous & non-flowering plants)* 

Cotton (Growth regulator) ** 

0.0072 

& 

0.0115 

3 0.0316 7 

Aerial or Ground Spray; 

Pre-bloom (the 21-day 

squaring period) 

Cotton (Harvest Aid)** * 0.2500 1 0.2500 NA Aerial or Ground Spray; 

before boll opening 

* Use purpose: growth regulator (formulations contains only one active ingredient: cyclanilide) 

** Use purpose: growth regulator (formulations contains two active ingredients: cyclanilide + mepiqual-Cl). The product 

is used during the crop growth (the squaring period) to regulate cotton plant growth and manage the vegetative vigor 

*** Use purpose harvest aid (formulation contains two active ingredients: cyclanilide + ethephon). The product is 

applied, at the end of the cotton season, before boll-opening, to promote boll opening, defoliation and inhibition of 

terminal foliar re-growth (i.e., bring cotton to maturity for harvest). Based on this information one application is assumed 

Screening Level Usage Analysis (SLUA, date 06/22/2010) report for cyclanilide was 

provided by BEAD. Based on this report, the only usage data were for cotton and indicate 

the following: 

• An average of 150,000 pounds of active ingredient was applied (values are 

calculated by merging pesticide usage data sources together; averaging across all 

observations, then rounding); 

• An average of 10 percent of crop was treated (values are calculated by merging 

data sources together; averaging by year, averaging across all years, & rounding 

to the nearest multiple of 5); and 

• A maximum of 20 percent of crop was treated (value is the single maximum value 

reported across all data sources, across all years, & rounded up to the nearest 

multiple of 5). 

Figure 1 shows cotton acreage throughout the US (NASS data 2002) in addition to 

the U.S. Geological Survey (USGS)3

 pesticide use map. Comparison between the

distribution of cotton acreage and the regional scale patterns in use intensity confirms 

that cotton is probably the main use pattern for cyclanilide with the exception of 

Arizona. No use is shown for the cotton areas in Arizona. 

 

3 The USGS pesticide maps are based on State level estimates of pesticide use rates for individual crops, which have 

been compiled by the National Center for Food and Agricultural Policy (NCFAP) for 1999 through 2004, and on the

2002 Census of Agriculture for county crop acreage crop. Please refer to 

(http://water.usgs.gov/nawqa/pnsp/usage/maps/compound_listing.php?year=02 ) for data limitation and to Method for 

Estimating Pesticide Use for a detailed discussion of how the pesticide use data were developed. 
7 

1Figure 1. Cotton acreage data compared to estimated usage data for cyclanilide 

In California, the pesticide is used on cotton with a total use of nearly 2,000 to 2,100 lbs 

of active ingredient (California usage data from CA Department of Pesticide Regulation 

“CA DPR” form 2006 to 20080)4

. 

3.3 Environmental Fate and Transport 

A summary of physicochemical properties of cyclanilide was obtained from previous risk 

assessment and is included in Table 2. 

2Table 2 Summary of physicochemical properties of cyclanilide 

 

4

 http://www.cdpr.ca.gov/docs/pur/purmain.htm 
8 

PARAMETER VALUE(S) (units) SOURCE

CAS Chemical Name 

1-[[(2,4-

dichlorophenyl)amino]carbonyl]cyclopropanecarboxylic 

acid 

Cyclanilide Fact Sheet May, 

1997 

http://www.epa.gov/opprd00

IUPAC Chemical Name 1/factsheets/cyclanilide.pdf 1-(2,4-

dichlorophenylaminocarbonyl)cyclopropanecarboxylic acid 

Chemical Formula C11H9Cl2NO3 From structure 

PC Code 026201 OPP Databases 

Chemical Structure 

Smiles Code: c1cc(Cl)cc(Cl)c1NC(=O)C2CC2C(=O)O 

http://pubchem.ncbi.nlm.n

ih.gov/image/structurefly.

cgi?cid=86133&width=40

0&height=400 

CAS Reg. No. 113136-77-9 Pesticide fact Sheet 

http://www.epa.gov/opprd00

1/factsheets/cyclanilide.pdf Molecular Weight 274.1 g/mole 

Solubility (20oC) 48 mg/L (ppm) 

Vapor Pressure (VP @ 50 oC) 6.3 x 10-8 torr MRID 433684-09 

Henry’s Law Constant 4.73 x 10-10 atm-m3

-mol-1 Calculated @ 50 oC

Octanol-Water Partition 

Coefficient (21oC) 

(log KOW and KOW) 

3.25, and 1,778 <7.52 x 10-10 atm-m3

-mol-1

Octanol-Air Partition 

Coefficient 

(log KOA and KOA) 

9.33 and 2.14 x 109 EPISuite v.4.0 Estimate 

Bio-magnification Potential 

Presumption*: If log KOA > 5, log KOW >2 and the rate of 

chemical transformation is low, the chemical may bio-magnify in 

terrestrial food chains►

For cyclanilide, log KOA=9.33, log KOW=3.25 rate of 

transformation is relatively low; it appears that cyclanilide has a 

potential to bio-magnify in terrestrial food chains 

► Gobas et al. 20035

support this presumption 

utilized here only as a broad 

reference to determine the 

potential for 

biomagnification 

 

5

 Gobas, F.A.P.C., B.C. Kelly and J.A. Arnot. 2003. Quantitative structure activity 

relationships for predicting the bioaccumulation of POPs in terrestrial food webs. QSAR 

Comb. Sci. 22:329-336. 
9 

Data in Table 2 indicate that cyclanilide has a molecular weight of 274.1 g/mol with a 

solubility of 48 ppm and an octanol/ water partition coefficient greater than 1,000 (KOW = 

1,778), it appears that cyclanilide has the potential to bio-accumulate/ bio-concentrate in 

aquatic organisms such as fish. 

For cyclanilide, the log KOA is 9.33 and the log KOW=3.25. For chemicals that are not 

readily metabolized in vivo, a log KOA and log KOW in this range (KOA > 5, log KOW >2) 

have been associated with bio-magnification in terrestrial-based food webs based on 

information presented in articles by Gobas et al. and Armitage & Gobas (2003 and 2007, 

respectively). However, this chemical may undergo substantial biotransformation in 

vivo. Even though the EFED has not adopted an official reference to distinguish 

chemicals that bio-magnify, their presumption was utilized here as a general or broad 

reference to detect the bio-magnification potential in terrestrial food chains. 

A summary of fate properties for cyclanilide from laboratory and field studies is listed in 

Table 3. 

3Table 3. Summary of Fate Properties of Cyclanilide 

Property Value (Source Reference)

Hydrolysis Stable @ pH 5, 7 and 9 (MRID 433684-51) 

Direct Aqueous Photolysis (half-life, days) 44 days (MRID 438683-25) 

Soil Photolysis (half life, days) 151 days (MRID 438683-26) 

Aerobic Soil Metabolism (half-life, days) 95 days (MRID 438683-27) 

62 days (MRID 4336844-52 & Amendment MR ID 438683-28) 

Anaerobic Aquatic Metabolism (half-life, days) Stable (MRID 438683-20) 

Kocs ( (milliliters/gram) 194 to 565 for sandy loam, loamy sand, silt loam, clay soil and 

sand sediment (MRID 433684-53& Amendment MR ID 445268-

01) 

Soil Dissipation (half-life, days) 73 day in Texas and 114 days in California (MRID 438683-30 

and MRID 439694-01 for storage stability 

Fish Accumulation (BCF); concentration in 

tissue to exposure concentration in water 

0.285X for edible, 2.7X for non-edible, and 1.28X for whole fish 

(wet weight). Depuration was rapid with approximately 75 % of 

accumulated residues depurating within 24 hours, and 100 % 

depurating within 14 days (MRIDs 440134-01 & 438683-33). 
10 

Based on laboratory studies, cyclanilide is stable to hydrolysis and highly persistent to 

photolysis in water and on soil. In anaerobic aquatic system, the chemical is expected to 

be stable. In contrast, the chemical appears to degrade slowly in aerobic soil systems 

(half-lives of approximately 62 to 95 days). 

Mobility data suggest that parent and main metabolite are mobile to moderately mobile 

(Kocs= 194 to 565 ml/g for parent cyclanilide and from 349 to 681 ml/g for 2, 4-

dichloroanilide in soils and 883 ml/g for sediment (MRIDs: 43368453 & 43868329). 

Additionally, in a 30-day aged column leaching study, <3% of the applied radioactivity 

was detected in the leachates. After leaching, the majority of the applied radioactivity 

remained in the 0 to 6 cm (57-77%) and 6 to 12 cm (3-16%) segments of each soil 

column. RPA 90946 was the predominant compound in both the uppermost soil column 

segments (>98% of the extractable radioactivity) and in the leachate (MRID 433684-54).

Four terrestrial field dissipation studies were conducted for cyclanilide in the main cotton 

producing areas (North Carolina, Mississippi, California, and Texas). Parent half-lives of 

30 days was observed at North Carolina and Mississippi site> In contrast, the first-order 

half-lives in Texas and California were 73 and 114 days; at both locations, residues 

declined until 2-3 months post-treatment, but then remained at a steady level until 6-8 

months post-treatment; they declined rapidly thereafter. At all four test sites, cyclanilide 

was found at greater than the Level of Quantitation (LOQ; 0.005 ppm) below the 0- to 

15-cm soil depth only twice and was not found at > LOQ below 30 cm. It was detected 

down to 45 cm at < LOQ only twice. Information on the field behaviour of the 

cyclanilide degradate 2, 4-dichloaniline is incomplete at this time. The cyclanilide 

degradate, 2,4-dichloroaniline, was found at >0.005 ppm only twice. 

