# Appendix A.

Review of predictive approaches for use in common effects

framework : QSAR Tools

Chris Russom

US Environmental Protection Agency

National Health and Environmental Research Laboratory

Mid

- Continent Ecology Division

Duluth, MN

Report to the

ORD/OW/OPP Common Effects Methodology Team

December 20 , 2011

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# Background:

Quantitative structure

- activity relationships (QSARs) attempt to quantify through the use of

algorithms the relationship between an aspect of chemical structure and an activity or property

imparted by that structure

. 

## This report documents methods and approaches for using publicly

available QSAR models

, and tools to build models

, as a source of toxicity data within the

common effects framework

.

In theory, the use of QSAR methods could provide a complete toxicity set ( i.e. , the 8

MDRs for CWA criteria) when combined with available empirical data , if acceptable, robust

models

, and data to build reliable models exist

. In order to determine whether a QSAR

estimate for a chemical and / or species of interest is appropriate to use within the framework,

a number of characteristics of the model need to be considered. These characteristics include

the applicability of the model to the endpoint or parameter of interest; applicability to the

chemical class, mode of action, group and structure of the chemical of interest; the

requirement for a quantitative or qualitative prediction; and whether the tool has inherent

biases or limitations. Many of the available predictive tools are qualitative and not suitable for

deriving predicted values

. Although qualitative tools may be useful in other aspects of the risk

assessment , they are not considered in the current analysis . Conversely, quantitative models

,

which pred ict values of concern ( e.g ., LC 50 

## , EC 50 

## )

, are available , but the use of these tools may

be limited when statistical rigor, predictive performance, domain of applicability, and the level

of validation of the statistical algorithm / 

## model are considered.

A cr itical evaluation of all existing QSAR model/tool s as they relate to use in the

common effects framework was not feasible based on time constraints , therefore model/tool

limitations are based on the restricted evaluation s undertaken. Specifically, only one mode of

action was assessed ; acetylcholinesterase inhibition ; and only three publicly available tools

were examined

, i.e., existing QSAR models for fish and daphnids within the Ecological Structure

Activity Relationship s ( ECOSAR ) 1



## , and Toxicity Estimation Software Tool ( T.E.S.T. ) 2 

## applications,

1 

### USEPA. 2011. Ecological Structure Activity Relationships.

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm

2 

### USEPA. 2011. Toxicity Estimation Software Tool. http://www.epa.gov/nrmrl/std/cppb/qsar/#TEST

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## and the O r g anization for E conomic C ooperation and D evelopment (OECD) QSAR Toolbox 3 

## was

used to develop new QSAR models . These tools were selected because they are freely

accessible

, regulatory authorities frequently rely on these tools when chemical

- specific

empirical data are not available , and they have undergone some level of validation as

prescribed by the OECD validation principles.

The purpose of t his evaluation was to address the following questions:

For each model /tool , what is the potential utility of it for developing quantitative values within

the common effects framework?

For each model, what are the strengths, weaknesses, uncertainties as the y relate to use in

filling taxa

- specific data gaps?

How do model predictions compare to an independently compiled empirical data collection?

What future research/work is required in order for predictive tools to be more useful t o the

common effects framework?

3 

### OECD. 2011. OECD Toolbox. Version 2.2.

h ttp://www.oecd.org/document/54/0,3746,en_2649_34379_42923638_1_1_1_1,00.html#Download_qsa

r_application_toolbox

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# Data Set s :

Chemical I dentification F ile :

Critical to any QSAR approach is the collection of reliable chemical identification data for

use as input variables to models, such as chemical name, Chemical Abstract Services Registry

(CAS) number, a computer recognizable way of identifying the chemical structure , in this case

SMILES (Simplified Molecular Input Line Entry System) notation , and basic property information

such t he log of the octanol/water partition coefficient (log P)

.

P rimary sources of chemical identification data used in this exercise in cluded :

the ECOtoxicology ( ECOTOX ) 4 

## database chemical file which is a component of the

USEPA Asssessment Tools for the Evaluation of Risk ( ASTER 5 

## ;

http://aster.rtpnc.epa.gov/aster/ ) application (chemical name, CAS number, SMILES),

the USEPA Distributed Structure

- Searchable Toxicity ( DSSTOX ;

http://www.epa.gov/NCCT/dsstox/ ) database network master chemical file (chemical

name, CAS Number, SMILES),

the Alan Wood database ( http://www.alanwood.net/ ) (chemical name, CAS number

,

structure , chemical category )

,

the BIOBYTE component of the BioLoom tool

( http://www.biobyte.com/bb/prod/bioloom.html ) (chemical name, CAS number,

SMILES, log P (measured and estimated using C log P ) )

,

ChemID Plus ( http://chem.sis.nlm.nih.gov/chemidplus/ ) (CAS num b er, SMILES) and

the USEPA ECOSAR tool ( http://www.epa.gov/oppt/newchems/tools/21ecosar.htm ) (

SMILES

, CAS , and log P via K ow W in )

.

These data sources have all undergone rigorous quality assurance measures, but w hen two

sources disagreed a third source was consulted. At times the CAS STN database

4 

### USE PA. 2011. Ecotoxicology Database. Version 4 http://cfpub.epa.gov/ecotox/

5 

### USEPA. 2011. Assessment Tools for the Evaluation of Risk (ASTER).

http://www.epa.gov/med/Prods_Pubs/aster.htm

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## ( http://www.cas.org/products/stnfamily/index.html ) was used to verify CAS number and

structure information. This is a ‘for fee’ database maintained by CAS, and was only consulted

when discrepancies could not be resolved. Typically differences were related to (a) alternate

formulations of compounds with distinct CAS numbers, (b) deleted CAS numbers that had not

been updated, and (c) differences in SMILES convention requirements within specific tools

( e.g

. , presentation of Kekula structures ).

. After quali ty ass urance steps were completed, a

chemical file was created for use in the analysis (Supplementa l Information T

- 1).

Toxicity data:

Availability of e mpirical toxicity data is necessary in modeling approaches in order to

determine the performance of existing QSAR models, and for use when building and validating

new QSAR models. The data sets used should be high quality, and meet certain experimental

design requirements to ensure comparisons across and within chemicals are reasonable. Data

compilatio ns used in this analysis included the Interspecies Correlation Estimator ( web

- ICE )

Modeling data sub set (Version 3.1), the ECOTOX database ( up to and including the June 2011

update), and compilation of databases within the OECD QSAR Toolbox (Version 2.2.1. 1120 ;

Database version: 2.1.8/1.0.0 )

. For the empirical data sets used in this analysis see the

Supplemental Information : T

- 2

. It should be noted that the QSAR tools used in this exercise,

ECOSAR and T.E.S.T., included empirical data for comparison purposes to model estimates. The

T.E.S.T. data although easily extractable from the outputs were not used for comparison

purposes because they did not have the same adherence to quality considerations as the web

ICE Modeling data sub set (see below)

, and specifically did not appear to evaluate the purity of

the test compound . The empirical data presented in ECOSAR tool was not used for model

evaluation because it was not easily mined from the version of the application available.

Web

- ICE Modeling Data S ubs et :

Version 3.1 of the web

- ICE t ool includes a database of 17,350 toxicity test results

from studies published in the open literature and government test results that are published in

gray literature. Data sources included

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## the USEPA ECOTOX database ( www.epa.gov/ecotox ; up to and including the February

2009 update),

the Mayer and Eller sieck data set (also referred to as the USGS Acute Toxicity Database

http://www.usgs.gov/science/cite

- view.php?cite=1336 ; Mayer and Ellersi e ck, 1986);

the Office of Pesticides Ecotoxicity d atabase (referred to here as the OPP database)

( http://www.ipmcenters.org/Ecotox/index.cfm ),

data tables from published Ambient Water Quality Criteria documents

( http://water.epa.gov/scitech/swguidance/standards/criteria/aqlife/index.cfm ),

data submitted to the USEPA under the High Production Volume (HPV) Challenge

Program ( http://www.epa.gov/hpv/ ), and

other EPA Office of Research and Development (ORD) and open literature studies not

captured in the above mentioned data collections.

The web

- ICE database also includes CBI (confidential business information) test results from

Toxic Substances Control Act (TSCA) data submissions, but these values were not included in

the web

- ICE data set provided.

To ensure the evaluation of model performance wa s not adversely influenced by the

empirical data used, an assessment was made as to the quality of the data provided. Two

subsets of the web

- ICE data set were reviewed prior to conducting the QSAR analysis: (a) the

empirical data approved for use in mode l development within the USEPA web

- ICE database

(hereafter referred to as the web

- ICE Modeling data sub set), and (b) ‘data rich’

acetylcholinesterase (AChE) inhibitors ( i.e. , substances that met the 8 MDR requirements)

(Garber 2011). The ‘data rich’ AChE inhibitor data set was compiled using the USEPA ’s Web

- ICE

Query Builder tool ( USEPA 2010). This tool uses the full web

- ICE data set as a base source of

data, and allows users to build searches including options to select test results based on specific

MDR requirements, experimental conditions, mode of action, taxonomic and chemical

information, water chemistry parameters, and whether the data were in the web

- ICE Model ing

d ata subs et. Although the ‘data rich’ data set has various data quality controls in p lace ( e.g.

,

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## >90% purity, species is resident of North America), a review of the data found entries with

transcription errors, and wide ranges of toxicity concentrations within data having the same

chemical, species, endpoint, and duration. In addition, si nce the focus were ‘data rich’

chemicals ( i.e. , those meeting the 8 MDRs), the number of chemicals were limited to nine

organophosphates and 3 carbamates. A more robust data set was required to conduct the full

evaluation of the QSAR models , therefore the web

- ICE Modeling data subset was used.

The web

- ICE Model ing d ata sub set included 4,740 test results (27% of the 17,350 data

records in web

- ICE Version 3.1). Within this file, 587 of the test records were associated with

71 chemicals having a mode of act ion of AChE inhibition. An examination of the web

- ICE

Modeling data sub set found only one of transcription error that had been identified in the ‘data

rich’ data set , but this test result was not included in this analysis because the species was not

associated with QSAR models that were evaluated or developed . Within the web

- ICE Modeling

data s ubs et, variances in data still existed for chemical, species, endpoint, and duration

combinations, but were greatly reduced due to methods used in compiling the data set.

Acceptability criteria and data quality filters : The web

- ICE Modeling data s ubs et was

composed of test results that met certain requirements related to experimental design, and

data quality. These limitations w ere set to provide a level of consistency across the various

studies

, to reduce test variability related to differences in experimental design

, and to ensure

that other chemicals ( e.g ., inerts) within a formulated product were not significantly

contributin g to toxicity. Assessments of acceptability of experimental design and other

parameters related to data quality were accomplished by either examining data fields within

the respective databases when test results were compiled from multiple sources such a s the

open literature ( e.g ., ECOTOX), or documentation on the test methods used for studies

compiled from one organization ( e.g ., Mayer and Ellersieck data set). The web

- ICE Modeling

data sub set was limited to studies that met the following criteria: (a) aquatic species; (b) animal

species; (c) EC/LC 50 

## endpoint; (d) compound purity > 90 %; (e) test durations of 48 or 96 hrs; (f)

effect of mortality or immobilization; (g) studies conducted in a laboratory; (h) concentration s

that are not open

- ended (indefini te) values ( i.e ., exclude >, < or ~ LC/EC 50 values), and (i)

documented temperature and dissolved oxygen measurements. If the values were not

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## reported for these parameters, the studies were excluded from the web

- ICE Modeling data

sub set. In addition, te st results were excluded if concentration units could not be converted to

a standard unit ( i.e ., ug/L), and species and/or chemical information could not be validated

( e.g

., incorrect CAS number; taxonomic information that could not be verified). Duplicat e

studies were removed by identifying studies where the CAS number , species, age, and LC/EC50

toxicity concentration were the same.

To reduce variation related to test methods used, several parameters were standardized

within the web

- ICE M odel ing data sub set. Life stage was standardized to either larvae, juvenile

or adult, with egg and embryo life stages excluded from the web

- ICE Modeling data sub set. For

fish, amphibians, mollusks, decapods, and aquatic insects, only data for juvenile life stage were

included; all others were excluded. For all other species, any life stage other than egg or

embryo was included in the web

- ICE Modeling data sub set. These life stage classifications, if

not reported directly in the parent database, were estimated based on age and/or size

information provided. When life stage could not be determined, test results were only included

in the web

- ICE Modeling data sub set for those species where any life stage could be used.

Using ASTM standard test protocols, species that w ere tested outside their optimal

temperature by + 6 C, or studies that were outside approved dissolved oxygen requirements

were excluded from the final data set. Once all requirements had been met an analysis of

outliers was performed. In instances where more than one toxicity value was available for a

chemical

, species , endpoint, duration combination , the ratio of the maximum and minimum

concentration values was calculated . When ratios exceed 10, the original publications were

examined, and if errors in data were identified these data were not included in the analysis. If

an outlier could not be determined ( e.g. , only two data points), then all data records were

removed if the ratio was greater than 10. See Vivian et al . 2009, for complete details on th e

composition of the web

- ICE Modeling subset within the web

- ICE tool. F or this analysis, web

- ICE

Modeling data subset test results associated with high to low toxicity values ratios that

approached 10 were compared to the original publication, if availabl e ( i.e. , data from third

party data collections such as the OPP data set could not be checked since original publications

were not available) to ensure information was properly represented

.

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## ECOTOX Database :

When chemical/species combinations did not have data within the web

- ICE Modeling

data subset, an examination of more recent versions of ECOTOX ( i.e ., June 2009

- June 2011

updates) was conducted and data for these groups were gathered. Data quality criteria used to

compile the web

- ICE Modeling data subset were applied to the ECOTOX empirical data to

ensure consistency between the data collections

. All ECOTOX data used were compared to the

original publication to ensure data were transcribed properly.

OECD QSAR Toolbox Data :

When constructing new QSAR models, in addition to the web

- ICE Modeling data subset,

databases housed within th e OECD QSAR toolbox were used. The OECD QSAR Toolbox

(referred to as OECD Toolbox herein) is a decision support system that allows users to utilize

extensive toxicity data bases ( in vivo and in vitro ) and physico/chemical property information to

form chemical categories, i.e

., to identify what is common among the chemicals. This subset of

data based on chemical categories can then be used to conduct an analysis to determine data

trends, identify data gaps, and fill data gaps using QSARs that already exist within the OECD

Toolbox o r QSARs developed by the user from within the OECD Toolbox . The OECD Toolbox

toxicity databases relevant to this effort include the ECOTOX database ( up to and including the

February 2009 update) , Japan MOE (Ministry of the Environment) Ecotoxicity Test Re sults

database ( http://www.safe.nite.go.jp/english/db.html ), the ECETOC (European Centre for

Ecotoxicology and Toxicology) Aquatic Database

( http://www.ecetoc.org/index.php?mact=MCSoap,cntnt01,details,0&cntnt 01by_category=5&c

ntnt01template=display_list_v2&cntnt01order_by=Reference%20Desc&cntnt01display_templa

te=display_details_v2&cntnt01document_id=269&cntnt01returnid=89 , and the OASIS Aquatic

Database which is a compilation of toxicity test data created speci fically for use in QSAR

development (Laboratory of Mathem a tical chemistry ( LMC), Bulgaria).

Acceptability criteria and data quality filters : In order to be consistent with the data

quality requirements used in creating the web

- ICE Modeling data sub set, s imilar filters were

applied to the OECD Toolbox data collections , where possible . As toxicity data were gathered

,

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## the OECD Toolbox present ed a table of suspected duplicate data. Similar to web

- ICE protocols

described above, duplicate test results w ere removed from the data set. Prior to applying data

gap approaches, the user must identify the species, endpoints and duration to include in the

analysis, therefore these were consistent within the modeling exercise. Prior to building final

models, the “Select Filter Data” function was used to filter data based on test conditions. The

OECD Toolbox does not include temperature and dissolved oxygen as test parameter review

options, but data were excluded if purity was <90% or not reported ( NR ) , and organ ism life

stage was confirmed either based on direct reporting or by a review of organism weight or

length. The system did not allow for effective review of extreme values, therefore the average

test result was used in the data gap trend analysis, and QSAR model building steps.

Chemical Category and Mode of Action Assignment :

The web

- ICE M odel ing data sub set includes information as to the acute mode of action

(MOA) of the chemicals to fish. These estimates were based on initial evalu a tions using the

ASTER modeling application ( http://www.epa.gov/med/Prods_Pubs/aster.htm ), and a

subsequent quality assurance and review of information. The ASTER application MOA is a rule

based system based on a detailed analysis of fish acute toxicity responses, and information

gleaned from the literature. The rule

- base ties structural fragments to specific MOAs (see

Russom et al

, 1997 for details on th e methods). In addition

, a separate data set of mode of

action to target species was compiled for this exercise using reliable resources such as the

Insecticide Resistance Action Committee (IRAC) website tool ( http://eclassification.irac

online.org/ ), and information published in the open literature. Since the focus of this analysis is

AChE inhibition, it is assumed that the acute mode of action in fish will be the same as in the

target species ( i.e

., insects) (Pezzementi et al ., 2011). Therefore, the web

- ICE model MOA was

compared to the MOA compiled using alternate sources based on target species and a unified

file was developed. The final chemical list included N=127 AChE inhibitors consisting of 3 4

carbamates and 93 organophosphates (OPs) (See Supplemental Information : T

- 1 for a complete

list of chemicals evaluated under this effort

. )

Carbamate Adverse Outcome Pathway :

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## Carbamates act through a reversible carbamylation of the AChE enzyme. Acetylcholine

mediates nerve impulses in the nervous systems of insects and vertebrate species. The binding

results in an accumulation of acetylcholine and subsequent adverse effects within

neuromuscular junctions of skeletal muscle, pre

- ganglio nic neurotransmitters, and post

ganglionic nerve endings of the autonomic nervous system, and neurotransmitters in the brain

or central nervous system. Symptoms may include muscle contraction and increased gland

secretion, depolarization of cell membrane potentials, increased excitatory responses, and

sensory and behavioral changes (NPIC 2011).

Organophosphate Adverse Outcome Pathway :

Organophosphates (OPs) act through a n irr eversible phosphorylation of the AChE

enzyme. As with carbamates, t he bindin g results in an accumulation of acetylcholine and

subsequent adverse effects as reported for carbamates. A rate limiting step for the thion ( i.e.

,

(RO

- ) 3 

## P=S rather than (RO

- ) 3 

## P=O) forms of OPs is the oxidative desulfuration to create the oxon

form which b inds to the AChE enzyme (Roberts and Hutson, 1989).



# QSAR Model ing Tools

In order to compare existing QSAR models to acceptable empirical test data, two

publicly available modeling applications were selected; the USEPA , OPPT’s ECOSAR application

(Version 1.0 and 1.1), and the USEPA ORD’s T.E.S.T. application (Version 4.0) . Both models have

undergone validation internally and have been published in the open literature (Martin and

Young, 2001; Martin et al

. 2008; USEPA 2011; Mayo

- Bean et al ., 2011 ). These tools were

selected since they are readily available to the OPP and Office of Water (OW), and they meet

OECD validation principles (OECD 2007). QSAR models were also available within the OECD

Toolbox, but this tool was not used to compare existi ng models with empirical data sets

because the available aquatic toxicity QSAR models were those from the ECOSAR tool, and the

version within the OECD Toolbox was an older version (V ersion 1.0) than the one included in

this analysis (V ersion 1.1) . ASTER a lso includes QSAR models, but this tool was not included in

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## this analysis since the models within ASTER are for non

- specific toxicity, and would only provide

information related to acute mode of action for these chemicals without an estimate of toxicity

using QSAR models.

For comparison purposes, log P was used in figures below and as the primary molecular

descriptor within the ECOSAR tool to describe toxicity . Although many models exist to estimate

log P (Tetko et al

. 2009) , the KowWin model within ECOSAR V ersion 1.1 (Mayo

- Bean et al

.,

2011) was used in this analysis . This was done primarily to be consistent with the estimates of

toxicity from the ECOSAR tool, where KowWin is the independent variable used to explain

t oxicity within QSAR models

. Prior to use comparisons were made to ensure that the KowWin

log P estimate was comparable to available empirical data. Of the 127 chemicals included in

this analysis; 77 had measured log P values within the Bio L oom product. For 88% of these, the

log P estimate was 1

- 1.5 fold different from the measured value. Omethoate, dichlorvos,

oxamyl, and dimethoate estimates differed by 2

- 2.8 fold from the measured log P value, and

mevinphos, azinophos

- ethyl, and monocrotoph os estimated values were 5

- 6.5 fold different

from measured log P values. For these chemicals a comparison was made to the ClogP model

within BioLoom, and only the dichlorvos log P estimate was improved ( i.e. , 1.2 fold different

from the measured value.) Since time was not available to determine if the method used for

measuring log P was appropriate, and both models did poorly in estimating these compounds,

the KowWin value was retained for use, but these chemicals were examined more closely

during any an a lysis of QSAR models when log P w as used as a molecular descriptor to describe

toxicity

.

ECOSAR (Ecological Structure Activity Relationships) Modeling Application :

Background:

The ECOSAR QSAR tool is a PC

- based application available for download at

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm. The application was built to support

risk assessments for new chemicals submitted for TSCA pre

- manufacturing notification (PMN)

reviews. Under TSCA, m anufacturers are required to submit any information available on the

compound of interest including its structure, but are not required to conduct a suite of tests as

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## is done under FIFRA. Risk assessors many times only have the structure of the chemical t o

make a determination of risk. Therefore QSAR models have been utilized historically to

determine potential hazard of PMN review compounds. These models are chemical

- class based

( i.e. , based on toxicophores related to specific activity of a compound), a nd have been revised

and expanded as new chemical structures have been identified. The data behind the QSAR

toxicity models include data submitted by manufacturers following OPPT guidelines, much of

which is confidential business information (CBI), and da ta collections developed for use in QSAR

modeling such as the USEPA fathead minnow database (Russom et al ., 1997). ECOSAR can be

run in either a batch mode or interactive / single chemical mode. Outputs are available as

either delimited or text file form at s , and as either concise or full reports.

ECOSAR Version 1.1 includes models for 111 chemical classes and 709 QSAR models to

estimate various toxic endpoints. ECOSAR includes acute predictions of L C /EC50 for fish

(saltwater and freshwater), mysid shrimp (96 hr)

, algae (72 and 96 hr), and daphnids (48 hr) and

chronic toxicity predictions ( i.e. , the chronic value or MATC) for fish (saltwater and freshwater),

mysid shrimp, daphnids, and algae. Most acute models are based on a QSAR model, but some

chr onic values are based on acute to chronic ratios. Log P and chemical structure via SMILES

string are required for models to work, but an extensive database of structures and the

KowWin log P model are included in the application so typically users only ne ed enter the CAS

number and both values will be populated. The models perform well within certain log P

ranges, with a domain of applicability of log P ranging from

- 3 to 8.0. Models were built for use

under TSCA and therefore historically did not includ e models for MOAs related to many

pesticide activities. Version 1.1 has begun expanding these models to include pesticides with

AChE activity.

ECOSAR QSAR Model Estimates

Version 1.1 of the USEPA ’s ECOSAR modeling application was utilized in this evalu ation

,

with some comparisons made back to Version 1.0

. As mentioned above, ECOSAR which was

developed primarily to support decisions under TSCA, has been expanded in Version 1.1 to

include a limited number of pesticide data within select models. These data were part of a

larger data set housed within the Ecological Effects Division at OPP of data which have been

## 14 | P a g e



## reviewed and categorized as acceptable for fulfillment of pesticide registration and re

registration guideline req uirements as explained under F ederal I nsecticide, Fungicide and

Rodenticide Act ( FIFRA) (B.Montague, personal communication)

. It should be noted that not all

pesticide data submitted to OPP have been included in ECOSAR Version 1.1, but a limited

number of carbamate and organophosphate data sets that fit existing chemical categories were

included and the associated chemical category QSAR models were updated (K. Mayo

- Bean

,

personal communication).

Since the focus of this project is the use of QSAR models to estimate acute toxicity to

ful f i ll aquatic MDRs , an examination was only made of the freshwater fish and daphnid acute

models

. ECOSAR models are generic for fish and daphnids , based on a variety of species

.

Frequently used species to develop the fish QSARs included bluegill sunfish ( Lepomis

macrochirus ), common carp ( Cyprinus carpio ), fathead minnow ( Pimephales promelas ), guppy

( Poecilia reticulat a ), rainbow trout ( Oncorhynchus mykiss ), medaka ( Oryzias latipes ), or

zebrafish ( Brachydanio rerio ). R ainbow trout or bluegill sunfish tended to be the most sensitive

fish species ( Figure 1 ) upon examination of the ICE modeling data subset . Since the ECOSAR

model is generic for fish, and a critical minimum data requirement ( MDR ) under the Water

Quality Criteria ( WQC ) Guidelines is a salmonid ( USEPA 1985) , comparisons of the ECOSAR fish

model were made to rainbow trout when possible. The average test concentration from the

various empirical test results were employed , using rainbow trout data if a value existed

(N= 5 8 )

, and using bluegill data (N= 6 ) only when no rainbow trout data were available (See

Supplemental Information : T

- 2 )

. The daphnid model within ECOSAR was predominately based

on D

. magna and D

. pulex data . The average web

- ICE M odel ing data sub set value used in

comparison to the ECOSAR model was primarily based on D

. magna (N= 44) data, but also

included values representing only D

. pulex (N=2 ) or both daphnid species (N= 4 ) (Supplemental

## 15 | P a g e



## Information: T

- 2)

.

The ECOSAR application generates models estimates for each chemical category

associated with a substance as well as a baseline narcosis model . For instance

, a carbamate

ester would be modeled as a narcotic, an ester, and a carbamate ester. In selecting the model

for use in this exercise the chemical category that was associated with organophosphate esters

or carbamates was selected, and in all cases but two this selection was the most hazardous

toxicity test model ( Supple mental Information : T

- 3 .) The two exceptions, t etrachlorvinphos and

c hlorfenvinphos

, reported a vinyl /allyl halide model as the lowest toxicity value, but the

toxicity estimates were very comparable to the ester phosphate model ; therefore, the latter

mo del was extracted and used in this analysis. This resulted in five models in V ersion 1.1 of

ECOSAR for the AChE data set: phenyl carbamate ester and oxime carbamate ester for the

carbamates, and phosphate ester, monothiophosphate ester, and dithiophospha te ester for the

OPs

. Between the daphnid and fish models a total of 65 AChE inhibitors were examined ( i.e

.,

had both an empirical test value and an estimated value) ranging in log P from

- 1.031 to 6.167

## 16 | P a g e



## ( Supplemental Information : T

- 3 )

. ECOSAR includes warnings for chemicals that are estimated

outside of solubility ranges ( i.e ., estimated value could be above solubility) . Four chemicals

within the list of N=127 AChE inhibitors had a flag to this effect, but only one of these, naled,

had concu rrent empirical data ( Supplemental Information : T

- 3 )

. The ECOSAR estimate for

naled was included in the comparison analysis, but during the evaluation this possible problem

with the estimate was considered.

