ECOSAR Class Definition: Acid Halides The Acid Halide class is identified by any of the following structures:



## C O Halogen P O Halogen S O Halogen

The Halogens include chlorine (Cl), br omine (Br), fluorine (F) and iodine (I). The C(=O) carbon, P(=O) phosp horus and S(=O) sulfur can hav e other attachments. In the current ECOSAR program, these other attachments can be anything. SMILES String Identifications : C(=O)Br C(=O)Cl C(=O)F C(=O)I P(=O)Br P(=O)Cl P(=O)F P(=O)I S(=O)Br S(=O)Cl S(=O)F S(=O)I

Associated ECOSAR Class(s) : None

Example Acid Halides:

CAS No. Name SMILES Notation 75

‐ 36

‐ 5 Acetyl chloride O=C(Cl)C 506

‐ 96

‐ 7 Acetyl bromide O=C(Br)C 98

‐ 88

‐ 4 Benzoyl chloride O=C(c(cccc1)c1)Cl 98

‐ 09

‐ 9 Benzenesulfonyl chloride c1ccccc1S(=O)(=O)Cl 824

‐ 72

‐ 6 Phosphonic dichloride, phenyl ‐ O=P(c(cccc1)c1)(Cl)ClECOSAR Class Definition: Acrylamides The Acrylamides class is identif ied by the follo wing structure:



## N C C O

C R1

R2 R3

R1 and R2 - must be hydrogen or alkyl, olefinic , acetylenic or aromatic carbon atoms (no other atoms currently allowed).
R3 - can be anything (no exclusions) ... There is no Methacrylamide class in ECOSAR. In the current ECOSAR program, the Acryla mides structure must meet the following criteria: (1) Exactly as depicted by the struct ure representation and R-substituents SMILES String Identifications : C=C(=O)N C=C(=O)NC C=C(=O)NC=C C=C(=O)NC#C C=C(=O)Nc1ccccc1

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a general class having a CC(=O)N or NC(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the other classes (such as Acrylamides).

Example Acrylamides:

CAS No. Name SMILES Notation 79-06-1 Acrylamide C=CC(=O)N 94-62-2 Piperine O=C(N(CCCC1)C1)C=CC=Cc(ccc(OCO2)c23)c3 107-58-4 t-Butylacrylam ide O=C(NC(C)(C)C)C=C 2210-25-5 N-Isopropylacryl amide O=C(NC(C)C)C=CECOSAR Class Definition: Acrylates

The Acrylates class is identified by the following structures:

NOTE: The previous version of ECOSAR (1.0 and before) characterized anything with an acrylate alert, including chemicals with internal double bonds, within this class. In version 1.1 of ECOSAR, we have restricted the definition to represent only those chemicals with terminal double bonds which more correctly represent the acrylate moiety (as shown above)

. R1

- attachment to the olefinic carbon (adjacent t o the carbonyl or thiocarbonyl) can be anything except a methyl group (CH3). If the R1 attachment is a methyl group (CH3), the structure is classified as a Methacrylate

. R2

- attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S}

- can be either oxygen (

- O

- ) or sulfur (

- S

- ) Internally, the ECOSAR program initially detects a carbonyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefinic attachment and one oxygen or sulfur attachment. If the olefinic carbon has a methyl (CH3) attachment, the classification will be a Methacrylate (instead of Acrylate). The oxygen or sulfur must have either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon attachment to be classified as ei ther an Acrylate or Methacrylate. Associated ECOSAR Class(s) : Methacrylates

- If the olefinic carbon has a methyl (CH3) attachment, the classification will be a possible Methacrylate (instead of Acrylate). Example Acrylates :

CAS No. Name SMILES Notation 96

- 33

- 3 Methyl acyrlate C=CC(=O)OC 140

- 88

- 5 Ethyl acrylate C=CC(=O)OCC 3066

- 71

- 5 Cyclohexyl acrylate C=CC(=O)OC1CCCCC1ECOSAR Class Definition: Aldehydes (Mono) The Aldehydes (Mono) class is identif ied by the following structure:



# H C R1 O

R1 - attachment must be either an alkyl carbon, aromatic carbon, carbonyl or hydrogen. The structure can contain only one aldehy de functional group to be classified as Aldehydes (Mono). If a st ructure contains more t han one aldehyde group, it will be classified as Aldehydes (Poly). If the R1 attachment is an olefinic carbon, acetylenic carbon or a llyl group (-CC=C), the structure will be classified as a Vinyl/Allyl Aldehyde. In the current ECOSAR program, structures classified as Vinyl/Allyl Aldehydes are not additionally classified as Aldehydes (Mono). SMILES String Identifications : O=C or O=C[ H] or O=CH O=CC ... (no other atta chments to carbonyl) O=Cc1ccccc1 ... (no other attachments to carbonyl)

Associated ECOSAR Class(s) : Aldehydes (Poly) - If a structure contains mo re than one aldehyde group, it will be classified as Aldehydes (Poly) instead of Aldehydes (Mono) Vinyl/Allyl Aldehydes - If the R1 attachment is an olef inic carbon, acetylenic carbon or allyl group (-CC=C), the struct ure will be classified as a Vi nyl/Allyl Aldehyde. In the current ECOSAR program, structures cl assified as Vinyl/Allyl Aldehydes are not additionally classified as Aldehydes (Mono).

Example Aldehydes (Mono):

CAS No. Name SMILES Notation 75

‐ 07

‐ 0 Acetaldehyde O=CC 123

‐ 72

‐ 8 Butanal O=CCCC 555

‐ 16

‐ 8 Benzaldehyde, 4

‐ nitro ‐ O=Cc(ccc(N(=O)(=O))c1)c1 148

‐ 53

‐ 8 o
‐ Vanillin O=Cc(c(O)c(OC)cc1)c1 454

‐ 89

‐ 7 Benzaldehyde, 3

‐ (trifluoromethyl) ‐ O=Cc(cccc1C(F)(F)F)c1ECOSAR Class Definition: Aldehydes (Poly) The Aldehydes (Poly) class is identified by the more than one occurrence of following functional group in the structure:



# H C R1 O

R1 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, ca rbonyl or hydrogen.
The structure must contain more than one al dehyde functional group to be classified as Aldehydes (Poly). If a stru cture contains only one aldehyde group, it will be classified as either an Aldehydes (Poly) or Vinyl/ Allyl Aldehydes cla ss depending on the R1 attachment. In the current ECOSAR program, a structur e can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes. SMILES String Identifications : O=C or O=C[ H] or O=CH O=CC ... (no other atta chments to carbonyl) O=CC=C ... (no other a ttachments to carbonyl) O=CC #C ... (no other a ttachments to carbonyl) O=Cc1ccccc1 ... (no other attachments to carbonyl) ... a combination of two or more of t hese partial SMILES strings must be present anywhere in the entire SMILES.
Associated ECOSAR Class(s) : Aldehydes (Mono) - If a structure cont ains only one aldehyde group, it will be classified as either an Aldehydes (Poly) or Vinyl/ Allyl Aldehydes cla ss depending on the R1 attachment. Vinyl/Allyl Aldehydes - In the current ECOSAR program, a structure can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes.

Example Aldehydes (Poly):

CAS No. Name SMILES Notation 111

‐ 30

‐ 8 Pentanedial O=CCCCC=O 542

‐ 78

‐ 9 1,3

‐ Propanedial O=CCC=OECOSAR Class Definition: 

### Aliphatic Amines ECOSAR currently identifies several different types of structures as Aliphatic Amines which are described separately below. Normal Aliphatic Amines:



## C NH 2 

## C NH C N C C

C

Carbon attachments to the nitrogen must be aliphatic carbons (alkyl, olefinic or acetylenic carbon); aromatic carbon is not allowed. SMILES String Identifications:

NH2 type (one attachment to N): NC [equivalent to: N([H])([H])C or N(H)(H)C] NC=C [equiva lent to: N([H ])([H])C=C or N(H)(H)C=C] NC#C [equivalent to: N([H])([H])C or N(H)(H)C]

NH type (two attachments to N): CNC [equivalent to : CN([H])C or CN(H)C] N type (three attachments t N): CN(C)(C)

... for NH and N type, the carbons must be alkyl, olefinic or acetylenic

Aliphatic Amines with Oxygen:



## C NH O R1

C N O R1

C

R1 - can be anything including hydrogen. The carbon attachments to the nitrogen must be aliphatic carbons (alkyl, olefinic or ac etylenic carbon); aromat ic carbon is not allowed. SMILES String Identifications: NH type (two attachments to N) : CNO [equi valent to: CN([H]) O or CN(H)O] N type (three attachment s t N): CN(C)O

... for NH and N type, the carbons must be alkyl, olefinic or acetylenic

Oximes as Aliphatic Amines:

### C N OH C N O C

Substitutions of the carbon c an be anything including hydrogen. SMILES String Identifications: C=NO C=NOC

Nitrosaminesas Aliphatic Amines:



### N R

R N O

R - at least one carbon a ttachment to the nitrogen. The carbon attachment must be aliphatic carbons (alkyl, olefin ic or acetylenic carbon); aromatic carbon is not allowed. SMILES String Identifiactions: O=N O=N(C)C

Amine Oxides and Nitrosyl s as Aliphatic Amines:

R – can be an aliphatic carbon (alkyl, olef inic or acetylenic carbon).Carbon chain lengths greater than 8 may result in surfactant-like effects. SMILES String Identifiactions: O=N(C) O=N(C)(C)C

Amidines and Guanidines as Aliphatic Amines: 

## O N R R R O

R'

## N N R

R'
R' 

# N N N R



# R'

R' R' R'

R - must be either hydrogen or carbon (alkyl, olefinic, acetylenic or aromatic carbon) ...
R’ - can be anything (no exclusions)

SMILES String Identifications: N=C(C)N [ equivalent to: [H]N=C(C)N([H])[H] or HN=C(C)N(H)H ] N=C(N)N Reducible Ammonium Salts as Aliphatic Amines: Like all salts in ECOSAR, the conjugate salt of ammonium salts shoul d be replaced with a hydrogen; however, reduction of ammonium salts at a neutral pH results in a loss of hydrogens, and the resulting structure should be entered into ECOSAR as an aliphatic amine for the purpose of ECOSAR estimations (examples d epicted below). Ammonium salts in which the ammonium cation has four bound carbons in the presence of a stabilizing anion (e.g., chloride ion) are excluded from this definition since reduction is less likely. Predictions for these more stable ammoni um salts are based on analogous chemicals

or the cationic surfactant QSAR 

## R H
C N + 

## R 

## Anion

R - can be an aliphatic carbon (alkyl, olef inic or acetylenic carbon) or hydrogen Associated ECOSAR Class(s): Oxyamine - identified by H 2 N-O-C- structure. Triazine, Aliphatic – a 6-membered aliphatic ring structure with 3 alternating nitrogens.

Example Aliphatic Amines:

CAS No. Name SMILES Notation 107-10-8 Propylamine NCCC 111-42-2 Diethanolamine OCCNCCO107-15-3 1,2-Ethanediamine NCCN 103-76-4 1-Pipe razineethanol OC CN(CCNC1)C1 107-11-9 Allyl amine NCC=CECOSAR Class Definition: Alkoxy Silanes (or Silanes, alkoxy) The Silanes (alkoxy) class is identifi ed by the following example structure:



## Si O R2
R3 R1 Alkyl Carbon

R1
, R2 and R3 - must be either hydrogen, oxygen or carbon (alkyl, olefinic, acetylenic, aromatic or a carbonyl). In the current ECOSAR program, the Alko xy Silane structure meets the following criteria: (1) Contains a silicon to oxygen attachment . The oxygen must also be attached to an alkyl carbon (or carbonyl).
Notation: the R1, R2 and R3 attachments are limited to the atoms listed above ... Any other atom attachments (e.g. ni trogen, sulfur, halogen, etc) will not result in an Alkoxy Silane identification. SMILES String Identifications : [Si]OC SiOC ... (ECOSAR allows Silicon to be either with or without brackets) ... other attachments to Silicon as defined above.

Associated ECOSAR Class(s) : None specifically.
The Silamines class is the only other ECOSAR cl ass specifically containing silicon.

Example Alkoxy Silanes:

CAS No. Name SMILES Notation 78-62-6 Dimethyl dietho xysilane C[Si](OCC)(OCC)C 18246-71-4 Silane, butoxyethoxyd imethyl- CCCCO[Si](C)(C)OCC 17841-46-2 Silane, methoxytripr opyl- [Si](OC)(CCC)(CCC)CCCECOSAR Class Definition: Amides The Amides class is identified by the following structures:



### R 1 

### C [or S]

N O

R 2



### R 3

R1 can be an aliphatic carbon with a single b ond to any atom other than a halogen, or an aromatic carbon.
R1 can not contain the following atoms below:
If R1 is an oxygen atom, ECOSAR will identify the structur e as a carbamate ester or derivatives
If R1 is a C=C, ECOSAR will identify the structure as an acrylamide
If R1 is a sulfur atom, ECOS AR will identify the struct ure as a thiocarbamate,
mono
If R1 is a nitrogen atom, ECOSAR will identify t he structure as a s ubstituted urea.
If R1 is C-halogen group, ECOSAR will identi fy the structure as a Haloacetamide.
R2 and R3 can be anything other t han a carbonyl group.
If either R2 or R3 are carbonyl groups, ECOSAR will identify the structure as a carbonyl urea. SMILES String Identifications: O=CN ... ( equivalent to: O=C(H)N or O= C([H])N formamide-type) CC(=O)N

NOTE : If R1 above is a benzene ring (6-member arom atic ring) with a nitro/nitroso attachment, then ECOSAR will also identify t he structure as nitro/nitroso-Benzamides. There are very limited empirical data for this class (fish acute only) so this substitution rule for R1 has not been implement as an excl usion for the amides class so that the user is presented with QSAR results for both classes. Example Amides:

CAS No. Name SMILES Notation 60-35-5 Acetamide NC(=O)C 2620-63-5 Glycin-amide,N-a cetyl CC(=O)NCC(=O)NAnilines (amino-meta) The Anilines (amino-meta) class is i dentified by the fo llowing structure:

In the current ECOSAR program, the An ilines (amino-meta) st ructure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in meta-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications : Nc1cc(N)ccc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N(H)(H)c1cc(N(H)H)cc1 ... aromatic ring can contain non-car bon members as in: Nc1cc(N)ccn1

Associated ECOSAR Class(s) : Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (a mino-meta) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-ortho) and Anilines (amino-para) - These classes are identified when a six-member aromatic ring has tw o -NH2 substituents in either a ortho- or para-position. When identified in conjunction with Anilines (amino-meta), they are both reported by ECOSAR.

Example Anilines (amino-meta):

CAS No. Name SMILES Notation 108-45-2 m-Phenylenediamine Nc(cccc1N)c1 608-32-2 1,2,3-Triaminobenzene Nc1c(cccc1N)N 94-10-0 Ethoxazene Nc1cc(N) c(N=Nc2ccc(OCC)cc2)cc1 95-86-3 2,4-Diaminophenol Nc1ccc(O)c(N)c1495-54-5 2,4-Diaminoazobenzene N( =Nc(cccc1)c1)c(c( N)cc(N)c2)c2Anilines (amino-ortho) The Anilines (amino-ortho) class is identified by the fo llowing structure:

In the current ECOSAR program, the Anili nes (amino-ortho) st ructure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in ortho-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications : Nc1c(N)cccc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N( H)(H)c1c(N(H)H)ccc1 ... aromatic ring can contain non-carbon members as in: Nc1c(N)cccn1 Associated ECOSAR Class(s) : Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (ami no-ortho) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-meta) and Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substi tuents in either a meta- or para-position. When identified in conjunction with Anilines (amino-ortho), they are both reported by ECOSAR.

Example Anilines (amino-ortho):

CAS No. Name SMILES Notation 95-54-5 o-Phenylenediamine Nc(c(N)ccc1)c1 91-95-2 1,1'-Biphenyl -3,3',4,4'-tetrami ne Nc(c(N)cc(c(ccc(N)c1N)c1)c2)c2 95-83-0 1,2-Benzenediamine, 4-chloro- Nc(c(N)cc(c1)Cl)c1 608-32-2 1,2,3-Triaminobenzene Nc1c(cccc1N)NAnilines (amino-para)

The Anilines (amino-para) class is identified by the following structure:

In the current ECOSAR program, the Anilines (amino-para) structure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in para-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications: Nc1ccc(N)cc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N(H)(H)c1ccc(N(H)H)c1 ... aromatic ring can contain non-carbon members as in: Nc1ccc(N)cn1 Associated ECOSAR Class(s): Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (amino-para) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-ortho) and Anilines (amino-meta) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either a meta- or ortho-position. When identified in conjunction with Anilines (amino-para), they are both reported by ECOSAR.

Example Anilines (amino-para):

CAS No. Name SMILES Notation 106-50-3 p-Phenylenediamine Nc(ccc(N)c1)c1 95-70-5 2,5-Diaminotoluene Nc(c(cc(N)c1)C)c1 615-71-4 1,2,4-Benzenetriamine Nc1c(N)cc(N)cc1ECOSAR Class Definition: Anilines (Hindered) The Anilines (Hindered) class is ident ified by the follo wing structure:

A carbon-based functional group must be atta ched ortho to the amine group (can be an aliphatic carbon [including alky l, olefinic, acetylenic, car bonyl] or an aromatic carbon [biphenyl-type attachment]). In the current ECOSAR program, the Anili ne (Hindered) structur e meets the following criteria: (1) A benzene ring (or any other aromatic ring including hetero-aromatic rings) that has an amine substituent as -NH2 (2) The aromatic ring can be fused to another ring. (3) An aliphatic carbon is pr esent in the ortho-position.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. The Anilines (Hinderd) SAR Sheet notes that N-substituted amines are less to xic than the SARs for this class SMILES String Identifications: Nc1ccccc1C Nc1c(C)cccc1 Associated ECOSAR Class(s): Anilines (Unhindered) - an R-substituent is not an carbon-bas ed ortho attachment. Dinitro Aromatic Amine (Dinitro Aniline)- If an aromatic ring has both the amine substituent (-NH2) and two or more nitro s ubstituents (-NO2), ECOSAR classifies the ring as Dinitro Aromatic Amine and also repo rts the Anilines (Hindered) identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. Example Anilines (Hindered):

CAS No. Name SMILES Notation 88-68-6 Benzamide, 2-amin o- O=C(N)c(c(N)ccc1)c1 24544--04-5 2,6-Diisopropylan iline Nc(c(ccc1)C(C)C)c1C(C)C 2894-51-1 2-Amino-4'-chlorobenzoph enone Nc1ccccc1C(= O)c2ccc(Cl)cc2ECOSAR Class Definition: Anilines (Unhindered) The Anilines (Unhindered) class is i dentified by the follo wing structure: 

## NH 2 

## R

R can not be a carbon-based fragment (including alkyl, olefinic, acetylenic, carbonyl or an aromatic carbon). A llowed attachments include hydrogen atoms, chlorine, secondary or tertiary nitrogens, sulfur, etc.
R can not be a prim ary amine. If R is a primary amine (NH2) then ECOSAR will identify the cl ass as amino-ortho anilines In the current ECOSAR program, the Aniline (Unhindered) structure meets the following criteria: A benzene ring (or any other aromatic ring incl uding hetero-aromatic rings) that has an amine substituent as -NH2. The aromatic ring can be fused to another ring.
An excluded R-substituent is not present in t he ortho-position.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. The Anilines (Unhinderd) SAR Sheet notes that N-substituted amines are less to xic than the SARs for this class. SMILES String Identifications: Nc1ccccc1 c1ccccc1N Associated ECOSAR Class(s): Anilines (Hindered) - an R-s ubstituent is an aliphatic or aromatic carbon-based attachment in the ortho position. Dinitro Aromatic Amine (Dinitro Aniline)- If an aromatic ring has both the amine substituent (-NH2) and two or more nitro s ubstituents (-NO2), ECOSAR classifies the ring as Dinitro Aromatic Amine and also repo rts the Anilines (Unhin dered) identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. Example Anilines (Unhindered):

CAS No. Name SMILES Notation 62-53-3 Anilin e Nc1ccccc1 371-40-4 4-Fluoroaniline Nc1ccc(F)cc1106-49-0 4-Toluidine Nc1ccc(C)cc1 3481-20-7 2,3,5,6-Tetrachloroan iline Nc1c(Cl)c(Cl)cc(Cl)c1ClECOSAR Class Definition: Aziridines
The Aziridines class is identifi ed by the following ring structure:



# N

ECOSAR identifies an Az iridine ring as follows: (1) a three member aliphatic ring consis ting of one aliphatic nitrogen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Aziridine ring can be part of a fused-ring system

SMILES String Identifications : N1CC1 ... (same as: C1NC1 or C1CN1 )

Associated ECOSAR Class(s) : Aliphatic Amines - In the current ECOSAR program, the nitrogen in an aziridine ring is not additionally classified as an Aliphatic Amine.