Data on fish accumulation suggest that cyclanilide is not likely to accumulate in fish. 

Although the octanol-water partition coefficient is greater than 1,000 (KOW= 1,778 at 

21o

C), a fish bio-concentration study suggests low bio-concentration (0.285X for edible, 

2.7X for non-edible, and 1.28X for whole fish on wet weight basis) and rapid/complete 

depuration evidenced by the fact that approximately 75 % of accumulated residues 

depurated within 24 hours, and 100 % depurated within 14 days (MRIDs 440134-01 & 

438683-33). 

Laboratory and field degradation profile for cyclanilide suggest that the primary 

terrestrial dissipation mechanism for cyclanilide is aerobic microbial degradation to 2,4-

dichloroaniline (Figure 2) and presumably further degradation to cyclopropane-1,1- dicarboxylic acid. In one of the soils, 2, 4-dichloroaniline shows decline (MRID 4336844-

52 & Amendment MR ID 438683-28); however in another soil no decline was observed 

(MRID 438683-27) 

. 

 
11 

2Figure 2. Structures for parent cyclanilide and main degradate 

 

 

 

Parent cyclanilide Main degradate 2,4 dichloroaniline 

Based on the degradation profile and the relative persistence of the main degradate 2,4 

dichloroaniline (which contains the main moiety of the parent); the registration review 

risk assessment will consider parent plus degradate as the stressor. 

4. Ecological Effects 

4.1 Aquatic and Terrestrial Effects 

As described in the Agency’s Overview Document (U.S EPA, 2004), the most sensitive 

endpoint for each taxonomic group will be used to calculate risk quotients (RQs). 

Assessment endpoints include direct toxic effects on the survival, reproduction, and 

growth of terrestrial and aquatic life as well as indirect effects such as reduction in prey 

base and/or modification of habitat. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with 

the available open literature are used to evaluate the potential direct effects of cyclanilide 

to the aquatic and terrestrial receptors identified in this section. This includes toxicity 

data on the technical grade active ingredient, degradates, and when available, formulated 

products. The open literature studies are identified through EPA’s ECOTOX database 

(http://cfpub.epa.gov/ecotox/), which employs a literature search engine for locating 

chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of 

both sources of data can also provide insight into the direct and indirect effects of 

cyclanilide on biotic communities from loss of species that are sensitive to the chemical 

and from changes in structure and functional characteristics of the affected communities. 

Other sources of information including the use of acute probit dose response relationship 

to establish the probability of an individual effect and reviews of the Ecological Incident 

Information System (EIIS) are conducted to further refine the characterization of 
12 

potential ecological effects with exposure to cyclanilide. A summary of the available 

ecotoxicity information and the incident information for cyclanilide are provided below. 

Table 4 provides a summary of the taxonomic groups and the surrogate species tested to 

help understand potential acute and chronic ecological effects of cyclanilide. In addition, 

the table provides a preliminary overview of the potential acute toxicity of cyclanilide by 

providing the acute toxicity classifications. 

Terrestrial Species 

Technical grade cyclanilide is classified as moderately toxic to birds on an acute oral 

basis and slightly toxic to birds on an acute dietary basis. There were no submitted avian 

reproduction studies for cyclanilide. These studies remain a requirement in order to 

estimate risk to birds on a chronic level. Although not an ecotoxicological requirement, a 

mammalian acute oral study with the rat showed that cyclanilide is moderately toxic. An 

acute contact toxicity study to the honey bee showed that cyclanilide is practically nontoxic to terrestrial insects. 

Chronic effects on avian species, as previously mentioned could not be characterized due 

to a lack of data. In a mammalian two generation study, reproductive toxicity was 

characterized as decreases in mean pup weights at the 300 and 1000 ppm dose levels. 

Mean pup weights were reduced by 10-32% at the 1000 ppm level throughout lactation 

for both generations. In the range finding study, reproductive effects seen at the 1400 

ppm dose level included reduced mating indices, reduced gestation index, decreased 

mean implantation sites, increased pup mortality, and decreased pup weights. 

Aquatic Species 

Cyclanilide is classified as slightly toxic to freshwater fish and invertebrates and 

estuarine/marine fish on an acute basis. Marine mollusk endpoint were more sensitive 

than mysid shrimp endpoints and therefore cyclanilide is classified as moderately toxic to 

marine/estuarine invertebrates on an acute basis. 

In a freshwater fish early life stage test, sublethal effects to the fathead minnow included 

statistically significant reduced total length and wet weight in the two highest treatment 

levels (5 and 10 ppm). There were no sings of toxicity observed during the course of the 

freshwater invertebrate life cycle test. There was no submitted study for chronic effect to 

a marine/estuarine fish species or a chronic study for marine/estuarine invertebrates. 

Terrestrial and Aquatic Plants 

A seedling emergence/vegetative vigor study was submitted in support of cyclanilide 

(MRID 43868318) in 1995 that was classified a supplemental for all species for the 

seedling emergence but unacceptable for all species for the vegetative vigor. The 

seedling emergence data was classified as supplemental due to the phytotoxic effects 

observations data being unusable as the phytotoxic effects were not rated. Furthermore, 
13 

the study failed to determine an NOAEL for phytotoxic observations for several of the 

test species. For the vegetative vigor study, a spray volume of approximately 1000 

gallons per acre was used which is much greater than the spray volume recommended for 

the label as well as the fact that much of the volume would run off into the soil. These 

studies were also conducted using technical grade cyclanilide. 40 CFR Part 158 

recommends Tier I and II terrestrial plant studies conducted with a typical end use (TEP) 

product. 

A seedling emergence (MRID 43868323) was submitted in 1995 in support of cyclanilide 

as the typical end use product FINISH® Harvest Aid. There was no accompanying 

vegetative vigor study. The study was classified as supplemental for all species due to 

the absence of a defined rating system when making phytotoxic observations. This was 

exemplified by cucumber in which the lowest three doses showed significant reductions 

and therefore endpoints could not be statistically calculated. Similarly in lettuce, since 

chlorosis was observed in a significant number of plants at all treatment levels, a NOAEL 

could not be determined. Data for cucumber and lettuce could therefore not be upgraded 

to acceptable status even if observations on phytotoxicity were provided. The most 

sensitive endpoints observed in this species were not as sensitive as the previously 

submitted study MRID 43868318. 

Previous assessments for cyclanilide did not account for a third set of seedling 

emergence/vegetative vigor studies being submitted in 1998 (MRID 44518602) which 

tested the TEP of cyclanilide on two species (lettuce and cucumber) for seedling 

emergence and all ten species for vegetative vigor. For seedling emergence, since MRID

43868323 was not able to calculate statistical endpoints for lettuce and cucumber, this 

study was submitted to provide these results. This study is currently in review. 

Cyclanilide is classified as highly toxic to all tested aquatic plants with the exception of 

blue-green algae for which it was very highly toxic (Table 4). 

4Table 4. Test Species Evaluated for Assessing Potential Acute and Chronic 

Ecological Effects of Cyclanilide. 

Taxonomic Group Surrogate Species 

Acute Toxicity (LC50, 

EC50, LD50, EC25) 

-- 

Chronic Toxicity 

(NOAEC, LOAEC, 

NOAEL, LOAEL) 

MRID Acute Toxicity 

Classification 

Birds1

Mallard duck (Anas 

platyrhynchos) 

LD50 = Not determined 

LC50 = 1740 ppm 

-- 

No Data 

43368413 

43368415 

-- 

No Data 

-- 

Slightly toxic 

-- 

Northern bobwhite 

quail (Colinus 

virginianus) 

LD50 = 240 ppm 

LC50 = 2580 ppm 

-- 

No Data 

43368414 

43368416 

-- 

No Data 

Moderately toxic 

Slightly toxic 

-- 
14 

Taxonomic Group Surrogate Species 

Acute Toxicity (LC50, 

EC50, LD50, EC25) 

-- 

Chronic Toxicity 

(NOAEC, LOAEC, 

NOAEL, LOAEL) 

MRID Acute Toxicity 

Classification 

Mammals Laboratory rat (Rattus 

norvegicus) 

LD50 = 208 mg/kg bw 

-- 

NOAEL = 30 ppm 

LOAEL = 300 ppm 

43368424 

43868313, 

44073701 

Moderately toxic 

-- 

Insects Honey bee (Apis 

mellifera) 

LD50 (contact) = > 100 

ug/a.i/bee 43868324 Practically nontoxic 

Freshwater Fish2

Rainbow trout 

(Oncorhynchus 

mykiss) 

96-hour LC50 = > 11 

mg/L 43368417 Slightly toxic 

Bluegill sunfish 

(Lepomis 

macrochirus) 

96-hour LC50 = > 16 

mg/L 43368418 Slightly toxic 

Fathead minnow NOAEC = 1.2 ppm 

LOAEC = 2.6 ppm 43868309 -- 

Freshwater 

invertebrates 

Water Flea (Daphnia 

magna) 

48-hour EC50 = >13 

ppm 

-- 

NOAEC = 12.6 ppm 

LOAEC = >12.6 

43368419 

43876701 

Slightly toxic 

-- 

Estuarine/marine 

fish 

Sheepshead minnow 

(Cyprinodon 

variegatus) 