T.E.S.T. (Toxicity Estimation Software Tool) :

Background:

T.E.S.T. is a PC

- based QSAR tool that provides toxicity estimates using a variety of QSAR

modeling methodologies (See Table 1 ). The tool provides model estimates for both toxicity and

physical/chemical property information. Users provide the structure by either using the T.E.S.T.

structure depiction tool to draw the chemical, as an SDF (structure data file) format using the

Mo lecular Design Limited (MDL) molfile convention (Dalby et al., 1992), or as a SMILES string.

Once structure(s) have been identified, the user selects the desired QSAR model. There is no

need to provide molecular descriptors because T.E.S.T. pulls this in formation from a database

of 790 two

- dimensional molecular descriptors. These molecular descriptors include electronic,

topological, connectivity, generalized molecular properties ( e.g. , log P), molecular distance

measures, and molecular fragments which a re used to build QSAR models. The QSAR model

can be requested as individual entry/output or via batch mode entry/output. Output options

include either a spreadsheet or html format. Toxicity estimates include the acute toxicity

(L C /EC50) to the fathead minnow ( Pimephales promelas ) and D. magna , the acute IGC50 (50%

inhibition of growth) to the ciliate, Tetrahymena pyriformis , and the acute oral LD50 to rats.

T.E.S.T. also includes estimates of developmental toxicity and mutagenicity based on Ames test

d ata.

T.E.S.T. estimates the toxicity based on up to six QSAR methodologies (See Table 1 ). An

overview of each method is provided below. All models described below are available for the

fathead minnow, and all but the Group Contribution method are avai lable for D. magna . See

the T.E.S.T. User Guide ( USEPA 2011) for further information and details on how the T.E.S.T.

tool implements each model.

## 17 | P a g e



## Hierarchical Clustering Model : Hierarchical clustering is a QSAR method whereby groups

or clusters havin g similar properties ( i.e. , structure, physical/chemical property, electronic

characteristics etc .) are developed. Structural similarity indices are used to determine how

similar / dissimilar chemicals are from one another. These clusters are analyzed, c ompared,

and merged, into new clusters. Within T.E.S.T. a Ward’s minimum variance method is used to

build clusters (Ward, 1963). This involves calculating the union of every possible pair of

clusters, and combing the two clusters that result in the small est sum of squared deviations.

After clusters are complete, T.E.S.T. uses a genetic algorithm approach to determine the

optimal molecular descriptors for use in the QSAR model. Genetic algorithm is a heuristic

method of building QSAR models which is base d on evolutionary principles of natural selection

(Niculescu 2003). A population of many models are built as possible QSARs, these are rated as

to fitness ( i.e. , how well they perform), parent models are selected and crossed to create child

models, which are also evaluated as to fitness. ‘Fit’ models continue; ‘unfit’ models are

removed. Evolution continues until the models converge and the child models do not differ

significantly from the parent models.

FDA Model: The FDA QSAR models available within T.E.S.T. are based on approaches

described in Contera et al., 2003, where unique clusters are created during each model building

session. The user selects a test chemical and a cluster is built based on chemicals that are

structurally similar to the sele cted chemical. Similarity is defined using a cosine similarity

coefficient, which is a measure of the cosine of the angle between two similar objects. Using a

genetic algorithm approach the molecular descriptors with the best fit are identified and the

f inal model is built.

Single Model : The T.E.S.T. Single M odel QSAR is a linear regression model that fits an

entire training set using multiple molecular descriptors. This does not cluster or determine

structural similarity prior to model development, bu t does evaluate molecular descriptor

performance within models similar to the other T.E.S.T. model methods.

Group Contribution Model : For the T.E.S.T. Group Contribution model, counts are made

of structural fragments within the training set, and these fr agment s are used to develop a linear

regression model using multiple molecular descriptors. Fragments are removed from the

## 18 | P a g e



## model if they appear in less than three chemicals within the training set, and subsequently all

chemicals with these fragment are re moved. T.E.S.T. requires that at least three chemical

structures within the final QSAR model training set have all fragment used in the Group

Contribution model.

Nearest Neighbor Model : The Nearest Neighbor model within T.E.S.T. defines similarity

of chemicals using the cosine similarity coeffic i ent. The QSAR estimate is the average of the

three most similar chemicals.

Consensus Method : The QSAR estimate using the Consensus method is calculated by

averaging all other T.E.S.T. QSAR model estimates for the test chemical.

T.E.S.T. QSAR Model Estimates

Version 4.0 of the T.E.S.T. tool was used in this analysis. For the purpose of this

e xercise, the models for fathead minnow and D. magna were used, and therefore, the web

- ICE

Modeling data subset was restricted to acute studies for these species (Supplemental

Information: T

- 2 ). As mentioned above, T.E.S.T. uses several methods to estimate toxicity . A

summary of each method is provided in Table 1

. Results of model outputs for the set of AChE

inhibitors are presented in Supplemental Information : T

- 4

.

Table 1: Descriptions of modeling methods available within T.E.S.T. modeling tool (tak en

from USEPA 2011)

Method Description Species

Hierarchical

Clustering The toxicity for a given chemical is estimated using the weighted

average of the predictions from several different models. The

different models are obtained by using hierarchical clustering

techniques . A genetic algorithm based method is used to

generate models for each cluster. The models are generated prior

to runtime. Fathead minnow

Daphnia magna

FDA The prediction for each test chemical is made using a new model

that is fit to the chemicals that are most similar to the test

compound. Each model is generated at runtime. Fathead minnow

Daphnia magna

Single Model Predictions are made using a multilinear regression model that is

fit to the training set (using molecular descriptors as independent

variables) using a genetic algorithm based approach. The

regression model is generated prior to runtime. Fathead minnow

Daphnia magna

Nearest Neighbor The predicted toxicity is estimated by taking an average of the 3

chemicals in the training set that are most similar to the test Fathead minnow

Daphnia magna

## 19 | P a g e chemical.

Group Contribution Predictions are made using a multilinear regression model that is

fit to the training set (using molecular fragment counts as

independent variables). The regression model is generated prior

to runtime. Fathead minnow

Consensus Model The predicted toxicity is estimated by taking an average of t he

predicted toxicities from the above QSAR methods (provided the

predictions are within the respective applicability domains). Fathead minnow

Daphnia magna



# Comparison of QSAR Estimates to Empirical Test Data

ECOSAR Model Estimation s :

A comparison was made of ECOSAR QSAR estimates ( Supplemental Information : T

- 3 ) to

acceptable empirical test data. A limiting factor in this analysis was the availability of

acceptable empirical data. Of the 127 AChE inhibitors selected for modeling purposes, only 64

had suitable empirical data available for comparison purposes (N=17 carbamates and N=47

OPs ) . An ECOSAR fish and daphnid estimat e from ECOSAR was available for all chemicals, but

only 64 had acceptable f ish test data (rainbow trout or bluegill) and only 50 had acceptable D.

magna or D. pulex data ( Figures 2 and 3 )

. For fish, d ichlofenthion, d isulfoton, f osthiazate,

t ebupirimfos, and t emephos were all estimated by ECOSAR to be more toxic than observed in

the empirical database, while a zinophos

- methyl, c hloropyrifos

- methyl oxon, d ichlorvos,

f ensulfothion, i sazofos, m alathion, m ethidathion, n aled, o xydemeton

- methyl, p horate,

p rofenofos, and t richlorfon were estimated to be more than 1 order of magnitude less toxic

than observed in the empirical data set. As mentioned previously there were flags within

ECOSAR that model estimates may be above water solubility, and naled had such a flag

. When

compared to the empirical test d ata, only the ECOSAR fish models associated with the

carbamate chemical categories ( i.e. , oxime carbamate ester and phenyl carbamate ester

models) estimated all values within an order of magnitude. O ther ECOSAR fish models had

substances (N=17) where pred icted values were +/

- 2 to 4 orders of magnitude different than

empirical test data (See Figure 2 )

. For daphnid species, t he ECOSAR models performed similarly

with 12 substances having estimated values +/

- 2 to 4 orders of magnitude dif ferent than

empirical test data. Aldicarb, d imethoate, d isulfoton, e thoprophos, and f osthiazate were

## 20 | P a g e



## estimated by the ECOSAR daphnid model to be more toxic than observed in the empirical data

set, while d ichlorvos, m ethyl parathion, n aled, q uinalphos, t eb upirimfos, t emephos , and

trichlorfon were estimated to be less toxic than empirical test results by 1

- 2 orders of

magnitude (Figure 3)

. Once again the ECOSAR daphnid models associated with the carbamate

chemical categorie s performed best with only one sub stance ( i.e. , aldicarb) not estimated

within an order of magnitude

. Both daphnid and fish estimates for fo sthiazate and disulfoton

were estimated to be 2 orders of magnitude more toxic when compared to the empirical test

data . Conversely, dichlorvos toxicity was 2 orders of magnitude more toxic than estimated by

ECOSAR models for both the daphnid and fish species. T he toxicity of t richlorfon for daphnid,

and methidathion and azinophos

- methyl for fish was also underestimated by 2 orders of

magnitude. The one chemical for fish that was more than 3 orders of magnitude more toxic

than predicted was chlorpyrifos

- methyl oxon, the metabolite of chlorpyrifos. This compound

did not have concurrent empirical data for daphnids. As re ported earlier, the oxon form s of the

OP pesticides binds directly to acetylcholinesterase , and the need to metabolize thion

- type OP

esters to the oxon form may be a rate limiting step. An examination of the results for ECOSAR

modeling found no discernabl e pattern of toxicity based on oxon vs

. sulfon form of the O Ps

although both types were equally present within the data set examined

. As mentioned earlier,

log P estimates using KowWIn may be problematic. For the chemicals with log P estimates

using Kow Win that varied significantly from measured log P values, only dichlorvos was an

outlier, found to be >2 orders of magnitude less toxic than estimated using either the fish or the

daphnid ECOSAR QSAR models where log P is the molecular descriptor used as t he independent

variable to describe toxicity.

The overall statistical performance of ECOSAR estimates for fish when compared to the

empirical data set , was poor with correlation coefficients ( R 2 

## ) ranging from 0.029

- 0.26, with an

overall R 2 

## for ECOSAR V ersion 1.1 of 0.23 ( Table 2 ). ECOSAR V ersion 1.1 d aphnid models

compared to the empirical data set had R 2 

## values ranging from 0.008

- 0.49, and an overall

correlation (R 2 

## ) of 0.46 ( Table 2 ). An examination was also made of how ECOSAR models

p er formed prior to inclusion of the OPP data (Version 1.0). The fish models in Version 1.1

improved significantly with the addition of the OPP data, with improved R 2 

## values and reduced

## 21 | P a g e



## variance ( Table 2 ) . Fish estimates using ECOSAR Version 1.0 had R 2 

## values ranging fr om 0.0011

– 0.28 when compared to empirical data

.

## 22 | P a g e

Table 2: Comparison of ECOSAR V ersion 1.1 estimations for fish and daphnids to empirical test data

for rainbow trout/bluegill and D. magna / D. pulex

. ECOSAR Version 1.0 reflects correlations prior to

inclusion of OP

- and carbamate

- specific data.

ECOSAR V 1.1 ECOSAR

v1.0

ECOSAR Model R 2

(RSME)



### Fish No.

Chemicals R 2

(RSME)



### Daphnid N o.

chemicals R 2

(RSME)



### Fish N o.

chemicals

Overall performance 0.23

(1.02) N=64 0.46

(1.10) N=50 0.093

(1.39) N=62

Phenyl carbamate Ester 0.26

(0.48) N=10 0.12

(0.43) N=9 0.0029

(0.80) N=10

Phosphate Esters 0.18

(1.16) N=13 0.008

(1.02) N=9 0.017

(1.81) N=13

Dithiophosphates Esters 0.048

(0.87) N=13 0.37

(0.83) N=10 0.0011

(1.11) N=12

Monothiophosphates

Esters 0.029

(0.69) N=21 0.28

(0.65) N=18 0.073

(1.15) N=21

Oxime Carbamate Ester 0.26

(0.50) N=7 0.49

(0.80) N=5 0.28

(0.76) N=6



## T.E.S.T Models :

Of the original set of 127 chemicals

, only 100 were examined using the T.E.S.T

application (N=25 carbamates; N=75 OPs )

. The reason for the missing outputs for the

## 23 | P a g e



## remaining 27 substances was not easily determined since a concurrent error report was not

generated by T.E.S.T. The av ailability of empirical test results and/or model

- estimated values

varied across the six QSAR models within the T.E.S.T. application ( Table 3 ). For instance, each

model within T.E.S.T. had some chemicals that did not result in an estimated value even when

empirical test data w ere available ( ranging from 1

- 11 chemicals ) depending on the model. As

with the ECOSAR model, from 35

- 71 substances were excluded from further analysis because

they did not have an acceptable experimental value even though a model estimate was

available ( Table 3 )

. These data gaps along with the reduced set of chemicals that were

examined

, resulted in a smaller set of chemicals compared to the ECOSAR analysis, for use in

evaluating model performance based on model estimates vs. empirical test results ( i.e ., from

18

- 27 for fathead minnow; and 38

- 45 for D

. magna .)

Table 3: Number of chemicals with empirical data and/or T.E.S.T. Version 4.0 QSAR model estimates

Model Number of Chemicals

Estimate d and

Empirical Values

Available Estimate d Value but

no Empirical Value

Available Empirical Value but No

Estimated V alue

Available Neither P redicted or

E mpirical D ata

A vailable

Fathead

minnow Daphnia

magna Fathead

minnow Daphnia

magna Fathead

minnow Daphnia

magna Fathead

minnow Daphnia

magna

Hierarchical

Clustering 18 38 57 35 2 11 23 16

FDA 25 38 57 35 3 10 15 17

Single Model 27 38 58 35 3 10 12 1 7

Nearest

Neighbor 25 42 60 42 3 6 12 10

Group

Contribution 20

- 40 11

- 29

-

Consensus

Model 27 45 71 48 1 3 1 4



## For fish, all of the T.E.S.T. models had estimated values that were more than +/

- 1 order

of magnitude different than the empirical values. For t emephos, the Consensus Model , FDA,

and Nearest Neighbor T.E.S.T methods estimated toxicity to be >1 order of m agnitude more

toxic than empirical test data, and the Single Model method estimate was >3 orders of

magnitude more toxic than empirical test data. The Nearest Neighbor model also

overestimated the toxicity of d iazinon, f ensulfothion, m alathion, and p hosme t by > 1 order of

## 24 | P a g e



## magnitude. The toxicity of t erbufos was underestimated by >1

- 2 orders of magnitude by all

T.E.S.T. model methods. All models except the Nearest Neighbor method estimated the toxicity

of a minocarb to be >1 order of magnitude less toxic t han empirical test results, and all but the

Nearest Neighbor and FDA methods underestimated toxicity by >1 order of magnitude for

t richlorfon. Other chemicals where the T.E.S.T. models underestimated toxicity by >1 order of

magnitude include c arbofuran ( Group Contribution model ), d ichlorvos (Group and Nearest

Neighbor models ), m ethomyl (Consensus, FDA, Single Model ), c arbofuran (Group model ), EPN

(Nearest Neighbor model ), e thion, p ropoxur (FDA model ), and o xamyl ( Single M odel ).

Similar to the fathead minnow results, all of the T.E.S.T. D

. magna models included

estimations that were >+/

- 1 order of magnitude different than empirical test data. Dimethoate

toxicity was estimated to be more toxic than empirical data by all models by >1 (Nearest

Neighbor and FDA models ), >2 (Con s ensus model ), or >3 (Hierarchical Clustering model , and

Single Model ) orders of magnitude. The toxicity of o xydemeton

- methyl was also estimated to

be more toxic than empirical D

. magna data using the FDA method. The T.E.S.T. models for D

.

magna had the highest number of substances where empirical test data were more toxic than

estimated toxicity values, with the toxicity of 7

- 14% of the chemicals underestimated by 1 order

## 25 | P a g e



## of magnitude and 5

- 9% of the chemical by 2

- >3 orders of magnitude. For instance, using the

FDA method, the ratio of the e stimated EC 50 

## value to empirical EC 50 

## value ranged from 515

–

3063 for the chemicals d ioxathion, n aled, a minocarb

, and e thoprophos . The largest model to

empirical data ratio was observed for p irimicarb using the Single Model ( i.e

., >29,000. )

The correlation of empirical data and T .E.S.T. model estimates varied depending on the

model chosen, with R 2 

## values ranging from 0.2

- 0.56 for the fathead minnow, and 0.24

- 0.46 in

D. magna . The Hierarchical Clustering model performed better than others for the fathead

minnow , while the Consensus Model performed better for the D. magna . Overall the fathead

minnow models performed better than the D. m agna for all models within T.E.S.T except the

C on sensus Model and N earest N eighbor methods.

## 26 | P a g e

Table 2: Comparison of T.E.S.T. V4.0 model estimations to empirical te st data for the fathead minnow and

Daphnia magna

T.E.S.T. Model R 2

(RSME)



### Fathead Minnow Number of

chemicals R 2

(RSME)



### Daphnia magna Number of

chemicals

Hierarchical

Clustering 0.56

(0.80) N=24 0.37

(1.38) N=38

FDA 0.45

(0.82) N=25 0.28

(1.41) N=38

Single Model 0.27

(0.90) N=27 0.24

(1.29) N=38

Nearest Neighbor 0.20

(0.75) N=25 0.39

(1.24) N

- 42

Group Contribution 0.30

(0.90) N=20

- -

Consensus Model 0.42

(0.78) N=27 0.46

(1.26) N=45



## C onsideration of the ECOSAR model performance to T.E.S.T. found comparable results.

Figure 6 presents data for the best performing T.E.S.T. method

, ( i.e

., Consensus Model) , and all

ECOSAR model results for the daphnid species compared to D

. magna empirical test data, and

Figure 7 presents the results of the Hierarchical Clustering model and ECOSAR model results

compared to the fathead minnow empirical test data

## 27 | P a g e



# Development of N ew QSAR M odels Using the OECD Toolbox

The OECD Toolbox (Version 2.2.1.1120 ) was used to perform trend analysis and

ultimately to create QSAR model s . Preliminary analysis found the use of the entire data file of

substances unwieldy, especially when trying to determine molecular descriptors for use as

independent variables in developing QSAR models

. This was mainly due to inadequate for use

in captur ing pesticide mode of action information or relevant chemical categories within the

“ Category Definition ” section of the OECD Toolbox

. It should be noted that ECOSAR categories

were included in the OECD T oolbox, but were from older versions of ECOSAR (Version 1.0 or

earlier) and were not used in order to be consistent with the V ersion 1.1 analysis previously

described . Because of an inability to create consistent models working with the entire data set

of AChE inhibitors, the file was divided into OPs and carbamates

, which analyzed separately

.

Files with CAS numbers (OPs and carbamates) were loaded into the OECD Toolbox.

Some form of information (physical/chemical property, empirical test data etc .) was in the

OECD Toolbox for 83 of the 93 OP s and 3 1 of the 3 4 carbamate pesticides

. All preselected

## 28 | P a g e



## options were used in gathering “Profile” data ( i.e. , physical/chemical property information,

substructures, etc .) As described below, two separate model d evelopment exercises were

undertaken: (1) using databases resident in the OECD Toolbox and (2) using the web

- ICE

modeling data subset. For models built using the OECD Toolbox resident databases, the aquatic

versions of the ECOTOX, Japan MOE, ECETOC, and O ASIS databases were selected from the

“Endpoint” selection screen

. Under this feature, duplicate empirical data were identified, and a

single value w as used in subsequent analysis . Since the data were already categorized by

structure / mode of action the Category Definition step within the OECD Toolbox was not

completed

. During model building exercises filter

, options were used to select studies that

reported > 90% purity for compounds, and to remove unacceptable organism life stages. In a

separate analysis, the web

- ICE Modeling data subset was loaded into the OECD Toolbox and

used to develop QSAR models. This provided a comparison of effectiveness of model

development using resident OECD empirical data collections vs. independently co mpiled,

empirical data collections screened for quality. It also was an attempt to build models with a

quality assured data set.

QSAR Models Developed Using OECD Empirical Data Sets

Organophosphate Salmonid Model

The OECD Toolbox was used to build a QSAR model for OP AChE inhibitors using

salmonid data available in the associated OECD databases. Salmonids were selected: (a) to

determine if a QSAR model at the family taxonomic level could be built to fulfill a critical MDR,

and (b) because the salmo nid family had more chemicals with available empirical 96 hr LC50

data. Prior to conducting “Data Gap” analysis or QSAR model building, the data were compiled.

The OECD Toolbox asks the user to choose from available concentration units, and only one

unit can be selected. Unfortunately, the OECD Toolbox has not converted all values to a

standard concentration unit ( e.g. , options included ug/L, mg/L, ppm, ppb, etc ). Selection of the

concentration unit was made based on the unit that resulted in the largest set of empirical test

data, but this screen removed all but 12 OPs from the modeling step ( i.e., for the OP chemical

list

, empirical test data were available for selected concentration unit

. ) A n anal ysis was

conducted to determine the most significant molecular descriptors to use as independent

## 29 | P a g e



## variables in QSAR models

. The molecular descriptors with the highest correlation (R 2 

## ) to the

empirical data set were found to be log P ( R 2



## = 0. 480 ), followed by: number of aromatic bonds

( R 2



## = 0. 410 ), number of rings ( R 2



## = 0. 410 ), m aximum diameter ( R 2 

## =0. 245 )

, van der waals surfaces

DPSA1 ( R 2



## = 0

. 166 ), van der waals volume ( R 2



## = 0. 136 )

, and volume polarizability ( R 2



## = 0. 029 ). After

the trend analysis was conducted, the data filters ( e.g., purity, organism life stage, etc .) were

applied to the empirical data for the remaining chemicals. After filtering the data, 11 chemicals

remained for use in QSAR model development. The average concentration value was then

selected. Init ially a model was built using log P as the sole parameter. This resulted in Equation

1 (See Supplemental Information : T

- 5 for summary of chemicals used in model)

.

Equation 1 : log (1/molar LC 50 

## ) = +4.94 +0.371*log P (N=11; R 2 

## =0.61; s=0.707)

T his equation was then used to estimate the toxicity for th e OP substances not in the model

training set (N=39), and resulted in a poorer performance than the ECOSAR model for fish with

an R 2 

## =0.0297 ( Figure 8 )

.

## 30 | P a g e



## QSAR Models Developed Using web

- ICE Modeling Data S ubs et

For this exercise

, the relevant chemical list ( i.e., carbamate, OP) was uploaded into the

OECD Toolbox as the source of structure information. Under the “ Endpoint ” gathering option

within the OECD Toolbox

, the web

- ICE Modeling data subset for fish was uploaded as an

empirical toxicity data source, and this was used as the only source of empirical data in QSAR

model development.

Carbamate Bluegill Model

The carbamate file (N=34) was loaded into the OECD Toolbox and empirical data were

gathered for bluegill from the ICE Modeling data subset. This resulted in 9 chemicals which had

relevant property and empirical test data available for use in model development. A n analysis

of molecular descriptors was conducted and the following parameters had the highest

correlation to the empirical data (R 2 

## ): dipole moment ( R 2



## = 0. 380 ), maximum donor

delocalizability ( R 2



## = 0. 223 ), log P ( R 2



## = 0. 098 ), van der waals surface ( R 2



## = 0.096 ), number of rings

( R 2



## = 0.094 ), and number of cyclic bonds ( R 2



## = 0.057 ). M odel built using either the dipole

moment (R 2



## = 0.380; s=0.60), maximum donor delocalizability (MDD) (R 2



## = 0.223; s=0.67), or log P

(R 2



## = 0.101; s=0.72) , all had low levels of significance, therefore , a multi

- parameter model was

developed. A general rule of thumb in QSAR development is that the ratio of the number of

compounds (in this case 9) divided by the number of descriptor variables (in this case 2) should

not exceed 3 (Richon and You ng, 1997 )

. After ensuring that parameters were not

intercorrelated , a model was developed using dipole moment and maximum donor

delocalizability result ing in Eq uation 2

.

Equation 2: Log(1/mol/L) LC 50 

## = 0.873 +0.332*Dipole +7.38* MDD (N=9; R 2 

## =0.547 ; s = 0.55)

Subsequently the model was used to estimate values for those substances lacking empirical

data and only one additional chemical could be added to the model ( Equation 3 ) which did not

improve it significantly ( Supplemental Information : T

- 6 )

.

Equati on 3: Log(1/mol/L) LC 50 

## = 0. 575 +0. 307 *Dipole + 8.71 * MDD ( N=10; R 2

- 

## =0.5 54 ; s = 0. 52 )

Organophosphate Salmonid Model

## 31 | P a g e



## The list of 97 OP chemicals w as loaded into the OECD Toolbox. Under the “ Endpoint ”

gathering area of the OECD Toolbox , the web

- ICE OP fish data set used to validate ECOSAR was

loaded and used for modeling purposes. For the web

- ICE Modeling data subset , the descriptors

with the best correlation (R 2 

## ) were log P ( 0.142 ), diameter distance ( R 2



## = 0. 109 ), maximum

distance ( R 2



## = 0. 0 98 ), number of cyclic bonds ( R 2



## = 0 .064 ), van der waals surface ( R 2



## = 0.060 ),

diameter effective ( R 2



## = 0 .045 ), and v olume of polarizability ( R 2



## = 0.042 ). Subsequent ly, models

were developed using various combinations of parameters , avoiding any with high inter

correlatio ns, but did not lead to an acceptable model with all having R 2 

## <0.2.

## 32 | P a g e



# Discussion:

Model Performance :

In order for QSAR models to be used effectively they must be predictive for chemicals of

interest. Using a benchmark of an R 2 

## of >0.6 for determining acceptability of QSAR models

(Tropsha 2010) , the OP model for salmonids ( Equation 1 ) developed in the OECD toolbox

passes this criterion, but fails after inclusion of the validation set. Using this benchmark as a

means of evaluating the pe rformance of the T.E.S.T. and ECOSAR models for estimating toxicity

of the AChE inhibitors, all models failed this criterion. QSAR models are typically identified as

predictive if they estimate the toxicity of compounds within an order of magnitude (Zeema n

1995). Using this benchmark, ECOSAR Version 1.1 estimated values for daphnids were within

an order of magnitude for 76% of the chemicals having empirical test data, with carbamate

models performing better (92.3%) than OPs models (70%). The ECOSAR Versi on 1.1 models for

fish were within an order of magnitude for 73.4% of the chemicals with empirical data, with

ECOSAR carbamate models (100%) performing better than the ECOSAR OP models (63.8%). For

the T.E.S.T. models for D. magna , 47

- 56% of the chemicals were estimated within an order of

magnitude when compared to empirical test data. Fathead minnow T.E.S.T. models performed

better with 68

- 88% of the model estimates within an order of magnitude of empirical values.