Example Aziridines:

CAS No. Name SMILES Notation 151-56-4 Aziridine N1CC1 1072-44-2 N-Methylaziridine CN1CC1 75-55-8 2-Methylaziridine N1CC1C 286-18-0 7-Azabicyclo[4.1. 0]heptane N(C1CC2)C1CC2 4055-40-7 Mitomycin B COC4=C(C)C(=O)C1 =C(C(COC(N)=O)C2(O)C3C(CN12)N3C)C4=OECOSAR Class Definitions: Benzodioxoles
The Benzodioxoles class is identif ied by the following structure:



## O

O

In the current ECOSAR program, the Benzodi oxole structure identification meets the following criteria: (1) The ECOSAR program identifies a five-m ember ring containing two aromatic carbon atoms, two aliphatic oxygen atoms and one alkyl carbon at om. Currently, the position of the atoms in the ring is not differentiated; for example, t he two oxygen atoms could sideby-side and the structure will still be identified as Benzod ioxoles (the two different structures would correspond to 1,3- benzodioxole and 1, 2-benzodioxole). (2) The aromatic ring that is fused to the five-member is not required to be a benzene ring; it can be any aromatic ring including hetero-aromatic rings. (3) The Benzodioxole ring structure can be fused to additional ring(s). SMILES String Identifications : Equivalent SMILES for 1,3-benzodioxole: c1cccc2OCOc12 c1ccc2OCOc2c1 c1cc2OCOc1cc1 c12ccccc1OCO2 C1=CC=C2OCOC2=C1 O1c2ccccc2OC1O=CC
Associated ECOSAR Class(s) :
None.

Examples Benxodioxoles:

CAS No. Name SMILES Notation 274-09-9 1,3-Benzodioxole c1ccc2OCOc2c1 51-03-6 Piperonyl butoxide O(c(c(O1)cc(c2CCC)COCCOCCOCCCC)c2)C1ECOSAR Class Definition: Benzotriazoles The Benzotriazoles class is identified by t he following structures (1H-Benzotriazole and 2H-Benzotriazole):



## N

N N

R N

N N R

R - can be anything (no exclusions) In the current ECOSAR program, the Benzotri azoles structure must meet the following criteria: (1) The triazole ring must be fused to a benzene ring. The ring to which the triazole ring is fused cannot be a hetero-aromatic ring. (2) The fused benzene ring can be fused to another ring SMILES String Identifications : c1ccc2nn[nH]c2c1 c1ccc2n[nH]nc2c1 c1ccc2nnnc2c1 c1ccc2N=NNc2c1 C1=CC2=NNN=C2C=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo. With respect to structures containing a triazole ring: Triazoles (Non-Fused) - a structure containing either a 1,2,4-triazole, 1,2,3-triazole or 1,3,4-triazole ring t hat is not fused to another aromatic ring. Triazole Pyrimidines - a triazole-pyrimidine fused ring structure Examples Benzotriazoles:

CAS No. Name SMILES Notation 95-14-7 1H-Benzotriazole c1ccc2nnnc2c1 273-02-9 2H-Benzotriazole c1ccc2nnnc2c1

36437-37-3 Phenol, 2-(2H-benzotriazol-2-yl)- 4-(1,1-dimethylethyl)-6-(1- methylpropyl)- Oc(c(cc(c1)C(C)(C) C)C(CC)C)c1n(nc(c2ccc3)c3)n2ECOSAR Class Definition: Benzoylcyclohexanedione The Benzoylcyclohexanedione class is ident ified by the following structure:



## C C C O O

O

In the current ECOSAR program, the B enzoylcyclohexanedione structure meets the following criteria: (1) A linear carbonyl [-C(=O)-] is attached to both a phenyl ring and a 2,6- cyclohexanedione ring at the position shown above. (2) The rings can be fused to other rings.
Notation : The current identification in ECOSAR is very strict ... The phenyl ring must be a phenyl ring (a hetero-aromat ic ring (e.g. pyridine) is not allowed) ... The cyclohexanedione ring must be a 2,6-dione only with the linear carbonyl attached at the 1-position. SMILES String Identifications : c1ccccc1C(=O)C2C(=O)CCCC2=O equivalent SMILES : O=C(c1ccccc1)C2C(=O)CCCC2=O

Associated ECOSAR Class(s) : None specifically.

Example Benzoylcyc lohexaediones:

CAS No. Name SMILES Notation 99105-77-8 Sulcotrione O=C1CCCC(=O)C1C(=O)c2ccc(S(=O)(=O)C)cc2ClECOSAR Class Definition: Benzyl Alcohols The Benzyl Alcohols class is ident ified by the following structure:



## C OH

In the current ECOSAR program, the Ben zyl Alcohol structur e meets the following criteria: (1) An alkyl carbon atom has both an hydr oxyl (-OH) attachment and benzene ring attachment. (2) A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ri ng can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications : c1ccccc1CO ... ( equivalent to : c1ccccc1COH or c1ccccc1CO[H] )

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other Alc ohol classes (such as Propargyl Alcohols, Vinyl/Allyl Alcohols, Ketone Alcohol, Halo Al cohols and Nitro Alcohols). ECOSAR also includes a variety of Benzyl classes.

Example Benzyl Alcohols:

CAS No. Name SMILES Notation 100-51-6 Benzyl alcohol c1ccccc1CO 4412-91-3 3-Hydroxymethylfuran OCc1ccoc1 115-32-2 Dicofol OC(c1ccc(Cl)cc 1)(c2ccc(Cl)cc2)C(Cl)(Cl)ClECOSAR Class Definition: Benzyl Halides The Benzyl Halides class is ident ified by the following structure:



### C Halogen

[ Halogen = Br, Cl or I ]

In the current ECOSAR program, the Ben zyl Halide structure meets the following criteria: (1) An alkyl carbon atom has both a benzene ring attachment and a Halogen attachment. For this class, halogens are lim ited to bromine, chlorine and iodine ... Fluorine is excluded. (2) A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ri ng can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications : with bromine: c(CBr) or c1CBr with chlorine: c(CCl) or c1CCl with iodine: c(CI) or c1CI

... with a complete ring : c1ccccc1CBr or c1ccccc1CCl or c1ccccc1CI
Associated ECOSAR Class(s) : None specifically. ECOSAR includes other Halide classes (such as Propargyl Halides, Vinyl/Allyl Halides, Acid Halides, Halo Acetamides, Halo Ethers, etc). ECOSAR also includes a variety of Benzyl classes.

Example Benzyl Halides:

CAS No. Name SMILES Notation 100-44-7 Benzene, (chloromethyl)- c(cccc1)(c1)CCl 611-19-8 o-Chlorobenzyl ch loride c(c(ccc1)Cl)(c1)CCl 623-25-6 Benzene, 1,4-bis(chloro methyl)- c(ccc(c1)CCl)(c1)CCl 30030-25-2 Chloromethyl styrene C=Cc1ccc(cc1)CClECOSAR Class Definition: Benzyl Imides The Benzyl Imides class is ident ified by the follo wing structure:

R 1 [S] O N R 2

R 3 O [S]

R1 and R3 can be anything except a nitrogen atom
If R1 or R3 are a nitrogen atom, ECOSAR wil l identify the class as carbonyl ureas. The carbonyl urea contains training set chemicals contain structures with the R1 or R3 as nitrogen atoms and the R2 as defined below.
R2 must be an alkyl carbon that is attached to a phenyl or other aromatic ring. A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and t he aromatic ring can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications: c(CN(C(=O))C(=O)) or c1CN(C(=O))C(=O) ... complete ring : c1ccccc1CN(C(=O))C(=O) c(CN(C(=S))C(=S)) or c1CN(C(=S))C(=S) ... complete ring : c1ccccc1CN(C(=S))C(=S) c(CN(C(=O))C(=S)) or c1CN(C(=O))C(=S) ... complete ring : c1ccccc1CN(C(=O))C(=S)

Example Benzyl Imides:

CAS No. Name SMILES Notation 2142-01-0 2-Benzyl-isoindole-1,3-dion e c12C(=O)N(Cc3cccc c3)C(=O)c1cccc2 32000-70-7 Uracil, 3-benzyl-5-bromo-1,6-dime thyl- N1(C)C(=O)N(Cc2c cccc2)C(=O)C(Br)=C1CECOSAR Class Definition: Benzyl Nitriles The Benzyl Nitriles class is ident ified by the follo wing structures:

C N

C C N

C Aromatic Ring

In the current ECOSAR program, the Benzyl Nitrile structure must meet the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl carbon which also has a pheny l or aromatic ring attachment. (2) A strict definition of “benzyl” implie s the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. Howeve r, in the current ECOSAR program, the single alkyl carbon can -CH2-, -CH< or >C< and the aromatic ring can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications: c(CC#N) or c1CC#N ... with a complete ring : c1ccccc1CC#N

... attachments to the alkyl carbon as defined above

Associated ECOSAR Class(s): Nitriles, Polyaliphatic - Two or more nitrile groups are atta ched to aliphatic atoms in the whole structure. When two or more nitrile groups are attached to the same alkyl or olefinic carbon, the structur e will be classified as both Viny l/Allyl Nitriles and Nitriles, Polyaliphatic. Pyrethroids - One of the two potential identif ying structures for pyrethroids contains the benzyl nitrile moiety. Due to the nature of t he pyrethroid class as a pesticide class with a complex structure and mode of action, compounds that fit t he pyrethroid definition are excluded from the benzyl nitriles class.
Other SAR Nitrile classes include: Halo Nit riles, Nitrile Alpha-OH, Phthalonitriles, Vinyl/Allyl Nitriles, Malonitril es, and Nitriles, Polyaliphatic.

Example Benzyl Nitriles:

CAS No. Name SMILES Notation 140-29-4 Benzyl nitrile c1ccccc1CC#NCarbamate Esters, Alkyl

The Carbamate Esters class is iden tified by the following structure:



## R N O R' O

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).
If R is a primary amine ECOSAR will id entify the class as a simple ester

R’ - can be anything except a 6-member aromatic ring (c 1ccccc1) or -N=C.

If R’ is an aromatic ring ECOSAR will id entify the class as carbamate esters, phenyl.

If R’ is an -N=C group, ECOSAR will identi fy the class as carbamates esters, oxime
In the current ECOSAR program, the Carbamate Esters class meets the criteria as shown in the structures above.
Associated ECOSAR Class(es): Carbamate Esters, Oxime - if R’ is -N=C, the ECOSAR class becomes Oxime Carbamate Ester, and the Carbamate Ester class is excluded.
Carbamate Esters, Phenyl - if R’ is a phe nyl ring, the ECOSAR class becomes Phenyl Carbamate Ester, and the Carbamate Ester class is excluded.
ECOSAR includes a variety of Th iocarbamate ester classes.
Example Carbamate Esters:

CAS No. Name SMILES Notation 101-21-3 Chlorp ropham CC(C)OC(=O)Nc1cccc(Cl)c1 6135-31-5 N-Methylethylcarbamate O=C(OC)NCC 539-71-9 Ethylidene O= C(OCC)NC(NC(=O)OCC)C

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamat e Esters, Alkyl Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however,data available for modeling were limited to methylcarbamates and, thus, the trend may be specific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not been fully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that carba mate esters with certa in steric properties may be hydrolytically degraded before the ca rbamate ester has an opportunity to inhibit the enzyme. Additionally, Fukuto (1990) indi cates “that methylcarbamate esters of alcohols are intrinsically unr eactive [compared to methyl carbamates substituted with phenols or oximes] and, therefore, they are generally poor anticholinesterases [e.g., poor inhibitorsof AChE]. A good fit of a methylcarbamate ester in the enzyme active site, i.e., formation of the enzyme-inhibitor complex pr ior to carbamylation, is crucial for high anti-cholinesterase activity.” Thus, the Carbamate Ester, Alkyl QSAR is considered to represent the least toxic carbamate ester QSAR class based on available data and supporting information. Fukuto (1990) provide s a more in depth discussion of the mechanism of inhibition of carbamate inse cticides, which support ecotoxicity trends observed in available carbamate esters data. Datasets for the below determined equations have excluded any studies using static tes ting methods without anal ytical monitoring of test concentrations due to potential for hydrolysis.
Desmedipham and phenmedipham were includ ed in Carbamate Esters, Alkyl QSAR based on data that suggested poor inhibiti on of acetylcholinesterase, which may be a result of hydrolytic instabili ty or poor formation of the enzyme-inhibitor complex, even though these compounds contain a carbamate es ter conjugated with a phenyl in addition to a carbamate ester conjugated with an alkyl . Some instances of hydrolytic instability and poor formation of the enzyme-inhibitor co mplex may need to be assessed on a caseby-case basis.

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.Carbamate Esters, Oxime

The Oxime Carbamate Ester class is iden tified by the following substructure:

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).

If R is a primary amine, ECOSAR will iden tify the class as a neutral organic. This is because for an ester classification, the functional group off the oxygen must be carbon based and therefore the –N=C does not qualify, nor do any other nitrogen functional group attachments.
In the current ECOSAR program, the Oxime Ca rbamate Ester class meets the criteria as shown in the structure above. Subst itutions on the oxime carbon are allowed.
Associated ECOSAR Class(es): Carbamate Esters - if the -N=C attached to the oxygen is replaced by something else (excluding a phenyl ring), the ECOSAR class becomes Carbamate Esters.
Phenyl Carbamate Esters - if the -N=C is replaced by a phenyl ring, the ECOSAR class becomes Phenyl Carbamate Ester, and th e Carbamate Ester class is excluded.
Example Oxime Carbamate Ester:

CAS No. Name SMILES Notation 23135-22-0 Oxamyl CNC( =O)ON=C(SC)C(=O)N(C)C 16752-77-5 Methomyl CNC(=O)ON=C(C)SC 116-06-3 Aldicarb O=C(ON=CC(SC)(C)C)NC

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamat e Esters, Oxime Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however, data available for modeling were limited to methylcarbamates and, thus, the trend may bespecific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not been fully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that “[m]ethylcarbamates of substituted phenols and oximes with good complementary fit to the [AChE] enzyme active site are generally strong inhibitors of AChE.” Furthermore, s ubstitution of “ phenols and oximes, each with pKa values in the region of 10, [make] methyl carbamates that are reactive to the degree that they are able to carbamylate the seri ne hydroxyl of AChE. Owing to the intrinsic reactivity of methylcarbamate esters, an elec tron-withdrawing substitu ent is not required in the aryl moiety for high anticholinesterase activity.” Fukuto (1990) provides a more in depth discussion of the mechanism of inhibiti on of carbamate insec ticides, which support ecotoxicity trends observed in available carb amate esters data. Datasets for the below determined equations have excluded any studi es using static tes ting methods without analytical monitoring of test concentr ations due to potential for hydrolysis.Carbamate Esters, Phenyl
The Phenyl Carbamate Ester class is id entified by the following structure:


### N O

O R

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).

If R is a primary amine, ECOSAR will id entify the class as a simple ester
In the current ECOSAR program, the Phenyl Carbamate Ester class meets the criteria as shown in the structure above.
Substitutions on the phenyl ring are allowed.
Associated ECOSAR Class(es): Carbamate Esters - if the phenyl ring atta ched to the oxygen is replaced by an aliphatic group, the ECOSAR class becomes Carbamate Esters.
Oxime Carbamate Esters - if the phenyl ri ng attached to the oxygen is -N=C, the ECOSAR class becomes Oxime Carbamate Ester, and the Carbamate Ester class is excluded.
Example Oxime Carbamate Ester:

CAS No. Name SMILES Notation 114-26-1 Propoxur CN C(=O)Oc1ccccc1OC(C)C 63-25-2 Carbaryl O=C(Oc(c(c(ccc1)cc2)c1)c2)NC 2686-99-9 Trimethacarb CN C(=O)Oc1cc(C)c(C)c(C)c1

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamate Esters, Phenyl Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however, data available for modeling were limited to methylcarbamates and, thus, the trend may be specific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not beenfully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that “[m]ethylcarbamates of substituted phenols and oximes with good complementary fit to the [AChE] enzyme active site are generally strong inhibitors of AChE.” Furthermore, s ubstitution of “ phenols and oximes, each with pKa values in the region of 10, [make] methyl carbamates that are reactive to the degree that they are able to carbamylate the seri ne hydroxyl of AChE. Owing to the intrinsic reactivity of methylcarbamate esters, an elec tron-withdrawing substitu ent is not required in the aryl moiety for high anticholinesterase activity.” Fukuto (1990) provides a more in depth discussion of the mechanism of inhibiti on of carbamate insec ticides, which support ecotoxicity trends observed in available carb amate esters data. Datasets for the below determined equations have excluded any studi es using static tes ting methods without analytical monitoring of test concentra tions due to potential for hydrolysis.
Fukuto (1990) suggests that “introduction of a nitro substituent into the phenyl ring of phenyl methylcarbamate results in a com pound of such high reactivity that it is hydrolytically degraded before it has an oppor tunity to inhibit the enzyme.” Aquatic toxicity data were not locat ed for compounds such as th is and, thus, the Carbamate Esters, Phenyl QSAR class does not account for this phenomenon.
In comparing the rates of reaction of [m-isopropyl compound] and [m-tert-butyl compound] with [ammonium co mpound], Fukoto suggests that “replacement of the central carbon atom [in the side chain] with a positively charged quaternary nitrogen atom [similar to Ammonium, (3-(methylcarbamo yloxy) phenyl)trimethyl-, chloride (CAS # 64051-06-5)] resulted in about a 50-fold in crease in anticholinesterase activity.” Aquatic toxicity data were not located fo r compounds such as this and, thus, the Carbamate Esters, Phenyl QSAR class does not account for this phenomenon. Additionally, compounds such as this are treated as cationic surfactants for the purpose of QSAR predictions.

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.ECOSAR Class Definition: Carbonyl Ureas In ECOSAR V1 and early, carbonyl ureas were identified as both imides and substituted ureas. The Carbonyl Urea class is identifi ed by the following ex ample structure in ECOSAR V1.1.

R 1 N N R 4 O O

R 2 R 3

The nitrogens must be aliphatic nitrogen atoms
R1 can be anything (no exclusions) If R1 is a sulfur atom, t here may be overlap with the thiocarbamates, mono class based on the training set chemicals, but to xicity profiles are similar for both classes to all organisms and therefore no re strictions will be applied at this time since thiocarbamates, mono class define only the [S-C=ON] por tion of the above base structure. R2, R3 and R4 can be anything except halogen atoms. If R2 or R3 or R4 are halogens, ECOSAR will identify the class as haloimides which show much higher toxicity to fish and daphnid than non-halogenated carbonyl ureas
R4 can be anything (no exclusions) The oxygen in the carbonyl(s) can not to be replaced by S or N atoms, as is done in other related classes. In this case, compounds containing C=S are included in the thioureas class definition, though the effects of the r epeating C=S (like the carbonyl does above) is unknown since simple thiourea (NC=SN) defines the training set. We have no structural analogs in ECOSAR for the C= N configuration of th is molecule. A related class is sulfonyl ureas where a sulfone group [S(=O)(=O)] replaces the second carbonyl group off of the R1 above.
SMILES String Identifications: Carbonyl Urea Group : C(=O)NC(=O)N
Example Carbonyl Urea:

CAS No. Name SMILES Notation 314-40-9 Bromacil N1C(=O )N(C(C)CC)C(=O)C(Br)=C1C 36734-19-7 Iprodione c1c(Cl)cc(Cl )cc1N2C(=O)C N(C(=O)NC( C)C)C2(=O) 78587-05-0 Hexythiazox c1cc(Cl)cc c1C2SC(=O)N(C(=O)NC3CCCCC3)C2C 57-43-2 Amobarbital CCC1( CCC(C)C)C(=O) NC(=O)NC1=OECOSAR Class Definition: Acid Halides The Acid Halide class is identified by any of the following structures:



## C O Halogen P O Halogen S O Halogen

The Halogens include chlorine (Cl), br omine (Br), fluorine (F) and iodine (I). The C(=O) carbon, P(=O) phosp horus and S(=O) sulfur can hav e other attachments. In the current ECOSAR program, these other attachments can be anything. SMILES String Identifications : C(=O)Br C(=O)Cl C(=O)F C(=O)I P(=O)Br P(=O)Cl P(=O)F P(=O)I S(=O)Br S(=O)Cl S(=O)F S(=O)I

Associated ECOSAR Class(s) : None

Example Acid Halides:

CAS No. Name SMILES Notation 75

‐ 36

‐ 5 Acetyl chloride O=C(Cl)C 506

‐ 96

‐ 7 Acetyl bromide O=C(Br)C 98

‐ 88

‐ 4 Benzoyl chloride O=C(c(cccc1)c1)Cl 98

‐ 09

‐ 9 Benzenesulfonyl chloride c1ccccc1S(=O)(=O)Cl 824

‐ 72

‐ 6 Phosphonic dichloride, phenyl ‐ O=P(c(cccc1)c1)(Cl)ClECOSAR Class Definition: Acrylamides The Acrylamides class is identif ied by the follo wing structure:



## N C C O

C R1

R2 R3

R1 and R2 - must be hydrogen or alkyl, olefinic , acetylenic or aromatic carbon atoms (no other atoms currently allowed).
R3 - can be anything (no exclusions) ... There is no Methacrylamide class in ECOSAR. In the current ECOSAR program, the Acryla mides structure must meet the following criteria: (1) Exactly as depicted by the struct ure representation and R-substituents SMILES String Identifications : C=C(=O)N C=C(=O)NC C=C(=O)NC=C C=C(=O)NC#C C=C(=O)Nc1ccccc1

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a general class having a CC(=O)N or NC(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the other classes (such as Acrylamides).