96-hour LC50 = 49 ppm 

-- 

No Data submitted 

43368422 

No data 

Slightly toxic 

-- 

Estuarine/marine 

invertebrates 

Mysid shrimp 

(Americamyis bahia) 96-hour EC50 = 5 ppm 43368421 Moderately toxic 

Eastern oyster 

(Crassotrea virginica) 96-hour EC50 = 19 ppm 43368420 Slightly toxic 

Terrestrial plants Multiple species 

Seedling Emergence3

: 

Monocot EC25 – 

>0.25lb a.i/A 

Monocot NOAEL -

0.0074 lb a.i/A 

Dicot EC25 – 0.017 lb 

a.i/A 

Dicot EC054

 -0.0011 lb 

a.i/A 

Vegetative Vigor – 

Unacceptable study 

43868318 -- 

Multiple Species Study in review 44518602 -- 

Aquatic plants 

Vascular Plant: 

Duckweed (Lemna 

gibba) 

Tier II: EC50 = >0.22 

ppm 

-- 

NOAEC = 0.2 ppm 

43868321 -- 

Non-vascular plants: 

Marine Diatom 

(Skeletonema 

costatum) 

Tier II: EC50 = >0.27 

ppm 

-- 

NOAEC = 0.13 ppm 

43868322 -- 

Blue-green algae Tier II: EC50 = 0.080 43868320 -- 
15 

Taxonomic Group Surrogate Species 

Acute Toxicity (LC50, 

EC50, LD50, EC25) 

-- 

Chronic Toxicity 

(NOAEC, LOAEC, 

NOAEL, LOAEL) 

MRID Acute Toxicity 

Classification 

(Anabaena flosaquae) ppm 

-- 

NOAEC = 0.030 ppm 

Freshwater diatom 

(Navicula pelliculosa) 

Tier II: EC50 = >0.17 

ppm 

-- 

NOAEC = 0.023 ppm 

43868319 -- 

Green Algae 

(Selenastrum 

capricoruntum) 

Tier II: EC50 = 1.0 ppm 

-- 

NOAEC = 0.0097 ppm 

43368450 -- 

1

Birds represent surrogates for terrestrial-phase amphibians and reptiles 

2

Freshwater fish represent surrogates for aquatic-phase amphibians 3

The endpoints listed are endpoints other than phytotoxic observations. Phytotoxic observations were the 

most sensitive endpoints but did not yield valid results. 

4

The EC05 may be used in lieu of a NOAEL if the NOAEL is higher than the EC25

4.2 Incident Database Review 

A preliminary review on September 29, 2010 of the Ecological Incident Information 

System (EIIS, Version, 2.1) which is maintained by the Agency’s Office of Pesticide 

Programs, and the Avian Monitoring Information System (AIMS), which is maintained 

by the American Bird Conservancy, indicated no reported ecological incident associated 

with the use of cyclanilide. 

Although no incidents have been reported to the Agency, the absence of reported 

incidents should not be construed as the absence of incidents. Incident reports for nontarget organisms typically provide information only on mortality events and plant damage

incidents. Except for phytotoxic effects in terrestrial plants, sublethal effects for

organisms such as reduced growth or impaired reproduction are rarely reported. EPA’s 

changes in the registrant reporting requirements for incidents in 1998 may account for a 

reduced number of reported incidents. Registrants are now only required to submit 

detailed information on “major,” fish, wildlife and plant incidents. Minor fish, wildlife, 

and plant incidents, as well as all other non-target incidents, are generally reported 

aggregately and are not included in EIIS. In addition, there have been changes in state 

monitoring effects due to a lack of resources. 

4.3 Ecosystems Potentially at Risk 

The ecosystems at risk are often extensive in scope, and as a result it may not be possible 

to identify specific ecosystems during the development of a baseline risk assessment. 

However, in general terms, terrestrial ecosystems potentially at risk could include the 

treated field and areas immediately adjacent to the treated field that may receive drift or 

runoff. Areas adjacent to the treated field could include cultivated fields, fencerows and 
16 

hedgerows, meadows, fallow fields or grasslands, woodlands, riparian habitats and other 

uncultivated areas. 

Aquatic ecosystems potentially at risk include water bodies adjacent to, or down stream 

from, the treated field and might include impounded bodies such as ponds, lakes and 

reservoirs, or flowing waterways such as streams or rivers. For uses in coastal areas, 

aquatic habitat also includes marine ecosystems, including estuaries. 

Cyclanilide is registered for use on cotton, ornamentals, non-bearing fruit nursery trees, 

and cut flowers. While the main harvest area for cotton is limited to the southeastern 

United States, locations for the other uses of cyclanilide are more widespread. 

4.4 Assessment Endpoints 

Assessment endpoints represent the actual environmental value that is to be protected, 

defined by an ecological entity (species, community, or other entity) and its attribute or 

characteristics (EPA, 1998). For cyclanilide, the ecological entities may include the 

following: birds, mammals, freshwater fish and invertebrates, estuarine/marine fish and 

invertebrates, terrestrial plants, insects, and aquatic plants and algae. The attributes for 

each of these entities may include growth, reproduction, and survival. 

4.5 Conceptual Model 

For a pesticide to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. An exposure pathway is the means by which a 

pesticide moves in the environment from a source to an ecological receptor. For an 

ecological pathway to be complete, it must have a source, a release mechanism, an 

environmental transport medium, a point of exposure for ecological receptors, and a 

feasible route of exposure. 

The conceptual model for cyclanilide provides a written description and visual 

representation of the predicted relationships between cyclanilide, potential routes of 

exposure, and the predicted effects for the assessment endpoint. According to EPA’s 

ecological risk assessment guidelines (U.S EPA, 1998) a conceptual model consist of two 

major components: a risk hypothesis and a conceptual diagram. 

Risk Hypothesis 

A risk hypothesis describes the predicted relationship among the stressor, exposure, and 

assessment endpoint response along with the rationale for their selection. For cyclanilide, 

the following ecological risk hypothesis is being employed for this national-level risk 

assessment: 

Cyclanilide, when used in accordance with registered labels, will likely lead to 

off-site movement of the compound via runoff, spray drift, and eroded soil leading 

to exposure of non-target plants and animals. Based on information on 

environmental fate, mode of action, direct toxicity, and potential indirect effect, 
17 

EFED assumes that registered uses of cyclanilide have the potential to cause 

reduced survival, growth, and reproduction to non-target terrestrial and/or 

aquatic animals and plants. 

Conceptual Diagram 

The conceptual site model is a generic graphic depiction of the risk hypothesis, and 

assumes that cyclanilide, having outdoor uses only, is capable of affecting aquatic and 

terrestrial animals provided that environmental concentrations are sufficiently elevated as 

a result of proposed label uses. Based on an examination the physicochemical properties 

of cyclanilide, the fate and disposition n in the environment, and mode of application, a 

conceptual model was developed that represents the possible relationships between the 

stressors, ecological receptors, and he assessment endpoints. Through a preliminary 

iterative process of examining available data, the conceptual model (i.e., the 

representation of the risk hypothesis) may be refined to reflect the likely exposure 

pathways and the organisms that are the most relevant and applicable to this assessment. 

It includes the potential pesticide or stressor (cyclanilide), the sources and/or transport 

pathways, exposure media, exposure points, biological receptor types, and attributes 

changes. The conceptual model depicted in Figures 3 and 4, is similarly applicable to 

the urban outdoor uses of cyclanilide. 

In order for a chemical to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. Exposure pathway is the means by which a 

pesticide movies in the environment from a source to an ecological receptor. For an 

ecological exposure pathway to be complete, it must have a source, a release mechanism, 

an environmental transport medium, a point of exposure for ecological receptors, and a 

feasible route of exposure. In addition, the potential mechanisms of degradation/ 

transformation (i.e. which degradation/transformation products may form in the 

environment, in which media, and how much) must be understood, especially if for the 

chemical, its metabolites/transformation products are of greater toxicological concern

than the parent compound. The assessment of ecological exposure pathways, therefore, 

includes an examination of the source and potential migration pathways for constituents, 

and the determination of potential exposure routes. 
18 

3Figure 3. A conceptual model for cyclanilide effects on aquatic organisms. 

Stressor 

Source

Receptors 

Attribute 

Change 

Cyclanilide applied to use site and resultant main degradate 2,4 dichloroaniline 

Spray drift 

Fish/aquatic-phase 

amphibians 

Eggs 

Larvae 

Juveniles / Adults 

Individual organisms 

Reduced survival 

Reduced growth 

Reduced reproduction 

Food chain 

Reduction in algae 

Reduction in prey 

Habitat integrity 

Reduction in primary productivity

Reduced cover 

Community change 

Surface water/ 

Sediment 

Runoff 

Aquatic Animals 

Invertebrates 

Vertebrates 

Exposure 

Media 

Uptake/gills 

or integument 

Ingestion Ingestion

Soil Ground water 

Uptake/gills 

or integument 

Aquatic Plants 

Non-vascular 

Vascular 

Uptake/cell, 

roots, leaves Riparian plant

terrestrial 

exposure 

pathways see 

Figure 2 
19 

4Figure 4. A conceptual model of cyclanilide effects on terrestrial organisms

5. Analysis Plan 

In order to address the risk hypothesis, the potential for adverse effect on the environment 

is estimated. The use, environmental fate, and ecological effects of cyclanilide are 

characterized and integrated to assess the risks. This is accomplished using a risk 

quotient (ratio of exposure concentration to effect concentration) approach. Although 

risk is often defined as the likelihood and magnitude of adverse ecological effects, the 

risk-quotient based approach does not provide a quantitative estimate of likelihood and/or 

magnitude of an adverse effect. However, as outlined in the Overview Document (U.S 

EPA, 2004), the likelihood of effects to individual organisms from particular uses of 

cyclanilide is estimated using the probit-dose response slope and either the level of 

concern (discussed below) or actual calculated risk quotient value. 