These benchmarks imply that m odels wit hin ECOSAR Version 1.1 and T.E.S.T. Version 4.0 may

have limited use in determining potency of acetylcholinesterase inhibitors for fish and

daphnids. The improvement of QSAR models from ECOSAR Version 1.0 to Version 1.1,

accomplished by expanding the data collection to include pesticide registration data,

demonstrates th at an expanded training set could improve the performance of both QSAR

tools. Even if these models improve significantly, a consideration will be whether an order of

magnitude is sufficien tly predictive when filling data gaps within the common effects

framework.

## 33 | P a g e



## Strengths, Weaknesses, and Uncertainties Related to the Use of QSAR Models in Filling Data

Gaps:

Currently, as described above, the existing QSAR models predict within an order of

magnitude for the majority of chemicals, but for some, the estimated values can be 3 or more

orders of magnitude different than the empirical data. Even with potential expansion of the

QSAR models to include a larger suite of pesticide data, risk asses sors will have to determine if

an order of magnitude prediction is sufficient for use in filling data gaps for MDRs.

Another consideration is that QSAR models require high quality data for sufficient

numbers of chemicals in order to develop reliable mod els. Evaluations of the OPP pesticide

database (4/17/2008 version) found that the data set is predominately fish, crustacea, with

only limited data for other aquatic taxonomic groups. The top three aquatic species, namely D.

magna , rainbow trout, and blu egill , represent 59% of all test results meeting acceptable

experimental protocols (labeled core studies in the database). Similar patterns of data

availability were found in the ICE Modeling data subset where these three species represent

50% of the test data for all chemicals. It is likely that sufficient QSAR models could be

developed for these freshwater species groups as well as Americamysis bahia (mysid), a

saltwater species that had the largest data sets within the OPP database and the web

- ICE

mode ling data subset

.

Another consideration is the quality of empirical data used in building models. QSARs

initially built under TSCA were primarily based on exper i ment al data that were specifically

generated for QSAR model development. For instance, the fathead minnow database was

developed using chemicals with >90% purity; all studies conducted in the same dilution water,

same test protocols, and the same fish culture where genetic stock sensitivity was monitored

when new breeding pairs were added. All reported LC50s were based on a measured

concentration that had acceptable spike recoveries and percent agreement between duplicate

measurements. By developing a database in this manner, you reduce variability related to

experimental design, thereby reduc ing noise in the model. Pesticide data from OPP may be the

best data set to use since registrants must follow the harmonized test method. Nevertheless

,

prior to use in QSAR modeling

, the OPP data set will require steps to ensure data quality and

## 34 | P a g e



## acceptability of test results. The development of consistent methods to identify a high quality

set of pesticide effects data will be critical to expansion of existing QSAR models.

As can be seen in the example of the OP salmonid model ( Equation 1 ) bu ilt using the

OECD data set, a model needs to be validated externally to ensure that it can be applied to the

class of chemicals of interest. Unfortunately, although the OECD Toolbox ha d large data sets

within the tool , it ha d limitations when selecting a nd filtering data . For instance, when prior to

the “Data Gap Filling” step , the user is required to either pick a taxonomic Class of organisms or

a particular species. Having a more robust taxonomic hierarchy would allow a user to more

easily develop a m odel on a F amily such as Salmonidae. In addition, the user is required to

select a concentration unit, and the system does not make conversions to standard units;

t herefore data are unnecessarily eliminated. Finally, within the OECD Toolbox, selection of

acceptable data using filters similar to those for the web

- ICE Modeling data subset is not easily

done, and may hinder the development of reliable QSAR models.

There are also concern s related to molecular descriptors used in model development.

The b es t descriptors for use in developing pesticide QSAR models , and specifically, molecular

descriptors reported in the QSAR literature for pesticide models may not be available via tools

such as the OECD Toolbox , or specific descriptors may only be available b y purchasing

commercial software packages

. For example, Mastrantonio et al., 2008 found the use of

conformation descriptors, specifically those that account for energy related to the free rotation

of the three phosphate ester bonds, may be a better predic tor of the capability of an OP to bind

to acetylcholinesterase than models based on two

- dimensional descriptors. De Bruijn and

Hermens postulated that QSAR models may be better informed by using rate constants that

describe the binding of AChE for the oxo n forms of the OPs, along with a better understanding

of the enzyme activity within the species of concern.

Potential Utility of QSAR Modeling Approaches within the Common Effects Framework:

A major consideration in using QSAR models to fill data gaps within the common effects

framework is that currently models do not exist for species that are associated with MDR data

gaps, and sufficient high quality data to use in QSAR model development do not appear to be

## 35 | P a g e



## readily available for these taxa. An examination of the ICE Modeling data subset found that

86% of the chemicals categorized as acetylcholinesterase inhibitors met the first MDR (a

salmonid fish), 93% met the second MDR (a non

- salmonid fi sh), 52% met the third MDR (a

species fro m a third chordate family), 70% met the fourth MDR (a planktonic crustacean), 48%

met the fifth MDR (a benthic crustacean), 25% met the sixth MDR (an insect), 8.7% met the

seventh MDR (species form a family in a phy lum other than chordata or arthropoda), and 7.2%

met the eighth MDR (species from a family in another order of insect or in a fourth phylum).

The QSAR models evaluated herein are not unique, in that typical QSAR model packages

estimate for fish, daphnids, and the ciliate Tetrahymena

. For AChE inhibitors , it is unlikely that

QSAR tools will be able to help complete MDR requirements, since most of the species

currently included in QSAR models tend to have empirical data available for the associated

MDRs.

Research Needs Required to Make QSAR Methods Useful to the Common Effects Framework:

Future research that directly supports the common effects framework, would include

the development of high quality toxicity data sets for pesticide active ingredients tested against

taxonomic groups having consistent MDR data gaps. This may require toxicity testing of species

underrepresented within current databases, and /or the curation of data sets from existing

databases. If sufficient data are available, high quality QSAR models for these taxonomic

groups would need to be developed that include the pesticides within the domain of

applicability.

In order to accompl ish t he development of high quality QSAR models for estimating

pesticide active ingredients, methods will need to be developed for consistent identification of

empirical test data acceptable for use in QSAR model development. In addition, QSAR models

with in existing tools need to be expanded to better include pesticide active ingredients within

their domain of applicability, and to expand the models to cover taxa associated with MDR data

gaps. In addition, t hese models should be developed based on the adv erse outcome pathway

and may require the inclusion of parameters other than log P to describe toxicity. To this end,

i t would be helpful to have information related to molecular descriptors that work best in

describing toxicity for specific chemical class es of pesticide structures . These descriptors should

## 36 | P a g e



## have some linkage to key events within the adverse outcome pathway, and would then provide

a means to develop reliable and consistent QSAR models . The literature is scant on which

particular parameters to use, especially for models for ecologically relevant species

. Another

need is a c ontrolled vocabulary for molecular descriptors used (Spjuth, et al. 2010) so that users

have a clear understanding of what the parameter is

, how it was calculated , and ca n compare it

back to similar descriptors calculated by other software tools

.

## 37 | P a g e



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## 41 | P a g e

Supplemental Information T

- 1: Pesticides included in the evaluation of QSAR models.

All have been identified as having a mode of action of acetylcholinesterase inhibition in the target species of (N=127).

Empirical data and model est imates were not available for all substances.

Pesticide CAS Registry

Number Chemical Class: Specific Structure: SMILES



## Carbamates

3,4,5

- Trimethylphenyl

methylcarbamate 2686

- 99

- 9 Phenyl methylcarbamate CNC(=O)Oc1cc(C)c(C)c(C)c1



## Alanycarb 83130

- 01

- 2 Oxime carbamate CCOC(=O)CCN(Cc1ccccc1)SN(C)C(=O)ON=C(C)SC



## Aldicarb 116

- 06

- 3 Oxime carbamate CNC(=O)ON=CC(C)(C)SC



## Aldoxycarb 1646

- 88

- 4 Oxime carbamate CNC(=O)ON=CC(C)(C)S(C)(=O)=O



## Aminocarb 2032

- 59

- 9 Phenyl methylcarbamate CNC(=O)Oc1ccc(N(C)C)c(C)c1



## Bendiocarb 22781

- 23

- 3 Carbamate CNC(=O)Oc1cccc2OC(C)(C)Oc12



## Benfuracarb 82560

- 54

- 1 Benzoforanyl methylcarbamate CCOC(=O)CCN(SN(C)C(=O)Oc1cccc2CC(C)(C)Oc12)C(C)C



## Butocarboxim 34681

- 10

- 2 Oxime carbamate CNC(=O)ON=C(C)C(C)SC



## Butoxycarboxim 34681

- 23

- 7 Oxime carbamate CNC(=O)ON=C(C)C(C)S(C)(=O)=O



## Carbaryl 63

- 25

- 2 Carbamate CNC(=O)Oc1cccc2ccccc12



## Carbofuran 1563

- 66

- 2 Benzoforanyl methylcarbamate CNC(=O)Oc1cccc2CC(C)(C)Oc12



## Carbosulfan 55285

- 14

- 8 Benzoforanyl methylcarbamate CCCCN(CCCC)SN(C)C(=O)Oc1cccc2CC(C)(C)Oc12



## cis

- Thiocarboxime 29118

- 87

- 4 Oxime carbamate CNC(=O)ON=C(C)SCCC(#N)



## Cloethocarb 51487

- 69

- 5 Phenyl methylcarbamate CNC(=O)Oc1ccccc1OC(OC)CCl



## endo

- 3

- Chloro

- exo

- 6

-

cyano

- 2

- norbornanone, o

- (Methylcarbamoyl)

oxime 15271

- 41

- 7 Oxime carbamate CNC(=O)ON=C1C(C2)C(C#N)CC2C1Cl



## Ethiofencarb 29973

- 13

- 5 Phenyl methylcarbamate CCSCc1ccccc1OC(=O)NC



## Fenobucarb 3766

- 81

- 2 Phenyl methylcarbamate CCC(C)c1ccccc1OC(=O)NC



## Formetanate 22259

- 30

- 9 Formamidine CNC(=O)Oc1cccc(N=CN(C)C)c1



## Formetanate

hydrochloride 23422

- 53

- 9 Formamidine CNC(=O)Oc1cccc(N=CN(C)C)c1



## Furathiocarb 65907

- 30

- 4 Benzoforanyl methylcarbamate CCCCOC(=O)N(C)SN(C)C(=O)Oc1cccc2CC(C)(C)Oc12



## Isoprocarb 2631

- 40

- 5 Phenyl methylcarbamate CNC(=O)Oc1ccccc1C(C)C



## Methiocarb 2032

- 65

- 7 Phenyl methylcarbamate CNC(=O)Oc1cc(C)c(SC)c(C)c1



## Methomyl 16752

- 77

- 5 Oxime carbamate CNC(=O)ON=C(C)SC



## Metolcarb 1129

- 41

- 5 Phenyl methylcarbamate CNC(=O)Oc1cccc(C)c1



## Mexacarbate 315

- 18

- 4 Phenyl methylcarbamate CNC(=O)Oc1cc(C)c(N(C)C)c(C)c1



## Oxamyl 23135

- 22

- 0 Oxime carbamate CNC(=O)ON=C(SC)C(=O)N(C)C



## Pirimicarb 23103

- 98

- 2 Dimethylcarbamate CN(C)C(=O)Oc1nc(nc(C)c1C)N(C)C



## Propoxur 114

- 26

- 1 Phenyl methylcarbamate CNC(=O)Oc1ccccc1OC(C)C



## Thiocarboxime 25171

- 63

- 5 Oxime carbamate CNC(=O)ON=C(C)SCCC(#N)

## 42 | P a g e Thiodicarb 59669

- 26

- 0 Oxime carbamate CSC(C)=NOC(=O)N(C)SN(C)C(=O)ON=C(C)SC



## Thiofanox 39196

- 18

- 4 Oxime carbamate CNC(=O)ON=C(CSC)C(C)(C)C



## Triazamate 112143

- 82

- 5 Unclassified CCOC(=O)CSc1nc(nn1C(=O)N(C)C)C(C)(C)C



## XMC 2655

- 14

- 3 Phenyl methylcarbamate CNC(=O)Oc1cc(C)cc(C)c1



## Xylylcarb 2425

- 10

- 7 Phenyl methylcarbamate O=C(Oc(ccc(c1C)C)c1)NC



## Organophosphates

Acephate 30560

- 19

- 1 Phosphoramidothioate COP(=O)(NC(C)=O)SC



## Amidithion 919

- 76

- 6 Aliphatic amide

organothiophosphate S=P(OC)(OC)SCC(=O)NCCOC



## Amiton 78

- 53

- 5 Aliphatic organothiophosphate CCOP(=O)(OCC)SCCN(CC)CC



## Azamethiphos 35575

- 96

- 3 Heterocyclic organothiophosphate COP(=O)(OC)SCn1c(=O)oc2cc(Cl)cnc12



## Azinphos

- ethyl 2642

- 71

- 9 Benzotriazine

organothiophosphate CCOP(=S)(OCC)SCn2nnc1ccccc1c2=O



## Azinphos

- methyl 86

- 50

- 0 Benzotriazine

organothiophosphate S=P(OC)(OC)SCN1N=Nc2ccccc2C1(=O)



## Cadusafos 95465

- 99

- 9 Aliphatic organothiophosphate CCOP(=O)(SC(C)CC)SC(C)CC



## Carbophenothion 786

- 19

- 6 Phenyl organothiophosphate CCOP(=S)(OCC)SCSc1ccc(Cl)cc1



## Chlorethoxyfos 54593

- 83

- 8 Aliphatic organothiophosphate CCOP(=S)(OCC)OC(Cl)C(Cl)(Cl)Cl



## Chlorfenvinphos 470

- 90

- 6 Organophosphate CCOP(=O)(OCC)OC(=CCl)c1ccc(Cl)cc1Cl



## Chlormephos 24934

- 91

- 6 Aliphatic organothiophosphate CCOP(=S)(OCC)SCCl



## Chlorpyrifos 2921

- 88

- 2 Pyridine organothiophosphate CCOP(=S)(OCC)Oc1nc(Cl)c(Cl)cc1Cl



## Chlorpyrifos

- methyl 5598

- 13

- 0 Pyridine organothiophosphate COP(=S)(OC)Oc1nc(Cl)c(Cl)cc1Cl



## Chlorpyrifos

- methyl

oxon 5598

- 52

- 7 Degradate

- Oxon O=P(OC)(OC)Oc1nc(Cl)cc(Cl)c1Cl



## Chlorthion 500

- 28

- 7 Phenyl organothiophosphate COP(=S)(OC)Oc1ccc(N(=O)=O)c(Cl)c1



## Coumaphos 56

- 72

- 4 Heterocyclic organothiophosphate S=P(OCC)(OCC)Oc1ccc2C(C)=C(Cl)C(=O)Oc2c1



## Crufomate 299

- 86

- 5 Phosphoramidate CNP(=O)(OC)Oc1ccc(cc1Cl)C(C)(C)C



## Cyanophos 2636

- 26

- 2 Phenyl organothiophosphate COP(=S)(OC)Oc1ccc(C#N)cc1



## Demeton 8065

- 48

- 3 Aliphatic organothiophosphate S=P(OCC)(OCC)OCCSCC + O=P(OCC)(OCC)OCCSCC



## Demeton

- S

- methyl 919

- 86

- 8 Aliphatic organothiophosphate CCSCCSP(=O)(OC)OC



## Diamidafos 1754

- 58

- 1 Organophosphate O=P(NC)(NC)Oc1ccccc1



## Diazinon 333

- 41

- 5 Pyrimidine organothiophosphate CCOP(=S)(OCC)Oc1cc(C)nc(n1)C(C)C



## Dichlofenthion 97

- 17

- 6 Phenyl organothiophosphate CCOP(=S)(OCC)Oc1ccc(Cl)cc1Cl



## Dichlorvos/DDVP 62

- 73

- 7 Organophosphate COP(=O)(OC)OC=C(Cl)Cl



## Dicrotophos 141

- 66

- 2 Organophosphate COP(=O)(OC)OC(C)=CC(=O)N(C)C



## Dimethoate 60

- 51

- 5 Aliphatic amide

organothiophosphate CNC(=O)CSP(=S)(OC)OC



## Dimethylvinphos 2274

- 67

- 1 Organophosphate COP(=O)(OC)OC(=CCl)c1ccc(Cl)cc1Cl

## 43 | P a g e Dioxathion 78

- 34

- 2 Heterocyclic organothiophosphate CCOP(=S)(OCC)SC1OCCOC1SP(=S)(OCC)OCC



## Disulfoton 298

- 04

- 4 Aliphatic organothiophosphate CCOP(=S)(OCC)SCCSCC



## EPN 2104

- 64

- 5 Phenyl phenylphosphonothioate CCOP(=S)(Oc1ccc(cc1)N(=O)=O)c2ccccc2



## Ethion 563

- 12

- 2 Aliphatic organothiophosphate CCOP(=S)(OCC)SCSP(=S)(OCC)OCC



## Ethoprophos 13194

- 48

- 4 Aliphatic organothiophosphate CCCSP(=O)(OCC)SCCC



## Famphur 52

- 85

- 7 Phenyl organothiophosphate COP(=S)(OC)Oc1ccc(cc1)S(=O)(=O)N(C)C



## Fenamiphos 22224

- 92

- 6 Phosphoramidate CCOP(=O)(NC(C)C)Oc1ccc(SC)c(C)c1



## Fenchlorphos 299

- 84

- 3 Phenyl organothiophosphate COP(=S)(OC)Oc1cc(Cl)c(Cl)cc1Cl



## Fenitrothion 122

- 14

- 5 Phenyl organothiophosphate COP(=S)(OC)Oc1ccc(N(=O)=O)c(C)c1



## Fensulfothion 115

- 90

- 2 Phenyl organothiophosphate CCOP(=S)(OCC)Oc1ccc(cc1)S(C)=O



## Fenthion 55

- 38

- 9 Phenyl organothiophosphate COP(=S)(OC)Oc1ccc(SC)c(C)c1



## Fonofos 944

- 22

- 9 Phenyl ethylphosphonothioate CCOP(=S)(CC)Sc1ccccc1



## Fosthiazate 98886

- 44

- 3 Heterocyclic organothiophosphate CCOP(=O)(SC(C)CC)N1CCSC1=O



## Fosthietan 21548

- 32

- 3 Phosphoramidate CCOP(=O)(OCC)N=C1SCS1



## Heptenophos 23560

- 59

- 0 Organophosphate COP(=O)(OC)OC1=C(Cl)C2C=CCC12



## Heterophos 40626

- 35

- 5 Phenyl organothiophosphate CCCSP(=O)(OCC)Oc1ccccc1



## Imicyafos 140163

- 89

- 9 Phosphonothioate CCOP(=O)(SCCC)N1C(=NC#N)N(CC)CC1



## Iodofenphos 18181

- 70

- 9 Phenyl organothiophosphate COP(=S)(OC)Oc1cc(Cl)c(I)cc1Cl



## Isamidofos 66602

- 87

- 7 Organothiophosphate CCOP(=O)(NC(C)C)SCC(=O)N(C)c1ccccc1



## Isazofos 42509

- 80

- 8 Triazole organothiophosphate CCOP(=S)(OCC)Oc1nc(Cl)n(n1)C(C)C



## Isofenphos 25311

- 71

- 1 Phosphoramidothioate CCOP(=S)(NC(C)C)Oc1ccccc1C(=O)OC(C)C



## Isoxathion 18854

- 01

- 8 Isoxazole organothiophosphate CCOP(=S)(OCC)Oc1cc(on1)c2ccccc2



## Leptophos 21609

- 90

- 5 Phenyl phenylphosphonothioate COP(=S)(Oc1cc(Cl)c(Br)cc1Cl)c2ccccc2



## Malathion 121

- 75

- 5 Aliphatic organothiophosphate CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC



## Mecarbam 2595

- 54

- 2 Aliphatic amide

organothiophosphate CCOC(=O)N(C)C(=O)CSP(=S)(OCC)OCC



## Methamidophos 10265

- 92

- 6 Phosphoramidothioate COP(N)(=O)SC



## Methidathion 950

- 37

- 8 Thiadiazole organothiophosphate COc1nn(CSP(=S)(OC)OC)c(=O)s1



## Methyl

carbophenothion 953

- 17

- 3 Phenyl organothiophosphate COP(=S)(OC)SCSc1ccc(Cl)cc1



## Mevinphos 7786

- 34

- 7 Organophosphate COC(=O)C=C(C)OP(=O)(OC)OC



## Monocrotophos 6923

- 22

- 4 Organophosphate CNC(=O)C=C(C)OP(=O)(OC)OC



## Naled 300

- 76

- 5 Organophosphate COP(=O)(OC)OC(Br)C(Cl)(Cl)Br



## Omethoate 1113

- 02

- 6 Aliphatic amide

organothiophosphate CNC(=O)CSP(=O)(OC)OC



## Oxydemeton

- methyl 301

- 12

- 2 Aliphatic organothiophosphate CCS(=O)CCSP(=O)(OC)OC



## Parathion 56

- 38

- 2 Phenyl organothiophosphate CCOP(=S)(OCC)Oc1ccc(cc1)N(=O)=O



## Parathion

- methyl 298

- 00

- 0 Phenyl organothiophosphate S=P(OC)(OC)O

- c(ccc1N(=O)=O)cc1



## Phenthoate 2597

- 03

- 7 Organothiophosphate CCOC(=O)C(SP(=S)(OC)OC)c1ccccc1



## Phorate 298

- 02

- 2 Aliphatic organothiophosphate CCOP(=S)(OCC)SCSCC

## 44 | P a g e Phosacetim 4104

- 14

- 7 Organothiophosphate Clc(ccc1OP(=S)(NC(=N)C)Oc(ccc2Cl)cc2)cc1



## Phosalone 2310

- 17

- 0 Heterocyclic organothiophosphate CCOP(=S)(OCC)SCn1c(=O)oc2cc(Cl)ccc12



## Phosmet 732

- 11

- 6 Isoindole organothiophosphate COP(=S)(OC)SCN2C(=O)c1ccccc1C2=O



## Phosphamidon 13171

- 21

- 6 Organophosphate CCN(CC)C(=O)C(Cl)=C(C)OP(=O)(OC)OC



## Phosphamidon (E

isomer) 297

- 99

- 4 Organophosphate CCN(CC)C(=O)C(Cl)=C(C)OP(=O)(OC)OC



## Phosphocarb 126069

- 54

- 3 Phenyl organothiophosphate CCCSP(=O)(OCC)Oc1ccccc1OC(=O)NC



## Phoxim 14816

- 18

- 3 Oxime organothiophosphate CCOP(=S)(OCC)ON=C(C#N)c1ccccc1



## Pirimiphos

- methyl 29232

- 93

- 7 Pyrimidine organothiophosphate CCN(CC)c1nc(C)cc(OP(=S)(OC)OC)n1



## Profenofos 41198

- 08

- 7 Phenyl organothiophosphate CCCSP(=O)(OCC)Oc1ccc(Br)cc1Cl



## Propaphos 7292

- 16

- 2 Organophosphate CCCOP(=O)(OCCC)Oc1ccc(SC)cc1



## Propetamphos 31218

- 83

- 4 Phosphoramidothioate CCNP(=S)(OC)OC(C)=CC(=O)OC(C)C



## Prothiofos 34643

- 46

- 4 Phenyl organothiophosphate CCCSP(=S)(OCC)Oc1ccc(Cl)cc1Cl



## Pyraclofos 77458

- 01

- 6 Heterocyclic organothiophosphate CCCSP(=O)(OCC)Oc1cnn(c1)c2ccc(Cl)cc2



## Pyridaphenthion 119

- 12

- 0 Heterocyclic organothiophosphate S=P(OCC)(OCC)OC1=NN(c2ccccc2)C(=O)C=C1



## Quinalphos 13593

- 03

- 8 Quinoxaline organothiophosphate CCOP(=S)(OCC)Oc2cnc1ccccc1n2



## SD

- 7438 2782

- 70

- 9 Organothiophosphate COP(=S)(OC)SCc1ccc(SP(=S)(OC)OC)cc1



## Sulfotep 3689

- 24

- 5 Aliphatic organothiophosphate CCOP(=S)(OCC)OP(=S)(OCC)OCC



## Tebupirimfos 96182

- 53

- 5 Pyrimidine organothiophosphate CCOP(=S)(OC(C)C)Oc1cnc(nc1)C(C)(C)C



## Temephos 3383

- 96

- 8 Phenyl organothiophosphate COP(=S)(OC)Oc2ccc(Sc1ccc(OP(=S)(OC)OC)cc1)cc2



## TEPP 107

- 49

- 3 Organophosphate CCOP(=O)(OCC)OP(=O)(OCC)OCC



## Terbufos 13071

- 79

- 9 Aliphatic organothiophosphate CCOP(=S)(OCC)SCSC(C)(C)C



## Tetrachlorvinphos 22248

- 79

- 9 Organophosphate COP(=O)(OC)OC(=CCl)c1cc(Cl)c(Cl)cc1Cl



## Tetrachlorvinphos (E

/ Z Isomer) 961

- 11

- 5 Organophosphate Cl

- c(cc(Cl)c1C(OP(=O)(OC)OC)=CCl)c(Cl)c1



## Thiometon 640

- 15

- 3 Aliphatic organothiophosphate CCSCCSP(=S)(OC)OC



## Thionazin 297

- 97

- 2 Heterocyclic organothiophosphate CCOP(=S)(OCC)Oc1cnccn1



## Triazophos 24017

- 47

- 8 Triazole organothiophosphate CCOP(=S)(OCC)Oc1ncn(n1)c2ccccc2



## Trichlorfon 52

- 68

- 6 Phosphonate COP(=O)(OC)C(O)C(Cl)(Cl)Cl



## Trichloronate 327

- 98

- 0 Phenyl ethylphosphonothioate CCOP(=S)(CC)Oc1cc(Cl)c(Cl)cc1Cl



## Vamidothion 2275

- 23

- 2 Aliphatic amide

organothiophosphate CNC(=O)C(C)SCCSP(=O)(OC)OC

## 45 | P a g e Supplemental Information T

- 2 : Empirical data set of acceptable quality data for acetylcholinesterase inhibitors for use in

comparison to QSAR model estimates. The ECOSAR Version 1.1 tool included generic fish and daphnid QSAR models.