Example Acrylamides:

CAS No. Name SMILES Notation 79-06-1 Acrylamide C=CC(=O)N 94-62-2 Piperine O=C(N(CCCC1)C1)C=CC=Cc(ccc(OCO2)c23)c3 107-58-4 t-Butylacrylam ide O=C(NC(C)(C)C)C=C 2210-25-5 N-Isopropylacryl amide O=C(NC(C)C)C=CECOSAR Class Definition: Acrylates

The Acrylates class is identified by the following structures:

NOTE: The previous version of ECOSAR (1.0 and before) characterized anything with an acrylate alert, including chemicals with internal double bonds, within this class. In version 1.1 of ECOSAR, we have restricted the definition to represent only those chemicals with terminal double bonds which more correctly represent the acrylate moiety (as shown above)

. R1

- attachment to the olefinic carbon (adjacent t o the carbonyl or thiocarbonyl) can be anything except a methyl group (CH3). If the R1 attachment is a methyl group (CH3), the structure is classified as a Methacrylate

. R2

- attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S}

- can be either oxygen (

- O

- ) or sulfur (

- S

- ) Internally, the ECOSAR program initially detects a carbonyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefinic attachment and one oxygen or sulfur attachment. If the olefinic carbon has a methyl (CH3) attachment, the classification will be a Methacrylate (instead of Acrylate). The oxygen or sulfur must have either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon attachment to be classified as ei ther an Acrylate or Methacrylate. Associated ECOSAR Class(s) : Methacrylates

- If the olefinic carbon has a methyl (CH3) attachment, the classification will be a possible Methacrylate (instead of Acrylate). Example Acrylates :

CAS No. Name SMILES Notation 96

- 33

- 3 Methyl acyrlate C=CC(=O)OC 140

- 88

- 5 Ethyl acrylate C=CC(=O)OCC 3066

- 71

- 5 Cyclohexyl acrylate C=CC(=O)OC1CCCCC1ECOSAR Class Definition: Aldehydes (Mono) The Aldehydes (Mono) class is identif ied by the following structure:



# H C R1 O

R1 - attachment must be either an alkyl carbon, aromatic carbon, carbonyl or hydrogen. The structure can contain only one aldehy de functional group to be classified as Aldehydes (Mono). If a st ructure contains more t han one aldehyde group, it will be classified as Aldehydes (Poly). If the R1 attachment is an olefinic carbon, acetylenic carbon or a llyl group (-CC=C), the structure will be classified as a Vinyl/Allyl Aldehyde. In the current ECOSAR program, structures classified as Vinyl/Allyl Aldehydes are not additionally classified as Aldehydes (Mono). SMILES String Identifications : O=C or O=C[ H] or O=CH O=CC ... (no other atta chments to carbonyl) O=Cc1ccccc1 ... (no other attachments to carbonyl)

Associated ECOSAR Class(s) : Aldehydes (Poly) - If a structure contains mo re than one aldehyde group, it will be classified as Aldehydes (Poly) instead of Aldehydes (Mono) Vinyl/Allyl Aldehydes - If the R1 attachment is an olef inic carbon, acetylenic carbon or allyl group (-CC=C), the struct ure will be classified as a Vi nyl/Allyl Aldehyde. In the current ECOSAR program, structures cl assified as Vinyl/Allyl Aldehydes are not additionally classified as Aldehydes (Mono).

Example Aldehydes (Mono):

CAS No. Name SMILES Notation 75

‐ 07

‐ 0 Acetaldehyde O=CC 123

‐ 72

‐ 8 Butanal O=CCCC 555

‐ 16

‐ 8 Benzaldehyde, 4

‐ nitro ‐ O=Cc(ccc(N(=O)(=O))c1)c1 148

‐ 53

‐ 8 o
‐ Vanillin O=Cc(c(O)c(OC)cc1)c1 454

‐ 89

‐ 7 Benzaldehyde, 3

‐ (trifluoromethyl) ‐ O=Cc(cccc1C(F)(F)F)c1ECOSAR Class Definition: Aldehydes (Poly) The Aldehydes (Poly) class is identified by the more than one occurrence of following functional group in the structure:



# H C R1 O

R1 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, ca rbonyl or hydrogen.
The structure must contain more than one al dehyde functional group to be classified as Aldehydes (Poly). If a stru cture contains only one aldehyde group, it will be classified as either an Aldehydes (Poly) or Vinyl/ Allyl Aldehydes cla ss depending on the R1 attachment. In the current ECOSAR program, a structur e can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes. SMILES String Identifications : O=C or O=C[ H] or O=CH O=CC ... (no other atta chments to carbonyl) O=CC=C ... (no other a ttachments to carbonyl) O=CC #C ... (no other a ttachments to carbonyl) O=Cc1ccccc1 ... (no other attachments to carbonyl) ... a combination of two or more of t hese partial SMILES strings must be present anywhere in the entire SMILES.
Associated ECOSAR Class(s) : Aldehydes (Mono) - If a structure cont ains only one aldehyde group, it will be classified as either an Aldehydes (Poly) or Vinyl/ Allyl Aldehydes cla ss depending on the R1 attachment. Vinyl/Allyl Aldehydes - In the current ECOSAR program, a structure can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes.

Example Aldehydes (Poly):

CAS No. Name SMILES Notation 111

‐ 30

‐ 8 Pentanedial O=CCCCC=O 542

‐ 78

‐ 9 1,3

‐ Propanedial O=CCC=OECOSAR Class Definition: 

### Aliphatic Amines ECOSAR currently identifies several different types of structures as Aliphatic Amines which are described separately below. Normal Aliphatic Amines:



## C NH 2 

## C NH C N C C

C

Carbon attachments to the nitrogen must be aliphatic carbons (alkyl, olefinic or acetylenic carbon); aromatic carbon is not allowed. SMILES String Identifications:

NH2 type (one attachment to N): NC [equivalent to: N([H])([H])C or N(H)(H)C] NC=C [equiva lent to: N([H ])([H])C=C or N(H)(H)C=C] NC#C [equivalent to: N([H])([H])C or N(H)(H)C]

NH type (two attachments to N): CNC [equivalent to : CN([H])C or CN(H)C] N type (three attachments t N): CN(C)(C)

... for NH and N type, the carbons must be alkyl, olefinic or acetylenic

Aliphatic Amines with Oxygen:



## C NH O R1

C N O R1

C

R1 - can be anything including hydrogen. The carbon attachments to the nitrogen must be aliphatic carbons (alkyl, olefinic or ac etylenic carbon); aromat ic carbon is not allowed. SMILES String Identifications: NH type (two attachments to N) : CNO [equi valent to: CN([H]) O or CN(H)O] N type (three attachment s t N): CN(C)O

... for NH and N type, the carbons must be alkyl, olefinic or acetylenic

Oximes as Aliphatic Amines:

### C N OH C N O C

Substitutions of the carbon c an be anything including hydrogen. SMILES String Identifications: C=NO C=NOC

Nitrosaminesas Aliphatic Amines:



### N R

R N O

R - at least one carbon a ttachment to the nitrogen. The carbon attachment must be aliphatic carbons (alkyl, olefin ic or acetylenic carbon); aromatic carbon is not allowed. SMILES String Identifiactions: O=N O=N(C)C

Amine Oxides and Nitrosyl s as Aliphatic Amines:

R – can be an aliphatic carbon (alkyl, olef inic or acetylenic carbon).Carbon chain lengths greater than 8 may result in surfactant-like effects. SMILES String Identifiactions: O=N(C) O=N(C)(C)C

Amidines and Guanidines as Aliphatic Amines: 

## O N R R R O

R'

## N N R

R'
R' 

# N N N R



# R'

R' R' R'

R - must be either hydrogen or carbon (alkyl, olefinic, acetylenic or aromatic carbon) ...
R’ - can be anything (no exclusions)

SMILES String Identifications: N=C(C)N [ equivalent to: [H]N=C(C)N([H])[H] or HN=C(C)N(H)H ] N=C(N)N Reducible Ammonium Salts as Aliphatic Amines: Like all salts in ECOSAR, the conjugate salt of ammonium salts shoul d be replaced with a hydrogen; however, reduction of ammonium salts at a neutral pH results in a loss of hydrogens, and the resulting structure should be entered into ECOSAR as an aliphatic amine for the purpose of ECOSAR estimations (examples d epicted below). Ammonium salts in which the ammonium cation has four bound carbons in the presence of a stabilizing anion (e.g., chloride ion) are excluded from this definition since reduction is less likely. Predictions for these more stable ammoni um salts are based on analogous chemicals

or the cationic surfactant QSAR 

## R H
C N + 

## R 

## Anion

R - can be an aliphatic carbon (alkyl, olef inic or acetylenic carbon) or hydrogen Associated ECOSAR Class(s): Oxyamine - identified by H 2 N-O-C- structure. Triazine, Aliphatic – a 6-membered aliphatic ring structure with 3 alternating nitrogens.

Example Aliphatic Amines:

CAS No. Name SMILES Notation 107-10-8 Propylamine NCCC 111-42-2 Diethanolamine OCCNCCO107-15-3 1,2-Ethanediamine NCCN 103-76-4 1-Pipe razineethanol OC CN(CCNC1)C1 107-11-9 Allyl amine NCC=CECOSAR Class Definition: Alkoxy Silanes (or Silanes, alkoxy) The Silanes (alkoxy) class is identifi ed by the following example structure:



## Si O R2
R3 R1 Alkyl Carbon

R1
, R2 and R3 - must be either hydrogen, oxygen or carbon (alkyl, olefinic, acetylenic, aromatic or a carbonyl). In the current ECOSAR program, the Alko xy Silane structure meets the following criteria: (1) Contains a silicon to oxygen attachment . The oxygen must also be attached to an alkyl carbon (or carbonyl).
Notation: the R1, R2 and R3 attachments are limited to the atoms listed above ... Any other atom attachments (e.g. ni trogen, sulfur, halogen, etc) will not result in an Alkoxy Silane identification. SMILES String Identifications : [Si]OC SiOC ... (ECOSAR allows Silicon to be either with or without brackets) ... other attachments to Silicon as defined above.

Associated ECOSAR Class(s) : None specifically.
The Silamines class is the only other ECOSAR cl ass specifically containing silicon.

Example Alkoxy Silanes:

CAS No. Name SMILES Notation 78-62-6 Dimethyl dietho xysilane C[Si](OCC)(OCC)C 18246-71-4 Silane, butoxyethoxyd imethyl- CCCCO[Si](C)(C)OCC 17841-46-2 Silane, methoxytripr opyl- [Si](OC)(CCC)(CCC)CCCECOSAR Class Definition: Amides The Amides class is identified by the following structures:



### R 1 

### C [or S]

N O

R 2



### R 3

R1 can be an aliphatic carbon with a single b ond to any atom other than a halogen, or an aromatic carbon.
R1 can not contain the following atoms below:
If R1 is an oxygen atom, ECOSAR will identify the structur e as a carbamate ester or derivatives
If R1 is a C=C, ECOSAR will identify the structure as an acrylamide
If R1 is a sulfur atom, ECOS AR will identify the struct ure as a thiocarbamate,
mono
If R1 is a nitrogen atom, ECOSAR will identify t he structure as a s ubstituted urea.
If R1 is C-halogen group, ECOSAR will identi fy the structure as a Haloacetamide.
R2 and R3 can be anything other t han a carbonyl group.
If either R2 or R3 are carbonyl groups, ECOSAR will identify the structure as a carbonyl urea. SMILES String Identifications: O=CN ... ( equivalent to: O=C(H)N or O= C([H])N formamide-type) CC(=O)N

NOTE : If R1 above is a benzene ring (6-member arom atic ring) with a nitro/nitroso attachment, then ECOSAR will also identify t he structure as nitro/nitroso-Benzamides. There are very limited empirical data for this class (fish acute only) so this substitution rule for R1 has not been implement as an excl usion for the amides class so that the user is presented with QSAR results for both classes. Example Amides:

CAS No. Name SMILES Notation 60-35-5 Acetamide NC(=O)C 2620-63-5 Glycin-amide,N-a cetyl CC(=O)NCC(=O)NAnilines (amino-meta) The Anilines (amino-meta) class is i dentified by the fo llowing structure:

In the current ECOSAR program, the An ilines (amino-meta) st ructure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in meta-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications : Nc1cc(N)ccc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N(H)(H)c1cc(N(H)H)cc1 ... aromatic ring can contain non-car bon members as in: Nc1cc(N)ccn1

Associated ECOSAR Class(s) : Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (a mino-meta) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-ortho) and Anilines (amino-para) - These classes are identified when a six-member aromatic ring has tw o -NH2 substituents in either a ortho- or para-position. When identified in conjunction with Anilines (amino-meta), they are both reported by ECOSAR.

Example Anilines (amino-meta):

CAS No. Name SMILES Notation 108-45-2 m-Phenylenediamine Nc(cccc1N)c1 608-32-2 1,2,3-Triaminobenzene Nc1c(cccc1N)N 94-10-0 Ethoxazene Nc1cc(N) c(N=Nc2ccc(OCC)cc2)cc1 95-86-3 2,4-Diaminophenol Nc1ccc(O)c(N)c1495-54-5 2,4-Diaminoazobenzene N( =Nc(cccc1)c1)c(c( N)cc(N)c2)c2Anilines (amino-ortho) The Anilines (amino-ortho) class is identified by the fo llowing structure:

In the current ECOSAR program, the Anili nes (amino-ortho) st ructure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in ortho-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications : Nc1c(N)cccc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N( H)(H)c1c(N(H)H)ccc1 ... aromatic ring can contain non-carbon members as in: Nc1c(N)cccn1 Associated ECOSAR Class(s) : Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (ami no-ortho) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-meta) and Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substi tuents in either a meta- or para-position. When identified in conjunction with Anilines (amino-ortho), they are both reported by ECOSAR.

Example Anilines (amino-ortho):

CAS No. Name SMILES Notation 95-54-5 o-Phenylenediamine Nc(c(N)ccc1)c1 91-95-2 1,1'-Biphenyl -3,3',4,4'-tetrami ne Nc(c(N)cc(c(ccc(N)c1N)c1)c2)c2 95-83-0 1,2-Benzenediamine, 4-chloro- Nc(c(N)cc(c1)Cl)c1 608-32-2 1,2,3-Triaminobenzene Nc1c(cccc1N)NAnilines (amino-para)

The Anilines (amino-para) class is identified by the following structure:

In the current ECOSAR program, the Anilines (amino-para) structure meets the following criteria: (1) A benzene ring (or any other six-member aromatic ring including hetero-aromatic rings) has amine substituent (as -NH2) in para-position to each other. (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications: Nc1ccc(N)cc1 ... aliphatic nitrogens as NH2 attached to aromatic carbons equivalent to: N(H)(H)c1ccc(N(H)H)c1 ... aromatic ring can contain non-carbon members as in: Nc1ccc(N)cn1 Associated ECOSAR Class(s): Anilines (Aromatic Amine) - An aromatic ring has one (or more) amine substituent (NH2). If the Anilines (amino-para) class is identified, ECOSAR excludes the Anilines (Aromatic Amines) identification. Anilines (amino-ortho) and Anilines (amino-meta) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either a meta- or ortho-position. When identified in conjunction with Anilines (amino-para), they are both reported by ECOSAR.

Example Anilines (amino-para):

CAS No. Name SMILES Notation 106-50-3 p-Phenylenediamine Nc(ccc(N)c1)c1 95-70-5 2,5-Diaminotoluene Nc(c(cc(N)c1)C)c1 615-71-4 1,2,4-Benzenetriamine Nc1c(N)cc(N)cc1ECOSAR Class Definition: Anilines (Hindered) The Anilines (Hindered) class is ident ified by the follo wing structure:

A carbon-based functional group must be atta ched ortho to the amine group (can be an aliphatic carbon [including alky l, olefinic, acetylenic, car bonyl] or an aromatic carbon [biphenyl-type attachment]). In the current ECOSAR program, the Anili ne (Hindered) structur e meets the following criteria: (1) A benzene ring (or any other aromatic ring including hetero-aromatic rings) that has an amine substituent as -NH2 (2) The aromatic ring can be fused to another ring. (3) An aliphatic carbon is pr esent in the ortho-position.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. The Anilines (Hinderd) SAR Sheet notes that N-substituted amines are less to xic than the SARs for this class SMILES String Identifications: Nc1ccccc1C Nc1c(C)cccc1 Associated ECOSAR Class(s): Anilines (Unhindered) - an R-substituent is not an carbon-bas ed ortho attachment. Dinitro Aromatic Amine (Dinitro Aniline)- If an aromatic ring has both the amine substituent (-NH2) and two or more nitro s ubstituents (-NO2), ECOSAR classifies the ring as Dinitro Aromatic Amine and also repo rts the Anilines (Hindered) identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. Example Anilines (Hindered):

CAS No. Name SMILES Notation 88-68-6 Benzamide, 2-amin o- O=C(N)c(c(N)ccc1)c1 24544--04-5 2,6-Diisopropylan iline Nc(c(ccc1)C(C)C)c1C(C)C 2894-51-1 2-Amino-4'-chlorobenzoph enone Nc1ccccc1C(= O)c2ccc(Cl)cc2ECOSAR Class Definition: Anilines (Unhindered) The Anilines (Unhindered) class is i dentified by the follo wing structure: 

## NH 2 

## R

R can not be a carbon-based fragment (including alkyl, olefinic, acetylenic, carbonyl or an aromatic carbon). A llowed attachments include hydrogen atoms, chlorine, secondary or tertiary nitrogens, sulfur, etc.
R can not be a prim ary amine. If R is a primary amine (NH2) then ECOSAR will identify the cl ass as amino-ortho anilines In the current ECOSAR program, the Aniline (Unhindered) structure meets the following criteria: A benzene ring (or any other aromatic ring incl uding hetero-aromatic rings) that has an amine substituent as -NH2. The aromatic ring can be fused to another ring.
An excluded R-substituent is not present in t he ortho-position.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. The Anilines (Unhinderd) SAR Sheet notes that N-substituted amines are less to xic than the SARs for this class. SMILES String Identifications: Nc1ccccc1 c1ccccc1N Associated ECOSAR Class(s): Anilines (Hindered) - an R-s ubstituent is an aliphatic or aromatic carbon-based attachment in the ortho position. Dinitro Aromatic Amine (Dinitro Aniline)- If an aromatic ring has both the amine substituent (-NH2) and two or more nitro s ubstituents (-NO2), ECOSAR classifies the ring as Dinitro Aromatic Amine and also repo rts the Anilines (Unhin dered) identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. Example Anilines (Unhindered):

CAS No. Name SMILES Notation 62-53-3 Anilin e Nc1ccccc1 371-40-4 4-Fluoroaniline Nc1ccc(F)cc1106-49-0 4-Toluidine Nc1ccc(C)cc1 3481-20-7 2,3,5,6-Tetrachloroan iline Nc1c(Cl)c(Cl)cc(Cl)c1ClECOSAR Class Definition: Aziridines
The Aziridines class is identifi ed by the following ring structure:



# N

ECOSAR identifies an Az iridine ring as follows: (1) a three member aliphatic ring consis ting of one aliphatic nitrogen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Aziridine ring can be part of a fused-ring system

SMILES String Identifications : N1CC1 ... (same as: C1NC1 or C1CN1 )

Associated ECOSAR Class(s) : Aliphatic Amines - In the current ECOSAR program, the nitrogen in an aziridine ring is not additionally classified as an Aliphatic Amine.

Example Aziridines:

CAS No. Name SMILES Notation 151-56-4 Aziridine N1CC1 1072-44-2 N-Methylaziridine CN1CC1 75-55-8 2-Methylaziridine N1CC1C 286-18-0 7-Azabicyclo[4.1. 0]heptane N(C1CC2)C1CC2 4055-40-7 Mitomycin B COC4=C(C)C(=O)C1 =C(C(COC(N)=O)C2(O)C3C(CN12)N3C)C4=OECOSAR Class Definitions: Benzodioxoles
The Benzodioxoles class is identif ied by the following structure:



## O

O

In the current ECOSAR program, the Benzodi oxole structure identification meets the following criteria: (1) The ECOSAR program identifies a five-m ember ring containing two aromatic carbon atoms, two aliphatic oxygen atoms and one alkyl carbon at om. Currently, the position of the atoms in the ring is not differentiated; for example, t he two oxygen atoms could sideby-side and the structure will still be identified as Benzod ioxoles (the two different structures would correspond to 1,3- benzodioxole and 1, 2-benzodioxole). (2) The aromatic ring that is fused to the five-member is not required to be a benzene ring; it can be any aromatic ring including hetero-aromatic rings. (3) The Benzodioxole ring structure can be fused to additional ring(s). SMILES String Identifications : Equivalent SMILES for 1,3-benzodioxole: c1cccc2OCOc12 c1ccc2OCOc2c1 c1cc2OCOc1cc1 c12ccccc1OCO2 C1=CC=C2OCOC2=C1 O1c2ccccc2OC1O=CC
Associated ECOSAR Class(s) :
None.