This analysis plan will be revisited and may be revised depending on the information 

submitted by the public in response to the opening of the Registration Review docket for 

cyclanilide. 

Stressor 

Source

Receptors 

Attribute 

Change 

Cyclanilide applied to use site and resultant main degradate 2,4 dichloroaniline

Direct 

Application Spray drift 

Birds / Terrestrialphase amphibians 

/ reptiles / 

mammals 

Terrestrial 

Insects 

Individual organisms 

Reduced survival 

Reduced growth 

Reduced reproduction 

Food chain 

Reduction in prey 

Habitat integrity 

Reduction in primary productivity

Reduced cover 

Community change 

Terrestrial/riparian plants 

grasses/forbs, fruit, seeds 

(trees, shrubs) 

Runoff 

Mammals 

Exposure 

Media 

Soil 

Ingestion 

Ingestion

Ingestion

Ingestion

Dermal uptake/Ingestion 

Root uptake 

Terrestrial food 

web 

Ingestion 
20 

5.1 Stressors of Concern 

The stressor of concern for this assessment will include parent compound (cyclanilide) 

and its main degradate 2,4 dichloroaniline. 

5.2 Measures of Exposure 

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

all exposure modeling and resulting risk conclusions will be based on maximum 

application rates for a given use. Measures of exposure are based on aquatic and 

terrestrial models that predict estimated environmental concentrations (EECs) of 

cyclanilide. The models that will be used to predict aquatic EECs are the Pesticide Root 

Zone Model coupled with the Exposure Analysis Model System (PRZM/EXAMS). The 

model used to predict terrestrial EECs on food items is T-REX. The model to derive 

EECs relevant to terrestrial and wetland plants is TerrPlant. These models are 

parameterized using relevant reviewed registrant-submitted environmental fate data. 

Although the log Kow for cyclanilide indicates that the chemical might have the potential 

to bioaccumulate, fish bioaccumulation studies confirmed that cyclanilide is mostly 

metabolized and that actual bioaccumulation in fish is low. EFED currently does not 

plan to investigate the risk from bioaccumulation further. 

Exposure estimates for terrestrial animals assumed to be in the target area or in an area 

exposed to spray drift are derived using the T-REX model (version 1.3.1, 12/07/2006). 

This model incorporates the Kenega nomograph, as modified by Fletcher et al. (1994), 

which is based on a large set of actual field residue data. The upper limit values from the 

nomograph represented the 95th percentile of residue values from actual field 

measurements (Hoerger and Kenega, 1972). The Fletcher et al. (1994) modifications to 

the Kenega nomograph are based on measured field residues from 249 published research 

papers, including information on 118 species of plants, 121 pesticides, and 17 chemical 

classes. EECs for terrestrial plants inhabiting dry and wetland areas are derived using 

TerrPlant (version 1.2.2, 12/26/2006). This model uses estimates of pesticides in runoff 

and in spray drift to calculate EECs. EECs are based upon solubility, application rate and 

minimum incorporation depth. 

5.3 Measures of Effect 

Ecological effect data are used as measures of direct and indirect effects to biological 

receptors. Data were obtained from registrant-submitted studies or from literature studies 

identified by ECOTOX. The ECOTOXicology database (ECOTOX) was searched on 

May 1, 2008 in order to provide more ecological effects data to bridge existing data gaps. 

ECOTOX is a source for locating single chemical toxicity data and potentially chemical 

mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was 

created and is maintained by the USEPA, Office of Research and Development, and the 

National Health and Environmental Effects Research Laboratory's Mid-Continent 

Ecology Division (ECOTOX, 2006). 
21 

Information on the potential effects of cyclanilide on non-target animals is also collected 

from the Ecological Incident Information System (EIIS; USEPA 2007c). The EIIS is a 

database containing adverse effect (typically mortality) reports on non-target organisms 

where such effects have been associated with the use of pesticides. Where available,

sublethal effects observed in both registrant-submitted and open literature studies will be 

evaluated qualitatively. Such effects have included behavioral changes (e.g., lethargy, 

changes in coloration and effects olfaction). Quantitative assessments of risks, though, 

are limited to those endpoints that can be directly linked to the Agency’s assessment 

endpoints of impaired survival, growth and reproduction. 

The assessment of risk for direct effects to non-target organisms makes the assumption 

that toxicity of cyclanilide to birds is similar to terrestrial-phase amphibians and reptiles. 

The same assumption is made for fish and aquatic-phase amphibians. 

The acute measures of effect used for animals in this screening-level assessment are the 

LD50, LC50 and EC50. LD stands for "Lethal Dose", and LD50 is the amount of a material, 

given all at once, that is estimated to cause the death of 50% of the test organisms. LC 

stands for “Lethal Concentration” and LC50 is the concentration of a chemical that is 

estimated to kill 50% of the test organisms. EC stands for “Effective Concentration” and 

the EC50 is the concentration of a chemical that is estimated to produce a specific effect in 

50% of the test organisms. Endpoints for chronic measures of exposure for listed and 

non-listed animals are the NOAEL/NOAEC and NOEC. NOAEL stands for “No 

Observed-Adverse-Effect-Level” and refers to the highest tested dose of a substance that 

has been reported to have no harmful (adverse) effects on test organisms. The NOAEC 

(i.e., “No-Observed-Adverse-Effect-Concentration”) is the highest test concentration at 

which none of the observed effects were statistically different from the control. The 

NOEC is the No-Observed-Effects-Concentration. For non-listed plants, only acute 

exposures are assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants); for 

listed plants, either the NOAEC or EC05 is used. 

5Table 5. Measures of Ecological Effects and Exposure for Cyclanilide
22 

Assessment Endpoint Surrogate Species and 

Measures of Ecological Effect1 

Measures of Exposure 

Birds2 Survival Bobwhite acute oral LD50

Bobwhite and mallard subacute 

dietary LC50

Maximum residues on food 

items (foliar) 

Reproduction and growth Bobwhite and mallard chronic 

reproduction NOAEC and 

LOAEC (no studies 

available) 

Mammals Survival Laboratory rat acute oral LD50

Reproduction and growth Laboratory rat oral reproduction 

chronic NOAEC and 

LOAEC 

Freshwater fish3 Survival Rainbow trout and bluegill 

sunfish acute LC50 (no 

valid study available) 

Peak EEC4 

Reproduction and growth Fathead minnow 

chronic (early life-stage) 

NOAEC and LOAEC 

60-day average EEC4

Freshwater invertebrates Survival Water flea (and other freshwater 

invertebrates) acute EC50 

Peak EEC4 

Reproduction and growth Water flea chronic (life cycle) 

LOAEC 

21-day average EEC4

Estuarine/marine fish Survival Sheepshead minnow acute LC50

(no study available)

Peak EEC4 

Reproduction and growth Sheepshead minnow chronic 

(early life-stage) NOAEC 

and LOAEC 

60-day average EEC4

Estuarine/marine 

invertebrates 

Survival Eastern oyster acute EC50 and 

mysid acute LC50

Peak EEC4 

Reproduction and growth Mysid chronic NOAEC and 

LOAEC 

21-day average EEC4

Terrestrial plants5 Survival and growth Monocot and dicot seedling 

emergence and vegetative 

vigor EC25, EC05, and 

NOAEC values

Estimates of runoff and spray 

drift to non-target areas 

Insects Survival (not 

quantitatively assessed) 

Honeybee acute contact LD50 (no 

study available)

Maximum application rate 

Aquatic plants and algae Survival and growth Algal and vascular plant (i.e., 

duckweed) EC50 and 

NOAEC values for growth 

rate and biomass 

measurements

Peak EEC 

1 If species listed in this table represent most commonly encountered species from registrant-submitted studies, risk 

assessment guidance indicates most sensitive species tested within taxonomic group are to be used for baseline risk 

assessments. 

2 Birds represent surrogates for amphibians (terrestrial phase) and reptiles. 
23 

3 Freshwater fish may be surrogates for amphibians (aquatic phase). 4 One in 10-year return frequency. 

5 Four species of two families of monocots - one is corn, six species of at least four dicot families, of which one is 

soybeans. LD50 = Lethal dose to 50% of the test population; NOAEC = No observed adverse effect concentration; 

LOAEC = Lowest observed adverse effect concentration; LC50 = Lethal concentration to 50% of the test population; 

EC50/EC25 = Effect concentration to 50%/25% of the test population.

5.4 Integration of Exposure and Effects 

Risk characterization is the integration of exposure and ecological effects characterization 

to determine the potential ecological risk from the use of pesticides and the likelihood of 

direct and indirect effects to non-target organisms in aquatic and terrestrial habitats. The 

exposure and toxicity effects data are integrated in order to evaluate the risks of adverse 

ecological effects on non-target species. For the assessment of risks, the risk quotient 

(RQ) method is used to compare exposure and measured toxicity values. EECs are 

divided by acute and chronic toxicity values. The resulting RQs are then compared to the 

Agency’s Levels of Concerns (LOCs) (U.S EPA, 2004). These criteria will be used to 

indicate when cyclanilide’s uses, as directed o the label, have the potential to cause 

adverse direct or indirect effects to non-target organisms. In addition, incident data from 

the EIIS will be considered as part of the risk characterization. 