For this exercise, fish model estimates were compared to either rainb ow trout ( Oncorhynchus mykiss ) or bluegill

( Lepomis macrochirus ) empirical data, and daphnid models were compared to Daphnia magna and/or Daphnia pulex

empirical data. T.E.S.T. Version 4.0 models were developed for Pimphales promelas and Daphnia magna , an d were

compared to empirical test data for these species.

Empirical Test Data

CAS

Registry

Number Pesticide QSAR

Model used

in

Comparison Species Minimum

Toxicity

(ug/L) Maximum

Toxicity

(ug/L) Average

Concentration

(ug/L) Number

of

Toxicity

Values Source of Empirical Data and

Comment s

52686 Trichlorfon ECOSAR Oncorhynchus mykiss 370 8800 1882.57 28 ICE Model Data set

55389 Fenthion ECOSAR Oncorhynchus mykiss 550 840 740 3 ICE Model Data set

56382 Parathion ECOSAR Oncorhynchus mykiss 864 1430 1214.67 3 ICE Model Data set

56724 Coumaphos ECOSAR Oncorhynchus mykiss 890 890 890 1 ICE Model Data set

60515 Dimethoate ECOSAR Oncorhynchus mykiss 6200 8600 7433.33 3 ICE Model Data set

62737 Dichlorvos/DDVP ECOSAR Oncorhynchus mykiss 100 100 100 1 ICE Model Data set

63252 Carbaryl ECOSAR Oncorhynchus mykiss 780 3500 1796.63 16 ICE Model Data set

78342 Dioxathion ECOSAR Oncorhynchus mykiss 69 69 69 1 ICE Model Data set

86500 Azinphos

- methyl ECOSAR Oncorhynchus mykiss 4.3 6.3 5.3 2 ICE Model Data set

97176 Dichlofenthion ECOSAR Oncorhynchus mykiss 1250 1250 1250 1 ICE Model Data set

114261 Propoxur ECOSAR Oncorhynchus mykiss 3700 3700 3700 1 ICE Model Data set

115902 Fensulfothion ECOSAR Lepomis macrochirus 72 72 72 1 ICE Model Data set

116063 Aldicarb ECOSAR Oncorhynchus mykiss 560 560 560 1 ICE Model Data set

121755 Malathion ECOSAR Oncorhynchus mykiss 30 200 105.6 5 ICE Model Data set

122145 Fenitrothion ECOSAR Oncorhynchus mykiss 1000 2700 2050 7 ICE Model Data set

141662 Dicrotophos ECOSAR Oncorhynchus mykiss 6300 6300 6300 1 ICE Model Data set

298000 Parathion

- methyl ECOSAR Oncorhynchus mykiss 2750 3700 3225 2 ICE Model Data set

298022 Phorate ECOSAR Oncorhynchus mykiss 13 21 17 2 ICE Model Data set

298044 Disulfoton ECOSAR Oncorhynchus mykiss 1850 1850 1850 1 ICE Model Data set

299843 Fenchlorphos ECOSAR Oncorhynchus mykiss 550 645 597.5 2 ICE Model Data set

299865 Crufomate ECOSAR Lepomis macrochirus 1800 1800 1800 1 ICE Model Data set

300765 Naled ECOSAR Oncorhynchus mykiss 132 195 167.33 3 ICE Model Data set

301122 Oxydemeton

methyl ECOSAR Oncorhynchus mykiss 730 730 730 1 ICE Model Data set

315184 Mexacarbate ECOSAR Oncorhynchus mykiss 4450 15000 9887.5 4 ICE Model Data set

327980 Trichloronate ECOSAR Oncorhynchus mykiss 140 140 140 1 ICE Model Data set

333415 Diazinon ECOSAR Lepomis macrochirus 136 460 254.67 3 ICE Model Data set

## 46 | P a g e

470906 Chlorfenvinphos ECOSAR Oncorhynchus mykiss 510 510 510 1 ICE Model Data set

563122 Ethion ECOSAR Oncorhynchus mykiss 500 500 500 1 ICE Model Data set

732116 Phosmet ECOSAR Oncorhynchus mykiss 105 4700 1142.08 12 ICE Model Data set

741582 bensulide ECOSAR Oncorhynchus mykiss 720 1400 1073.33 3 ICE Model Data set

786196 Carbophenothion ECOSAR Lepomis macrochirus 13 13 13 1 ICE Model Data set

944229 Fonofos ECOSAR Oncorhynchus mykiss 20 50 35 2 ICE Model Data set

950378 Methidathion ECOSAR Oncorhynchus mykiss 10 14 12 2 ICE Model Data set

953173 Methyl

carbophenothion ECOSAR Oncorhynchus mykiss 760 760 760 1 ICE Model Data set

1563662 Carbofuran ECOSAR Oncorhynchus mykiss 380 600 466.67 3 ICE Model Data set

1646884 Aldoxycarb ECOSAR Oncorhynchus mykiss 42000 42000 42000 1 ICE Model Data set

2032599 Aminocarb ECOSAR Oncorhynchus mykiss 12000 25000 18314.29 7 ICE Model Data set

2032657 Methiocarb ECOSAR Oncorhynchus mykiss 436 750 593 2 ICE Model Data set

2104645 EPN ECOSAR Oncorhynchus mykiss 210 210 210 1 ICE Model Data set

2686999 3,4,5

-

Trimethylphenyl

methylcarbamate ECOSAR Oncorhynchus mykiss 4700 4700 4700 1 ICE Model Data set

2782709 SD

- 7438 ECOSAR Oncorhynchus mykiss 34 34 34 1 ICE Model Data set

2921882 Chlorpyrifos ECOSAR Oncorhynchus mykiss 7.1 25 13.37 3 ICE Model Data set

3383968 Temephos ECOSAR Oncorhynchus mykiss 3490 6800 5145 2 ICE Model Data set

3689245 Sulfotep ECOSAR Oncorhynchus mykiss 1000 1000 1000 1 ICE Model Data set

5598130 Chlorpyrifos

- methyl ECOSAR Oncorhynchus mykiss 120 301 210.5 2 ICE Model Data set

5598527 Chlorpyrifos

- methyl

oxon ECOSAR Oncorhynchus mykiss 1.7 2 1.85 2 ICE Model Data set

6923224 Monocrotophos ECOSAR Lepomis macrochirus 12100 12100 12100 1 ICE Model Data set

8065483 Demeton ECOSAR Oncorhynchus mykiss 520 600 560 2 ICE Model Data set

13194484 Ethoprophos ECOSAR Oncorhynchus mykiss 1150 1150 1150 1 ICE Model Data set

15271417 endo

- 3

- Chloro

- exo

6

- cyano

- 2

- norbornanone, o

- (Methylcarbamoyl)

oxime ECOSAR Oncorhynchus mykiss 13000 13000 13000 1 ICE Model Data set

16752775 Methomyl ECOSAR Oncorhynchus mykiss 1050 1600 1308.33 6 ICE Model Data set

18181709 Iodofenphos ECOSAR Oncorhynchus mykiss 16.2 16.2 16.2 1 ICE Model Data set

## 47 | P a g e

22781233 Bendiocarb ECOSAR Oncorhynchus mykiss 1200 1200 1200 1 ICE Model Data set

23103982 Pirimicarb ECOSAR Oncorhynchus mykiss 79000 79000 79000 1 ICE Model Data set

23135220 Oxamyl ECOSAR Oncorhynchus mykiss 4200 4700 4450 2 ICE Model Data set

23422539 Formetanate

hydrochloride ECOSAR Oncorhynchus mykiss 4400 4400 4400 1 ICE Model Data set

25311711 Isofenphos ECOSAR Lepomis macrochirus 1400 1400 1400 1 ICE Model Data set

29118874 cis

- Thiocarboxime ECOSAR Oncorhynchus mykiss 1500 1500 1500 1 ICE Model Data set

30560191 Acephate ECOSAR Oncorhynchus mykiss 110000 110000 110000 1 ICE Model Data set

31218834 Propetamphos ECOSAR Oncorhynchus mykiss 940 2600 1770 2 ICE Model Data set

41198087 Profenofos ECOSAR Oncorhynchus mykiss 21 23.5 22.25 2 ICE Model Data set

42509808 Isazofos ECOSAR Oncorhynchus mykiss 18.7 18.7 18.7 1 ICE Model Data set

59669260 Thiodicarb ECOSAR Oncorhynchus mykiss 2650 2650 2650 1 ICE Model Data set

96182535 Tebupirimfos ECOSAR Oncorhynchus mykiss 2220 2220 2220 1 ICE Model Data set

98886443 Fosthiazate ECOSAR Oncorhynchus mykiss 111000 111000 111000 1 ICE Model Data set

52686 Trichlorfon ECOSAR Daphnia magna;

Daphnia pulex 0.12 0.35 0.226667 3 Augmented ICE (one OPP data

record) Chemical/species not

in Original ICE Model Data set;

Added from ECOTOX Data set

of 3 values

55389 Fenthion ECOSAR Daphnia magna;

Daphnia pulex 0.8 5.7 3.9 3 All from OPP data set

56382 Parathion ECOSAR Daphnia magna;

Daphnia pulex 0.38 1.4 1.018333 12 ICE Model Data set had two

values of 1 and 1.27 ug/L;

augmented with ECOTOX data;

Average not sig diff

56724 Coumaphos ECOSAR Daphnia magna 0.192 0.192 0.192 1 OPP data set value

60515 Dimethoate ECOSAR Daphnia magna 1500 6400 2716.667 6 Verified data against two

publications; EcoRef 5675 and

600)

62737 Dichlorvos/DDVP ECOSAR Daphnia magna 0.085 0.266 0.1755 2 Looked at both empirical

values; one from Dutch data

set (EcoREf 5370 doc not

available) the other is a UWS

study verified (EcoRef 17138)

63252 Carbaryl ECOSAR Daphnia magna 9.5 10.1 9.8 2

78342 Dioxathion ECOSAR Daphnia magna 0.35 0.35 0.35 1 M&E Value

86500 Azinphos

- methyl ECOSAR Daphnia magna 1.13 1.13 1.13 1 OPP data set value

114261 Propoxur ECOSAR Daphnia magna 11 27.2 19.1 2

116063 Aldicarb ECOSAR Daphnia magna 410.7 696 553.35 2

119120 Pyridaphenthion ECOSAR Daphnia magna 0.92 0.92 0.92 1

121755 Malathion ECOSAR Daphnia magna 1.6 1.6 1.6 1

122145 Fenitrothion ECOSAR Daphnia magna 11 11 11 1 OPP data set value

## 48 | P a g e

298000 Parathion

- methyl ECOSAR Daphnia magna 0.14 0.16 0.15 2

298044 Disulfoton ECOSAR Daphnia magna 13 13 13 1

300765 Naled ECOSAR Daphnia magna 0.3 0.3 0.3 1

301122 Oxydemeton

methyl ECOSAR Daphnia magna 240 240 240 1

333415 Diazinon ECOSAR Daphnia magna 0.96 0.96 0.96 1

563122 Ethion ECOSAR Daphnia magna;

Daphnia pulex 0.056 2.8 1.42 2 OPP Data Set

732116 Phosmet ECOSAR Daphnia magna 5.6 5.6 5.6 1

741582 bensulide ECOSAR Daphnia magna 580 580 580 1 OPP Data set

944229 Fonofos ECOSAR Daphnia magna 2 2 2 1

950378 Methidathion ECOSAR Daphnia magna 6.4 6.4 6.4 1

1113026 Omethoate ECOSAR Daphnia magna 21 21 21 1

1563662 Carbofuran ECOSAR Daphnia magna 29 92 62.82 5 ICE Model Data set had two

values of 29 and 86.1 ug/L;

augmented with ECOTOX

data; Average not sig diff

1646884 Aldoxycarb ECOSAR Daphnia magna 280 280 280 1

2032599 Aminocarb ECOSAR Daphnia magna 17.5 17.5 17.5 1

2032657 Methiocarb ECOSAR Daphnia magna 19 19 19 1

2104645 EPN ECOSAR Daphnia magna 0.3 0.3 0.3 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

2597037 Phenthoate ECOSAR Daphnia magna 0.34 0.34 0.34 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

2921882 Chlorpyrifos ECOSAR Daphnia magna 0.1 1.7 0.663333 3 OPP data and lowest value

from EcoREf 96171 confirmed

3383968 Temephos ECOSAR Daphnia magna 0.011 0.011 0.011 1 OPP Data set

3689245 Sulfotep ECOSAR Daphnia magna 2.5 2.5 2.5 1

5598130 Chlorpyrifos

- methyl ECOSAR Daphnia magna 0.79 1.11 0.95 2

8065483 Demeton ECOSAR Daphnia pulex 14 14 14 1

13171216 Phosphamidon ECOSAR Daphnia magna 12.7 12.7 12.7 1

13194484 Ethoprophos ECOSAR Daphnia magna 93 93 93 1

13593038 Quinalphos ECOSAR Daphnia magna 0.21 0.21 0.21 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

## 49 | P a g e

16752775 Methomyl ECOSAR Daphnia magna 8.8 31.7 21.934 5 ICE Model Data set had two

values of 8.8

- 31.7 ug/L;

average 20.25 ug/l;

augmented with ECOTOX data

not in ICE; Average not sig diff

22781233 Bendiocarb ECOSAR Daphnia magna 29.2 29.2 29.2 1

23103982 Pirimicarb ECOSAR Daphnia magna;

Daphnia pulex 6.5 19.1 14.87 3

23135220 Oxamyl ECOSAR Daphnia magna 5700 5700 5700 1 OPP Data set

23422539 Formetanate

hydrochloride ECOSAR Daphnia magna 86.8 86.8 86.8 1

25311711 Isofenphos ECOSAR Daphnia magna 2.6 3.9 3.25 2 ICE Model data set had one

value (3.9 ug/L from OPP);

augmented with ECOTOX

value (2.6 ug/L) from EcoRef

96171

29232937 Pirimiphos

- methyl ECOSAR Daphnia magna 0.21 0.44 0.325 2 ICE Model data set had one

value (0.219 ug/L from OPP);

augmented with ECOTOX

value (0.44 ug/L) from EcoRef

96171

31218834 Propetamphos ECOSAR Daphnia magna 3.3 14 8.65 2

41198087 Profenofos ECOSAR Daphnia magna 0.93 2.8 1.865 2

59669260 Thiodicarb ECOSAR Daphnia magna 27 27 27 1

96182535 Tebupirimfos ECOSAR Daphnia magna 0.078 0.078 0.078 1

98886443 Fosthiazate ECOSAR Daphnia magna 260 260 260 1

52686 Trichlorfon T.E.S.T. Pimephales promelas 7900 7900 7900 1 ICE Model Data Set

55389 Fenthion T.E.S.T. Pimephales promelas 3200 3500 3333.33 3 ICE Model Data Set

56382 Parathion T.E.S.T. Pimephales promelas 2350 2350 2350 1 ICE Model Data Set;

62737 Dichlorvos/DDVP T.E.S.T. Pimephales promelas 4000 4000 4000 1 ICE Model Data Set

63252 Carbaryl T.E.S.T. Pimephales promelas 3940 14600 7926.47 17 ICE Model data set had 8

values (8231 (5171

- 13000)

ug/L; augmented with ECOTOX

data

78342 Dioxathion T.E.S.T. Pimephales promelas 9300 10000 5150 2 ICE Model Data Set rejected

these data point, but one

value (300 ug/L) was incorrect

and should be 9,000 ug/L; it is

assumed they were rejected

due to high max/min ratio;

Modified MIN; to 9300 ug/L

and included data; both from

sa me paper (EcoRef 2893)

86500 Azinphos

- methyl T.E.S.T. Pimephales promelas 100 3260 1694.38 16 ICE Model Data Set & ECOTOX;

studies range from 64

- 3260

ug/L; lowest value (64 ug/L)

from UWS

114261 Propoxur T.E.S.T. Pimephales promelas 8800 8800 8800 1 ICE Model Data Set

115902 Fensulfothion T.E.S.T. Pimephales promelas 43100 43100 43100 1 ICE Model Data Set

## 50 | P a g e

116063 Aldicarb T.E.S.T. Pimephales promelas 861 1370 1115.5 2 ICE Model Data Set

121755 Malathion T.E.S.T. Pimephales promelas 14100 14100 14100 1 ICE Model Data Set

122145 Fenitrothion T.E.S.T. Pimephales promelas ICE data base

298000 Parathion

- methyl T.E.S.T. Pimephales promelas 8900 8900 8900 1 ICE data base

298022 Pho rate T.E.S.T. Pimephales promelas 250 250 250 1 Data from ECOTOX;

Chemical/Species pair not in

ICE Full or Model data set;

Data from EcoRef 8096 and

confirmed

298044 Disulfoton T.E.S.T. Pimephales promelas 1870 4100 3370 5 ICE Model Data Set

300765 Naled T.E.S.T. Pimephales promelas ICE data base

333415 Diazinon T.E.S.T. Pimephales promelas 6600 10000 7800 4 ICE Model Data Set

563122 Eth ion T.E.S.T. Pimephales promelas 720 720 720 2 ICE Model Data Set

732116 Phosmet T.E.S.T. Pimephales promelas 7300 7300 7300 1 ICE Model Data Set

786196 Carbophenothion T.E.S.T. Pimephales promelas 220 237 228.5 2 Chemical/Species not included

in ICE model data set; one

value (220 ug/L) is in ICE data

set but rejected; ECOTOX had

these two values. One from

UWS and considered reliable;

used both due to agreement

944229 Fonofos T.E.S.T. Pimephales promelas 1090 1090 1090 1 TEST provides a comparison

value from the ECOTOX

database (EcoRef 15169),

Purity is not identified, but

authors provide a measured

concentration value; will use

for comparison purposes

1563662 Carbofuran T.E.S.T. Pimephales promelas 844 1990 1235.33 3 ICE Model Data Set

2032599 Aminocarb T.E.S.T. Pimephales promelas 1950 1950 1950 1 ICE Model Data Set

2104645 EPN T.E.S.T. Pimephales promelas 78.6 78.6 78.6 1 ICE Model Data Set

2921882 Chlorpyrifos T.E.S.T. Pimephales promelas 140 542 280.57 7 ICE Model Data Set had only 2

values (200

- 203 ug/L);

ECOTOX included 5 studies

ranging from 200

- 506 ug/L

from Duluth which were

included

3383968 Temephos T.E.S.T. Pimephales promelas 34100 34100 34100 1 ICE Model Data Set

5598130 Chlorpyrifos

- methyl T.E.S.T. Pimephales promelas ICE data base

13071799 Terbufos T.E.S.T. Pimephales promelas 13.3 13.3 13.3 1 ICE Model Data Set

16752775 M ethomyl T.E.S.T. Pimephales promelas 2110 2110 2110 1 ICE Model Data Set

23135220 Oxamyl T.E.S.T. Pimephales promelas 5480 8300 6890 2 ICE Model Data Set

41198087 Profenofos T.E.S.T. Pimephales promelas 333 333 333 1 ICE Model Data Set

52686 Trichlorfon T.E.S.T. Daphnia magna 0.12 0.35 0.23 3 Chemical/species not in

Original ICE Model Data set;

Added from ECOTOX Data set

of 3 values

55389 Fenthion T.E.S.T. Daphnia magna 5.2 5.7 5.45 2 ICE Model Data

## 51 | P a g e

56382 Parathion T.E.S.T. Daphnia magna 0.38 1.4 1.02 12 ICE Model Data set had two

values of 1 and 1.27 ug/L;

augmented with ECOTOX data

56724 Coumaphos T.E.S.T. Daphnia magna 0.19 0.19 0.19 1 ICE Model Data; Confirmed

Exp value; no new data in

ECOTOX

60515 Dimethoate T.E.S.T. Daphnia magna 1500 6400 2716.67 6 ICE Model data set; ECOTOX

had additional data but

average value did not change

significantly

62737 Dichlorvos/DDVP T.E.S.T. Daphnia magna 0.09 0.27 0.18 2 ICE Model Data

63252 Carbaryl T.E.S.T. Daphnia magna 9.5 10.1 9.8 2 ICE Model data set; ECOTOX

had additional data but

average value did not change

significantly

78342 Dioxathion T.E.S.T. Daphnia magna 0.35 0.35 0.35 1 ICE Model Data; M&E value

86500 Azinphos

- methyl T.E.S.T. Daphnia magna 1.1 1.6 1.45 4 ICE Model data set only had

one value (1.13 ug/L); ECOTOX

had four that met criteria used

ECOTOX

97176 Dichlofenthion T.E.S.T. Daphnia magna 1.1 1.1 1.1 1 ICE Model data set; no new

data in ECOTOX; Confirmed

Exp value

114261 Propoxur T.E.S.T. Daphnia magna 11 27.2 19.1 2 ICE Model data set; ECOTOX

had additional data but

average value did not change

significantly

116063 Aldicarb T.E.S.T. Daphnia magna 410.7 696 553.35 2 ICE Model data set; ECOTOX

had additional data but was

higher test temperature

119120 Pyridaphenthion T.E.S.T. Daphnia magna 0.92 0.92 0.92 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

121755 Malathion T.E.S.T. Daphnia magna 1.6 1.6 1.6 1 ICE Model data set; ECOTOX

had additional data (N=10); all

but one were in the range of

0.9

- 2.2 ug/L; used ICE values

122145 Fenitrothion T.E.S.T. Daphnia magna 0.73 50 5.58 5 ICE database had one value

from M&E data set (11 ug/L);

ECOTOX had four additional

results ranging from 0.73

- 4.98

ug/l all from the same paper

(EcoRef 104270) where the

authors tested four strains of

daphnia and found a range of

toxicity; used ECOTOX data

298000 Parathion

- methyl T.E.S.T. Daphnia magna 0.14 0.16 0.15 2 ICE model data set; additional

data in ECOTOX but rejected

for ICE (unsure why) would

have had an average of 5.37

ug/L and ranged from 0.14

- 86

ug/L

298044 Disulfoton T.E.S.T. Daphnia magna 13 13 13 1 ICE Model data set; from OPP

Data set; no additional data in

ECOTOX

## 52 | P a g e

300765 Naled T.E.S.T. Daphnia magna 0.3 0.3 0.3 1 ICE Model data set; from OPP

Data set; no additional data in

ECOTOX

301122 Oxydemeton

-

methyl T.E.S.T. Daphnia magna 240 240 240 1 ICE Model data set; from OPP

Data set; no additional data in

ECOTOX

333415 Diazinon T.E.S.T. Daphnia magna 0.96 0.96 0.96 1 ICE Model data set; ECOTOX

had additional values not used

by ICE ranging from 0.7

- 6.1

ug/L

563122 Ethion T.E.S.T. Daphnia magna 0.06 0.06 0.06 2 ICE Model Data Set; OPP and

M&E data sets

732116 Phosmet T.E.S.T. Daphnia magna 5.6 5.6 5.6 1 ICE Model Data Set; M&E

value

944229 Fonofos T.E.S.T. Daphnia magna 2 2 2 1 ICE Model data set; ECOTOX

did not have this values but

had another one from the

published literature (2.7 ug/L)

1113026 Omethoate T.E.S.T. Daphnia magna 21 21 21 1 ICE Model Data set; OECDN

data set (EcoRef 5180)

1563662 Carbofuran T.E.S.T. Daphnia magna 29 92 62.82 5 ICE Model Data set had two

values of 29 and 86.1 ug/L;

augmented with ECOTOX

data; Average not sig diff

1646884 Aldoxycarb T.E.S.T. Daphnia magna 280 280 280 1 ICE Model Data Set; from OPP

data base

2032599 Aminocarb T.E.S.T. Daphnia magna 17.5 17.5 17.5 1 OPP Data set; not in ECOTOX;

from OPP database

2104645 EPN T.E.S.T. Daphnia magna 0.3 0.3 0.3 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

2597037 Phenthoate T.E.S.T. Daphnia magna 0.34 0.34 0.34 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

2921882 Chlorpyrifos T.E.S.T. Daphnia magna 0.1 1.7 0.66 3 ICE Model data set; additional

data in ECOTOX but not used

but had the same range of

values; average was 0.639

ug/L

3383968 Temephos T.E.S.T. Daphnia magna 0.01 0.01 0.01 1 ICE Model Data set; from OPP

Data set

3689245 Sulfotep T.E.S.T. Daphnia magna 2.5 2.5 2.5 1 ICE Model Data set; from OPP

Data set

5598130 Chlorpyrifos

- methyl T.E.S.T. Daphnia magna 0.79 1.11 0.95 2 ICE Mode Data Set; Confirmed

low Exp value; other from OPP

10265926 Methamidophos T.E.S.T. Daphnia magna There were three data points

in ECOTOX but rejected by ICE

model data set; most likely

due to range in toxicity (33.8

- 237.9 ug/L)

13171216 Phosphamidon T.E.S.T. Daphnia magna 12.7 12.7 12.7 1 ICE Model Data set; from OPP

Data set

13194484 E thoprophos T.E.S.T. Daphnia magna 93 93 93 1 ICE Model Data set; from OPP

## 53 | P a g e Data set

13593038 Quinalphos T.E.S.T. Daphnia magna 0.21 0.21 0.21 1 Chemical/species not in

original ICE Model Data Set;

Added from ECOTOX

database; Confirmed Exp value

from EcoRef 96171

16752775 Methomyl T.E.S.T. Daphnia magna 8.8 31.7 21.93 5 ICE Model Data set had two

values of 8.8

- 31.7 ug/L;

average 20.25 ug/l;

augmented with ECOTOX data

not in ICE; Average not sig diff

22781233 Bendiocarb T.E.S.T. Daphnia magna 29.2 29.2 29.2 1 ICE Model Data set; from OPP

Data set

23103982 Pirimicarb T.E.S.T. Daphnia magna 6.5 19 12.75 2 ICE Model Data set; from OPP

Data set

23135220 Oxamyl T.E.S.T. Daphnia magna 5700 5700 5700 1 ICE Model data set; from OPP

Data set

23422539 Formetanate

hydrochloride T.E.S.T. Daphnia magna 86.8 86.8 86.8 1 ICE Model Data set; from OPP

Data set

25311711 Isofenphos T.E.S.T. Daphnia magna 2.6 3.9 3.25 2 ICE Model data set had one

value (3.9 ug/L from OPP);

augmented with ECOTOX

value (2.6 ug/L) from EcoRef

96171

29232937 Pirimiphos

- methyl T.E.S.T. Daphnia magna 0.21 0.44 0.33 2 ICE Model data set had one

value (0.219 ug/L from OPP);

augmented with ECOTOX

value (0.44 ug/L) from EcoRef

96171

31218834 Propetamphos T.E.S.T. Daphnia magna 3.3 14 8.65 2 ICE Model Data set; from OPP

Data set

41198087 Profenofos T.E.S.T. Daphnia magna 0.93 2.8 1.87 2 ICE Model data set; from OPP

Data set

59669260 Thiodicarb T.E.S.T. Daphnia magna 27 27 27 1 ICE Model Data set; from OPP

Data set

96182535 Tebupirimfos T.E.S.T. Daphnia magna 0.08 0.08 0.08 1 ICE Model Data set; from OPP

Data set

98886443 Fosthiazate T.E.S.T. Daphnia magna 260 260 260 1 ICE Model Data set; from OPP

Data set

## 54 | P a g e Supplemental Information T

- 3 : Comparison of ECOSAR model (Version 1.0 and 1.1) estimates for fish and daphnids to the

average L C /EC50 value (mg/L) from acceptable empirical data collection (See Supplemental Information Table 2 for

details on source and other details related to empirical test data.) ECOSA R Class Model is the QSAR chemical category

equation used to estimate toxicity for this exercise. ECOSAR provided results for other chemical class QSAR models, but

these models were selected because they best represent the acetylcholinesterase chemical ca tegory.