Examples Benxodioxoles:

CAS No. Name SMILES Notation 274-09-9 1,3-Benzodioxole c1ccc2OCOc2c1 51-03-6 Piperonyl butoxide O(c(c(O1)cc(c2CCC)COCCOCCOCCCC)c2)C1ECOSAR Class Definition: Benzotriazoles The Benzotriazoles class is identified by t he following structures (1H-Benzotriazole and 2H-Benzotriazole):



## N

N N

R N

N N R

R - can be anything (no exclusions) In the current ECOSAR program, the Benzotri azoles structure must meet the following criteria: (1) The triazole ring must be fused to a benzene ring. The ring to which the triazole ring is fused cannot be a hetero-aromatic ring. (2) The fused benzene ring can be fused to another ring SMILES String Identifications : c1ccc2nn[nH]c2c1 c1ccc2n[nH]nc2c1 c1ccc2nnnc2c1 c1ccc2N=NNc2c1 C1=CC2=NNN=C2C=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo. With respect to structures containing a triazole ring: Triazoles (Non-Fused) - a structure containing either a 1,2,4-triazole, 1,2,3-triazole or 1,3,4-triazole ring t hat is not fused to another aromatic ring. Triazole Pyrimidines - a triazole-pyrimidine fused ring structure Examples Benzotriazoles:

CAS No. Name SMILES Notation 95-14-7 1H-Benzotriazole c1ccc2nnnc2c1 273-02-9 2H-Benzotriazole c1ccc2nnnc2c1

36437-37-3 Phenol, 2-(2H-benzotriazol-2-yl)- 4-(1,1-dimethylethyl)-6-(1- methylpropyl)- Oc(c(cc(c1)C(C)(C) C)C(CC)C)c1n(nc(c2ccc3)c3)n2ECOSAR Class Definition: Benzoylcyclohexanedione The Benzoylcyclohexanedione class is ident ified by the following structure:



## C C C O O

O

In the current ECOSAR program, the B enzoylcyclohexanedione structure meets the following criteria: (1) A linear carbonyl [-C(=O)-] is attached to both a phenyl ring and a 2,6- cyclohexanedione ring at the position shown above. (2) The rings can be fused to other rings.
Notation : The current identification in ECOSAR is very strict ... The phenyl ring must be a phenyl ring (a hetero-aromat ic ring (e.g. pyridine) is not allowed) ... The cyclohexanedione ring must be a 2,6-dione only with the linear carbonyl attached at the 1-position. SMILES String Identifications : c1ccccc1C(=O)C2C(=O)CCCC2=O equivalent SMILES : O=C(c1ccccc1)C2C(=O)CCCC2=O

Associated ECOSAR Class(s) : None specifically.

Example Benzoylcyc lohexaediones:

CAS No. Name SMILES Notation 99105-77-8 Sulcotrione O=C1CCCC(=O)C1C(=O)c2ccc(S(=O)(=O)C)cc2ClECOSAR Class Definition: Benzyl Alcohols The Benzyl Alcohols class is ident ified by the following structure:



## C OH

In the current ECOSAR program, the Ben zyl Alcohol structur e meets the following criteria: (1) An alkyl carbon atom has both an hydr oxyl (-OH) attachment and benzene ring attachment. (2) A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ri ng can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications : c1ccccc1CO ... ( equivalent to : c1ccccc1COH or c1ccccc1CO[H] )

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other Alc ohol classes (such as Propargyl Alcohols, Vinyl/Allyl Alcohols, Ketone Alcohol, Halo Al cohols and Nitro Alcohols). ECOSAR also includes a variety of Benzyl classes.

Example Benzyl Alcohols:

CAS No. Name SMILES Notation 100-51-6 Benzyl alcohol c1ccccc1CO 4412-91-3 3-Hydroxymethylfuran OCc1ccoc1 115-32-2 Dicofol OC(c1ccc(Cl)cc 1)(c2ccc(Cl)cc2)C(Cl)(Cl)ClECOSAR Class Definition: Benzyl Halides The Benzyl Halides class is ident ified by the following structure:



### C Halogen

[ Halogen = Br, Cl or I ]

In the current ECOSAR program, the Ben zyl Halide structure meets the following criteria: (1) An alkyl carbon atom has both a benzene ring attachment and a Halogen attachment. For this class, halogens are lim ited to bromine, chlorine and iodine ... Fluorine is excluded. (2) A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ri ng can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications : with bromine: c(CBr) or c1CBr with chlorine: c(CCl) or c1CCl with iodine: c(CI) or c1CI

... with a complete ring : c1ccccc1CBr or c1ccccc1CCl or c1ccccc1CI
Associated ECOSAR Class(s) : None specifically. ECOSAR includes other Halide classes (such as Propargyl Halides, Vinyl/Allyl Halides, Acid Halides, Halo Acetamides, Halo Ethers, etc). ECOSAR also includes a variety of Benzyl classes.

Example Benzyl Halides:

CAS No. Name SMILES Notation 100-44-7 Benzene, (chloromethyl)- c(cccc1)(c1)CCl 611-19-8 o-Chlorobenzyl ch loride c(c(ccc1)Cl)(c1)CCl 623-25-6 Benzene, 1,4-bis(chloro methyl)- c(ccc(c1)CCl)(c1)CCl 30030-25-2 Chloromethyl styrene C=Cc1ccc(cc1)CClECOSAR Class Definition: Benzyl Imides The Benzyl Imides class is ident ified by the follo wing structure:

R 1 [S] O N R 2

R 3 O [S]

R1 and R3 can be anything except a nitrogen atom
If R1 or R3 are a nitrogen atom, ECOSAR wil l identify the class as carbonyl ureas. The carbonyl urea contains training set chemicals contain structures with the R1 or R3 as nitrogen atoms and the R2 as defined below.
R2 must be an alkyl carbon that is attached to a phenyl or other aromatic ring. A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. However, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and t he aromatic ring can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications: c(CN(C(=O))C(=O)) or c1CN(C(=O))C(=O) ... complete ring : c1ccccc1CN(C(=O))C(=O) c(CN(C(=S))C(=S)) or c1CN(C(=S))C(=S) ... complete ring : c1ccccc1CN(C(=S))C(=S) c(CN(C(=O))C(=S)) or c1CN(C(=O))C(=S) ... complete ring : c1ccccc1CN(C(=O))C(=S)

Example Benzyl Imides:

CAS No. Name SMILES Notation 2142-01-0 2-Benzyl-isoindole-1,3-dion e c12C(=O)N(Cc3cccc c3)C(=O)c1cccc2 32000-70-7 Uracil, 3-benzyl-5-bromo-1,6-dime thyl- N1(C)C(=O)N(Cc2c cccc2)C(=O)C(Br)=C1CECOSAR Class Definition: Benzyl Nitriles The Benzyl Nitriles class is ident ified by the follo wing structures:

C N

C C N

C Aromatic Ring

In the current ECOSAR program, the Benzyl Nitrile structure must meet the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl carbon which also has a pheny l or aromatic ring attachment. (2) A strict definition of “benzyl” implie s the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. Howeve r, in the current ECOSAR program, the single alkyl carbon can -CH2-, -CH< or >C< and the aromatic ring can be any aromatic ring including hetero-aromatic rings. SMILES String Identifications: c(CC#N) or c1CC#N ... with a complete ring : c1ccccc1CC#N

... attachments to the alkyl carbon as defined above

Associated ECOSAR Class(s): Nitriles, Polyaliphatic - Two or more nitrile groups are atta ched to aliphatic atoms in the whole structure. When two or more nitrile groups are attached to the same alkyl or olefinic carbon, the structur e will be classified as both Viny l/Allyl Nitriles and Nitriles, Polyaliphatic. Pyrethroids - One of the two potential identif ying structures for pyrethroids contains the benzyl nitrile moiety. Due to the nature of t he pyrethroid class as a pesticide class with a complex structure and mode of action, compounds that fit t he pyrethroid definition are excluded from the benzyl nitriles class.
Other SAR Nitrile classes include: Halo Nit riles, Nitrile Alpha-OH, Phthalonitriles, Vinyl/Allyl Nitriles, Malonitril es, and Nitriles, Polyaliphatic.

Example Benzyl Nitriles:

CAS No. Name SMILES Notation 140-29-4 Benzyl nitrile c1ccccc1CC#NCarbamate Esters, Alkyl

The Carbamate Esters class is iden tified by the following structure:



## R N O R' O

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).
If R is a primary amine ECOSAR will id entify the class as a simple ester

R’ - can be anything except a 6-member aromatic ring (c 1ccccc1) or -N=C.

If R’ is an aromatic ring ECOSAR will id entify the class as carbamate esters, phenyl.

If R’ is an -N=C group, ECOSAR will identi fy the class as carbamates esters, oxime
In the current ECOSAR program, the Carbamate Esters class meets the criteria as shown in the structures above.
Associated ECOSAR Class(es): Carbamate Esters, Oxime - if R’ is -N=C, the ECOSAR class becomes Oxime Carbamate Ester, and the Carbamate Ester class is excluded.
Carbamate Esters, Phenyl - if R’ is a phe nyl ring, the ECOSAR class becomes Phenyl Carbamate Ester, and the Carbamate Ester class is excluded.
ECOSAR includes a variety of Th iocarbamate ester classes.
Example Carbamate Esters:

CAS No. Name SMILES Notation 101-21-3 Chlorp ropham CC(C)OC(=O)Nc1cccc(Cl)c1 6135-31-5 N-Methylethylcarbamate O=C(OC)NCC 539-71-9 Ethylidene O= C(OCC)NC(NC(=O)OCC)C

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamat e Esters, Alkyl Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however,data available for modeling were limited to methylcarbamates and, thus, the trend may be specific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not been fully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that carba mate esters with certa in steric properties may be hydrolytically degraded before the ca rbamate ester has an opportunity to inhibit the enzyme. Additionally, Fukuto (1990) indi cates “that methylcarbamate esters of alcohols are intrinsically unr eactive [compared to methyl carbamates substituted with phenols or oximes] and, therefore, they are generally poor anticholinesterases [e.g., poor inhibitorsof AChE]. A good fit of a methylcarbamate ester in the enzyme active site, i.e., formation of the enzyme-inhibitor complex pr ior to carbamylation, is crucial for high anti-cholinesterase activity.” Thus, the Carbamate Ester, Alkyl QSAR is considered to represent the least toxic carbamate ester QSAR class based on available data and supporting information. Fukuto (1990) provide s a more in depth discussion of the mechanism of inhibition of carbamate inse cticides, which support ecotoxicity trends observed in available carbamate esters data. Datasets for the below determined equations have excluded any studies using static tes ting methods without anal ytical monitoring of test concentrations due to potential for hydrolysis.
Desmedipham and phenmedipham were includ ed in Carbamate Esters, Alkyl QSAR based on data that suggested poor inhibiti on of acetylcholinesterase, which may be a result of hydrolytic instabili ty or poor formation of the enzyme-inhibitor complex, even though these compounds contain a carbamate es ter conjugated with a phenyl in addition to a carbamate ester conjugated with an alkyl . Some instances of hydrolytic instability and poor formation of the enzyme-inhibitor co mplex may need to be assessed on a caseby-case basis.

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.Carbamate Esters, Oxime

The Oxime Carbamate Ester class is iden tified by the following substructure:

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).

If R is a primary amine, ECOSAR will iden tify the class as a neutral organic. This is because for an ester classification, the functional group off the oxygen must be carbon based and therefore the –N=C does not qualify, nor do any other nitrogen functional group attachments.
In the current ECOSAR program, the Oxime Ca rbamate Ester class meets the criteria as shown in the structure above. Subst itutions on the oxime carbon are allowed.
Associated ECOSAR Class(es): Carbamate Esters - if the -N=C attached to the oxygen is replaced by something else (excluding a phenyl ring), the ECOSAR class becomes Carbamate Esters.
Phenyl Carbamate Esters - if the -N=C is replaced by a phenyl ring, the ECOSAR class becomes Phenyl Carbamate Ester, and th e Carbamate Ester class is excluded.
Example Oxime Carbamate Ester:

CAS No. Name SMILES Notation 23135-22-0 Oxamyl CNC( =O)ON=C(SC)C(=O)N(C)C 16752-77-5 Methomyl CNC(=O)ON=C(C)SC 116-06-3 Aldicarb O=C(ON=CC(SC)(C)C)NC

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamat e Esters, Oxime Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however, data available for modeling were limited to methylcarbamates and, thus, the trend may bespecific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not been fully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that “[m]ethylcarbamates of substituted phenols and oximes with good complementary fit to the [AChE] enzyme active site are generally strong inhibitors of AChE.” Furthermore, s ubstitution of “ phenols and oximes, each with pKa values in the region of 10, [make] methyl carbamates that are reactive to the degree that they are able to carbamylate the seri ne hydroxyl of AChE. Owing to the intrinsic reactivity of methylcarbamate esters, an elec tron-withdrawing substitu ent is not required in the aryl moiety for high anticholinesterase activity.” Fukuto (1990) provides a more in depth discussion of the mechanism of inhibiti on of carbamate insec ticides, which support ecotoxicity trends observed in available carb amate esters data. Datasets for the below determined equations have excluded any studi es using static tes ting methods without analytical monitoring of test concentr ations due to potential for hydrolysis.Carbamate Esters, Phenyl
The Phenyl Carbamate Ester class is id entified by the following structure:


### N O

O R

R - can be anything except two hydrogens (mak ing the nitrogen atom a primary amine).

If R is a primary amine, ECOSAR will id entify the class as a simple ester
In the current ECOSAR program, the Phenyl Carbamate Ester class meets the criteria as shown in the structure above.
Substitutions on the phenyl ring are allowed.
Associated ECOSAR Class(es): Carbamate Esters - if the phenyl ring atta ched to the oxygen is replaced by an aliphatic group, the ECOSAR class becomes Carbamate Esters.
Oxime Carbamate Esters - if the phenyl ri ng attached to the oxygen is -N=C, the ECOSAR class becomes Oxime Carbamate Ester, and the Carbamate Ester class is excluded.
Example Oxime Carbamate Ester:

CAS No. Name SMILES Notation 114-26-1 Propoxur CN C(=O)Oc1ccccc1OC(C)C 63-25-2 Carbaryl O=C(Oc(c(c(ccc1)cc2)c1)c2)NC 2686-99-9 Trimethacarb CN C(=O)Oc1cc(C)c(C)c(C)c1

Mechanism of Action Information:
Carbamate esters act by inhibiti ng acetylcholinesterase (AChE) in the nervous system, as well as inhibition of other es terases (IPCS, 1986). Toxicity of carbamate esters, based on available data (presented in the Carbamate Esters, Phenyl Manual Sheets), appears to correlate with the substituent on the oxygen (O-alkyl, O-phenyl, or O-oxime); however, data available for modeling were limited to methylcarbamates and, thus, the trend may be specific to methylcarbamates. Additionall y, compounds with a large substitution on the nitrogen may not fit in to the active site of AChE and, thus, the mechanism of action may be inhibited. Hydrolysis of carbamate esters in aquatic c onditions may factor in to the ultimate toxicity of the compound; however, hydrolysis as it pe rtains to O-alkyl substituted, O-phenyl substituted, and O-oxime substituted carbamate esters has not beenfully characterized and correlated with standa rd endpoint effect leve ls (e.g., insufficient information). Fukuto (1990) indicates that “[m]ethylcarbamates of substituted phenols and oximes with good complementary fit to the [AChE] enzyme active site are generally strong inhibitors of AChE.” Furthermore, s ubstitution of “ phenols and oximes, each with pKa values in the region of 10, [make] methyl carbamates that are reactive to the degree that they are able to carbamylate the seri ne hydroxyl of AChE. Owing to the intrinsic reactivity of methylcarbamate esters, an elec tron-withdrawing substitu ent is not required in the aryl moiety for high anticholinesterase activity.” Fukuto (1990) provides a more in depth discussion of the mechanism of inhibiti on of carbamate insec ticides, which support ecotoxicity trends observed in available carb amate esters data. Datasets for the below determined equations have excluded any studi es using static tes ting methods without analytical monitoring of test concentra tions due to potential for hydrolysis.
Fukuto (1990) suggests that “introduction of a nitro substituent into the phenyl ring of phenyl methylcarbamate results in a com pound of such high reactivity that it is hydrolytically degraded before it has an oppor tunity to inhibit the enzyme.” Aquatic toxicity data were not locat ed for compounds such as th is and, thus, the Carbamate Esters, Phenyl QSAR class does not account for this phenomenon.
In comparing the rates of reaction of [m-isopropyl compound] and [m-tert-butyl compound] with [ammonium co mpound], Fukoto suggests that “replacement of the central carbon atom [in the side chain] with a positively charged quaternary nitrogen atom [similar to Ammonium, (3-(methylcarbamo yloxy) phenyl)trimethyl-, chloride (CAS # 64051-06-5)] resulted in about a 50-fold in crease in anticholinesterase activity.” Aquatic toxicity data were not located fo r compounds such as this and, thus, the Carbamate Esters, Phenyl QSAR class does not account for this phenomenon. Additionally, compounds such as this are treated as cationic surfactants for the purpose of QSAR predictions.

References: IPCS. 1986. Carbamate Pesticides: A Genera l Introduction. International Programme on Chemical Safety (IPCS) Environmental He alth Criteria (EHC) 64, ISBN: 92 4 154264 0. [http://www.inchem.org/documents/ehc/ehc/ehc64.htm]

Fukoto T.R. 1990. Mechanism of Acti on of Organophosphorus and Carbamate Insecticide. Environmental He alth Perspectives, 87:245-254.ECOSAR Class Definition: Carbonyl Ureas In ECOSAR V1 and early, carbonyl ureas were identified as both imides and substituted ureas. The Carbonyl Urea class is identifi ed by the following ex ample structure in ECOSAR V1.1.

R 1 N N R 4 O O

R 2 R 3

The nitrogens must be aliphatic nitrogen atoms
R1 can be anything (no exclusions) If R1 is a sulfur atom, t here may be overlap with the thiocarbamates, mono class based on the training set chemicals, but to xicity profiles are similar for both classes to all organisms and therefore no re strictions will be applied at this time since thiocarbamates, mono class define only the [S-C=ON] por tion of the above base structure. R2, R3 and R4 can be anything except halogen atoms. If R2 or R3 or R4 are halogens, ECOSAR will identify the class as haloimides which show much higher toxicity to fish and daphnid than non-halogenated carbonyl ureas
R4 can be anything (no exclusions) The oxygen in the carbonyl(s) can not to be replaced by S or N atoms, as is done in other related classes. In this case, compounds containing C=S are included in the thioureas class definition, though the effects of the r epeating C=S (like the carbonyl does above) is unknown since simple thiourea (NC=SN) defines the training set. We have no structural analogs in ECOSAR for the C= N configuration of th is molecule. A related class is sulfonyl ureas where a sulfone group [S(=O)(=O)] replaces the second carbonyl group off of the R1 above.
SMILES String Identifications: Carbonyl Urea Group : C(=O)NC(=O)N
Example Carbonyl Urea:

CAS No. Name SMILES Notation 314-40-9 Bromacil N1C(=O )N(C(C)CC)C(=O)C(Br)=C1C 36734-19-7 Iprodione c1c(Cl)cc(Cl )cc1N2C(=O)C N(C(=O)NC( C)C)C2(=O) 78587-05-0 Hexythiazox c1cc(Cl)cc c1C2SC(=O)N(C(=O)NC3CCCCC3)C2C 57-43-2 Amobarbital CCC1( CCC(C)C)C(=O) NC(=O)NC1=OECOSAR Class Definition: Diazoniums, Aromatic The Diazoniums, Aromatic class is i dentified by the following structure:



## [N+] A r omatic Rin g N

An aromatic ring is attached to a char ged nitrogen that is triple bonded to another nitrogen. The SMILES notation represent ing a diazonium func tion required by ECOSAR is either of the following: (1) [N+]#N ... as in c1ccccc1[N+]#N (2) N#N ... as in c1ccccc1N#N SMILES String Identifications : N#N [N+]#N

... (requires aromatic attachment)

Associated ECOSAR Class(s) :
Diazoniums - the Aromatic Ring attachment to t he charged nitrogen atom is replaced by an aliphatic atom attachment.
Azides - the Aromatic Ring attachment is re placed by a nitrogen double bonded to the charged nitrogen (which will no longer be charged).

Example Diazoniums, Aromatic:

CAS No. Name SMILES Notation 6087-56-5 Benzenediazonium,4-(dimethy lamino)- c1cc(N(C)C)ccc1[N+]#N 52572-38-0 4-Diazo-2-methylpyrrolidinobenze ne ZnCl N1(c2c(C)cc([N+]#N)cc2)CCCC1Diketones
The Diketones class is identifi ed by the following structure:

To be classified as Diketones by the current ECOSAR program, the st ructure must meet the following criteria: (1) The diketone fragment must be a 1,3-di ketone. The two carbonyl groups must be separated by one carbon atom; this carbon atom must be an alkyl or olefinic carbon. The carbon atoms on the ends of the diketone fragment must be alkyl, olefinic, acetylenic or aromatic carbons. (2) The diketone fragment must be acyclic. The carbon atom in the middle cannot occur in a ring. SMILES String Identifications : CC(=O)CC(=O)C CC(=O)CC(=O)C=C CC(=O)CC(=O)C#C CC(=O)CC(=O)c ... (aromatic attachment)

... full ring : CC(=O)CC(=O)c1ccccc1

... (attachments as defined above)

Associated ECOSAR Class(s) : In addition to the Diketones class, the EC OSAR program will add any of the classes below to the to the program output if identified in a structure. Vinyl/Allyl Ketones - a ketone with a vinyl (-C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl Halo Ketones (0-1 Free H) - a ketone with a -CH- Halogen (or -C-Halogen) attachment to a carbon atom at the alpha- or beta-position to the carbonyl

Example Diketones:

CAS No. Name SMILES Notation 123

‐ 54

‐ 6 2,4

‐ Pentanedione CC(=O)CC(=O)C 3002

‐ 24

‐ 2 2,4

‐ Hexanedione CC(=O)CC(=O)CC 69725

‐ 37

‐ 7 3,5

‐ Octanedione, 2,2,7

‐ trimethyl ‐ O=C(C(C)(C)C)CC(=O)CC(C)CECOSAR Class Definition: Epoxides, Mono The Epoxides, Mono class is identifi ed by the following ring structure:


# O

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system To be classified as Epoxides, Mono, a stru cture must contain only one epoxide ring. SMILES String Identifications : O1CC1 ... equivalent to : C1OC1 or C(O1)C1

Associated ECOSAR Class(s) : Epoxides, Poly - if a structure contains two or more epoxide rings, it will be classified as Epoxides, Poly instead of Epoxides, Mono Epoxides, Mono Acid Substituted - contains one epoxide ring plus an acid function. Structures classified as Epoxi des, Mono Acid Substituted are not additionally classified as Epoxides, Mono Halo Epoxides - structures containing an epoxide ri ng and a halogen attached directly to the ring or on an alkyl carbon attached to the ring). In the current ECOSAR program, structures identified as Halo Epoxides are not additionally classified as Epoxides, Mono.