 5.5 Endangered Species Assessments 

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), 

the Agency will evaluate risks to Federally-listed threatened and/or endangered (listed) 

species from registered uses of cyclanilide. This assessment will be conducted in 

accordance with the Overview Document (USEPA 2004), provisions of the ESA, and the 

Services’ Endangered Species Consultation Handbook (USFWS/NMFS, 1998). 

The assessment of effects associated with the registration of cyclanilide is based on an 

action area. The action area is considered to be the area directly or indirectly affected by 

the federal action, as indicated by the exceedance of Agency Levels of Concern (LOCs) 

used to evaluate direct or indirect effects. The Agency’s approach to defining the action 

area under the provisions of the Overview Document (USEPA 2004) considers the results 

of the risk assessment process to establish boundaries for that action area with the 

understanding that exposures below the Agency’s defined LOCs constitute a no-effect 

threshold. For the purposes of this assessment, attention will be focused on the footprint 

of the action (i.e., the area where cyclanilide application occurs), plus all areas where 

offsite transport may result in potential exposure that exceeds the Agency’s LOCs. 

Specific measures of ecological effect that define the action area for listed species include 

any direct and indirect effects and/ or potential modification of its critical habitat, 

including reduction in survival, growth, and reproduction as well as the full suite of sublethal effects available in the effects literature. Therefore, the action area extends to a 

point where environmental exposures are below any measured lethal or sub-lethal effect 

threshold for any biological entity at the whole organism, organ, tissue, and/ or cellular 

level of organization. In situations where it is not possible to determine the threshold for 

an observed effect, the action area is not spatially limited and is assumed to be the entire
24 

United States. 

5.6 Monitoring Data 

The USGS NAWQA6

 databases were searched, and no monitoring data on the

concentration of cyclanilide in surface water, groundwater, or sediment were found at the 

present time. It appears that cyclanilide was not included in the USGS NAWQA list of 

analytes.

 5.7 Clean Water Act 

Cyclanilide is not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_grou

p_id=885. In addition, no Total Maximum Daily Loads (TMDL) has been developed for 

cyclanilide, based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_gr

oup_id=885&p_pollutant_group_name=PESTICIDES. More information on impaired 

water bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/. 

The Agency invites submission of water quality data for this pesticide. To the extent 

possible, data should conform to the quality standards in Appendix A of the OPP 

Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water 

Quality Data in OPP’s Registration Review Risk Assessment and Management Process

(see: http://www.epa.gov/oppfead1/cb/ppdc/2006/november06/session1-sop.pdf), in 

order to ensure they can be used quantitatively or qualitatively in pesticide risk 

assessments. 

5.8 Endocrine Disrupter Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential 

adverse outcomes from exposure to chemicals. Collectively, these studies include acute, 

subchronic and chronic toxicity, including assessments of 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, estrous 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 its reregistration decision, EPA reviewed these data and selected the most sensitive 

endpoints for relevant risk assessment scenarios from the existing hazard database. 

However, as required by FFDCA section 408(p), cyclanilide is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

 

6 http://infotrek.er.usgs.gov/nawqa_queries/swmaster/index.jsp (visited October, 27, 2010) 
25 

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. 

Cyclanilide is not among the group of 58 pesticide active ingredients on the initial list to 

be screened under the EDSP. Accordingly, as part of registration review, EPA will issue 

future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for

cyclanilide. 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/. 

5.9 Uncertainty and Preliminary Identification of Data Gaps 

Environmental Fate & Transport 

Two previous assessments were executed for cyclanilide and no fate and transport data 

gaps or uncertainties were identified except for the terrestrial field dissipation data 

(TFD). The latter study was classified as up-gradable by submission of the complete 

report on storage stability. Such report appear not be submitted as of to date. 

The list of studies that were submitted is included previously in Table 3. Based on 

examination of the available data and its quality, EFED recommends the following:

- Submittal of the complete report on storage stability and required data to upgrade the 

already submitted terrestrial field dissipation studies (MRIDs 440134-01 and 

438683-33. 

- Submittal of two new aerobic soil studies (Guideline No. 835.4100) in which 

representative soils are used, degradation profile is determined (all degradates 

included), and extraction procedure is appropriate (able to extract bound residue or 

bound residue is identified when >10%) 

- Upgrade previously submitted environmental chemistry method (MRID 438683-34; 

Guideline No. 835.6100) for determination of cyclanilide in soils possibly by 
26 

modifying the method to be a state-of- the-art with appropriate LOQ. In addition an 

independent laboratory validation (ILV) is required as per guideline. Validation is to 

be performed by an independent laboratory as per the guideline. Submitted validation 

study (MRID 438683-31) appears to be conducted by the registrant. 

- Submit a new state-of-the art environmental chemistry method (ECM) for 

determination of cyclanilide in water with an appropriate LOQ and an independent 

laboratory validation (ILV) as per the ECM/ILV Guideline No. 835.6200.

Effects 

Uncertainties and data gaps from previous assessment include a lack of avian 

reproduction studies to characterize chronic risk to birds, no early life stage test for an 

estuarine/marine fish spices, and no chronic life cycle test for an estuarine/marine 

invertebrate species. 

Additionally, the previous seedling emergence study (MRID 43868323), was classified 

Supplemental for all species due to the severity of phytotoxic observations being not 

measured with a defined rating system. Furthermore, for lettuce and cucumber, the EC25

and NOAEL could not be established due to significant reductions in all treatment groups 

precluded the ability to statistically determine these endpoints. A new seedling 

emergence study for lettuce and cucumber and vegetative vigor study for all ten species 

(MRID 44518602) was submitted, reviewed, and is classified as acceptable. This data 

now makes it possible to estimate risk to terrestrial plants. 

The primary degradate of concern, 2,4 dichloroaniline, was identified in both aerobic soil 

metabolism studies submitted reaching consistent levels of 7-11%. The un-extractable 

residues for one of the submitted studies reach 30%, creating uncertainty in exactly how 

much of the parent or degradate remains after the study. The degradate of concern was 

shown to be very persistent as maximum concentrations reached 16% at day-30 but 

remained at detectable levels throughout the 180-day study. 

There are no submitted ecotoxicity studies in with 2,4 dichloroaniline. Toxicity to 

aquatic taxa can be estimated using the EPI WEB v 4 ECOSAR tool which provides 

structure activity relationship estimates. For fish (freshwater and marine/estuarine), the 

tool predicts a 96-h LC50 of 61 mg/L. This is a less toxic value than acute studies 

submitted for cyclanilide for freshwater and estuarine/marine fish (LC50s of >11 mg/L 

and 49 mg/L, respectively). The predicted 48-hour LC50 for Daphnia magna representing 

freshwater invertebrate is 37 mg/L which is less toxic than the LC50 of >13 mg/L value 

for Daphnia magna from exposure to cyclanilide. The green algae predicted 96-hour 

EC50 value was 19 mg/L which is less toxic than the >0.22 mg/L EC50 for the most 

sensitive aquatic plant study submitted for cyclanilide (duckweed). Predicted chronic 

values for fish, Daphnia magna, and green algae are 5.7, 3.6, and 7.2, respectively. The 

value for fish is less toxic than that of the study submitted for cyclanilide (only a 

freshwater fish study was submitted), yet this was a more toxic value than the life cycle 

study submitted for freshwater invertebrates with cyclanilide. 
27 

Although there are uncertainties with these values, as well as these values not 

distinguishing between fish in freshwater and marine/estuarine environments, they 

provide an indication that the 2,4 dichloroaniline is less toxic to aquatic organisms than 

parent cyclanilide. Again, there is uncertainty with this statement, and the only way to be 

sure of the toxicity of 2,4 dichloroaniline and the characterization of sublethal effects to 

aquatic taxa would be a submission of ecotoxicity studies, but the Agency feels at this 

time that these studies are not warranted, especially since the residues of the primary 

degradate in the aerobic metabolism studies is somewhat uncertain and will be until a 

new study is submitted. 

Regarding toxicity to terrestrial taxa, the ECOSAR tool only predicts toxicity endpoints 

for aquatic organisms. It is unclear if the primary degradate, 2,4 dichloroaniline would 

pose a greater toxic risk to birds, small mammals, and terrestrial invertebrates, however 

for the same reasons listed as above with the aquatic taxa, the Agency at this time is not 

requesting terrestrial ecotoxicity studies with 2,4 dichloroaniline. 

For registration review, the following studies are being requested to fulfill any data gaps: 

Guideline Number: 850.2100 – Passerine Acute Avian Oral 

Although two acute avian oral studies were received for the mallard duck and bobwhite 

quail, the Agency updated its data requirements in 40 CFR Part 158 (October 26, 2007) 

to include an acute oral toxicity study for both a passerine species and either a waterfowl 

or an upland game species. Furthermore, an LD50 was not achieved in the mallard acute 

oral study due to regurgitation issues. Prior to starting toxicity testing, a protocol will 

need to be provided for review. It is likely that, for most pesticide use patterns, 

passerines are more likely to be exposed than upland games species and waterfowl. 

Passerines are smaller and have faster metabolisms than the species commonly used in 

acute oral testing for birds which could impact their sensitivity to chemicals. 

Guideline Number: 850.1400 – Fish Early Life Stage (saltwater) 

Cyclanilide has the potential to enter estuarine/marine water bodies based on its current 

use patterns that have proximity to coastal areas in the southeastern United States. Use 

patterns for cyclanilide include heavy uses along the Mississippi River which, from spray 

drift or runoff, have the potential to enter estuarine/marine environments. Furthermore, 

hydrolysis studies have shown cyclanilide to persist in water for more than 50 days 

(significantly more than the cutoff outlined in 40 CFR Part 158 of this study being 

required when the half life is greater than or equal to 4 days.) 