ECOSAR Version 1.1 Model Estimates and Average Empirical Test Data

- Fish

CAS

Registry

Number Pesticide General

Chemical Class Version 1.1

–

ECOSAR Class Model Version

1.1

-

KowWin

LogP Version 1.1

ECOSAR Fish

96 hr LC50

Estimate

( mg/L ) Average of

Acceptable

Empirical

Fish 96 hr

LC50

values

( mg/L ) Ratio of

ECOSAR

Estimated

value by

Empirical

Test data

83130012 Alanycarb Carbamate Oxime Carbamate Ester 3.165 0.429

- 99.00

- 99.00

91976 6 Amidithion Organophosphate Esters, Dithiophosphates 0.444 9.535

- 99.00

- 99.00

78535 Amiton Organophosphate Esters (phosphate) 1.703 7.43

- 99.00

- 99.00

35575 963 Azamethiphos Organophosphate Carbamate esters, phenyl 0.999 17.76

- 99.00

- 99.00

2642719 Azinphos

- ethyl Organophosphate Esters, Dithiophosphates 3.514 0.356

- 99.00

- 99.00

82560 541 Benfuracarb Carbamate Carbamate esters, phenyl 4.057 1.94

- 99.00

- 99.00

34681102 Butocarboxim Carbamate Oxime Carbamate Ester 1.214 1.26

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamate Oxime Carbamate Ester

- 0.811 9.713

- 99.00

- 99.00

95465 999 Cadusafos Organophosphate Esters (phosphate) 3.976 1.193

- 99.00

- 99.00

55285148 Carbosulfan Carbamate Carbamate esters, phenyl 5.572 0.534 #

- 99.00

- 99.00

54593 838 Chlorethoxyfos Organophosphate Esters, Monothiophosphates 4.173 0.2

- 99.00

- 99.00

24934916 Chlormephos Organophosphate Esters, Dithiophosphates 3.043 0.415

- 99.00

- 99.00

50028 7 Chlorthion Organophosphate Esters, Monothiophosphates 3.393 0.512

- 99.00

- 99.00

51487695 Cloethocarb Carbamate Carbamate esters, phenyl 1.404 10.264

- 99.00

- 99.00

26362 62 Cyanophos Organophosphate Esters, Monothiophosphates 2.758 0.992

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate Esters (phosphate) 1.01 11.11

- 99.00

- 99.00

1754581 Diamidafos Organophosphate Esters (phosphate) 0.325 16.792

- 99.00

- 99.00

22746 71 Dimethylvinphos Organophosphate Esters (phosphate) 3.164 2.815

- 99.00

- 99.00

29973135 Ethiofencarb Carbamate Carbamate esters, phenyl 2.039 5.358

- 99.00

- 99.00

52857 Famphur Organophosphate Esters, Monothiophosphates 1.985 3.793

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate Esters (phosphate) 3.293 2.32

- 99.00

- 99.00

37668 12 Fenobucarb Carbamate Carbamate esters, phenyl 2.78 2.552

- 99.00

- 99.00

22259309 Formetanate Carbamate Carbamate esters, phenyl 0.879 13.318

- 99.00

- 99.00

21548 323 Fosthietan Organophosphate Esters (phosphate) 0.676 15.242

- 99.00

- 99.00

65907304 Furathiocarb Carbamate Carbamate esters, phenyl 4.425 1.345

- 99.00

- 99.00

23560590 Heptenophos Organophosphate Esters (phosphate) 1.408 8.777

- 99.00

- 99.00

40626 355 Hepterophos Organophosphate Esters (phosphate) 3.282 2.008

- 99.00

- 99.00

140163899 Imicyafos Organophosphate Esters (phosphate) 2.08 6.196

- 99.00

- 99.00

66602 877 Isamidofos Organophosphate Esters (phosphate) 1.815 8.327

- 99.00

- 99.00

2631405 Isoprocarb Carbamate Carbamate esters, phenyl 2.31 3.525

- 99.00

- 99.00

18854 018 Isoxathion Organophosphate Esters, Monothiophosphates 3.899 0.271

- 99.00

- 99.00

## 55 | P a g e 21609905 Leptophos Organophosphate Esters, Monothiophosphates 6.343 0.013

- 99.00

- 99.00

25955 42 Mecarbam Organophosphate Esters, Dithiophosphates 2.729 0.835

- 99.00

- 99.00

10265 926 Methamidophos Organophosphate Esters (phosphate)

- 0.926 32.482

- 99.00

- 99.00

1129415 Metolcarb Carbamate Carbamate esters, phenyl 1.7 5.072

- 99.00

- 99.00

77863 47 Mevinphos Organophosphate Esters (phosphate) 0.762 13.21

- 99.00

- 99.00

1113026 Omethoate Organophosphate Esters (phosphate)

- 0.787 43.86

- 99.00

- 99.00

25970 37 Phenthoate Organophosphate Esters, Dithiophosphates 3.473 0.346

- 99.00

- 99.00

4104147 Phosacetim Organophosphate Esters, Monothiophosphates 3.438 0.607

- 99.00

- 99.00

23101 70 Phosalone Organophosphate Esters, Dithiophosphates 4.38 0.155

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate Esters (phosphate) 1.379 10.741 #

- 99.00

- 99.00

29799 4 Phosphamidon (E

isomer) Organophosphate Esters (phosphate) 1.379 10.741 #

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate Carbamate esters, phenyl 2.203 6.949

- 99.00

- 99.00

14816183 phoxim Organophosphate Esters, Monothiophosphates 4.39 0.132

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate Esters, Monothiophosphates 4.002 0.23

- 99.00

- 99.00

7292162 Propaphos Organophosphate Esters (phosphate) 3.731 1.635

- 99.00

- 99.00

34643464 Prothiofos Organophosphate Esters, Dithiophosphates 6.337 0.014

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate Esters (phosphate) 3.756 1.899

- 99.00

- 99.00

11912 0 Pyridaphenthion Organophosphate Esters, Monothiophosphates 3.66 0.407

- 99.00

- 99.00

13593038 quinalphos Organophosphate Esters, Monothiophosphates 3.036 0.834

- 99.00

- 99.00

10749 3 TEPP Organophosphate Esters (phosphate) 0.45 22.004

- 99.00

- 99.00

13071799 Terbufos Organophosphate Esters, Dithiophosphates 4.488 0.097

- 99.00

- 99.00

22248799 Tetrachlorvinphos Organophosphate Esters (phosphate) 3.808 1.847

- 99.00

- 99.00

96111 5 Tetrachlorvinphos (E Z

isomers) Organophosphate Esters (phosphate) 3.808 1.847

- 99.00

- 99.00

25171 635 Thiocarboxime Carbamate Oxime Carbamate Ester 0.123 3.684

- 99.00

- 99.00

39196 184 Thiofanox Carbamate Oxime Carbamate Ester 2.158 0.599

- 99.00

- 99.00

640153 Thiometon Organophosphate Esters, Dithiophosphates 3.086 0.415

- 99.00

- 99.00

29797 2 Thionazin Organophosphate Esters, Monothiophosphates 1.86 3.43

- 99.00

- 99.00

112143825 Triazamate Carbamate Esters 2.394 24.742

- 99.00

- 99.00

24017 478 Triazophos Organophosphate Esters, Monothiophosphates 3.373 0.554

- 99.00

- 99.00

2275232 Vamidothion Organophosphate Esters (phosphate) 0.058 29.887

- 99.00

- 99.00

2655143 XMC Carbamate Carbamate esters, phenyl 2.23 3.55

- 99.00

- 99.00

24251 07 Xylylcarb Carbamate Carbamate esters, phenyl 2.09 3.55

- 99.00

- 99.00

33839 68 Temephos Organophosphate Esters, Monothiophosphates 6.167 0.019 5.15 0.00 4

97176 Dichlofenthion Organophosphate Esters, Monothiophosphates 5.202 0.046 1.25 0.04

98886443 Fosthiazate Organophosphate Esters (phosphate) 2.471 4.207 111.00 0.04

29804 4 Disulfoton Organophosphate Esters, Dithiophosphates 4.068 0.15 1.85 0.08

96182535 Tebupirimfos Organophosphate Esters, Monothiophosphates 4.188 0.186 2.22 0.08

25311 711 Isofenphos Organophosphate Esters, Monothiophosphates 4.404 0.15 1.40 0.11

23103982 Pirimicarb Carbamate Carbamate esters, phenyl 1.399 9.456 79.00 0.12

299843 Fenchlorphos Organophosphate Esters, Monothiophosphates 4.865 0.075 0.60 0.13

## 56 | P a g e 15271 417 endo

- 3

- Chloro

- exo

- 6

-

cyano

- 2

- norbornanone,

o

- (Methylcarbamoyl)

oxime Carbamate Oxime Carbamate Ester 1.089 1.797 13.00 0.14

327980 Trichloronate Organophosphate Esters, Monothiophosphates 5.863 0.02 0.14 0.14

95317 3 Methyl carbophenothion Organophosphate Esters, Dithiophosphates 4.463 0.109 0.76 0.14

563122 Ethion Organophosphate Esters, Dithiophosphates 4.996 0.072 0.50 0.14

56724 Coumaphos Organophosphate Esters, Monothiophosphates 4.473 0.144 0.89 0.16

1646884 Aldoxycarb Carbamate Oxime Carbamate Ester

- 0.666 8.483 42.00 0.20

31218 834 Propetamphos Organophosphate Esters, Monothiophosphates 3.507 0.415 1.77 0.23

3689245 Sulfotep Organophosphate Esters, Monothiophosphates 3.98 0.25 1.00 0.25

55389 Fenthion Organophosphate Esters, Monothiophosphates 4.079 0.189 0.74 0.26

56382 Parathion Organophosphate Esters, Monothiophosphates 3.731 0.317 1.21 0.26

122145 Fenitrothion Organophosphate Esters, Monothiophosphates 3.296 0.544 2.05 0.27

20325 99 Aminocarb Carbamate Carbamate esters, phenyl 1.9 5.547 18.31 0.30

298000 Parathion

- methyl Organophosphate Esters, Monothiophosphates 2.749 1.087 3.23 0.34

30560 191 Acephate Organophosphate Esters (phosphate)

- 0.902 41.359 110.00 0.38

315184 Mexacarbate Carbamate Carbamate esters, phenyl 2.56 3.819 9.89 0.39

59669 260 Thiodicarb Carbamate Oxime Carbamate Ester 1.915 1.221 2.65 0.46

2686999 3,4,5

- Trimethylphenyl

methylcarbamate Carbamate Carbamate esters, phenyl 3.4 2.469 4.70 0.53

2104645 EPN Organophosphate Esters, Monothiophosphates 4.473 0.128 0.21 0.61

60515 Dimethoate Organophosphate Esters, Dithiophosphates 0.718 5.839 7.43 0.79

732116 Phosmet Organophosphate Esters, Dithiophosphates 2.483 1.067 1.14 0.93

55981 30 Chlorpyrifos

- methyl Organophosphate Esters, Monothiophosphates 4.126 0.205 0.21 0.97

8065483 Demeton Organophosphate Esters, Monothiophosphates 3.215 0.567 0.56 1.01

33341 5 Diazinon Organophosphate Esters, Monothiophosphates 3.864 0.276 0.25 1.08

299865 Crufomate Organophosphate Esters (phosphate) 3.299 2.22 1.80 1.23

16752 775 Methomyl Carbamate Oxime Carbamate Ester 0.609 1.886 1.31 1.44

114261 Propoxur Carbamate Carbamate esters, phenyl 1.52 5.546 3.70 1.50

13194484 Ethoprophos Organophosphate Esters (phosphate) 3.14 2.097 1.15 1.82

11606 3 Aldicarb Carbamate Oxime Carbamate Ester 1.359 1.1 0.56 1.96

63252 Carbaryl Carbamate Carbamate esters, phenyl 2.36 3.734 1.80 2.08

29118 874 cis

- Thiocarboxime Carbamate Oxime Carbamate Ester 0.123 3.684 1.50 2.46

69232 24 Monocrotophos Organophosphate Esters (phosphate)

- 0.307 31.165 12.10 2.58

47090 6 Chlorfenvinphos Organophosphate Esters (phosphate) 4.146 1.382 0.51 2.71

18181709 Iodofenphos Organophosphate Esters, Monothiophosphates 5.387 0.047 0.02 2.90

22781 233 Bendiocarb Carbamate Carbamate esters, phenyl 2.552 3.521 1.20 2.93

786196 Carbophenothion Organophosphate Esters, Dithiophosphates 5.445 0.039 0.01 3.00

23422539 Formetanate

hydrochloride Carbamate Carbamate esters, phenyl 0.879 13.318 4.40 3.03

23135 220 Oxamyl Carbamate Oxime Carbamate Ester

- 1.199 13.758 4.45 3.09

2782709 SD

- 7438 Organophosphate Esters, Dithiophosphates 4.545 0.128 0.03 3.76

94422 9 Fonofos Organophosphate Esters, Dithiophosphates 4.022 0.142 0.04 4.06

## 57 | P a g e 2921882 Chlorpyrifos Organophosphate Esters, Monothiophosphates 5.108 0.059 0.01 4.41

14166 2 Dicrotophos Organophosphate Esters (phosphate)

- 0.096 27.934 6.30 4.43

2032657 Methiocarb Carbamate Carbamate esters, phenyl 2.92 2.758 0.59 4.65

78342 Dioxathion Organophosphate Esters, Dithiophosphates 3.446 0.509 0.07 7.38

1563662 Carbofuran Carbamate Carbamate esters, phenyl 2.32 4.266 0.47 9.14

52686 Trichlorfon Organophosphate Esters (phosphate) 0.423 19.951 1.88 10.60

121755 Malathion Organophosphate Esters, Dithiophosphates 2.288 1.39 0.11 13.16

298022 Phorate Organophosphate Esters, Dithiophosphates 3.617 0.239 0.02 14.06

42509 808 Isazofos Organophosphate Esters, Monothiophosphates 3.709 0.351 0.02 18.77

115902 Fensulfothion Organophosphate Esters, Monothiophosphates 2.35 2.19 0.07 30.42

41198 087 Profenofos Organophosphate Esters (phosphate) 4.817 0.836 0.02 37.57

300765 Naled Organophosphate Esters (phosphate) 1.605 11.374 # 0.17 67.97

30112 2 Oxydemeton

- methyl Organophosphate Esters (phosphate)

- 1.031 61.686 0.73 84.50

62737 Dichlorvos Organophosphate Esters (phosphate) 0.603 14.811 0.10 148.11

86500 Azinphos

- methyl Organophosphate Esters, Dithiophosphates 2.532 1.01 0.01 190.57

95037 8 Methidathion Organophosphate Esters, Dithiophosphates 1.584 2.851 0.01 237.58

5598527 Chlorpyrifos

- methyl

oxon Organophosphate Esters (phosphate) 1.911 7.151 0.00 3865.41



### ECOSA R Version 1.1 Model Estimates and Average Empirical Test Data

- Daphnid

CAS

Registry

Number Pesticide General

Chemical Class Version 1.1

–

ECOSAR Class Model Version

1.1

-

KowWin

LogP Version

1.1

ECOSAR

Daphnid

48 hr

Estimate

( mg/L ) Average of

Acceptable

Empirical

Daphnid

Acute

L C /E C50

values

( mg/L ) Ratio of

ECOSAR

Estimated

value by

Empirical

Test data

52857 Famphur Organophosphate Esters, Monothiophosphates 1.985 0.012

- 99.00

- 99.00

78535 Amiton Organophosphate Esters (phosphate) 1.703 0.014

- 99.00

- 99.00

97176 dichlofenthion Organophosphate Esters, Monothiophosphates 5.202 0.000267

- 99.00

- 99.00

107493 TEPP Organophosphate Esters (phosphate) 0.45 0.045

- 99.00

- 99.00

115902 fensulfothion Organophosphate Esters, Monothiophosphates 2.35 0.007

- 99.00

- 99.00

141662 Dicrotophos Organophosphate Esters (phosphate)

- 0.096 0.06

- 99.00

- 99.00

297972 thionazin Organophosphate Esters, Monothiophosphates 1.86 0.01

- 99.00

- 99.00

297994 Phosphamidon (E

isomer) Organophosphate Esters (phosphate) 1.379 0.021

- 99.00

- 99.00

298022 Phorate Organophosphate Esters, Dithiophosphates 3.617 0.00116

- 99.00

- 99.00

299843 Fenchlorphos Organophosphate Esters, Monothiophosphates 4.865 0.000404

- 99.00

- 99.00

299865 Crufomate Organophosphate Esters (phosphate) 3.299 0.004

- 99.00

- 99.00

315184 Mexacarbate Carbamate Carbamate esters, phenyl 2.56 0.007

- 99.00

- 99.00

327980 Trichloronate Organophosphate Esters, Monothiophosphates 5.863 0.000131

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate Esters (phosphate) 4.146 0.002

- 99.00

- 99.00

500287 Chlorthion Organophosphate Esters, Monothiophosphates 3.393 0.002

- 99.00

- 99.00

640153 Thiometon Organophosphate Esters, Dithiophosphates 3.086 0.00142

- 99.00

- 99.00

786196 carbophenothion Organophosphate Esters, Dithiophosphates 5.445 0.000619

- 99.00

- 99.00

919766 Amidithion Organophosphate Esters, Dithiophosphates 0.444 0.006

- 99.00

- 99.00

## 58 | P a g e

919868 Demeton

- S

- methyl Organophosphate Esters (phosphate) 1.01 0.022

- 99.00

- 99.00

953173 Methyl carbophenothion Organophosphate Esters, Dithiophosphates 4.463 0.000923

- 99.00

- 99.00

961115 Tetrachlorvinphos (E Z

isomers) Organophosphate Esters (phosphate) 3.808 0.003

- 99.00

- 99.00

1129415 Metolcarb Carbamate Carbamate esters, phenyl 1.7 0.022

- 99.00

- 99.00

1754581 diamidafos Organophosphate Esters (phosphate) 0.325 0.035

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate Esters (phosphate) 3.164 0.005

- 99.00

- 99.00

2275232 Vamidothion Organophosphate Esters (phosphate) 0.058 0.063

- 99.00

- 99.00

2310170 Phosalone Organophosphate Esters, Dithiophosphates 4.38 0.00117

- 99.00

- 99.00

2425107 Xylylcarb Carbamate Carbamate esters, phenyl 2.09 0.008

- 99.00

- 99.00

2595542 Mecarbam Organophosphate Esters, Dithiophosphates 2.729 0.002

- 99.00

- 99.00

2631405 Isoprocarb Carbamate Carbamate esters, phenyl 2.31 0.007

- 99.00

- 99.00

2636262 Cyanophos Organophosphate Esters, Monothiophosphates 2.758 0.004

- 99.00

- 99.00

2642719 Azinphos

- ethyl Organophosphate Esters, Dithiophosphates 3.514 0.00162

- 99.00

- 99.00

2655143 XMC Carbamate Carbamate esters, phenyl 2.23 0.008

- 99.00

- 99.00

2686999 3,4,5

- Trimethylphenyl

methylcarbamate Carbamate Carbamate esters, phenyl 3.4 0.003

- 99.00

- 99.00

2782709 SD

- 7438 Organophosphate Esters, Dithiophosphates 4.545 0.00114

- 99.00

- 99.00

3766812 Fenobucarb Carbamate Carbamate esters, phenyl 2.78 0.003

- 99.00

- 99.00

4104147 phosacetim Organophosphate Esters, Monothiophosphates 3.438 0.002

- 99.00

- 99.00

5598527 Chlorpyrifos

- methyl

oxon Organophosphate Esters (phosphate) 1.911 0.013

- 99.00

- 99.00

6923224 monocrotophos Organophosphate Esters (phosphate)

- 0.307 0.068

- 99.00

- 99.00

7292162 Propaphos Organophosphate Esters (phosphate) 3.731 0.003

- 99.00

- 99.00

7786347 mevinphos Organophosphate Esters (phosphate) 0.762 0.027

- 99.00

- 99.00

10265926 methamidophos Organophosphate Esters (phosphate)

- 0.926 0.074

- 99.00

- 99.00

13071799 Terbufos Organophosphate Esters, Dithiophosphates 4.488 0.000835

- 99.00

- 99.00

14816183 phoxim Organophosphate Esters, Monothiophosphates 4.39 0.000651

- 99.00

- 99.00

15271417 endo

- 3

- Chloro

- exo

- 6

-

cyano

- 2

- norbornanone,

o

- (Methylcarbamoyl)

oxime Carbamate Oxime Carbamate Ester 1.089 0.082

- 99.00

- 99.00

18181709 Iodofenphos Organophosphate Esters, Monothiophosphates 5.387 0.000282

- 99.00

- 99.00

18854018 Isoxathion Organophosphate Esters, Monothiophosphates 3.899 0.00121

- 99.00

- 99.00

21548323 fosthietan Organophosphate Esters (phosphate) 0.676 0.031

- 99.00

- 99.00

21609905 Leptophos Organophosphate Esters, Monothiophosphates 6.343 9.22E

- 05

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate Esters (phosphate) 3.293 0.004

- 99.00

- 99.00

22248799 Tetrachlorvinphos Organophosphate Esters (phosphate) 3.808 0.003

- 99.00

- 99.00

22259309 formetanate Carbamate Carbamate esters, phenyl 0.879 0.155

- 99.00

- 99.00

23560590 heptenophos Organophosphate Esters (phosphate) 1.408 0.017

- 99.00

- 99.00

24017478 Triazophos Organophosphate Esters, Monothiophosphates 3.373 0.002

- 99.00

- 99.00

24934916 Chlormephos Organophosphate Esters, Dithiophosphates 3.043 0.00139

- 99.00

- 99.00

25171635 Thiocarboxime Carbamate Oxime Carbamate Ester 0.123 0.234

- 99.00

- 99.00

29118874 cis

- Thiocarboxime Carbamate Oxime Carbamate Ester 0.123 0.234

- 99.00

- 99.00

29973135 Ethiofencarb Carbamate Carbamate esters, phenyl 2.039 0.016

- 99.00

- 99.00

## 59 | P a g e 30560191 Acephate Organophosphate Esters (phosphate)

- 0.902 0.094

- 99.00

- 99.00

34643464 Prothiofos Organophosphate Esters, Dithiophosphates 6.337 0.000402

- 99.00

- 99.00

34681102 butocarboxim Carbamate Oxime Carbamate Ester 1.214 0.055

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamate Oxime Carbamate Ester

- 0.811 0.849

- 99.00

- 99.00

35575963 Azamethiphos Organophosphate Carbamate esters, phenyl 0.999 0.179

- 99.00

- 99.00

39196184 thiofanox Carbamate Oxime Carbamate Ester 2.158 0.019

- 99.00

- 99.00

40626355 Hepterophos Organophosphate Esters (phosphate) 3.282 0.003

- 99.00

- 99.00

42509808 isazofos Organophosphate Esters, Monothiophosphates 3.709 0.00152

- 99.00

- 99.00

51487695 cloethocarb Carbamate Carbamate esters, phenyl 1.404 0.064

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate Esters, Monothiophosphates 4.173 0.000945

- 99.00

- 99.00

55285148 Carbosulfan Carbamate Carbamate esters, phenyl 5.572 0.000024

8 - 99.00

- 99.00

65907304 Furathiocarb Carbamate Carbamate esters, phenyl 4.425 0.000241

- 99.00

- 99.00

66602877 isamidofos Organophosphate Esters (phosphate) 1.815 0.016

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate Esters (phosphate) 3.756 0.003

- 99.00

- 99.00

82560541 Benfuracarb Carbamate Carbamate esters, phenyl 4.057 0.000536

- 99.00

- 99.00

83130012 alanycarb Carbamate Oxime Carbamate Ester 3.165 0.01

- 99.00

- 99.00

95465999 cadusafos Organophosphate Esters (phosphate) 3.976 0.00192

- 99.00

- 99.00

112143825 Triazamate Carbamate Esters 2.394 49.307

- 99.00

- 99.00

126069543 phosphocarb Organophosphate Carbamate esters, phenyl 2.203 0.017

- 99.00

- 99.00

140163899 imicyafos Organophosphate Esters (phosphate) 2.08 0.011

- 99.00

- 99.00

60515 dimethoate Organophosphate Esters, Dithiophosphates 0.718 0.004 2.716667 0.00