Example Epoxides, Mono:

CAS No. Name SMILES Notation 75-21-8 Ethylene oxide O1CC1 3266-23-7 Oxirane, 2,3-dimethyl- O(C1C)C1C 122-60-1 Phenyl glycidyl ether O1CC1COc2ccccc2 72-20-8 Endrin ClC4=C(Cl)C5(Cl)C3C1CC(C2OC12)C3C4(Cl)C5(Cl)ClECOSAR Class Definition: Epoxides, Poly The Epoxides, Poly class is identified by more than one occurence the following ring structure:



# O

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system To be classified as Epoxides, Poly, a structur e must contain two or more epoxide rings. SMILES String Identifications : O1CC1 ... equivalent to : C1OC1 or C(O1)C1

Associated ECOSAR Class(s) : Epoxides, Mono - if a structure cont ains only one epoxide ring, it will be classified as Epoxides, Mono instead of Epoxides, Poly Epoxides, Mono Acid Substituted - contains one epoxide ring and an acid function Halo Epoxides - structures containing an epoxide ring and a halogen attached directly to the ring or on an alkyl carbon attached to the ring). In the current ECOSAR program, structures can be classified as both Halo Epoxides and Epoxides, Poly.

Example Epoxides, Poly:

CAS No. Name SMILES Notation 3568-29-4 Glycerin, 1,3-diglycidyl ether O(C1COCC(O)COCC(O2)C2)C1 54208-63-8 Bisphenol, diglycidyl ether O( C1COc(c(ccc2)Cc(c(OC C(O3)C3)ccc4)c4)c2)C1

### ECOSAR Class Definition: Esters ECOSAR includes a variety of structures ident ified in the Esters class. The various structures identified as Esters are listed below.

Esters (as Formic Acid Esters) Formic acid and thioformic acid esters are identified by the following structures



### H C O O C H C S O C

The carbon must be alkyl, olefinic , acetylenic or aromatic carbon. SMILES String Identifications : O=COC ... equivalent to : O=C(H)OC or O=C([H])OC O=CSC ... equivalent to : O=C(H)SC or O=C([H])SC ... (the carbon must be alkyl, ol efinic, acetylenic or aromatic): O=COC=C O=COC#C O=COc

Esters (as Carboxylic Acid Esters) Carboxylic acid esters and thiocarboxylic ac id esters [-C(=O)-S-] are identified by the following structures:



## R1 C O O
R2 R1 C S O
R2

R1 - must be alkyl, acetylenic, or aromatic carbon or a carbonyl;.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included); silicon allowed if attached to oxygen.
Notation: If R1 is olefinic (-C=C ), ECOSAR will classify the structure as an Acrylate (or Methacrylate), and the Esters class will be excluded from the ECOSAR report. SMILES String Identifications : C(=O)O or C(=O)S

... (attachments as defined above)

Esters (as Carbonates and Thiocarbonates)
Carbonic acid esters are identif ied by the following structures:

### O C O O
R R S C S O
R R O C S O
R R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included); silicon allowed if atta ched to oxygen. SMILES String Identifications : OC(=O)O or SC(=O)S or OC(=O)S

... (attachments as defined above)

Esters (as Carbamic Acid Esters)
Carbamic acid esters are ident ified by the follo wing structures:



### N C O O R1 R N C S O R1 R

R1 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included); silicon allowed if attached to oxygen.
R - attachments to th e nitrogen can be anything
Notation: ECOSAR will classify the structure as a Carbamate Ester or Thiocarbamate. SMILES String Identifications : NC(=O)O or NC(=O)S { equivalent to : N(H)(H)C(=O)O or N(H)(H)C(=O)S

... (attachments as defined above)

Esters (as Carbamimidic Acid Esters)
Carbamimidic acid esters are id entified by the following structures:



### N C O NH
R2 R1 N C O N R2 R3

R1

R1 and R3 - can be anything (no exclusions).
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : NC(=N)O

... (attachments as defined above)Esters (as Thioformic Acid Esters)



### H C O S R H C S S R

R - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : S=CO or S=CS { equivalent to : S=C(H)O or S=C(H)S

... (attachments as defined above)

Esters (as Thiocarboxylic Acid Esters)



### R1 C O S
R2 R1 C S S
R2

R1 - must be alkyl, acetylenic, or aromatic carbon or a carbonyl.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included).
Notation: If R1 is olefinic (-C=C ), ECOSAR will classify the structure as an Acrylate (or Methacrylate) in addition to the Esters class ... Note : this differs from the Carboxylic acid esters which are excluded from the ECOSAR report when Acrylates (or Methacrylates) are identified. SMILES String Identifications : C(=S)O or C(=S)S

... (attachments as defined above)

Esters (as Thiocarbamic Acid Esters)
Thiocarbamic acid esters are ident ified by the following structures:



### N H 2 

### C O S R N H 2 

### C S S R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included).
Notation: the amine (-NH2) must be -NH2 ... if a hydrogen is substituted by a carbon, ECOSAR will classify the structure as a Thiocarbamate or Dit hiocarbamate, and the Esters class will be excluded from the ECOSAR report. SMILES String Identifications : NC(=S)O or NC(=S)S { equivalent to : N(H)(H)C(=S)O or N(H)(H)C(=S)S

... (attachments as defined above)Esters (as Thiocarbonates [C(=S)] )
Thiocarbonate acid esters are id entified by the following structures:



### O C O S
R R S C S S
R R O C S S
R R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included). In addition, R can be an aromatic nitrogen.
Notation: the carbonate and thiocarbonate Esters (where the carbonyl is C(=O) instead of C(=S)), do not allow the R attachment to be an aromatic nitrogen. SMILES String Identifications : OC(=S)O or SC(=S)S or OC(=S)S

... (attachments as defined above)

Esters (as Phosphate-type) Phosphate esters are identifi ed by the following structures:



### O P R3 O

R2 R1 S P R3 O

R2 R4

R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, a carbonyl, phosphorus, sulf ur, oxygen or nitrogen.
R2 and R3 - can be anything except a hydroxy group (-OH).
R4 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus
Notation: Esters (Phosphates) are a separate ECOSAR class. When identified, ECOSAR reports both Esters and Esters (Phosphates). SMILES String Identifications : P(=O)O or P(=O)S

... (attachments as defined above)

Esters (as Thiophosphate-type) Thiophosphate esters are identif ied by the following structure:



### S P R3 S

R2 R1R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus.
R2 and R3 - can be anything except oxygen.
Notation: Esters, Monothiophosphates and Este rs, Dithiophosphates are separate ECOSAR classes from Esters. When either of the two separate cl asses are identified ECOSAR excludes the Esters identification. SMILES String Identifications : P(=S)S

... (attachments as defined above)

Esters (as Sulfuric Acid or Sulfonate Esters)
Sulfonate and sulfuric acid esters are identified by the fo llowing structures:



### O S O O

O R1 R1 R2 S O O

O R1

R1 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). In addition, R1 can be silicon.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : OS(=O)(=O)O or S(=O)(=O)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Other ester classes reported in conjunction with the Esters class by ECOSAR: Esters (Phosphates) Vinyl/Allyl Esters
Ester classes that explicitly exclude the Esters class or ECOSAR generally does not report both if both are identified: Carbamate Esters Oxime Carbamate Esters Thiocarbamates ... (includes a vari ety of Thiocarbamate classes ... depending on structure, ECOSAR may report both). Beta-Halo Esters Propargyl Carbamates Acrylates Methacrylates Esters (imidic) Esters, Monothiophosphates Esters, (Phosphinates) Esters, DithiophosphatesExample Esters :

CAS No. Name SMILES Notation Formates 107-31-3 Methyl formate O=COC Carboxylates 141-78-6 Ethyl ac etate CC(=O)OCC 138-22-7 Butyl lactate O=C(OCCCC)C(O)C 131-11-3 Dimethyl phthalate O=C(OC)c(c(ccc 1)C(=O)OC)c1 Carbonates 105-58-8 Diethyl carb onate O=C(OCC)OCC Carbamic Acid Esters 51-79-6 Carbamic acid, ethyl ester O=C(OCC)N Carbamimidic Acid Esters 64037-23-6 Benzoxazoline, 5-chloro-2-imi no-3-methyl- c12N(C)C(=N)Oc1ccc(Cl)c2 Thioformic Acid Esters O-Methyl thioformate S=COC Thiocarboxylic Acid Esters 2168-84-5 Methyl dithioacetate CC(=S)SC Thiocarbonates 822-38-8 1,3-Dithiolane-2-thione S(C(SC1)=S)C1 Phosphates 78-40-0 Triethyl phosphate O=P(OCC)(OCC)OCC 62-73-7 Dichlorvos O=P(OC)(OC)OC=C(Cl)Cl Thiophosphates 996-05-4 Phosphonotrithioic acid, methyl-,dipropyl CCCSP(=S)(C)SCCC Sulfonates & Sulfuric acid esters 62-50-0 Methanesulfonic acid , ethyl ester O=S(=O)(OCC)C 515-46-8 Ethylbenzene sulfonate S(=O)(=O)(OCC)c(ccc1)cc1 64-67-5 Sulfuric acid, diet hyl ester O=S(=O)(OCC)OCCECOSAR Class Definition: Esters, Dithiophosphates The Esters, Dithiophosphates class is i dentified by the fo llowing structure:



## R1 P O S R3
S R2

R1 - can be anything except sulfur (additional sulfur s change the “dithio” class identification).
R2 - must be hydrogen, carbon (a lkyl, olefinic, acetylenic, aromatic, or carbonyl) or phosphorus.
R3 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur. In the current ECOSAR program, the Esters , Dithiophosphates class meets the criteria as shown in the structures above.
Notation : Currently, ECOSAR does not identify compounds having a structure such as P(=O)(S)(S) as a possible Dithiophosphate. SMILES String Identifications : S=P(S)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Esters, Monothiophosphates - contains the P(=S)-O- st ructure (only one sulfur bonded to the phosphorus).
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters, Dithiophosphates class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates) and Esters (Phosphinates)

. Example Esters, Dithiophosphates:

CAS No. Name SMILES Notation 000060-51-5 Dimethoate O=C(NC)CSP(OC)(OC)=S 121-75-5 Malathion CCOC(=O) CC(SP(=S)(OC)OC)C(=O)OCC 298-04-4 Disulfoton CCOP(=S)(OCC)SCCSCC 13071-79-9 Terbufos CCOP (=S)(OCC)SCS C(C)(C)CECOSAR Class Definition: Esters, Monothiophosphates The Esters, Monothiophosphates class is identified by the following structure:



## R1 P O S R3
R2

R1 and R2 - can be anything except sulfur (additional sulfurs change the “monothio” class identification).
R3 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur. In the current ECOSAR program, the Es ters, Monothiophosphates class meets the criteria as shown in the structures above.
Notation : Currently, ECOSAR does not identify compounds having a structure such as P(=O)S as a possibl e Monothiophosphate. SMILES String Identifications : S=P(O) ... ( attachments as defined above)

Associated ECOSAR Class(s) : Esters, Dithiophosphates - contains the P(=S)-S- structure.
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters, Monothiophosp hates class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates) and Esters (Phosphinates)

.

Example Esters, Monothiophosphates:

CAS No. Name SMILES Notation 115-90-2 Fensulfothion CCOP(= S)(OCC)Oc1ccc(cc1)S(C)=O 8000-97-3 Demeton S=P(OCC)(OCC)OCCSCC 333-41-5 Diazinon O(P(OCC)(O c(nc(nc1C)C(C)C)c1)=S)CC 2921-88-2 Chlorpyrifos CCOP(= S)(OCC)Oc1nc(Cl)c(Cl)cc1Cl 2104-64-5 EPN CCOP(=S)(Oc1cc c(cc1)N(=O)=O)c2ccccc2ECOSAR Class Definition: Esters, Phosphates The Esters, Phosphates class is identif ied by the following structures:



## O P R3 O

R2 R1 S P R3 O

R2 R4

R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, a carbonyl, phosphorus, sulf ur, oxygen or nitrogen.
R2 and R3 - can be anything except a hydroxy group (-OH.
R4 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus. In the current ECOSAR program, the Esters , Phosphates class meets the criteria as shown in the structures above. SMILES String Identifications : O=P(O) O=P(S)

... (attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to report the Ester class whenever the Esters, Phosphates class is reported Other phosphorus esters classes in ECOS AR include Esters, Monothiophosphates
, Esters (Phosphinates) and Esters, Dithiophosphates ... the Esters, Phosphates class structure is not identified when these cl asses are identified.

Example Esters, Phosphates:

CAS No. Name SMILES Notation 512-56-1 Trimethyl phosp hate O=P(OC)(OC)OC 115-96-8 Tris(beta-chloroethyl) phosphate O=P(OCCCl)(OCCCl)OCCCl 1080-32-6 Diethyl benzylphosph onate O=P(OCC)(OCC)Cc(cccc1)c1 126-72-7 Tris(2,3-dibromopropyl)phosphat e O=P(OCC(Br)CBr)(O CC(Br)CBr)O CC(Br)CBrECOSAR Class Definition: Esters (Phosphinates) The Esters (Phosphinates) class is i dentified by the fo llowing structure:



## R1 P O O R2
Carbon

R1 - can be anything except oxygen.
R2 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur.
Carbon - alkyl, olefinic, acetylenic, or arom atic carbon (not including carbonyl). In the current ECOSAR program, the Esters (Phosphinates) class m eets the criteria as shown in the structure above. SMILES String Identifications : O=P(O)C ... ( attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters (Phosphinates) class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates)

.

Example Esters (Phosphinates):

CAS No. Name SMILES Notation 96-64-0 Soman CC(OP(C)(F)=O)C(C)(C)C 107-44-8 Sarin CC(C)OP(C)(F)=O 1224-64-2 Nibufin N(=O)(=O)c1ccc(OP (=O)(CCCC )CCCC)cc1 2511-09-3 Phosphinic acid,phenyl- ,ethyl ester O=P(c1ccccc1)OCCHaloacetamide: The haloacetamide class is identif ied by the following structure:

R1 and R2 - can be anything except a carbonyl group. If a carbonyl group is attached at R1 or R2, then ECOSAR will identify the class as imides In the current ECOSAR program, the haloacet amide structure must meet the following criteria: The carbonyl group has an aliphatic nitrogen and an alkyl carbon substituent, [NC(=O)C] and the alkyl carbon has one or more halogen substituents.
Notation: Currently, if alkyl carbon has two or more fluorine attach ments (and no other halogen attachments), the hal oacetamide identific ation is not counted by ECOSAR. SMILES String Identifications: NC(=O)CBr NC(=O)CCl NC(=O)CF NC(=O)CI

... (attachments as defined above)

Associated ECOSAR Class(s): Example haloacetamide:

CAS No. Name SMILES Notation 683-72-7 Acetamide, 2,2- dichloro- O=C(N)C(Cl)Cl 10222-01-2 Acetamide, 2,2-dibr omo-2-cyano- O=C( N)C(C#N)(Br)Br 15972-60-8 Alachlor CCc1cc cc(CC)c1N(CO C)C(=O)CClECOSAR Class Definition: Haloacids
The Haloacid class is identifi ed by the following structures:

C C OH O Halogen C C OH O Halogen

C C C O O Halogen { Na, K, Li }

In the current ECOSAR program, the Ha loacid structure m eets the following: (1) a carboxylic acid function [-C(=O)-OH] is attached to an alkyl or olefinic carbon atom. (2) the alkyl or olefinic carbon atom has an attached halogen (bromine, chlorine, fluorine or iodine). (3) the hydrogen atom in the carboxylic ac id function [-C(=O)-OH] can be substituted with a sodium, potassium or lithium atom.

SMILES String Identifications : OC(=O)CCl or OC(=O)CBr or OC(=O)CF or OC(=O)CI OC(=O)C(Br)=C [Na]OC(=O)CBr

... (halogen attachments can be Cl or Br or F or I)

Associated ECOSAR Class(s) : None specifically.

Example Haloacids:

CAS No. Name SMILES Notation 79-11-8 Monochloroacetic acid O=C(O)CCl 76-03-9 Trichloroacetic acid O=C(O)C(Cl)(Cl)Cl 75-99-0 2,2-Dichloropropionic acid O=C(O)C(Cl)(Cl)C 127-20-9 Dalapon CC(Cl)(Cl)C(O[Na])=OECOSAR Class Definition: Halo Alcohols
The Halo Alcohols class is identifi ed by the following ex ample structures:



### O H C {Br,Cl,I} C C O H {Br,Cl,I} C C O H C {Br,Cl,I}

In the current ECOSAR program, the Halo Al cohols structure meets one of the following criteria: (1) a single alkyl carbon atom has both an hydroxy attachment (-OH) and a halogen attachment. For all criteria here halogens are limited to bromine, chlorine and iodine (fluorine is excluded). (2) an alkyl carbon is attached to another alkyl carbon (or olefinic carbon). The halogen and hydroxy (-OH) are on different carbons. A maximum of thr ee carbon atoms can occur between the halogen and hydroxy (-OH). SMILES String Identifications : OCBr or OCCl or OCI OCCBr or OCCCl or OCCI OCCCBr or OCCCCl or OCCCI

... initial OC equivalent to : HOC or [H]OC

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other classes containing alcohol or halogens, but not in combination in the same class.

Example Halo Alcohols:

CAS No. Name SMILES Notation 107-07-3 2-Chloroethanol OCCCl 627-30-5 1-Propanol, 3-chloro- OCCCCl 96-13-9 1-Propanol, 2,3-dibromo- OCC(Br)CBr 115-20-8 Ethanol, 2,2,2-trichloro- OCC(Cl)(Cl)ClHalo Epoxides The Halo Epoxides class is identified by the occurrence following ring structure(s):

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system In addition to one or more epoxide rings, to be classified as Halo Epoxides, a structure must contain: a halogen at om (Br, Cl, F, I) attached directly to an epoxide ring or a halogen atom (Br, Cl, F, I) attached to an alkyl carbon that is attached directly to an epoxide ring. Halogen atoms further removed from the epoxide ring are not currently included in the Halo E poxide identification. SMILES String Identifications : O1CC1Br or O1CC1Cl or O1CC1F or O1CC1I O1CC1CBr or O1CC1CCl or O1CC1CF or O1CC1CI
Associated ECOSAR Class(s) : Epoxides, Mono - - if a structure cont ains one epoxide rings and no acid function, it will be classified as Epoxides, Mono. In the current ECOSAR program, a structure classified as Halo Epoxides cannot be additionally classified as Epoxides, Mono. Epoxides, Mono Acid Substituted - contains one epoxide ring and an acid function. In the current ECOSAR program , a structure classified as Halo Epoxides cannot be additionally classified as Epox ides, Mono Acid Subsituted. Epoxides, Poly - if a structure contains two or more epoxide rings, it will be classified as Epoxides. In the current EC OSAR program, a structure c an be classified as both Halo Epoxides and Epoxides, Poly Example Halo Epoxides :

CAS No. Name SMILES Notation 106

‐ 89

‐ 8 Epichlorohydrin O(C1CCl)C1 3132

‐ 64

‐ 7 Epibromohydrin O(C1CBr)C1ECOSAR Class Definition: Halo Esters
The Halo Esters class is identif ied by the following structures:



### C C O O Halogen R C O O R Halogen

R - must be alkyl, oelfinic, acetylenic or aromatic carbon (carbonyl not included). Halogen - bromine (Br), chlorine (Cl) , fluorine (F) or iodine (I). In the current ECOSAR program, the Halo Este rs class meets the criteria as shown in the structure above and the following: (1) the carbon atom (to whic h the Halogen is attached) mu st be an alkyl carbon (an olefinic carbon not currently a llowed). The halogen can be in either the alpha- or betapositions where the alpha-pos ition is direct attach ment to the carbonyl. (2) Fluorine was previously excluded, but is now included in this class. SMILES String Identifications : OC(=O)CBr or OC(=O)CCl or OC(=O)CI or OC(=O)F OC(=O)Br or OC(=O)Cl or OC(=O)CI or OC(=O)F

... (attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Halo Esters class is reported.
Acid Halides - the Acid Halides class includes any structure with C(=O)-Halogen; ECOSAR reports both classes when present in a structure.