Guidelines Number 850.1350 – Aquatic Invertebrate Life-Cycle (saltwater) 

The acute toxicity of cyclanilide to estuarine/marine invertebrates indicates the potential 

for chronic risk, especially since the potential for chronic exposure exists. Cyclanilide 

has the potential to enter estuarine/marine water bodies based on its current use patterns 

that have proximity to coastal areas in the southeastern United States. Use patterns for 

cyclanilide include heavy uses along the Mississippi River which, from spray drift or 

runoff, have the potential to enter estuarine/marine environments. 
28 

Table 6 lists the status of the ecological effects data requirements for cyclanilide. 

 6 Table 6. Ecological Effects Data Requirements for Cyclanilide 

Guideline Data Requirement Test Species MRID 

Preliminary 

Study 

Classification 

More Data 

Needed for 

Risk 

Assessment? 

71-1 

(850.2100) Avian Oral LD50 

Mallard duck 

Bobwhite 

quail 

Passerine 

species 

43368413 

43368414 

No Data 

Supplemental 

Acceptable 

No Data 

No 

No 

Yes1

71-2 

(850.2100) Avian Dietary LC50 

Mallard duck 

Bobwhite 

quail 

43368415 

43368416 

Acceptable 

Acceptable 

No 

71-4 

(850.2300) Avian Reproduction 

Mallard duck 

Bobwhite 

quail 

No data 

No data 

No data 

No data 

Yes 

72-1 

(850.1075) 

Freshwater Fish 

LC50

Rainbow 

trout 

Bluegill 

sunfish 

43368417 

43368418 

Supplemental 

Supplemental 

No 

72-2 

(850.1010) 

Freshwater 

Invertebrate Acute 

LC50

Water flea 43368419 Supplemental No 

72-3(a) 

(850.1075) 

Estuarine/Marine 

Fish LC50

Sheepshead 

minnow 43368422 Acceptable No 

72-3(b) 

(850.1025 or 

850.1055) 

Estuarine/Marine 

Mollusk EC50 

Eastern 

oyster 433688420 Acceptable No 

72-3(c) 

(850.1035 or 

850.1045) 

Estuarine/Marine 

Invertebrate EC50

Mysid shrimp 43368421 Acceptable No 

72-4(a) 

(850.1400) 

Freshwater Fish 

Early Life Stage 

Fathead 

minnow 43868309 Acceptable No 

72-4(b) 

(850.1300) 

Freshwater 

Invertebrate Life 

Cycle 

Water flea 43876701 Acceptable No 

72-4(c) 

850.1350 

Estuarine/marine 

Invertebrate Life 

Cycle 

Mysid 

Shrimp No Data No Data Yes2

72-4(d) 

(850.1400) 

Estuarine/Marine 

Fish Early Life 

Stage 

Sheepshead 

minnow No Data No Data Yes2 

122-1(a) 

850.1400 

Seed germination 

test 

Multiple 

species 43868318 Acceptable No 
29 

Guideline Data Requirement Test Species MRID 

Preliminary 

Study 

Classification 

More Data 

Needed for 

Risk 

Assessment? 

122-1(b) 

(850.4100) 

Seedling Emergence 

(Tier I) 

Multiple 

species 43868318 Supplemental No 

122-1(c) 

(850.4150) 

Vegetative Vigor 

(Tier I) 

Multiple 

species 43868318 Unacceptable No 

123-1(a) 

(850.4100) 

Seedling Emergence 

(Tier II) 

Multiple 

species 

43868318 

43868323 

44518602 

Supplemental 

Supplemental 

In review 

No 

123-1(b) 

(850.4150) 

Vegetative Vigor 

(Tier II) 

Multiple 

species 44518602 Acceptable No 

122-2(a) 

(850.4400) 

Aquatic vascular 

plants (Tiers I and 

II) 

Duckweed 43868321 Acceptable No 

122-2(b) 

(850.5400) 

Aquatic 

Nonvascular (Tiers I 

and II) 

Marine 

Diatom 43868322 Acceptable 

No 

Blue-green 

algae 43868320 Acceptable 

Freshwater 

Diatom 43868319 Acceptable 

Freshwater 

algae 43368450 Acceptable 

141-1 

(850.3020) 

Honey bee acute 

contact toxicity Honey bee 43868324 Acceptable No 

 1Data are required for one passerine species and either one waterfowl or one upland game bird species. At 

this time, only an acute oral test for a game bird species has been submitted.

2

Data required based on cyclanilide use patterns near coastal and/r estuarine areas, as well as a persistence 

of water (half life ≥4 days) 
30 

Bibliography 

U.S. Environmental Protection Agency. 1998. Guidelines for Ecological Risk 

Assessment. Risk Assessment Forum, Office of Research and Development, 

Washington, D.C. EPA/630/R-95/002F. April 1998. 

U.S. Environmental Protection Agency. 2000. Risk Characterization Handbook. 

Science Policy Council, U.S. Environmental Protection Agency, Washington, 

D.C. 20460. EPA 100-B-00-002. December 2000. 

U.S. Environmental Protection Agency. 2004. Overview of the Ecological Risk 

Assessment Process in the Office of Pesticide Programs, U.S. Environmental 

Protection Agency. Endangered and Threatened Species Effects Determinations. 

Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide 

Programs, Washington, D.C. January 23, 2004. 

U.S. Environmental Protection Agency. 2005. Generic Format and Guidance for the 

Level I Screening Ecological Risk Assessments Conducted in the Environmental 

Fate and Effects Division. Office of Pesticide Programs, Washington, D.C. 

January 24, 2005. 

U. S. Environmental Protection Agency. 2007c. Ecological Incident Information System. 

http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

Environmental Fate References 

MRID 43368451. Feung, C. (1992) Hydrolysis of (carbon 14)-RPA 90946 in Aqueous 

Buffer Solutions at pH 5, 7, and 9: Lab Project Number: EC-90-129: 40913. Unpublished 

study prepared by Rhone-Poulenc Ag Co. 33 p. 

MRID 43868325. Corgier, M.; Plewa, A. (1994) (Carbon 14)-RPA 090946: 

Photodegradation in Water: Lab Project Number: 92-38: R&D/CRLD/AN/941697. 

Unpublished study prepared by Rhone-Poulenc Secteur Agro. 136 p. 

MRID 43868326. Concha, M.; Shepler, K. (1994) Photodegradation of (carbon 14)-

RPA-90946 on Soil by Natural Sunlight: Lab Project Number: 462W-1: 462W: EC-94-

255. Unpublished study prepared by PTRL West, Inc. 88 p. 

MRID 43368452. Feung, C.; Stillwell, D. (1994) Aerobic Soil Metabolism of RPA 

090946: Lab Project Number: EC-93-248: 44391. Unpublished study prepared by RhonePoulenc Ag Co. 175 p. 

MRID 43868327. Feung, C.; Stillwell, D. (1995) RPA 090946: Rate of Degradation in 

Soil Under Aerobic Conditions: Lab Project Number: EC-94-280. Unpublished study 

prepared by Rhone-Poulenc Ag Co. and Agvise Labs. 156 p. 
31 

MRID 43868328. Concha, M.; Shepler, K. (1995) Anaerobic Aquatic Metabolism of 

(carbon 14)-RPA-90946: Amended Report: Lab Project Number: 461W-1: 461W: EC94-254. Unpublished study prepared by PTRL West, Inc. 110 p. 

MRID 43868320. Concha, M. and K. Shepler (1995) Anaerobic Aquatic Metabolism of 

14C-RPA-90946. Laboratory Project No. EC 94-254. Unpublished Study Performed by 

PTRL West, Richmond, CA and Submitted by Rhone Poulenc Ag Co. RTP. NC 

(43868320, citation same as above). 

MRID 43368453. Mislanker, S.; Estes, T. (1994) Adsorption/Desorption of (carbon 14)-

RPA 090946: Lab Project Number: EC-94-259. Unpublished study prepared by RhonePoulenc Ag Co. 93 p. 

MRID 43368454. Mislanker, S. (1994) Aged Leaching Study of (carbon 14)-RPA 

090946: Lab Project Number: EC-94-256. Unpublished study prepared by RhonePoulenc Ag Co. 59 p. 

MRID 43868329. Feung, C.; Stilwell, D. (1995) Soil Adsorption/Desorption of 

Cyclanilide Metabolite 2,4-Dichloroaniline: Lab Project Number: EC-94-290. 

Unpublished study prepared by Rhone-Poulenc Ag Co. and Agvise Labs. 147 p. 

MRID 44526801. Mislankar, S.; Estes, T. (1994) Adsorption/Desorption of (carbon 14)-

RPA 090946: Amended Final Report: Lab Project Number: EC-94-259. Unpublished 

study prepared by Rhone-Poulenc Ag Co. 98 p. 

MRID 43868330. Chancey, E. (1995) A terrestrial soil dissipation study with cyclanilide 

(RP 90946). Rhône-Poulenc Ag Company Project Identification File Number 44805; 

Protocol and Study Number US93I02R. Unpublished study performed by South Texas 

Ag Research, Inc., Levelland, TX; and Rhône-Poulenc Ag Company: Leland, MS; 

Clayton, NC; and San Juan Bautista, CA. Laboratory analyses performed by Agvise, 

Inc., Northwood, ND, and Rhône-Poulenc Ag Company, Research Triangle Park, NC. 