98886443 fosthiazate Organophosphate Esters (phosphate) 2.471 0.008 0.26 0.03

13194484 Ethoprophos Organophosphate Esters (phosphate) 3.14 0.004 0.093 0.04

298044 Disulfoton Organophosphate Esters, Dithiophosphates 4.068 0.000977 0.013 0.08

116063 aldicarb Carbamate Oxime Carbamate Ester 1.359 0.046 0.55335 0.08

8065483 Demeton Organophosphate Esters, Monothiophosphates 3.215 0.002 0.014 0.14

1563662 Carbofuran Carbamate Carbamate esters, phenyl 2.32 0.009 0.06282 0.14

2032657 Methiocarb Carbamate Carbamate esters, phenyl 2.92 0.003 0.019 0.16

122145 Fenitrothion Organophosphate Esters, Monothiophosphates 3.296 0.002 0.011 0.18

31218834 propetamphos Organophosphate Esters, Monothiophosphates 3.507 0.00172 0.00865 0.20

22781233 Bendiocarb Carbamate Carbamate esters, phenyl 2.552 0.006 0.0292 0.21

55389 fenthion Organophosphate Esters, Monothiophosphates 4.079 0.000873 0.0039 0.22

25311711 Isofenphos Organophosphate Esters, Monothiophosphates 4.404 0.000742 0.00325 0.23

23135220 Oxamyl Carbamate Oxime Carbamate Ester

- 1.199 1.374 5.7 0.24

732116 Phosmet Organophosphate Esters, Dithiophosphates 2.483 0.002 0.0056 0.36

944229 Fonofos Organophosphate Esters, Dithiophosphates 4.022 0.000897 0.002 0.45

3689245 sulfotep Organophosphate Esters, Monothiophosphates 3.98 0.00113 0.0025 0.45

2921882 chlorpyrifos Organophosphate Esters, Monothiophosphates 5.108 0.000331 0.000663 0.50

301122 Oxydemeton

- methyl Organophosphate Esters (phosphate)

- 1.031 0.141 0.24 0.59

563122 Ethion Organophosphate Esters, Dithiophosphates 4.996 0.000866 0.00142 0.61

950378 Methidathion Organophosphate Esters, Dithiophosphates 1.584 0.004 0.0064 0.63

## 60 | P a g e 41198087 Profenofos Organophosphate Esters (phosphate) 4.817 0.00127 0.001865 0.68

63252 carbaryl Carbamate Carbamate esters, phenyl 2.36 0.008 0.0098 0.82

114261 Propoxur Carbamate Carbamate esters, phenyl 1.52 0.019 0.0191 0.99

5598130 Chlorpyrifos

- methyl Organophosphate Esters, Monothiophosphates 4.126 0.000958 0.00095 1.01

2032599 aminocarb Carbamate Carbamate esters, phenyl 1.9 0.019 0.0175 1.09

333415 diazinon Organophosphate Esters, Monothiophosphates 3.864 0.00123 0.00096 1.28

56382 parathion Organophosphate Esters, Monothiophosphates 3.731 0.00137 0.001018 1.35

59669260 thiodicarb Carbamate Oxime Carbamate Ester 1.915 0.042 0.027 1.56

13171216 Phosphamidon Organophosphate Esters (phosphate) 1.379 0.021 0.0127 1.65

86500 Azinphos

- methyl Organophosphate Esters, Dithiophosphates 2.532 0.002 0.00113 1.77

23422539 formetanate

hydrochloride Carbamate Carbamate esters, phenyl 0.879 0.155 0.0868 1.79

121755 Malathion Organophosphate Esters, Dithiophosphates 2.288 0.003 0.0016 1.88

119120 Pyridaphenthion Organophosphate Esters, Monothiophosphates 3.66 0.00174 0.00092 1.89

2104645 EPN Organophosphate Esters, Monothiophosphates 4.473 0.000641 0.0003 2.14

1646884 aldoxycarb Carbamate Oxime Carbamate Ester

- 0.666 0.706 0.28 2.52

29232937 pirimiphos

- methyl Organophosphate Esters, Monothiophosphates 4.002 0.00105 0.000325 3.23

56724 Coumaphos Organophosphate Esters, Monothiophosphates 4.473 0.000719 0.000192 3.74

23103982 Pirimicarb Carbamate Carbamate esters, phenyl 1.399 0.06 0.01487 4.03

2597037 Phenthoate Organophosphate Esters, Dithiophosphates 3.473 0.00153 0.00034 4.50

16752775 Methomyl Carbamate Oxime Carbamate Ester 0.609 0.101 0.021934 4.60

1113026 Omethoate Organophosphate Esters (phosphate)

- 0.787 0.099 0.021 4.71

78342 Dioxathion Organophosphate Esters, Dithiophosphates 3.446 0.002 0.00035 5.71

96182535 Tebupirimfos Organophosphate Esters, Monothiophosphates 4.188 0.00088 0.000078 11.28

3383968 Temephos Organophosphate Esters, Monothiophosphates 6.167 0.000128 0.000011 11.64

13593038 quinalphos Organophosphate Esters, Monothiophosphates 3.036 0.003 0.00021 14.29

298000 Parathion

- methyl Organophosphate Esters, Monothiophosphates 2.749 0.004 0.00015 26.67

300765 Naled Organophosphate Esters (phosphate) 1.605 0.022 0.0003 73.33

62737 Dichlorvos/DDVP Organophosphate Esters (phosphate) 0.603 0.03 0.000176 170.94

52686 Trichlorfon Organophosphate Esters (phosphate) 0.423 0.041 0.000227 180.88



### Comparison of ECOSAR Version 1.0 and Version 1.1 Fish Models

CAS

Registry

Number Pesticide General

Chemical Class Version 1 .0

ECOSAR Class

Model Version 1.1

–

ECOSAR Class

Model Version

1. 0

ECOSAR

Fish 96 hr

LC50

Estimate

( mg/L ) Version 1. 1

ECOSAR Fish

96 hr LC50

Estimate

( mg/L ) Average of

Acceptable

Empirical

Fish Acute

LC50 value

( mg/L )

2686999 3,4,5

- Trimethylphenyl

methylcarbamate Carbamate Carbamate Esters Carbamate

esters, phenyl 5.164 2.469 4.70

## 61 | P a g e 30560191 Acephate Organophosphate Esters (phosphate) Esters

(phosphate) 15398.78 41.359 110.00

116063 aldicarb Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 1.668 1.1 0.56

1646884 aldoxycarb Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 4.788 8.483 42.00

2032599 aminocarb Carbamate Carbamate Esters Carbamate

esters, phenyl 23.795 5.547 18.31

86500 Azinphos

- methyl Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.586 1.01 0.005

22781233 Bendiocarb Carbamate Carbamate Esters Carbamate

esters, phenyl 9.046 3.521 1.20

63252 carbaryl Carbamate Carbamate Esters Carbamate

esters, phenyl 11.25 3.734 1.80

1563662 Carbofuran Carbamate Carbamate Esters Carbamate

esters, phenyl 13.341 4.266 0.47

786196 carbophenothion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.021 0.039 0.013

470906 Chlorfenvinphos Organophosphate Esters (phosphate) Esters

(phosphate) 3.06 1.382 0.51

2921882 chlorpyrifos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.701 0.059 0.013

5598130 Chlorpyrifos

- methyl Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 2.445 0.205 0.21

## 62 | P a g e 5598527 Chlorpyrifos

- methyl oxon Organophosphate Esters (phosphate) Esters

(phosphate) 153.064 7.151 0.0019

29118874 cis

- Thiocarboxime Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 3.055 3.684 1.50

56724 Coumaphos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.933 0.144 0.89

299865 Crufomate Organophosphate Esters (phosphate) Esters

(phosphate) 11.607 2.22 1.80

8065483 Demeton Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 3.664 0.567 0.56

333415 diazinon Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 1.788 0.276 0.25

97176 dichlofenthion Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.301 0.046 1.25

62737 Dichlorvos/DDVP Organophosphate Esters (phosphate) Esters

(phosphate) 1196.118 14.811 0.10

141662 Dicrotophos Organophosphate Esters (phosphate) Esters

(phosphate) 28355.13 27.934 6.30

60515 dimethoate Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 7.47 5.839 7.43

78342 Dioxathion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.263 0.509 0.069

298044 Disulfoton Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.093 0.15 1.85

## 63 | P a g e 15271417 endo

- 3

- Chloro

- exo

- 6

-

cyano

- 2

- norbornanone,

o

- (Methylcarbamoyl)

oxime Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 2.389 1.797 13.00

2104645 EPN Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.831 0.128 0.21

563122 Ethion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.042 0.072 0.50

13194484 Ethoprophos Organophosphate Esters (phosphate) Esters

(phosphate) 12.882 2.097 1.15

299843 Fenchlorphos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.486 0.075 0.60

122145 Fenitrothion Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 3.521 0.544 2.05

115902 fensulfothion Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 14.141 2.19 0.072

55389 fenthion Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 1.221 0.189 0.74

944229 Fonofos Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.068 0.142 0.035

23422539 formetanate

hydrochloride Carbamate Carbamate Esters Carbamate

esters, phenyl 126.881 13.318 4.40

## 64 | P a g e 98886443 fosthiazate Organophosphate Esters (phosphate) Esters

(phosphate) 51.002 4.207 111.00

18181709 Iodofenphos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.307 0.047 0.016

42509808 isazofos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 4.189 0.351 0.019

25311711 Isofenphos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.694 0.15 1.40

121755 Malathion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.832 1.39 0.11

950378 Methidathion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 1.865 2.851 0.012

2032657 Methiocarb Carbamate Carbamate Esters Carbamate

esters, phenyl 5.531 2.758 0.59

16752775 Methomyl Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 1.984 1.886 1.31

953173 Methyl carbophenothion Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.068 0.109 0.76

315184 Mexacarbate Carbamate Carbamate Esters Carbamate

esters, phenyl 10.671 3.819 9.89

6923224 monocrotophos Organophosphate Esters (phosphate) Esters

(phosphate) 39199.48 31.165 12.10

300765 Naled Organophosphate Esters (phosphate) Esters

(phosphate) 332.247 # 11.374 # 0.17

## 65 | P a g e 23135220 Oxamyl Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 5.985 13.758 4.45

301122 Oxydemeton

- methyl Organophosphate Esters (phosphate) Esters

(phosphate) 26167.12 61.686 0.73

56382 parathion Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 2.049 0.317 1.21

298000 Parathion

- methyl Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 7.027 1.087 3.23

298022 Phorate Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.166 0.239 0.017

732116 Phosmet Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.623 1.067 1.14

23103982 Pirimicarb Carbamate Carbamate Esters Carbamate

esters, phenyl 59.921 9.456 79.00

41198087 Profenofos Organophosphate Esters (phosphate) Esters

(phosphate) 0.936 0.836 0.022

31218834 propetamphos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 10.428 0.415 1.77

114261 Propoxur Carbamate Carbamate Esters Carbamate

esters, phenyl 23.677 5.546 3.70

2782709 SD

- 7438 Organophosphate Esters,

Dithiophosphates Esters,

Dithiophosphate

s 0.057 0.128 0.034

3689245 sulfotep Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 1.616 0.25 1.00

## 66 | P a g e 96182535 Tebupirimfos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 1.205 0.186 2.22

3383968 Temephos Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.12 0.019 5.15

59669260 thiodicarb Carbamate Oxime Carbamate

Ester Oxime

Carbamate Ester 2.428 1.221 2.65

52686 Trichlorfon Organophosphate Esters (phosphate) Esters

(phosphate) 6924.113 19.951 1.88

327980 Trichloronate Organophosphate Esters,

Monothiophospha

tes Esters,

Monothiophosph

ates 0.13 0.02 0.14



### - 99.00: Not empirical data of were available after quality control measures were taken, therefore no comparisons were possibl e

#: ECOSAR estimate for fish toxicity may be over water solubility

## 67 | P a g e Supplemental Information T

- 4 : Comparison of T.E.S.T. model (Version 4.0) estimates for fathead minnow and Daphnia

magna to the average L C /EC50 value (mg/L) from acceptable empirical data collection (See Supplemental Information

Table 2 for details on source and other details related to empirical test data.) T.E.S.T. QSAR Model method identifies the

specific model used to generate estimated values

.

CAS

Registry

Number Pesticide General

Chemical Class T.E.S.T. QSAR Model Method T.E.S.T. V4.0

48 hr

Estimated

Value

( mg/L ) Average of the

Acceptable Empirical

Acute L C /EC50 values

(mg/ L) Predicted

EC50/Measured

EC50



## Daphnia magna

52686 Trichlorfon Organophosphate TEST: Consensus 0.01 0.000227 55.15

52686 Trichlorfon Organophosphate TEST: FDA 0.01 0.000227 22.90

52686 Trichlorfon Organophosphate TEST: Hierarchical Clustering 0.0015 0.000227 6.49

52686 Trichlorfon Organophosphate TEST: Nearest Neighbor 0.02 0.000227 88.24

52686 Trichlorfon Organophosphate TEST: Single Model 0.16 0.000227 710.29

52857 Famphur Organophosphate TEST: Consensus 0.0027

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Nearest Neighbor 0.0027

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

55389 Fenthion Organophosphate TEST: Consensus 0.0045 0.0055 0.83

55389 Fenthion Organophosphate TEST: FDA 0.0087 0.0055 1.59

55389 Fenthion Organophosphate TEST: Hierarchical Clustering 0.0050 0.0055 0.91

55389 Fenthion Organophosphate TEST: Nearest Neighbor 0.0019 0.0055 0.35

55389 Fenthion Organophosphate TEST: Single Model 0.0050 0.0055 0.91

56382 Parathion Organophosphate TEST: Consensus 0.0053 0.001018 5.21

56382 Parathion Organophosphate TEST: FDA 0.0065 0.0010 6.38

56382 Parathion Organophosphate TEST: Hierarchical Clustering 0.0050 0.0010 4.87

56382 Parathion Organophosphate TEST: Nearest Neighbor 0.0024 0.0010 2.36

56382 Parathion Organophosphate TEST: Single Model 0.0103 0.0010 10.11

56724 Coumaphos Organophosphate TEST: Consensus 0.0023 0.000192 12.03

56724 Coumaphos Organophosphate TEST: FDA 0.0017 0.000192 9.01

56724 Coumaphos Organophosphate TEST: Hierarchical Clustering 0.0026 0.000192 13.33

56724 Coumaphos Organophosphate TEST: Nearest Neighbor 0.0025 0.000192 13.07

56724 Coumaphos Organophosphate TEST: Single Model 0.0026 0.000192 13.33

60515 Dimethoate Organophosphate TEST: Consensus 0.0098 2.72 0.00362

60515 Dimethoate Organophosphate TEST: FDA 0.11 2.72 0.04

60515 Dimethoate Organophosphate TEST: Hierarchical Clustering 0.0016 2.72 0.00057

60515 Dimethoate Organophosphate TEST: Nearest Neighbor 0.0368 2.72 0.01

60515 Dimethoate Organophosphate TEST: Single Model 0.0016 2.72 0.00057

62737 Dichlorvos Organophosphate TEST: Consensus 0.0029 0.000176 16.24

62737 Dichlorvos Organophosphate TEST: FDA 0.000149 0.000176 0.85

62737 Dichlorvos Organophosphate TEST: Hierarchical Clustering 0.000689 0.000176 3.93

62737 Dichlorvos Organophosphate TEST: Nearest Neighbor 0.0171 0.000176 97.44

## 68 | P a g e

62737 Dichlorvos Organophosphate TEST: Single Model 0.0377 0.000176 214.81

63252 Carbaryl Carbamates TEST: Consensus 0.59 0.0098 59.80

63252 Carbaryl Carbamates TEST: FDA 3.67 0.0098 374.49

63252 Carbaryl Carbamates TEST: Hierarchical Clustering 0.0862 0.0098 8.80

63252 Carbaryl Carbamates TEST: Nearest Neighbor 1.29 0.0098 131.63

63252 Carbaryl Carbamates TEST: Single Model 0.29 0.0098 29.29

78342 Dioxathion Organophosphate TEST: Consensus 0.0054 0.000350 15.49

78342 Dioxathion Organophosphate TEST: FDA 0.31 0.000350 894.29

78342 Dioxathion Organophosphate TEST: Hierarchical Clustering 0.0012 0.000350 3.37

78342 Dioxathion Organophosphate TEST: Nearest Neighbor 0.0054 0.000350 15.37

78342 Dioxathion Organophosphate TEST: Single Model 0.000435 0.000350 1.24

78535 Amiton Organophosphate TEST: Consensus 0.24

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: FDA 49.30

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Hierarchical Clustering 0.0417

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Nearest Neighbor 0.12

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Single Model 0.0133

- 99.00

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Consensus 0.0028 0.001450 1.91

86500 Azinphos

- methyl Organophosphate TEST: FDA

- 99.00 0.0015

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Hierarchical Clustering

- 99.00 0.0015

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Nearest Neighbor 0.0028 0.0015 1.91

86500 Azinphos

- methyl Organophosphate TEST: Single Model

- 99.00 0.0015

- 99.00

97176 Dichlofenthion Organophosphate TEST: Consensus 0.0053 0.001100 4.83

97176 Dichlofenthion Organophosphate TEST: FDA 0.0015 0.0011 1.33

97176 Dichlofenthion Organophosphate TEST: Hierarchical Clustering 0.0119 0.0011 10.82

97176 Dichlofenthion Organophosphate TEST: Nearest Neighbor 0.0042 0.0011 3.78

97176 Dichlofenthion Organophosphate TEST: Single Model 0.0110 0.0011 10.00

107493 TEPP Organophosphate TEST: Consensus 0.86

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Nearest Neighbor 0.86

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

114261 Propoxur Carbamates TEST: Consensus 2.36 0.0191 123.56

114261 Propoxur Carbamates TEST: FDA 1.88 0.0191 98.43

114261 Propoxur Carbamates TEST: Hierarchical Clustering 1.91 0.0191 100.00

114261 Propoxur Carbamates TEST: Nearest Neighbor 8.58 0.0191 449.21

114261 Propoxur Carbamates TEST: Single Model 1.00 0.0191 52.36

115902 Fensulfothion Organophosphate TEST: Consensus 0.0149

- 99.00

- 99.00

115902 Fensulfothion Organophosphate TEST: FDA 0.0030

- 99.00

- 99.00

115902 Fensulfothion Organophosphate TEST: Hierarchical Clustering 0.0113

- 99.00

- 99.00

115902 Fensulfothion Organophosphate TEST: Nearest Neighbor 0.13

- 99.00

- 99.00

115902 Fensulfothion Organophosphate TEST: Single Model 0.0113

- 99.00

- 99.00

## 69 | P a g e

116063 Aldicarb Carbamates TEST: Consensus 1.40 0.55 2.53

116063 Aldicarb Carbamates TEST: FDA 1.27 0.55 2.30

116063 Aldicarb Carbamates TEST: Hierarchical Clustering 1.34 0.55 2.42

116063 Aldicarb Carbamates TEST: Nearest Neighbor

- 99.00 0.55

- 99.00

116063 Aldicarb Carbamates TEST: Single Model 1.61 0.55 2.91

119120 Pyridaphenthion Organophosphate TEST: Consensus 0.0059 0.000920 6.43

119120 Pyridaphenthion Organophosphate TEST: FDA

- 99.00 0.000920

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Hierarchical Clustering

- 99.00 0.000920

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Nearest Neighbor 0.0059 0.000920 6.43

119120 Pyridaphenthion Organophosphate TEST: Single Model

- 99.00 0.000920

- 99.00

121755 Malathion Organophosphate TEST: Consensus 0.0101 0.001600 6.31

121755 Malathion Organophosphate TEST: FDA 0.0406 0.0016 25.38

121755 Malathion Organophosphate TEST: Hierarchical Clustering 0.0231 0.0016 14.44

121755 Malathion Organophosphate TEST: Nearest Neighbor 0.0060 0.0016 3.77

121755 Malathion Organophosphate TEST: Single Model 0.0018 0.0016 1.14

122145 Fenitrothion Organophosphate TEST: Consensus 0.0026 0.0056 0.47

122145 Fenitrothion Organophosphate TEST: FDA 0.000687 0.0056 0.12

122145 Fenitrothion Organophosphate TEST: Hierarchical Clustering 0.0051 0.0056 0.92

122145 Fenitrothion Organophosphate TEST: Nearest Neighbor 0.0023 0.0056 0.41

122145 Fenitrothion Organophosphate TEST: Single Model 0.0058 0.0056 1.05

141662 Dicrotophos Organophosphate TEST: Consensus 0.0326

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: FDA 0.0258

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Hierarchical Clustering 0.0616

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Nearest Neighbor 0.0894

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Single Model 0.0080

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Consensus 0.0221

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: FDA 1.90

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Hierarchical Clustering 0.0044

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Nearest Neighbor 0.000591

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Single Model 0.0478

- 99.00

- 99.00

298000 Parathion

- methyl Organophosphate TEST: Consensus 0.0037 0.000150 24.87

298000 Parathion

- methyl Organophosphate TEST: FDA 0.0022 0.000150 14.33

298000 Parathion

- methyl Organophosphate TEST: Hierarchical Clustering 0.0045 0.000150 29.67

298000 Parathion

- methyl Organophosphate TEST: Nearest Neighbor 0.0022 0.000150 14.40

298000 Parathion

- methyl Organophosphate TEST: Single Model 0.0094 0.000150 62.47

298022 Phorate Organophosphate TEST: Consensus 0.0234

- 99.00

- 99.00

298022 Phorate Organophosphate TEST: FDA 0.0029

- 99.00

- 99.00

298022 Phorate Organophosphate TEST: Hierarchical Clustering 0.12

- 99.00

- 99.00

298022 Phorate Organophosphate TEST: Nearest Neighbor 0.0418

- 99.00

- 99.00

298022 Phorate Organophosphate TEST: Single Model 0.0212

- 99.00

- 99.00

298044 Disulfoton Organophosphate TEST: Consensus 0.0328 0.0130 2.52

## 70 | P a g e

298044 Disulfoton Organophosphate TEST: FDA 0.0694 0.0130 5.34

298044 Disulfoton Organophosphate TEST: Hierarchical Clustering 0.0352 0.0130 2.71

298044 Disulfoton Organophosphate TEST: Nearest Neighbor 0.0305 0.0130 2.35

298044 Disulfoton Organophosphate TEST: Single Model 0.0155 0.0130 1.19

300765 Naled Organophosphate TEST: Consensus 0.0062 0.000300 20.70

300765 Naled Organophosphate TEST: FDA 0.92 0.000300 3063.33

300765 Naled Organophosphate TEST: Hierarchical Clustering 0.000129 0.000300 0.43

300765 Naled Organophosphate TEST: Nearest Neighbor

- 99.00 0.000300

- 99.00

300765 Naled Organophosphate TEST: Single Model 0.0020 0.000300 6.70

301122 Oxydemeton

- methyl Organophosphate TEST: Consensus 0.0363 0.24 0.15

301122 Oxydemeton

- methyl Organophosphate TEST: FDA 0.0016 0.24 0.01

301122 Oxydemeton

- methyl Organophosphate TEST: Hierarchical Clustering 0.0245 0.24 0.10

301122 Oxydemeton

- methyl Organophosphate TEST: Nearest Neighbor 0.24 0.24 0.99

301122 Oxydemeton

- methyl Organophosphate TEST: Single Model 0.18 0.24 0.75

333415 Diazinon Organophosphate TEST: Consensus 0.0045 0.000960 4.64

333415 Diazinon Organophosphate TEST: FDA 0.0086 0.0010 8.99

333415 Diazinon Organophosphate TEST: Hierarchical Clustering 0.0020 0.0010 2.08

333415 Diazinon Organophosphate TEST: Nearest Neighbor 0.000725 0.0010 0.76

333415 Diazinon Organophosphate TEST: Single Model 0.0314 0.0010 32.71

470906 Chlorfenvinphos Organophosphate TEST: Consensus 0.25

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: FDA 1.50

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Hierarchical Clustering 1.68

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Nearest Neighbor 0.0700

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Single Model 0.0237

- 99.00

- 99.00

563122 Ethion Organophosphate TEST: Consensus 0.0032 0.000056 56.25

563122 Ethion Organophosphate TEST: FDA 0.0174 0.000056 310.71

563122 Ethion Organophosphate TEST: Hierarchical Clustering 0.000105 0.000056 1.88

563122 Ethion Organophosphate TEST: Nearest Neighbor 0.0428 0.000056 764.29

563122 Ethion Organophosphate TEST: Single Model 0.0013 0.000056 22.68

640153 Thiometon Organophosphate TEST: Consensus 0.0205

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: FDA 0.0071

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Hierarchical Clustering 0.0280

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Nearest Neighbor 0.0395

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Single Model 0.0223

- 99.00

- 99.00

732116 Phosmet Organophosphate TEST: Consensus 0.0018 0.0056 0.31

732116 Phosmet Organophosphate TEST: FDA 0.0013 0.0056 0.23

732116 Phosmet Organophosphate TEST: Hierarchical Clustering 0.000594 0.0056 0.11

732116 Phosmet Organophosphate TEST: Nearest Neighbor 0.0069 0.0056 1.23

732116 Phosmet Organophosphate TEST: Single Model 0.0018 0.0056 0.33

786196 Carbophenothion Organophosphate TEST: Consensus 0.0053

- 99.00

- 99.00

786196 Carbophenothion Organophosphate TEST: FDA 0.0045

- 99.00

- 99.00

## 71 | P a g e

786196 Carbophenothion Organophosphate TEST: Hierarchical Clustering 0.0065

- 99.00

- 99.00

786196 Carbophenothion Organophosphate TEST: Nearest Neighbor 0.0040

- 99.00

- 99.00

786196 Carbophenothion Organophosphate TEST: Single Model 0.0065

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Consensus 0.12

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: FDA 0.0160

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Hierarchical Clustering 0.54

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Nearest Neighbor 0.22

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Single Model 0.10

- 99.00

- 99.00

944229 Fonofos Organophosphate TEST: Consensus 0.0065 0.002000 3.25

944229 Fonofos Organophosphate TEST: FDA 0.0058 0.0020 2.91

944229 Fonofos Organophosphate TEST: Hierarchical Clustering 0.0023 0.0020 1.13

944229 Fonofos Organophosphate TEST: Nearest Neighbor 0.0395 0.0020 19.75

944229 Fonofos Organophosphate TEST: Single Model 0.0034 0.0020 1.72

1113026 Omethoate Organophosphate TEST: Consensus 0.0172 0.0210 0.82

1113026 Omethoate Organophosphate TEST: FDA 0.0077 0.0210 0.37

1113026 Omethoate Organophosphate TEST: Hierarchical Clustering 0.0058 0.0210 0.27

1113026 Omethoate Organophosphate TEST: Nearest Neighbor 0.34 0.0210 16.24

1113026 Omethoate Organophosphate TEST: Single Model 0.0058 0.0210 0.27

1129415 Metolcarb Carbamates TEST: Consensus 1.66

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: FDA 1.04

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Hierarchical Clustering 3.11