Example Halo Esters:

CAS No. Name SMILES Notation 14064-10-9 Diethyl chloromal onate O=C(OCC)C( C(=O)OCC)Cl 105-39-5 Acetic acid, chloro -, ethyl ester O=C(OCC)CCl 599-99-5 Tribromoacetic acid, et hyl ester BrC(Br)(Br)C(=O)OCC 356-24-1 Butanoic acid, heptafluoro-, meth yl ester O=C(OC)C(F )(F)C(F)(F)C(F)(F)F 623-48-3 Acetic acid, iodo- , ethyl ester O=C(OCC)CIECOSAR Class Definition: Halo Ethers
The Halo Ethers class is identif ied by the following structures:



## C O C Halogen C O C C Halogen

The ether function is identified as an ali phatic oxygen attached to two carbons atoms (alkyl, olefinic, acetylenic or aromatic carbon).
Note: The oxygen may not be contained within a 3 member ring. If so, ECOSAR will classify that chemical as a halo epoxide In the current ECOSAR program, the Halo Ether structure must meet one of the following criteria: (1) an alkyl carbon of an ether function has a halogen attachment (Br, Cl, F or I). (2) an alkyl carbon (that is attached to an alkyl carbon of an et her function) has a halogen attachment (Br, Cl, F or I). In the current ECOSAR progr am, the halogen can be in eith er the alpha- or betaposition. SMILES String Identifications: COCBr or COCCl or COCF or COCI COCCBr or COCCCl or COCCF or COCCI

... (attachments as defined above)

Associated ECOSAR Class(s): None specifically.
The ether function also occurs in the Vinyl/Allyl Ether class.

Example Halo Ethers:

CAS No. Name SMILES Notation 3188-13-4 Chloromethyl ethyl ether CCOCCl 111-44-4 Bis(2-chloroet hyl)ether O(CCCl)CCCl 34723-82-5 (2-Bromomethyl)-t etrahaydropyra n BrCC1CCCCO1ECOSAR Class Definition: Haloimides

The Haloimides class is identified by the following structure:

R1 or R3 can be anythi ng (no exclusions). Please note that in the parent imide class R1 and R3 can not be a nitrogen atom , otherwise ECOSAR will identify the class as carbonyl ureas. But for this class there are many training set chemicals containing a nitrogen atom with a halogen attachment in the R1 or R3 position, and all are much more toxic to fish and d aphnid than the carbonyl urea estimates. It appears these halogen attachments are driving toxicity. Therefore we are not excluding these attachments so that the haloimides estimates will be provided displaying more accurate toxicity estimates based on an alogs.
R 2

- must be a Cl, Br, I or F Haloimides class does not currently have acute or chronic QSARs for Green Alg ae

. However, based on the fact that associated chemicals are used as herbicides, toxicity to green algae is expected to be significant.
In the current ECOSAR program, the Haloimides structure must meet the following criteria:
Notation: Currently, the halogen must be attached to the nitrogen

. SMILES String Identification s : Haloimide Group : C(=O)N(Cl, Br, or I)C(=O) C(=S)N(Cl, Br, or I)C(=S) C(=N)N(Cl, Br, or I)C(=N) ... equivalent to : C(=NH)NC(=NH)

... (or any combination of the various carbonyl

- types)

... (attachments as defined above)

Example Haloimides :

CAS No. Name SMILES Notation 77

- 48

- 5 2,4

- Imidazolidinedione, 1,3

- dibrom o
- 5,5

- dimethyl

- O=C(N(C(C1(=O))(C)C)Br)N1Br 118

- 52

- 5 1,3

- Dichloro

- 5,5

- dimethylhydantoin O=C(N(C(C1(=O))(C)C)Cl)N1Cl 126

- 06

- 7 3

- Bromo

- 1

- chloro

- 5,5

- dimethylhydantoin O=C(N(C(C1(=O))(C)C)Cl)N1BrECOSAR Class Definition: Halo Ketones (2 Free Hydrogens) Halo Ketones (2 Free H) are ident ified by the following structures:



## C 

## CH 2 

## Halogen 

## O

C 

## C O 

## CH 2 

## Halogen

To be classified as Halo Ketones (2 Free H) by the current ECOSAR program, the structure must meet the following criteria: (1) The basic ketone fragment is identified as a carbony l group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. To be classified as Halo Ketones (2 Free H), the Halogen atom (bromine, chlorine, fluorine or iodine) must be attached at an alpha- or beta-position carbon to the carbonyl. In addition, the Halogen must be attached to a CH2 alkyl carbon (two free hydrogens on the alkyl carbon). SMILES String Identifications: CC(=O)CBr or CC(=O)CCl or CC(=O)CF or CC(=O)CI CC(=O)CCBr or CC(=O)CCCl or CC(=O)CCF or CC(=O)CCI

... (attachments as defined above)

Associated ECOSAR Class(s): In addition to the Halo Ketones (2 Free H) class, the ECOSAR program will add any of the classes below to the to the progra m output if identified in a structure.
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Benzyl Ketones (e.g. SMILES: c1ccccc1CC(=O)CC(=O)CC). Vinyl/Allyl Ketones - a ketone with a vinyl (- C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aroma tic ring attachment to the carbonyl Example Halo Ketones (2 Free H):

CAS No. Name SMILES Notation 1204-21-3 Bromomethyl-2,5-dimethoxypheny l ketone COc1ccc(OC)c(c1)C(=O)CBr 78-95-5 2-Propanone, 1-chloro- O=C(CCl)CHalo Nitriles
The Halo Nitriles class is identif ied by the following structures:

In the current ECOSAR program, the Halo Nitr iles structure meets t he following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl carbon. (2) An alkyl carbon in the alpha- or beta- position to the nitrile has one (or more) halogen attachments (bromine, ch lorine, fluorine or iodine). (3) The alkyl carbons (alpha- or beta-posit ion) can have other a ttachments (no current exclusions).
Notations: Halogens attached to olefinic, acet ylenic or aromatic carbons are not currently included in the class identification. Halogens further re moved from a nitrile group are not included (further than alpha- or beta-position). SMILES String Identifications : BrCC#N or ClCC#N or FCC#N or ICC#N BrCCC#N or ClCCC#N or FCCC#N or ICCC#N

Associated ECOSAR Class(s) : None specifically.
Other SAR Nitrile classes include: Azoni triles, Nitrile Esters, Nitrile Alpha-OH, Phthalonitriles, Vinyl/Allyl Nitr iles, and Nitriles, Polyaliphatic.

Example Halo Nitriles:

CAS No. Name SMILES Notation 107-14-2 Acetonitrile, chloro- N#CCCl 3252-43-5 Acetonitrile, dibromo- N#CC(Br)Br 375-00-8 Butanenitrile, heptafluor o- N#CC(F)(F)C(F)(F)C(F)(F)FHalo Pyridines The Halo Pyridines class is ident ified by the follo wing structure:

In the current ECOSAR program, the Halo Py ridines structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aromatic ring containing five carbon atoms and one nitrogen atom (a pyridine ring). (2) The aromatic car bon atoms on the pyridine ring have one or more halogen attachments (halogens include bromine, chlorine, fluorine or iodine). (3) The pyridine ring can be fused to additional ring(s). SMILES String Identifications : n1ccccc1Br n1ccccc1Cl n1ccccc1F n1ccccc1I

... (the halogen can be attached to any of the aromatic carbons)

Associated ECOSAR Class(s) : Other ECOSAR classes specifica lly containing a Pyridine ring: Pyridine-alpha-Acid - a carboxylic acid group (-C(=O) -OH) is attached to the pyridine ring in an ortho-position to the nitrogen atom. A structure can be classified as both a Pyridine-alpha-Acid and a Halo Pyridine.
Notation: the Pyridine Thiones class does not contain an aromatic pyridine ring (the ring is an aliphatic thione ring wit h C(=S) as part of the ring).

Examples Halo Pyridines:

CAS No. Name SMILES Notation 109

‐ 09

‐ 1 2

‐ Chloropyridine n1ccccc1Cl 626

‐ 55

‐ 1 3

‐ Bromopyridine n1cccc(Br)c1 1929

‐ 82

‐ 4 Pyridine, 2

‐ chloro

‐ 6

‐ (trichloromethyl) ‐ n(c(ccc1)C(Cl)(Cl)Cl)c1Cl 2176

‐ 62

‐ 7 Pyridine, pentachloro ‐ n(c(c(c(c1Cl)Cl)Cl)Cl)c1ClECOSAR Class Definition: Hydrazines ECOSAR currently identifies several different types of structures as Hydrazines which are described separately below.

Common Hydrazines :



### N N R1

R2 R4 R3

Common hydrazines are identified by two aliphatic nitrogen atoms attached with a single-bond. At least one of the R1, R2, R3 or R4 s ubstituents muct be an alkyl, olefinic, acetylentic or aromatic carbon.
Notation: In the current ECOSAR program, the R1, R2, R3 and R4 substituents can be anything. SMILES String Identifications: NN

... (attachments as defined above)

Hydrazones as Hydrazines : 

### N N C C N N C R
The R substituent can be anything. SMILES String Identifications: C=NN=C C=NN

... (attachments as defined above)

Hydrazides, Semicarbazides and Thiosemicarbazides as Hydrazines :



### N N C R O N N C R S N N C C O

The R substituent can be anything. ECOSAR identifies various hydrazides, carbazides and carbazones as Hydrazines. SMILES String Identifications: C(=O)NN C(=S)NNC(=O)NN=C

... (attachments as defined above)

Notation : Azo Structures as Hydrazines : 

### N N R1 R2
In ECOSAR versions prior to v1.10, t he linear azo structure was identified as a Hydrazine. However, this azo struct ure is no longer identified as an ECOSAR Hydrazine.

Previously Associat ed ECOSAR Class(s): Semicarbazide (Aryl-Ortho), Semicarbazide (Aryl-Meta/Para), Semicarbazide (Akyl) - identified by N-N-C(=O)-N-R ... These previously identif ied classes (but no longer identified ECOSAR classes) do not have SAR equations. The Hydrazine class is identified and used by ECOSAR.

Example Hydrazines:

CAS No. Name SMILES Notation 302-01-2 Hydrazine NN 57-14-7 1,1-Dimethylhydrazine NN(C)C 122-66-7 Hydrazine, 1,2-dipheny l- N(Nc(cccc1)c1)c(cccc2)c2 79-19-6 Thiosemicarbazide NC(=S)NN 54-85-3 Isoniazid NNC(=O)c1ccncc1 537-47-3 4-Phenylsemicarbazide c1ccccc1NC(=O)NNECOSAR Class Definition: Hydroquinones The Hydroquinones class is identified by the following example structures:



### OH OH

In the current ECOSAR program, a hydr oquinone is a six-member aromatic ring (benzene or any other aromatic ring including hetero-aromatic rings) that has hydroxyl groups [-OH] in para-position. The arom atic ring can be fused to another ring. SMILES String Identifications : Oc1ccc(O)cc1
Associated ECOSAR Class(s) : Quinone – Under environmental conditions, a re versible reduction-oxidation (redox) change from hydroquinone to semiquino ne and to quinone may occur. Phenols, Poly - the hydroquinone identific ation is a more toxic sub-class of the Phenols, Poly class. ECOSAR reports both classes.

Example Hydroquinones:

CAS No. Name SMILES Notation 123-31-9 1,4-Hydroquinone Oc1ccc(O)cc1 58-27-5 2-Methyl-1,4-hydroquinone Oc1cc(C)c(O)cc1ECOSAR Class Definition: Imidazoles
The Imidazoles class is identif ied by the following structure:



# N

N

In the current ECOSAR program, the Imidaz oles structure must meet the following criteria: (1) The Imidazole ring is a five-member ar omatic ring with nitrogen atoms at the 1- and 3-positions. The 1-position is [NH] if uns ubstituted, but the hydrogen can be replaced by another substituent. (2) The imidazole ring can be fus ed to another ring (e.g. Benzimidazole) SMILES String Identifications : [nH]1cncc1 n1cncc1 c1ncnc1 c(n1)cnc1 N1C=NC=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Benzotriazoles, Triazoles, Tr iazole Pyrimidines and Thiazole, Benzo.

Examples Imidazoles:

CAS No. Name SMILES Notation 288-32-4 1H-Imidazole N1C=NC=C1 51-17-2 1H-Benzimidazole n(c(c(n1)ccc2)c2)c1 58-08-2 Caffeine CN1C(=O)N(C)c2ncn(C)c2C1(=O) 693-98-1 2-Methylimidazole N(C=CN1)=C1C 2034-22-2 2,4,5-Tribromoimid azole BrC1=NC(Br)=C(Br)N1ECOSAR Class Definition: Imides The Imides class is identified by the following example structures:



### N [S or N] O

R 1 

### R 2



### O [S or N] R 3

R1 and R3 can be anything except a nitrogen atom.
If R1 or R3 are a nitrogen atoms, ECOSAR wil l identify the class as carbonyl
ureas. Note that If R1 or R3 are an oxygen at oms, ECOSAR will also identify the class as carbamate, esters. At this time substitution of the oxygen atom is not being excluded because we do not have supporting evidence indicating which class has higher toxi city potential or if any chemicals actually contain a hybrid of both functional groups.
R2 can be anything except a halogen atom or a [C-aromatic] group:
If R2 is a halogen attachment, ECOSAR wi ll identify the class as haloimides
If R2 is a [C-aromatic] group, ECOSAR will identify the class as benzyl imides. A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. Howe ver, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ring can be any aromatic ring including hetero-aromatic rings. The oxygen in the carbonyl(s) could be repl aced by sulfur or NH. The structure can have any combination of C=O, C=S or C=NH as long as the nitrogen has two such attachments. SMILES String Identifications: Imide Group : C(=O)NC(=O) C(=S)NC(=S) C(=N)NC(=N) ... equivalent to : C(=NH)NC(=NH)

... (or any combination of the various carbonyl-types)

... (attachments as defined above)

Example Imides:

CAS No. Name SMILES Notation 123-56-8 Succinimide O=C(NC(=O)C1)C1ECOSAR Class Definition: Thiazolones (Iso) or Isothiazolones
The Isothiazolone class is identif ied by the follo wing structures:



### N S C O

S N C O

N S C O

In the current ECOSAR program, the Is othiazolone structure meets the following criteria: (1) a five-member ring containing one ca rbonyl, one aliphatic sulfur, one aliphatic nitrogen and two carbon atoms. The two carbon atoms can be aromatic if the isothiazolone ring is fused to an aromatic ring. If there are no arom atic carbon atoms in the ring, the ring has one double bond. (2) the sulfur and nitrogen atoms in the ring are adjacent to each other. (3) The atoms in the ring can have other attachments (no exclusions). SMILES String Identifications : O=C 1NSC=C1 O=C1SNC=C1 O-C1C=NSC1

Associated ECOSAR Class(s) : None specifically.
The Thiazolidinone class ring also contains a carbony l, one sulfur, one nitrogen and two carbon atoms, but in a different order.

Example Isothiazolones:

CAS No. Name SMILES Notation 26530-20-1 3(2H)-Isothiazolone, 2-octyl- O=C1C=CSN1CCCCCCCC 2682-20-4 3(2H)-Isothiazolone, 2-methyl- S1N(C)C(=O)C=C1ECOSAR Class Definition: Ketone Alcohols (or a-,b-Ketone Alcohol)
The Ketone Alcohols class is ident ified by the following structures:



## C C C O OH C C C O C OH

To be classified as Ketone Alcohols by t he current ECOSAR program, the structure must meet the fo llowing criteria: (1) The basic ketone fragment is identified as a carbony l group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. (2) An hydroxy group (-OH) is attached to an alkyl carbon at an alpha- or beta-position to the ketone carbonyl. SMILES String Identifications : CC(=O)CO ... equivalent to : CC(=O)COH or CC(=O)CO[H] CC(=O)CCO ... equivalent to : CC(=O)CCOH or CC(=O)CCO[H]

Associated ECOSAR Class(s) :
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Benzyl Ketones (e.g. SMILES: c1ccccc1CC(=O)CC(=O)CC). Vinyl/Allyl Ketones - a ketone with a vinyl (-C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl

Example Ketone Alcohols:

CAS No. Name SMILES Notation

123-42-2 2-Pentanone, 4-hydroxy-4- methyl- O=C(CC(O)(C)C)C

50-02-2 Dexamethasone C1(=O)C=C2CCC3C4CC(C)C(O)(C(=O)CO)C4(C)CC(O)C3(F) C2(C)C=C1 50-22-6 Corticosterone CC34CC(O)C 1C(CCC2=CC(=O)CCC12C)C3CCC4C(=O)CO

96-26-4 2-Propanone, 1,3- dihydroxy- O=C(CO)COECOSAR Class Definition: Malonitriles
The Malonitrile class is characte rized by the following structure:



### C N
C C N C N
C C N

C
In the current ECOSAR program, the Malonitrile structure must have two or more nitrile groups (carbon triple-bonded to nitrogen; SMILES of C#N) attached to a single carbon in the structure. The carbon must be either an alkyl or olefinic carbon. SMILES String Identifications : N#CCC#N C=C(C#N)C#N

Associated ECOSAR Class(s) : Nitrile, Polyaliphatic - Malonitriles are a more to xic sub-class of the Nitriles, Polyaliphatic. In the Polyal iphatic, Nitriles class, the tw o or more cyano groups do not need to be attached to the same carbon. ECOSAR reports both classes when identified. Vinyl/Allyl Nitriles - basically, a vinyl (-C=C) or a llyl group (-C-C=C) is attached to one or more nitriles groups. When two or more ni trile groups are attached to the same alkyl or olefinic carbon, the stru cture will be classified as a Vi nyl/Allyl Nitriles and either a Nitriles, Polyaliphatic or a Malonitriles. Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Malonitriles:

CAS No. Name SMILES Notation 2698-41-1 O-Chlorobenzylidene malononi trile N#CC(C#N)=Cc(c(ccc1)Cl)c1 109-77-3 Malononitrile C(#N)CC(#N)Melamines
The Melamines class is identifi ed by the following structure:

R1
, R2 and R3 - can be hydrogen or any other single-bonded atom. In the current ECOSAR program, the Mela mine structure must meet the following criteria: (1) A six-member aromatic ring with three nitrogen atoms in sym-positions. The three carbon atoms have aliphatic nitrogen subsitiuents as either -NH2 or -NH- (the aliphatic nitrogen must have at least one hydrogen). Associated ECOSAR Class(s): Anilines (amino-meta) - this class current ly allows hetero-arom atic rings. Amino substituents in the meta-position (as Melami nes allows) are additionally classified by ECOSAR as Anilines (amino-meta). Example Melamines:

CAS No. Name SMILES Notation 108-78-1 Melamine Nc1nc(N)nc(N)n1 2827-46-5 2,4,6-Trimethylmelamine n1c(NC)nc(NC)nc1NC 66215-27-8 Cyromazine n1c(N)nc(N)nc1NC2CC2ECOSAR Class Definition: Methacrylates The Methacrylates class is identif ied by the follo wing structures:



### C C {O,S} O

C R2 CH 3 

### C C {O,S} S

C R2 CH 3

R2 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S} - can be either oxygen (-O-) or sulfur (-S-) Internally, the ECOSAR progr am initially detects a carb onyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefin ic attachment and one oxygen or sulfur attachment. The olefinic carbon attac hed to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a Methacrylate to an Acryla te. The oxygen or sulf ur must have either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon attachment to be classified as either a Me thacrylate or Acrylate. SMILES String Identifications : C=C(C)C(=O)O ... equivalent to : C=C(C(H)(H)H)C(=O)O C=C(C)C(=O)S C=C(C)C(=S)O C=C(C)C(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Acrylates - The olefinic carbon attached to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a Methac rylate to an Acrylate. Thiomethacrylates - Thiomethacrylates are methacry lates with having a thiocarbonyl or a sulfur attached to the carbonyl function. In the current ECOSAR program, structures classified as Thiomethacrylates are also classified as Methacrylates.

Example Methacrylates:

CAS No. Name SMILES Notation 80-62-6 Methyl methac rylate C=C(C)C(=O)OC 96-05-9 Allyl methacryla te C=C(C)C(=O)OCC=C 2495-37-6 Benzyl methacryla te C=C(C)C(=O)OCc1ccccc1O-Methyl thiomethac rylate C=C(C)C(=S)OC S-Methyl thiomethac rylate C=C(C)C(=O)SCECOSAR Class Definition: Neonicotinoids Neonicotinoids act as agonists of the nicoti nic acetylcholine receptor (nAChR) in a similar mechanism as nicotinoids; however, the presence of a elec tronegative nitro or cyano group attached to the aliphatic nitrogen in neonicotinoids alters the binding potential compared to nicotino ids and results in varied toxicity in mammals and insects (Tomizawa & Casida, 2003). Although toxicity of nicotinoids and neonicotinoids in aquatic organisms appear to differ based on a few available data points, insufficient information and data are available for aquatic organisms to make any firm conclusions. Additional uncertainties include the effe ct a halogen substitution has on the pyridine ring. Thus, further research is needed to confirm the separate classification of nicotinoids and neonicotinoids for aquatic toxicity.
Neonicotinoids are identified by the following structures:



### N N R N N R



### N N R N N R
R = an electronegative nitro or cyano group (e.g., -C=NC#N or -C=NT). In the current ECOSAR program, the Neonicoti noids class meets the criteria as shown in the structure above. Substitutions on t he pyridine or pyrrole ring are allowed. SMILES String Identifications :

Associated ECOSAR Class(s) :
Nicotinoids: Are neonicotinoids without an elec tronegative nitro or cyano substitution on the aliphatic nitrogen. Example Neonicotinoids:

CAS No. Name SMILES Notation 138261-41-3 Imidacloprid c1 cc(Cl)ncc1CN2CCNC2=NT 210880-92-5 Clothianidin c1nc(Cl)sc1CNC(=NT)NC 153719-23-4 Thiamethoxam c1nc (Cl)sc1CN2C(=NT)N(C)COC2 135410-20-7 Acetamiprid c1cc (Cl)ncc1cn(C)C(C)=NC#N 111988-49-9 Thiacloprid c1cc (Cl)ncc1CN2C(=NC#N)SCC2

References: Tomizawa M., Casida J.E. 2003. Selective toxicity of neoni cotinoids attributable to specificity of insect and mammalian nicotini c receptors. Annu. Rev. Entomol., 48:339- 64.ECOSAR Class Definition: Nereistoxin Analogues The Nereistoxin Analogues class is ident ified by the following sub-structure:



### N

S S
In the current ECOSAR program, the Nere istoxin Analogues structure meets the following criteria: (1) The structure as depicted above. The nitrogen cannot be aromatic. (2) Attachments to the thiol can be anything including hydrogen, sulfur, or carbons (alkyl, olefinic or acetylenic). SMILES String Identifications : CN(C)C(CS)CS
(attachments as defined above)

Associated ECOSAR Class(s) : Aliphatic Amines – Nitrogens with aliphatic carbon attachments (alkyl, olefinic or acetylenic carbon). Thiols & Mercaptans - A thiol-mercaptan functi on (-SH) attached to an alkyl, olefinic, acetylenic or arom atic carbon atom.