Submitted by Rhône-Poulenc Ag Company, Research Triangle Park, NC. 621 p. 

MRID 43969401. Hurst, K.M. (1996). Interim report - Storage stability of cyclanilide 

residues in soil. Rhône-Poulenc Ag Company Study Number EC-95-311. Unpublished 

study performed and submitted by Rhône-Poulenc Ag Company, Research Triangle Park, 

NC. 

MRID 43368409. Cousin, J. (1993) RPA 090946 Active Ingredient: Physical and 

Chemical Characteristics: Part F Vapour Pressure: Lab Project Number: 91-48 PART F: 

R&D/CRLD/AN/9315944: 91-48. Unpublished study prepared by Rhone-Poulenc 

Secteur Agro. 44 p. 

MRID 43868333. Wyness, L. (1995) Bioconcentration of (carbon 14)-RPA 090946 in 

Lepomis macrochirus Under Flow-Through Conditions: Amended Final Report: Lab 

Project Number: 198/79: 198/79-1018. Unpublished study prepared by Corning Hazleton 
32 

(Europe). 79 p. 

MRID 44013401. Jesudason, P.; Mackie, S. (1996) Cyclanilide--Bioconcentration, 

Metabolism, and Elimination of (carbon 14) Residues by Bluegill Sunfish (Lepomis 

macrochirus): Lab Project Number: EC-95-329: 10566-0196-6386-140: 96-4-6446. 

Unpublished study prepared by Rhone-Poulenc Ag Co.; Springborn Labs, Inc.; and 

Lancaster Labs, Inc. 281 p. 

MRID 43868301. Guyton, C. (1995) Rationale for Site of (carbon 14)-Labeling of 

Cyclanilide in Environmental and Metabolism Studies: Lab Project Number: 44814. 

Unpublished study prepared by Rhone-Poulenc Ag Co. 54 p. 

MRID 43868331. Ibrahim, A. (1995) Validation of the Method of Analysis for Residues 

of RPA 90946 and its Metabolite 2,4-Dichloroaniline in Soil: Final Report: Lab Project 

Number: EC-95-302: 44854. Unpublished study prepared by Rhone-Poulenc Ag Co. 221 

p. 

MRID 43868334. Schuster, L. (1995) Method Confirmation for RPA 90946 and its 

Metabolite 2,4-Dichloroaniline in Soil: Lab Project Number: 95469: EC-95-306. 

Unpublished study prepared by ABC Labs, Pan-Ag Division. 104 p. 

Ecological Effects References 

MRID 43368413. C. A. Pendersen and A. M. Solatycki. RPA 90946: 14-day Acute 

Oral LD50 Study in Mallard Ducks. Study Completion Date: August 26, 1993. 

Laboratory: Bio-life Associates, Ltd. Rhone-Poulenc Ag Company. Laboratory Report 

ID: BLAL # 108-011-04. 

MRID 43368414. C. A. Pendersen and D. W. Fletcher. RPA 90946: 14-day Acute Oral 

LD50 Study in Bobwhite Quail. Study Completion Date: August 26, 1993. Laboratory: 

Bio-life Associates, Ltd. Sponsor: Rhone-Poulenc Ag Company. Laboratory Report ID: 

BLAL # 90 QD 150. 

MRID 43368415. Carol A. Pedersen and Ann M. Solatycki. RPA 90946: 8-Day Acute 

Dietary LC50 Studying Mallard Ducklings. Study Completion Date: June 10, 1993. 

Laboratory: Bio-Life Associates, Ltd. Sponsored by Rhone-Poulenc Ag Company 

Laboratory Report ID:BLAL NO. 108-010-02. 

MRID 43368416. Carol A. Pedersen and Ann M. Solatycki. RPA 90946: 8-Day Acute 

Dietary LC50 Study in Bobwhite Quail. Study Completion Date: June 10, 1993. 

Laboratory: Bio-Life Associates, Ltd. Sponsored by Rhone-Poulenc Ag Company. 

Laboratory Report ID: BLAL No. 108-009-01. 

MRID 43368417. Bowman, Jane and Reed Herzig. Acute Flow-Through Toxicity of 

RPA 90946to Rainbow Trout (Onchorhynchus mykiss). Study Completion Date: 
33 

September 17, 1993. Laboratory: ABC Laboratory, Inc. Sponsored by Rhone-Poulenc 

Ag Company.Laboratory Report ID: 38989. 

MRID 43368418. Bowman, Jane and Reed Herzig. Acute Flow-Through Toxicity of 

RPA 90946 to Bluegill (Lepomis macrochirus). Study Completion Date: September 17, 

1993. Laboratory: ABC Laboratories, Inc. Sponsored by: Rhone-Poulenc Ag Company

Laboratory Report ID: 38990. 

MRID 43368419. Burgess, David. Acute Flow-through Toxicity of RPA 90946 to 

Daphnia magna. Study Completion Date: September 17, 1993. Laboratory: ABC 

Laboratories, Inc. Sponsored by: Rhone-Poulenc Ag Company. Laboratory Report ID: 

38515. 

MRID 43368420. Dionne, Emily. RPA 090946 - Acute Toxicity to Eastern Oyster 

(Crassostrea virginica) under Flow-Through Conditions. Study Completion Date: June 

21, 1994. Laboratory: Springborn Laboratories, Inc. Sponsored: Rhone-Poulenc Ag 

Company. Laboratory Report ID: 94-6-5296. 

MRID 43368421. Bettencourt, Michael J. RPA 090946 - Acute Toxicity to Mysid

Shrimp (Mysidopsis bahia) Under Flow-Through Conditions. Study Completion Date: 

June 28, 1994. Laboratory: Springborn Laboratories, Inc. Sponsored by Rhone-Poulenc 

Company. Laboratory Report ID: 94-6-5311. 

MRID 43368422. Bettencourt, Michael J. RPA 090946 - Acute Toxicity to Sheepshead

Minnow (Cyprinodon variegatus) Under Flow-Through Conditions. Study Completion 

Date: July 21, 1994. Laboratory: Springborn Laboratories, Inc. Sponsored by RhonePoulenc Company. Laboratory Report ID: 94-7-5373. 

MRID 43368450. Hoberg, James R. Title: RPA 090946 - 5-day Toxicity to the 

Freshwater Green Alga, Selenastrum capricornutum. Study Completion Date: 29 March 

1994. Laboratory: Springborn Laboratories, Inc. Sponsor: Rhone-Poulenc Ag Company 

Laboratory Report ID: 94-4-5250. 

MRID 43868309. Machado, Mark W. RPA 090946 - The Toxicity to Fathead minnow 

(Pimephales promelas) during an Early Life-Stage Exposure. Study Completion Date: 

June 22, 1995. Laboratory: Springborn Laboratories, Inc., Wareham, MA. Laboratory 

Report ID: 95-5-5884. Sponsored by Rhone-Poulenc Ag Company, Sophia Antipolis, 

France. 

MRID 43868318. Hoberg, James R. RPA 090946 - Determination of Effects on Seed 

Germination, Seedling Emergence and, Vegetative Vigor of Ten plant Species. Study 

Completion Date: January 19, 1995. Laboratory: Springborn Laboratories, Inc., 

Wareham, MA. Sponsored by Rhone-Poulenc Ag Company, Research Triangle Park, 

NC. Laboratory Report ID: 94-10-5490. 
34 

MRID 43868319. Hoberg, James R. RPA 90946 - Toxicity to the Freshwater Diatom, 

Navicula pelliculosa. Study Completion Date: July 11, 1995. Laboratory: Springborn 

Laboratories, Inc., Wareham, MA. Sponsor: Rhone-Poulenc Ag Company, Research 

Triangle Park, NC. Laboratory Report ID: 95-6-5895. 

MRID 43868320. Hoberg, James R. RPA- 090946 - Toxicity to the Freshwater - BlueGreen Alga, Anabaena flos-aquae. Study completion Date: July 11, 1995. Laboratory: 

Springborn Laboratories, Inc., Wareham, MA. Sponsored by Rhone-Poulenc Ag 

Company, Research Triangle Park, NC. Laboratory Report ID: 95-6-5883. 

MRID 4386832. Hoberg, James R. RPA 090946 - Toxicity- to Duckweed, Lemna

gibba. Study Completion Date: July 13, 1995. Laboratory: Springborn Laboratories, 

Inc., Wareham, MA. Sponsored by Rhone-Poulenc Ag Company, Research Triangle 

Park, NC. Laboratory Report ID: 95-6-5922. 

MRID 43868322. Hoberg, James R. RPA 090946. Toxicity to the Marine Diatom, 

Skeletonema costatum. Study completion Date: July 14, 1995. Laboratory: Springborn 

Laboratories., Wareham, MA. Sponsored by: Rhone-Poulenc Ag Company, Research 

Triangle Park, NC. Laboratory. Report ID: 95-6-5913. 

MRID 43868323. Hoberg, James R. EXP-31039B - Determination of Effects on 

Seedling Emergence and Vegetative Vigor of Ten Plant Species. Study Completion 

Date: July 17, 1995. Laboratory: Springborn Laboratories, Inc., Wareham, MA. 

Sponsored by Rhone-Poulenc Ag Company, Research Triangle Park, NC. Laboratory 

Report ID: 95-5-5867.