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Single Model 1.42

- 99.00

- 99.00

1563662 Carbofuran Carbamates TEST: Consensus 1.31 0.0628 20.85

1563662 Carbofuran Carbamates TEST: FDA 0.74 0.0628 11.70

1563662 Carbofuran Carbamates TEST: Hierarchical Clustering 2.99 0.0628 47.60

1563662 Carbofuran Carbamates TEST: Nearest Neighbor 5.19 0.0628 82.62

1563662 Carbofuran Carbamates TEST: Single Model 0.26 0.0628 4.06

1646884 Aldoxycarb Carbamates TEST: Consensus 0.74 0.28 2.64

1646884 Aldoxycarb Carbamates TEST: FDA 2.47 0.28 8.82

1646884 Aldoxycarb Carbamates TEST: Hierarchical Clustering 0.91 0.28 3.26

1646884 Aldoxycarb Carbamates TEST: Nearest Neighbor

- 99.00 0.28

- 99.00

1646884 Aldoxycarb Carbamates TEST: Single Model 0.18 0.28 0.64

2032599 Aminocarb Carbamates TEST: Consensus 7.70 0.0175 440.00

2032599 Aminocarb Carbamates TEST: FDA 39.00 0.0175 2228.57

2032599 Aminocarb Carbamates TEST: Hierarchical Clustering 23.20 0.0175 1325.71

2032599 Aminocarb Carbamates TEST: Nearest Neighbor 5.81 0.0175 332.00

2032599 Aminocarb Carbamates TEST: Single Model 0.67 0.0175 38.29

2032657 Methiocarb Carbamates TEST: Consensus 0.71

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: FDA 0.85

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Hierarchical Clustering 0.64

- 99.00

- 99.00

## 72 | P a g e

2032657 Methiocarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Single Model 0.64

- 99.00

- 99.00

2104645 EPN Organophosphate TEST: Consensus 0.0219 0.000300 73.00

2104645 EPN Organophosphate TEST: FDA 0.0621 0.000300 207.00

2104645 EPN Organophosphate TEST: Hierarchical Clustering 0.0152 0.000300 50.67

2104645 EPN Organophosphate TEST: Nearest Neighbor 0.0224 0.000300 74.67

2104645 EPN Organophosphate TEST: Single Model 0.0109 0.000300 36.33

2274671 Dimethylvinphos Organophosphate TEST: Consensus 0.0343

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: FDA 0.0029

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Hierarchical Clustering 1.51

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Nearest Neighbor 0.0123

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Single Model 0.0255

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Consensus 0.0097

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: FDA 0.000460

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Hierarchical Clustering 0.17

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Nearest Neighbor 0.0127

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Single Model 0.0087

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Consensus 0.0408

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: FDA 0.26

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Hierarchical Clustering 0.0948

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Nearest Neighbor 0.0529

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Single Model 0.0021

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Consensus 0.0124 0.000340 36.47

2597037 Phenthoate Organophosphate TEST: FDA 0.0580 0.000340 170.59

2597037 Phenthoate Organophosphate TEST: Hierarchical Clustering 0.0457 0.000340 134.41

2597037 Phenthoate Organophosphate TEST: Nearest Neighbor 0.0050 0.000340 14.68

2597037 Phenthoate Organophosphate TEST: Single Model 0.0018 0.000340 5.21

2631405 Isoprocarb Carbamates TEST: Consensus 5.21

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: FDA 32.10

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Hierarchical Clustering 4.18

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Single Model 1.06

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Consensus 0.000726

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: FDA 0.0046

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Hierarchical Clustering 0.000138

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Nearest Neighbor 0.0032

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Single Model 0.000138

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Consensus 5.37

- 99.00

- 99.00

2655143 XMC Carbamates TEST: FDA 15.90

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Hierarchical Clustering 6.43

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

## 73 | P a g e

2655143 XMC Carbamates TEST: Single Model 1.51

- 99.00

- 99.00

2921882 Chlorpyrifos Organophosphate TEST: Consensus 0.0062 0.000663 9.33

2921882 Chlorpyrifos Organophosphate TEST: FDA 0.0016 0.000663 2.38

2921882 Chlorpyrifos Organophosphate TEST: Hierarchical Clustering 0.0104 0.000663 15.68

2921882 Chlorpyrifos Organophosphate TEST: Nearest Neighbor 0.0024 0.000663 3.66

2921882 Chlorpyrifos Organophosphate TEST: Single Model 0.0370 0.000663 55.78

3383968 Temephos Organophosphate TEST: Consensus 0.0032 0.000011 293.64

3383968 Temephos Organophosphate TEST: FDA

- 99.00 0.0000110

- 99.00

3383968 Temephos Organophosphate TEST: Hierarchical Clustering

- 99.00 0.0000110

- 99.00

3383968 Temephos Organophosphate TEST: Nearest Neighbor 0.0032 0.0000110 293.64

3383968 Temephos Organophosphate TEST: Single Model

- 99.00 0.0000110

- 99.00

3689245 Sulfotep Organophosphate TEST: Consensus 0.0045 0.002500 1.78

3689245 Sulfotep Organophosphate TEST: FDA

- 99.00 0.0025

- 99.00

3689245 Sulfotep Organophosphate TEST: Hierarchical Clustering

- 99.00 0.0025

- 99.00

3689245 Sulfotep Organophosphate TEST: Nearest Neighbor 0.0045 0.0025 1.78

3689245 Sulfotep Organophosphate TEST: Single Model

- 99.00 0.0025

- 99.00

3766812 Fenobucarb Carbamates TEST: Consensus 2.90

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: FDA 7.14

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Hierarchical Clustering 2.75

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Nearest Neighbor 4.86

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Single Model 0.74

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Consensus 0.0133 0.000950 14.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: FDA 0.0232 0.0010 24.42

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Hierarchical Clustering 0.0133 0.0010 14.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Nearest Neighbor 0.0031 0.0010 3.22

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Single Model 0.0328 0.0010 34.53

6923224 Monocrotophos Organophosphate TEST: Consensus 0.0184

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: FDA 0.0269

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Hierarchical Clustering 0.0403

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Nearest Neighbor 0.0164

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Single Model 0.0065

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Consensus 0.0461

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: FDA 0.15

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Hierarchical Clustering 0.0323

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Nearest Neighbor 0.0291

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Single Model 0.0323

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Consensus 0.0138

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: FDA 0.0173

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Hierarchical Clustering 0.0113

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Nearest Neighbor 0.0164

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Single Model 0.0113

- 99.00

- 99.00

## 74 | P a g e

10265926 Methamidophos Organophosphate TEST: Consensus 153.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Nearest Neighbor 153.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: Consensus 0.0136

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: FDA 0.0121

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: Hierarchical Clustering 0.0113

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: Nearest Neighbor 0.0463

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: Single Model 0.0054

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate TEST: Consensus 0.0652 0.0127 5.13

13171216 Phosphamidon Organophosphate TEST: FDA 0.0173 0.0127 1.36

13171216 Phosphamidon Organophosphate TEST: Hierarchical Clustering 0.41 0.0127 32.13

13171216 Phosphamidon Organophosphate TEST: Nearest Neighbor 0.0293 0.0127 2.31

13171216 Phosphamidon Organophosphate TEST: Single Model 0.0875 0.0127 6.89

13194484 Ethoprophos Organophosphate TEST: Consensus 0.32 0.0930 3.40

13194484 Ethoprophos Organophosphate TEST: FDA 47.90 0.0930 515.05

13194484 Ethoprophos Organophosphate TEST: Hierarchical Clustering 0.22 0.0930 2.38

13194484 Ethoprophos Organophosphate TEST: Nearest Neighbor 0.0270 0.0930 0.29

13194484 Ethoprophos Organophosphate TEST: Single Model 0.0347 0.0930 0.37

13593038 Quinalphos Organophosphate TEST: Consensus 0.0074 0.000210 35.24

13593038 Quinalphos Organophosphate TEST: FDA 0.0081 0.000210 38.76

13593038 Quinalphos Organophosphate TEST: Hierarchical Clustering 0.0228 0.000210 108.57

13593038 Quinalphos Organophosphate TEST: Nearest Neighbor 0.000711 0.000210 3.39

13593038 Quinalphos Organophosphate TEST: Single Model 0.0228 0.000210 108.57

14816183 Phoxim Organophosphate TEST: Consensus 0.0021

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Nearest Neighbor 0.0021

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

16752775 Methomyl Carbamates TEST: Consensus

- 99.00 0.0219

- 99.00

16752775 Methomyl Carbamates TEST: FDA

- 99.00 0.0219

- 99.00

16752775 Methomyl Carbamates TEST: Hierarchical Clustering

- 99.00 0.0219

- 99.00

16752775 Methomyl Carbamates TEST: Nearest Neighbor

- 99.00 0.0219

- 99.00

16752775 Methomyl Carbamates TEST: Single Model

- 99.00 0.0219

- 99.00

18854018 Isoxathion Organophosphate TEST: Consensus 0.0089

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: FDA 0.0027

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Hierarchical Clustering 0.0063

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Nearest Neighbor 0.0294

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Single Model 0.0122

- 99.00

- 99.00

21548323 Fosthietan Organophosphate TEST: Consensus

- 99.00

- 99.00

- 99.00

## 75 | P a g e

21548323 Fosthietan Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

21548323 Fosthietan Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

21548323 Fosthietan Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

21548323 Fosthietan Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Consensus 0.0037

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Nearest Neighbor 0.0037

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Consensus 9.07

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Nearest Neighbor 9.07

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Consensus 0.23 0.0292 7.84

22781233 Bendiocarb Carbamates TEST: FDA 0.0105 0.0292 0.36

22781233 Bendiocarb Carbamates TEST: Hierarchical Clustering 1.48 0.0292 50.68

22781233 Bendiocarb Carbamates TEST: Nearest Neighbor 0.53 0.0292 17.98

22781233 Bendiocarb Carbamates TEST: Single Model 0.34 0.0292 11.54

23103982 Pirimicarb Carbamates TEST: Consensus 5.50 0.0128 431.37

23103982 Pirimicarb Carbamates TEST: FDA 3.64 0.0128 285.49

23103982 Pirimicarb Carbamates TEST: Hierarchical Clustering 52.60 0.0128 4125.49

23103982 Pirimicarb Carbamates TEST: Nearest Neighbor 0.0143 0.0128 1.12

23103982 Pirimicarb Carbamates TEST: Single Model 334.00 0.0128 26196.08

23135220 Oxamyl Carbamates TEST: Consensus

- 99.00 5.70

- 99.00

23135220 Oxamyl Carbamates TEST: FDA

- 99.00 5.70

- 99.00

23135220 Oxamyl Carbamates TEST: Hierarchical Clustering

- 99.00 5.70

- 99.00

23135220 Oxamyl Carbamates TEST: Nearest Neighbor

- 99.00 5.70

- 99.00

23135220 Oxamyl Carbamates TEST: Single Model

- 99.00 5.70

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Consensus 9.07 0.0868 104.49

23422539 Formetanate

hydrochloride Carbamates TEST: FDA

- 99.00 0.0868

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Hierarchical Clustering

- 99.00 0.0868

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Nearest Neighbor 9.07 0.0868 104.49

23422539 Formetanate

hydrochloride Carbamates TEST: Single Model

- 99.00 0.0868

- 99.00

23560590 heptenophos Organophosphate TEST: Consensus 0.15

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: FDA 0.0491

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Hierarchical Clustering 1.14

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Single Model 0.0653

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Consensus 0.0209

- 99.00

- 99.00

## 76 | P a g e

24017478 Triazophos Organophosphate TEST: FDA 0.0010

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Hierarchical Clustering 0.12

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Nearest Neighbor 0.35

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Single Model 0.0048

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Consensus 0.0794

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: FDA 0.93

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Hierarchical Clustering 0.0336

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Nearest Neighbor 0.0377

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Single Model 0.0336

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Consensus 0.0068 0.003250 2.10

25311711 Isofenphos Organophosphate TEST: FDA

- 99.00 0.0033

- 99.00

25311711 Isofenphos Organophosphate TEST: Hierarchical Clustering

- 99.00 0.0033

- 99.00

25311711 Isofenphos Organophosphate TEST: Nearest Neighbor 0.0068 0.0033 2.10

25311711 Isofenphos Organophosphate TEST: Single Model

- 99.00 0.0033

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Consensus 0.0020 0.000325 6.25

29232937 Pirimiphos

- methyl Organophosphate TEST: FDA 0.000769 0.000325 2.37

29232937 Pirimiphos

- methyl Organophosphate TEST: Hierarchical Clustering 0.0027 0.000325 8.25

29232937 Pirimiphos

- methyl Organophosphate TEST: Nearest Neighbor 0.000728 0.000325 2.24

29232937 Pirimiphos

- methyl Organophosphate TEST: Single Model 0.0113 0.000325 34.77

29973135 Ethiofencarb Carbamates TEST: Consensus 2.80

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: FDA 9.41

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Hierarchical Clustering 8.10

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Nearest Neighbor 2.15

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Single Model 0.38

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Consensus 0.38

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Nearest Neighbor 0.38

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Consensus 0.0051 0.0087 0.59

31218834 Propetamphos Organophosphate TEST: FDA

- 99.00 0.0087

- 99.00

31218834 Propetamphos Organophosphate TEST: Hierarchical Clustering

- 99.00 0.0087

- 99.00

31218834 Propetamphos Organophosphate TEST: Nearest Neighbor 0.0051 0.0087 0.59

31218834 Propetamphos Organophosphate TEST: Single Model

- 99.00 0.0087

- 99.00

34643464 Prothiofos Organophosphate TEST: Consensus 0.0108

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: FDA 0.10

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Hierarchical Clustering 0.0084

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Nearest Neighbor 0.0041

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Single Model 0.0041

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Consensus

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

## 77 | P a g e

34681102 Butocarboxim Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Consensus

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Consensus

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Consensus 0.0290

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: FDA 0.0549

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Hierarchical Clustering 0.0811

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Nearest Neighbor 0.0230

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Single Model 0.0069

- 99.00

- 99.00

41198087 Profenofos Organophosphate TEST: Consensus 0.0046 0.001865 2.48

41198087 Profenofos Organophosphate TEST: FDA 0.0047 0.0019 2.53

41198087 Profenofos Organophosphate TEST: Hierarchical Clustering 0.0053 0.0019 2.84

41198087 Profenofos Organophosphate TEST: Nearest Neighbor 0.0035 0.0019 1.87

41198087 Profenofos Organophosphate TEST: Single Model 0.0053 0.0019 2.84

42509808 Isazofos Organophosphate TEST: Consensus 0.30

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: FDA 0.32

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Hierarchical Clustering 0.56

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Nearest Neighbor 0.73

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Single Model 0.0629

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Consensus 0.0307

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: FDA 0.0070

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Hierarchical Clustering 8.74

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Nearest Neighbor 0.0017

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Single Model 0.0087

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Consensus 0.0799

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Nearest Neighbor 0.0799

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Consensus

- 99.00 0.0270

- 99.00

59669260 Thiodicarb Carbamates TEST: FDA

- 99.00 0.0270

- 99.00

59669260 Thiodicarb Carbamates TEST: Hierarchical Clustering

- 99.00 0.0270

- 99.00

## 78 | P a g e

59669260 Thiodicarb Carbamates TEST: Nearest Neighbor

- 99.00 0.0270

- 99.00

59669260 Thiodicarb Carbamates TEST: Single Model

- 99.00 0.0270

- 99.00

65907304 Furathiocarb Carbamates TEST: Consensus 0.35

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Nearest Neighbor 0.35

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Consensus 0.0790

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Nearest Neighbor 0.0790

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Consensus 0.15

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: FDA 0.19

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Hierarchical Clustering 0.22

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Nearest Neighbor 3.35

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Single Model 0.0038

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Consensus 0.0100

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Nearest Neighbor 0.0100

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Consensus 0.31

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Nearest Neighbor 0.31

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Consensus 0.0464

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: FDA 0.0816

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Hierarchical Clustering 0.0894

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Nearest Neighbor 0.0301

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Single Model 0.0212

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Consensus 0.0019 0.000078 24.10

96182535 Tebupirimfos Organophosphate TEST: FDA 0.000304 0.000078 3.90

96182535 Tebupirimfos Organophosphate TEST: Hierarchical Clustering 0.0037 0.000078 46.79

96182535 Tebupirimfos Organophosphate TEST: Nearest Neighbor 0.000759 0.000078 9.73

96182535 Tebupirimfos Organophosphate TEST: Single Model 0.0149 0.000078 191.03

98886443 Fosthiazate Organophosphate TEST: Consensus 0.20 0.26 0.77

98886443 Fosthiazate Organophosphate TEST: FDA 0.19 0.26 0.73

98886443 Fosthiazate Organophosphate TEST: Hierarchical Clustering 0.41 0.26 1.59

98886443 Fosthiazate Organophosphate TEST: Nearest Neighbor 0.0315 0.26 0.12

## 79 | P a g e

98886443 Fosthiazate Organophosphate TEST: Single Model 0.65 0.26 2.48

112143825 Triazamate Carbamates TEST: Consensus 9.66

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: FDA 12.30

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Hierarchical Clustering 8.56

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Single Model 8.56

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Consensus 0.0160

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: FDA 0.16

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Hierarchical Clustering 0.0432

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Nearest Neighbor 0.0082

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Single Model 0.0012

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Consensus 1.29

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Nearest Neighbor 1.29

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00



## Fathead minnow

52686 Trichlorfon Organophosphate TEST: Consensus 83.60 7.90 10.58

52686 Trichlorfon Organophosphate TEST: FDA 45.90 7.90 5.81

52686 Trichlorfon Organophosphate TEST: Group Contribution 358.00 7.90 45.32

52686 Trichlorfon Organophosphate TEST: Hierarchical Clustering 0.0015 7.90 0.00019

52686 Trichlorfon Organophosphate TEST: Nearest Neighbor 10.40 7.90 1.32

52686 Trichlorfon Organophosphate TEST: Single Model 143.00 7.90 18.10

52857 Famphur Organophosphate TEST: Consensus 3.65

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Nearest Neighbor 3.65

- 99.00

- 99.00

52857 Famphur Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

55389 Fenthion Organophosphate TEST: Consensus 2.44 3.33 0.73

55389 Fenthion Organophosphate TEST: FDA 13.00 3.33 3.90

55389 Fenthion Organophosphate TEST: Group Contribution

- 99.00 3.33

- 99.00

55389 Fenthion Organophosphate TEST: Hierarchical Clustering 0.0050 3.33 0.00149

55389 Fenthion Organophosphate TEST: Nearest Neighbor 0.48 3.33 0.14

55389 Fenthion Organophosphate TEST: Single Model 1.75 3.33 0.53

56382 Parathion Organophosphate TEST: Consensus 1.83 2.35 0.78

56382 Parathion Organophosphate TEST: FDA 1.76 2.35 0.75

56382 Parathion Organophosphate TEST: Group Contribution 1.07 2.35 0.46

56382 Parathion Organophosphate TEST: Hierarchical Clustering 0.0050 2.35 0.00211

56382 Parathion Organophosphate TEST: Nearest Neighbor 3.27 2.35 1.39

56382 Parathion Organophosphate TEST: Single Model 2.09 2.35 0.89

## 80 | P a g e

56724 Coumaphos Organophosphate TEST: Consensus 0.47

- 99.00

- 99.00

56724 Coumaphos Organophosphate TEST: FDA 0.51

- 99.00

- 99.00

56724 Coumaphos Organophosphate TEST: Group Contribution 0.42

- 99.00

- 99.00

56724 Coumaphos Organophosphate TEST: Hierarchical Clustering 0.77

- 99.00

- 99.00

56724 Coumaphos Organophosphate TEST: Nearest Neighbor 0.47

- 99.00

- 99.00

56724 Coumaphos Organophosphate TEST: Single Model 0.28

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: Consensus 22.80

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: FDA 16.00

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: Group Contribution 116.00

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: Hierarchical Clustering 0.0016

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: Nearest Neighbor 0.57

- 99.00

- 99.00

60515 Dimethoate Organophosphate TEST: Single Model 71.30

- 99.00

- 99.00

62737 Dichlorvos Organophosphate TEST: Consensus 18.20 4.00 4.55

62737 Dichlorvos Organophosphate TEST: FDA 0.99 4.00 0.25

62737 Dichlorvos Organophosphate TEST: Group Contribution 42.40 4.00 10.60

62737 Dichlorvos Organophosphate TEST: Hierarchical Clustering 0.000689 4.00 0.00017

62737 Dichlorvos Organophosphate TEST: Nearest Neighbor 112.00 4.00 28.00

62737 Dichlorvos Organophosphate TEST: Single Model 35.00 4.00 8.75

63252 Carbaryl Carbamates TEST: Consensus 8.58 7.93 1.08

63252 Carbaryl Carbamates TEST: FDA 22.10 7.93 2.79

63252 Carbaryl Carbamates TEST: Group Contribution 5.76 7.93 0.73

63252 Carbaryl Carbamates TEST: Hierarchical Clustering 0.0862 7.93 0.01

63252 Carbaryl Carbamates TEST: Nearest Neighbor 4.53 7.93 0.57

63252 Carbaryl Carbamates TEST: Single Model 13.00 7.93 1.64

78342 Dioxathion Organophosphate TEST: Consensus 1.29 5.15 0.25

78342 Dioxathion Organophosphate TEST: FDA 3.57 5.15 0.69

78342 Dioxathion Organophosphate TEST: Group Contribution 0.66 5.15 0.13

78342 Dioxathion Organophosphate TEST: Hierarchical Clustering 0.0012 5.15 0.00023

78342 Dioxathion Organophosphate TEST: Nearest Neighbor 1.15 5.15 0.22

78342 Dioxathion Organophosphate TEST: Single Model 0.29 5.15 0.06

78535 Amiton Organophosphate TEST: Consensus 9.03

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: FDA 0.90

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Group Contribution 19.90

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Hierarchical Clustering 0.0417

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Nearest Neighbor 6.60

- 99.00

- 99.00

78535 Amiton Organophosphate TEST: Single Model 64.00

- 99.00

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Consensus 2.46 1.69 1.45

86500 Azinphos

- methyl Organophosphate TEST: FDA

- 99.00 16.94

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Group Contribution

- 99.00 1.69

- 99.00

86500 Azinphos

- methyl Organophosphate TEST: Hierarchical Clustering 2.89 1.69 1.71

86500 Azinphos

- methyl Organophosphate TEST: Nearest Neighbor 1.52 1.69 0.90

## 81 | P a g e

86500 Azinphos

- methyl Organophosphate TEST: Single Model 3.39 1.69 2.00

97176 Dichlofenthion Organophosphate TEST: Consensus 0.42

- 99.00

- 99.00

97176 Dichlofenthion Organophosphate TEST: FDA 0.57

- 99.00

- 99.00

97176 Dichlofenthion Organophosphate TEST: Group Contribution 0.52

- 99.00

- 99.00

97176 Dichlofenthion Organophosphate TEST: Hierarchical Clustering 0.0119

- 99.00

- 99.00

97176 Dichlofenthion Organophosphate TEST: Nearest Neighbor 0.21

- 99.00

- 99.00

97176 Dichlofenthion Organophosphate TEST: Single Model 0.63

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Consensus 28.50

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: FDA 13.20

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Nearest Neighbor 38.20

- 99.00

- 99.00

107493 TEPP Organophosphate TEST: Single Model 65.90

- 99.00

- 99.00

114261 Propoxur Carbamates TEST: Consensus 19.40 8.80 2.20

114261 Propoxur Carbamates TEST: FDA 92.40 8.80 10.50

114261 Propoxur Carbamates TEST: Group Contribution 32.00 8.80 3.64

114261 Propoxur Carbamates TEST: Hierarchical Clustering 1.91 8.80 0.22

114261 Propoxur Carbamates TEST: Nearest Neighbor 4.71 8.80 0.54

114261 Propoxur Carbamates TEST: Single Model 20.10 8.80 2.28

115902 Fensulfothion Organophosphates TEST: Consensus 12.20 43.10 0.28

115902 Fensulfothion Organophosphate TEST: FDA 6.12 43.10 0.14

115902 Fensulfothion Organophosphate TEST: Group Contribution

- 99.00 43.10

- 99.00

115902 Fensulfothion Organophosphate TEST: Hierarchical Clustering 0.0113 43.10 0.00026

115902 Fensulfothion Organophosphate TEST: Nearest Neighbor 3.56 43.10 0.08

115902 Fensulfothion Organophosphate TEST: Single Model 56.60 43.10 1.31

116063 Aldicarb Carbamates TEST: Consensus

- 99.00 11.16

- 99.00

116063 Aldicarb Carbamates TEST: FDA

- 99.00 11.16

- 99.00

116063 Aldicarb Carbamates TEST: Group Contribution

- 99.00 1.12

- 99.00

116063 Aldicarb Carbamates TEST: Hierarchical Clustering 1.34 1.12 1.20

116063 Aldicarb Carbamates TEST: Nearest Neighbor

- 99.00 1.12

- 99.00

116063 Aldicarb Carbamates TEST: Single Model

- 99.00 1.12

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Consensus 1.82

- 99.00

- 99.00

119120 Pyridaphenthion Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Hierarchical Clustering 4.21

- 99.00

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Nearest Neighbor 0.44

- 99.00

- 99.00

119120 Pyridaphenthion Organophosphate TEST: Single Model 3.27

- 99.00

- 99.00

121755 Malathion Organophosphate TEST: Consensus 4.76 14.10 0.34

121755 Malathion Organophosphate TEST: FDA 8.43 14.10 0.60

121755 Malathion Organophosphate TEST: Group Contribution 2.77 14.10 0.20

121755 Malathion Organophosphate TEST: Hierarchical Clustering 0.0231 14.10 0.00164

## 82 | P a g e

121755 Malathion Organophosphate TEST: Nearest Neighbor 0.94 14.10 0.07

121755 Malathion Organophosphate TEST: Single Model 11.50 14.10 0.82

122145 Fenitrothion Organophosphate TEST: Consensus 3.30

- 99.00

- 99.00

122145 Fenitrothion Organophosphate TEST: FDA 2.84

- 99.00

- 99.00

122145 Fenitrothion Organophosphate TEST: Group Contribution 2.08

- 99.00

- 99.00

122145 Fenitrothion Organophosphate TEST: Hierarchical Clustering 0.0051

- 99.00

- 99.00

122145 Fenitrothion Organophosphate TEST: Nearest Neighbor 3.11

- 99.00

- 99.00

122145 Fenitrothion Organophosphate TEST: Single Model 2.57

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Consensus 179.00

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: FDA 201.00

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Group Contribution 1130.00

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Hierarchical Clustering 0.0616