Example Nereistoxin Analogues:

CAS No. Name SMILES Notation 15263-53-3 Cartap CN(C )C(CSC(=O)N)CSC(=O)N 31895-21-3 Thiocyclam C1SSSCC1N(C)CECOSAR Class Definition: Neutral Organics

The following types of example classes are represented by the neutral organics class which assumes a simple non

- polar narcosis mechanism of action for s olvents and non
reactive, non

- ionizable organic compounds

1 . Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di

- sulfides 11. Sulfoxides and sulfones

Please note: If there are no positive identificat ions of any other associated SAR classes for the query chemical , ECOSAR reports the structure as a Neutral Organic (regardless of what chemical functions may occur in the structure). When this occurs, the user will be promoted with the following flag:

Example Neutral Organics from the SAR Sheet : CAS No. Name SMILES Notation 112

- 27

- 6 Triethylene glycol O(CCOCCO)CCO 67

- 68

- 5 Dimethyl sulfoxide CS(=O)C 67

- 64

- 1 Acetone O=C(C)C 110

- 86

- 1 Pyridine n1ccccc1 60

- 29

- 7 Diethyl ether CCOCC 110

- 00

- 9 Furan O1C=CC =C1 71

- 43

- 2 Benzene c1ccccc1 100

- 61

- 8 N

- Methylaniline CNc1ccccc1ECOSAR Class Definition: Nicotinoids Nicotinoids act as agonists of the nicotinic acetylcholine re ceptor (nAChR) in a similar mechanism as neonicotinoids; however, the absence of a electronegative nitro or cyano group attached to the aliphatic nitrogen in ni cotinoids alters the binding potential compared to neonicotinoids and results in va ried toxicity in mammals and insects (Tomizawa & Casida, 2003). Although toxicity of nicotinoids and neonicotinoids in aquatic organisms appear to differ based on a few available data points, insufficient information and data are available for aquatic organisms to make any firm conclusions. Additional uncertainties include the affe ct a halogen substitution has on the pyridine ring. Thus, further research is needed to confirm the separate classification of nicotinoids and neonicotinoids for aquatic toxicity. Nicotines are identified by the following structures:



### N N

N N



### N N N N
In the current ECOSAR program, the Nicotinoi ds class meets the cr iteria as shown in the structure above. Substitutions on the pyridine or pyrrole ring are allowed.

SMILES String Identifications :

Associated ECOSAR Class(s) :
Neonicotinoids: A sub-classification of nicotinoids with a substitution of an electronegative cyano or nitro group on the aliphatic nitrogen. Example Nicotines:

CAS No. Name SMILES Notation 140111-52-0 Epibatidine c1cc (Cl)ncc1C2C3NC(CC3)C2 54-11-5 Nicotine c1ccncc1C2N(C)CCC2 525-74-6 Dihydronicotyri ne c1ccncc1C2=CCCN2C 494-52-0 Anabasine c1ccncc1C2NCCCC2 494-97-3 Nornicotine c1ccncc1C2NCCC2

References: Tomizawa M., Casida J.E. 2003. Selective toxicity of neoni cotinoids attributable to specificity of insect and mammalian nicotini c receptors. Annu. Rev. Entomol., 48:339- 64.ECOSAR Class Definition: Nitrile Alpha-OH The Nitrile Alpha-OH class is iden tified by the following structures:



## C C N

OH C C N C

OH

In the current ECOSAR progr am, the Nitrile Alpha-OH st ructure meets the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl or olefinic carbon. In addition, an hy droxyl group (-OH) is attached to the same alkyl or olefinic carbon. (2) The alkyl carbon can have other a ttachments (no curr ent exclusions). SMILES String Identifications : C(O)C#N ... equivalent to : C(OH)C#N or C(O[H])C#N C=C(O)C#N ... equivalent to : C=C(OH)C#N or C=C(O[H])C#N

... (attachment as defined above)

Associated ECOSAR Class(s) : None specifically.
Other SAR Nitrile classes include: Azoni triles, Nitrile Esters, Halo Nitriles, Phthalonitriles, Vinyl/Allyl Nitr iles, and Nitriles, Polyaliphatic.

Example Nitrile Alpha-OH:

CAS No. Name SMILES Notation 78-97-7 Lactonitrile N#CC(O)C 75-86-5 Acetone Cyanohydrin N#CC(O)(C)C 513-96-2 3,3,3-Trichlorolacto nitrile ClC(Cl)(Cl)C(O)C#N 532-28-5 Mandelonitrile N#CC(O)c(cccc1)c1ECOSAR Class Definition: Nitro Alcohols
The Nitro Alcohols class is identifi ed by the following ex ample structures:



### O H C NO 2 

### C C O H NO 2 

### C C O H C NO 2

In the current ECOSAR program, the Nitro Alc ohols structure meets one of the following criteria: (1) a single alkyl carbon atom has both an hydroxy attachment (-OH) and a nitro function attachment (NO 2 ). (2) an alkyl carbon is attached to another al kyl carbon (or olefinic carbon). The nitro function (NO 2 ) and hydroxy (-OH) are on different ca rbons. A maximum of three carbon atoms can occur between the nitro function (NO 2 ) and hydroxy (-OH). SMILES String Identifications : OCN(=O)(=O) ... equivalent to : HOCN(=O)(=O) or [H]OCN(=O)(=O) OCCN(=O)(=O) OCCCN(=O)(=O)

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) OC[N+](=O)([O-]) or OCC[N+](=O)([O-]) or OCCC[N+](=O)([O-])

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs OCT or OCCT or OCCCT

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other classes containing alcohol or nitro functions, but not in combination in the same class.

Example Nitro Alcohols:

CAS No. Name SMILES Notation 52-51-7 1,3-Propanediol, 2-brom o-2-nitro- N(=O)(=O)C(Br)(CO)CO 760-40-7 3-Nitro-1,1,1-trichloro-2- propanol ClC(Cl)(Cl)C(O)CN(=O)=O 89167-84-0 2-Propanol, 1,1-dinitr o- N(=O)(=O)C(N(=O)(=O))C(O)CECOSAR Class Definition: Nitro-/Nitroso-Benzamides
The Nitro-/Nitroso-Benzamides class is i dentified by the following structures:

C N O R2 R1

NO 2 C N O R2 R1

N O

R1 an d R2 - must be either hydrogen or alkyl, olefinic, acetylenic or aromatic carbon (carbonyl not included). In the current ECOSAR program, the Nitro -/Nitroso-Benzamide structure meets the following criteria: (1) A six-member aromatic ring (benzene or any other aromatic ring including heteroaromatic rings) has both an amide-substit uent (as noted above in the structure) and either a nitro substituent (-NO2) or a nitros o substituent (-N=O). The positioning on the ring does not matter. (2) The aromatic ring can be fused to another ring. SMILES String Identifications : Nitrosobenzamide (ortho-isomer only SMILES) : O=Nc1ccccc1C(=O)N Nitrobenzamide (ortho-isomer only SMILES) : N(=O)(=O)c1ccccc1C(=O)N

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) [N+](=O)([O- ])c1ccccc1C(=O)N

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs Tc1ccccc1C(=O)N

... (attachments as defined above)

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a general class having a CC(=O)N or NC(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the other classes (as in Nitro-/Nitroso-Benzamides). Example Nitro-/Nitroso-Benzamides:

CAS No. Name SMILES Notation 619-80-7 4-Nitrobenzamide O= C(N)c(ccc(N(=O)(=O))c1)c1 144189-66-2 3-Nitrosobenzami de NC(=O)c1cc(N=O)ccc1 3011-89-0 Aklomide Clc1cc(N(=O)(=O))ccc1C(=O)N 13160-58-2 Pyridine, 4-(p-nitrobenzamido )- n1ccc(NC(=O)c2ccc(N(=O)=O)cc2)cc1ECOSAR Class Definition: Omadines
The Omadines class is identifi ed by the following structures:



### N S

O N S O N SH O

In the current ECOSAR program, the Om adine structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aliphatic ring cont aining four olefinic carbon atoms (and two double bonds), one nitrogen atom (as N=O) and one thiocarbonyl group [C(=S)]. (2) Also identified is an aromatic pyridi ne-N-oxide ring with a thiol [-SH] at an orthoposition. (3) The omadine ring can be fused to additional ring(s). SMILES String Identifications : S=C1C=CN(=O)C=C1 S=C1N(=O)C=CC=C1 O=n1c(S)cccc1

Associated ECOSAR Class(s) : None specifically related to the whole Omadine ring. Vinyl/Allyl Amines - both ring structures above are addi tionally classified as Vinyl/Allyl Amines Aliphatic Amines - the first ring structure above (nitrogen para-position to thiocarbonyl) is additionally classified as an Aliphatic Amine.

Example Omadines: None specifically. Experimental data is CBI (Confidential Business Information).ECOSAR Class Definition: Oxetanes
The Oxetanes class is identifi ed by the following structure:



### O

C
C C

In the current ECOSAR program, the Ox etane structure identification meets the following criteria: (1) The ECOSAR program identifies a f our-member ring containi ng three alkyl carbon atoms and one oxygen atom. (2) The alkyl carbon atoms can have any substituent attachments; the substituent attachments are not included in the Oxetane i dentification. (3) The Oxetane ring can be fused to additional ring(s). SMILES String Identifications : O1CCC1 C1OCC1 O(C1)CC1

Associated ECOSAR Class(s) :
None.

Examples Oxetanes:

CAS No. Name SMILES Notation 503-30-0 Oxetane O1CCC1 68797-60-4 Oxetane, dibr omo- BrC1C(CO1)Br 425-82-1 Hexafluoro oxetane O1C(F)(F)C(F)(F)C1(F)F 3047-32-3 3-Oxetanemethanol, 3-ethyl- O(CC1(CC)CO)C1ECOSAR Class Definition: Oxyamines The Oxyamines class is identifi ed by the following structure:



## R2 N O R3 R1

R1 and R2 - must be hydrogen.
R3 - attachments must be alkyl, olefinic, ac etylenic or aromatic carbon (hydrogen not included). In the current ECOSAR program, the Oxyamine structure meets the criteria as defined above. SMILES String Identifications : NOC NOC=C NOC#C NOc1ccccc1

... (nitrogen attachments as defined above)

Associated ECOSAR Class(s) : Aliphatic Amines - under the current identificat ion scheme, ECOSAR commonly classifies a structure as both Aliphatic Am ines and Oxyamines. ECOSAR reports both identifications.

Example Oxyamines:

CAS No. Name SMILES Notation 29812-79-1 o-Decylhyd roxylamine NOCCCCCCCCCCECOSAR Class Definition: Peroxy Acids The Peroxy Acids class is identif ied by the follo wing structure:



## R1 O O R2

R1 and R2 - In the current ECOSAR program, c an be anything with one exception. The exception is that either R1 or R2 is a carbonyl [C (=O)] and the other is not a hydrogen ... This exception identif ies the Peroxy Ester class. The ECOSAR program initially identifies any -O-O- stru cture as a Peroxy Acid. Whenever a Peroxy Ester class is identified, t he previous Peroxy Acid identification is negated to give precedence to the more specific Peroxy Ester class.

SMILES String Identifications : OO

... (attachments as defined above)

Associated ECOSAR Class(s) : Peroxy Esters - an Ester class identified by C(=O)- O-O-X (where X is anything except hydrogen).

Example Peroxy Acids:

CAS No. Name SMILES Notation 79-21-0 Peroxyacetic acid CC(=O)OO 628-37-5 Diethyl peroxide CCOOCC 29914-92-9 Dipropyl peroxide CCCOOCCCECOSAR Class Definition: Peroxy Esters The Peroxy Esters class is ident ified by the follo wing structure:



## O O R2 C R1 O

R1 - can be anything (no exclusions).
R2 - can be anything except hydrogen (hydr ogen would make it a Peroxy Acid). The ECOSAR program initially identifies any -O-O- stru cture as a Peroxy Acid. Whenever a Peroxy Ester class is identified, the previous Peroxy Acid identification is negated to give precedence to the more specific Peroxy Ester class.

SMILES String Identifications : C(=O)OO

... (attachments as defined above)

Associated ECOSAR Class(s) : Peroxy Acids - a peroxy class ident ified by -O-OExample Peroxy Esters:

CAS No. Name SMILES Notation 16066-38-9 Peroxydicarbonic acid, di propyl ester O=C(OC CC)OOC(=O)OCCC 3313-92-6 Peroxydicarbonic acid, disodium salt [Na]OC(=O)OOC(=O)O[Na] 110-22-5 Peroxide, diacetyl O=C(OOC(=O)C)CECOSAR Class Definition: Phenol Amines The Phenol Amines class is identified by the following structure combination:



### OH 

## + an Amine

[ Phenol ring can also be Hetero-Aromatic ]

The current ECOSAR program identifies the Phenol Amines class using identifications of other ECOSAR classes and the following logic: (1) First, the structure must already be classified as (a) Phenols, (b) Dinitrophenols or (c) Phenols, Poly. (2) If the first criteria is satisfied and the structure is addi tionally classified as any one of the ECOSAR Amine classes, then the structure is additiona lly classified as Phenol Amines. The ECOSAR Amine classes inclu de Aliphatic Amines, Anilines (Aromatic Amines), Dinitro Aromatic Amine, Ben zyl Amines, Propargyl Amines, Amides, and Vinyl/Allyl Ether Amines. SMILES String Identifications : c(O) or c1O ... full ring : c1ccccc1O ... equivalent to : c1ccccc1OH or c1ccccc1O[H]

... Plus any of the SAR Amine Classes listed above ( see the individual definition documents )

Associated ECOSAR Class(s) : See criteria (1) and (2) above.

Examples Phenol Amines:

CAS No. Name SMILES Notation 119-34-6 4-Amino-2-nitrophenol O=N(=O)c(c(O)ccc1N)c1 94-67-7 Salicyclaldoxime N(O)=Cc(c(O)ccc1)c1 133-11-9 Phenyl-4-aminosalicylat e Oc1cc(N)ccc1C(=O)Oc2ccccc2 123-30-8 4-Aminophenol Oc(ccc(N)c1)c1 103-90-2 Acetamide, N-(4-hydro xyphenyl)- O=C(Nc(ccc(O)c1)c1)C 591-27-5 3-Aminophenol Oc(cccc1N)c1ECOSAR Class Definition: Phenols, Poly The Phenols, Poly class is identif ied by the follo wing structures:



### OH

OH X O H OH

[ Rings can also be Hetero-Aromatics ]

X - can be either a direct connection of two rings or another fragment separating the rings In the current ECOSAR program, the Phenols, Poly structure must meet the following criteria: (1) More than one hydroxyl (-OH) group are attached to aromatic rings in the structure. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) The hydroxyl (-OH) groups attached to ar omatic ring(s) can either be on the same ring or separate rings. SMILES String Identifications : c(O) or c1O ... equivalent to : c(OH) or c(OH) or c(O[H]) or c1O[H]

... example complete ring : Oc1ccccc1O ... equivalent to : HOc1ccccc1OH Associated ECOSAR Class(s) :
Phenols - Only one hydroxyl group can be attached to aromatic rings in the structure. Dinitrophenols - Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group. Hydroquinone - the hydroquinone identific ation is a more toxic sub-class of the Phenols, Poly class. ECOSAR reports both classes.

Examples Phenols:

CAS No. Name SMILES Notation 80-05-7 Bisphenol A Oc(ccc(c 1)C(c(ccc(O)c2)c2)(C)C)c1 97-23-4 Phenol, 2,2'-methylenebis 4-chloro - Oc(c(cc(c1)Cl)Cc (c(O)ccc2Cl)c2)c1

79-95-8 Phenol, 4,4'-(1-methylethylidene)bis 2,6- dichloro- Oc(c(cc(c1)C(c(cc(c(O)c2Cl)Cl)c2)(C)C)Cl)c1Cl 70-30-4 Phenol, 2,2'-methylenebis 3,4,6-trichloro- Oc(c(c(c(c1)Cl)Cl)Cc(c(c (cc2Cl)Cl)Cl)c2O)c1ClECOSAR Class Definition: Phenols The Phenols class is identified by the following structures:



### OH

Hetero-Aromatic Ring OH

In the current ECOSAR program, the Phenols st ructure must meet t he following criteria: (1) An hydroxyl (-OH) group is attached to an aromatic ring. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) The structure can cont ain only one hydroxyl (-OH) gr oup attached to an aromatic ring. Multiple hydroxyl groups attached to aromatic rings changes the classification to Phenols, Poly. SMILES String Identifications : c(O) or c1O ... equivalent to : c(OH) or c(OH) or c(O[H]) or c1O[H]

... example complete ring : c1ccccc1O ... equivalent to : c1ccccc1OH

Associated ECOSAR Class(s) : Phenols, Poly - More than one hydroxyl groups are attached to aromatic rings in the structure. Dinitrophenols - Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group.

Examples Phenols:

CAS No. Name SMILES Notation 108

‐ 95

‐ 2 Phenol Oc1ccccc1 150

‐ 76

‐ 5 4

‐ Methoxyphenol Oc1ccc(OC)cc1 88

‐ 75

‐ 5 2

‐ Nitrophenol Oc1ccccc1N(=O)=O 95

‐ 48

‐ 7 o
‐ Cresol Oc1ccccc1C 90

‐ 15

‐ 3 1

‐ Naphthol Oc(c(c(ccc1)cc2)c1)c2ECOSAR Class Definition: Phosphine Oxide The Phosphine Oxide class is iden tified by the following structure:



# P O R3 R1 R2

R1
, R2 and R3 - must be hydrogen or an alkyl, olef inic, acetylenic or aromatic carbon. In the current ECOSAR program, the P hosphine Oxide structur e must meet the following criteria: (1) A P(=O) function is attached to hydrogen at oms or to alkyl, olefinic, acetylenic or aromatic carbon atoms. SMILES String Identifications : O=P or P(=O) ... (attachments atta chments as defined above) example string: O=P(C)(C) ... equivalent to : O=P(C)(C)H

Associated ECOSAR Class(s) : None specifically.

Example Phosphine Oxides:

CAS No. Name SMILES Notation 791-28-6 Triphenylphosphine oxide O= P(c(cccc1)c1 )(c(cccc2)c2)c(cccc3)c3 1638-75-1 Phosphine oxide, (chlor omethyl)dimethyl- O=P(CCl)(C)C 14717-29-4 Phosphine oxide, dicycl ohexyl- P(=O)(C(CCC1) CC1)C(CCC2)CC2ECOSAR Class Definition: Phthalonitriles
The Phthalonitriles class is identif ied by the following structure:



## C

C N

N

In the current ECOSAR program, the Pht halonitriles structure meets the following criteria: (1) Two nitrile groups (carbon triple-bonded to nitrogen; SMILES of C#N) are attached to an aromatic ring in ort ho-positions to each other. (2) The aromatic ring must be six-member aromatic ring. The ring can be a benzene ring or a hetero-aromatic ring (such as pyridine). SMILES String Identifications : N#Cc1ccccc1C#N c1cc(C#N)c(C#N)cc1 c(c1C#N)cccc1C#N

Associated ECOSAR Class(s) : None specifically. Other SAR Nitrile classes include: Azonitriles, Nitrile Esters, Halo Nitriles, Vinyl/Allyl Nitriles, Nitriles Alpha-OH, and Nitriles, Polyaliphatic.