MRID 43868324. Petto, Ralf. Laboratory Testing for Toxicity (Acute Contact and Oral 

LD50) of RPA 090946 to Honeybees (Apis mellifera L.)(Hymenoptera, Apidae). Study 

Completion Date: July 28, 1994. Laboratory: RCC Umweltchemie GmbH & Co KG, 

Rossdorf, Germany. Laboratory Report ID: 463700. Sponsored by Rhone-Poulenc 

Agro, Lyon Cedex, France. 

MRID 43876701. Mc Elligott, A.:RPA 090946 - Daphnia magna Life Cycle (21-Day 

Static Renewal) Chronic Toxicity Study. Study Completion Date: July 7, 1995. 

Laboratory: Rhone-Poulenc Agrochimie. Centre de Recherche, Sophia Antipolis, France. 

Sponsored by Rhone-Poulenc Ag Company. Research Triangle Park, NC. Laboratory 

Report ID: SA 95206. 

MRID 44518602. Teixeira, D. EXP-31039C - Determination of Effects on Seedling 

Emergence of Two Plant Species and Vegetative Vigor of Ten Plant species. Study 

Completion Date: March 10, 1998. Laboratory: Springborn Laboratories, Inc., Wareham, 

MA. Sponsored Rhone-Poulenc Ag Company, Research Triangle Park, NC. Laboratory 

Report ID: 97-12-7199.
35 

Appendix A. PRD Data Request Justification Tables 

(1) Ecological Data 

Guideline Number: 850.2100 

Study Title: Passerine Acute Avian Oral 

Rationale for Requiring the Data 

Although an acute avian oral study was received for the bobwhite quail, the Agency updated its 

data requirements in 40 CFR Part 158 (October 26, 2007) to include an acute oral toxicity study 

for both a passerine species and either a waterfowl or an upland game species. Furthermore, the 

submitted mallard acute oral study did not achieve an LD50 due to regurgitation issues. Prior to 

starting toxicity testing, a protocol will need to be provided for review. 

o Many passerine species utilize agricultural fields, forests, residential areas 

and surrounding areas, and, therefore, have the potential to be exposed to 

pesticides used in agricultural, forest, and residential settings 

 It is likely that, for most pesticide use patterns, passerines are more 

likely to be exposed to pesticides than upland game species and 

waterfowl 

o Passerines are smaller and have faster metabolisms than the waterfowl and 

upland game bird species traditionally used in avian toxicity tests which 

could impact their sensitivity to chemicals. 

Practical Utility of the Data 

How did the Agency make its registration decision without these data? 

Since this is a new requirement, EPA was using the results from the toxicity tests for the upland 

gamebird species (Note: A study on a waterfowl species was submitted but did not achieve an 

LD50). 

How will the data be used? 

Data from passerine toxicity studies will be used to estimate potential risks to birds associated 

with uses of cyclanilide. The data will reduce uncertainties associated with the current risk 

assessment for passerine species and will improve our understanding of the potential effects of 

cyclanilide. 

How could the data impact the Agency’s future decision-making? 

Because birds significantly contribute to overall environmental quality, a solid understanding of 

the potential risks to birds, including passerine species, is essential for sound environmental 

management. Without acceptable data for cyclanilide, the Agency cannot determine the levels of 

cyclanilide that result in effects to passerine species. The lack of these data will limit the 

flexibility the Agency and registrants have in coming into compliance with the Endangered 

Species Act, and could result in use restrictions for cyclanilide which may otherwise be avoided, 

or which are unnecessarily severe. 
36 

Guideline Number: 850.1400 

Study Title: Fish Early Life Stage (saltwater) 

Rationale for Requiring the Data 

Cyclanilide has the potential to enter estuarine/marine water bodies based on current usage patterns that 

include coastal areas. As cotton is grown mostly in the southeastern United States and in many areas along 

the Mississippi River, the potential for cyclanilide to enter estuarine/marine water bodies via spray drift or 

run exists. Furthermore, hydrolysis studies have shown cyclanilide to persist in water for more than 50 

days which is far greater than the ≥4 days half-life requirement of necessitating the study in 40 CFR Part 

158.

Practical Utility of the Data 

How did the Agency make its re-registration decision without this data? 

Previous risk assessments noted that the extremely low (ppb) concentrations of cyclanilide in the water 

based on current use patterns yielded RQs several magnitudes of order below the chronic LOC for 

freshwater species. Chronic risk to marine/estuarine remained un-estimated. 

How will the data be used? 

The estuarine/marine fish early life stage study would allow the Agency to analyze chronic effects, 

including effects on reproductive success and growth, to estuarine/marine fish. The effects data would be 

used to determine the likelihood that the chronic risks can potentially impact aquatic communities, either 

by direct effects on fish or by indirect effects via invertebrates by reducing their food sources. 

How could the data impact the Agency’s future decision-making? 

If future endangered species risk assessments are performed without these data, the Agency would have to 

assume that cyclanilide "may affect" endangered fish directly (and endangered species from other taxa 

indirectly), and use of cyclanilide might need to be restricted in areas where endangered species could be 

exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into 

compliance with the Endangered Species Act and could result in use restrictions for cyclanilide which are 

unnecessarily severe. 

Guideline Number: 850.1350 

Study Title: Aquatic Invertebrate Life-Cycle (saltwater) 

Rationale for Requiring the Data 

The acute toxicity of cyclanilide to estuarine/marine invertebrates indicates the potential for chronic risk to 

animals in this taxon, and the potential for chronic exposure exists. Cyclanilide has the potential to enter 

estuarine/marine water bodies based on current usage patterns that include coastal areas. Furthermore, 

hydrolysis studies have shown cyclanilide to persist in water for more than 50 days which is far greater 

than the ≥4 days half-life requirement of necessitating the study in 40 CFR Part 158.

Practical Utility of the Data 

How did the Agency make its re-registration decision without this data? 

Previous risk assessments noted that the extremely low (ppb) concentrations of cyclanilide in the water 

based on current use patterns yielded RQs several magnitudes of order below the chronic LOC for 

freshwater species. Chronic risk to marine/estuarine remained un-estimated. 

How will the data be used? 

The aquatic invertebrate life-cycle study would allow the Agency to analyze chronic effects, including 

effects on reproductive success and growth, to saltwater invertebrates. The effects data would be used to 

determine the likelihood that the chronic risks can potentially impact aquatic communities, either by direct 

effects on invertebrates or by indirect effects on fish by reducing their food sources. 

How could the data impact the Agency’s future decision-making? 
37 

If future endangered species risk assessments are performed without these data, the Agency would have to 

assume that cyclanilide "may affect" endangered invertebrates directly (and endangered species from other 

taxa indirectly), and use of cyclanilide might need to be restricted in areas where endangered species could 

be exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into 

compliance with the Endangered Species Act and could result in use restrictions for cyclanilide which are 

unnecessarily severe. 

(2) Fate & Transport Data 

Guideline Number: 835.6100 

Study Title: Environmental Chemistry Method and Associated Independent Laboratory Validation 

for soil 

Rationale for Requiring the Data 

Previously submitted study needed to be upgraded for determining this chemical and major degradate in 

soils. 

Practical Utility of the Data 

How will the data be used? 

Data will be used to determine levels of cyclanilide and its major degradate in soils with high 

precision, accuracy, and appropriate detection/quantification limits. In addition, the method 

should be validated by an independent laboratory. State-of the-art and validated analytical method 

is required in order to have it available for the public to be used in determining the concentration 

of the chemical and its major degradate in soils. Also the method is to be used in fate and 

transport studies to determine cyclanilide and/or major degradate following application to soil in 

addition to monitoring and/or spills. 

Guideline Number: 835.6200

Study Title: Environmental Chemistry Method and Associated Independent Laboratory Validation 

for water 

Rationale for Requiring the Data 

No method or validation was submitted for determining this chemical and major degradate in water. 

Practical Utility of the Data 

How will the data be used? 

Data will be used to determine levels of cyclanilide and its major degradate in water with high 

precision, accuracy, and appropriate detection/quantification limits. In addition, the method 

should be validated by an independent laboratory. State-of the-art and validated analytical method 

is required in order to have it available for the public to be used in determining the concentration 

of the chemical and its major degradate in water. Also the method is to be used in fate and 

transport studies to determine cyclanilide and/or major degradate following application to soil in 

addition to monitoring and/or spills. 

Guideline Number: 835.4100

Study Title: Aerobic soil metabolism 

Rationale for Requiring the Data 

In the registration review risk assessment, the Agency will consider parent plus degradate as the 

stressor. However, current data on the degradation profile of cyclanilide in aerobic soil systems 

suggests formation of a major degradate, 2, 4-dichloroaniline metabolite. Metabolite 2, 4-

dichloroaniline contain its parent’s moiety and appears to be persistence in at least one of the two 

soil systems examined. Data is needed to confirm persistence/non-persistence of the main 

degradate and confirm complete extraction of residues left in the soil and considered to be bound 

residue.

Practical Utility of the Data 

How will the data be used?
38 

Additional aerobic soil metabolism data will facilitate a better understanding of the fate of cyclanilide and 

the degradation profile in the most important compartment of the environment (the soil system). The soil 

system is expected to eventually receive applied pesticide. 

How could the data change the Agency’s decision or impact the Agency’s future decision-making? 

In the absence of the required data, cyclanilide degradation profile will be assumed, conservatively, to 

include the major soil degradate in addition to the assumption that it is as toxic as the parent. Therefore, 

the expected environmental concentration will be much higher because it will be based on the total residue 

of concern (parent + degradate) and consequently Risk quotient will be higher resulting in possibly 

conclusions of higher risk.