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Nearest Neighbor 9.22

- 99.00

- 99.00

141662 Dicrotophos Organophosphate TEST: Single Model 776.00

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Consensus 4.87

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: FDA 1.15

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Group Contribution 46.40

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Hierarchical Clustering 0.0044

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Nearest Neighbor 0.41

- 99.00

- 99.00

297972 Thionazin Organophosphate TEST: Single Model 50.80

- 99.00

- 99.00

298000 Parathion

- methyl Organophosphate TEST: Consensus 4.76 8.90 0.53

298000 Parathion

- methyl Organophosphate TEST: FDA 6.37 8.90 0.72

298000 Parathion

- methyl Organophosphate TEST: Group Contribution 3.95 8.90 0.44

298000 Parathion

- methyl Organophosphate TEST: Hierarchical Clustering 0.0045 8.90 0.00050

298000 Parathion

- methyl Organophosphate TEST: Nearest Neighbor 2.95 8.90 0.33

298000 Parathion

- methyl Organophosphate TEST: Single Model 5.75 8.90 0.65

298022 Phorate Organophosphate TEST: Consensus 0.79 0.25 3.16

298022 Phorate Organophosphate TEST: FDA 0.16 0.25 0.65

298022 Phorate Organophosphate TEST: Group Contribution 2.29 0.25 9.16

298022 Phorate Organophosphate TEST: Hierarchical Clustering 0.12 0.25 0.47

298022 Phorate Organophosphate TEST: Nearest Neighbor 0.65 0.25 2.61

298022 Phorate Organophosphate TEST: Single Model 2.45 0.25 9.80

298044 Disulfoton Organophosphate TEST: Consensus 1.40 3.37 0.42

298044 Disulfoton Organophosphate TEST: FDA 1.60 3.37 0.47

298044 Disulfoton Organophosphate TEST: Group Contribution 1.19 3.37 0.35

298044 Disulfoton Organophosphate TEST: Hierarchical Clustering 0.0352 3.37 0.01

298044 Disulfoton Organophosphate TEST: Nearest Neighbor 0.69 3.37 0.20

298044 Disulfoton Organophosphate TEST: Single Model 3.19 3.37 0.95

300765 Naled Organophosphate TEST: Consensus 7.40

- 99.00

- 99.00

300765 Naled Organophosphate TEST: FDA 2.51

- 99.00

- 99.00

300765 Naled Organophosphate TEST: Group Contribution 10.80

- 99.00

- 99.00

## 83 | P a g e

300765 Naled Organophosphate TEST: Hierarchical Clustering 0.000129

- 99.00

- 99.00

300765 Naled Organophosphate TEST: Nearest Neighbor 15.40

- 99.00

- 99.00

300765 Naled Organophosphate TEST: Single Model 5.62

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: Consensus 802.00

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: FDA 659.00

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: Group Contribution 1320.00

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: Hierarchical Clustering 0.0245

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

301122 Oxydemeton

- methyl Organophosphate TEST: Single Model 1220.00

- 99.00

- 99.00

333415 Diazinon Organophosphate TEST: Consensus 1.91 7.80 0.24

333415 Diazinon Organophosphate TEST: FDA 3.88 7.80 0.50

333415 Diazinon Organophosphate TEST: Group Contribution 4.35 7.80 0.56

333415 Diazinon Organophosphate TEST: Hierarchical Clustering 0.0020 7.80 0.00026

333415 Diazinon Organophosphate TEST: Nearest Neighbor 0.33 7.80 0.04

333415 Diazinon Organophosphate TEST: Single Model 3.64 7.80 0.47

470906 Chlorfenvinphos Organophosphate TEST: Consensus 1.18

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: FDA 0.32

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Group Contribution 0.49

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Hierarchical Clustering 1.68

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Nearest Neighbor 12.30

- 99.00

- 99.00

470906 Chlorfenvinphos Organophosphate TEST: Single Model 1.09

- 99.00

- 99.00

563122 Ethion Organophosphate TEST: Consensus 1.48 0.72 2.06

563122 Ethion Organophosphate TEST: FDA 9.53 0.72 13.24

563122 Ethion Organophosphate TEST: Group Contribution 0.14 0.72 0.19

563122 Ethion Organophosphate TEST: Hierarchical Clustering 0.000105 0.72 0.00015

563122 Ethion Organophosphate TEST: Nearest Neighbor 2.73 0.72 3.79

563122 Ethion Organophosphate TEST: Single Model 0.41 0.72 0.57

640153 Thiometon Organophosphate TEST: Consensus 4.07

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: FDA 20.00

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Group Contribution 4.37

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Hierarchical Clustering 0.0280

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Nearest Neighbor 0.62

- 99.00

- 99.00

640153 Thiometon Organophosphate TEST: Single Model 8.17

- 99.00

- 99.00

732116 Phosmet Organophosphate TEST: Consensus 4.90 7.30 0.67

732116 Phosmet Organophosphate TEST: FDA 3.76 7.30 0.52

732116 Phosmet Organophosphate TEST: Group Contribution 38.80 7.30 5.32

732116 Phosmet Organophosphate TEST: Hierarchical Clustering 0.000594 7.30 0.00008

732116 Phosmet Organophosphate TEST: Nearest Neighbor 0.68 7.30 0.09

732116 Phosmet Organophosphate TEST: Single Model 3.15 7.30 0.43

786196 Carbophenothion Organophosphate TEST: Consensus 0.42 0.23 1.83

786196 Carbophenothion Organophosphate TEST: FDA 0.29 0.23 1.29

## 84 | P a g e

786196 Carbophenothion Organophosphate TEST: Group Contribution

- 99.00 0.23

- 99.00

786196 Carbophenothion Organophosphate TEST: Hierarchical Clustering 0.0065 0.23 0.03

786196 Carbophenothion Organophosphate TEST: Nearest Neighbor 1.89 0.23 8.27

786196 Carbophenothion Organophosphate TEST: Single Model 0.25 0.23 1.09

919868 Demeton

- S

- methyl Organophosphate TEST: Consensus 8.33

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: FDA 15.30

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Group Contribution 25.20

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Hierarchical Clustering 0.54

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Nearest Neighbor 0.58

- 99.00

- 99.00

919868 Demeton

- S

- methyl Organophosphate TEST: Single Model 37.90

- 99.00

- 99.00

944229 Fonofos Organophosphate TEST: Consensus 1.00 1.09 0.91

944229 Fonofos Organophosphate TEST: FDA 0.45 1.09 0.42

944229 Fonofos Organophosphate TEST: Group Contribution 2.71 1.09 2.49

944229 Fonofos Organophosphate TEST: Hierarchical Clustering 0.0023 1.09 0.00207

944229 Fonofos Organophosphate TEST: Nearest Neighbor 0.21 1.09 0.19

944229 Fonofos Organophosphate TEST: Single Model 2.09 1.09 1.92

1113026 Omethoate Organophosphate TEST: Consensus 156.00

- 99.00

- 99.00

1113026 Omethoate Organophosphate TEST: FDA 145.00

- 99.00

- 99.00

1113026 Omethoate Organophosphate TEST: Group Contribution 669.00

- 99.00

- 99.00

1113026 Omethoate Organophosphate TEST: Hierarchical Clustering 0.0058

- 99.00

- 99.00

1113026 Omethoate Organophosphate TEST: Nearest Neighbor 8.42

- 99.00

- 99.00

1113026 Omethoate Organophosphate TEST: Single Model 271.00

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Consensus 18.30

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: FDA 10.00

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Group Contribution 51.60

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Hierarchical Clustering 3.11

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Nearest Neighbor 10.00

- 99.00

- 99.00

1129415 Metolcarb Carbamates TEST: Single Model 19.80

- 99.00

- 99.00

1563662 Carbofuran Carbamates TEST: Consensus 5.87 1.24 4.75

1563662 Carbofuran Carbamates TEST: FDA 1.34 1.24 1.08

1563662 Carbofuran Carbamates TEST: Group Contribution 22.90 1.24 18.54

1563662 Carbofuran Carbamates TEST: Hierarchical Clustering 2.99 1.24 2.42

1563662 Carbofuran Carbamates TEST: Nearest Neighbor 4.98 1.24 4.03

1563662 Carbofuran Carbamates TEST: Single Model 8.44 1.24 6.83

1646884 Aldoxycarb Carbamates TEST: Consensus

- 99.00

- 99.00

- 99.00

1646884 Aldoxycarb Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

1646884 Aldoxycarb Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

1646884 Aldoxycarb Carbamates TEST: Hierarchical Clustering 0.91

- 99.00

- 99.00

1646884 Aldoxycarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

1646884 Aldoxycarb Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

2032599 Aminocarb Carbamates TEST: Consensus 24.50 1.95 12.56

## 85 | P a g e

2032599 Aminocarb Carbamates TEST: FDA 19.80 1.95 10.15

2032599 Aminocarb Carbamates TEST: Group Contribution 50.30 1.95 25.79

2032599 Aminocarb Carbamates TEST: Hierarchical Clustering 23.20 1.95 11.90

2032599 Aminocarb Carbamates TEST: Nearest Neighbor 6.04 1.95 3.10

2032599 Aminocarb Carbamates TEST: Single Model 26.70 1.95 13.69

2032657 Methiocarb Carbamates TEST: Consensus 6.52

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: FDA 86.70

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Hierarchical Clustering 0.64

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Nearest Neighbor 1.89

- 99.00

- 99.00

2032657 Methiocarb Carbamates TEST: Single Model 3.37

- 99.00

- 99.00

2104645 EPN Organophosphate TEST: Consensus 0.57 0.0786 7.28

2104645 EPN Organophosphate TEST: FDA 0.61 0.0786 7.72

2104645 EPN Organophosphate TEST: Group Contribution 0.39 0.0786 4.90

2104645 EPN Organophosphate TEST: Hierarchical Clustering 0.0152 0.0786 0.19

2104645 EPN Organophosphate TEST: Nearest Neighbor 0.98 0.0786 12.51

2104645 EPN Organophosphate TEST: Single Model 0.48 0.0786 6.09

2274671 Dimethylvinphos Organophosphate TEST: Consensus 0.70

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: FDA 0.36

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Group Contribution 1.86

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Hierarchical Clustering 1.51

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Nearest Neighbor 0.19

- 99.00

- 99.00

2274671 Dimethylvinphos Organophosphate TEST: Single Model 2.78

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Consensus 15.00

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: FDA 2.44

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Group Contribution 66.90

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Hierarchical Clustering 0.17

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Nearest Neighbor 2.45

- 99.00

- 99.00

2275232 Vamidothion Organophosphate TEST: Single Model 78.70

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Consensus 7.72

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: FDA 87.10

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Group Contribution 8.16

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Hierarchical Clustering 0.0948

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Nearest Neighbor 0.76

- 99.00

- 99.00

2595542 Mecarbam Organophosphate TEST: Single Model 5.77

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Consensus 0.87

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: FDA 0.0770

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Group Contribution 1.31

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Hierarchical Clustering 0.0457

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Nearest Neighbor 2.58

- 99.00

- 99.00

2597037 Phenthoate Organophosphate TEST: Single Model 2.08

- 99.00

- 99.00

## 86 | P a g e

2631405 Isoprocarb Carbamates TEST: Consensus 9.25

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: FDA 6.04

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Group Contribution 18.50

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Hierarchical Clustering 4.18

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Nearest Neighbor 5.60

- 99.00

- 99.00

2631405 Isoprocarb Carbamates TEST: Single Model 7.00

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Consensus 8.92

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: FDA 4.19

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Group Contribution 16.70

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Hierarchical Clustering 0.000138

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Nearest Neighbor 2.73

- 99.00

- 99.00

2636262 Cyanophos Organophosphate TEST: Single Model 17.20

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Consensus 9.48

- 99.00

- 99.00

2655143 XMC Carbamates TEST: FDA 2.06

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Group Contribution 28.00

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Hierarchical Clustering 6.43

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Nearest Neighbor 10.90

- 99.00

- 99.00

2655143 XMC Carbamates TEST: Single Model 10.30

- 99.00

- 99.00

2921882 Chlorpyrifos Organophosphate TEST: Consensus 0.34 0.28 1.21

2921882 Chlorpyrifos Organophosphate TEST: FDA 0.24 0.28 0.86

2921882 Chlorpyrifos Organophosphate TEST: Group Contribution 0.54 0.28 1.91

2921882 Chlorpyrifos Organophosphate TEST: Hierarchical Clustering 0.0104 0.28 0.04

2921882 Chlorpyrifos Organophosphate TEST: Nearest Neighbor 0.30 0.28 1.07

2921882 Chlorpyrifos Organophosphate TEST: Single Model 0.44 0.28 1.56

3383968 Temephos Organophosphate TEST: Consensus 1.21 34.10 0.04

3383968 Temephos Organophosphate TEST: FDA 2.08 34.10 0.06

3383968 Temephos Organophosphate TEST: Group Contribution

- 99.00 34.10

- 99.00

3383968 Temephos Organophosphate TEST: Hierarchical Clustering

- 99.00 34.10

- 99.00

3383968 Temephos Organophosphate TEST: Nearest Neighbor 2.81 34.10 0.08

3383968 Temephos Organophosphate TEST: Single Model 0.11 34.10 0.00334

3689245 Sulfotep Organophosphate TEST: Consensus 3.70

- 99.00

- 99.00

3689245 Sulfotep Organophosphate TEST: FDA 3.70

- 99.00

- 99.00

3689245 Sulfotep Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

3689245 Sulfotep Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

3689245 Sulfotep Organophosphate TEST: Nearest Neighbor 3.06

- 99.00

- 99.00

3689245 Sulfotep Organophosphate TEST: Single Model 3.22

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Consensus 5.59

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: FDA 7.30

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Group Contribution 9.84

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Hierarchical Clustering 2.75

- 99.00

- 99.00

3766812 Fenobucarb Carbamates TEST: Nearest Neighbor 4.67

- 99.00

- 99.00

## 87 | P a g e

3766812 Fenobucarb Carbamates TEST: Single Model 4.79

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Consensus 0.75

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: FDA 0.87

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Group Contribution 2.01

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Hierarchical Clustering 0.0133

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Nearest Neighbor 0.31

- 99.00

- 99.00

5598130 Chlorpyrifos

- methyl Organophosphate TEST: Single Model 1.03

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Consensus 343.00

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: FDA 261.00

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Group Contribution 990.00

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Hierarchical Clustering 0.0403

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Nearest Neighbor 39.40

- 99.00

- 99.00

6923224 Monocrotophos Organophosphate TEST: Single Model 678.00

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Consensus 4.91

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: FDA 23.30

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Hierarchical Clustering 0.0323

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Nearest Neighbor 6.83

- 99.00

- 99.00

7292162 Propaphos Organophosphate TEST: Single Model 1.59

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Consensus 80.50

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: FDA 1730.00

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Hierarchical Clustering 0.0113

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Nearest Neighbor 8.71

- 99.00

- 99.00

7786347 Mevinphos Organophosphate TEST: Single Model 322.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Consensus 182.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Nearest Neighbor 182.00

- 99.00

- 99.00

10265926 Methamidophos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

13071799 Terbufos Organophosphate TEST: Consensus 0.50 0.0133 37.22

13071799 Terbufos Organophosphate TEST: FDA 0.22 0.0133 16.54

13071799 Terbufos Organophosphate TEST: Group Contribution 1.77 0.0133 133.08

13071799 Terbufos Organophosphate TEST: Hierarchical Clustering 0.0113 0.0133 0.85

13071799 Terbufos Organophosphate TEST: Nearest Neighbor 0.24 0.0133 18.12

13071799 Terbufos Organophosphate TEST: Single Model 1.14 0.0133 85.71

13171216 Phosphamidon Organophosphate TEST: Consensus 65.50

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate TEST: FDA 113.00

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate TEST: Group Contribution 58.60

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate TEST: Hierarchical Clustering 0.41

- 99.00

- 99.00

## 88 | P a g e

13171216 Phosphamidon Organophosphate TEST: Nearest Neighbor 23.40

- 99.00

- 99.00

13171216 Phosphamidon Organophosphate TEST: Single Model 77.20

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: Consensus 1.44

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: FDA 2.21

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: Hierarchical Clustering 0.22

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: Nearest Neighbor 0.61

- 99.00

- 99.00

13194484 Ethoprophos Organophosphate TEST: Single Model 2.58

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: Consensus 2.92

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: FDA 13.70

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: Group Contribution 2.55

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: Hierarchical Clustering 0.0228

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: Nearest Neighbor 0.33

- 99.00

- 99.00

13593038 Quinalphos Organophosphate TEST: Single Model 5.00

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Consensus 1.51

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: FDA 2.65

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Nearest Neighbor 0.92

- 99.00

- 99.00

14816183 Phoxim Organophosphate TEST: Single Model 0.66

- 99.00

- 99.00

16752775 Methomyl Carbamates TEST: Consensus 25.20 2.11 11.94

16752775 Methomyl Carbamates TEST: FDA 41.40 2.11 19.62

16752775 Methomyl Carbamates TEST: Group Contribution

- 99.00 2.11

- 99.00

16752775 Methomyl Carbamates TEST: Hierarchical Clustering

- 99.00 2.11

- 99.00

16752775 Methomyl Carbamates TEST: Nearest Neighbor

- 99.00 2.11

- 99.00

16752775 Methomyl Carbamates TEST: Single Model 59.70 2.11 28.29

18854018 Isoxathion Organophosphate TEST: Consensus 1.08

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: FDA 1.24

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Group Contribution 0.44

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Hierarchical Clustering 0.0063

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Nearest Neighbor 1.22

- 99.00

- 99.00

18854018 Isoxathion Organophosphate TEST: Single Model 1.96

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: Consensus 3.90

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: FDA 2.54

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

21548323 Fosthietan organophosphate TEST: Single Model 4.84

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Consensus 6.81

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

## 89 | P a g e

22224926 Fenamiphos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Nearest Neighbor 6.81

- 99.00

- 99.00

22224926 Fenamiphos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Consensus 4.98

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Nearest Neighbor 4.98

- 99.00

- 99.00

22259309 Formetanate Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Consensus 22.50

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: FDA 9.46

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Group Contribution 141.00

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Hierarchical Clustering 1.48

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Nearest Neighbor 12.10

- 99.00

- 99.00

22781233 Bendiocarb Carbamates TEST: Single Model 24.80

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: Consensus 18.10

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: FDA 0.36

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: Group Contribution 304.00

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: Hierarchical Clustering 52.60

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

23103982 Pirimicarb Carbamates TEST: Single Model 51.00

- 99.00

- 99.00

23135220 Oxamyl Carbamates TEST: Consensus 39.40 6.89 5.72

23135220 Oxamyl Carbamates TEST: FDA 21.10 6.89 3.06

23135220 Oxamyl Carbamates TEST: Group Contribution

- 99.00 6.89

- 99.00

23135220 Oxamyl Carbamates TEST: Hierarchical Clustering

- 99.00 6.89

- 99.00

23135220 Oxamyl Carbamates TEST: Nearest Neighbor

- 99.00 6.89

- 99.00

23135220 Oxamyl Carbamates TEST: Single Model 224.00 6.89 32.51

23422539 Formetanate

hydrochloride Carbamates TEST: Consensus 4.98

- 99.00

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Nearest Neighbor 4.98

- 99.00

- 99.00

23422539 Formetanate

hydrochloride Carbamates TEST: Single Model

- 99.00

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Consensus 8.58

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: FDA 1.58

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Group Contribution 11.10

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Hierarchical Clustering 1.14

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

23560590 heptenophos Organophosphate TEST: Single Model 16.60

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Consensus 2.15

- 99.00

- 99.00

## 90 | P a g e

24017478 Triazophos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Hierarchical Clustering 0.12

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Nearest Neighbor 0.34

- 99.00

- 99.00

24017478 Triazophos Organophosphate TEST: Single Model 5.37

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Consensus 3.85

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: FDA 3.04

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Group Contribution 5.68

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Hierarchical Clustering 0.0336

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Nearest Neighbor 0.59

- 99.00

- 99.00

24934916 Chlormephos Organophosphate TEST: Single Model 9.13

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Consensus 0.38

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Nearest Neighbor 0.38

- 99.00

- 99.00

25311711 Isofenphos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Consensus 5.83

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: FDA 6.33

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Group Contribution 22.00

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Hierarchical Clustering 0.0027

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Nearest Neighbor 0.50

- 99.00

- 99.00

29232937 Pirimiphos

- methyl Organophosphate TEST: Single Model 13.50

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Consensus 5.35

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: FDA 13.00

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Group Contribution 5.08

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Hierarchical Clustering 8.10

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Nearest Neighbor 6.53

- 99.00

- 99.00

29973135 Ethiofencarb Carbamates TEST: Single Model 8.41

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Consensus 92.70

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Nearest Neighbor 92.70

- 99.00

- 99.00

30560191 Acephate Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Consensus 4.58

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Nearest Neighbor 4.58

- 99.00

- 99.00

31218834 Propetamphos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

## 91 | P a g e

34643464 Prothiofos Organophosphate TEST: Consensus 0.21

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: FDA 0.46

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Group Contribution 0.0553

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Hierarchical Clustering 0.0084

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Nearest Neighbor 0.20

- 99.00

- 99.00

34643464 Prothiofos Organophosphate TEST: Single Model 0.0826

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Consensus 10.10

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: FDA 3.69

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

34681102 Butocarboxim Carbamates TEST: Single Model 72.30

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Consensus 68.70

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: FDA 37.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

34681237 Butoxycarboxim Carbamates TEST: Single Model 79.30

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Consensus 8.67

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: FDA 16.50

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

39196184 Thiofanox Carbamates TEST: Single Model 14.50

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Consensus 3.89

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: FDA 9.73

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Group Contribution 2.96

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Hierarchical Clustering 0.0811

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Nearest Neighbor 7.11

- 99.00

- 99.00

40626355 Hepterophos Organophosphate TEST: Single Model 2.55

- 99.00

- 99.00

41198087 Profenofos Organophosphate TEST: Consensus 0.24 0.33 0.72

41198087 Profenofos Organophosphate TEST: FDA

- 99.00 3.33

- 99.00

41198087 Profenofos Organophosphate TEST: Group Contribution 0.18 0.33 0.53

41198087 Profenofos Organophosphate TEST: Hierarchical Clustering 0.0053 0.33 0.02

41198087 Profenofos Organophosphate TEST: Nearest Neighbor 0.21 0.33 0.64

41198087 Profenofos Organophosphate TEST: Single Model 0.30 0.33 0.89

42509808 Isazofos Organophosphate TEST: Consensus 3.29

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: FDA 1.46

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Hierarchical Clustering 0.56

- 99.00

- 99.00

42509808 Isazofos Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

## 92 | P a g e

42509808 Isazofos Organophosphate TEST: Single Model 4.95

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Consensus 3.75

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: FDA 133.00

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Group Contribution 1.13

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Hierarchical Clustering 8.74

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Nearest Neighbor 0.32

- 99.00

- 99.00

54593838 Chlorethoxyfos Organophosphate TEST: Single Model 4.49

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Consensus 0.11

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: FDA 0.0817

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Group Contribution 0.0084

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Nearest Neighbor 2.01

- 99.00

- 99.00

55285148 Carbosulfan Carbamates TEST: Single Model 0.12

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Consensus 11.60

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: FDA 5.42

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

59669260 Thiodicarb Carbamates TEST: Single Model 4.49

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Consensus 0.30

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: FDA 0.17

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Nearest Neighbor 0.27

- 99.00

- 99.00

65907304 Furathiocarb Carbamates TEST: Single Model 0.41

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Consensus 0.47

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Nearest Neighbor 0.47

- 99.00

- 99.00

66602877 Isamidofos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Consensus 0.81

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Hierarchical Clustering 0.22

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Nearest Neighbor 0.37

- 99.00

- 99.00

77458016 Pyraclofos Organophosphate TEST: Single Model 1.19

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Consensus 0.35

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: FDA 0.19

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Group Contribution 0.0200

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

## 93 | P a g e

82560541 Benfuracarb Carbamates TEST: Nearest Neighbor 2.17

- 99.00

- 99.00

82560541 Benfuracarb Carbamates TEST: Single Model 0.76

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Consensus 1.88

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: FDA 1.06

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Nearest Neighbor 1.72

- 99.00

- 99.00

83130012 Alanycarb Carbamates TEST: Single Model 3.57

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Consensus 1.98

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: FDA 23.20

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Hierarchical Clustering 0.0894

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Nearest Neighbor 0.55

- 99.00

- 99.00

95465999 Cadusafos Organophosphate TEST: Single Model 0.97

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Consensus 1.54

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: FDA 0.27

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Group Contribution 4.09

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Hierarchical Clustering 0.0037

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Nearest Neighbor 0.35

- 99.00

- 99.00

96182535 Tebupirimfos Organophosphate TEST: Single Model 5.42

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: Consensus 6.49

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: FDA 7.99

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: Hierarchical Clustering 0.41

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

98886443 Fosthiazate Organophosphate TEST: Single Model 5.50

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Consensus 6.78

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: FDA

- 99.00

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Group Contribution

- 99.00

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Hierarchical Clustering 8.56

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Nearest Neighbor

- 99.00

- 99.00

- 99.00

112143825 Triazamate Carbamates TEST: Single Model 6.78

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Consensus 2.30

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: FDA 7.85

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Group Contribution 1.74

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Hierarchical Clustering 0.0432

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Nearest Neighbor 0.82

- 99.00

- 99.00

126069543 Phosphocarb Organophosphate TEST: Single Model 2.16

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Consensus 2.58

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: FDA

- 99.00

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Group Contribution

- 99.00

- 99.00

- 99.00

## 94 | P a g e 140163899 Imicyafos Organophosphate TEST: Hierarchical Clustering

- 99.00

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Nearest Neighbor 2.58

- 99.00

- 99.00

140163899 Imicyafos Organophosphate TEST: Single Model

- 99.00

- 99.00

- 99.00



### - 99.00 Not available