Example Phthalonitriles:

CAS No. Name SMILES Notation 91-15-6 1,2-Benzenedicarbonitrile C(#N)c(c(C(#N))ccc1)c1 712-74-3 Tetracyanobenzene N# Cc1c(C#N)cc(C# N)c(C#N)c1 1835-65-0 Tetrafluorophthalonitrile Fc(c(F)c(F)c1C#N)c(F)c1C#N 1953-99-7 Tetrachlorophthalonitrile Clc(c(Cl)c(Cl)c1C#N)c(Cl)c1C#NECOSAR Class Definition: Nitriles, Polyaliphatic The Nitriles, Polyaliphatic class is c haracterized by the following structure:



### C N C N Structure
(2 or more cyano groups attached to aliphatic atoms)

In the current ECOSAR program , the Nitriles, Polyaliphati c structure must meet the following criteria: (1) Two or more nitrile groups (carbon tr iple-bonded to nitrogen; SMILES of C#N) are attached to aliphatic atoms in the structure. The aliphatic atoms include alkyl carbon, olefinic carbon, acetylenic carbon, nitr ogen, sulfur and phosphorus . Other aliphatic atoms are not currently included (e.g. oxygen). SMILES String Identifications : CC#N C=CC#N C#CC#N NC#N SC#N PC#N

... (two or more of these cyano [C#N] attachments required)

Associated ECOSAR Class(s) :
Malonitriles - Malonitriles are a more toxic sub-cl ass of the Nitriles, Polyaliphatic class that consist of 2 cyano groups separated by a single carbon. Vinyl/Allyl Nitriles - basically, a vinyl (-C=C) or a llyl group (-C-C=C) is attached to one or more nitriles groups. When two or more ni trile groups are attached to the same alkyl or olefinic carbon, the stru cture will be classified as a Vi nyl/Allyl Nitriles and either a Nitriles, Polyaliphatic or Malonitriles. Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Vinyl/Allyl Nitriles:

CAS No. Name SMILES Notation 2698-41-1 O-Chlorobenzylidene malononi trile N#CC(C#N)=Cc(c(ccc1)Cl)c1 109-77-3 Malononitrile C(#N)CC(#N) 110-61-2 Butanedinitrile C(#N)CCC(#N) 111-69-3 Hexanedinitrile C(#N)CCCCC(#N)ECOSAR Class Definition: Polynitroan ilines (Polynitro Aromatic Amine) The Polynitroanilines class is iden tified by the following structure:


### NH 2



### NO 2 

### O 2 

### N

In the current ECOSAR program, the Poly nitroaniline structure meets the following criteria: (1) A benzene ring (or any other aromatic ri ng including hetero-aromatic rings) has one (or more) amine substituent (a s -NH2) and two (or more) ni tro substituents (-NO2). (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications: Nc1c(N(=O)(=O))cccc1N(=O)=O Nc1c([N+](=O)([O-] ))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Nc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs
Associated ECOSAR Class(s): Anilines (Unhindered) - An aromatic ring has an amine substituent (-NH2) that is not hindered by specific ortho-substituents. If the Polynitroanilines class is identified, ECOSAR reports both identifications. Anilines (Hindered) - An ar omatic ring has an amine substi tuent (-NH2) that is hindered by specific ortho-substituent s. If the Polynitroanilines cl ass is identified, ECOSAR reports both identifications Dinitrobenzenes - An aromatic ring has two (or more) -NO2 substituents. If the Polynitroanilines class is identified, ECOSAR excludes the Polynitrobenzene identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. When identified in conjunction with Polynitroanilines, they are also reported by ECOSAR. Example Polynitroanilines:

CAS No. Name SMILES Notation 97-02-9 2,4-Dinitroaniline N(=O )(=O)c(ccc(N)c1N(=O)(=O))c1 96-91-3 Picramic acid Nc1cc(cc(N(=O)=O)c1O)N(=O)=O 489-98-5 2,4,6-Trinitroaniline Nc1c (cc(cc1N(=O)=O)N (=O)=O)N(=O)=OECOSAR Class Definition: Polynitrobenzenes The Polynitrobenzenes class is identif ied by the following structures: 

### NO 2



### NO 2 or ... Hetero-Aromatic Ring with two or more -NO2

In the current ECOSAR program, the Poly nitrobenzenes structure identification meets the following criteria: (1) The ECOSAR program looks for an arom atic ring (either a benzene or any heteroaromatic ring) with two or more nitro groups (-NO2) attached to t he same ring. The position of the NO2 groups on the ring does not matter. (2) The aromatic ring can not additionally have the following attachments: -OH or an amine (NH2). The presence of thes e groups changes the current ECOSAR classification to Polyni trophenols or Polynitroanilines. (3) The aromatic ring can be fus ed to one additional aromatic ring. SMILES String Identifications: c1c(N(=O)(=O))cccc1N(=O)=O c1c([N+](=O)([O-]))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Nc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs Associated ECOSAR Class(s): Polynitroanilines - an aromatic ring containing two or more nitro substituents (NO2) plus an amine substituent (e.g. -NH2). In the current ECOSAR program, an aromatic ring will not be classified as both Dinitrobenz ene and Dinitroaniline (t he Amine is given precedence). Polynitrophenols - an aromatic ring containing tw o or more nitro substituents (NO2) plus an hydroxyl (-OH) substituent. In the current ECOSAR pr ogram, an aromatic ring will not be classified as both Polynitrobenz enes and Polynitrophenols (the phenol is given precedence).

Example Polynitrobenzenes:

CAS No. Name SMILES Notation 100-25-4 1,4-Dinitrobenzene N( =O)(=O)c(ccc(N(=O)(=O))c1)c1 528-29-0 1,2-Dinitrobenzene O=N(=O)c1ccccc1N(=O)=O 121-14-2 Benzene, 1-methyl-2,4-dinit ro- N(=O)(=O)c(ccc (c1N(=O)(=O))C)c1 3698-83-7 Benzene, 1,5-dichloro-2,4-dinit ro- O=N(=O)c(c(cc(c1 N(=O)=O)Cl)Cl)c1ECOSAR Class Definition: Polynitrophenols The Polynitrophenols class is identifi ed by the following structures:



### OH

NO 2 

### O 2 

### N

[ Ring can also be Hetero-Aromatic ]

In the current ECOSAR program, the Polyni trophenols structure must meet the following criteria: (1) One or more hydroxyl (-O H) groups are attached to an ar omatic ring. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group. SMILES String Identifications: Oc1c(N(=O)(=O))cccc1N(=O)=O Oc1c([N+](=O)([O-] ))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Oc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs

Associated ECOSAR Class(s): Phenols - Only one hydroxyl group can be attac hed to aromatic rings in the structure. Phenols, Poly - More than one hydroxyl groups are attached to aromatic rings in the entire structure.

Examples Polynitrophenols:

CAS No. Name SMILES Notation 51-28-5 2,4-Dinitrophenol N(=O )(=O)c(ccc(O)c1N(=O)(=O))c1 88-89-1 2,4,6-Trinitrophenol N(=O)(=O )c(cc(N(=O)( =O))c(O)c1N( =O)(=O))c1 534-52-1 4,6-Dinitro-o-cresol N(=O )(=O)c(cc(N(=O)( =O))c(O)c1C)c1Propargyl Alcohols-Hindered The Propargyl Alcohols-Hindered class is identified by the following structures:



### C C C OH
R R
C C C C OH
R R R

R

R - is attached to alkyl carbons. These al kyl carbons can have two attachments each; the combination R attachments that i dentify Propargyl Alcoho ls-Hindered are noted below. In the current ECOSAR program, the hy droxy group (-OH) can be attached to the propargyl function (C#C-C-) at either an alpha- or beta-position. The Propargyl AlcoholHindered structure meets one of the following criteria: (1) In the first structure abov e, the hydroxyl group (-OH) is attached to an alkyl carbon that attached directly to an acetylenic carb on (alpha-position) . Neither of the Rsubstituents can be hydrogen (if either R is hydrogen, the structure is identified as a Propargyl Alcohol). (2) In the second structur e above, an hydroxyl group (-OH) is attached at the betaposition. If both R-substituents off the beta-carbon are not hydrogen, then the Propargyl Alcohol-Hindered class is ident ified (regardless of the alpha-carbon subs tituents). If either substituent off the alpha-carbon is not hydrogen, then the Propargyl AlcoholHindered class is identified (regardless of the beta-carbon substituents).
Notation: The ECOSAR classification changes from Propargyl Alcohols-Hindered to Propargyl Alcohols when the basic structure is identified, but the R-substituents do not meet the criteria above.. SMILES String Identifications : C#CCO ... equivalent to : C#CCOH or C#CCO[H] C#CCCO ... equivalent to : C#CCCOH or C#CCCO[H]

... (attachments as defined above)

Associated ECOSAR Class(s) : Propargyl Alcohols - see notation above.

Example Propargyl Al cohols-Hindered:

CAS No. Name SMILES Notation 115-19-5 3-Butyn-2-ol, 2-methyl- OC(C#C)(C)C 77-75-8 1-Pentyn-3-ol, 3-methyl- OC(C#C)(CC)C 127-66-2 2-Phenyl-3-butyn-2 -ol OC(C#C)(c(cccc1)c1)CPropargyl Alcohols The Propargyl Alcohols class is identified by the following structures:



### C C CH OH R 

### C C CH 2 

### CH OH R

R - can be anything (no exclusions) In the current ECOSAR program , the Propargyl Alcohol struct ure is identified as shown above. The hydroxy group (-OH) can be atta ched to the propargyl function (C#C-C-) at either an alpha- or beta-position.
Notation: The Propargyl Alcohols class is dist inguished from the Propargyl AlcoholsHindered class in that the hydroxyl (-OH) is at tached to a straight-chain alkyl carbon. In the first structure above, the -OH is attached to a -CH- (with only o ne substituent). In the second structure (beta- position), the chain must be -CH2-CH- (with only one substituent off the second carbon) ... If t he alkyl carbons have additional substituents replacing the designated hydrogens, then the Propargyl Alcohols-Hin dered class will be identified. SMILES String Identifications : C#CCO ... equivalent to : C#CCOH or C#CCO[H] C#CCCO ... equivalent to : C#CCCOH or C#CCCO[H] C#CC(O)C ... equivalent to : C#CC(OH)C or C#CC(O[H])C

... (attachments as defined above)

Associated ECOSAR Class(s) : Propargyl Alc ohol-Hindered - see notation above.

Example Propargyl Alcohols:

CAS No. Name SMILES Notation 107-19-7 Propargyl alcohol OCC#C 110-65-6 2-Butyne-1, 4-diol OCC#CCO 927-74-2 3-Butyn-1-ol OCCC#C 764-01-2 2-Butyn-1-ol CC#CCO 4117-14-0 2-Decyn- 1-ol OCC#CCCCCCCCECOSAR Class Definition: Propargyl Ethers The Propargyl Ethers class is identi fied by the following structure:



## C C C O Carbon

In the current ECOSAR program, the Propar gyl Ether structure meets the following criteria: (1) An ether oxygen is attached to an alkyl carbon that is attached to an acetylenic carbon. (2) The “Carbon” in the structure above can be alkyl, olefinic, acetylenic or aromatic carbon. SMILES String Identifications : C#CCOC C#CCOC=C C#CCOC#C C#CCOc1ccccc1

Associated ECOSAR Class(s) : None specifically. Vinyl/Allyl Ethers - the propargyl group (C#C-C-O-C ) is replaced by an allyl group (C=C-C-O-C)

Example Propargyl Ethers:

CAS No. Name SMILES Notation 6921-27-3 Dipropargyl ether O(CC#C)CC#C 53135-64-1 1-Propyne, 3-propoxy- CCCOCC#CECOSAR Class Definition: Propargyl Halides The Propargyl Halides class is identif ied by the following structures:



## C C Halogen C C C Halogen

In the current ECOSAR program, the Propar gyl Halides structur e meets one of the following criteria: (1) A halogen atom (Br, Cl, F, or I) is attached directly to an acetylenic carbon. (2) A halogen atom (Br, Cl, F, or I) is attached to an alkyl carbon that is attached directly to an acetylenic carbon.
Notation: In the current ECOSAR program, t he first criteria above overlaps with a criteria used by the Vinyl/Ally Halides cl ass. ECOSAR identif ies and reports both classes for a compound such as bromoacetylene (BrC#C). SMILES String Identifications : C#CBr or C#CCl or C#CF or C#CI C#CCBr or C#CCCl or C#CCF or C#CCI

Associated ECOSAR Class(s) : Vinyl/Allyl Halides - the propargyl group (C#C-C-) is r eplaced by a vinyl group (-C=C) or an allyl group (C=C-C-).

Example Propargyl Halides:

CAS No. Name SMILES Notation 624-65-7 Propargyl chloride C(#C)CC 106-96-7 1-Propyne, 3-bromo- C(#C)CBr 7572-29-4 Dichloroacetylene ClC#CClPyrazoles/Pyrroles The Pyrazoles/Pyrroles class is ident ified by the following structures:



## N H N H
N

In the current ECOSAR program, the Pyrazo les/Pyrroles structure identification meets the following criteria: (1) The ECOSAR program looks for an aromat ic ring with the followin g characteristics: (a) a five-member aromatic ring containing four carbon at oms and one nitrogen atom (a pyrrole ring) or (b) a five-member aromat ic ring containing th ree carbon atoms and two nitrogen atoms that are adjacent to each other (a pyrazole ring). (2) The [nH] in either the pyrazole ring or pyrrole ring can have the hydrogen atom attachment replaced by another atom. (3) Either ring can be fused to one additional aromatic ring. SMILES String Identifications : Pyrrole : n1cccc1 Hn1cccc1 [nH]1cccc1 N1C=CC=C1 Pyrazole : n1nccc1 Hn1nccc1 [nH]1nccc1 N1N=CC=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo.

Example Pyrazoles/Pyrroles:

CAS No. Name SMILES Notation 288-13-1 1H-Pyrazole N1N=CC=C1 109-97-7 1H-Pyrrole C1=CC=CN1 122453-73-0 Chlorfenapyr N#Cc1c(Br)c( C(F)(F)F)n(COCC) c1c2ccc(Cl)cc2 71561-11-0 Pyrazoxyfen Clc1cc(Cl)ccc1 C(=O)c2c(C)nn(C)c2 OCC(=O)c 3ccccc3 82692-44-2 Benzofenap c1cc(C)ccc1C(=O) COc2n(C)nc(C)c2C(= O)c3ccc(Cl)c(C)c3ClECOSAR Class Definition: Pyrethroids The Pyrethroids class is identifi ed by the following base structures:



### C H 3 

### CH 3



### C O C C C

O Aromatic/Aliphatic Ring

O O C N O CH 3


### C H 3

Attachments can be anything (no exclusions) In the current ECOSAR program, the Pyrethro id structure must me et either of the structures depicted above.
Notation: The structures are explicit for Pyreth roid identification. For example, the CH3 groups must be CH3 groups and the vinyl group on the fi rst structure (C=C) must be a vinyl group.

Associated ECOSAR Class(s) : None specifically.

Example Pyrethroids:

CAS No. Name SMILES Notation 70124-77-5 Flucythrinate CC(C)C(C(=O)OC(C #N)c2cccc(Oc1ccccc1) c2)c3ccc(OC(F)F)cc3 10453-86-8 Resmethrin CC(C)=CC3C(C (=O)OCc2coc(Cc1c cccc1)c2)C3(C)C 52918-63-5 Deltamethrin CC 1(C)C(C=C(Br)Br)C1 C(=O)OC(C#N)c3cccc(Oc2ccccc2)c3 52315-07-8 Cypermethrin ClC(Cl)=CC1C(C)( C)C1C(=O)OC(C#N)c2cccc(Oc3ccccc3)c2ECOSAR Class Definition: Pyridine-alpha-Acid The Pyridine-alpha-Acid class is i dentified by the following structure:



## N OH 

## O

In the current ECOSAR program, the Pyridi ne-alpha-Acid structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aromatic ring containing five carbon atoms and one nitrogen atom (a pyridine ring). (2) A carboxylic acid gr oup (-C(=O)-OH) is attached to the pyridine ring in an orthoposition to the nitrogen atom. (3) The pyridine ring can be fused to additional ring(s). SMILES String Identifications : n1ccccc1C(=O)O ... equivalent to : n1ccccc1C(=O)OH or n1ccccc1C(=O)O[H] N1=CC=CC=C1C(=O)O

Associated ECOSAR Class(s) : Other ECOSAR classes specifica lly containing a Pyridine ring: Halo Pyridines - one or more halogen atoms are attached to a pyridine ring. A structure can be classified as both a Pyridine-alpha-Acid and a Halo Pyridine.

Notation: the Pyridine Thiones class does not contain an aromatic pyridine ring (the ring is an aliphatic thione ring wit h C(=S) as part of the ring).

Examples Pyridine-alpha-Acid:

CAS No. Name SMILES Notation 98-98-6 2-Pyridinecarboxylic acid O=C(O)c(nccc1)c1 10469-09-7 2-Pyridinecarboxylic acid, 3,4,5, 6-tetrachloro- O=C(O) c(nc(c(c1Cl)Cl)Cl)c1Cl 499-83-2 2,6-Pyridinedicarboxylic acid O=C(O)c(nc(cc1)C(=O)O)c1ECOSAR Class Definition: Quinones The Quinones/Hydroquinones class is ident ified by the following example structures:

C C O

O C C O

O C C O

O
In the current ECOSAR program, the Qui nones structure meets one of the following criteria: (1) A six-member aliphatic ring with two car bonyls [C(=O)] at para-positions. The other four ring members (that are not carbonyl) must be either (a) four olefinic carbons with two double-bonds, (b) two olefinic car bons with a double-bond and two aromatic carbons as part of a fused ring, or (c) four aromatic carbons as part of a fused ring. SMILES String Identifications : O=C1C=CC(=O)C=C1 O=C1C=CC(=O)c2ccccc2c1 c1ccc2C(=O)c3ccccc3C(=O)c2c1

Associated ECOSAR Class(s) : Vinyl/Allyl Ketones - a Quinone ring (with olefinic carbon s) also fits the identification of the Vinyl/Allyl Ketone class ... However, ECOSAR currently excludes the ketone identification when a Quinon e ring is identified.

Example Quinones:

CAS No. Name SMILES Notation 106-51-4 1,4-Benzoquinone C1(=O)C=CC(=O)C=C1 58-27-5 1,4-Naphthalenedione, 2-meth yl- c1cc2C(=O)C= C(C)C(=O)c2cc1 84-65-1 Anthraquinone O=C(c(c(C(=O)c1cccc2)ccc3)c3)c12ECOSAR Class Definition: Rosins The Rosins class is identified by the following example structures:

O OH O OH O OH

Abietic Acid Pimaric Acid

The primary constituents of ro sin are resins acids of t he abietic and pimaric types having a phenanthrene- shaped ring nucleus. In the current ECOSAR program, the Rosi n structure meets th e following criteria: (1) the structure contains a fused three-ri ng unit comprised of th ree six-member rings having all carbon atoms. The rings are positioned in a phenanthrene-shaped configuration. (2) At least two of the rings must be primarily aliphatic in nature (comprised mostly of aliphatic carbons) ... only one ring can be aromatic (a benzene ring). (3) The structure must contain one (or more ) carboxylic acid groups [-C(=O)OH]. The carboxylic acid group can be loca ted anywhere in the structure. SMILES String Identifications : Abietic acid ring unit : C1CCC2CC=C3C=CCCC3C2C1 Pimaric acid ring unit : C1CCC2CCC3=CCCCC3C2C1 Ring unit with one aromatic ring : C1CCC2CCc3ccccc3C2C1 Plus a Carboxylic Acid: C(=O)O ... equivalent to : C(=O)OH or C(=O)O[H]

Associated ECOSAR Class(s) : None specifically. Example Rosins:

CAS No. Name SMILES Notation 1740-19-8 Dehydroabietic acid O=C(O)C(C( C(c(c(cc(c1)C( C)C)C2)c1)(CC3)C)C2)(C3)C 514-10-3 Abietic acid O=C( O)C(C(C(C(C(=C1)C=C(C2)C (C)C)C2)(CC3)C)C1)(C3)C 5835-26-7 Isopimaric acid CC3(CCC1C( =CCC2C1(C)CCCC2(C) C(=O)(O))C3)C=C 471-77-2 Neoabietic acid C(C(CC1)=C(C )C)=C(CCC2C(C3)(C(=O)O)C)C1C2(CC3)CECOSAR Class Definition: Schiff Bases-Azomethine
The Schiff Bases class is identif ied by the follo wing structure:



### C N R3 R2 R1

R1 and R2 - must be hydrogen or alkyl, olefinic, ac etylenic or aromatic carbon atoms (no other atoms allowed).
R3 - cannot be hydrogen In the current ECOSAR program , the Schiff Base structure m eets the following criteria: (1) The structure as depicted ab ove. The C=N fragment cannot be part of a ring structure. SMILES String Identifications : C=N

... (attachments as defined above)

Associated ECOSAR Class(s) : None specifically.

Example Schiff Bases:

CAS No. Name SMILES Notation

64611-40-1 Methanamine, Nethylidene-, (Z)- CC=NC

104-71-2 1,2-Ethanediamine, N,N'- bis(phenylmethylene)- N(CCN= Cc(cccc1)c1)=Cc(cccc2)c2 92-29-5 Hydrobenzamide c1ccccc1C=NC(c2ccccc2)N=Cc3ccccc3ECOSAR Class Definition: Substituted Ureas
The Substituted Ureas class is ident ified by the following structure:



## N O

N R 1



## R 2 

## R 4 

## R 3

In the current ECOSAR program, the Subs tituted Ureas struct ure must meet the following criteria:
R1 and R2 can be either a hydrogen or oxygen atom or alkyl, olefinic, acetylenic or aromatic carbon atoms, but at least one attachment mu st be to a carbon atom.
R3 and R4 can be anything except a carbonyl group.
If R3 or R4 contain a carbonyl group, then EC OSAR will identify the class as carbonyl ureas. SMILES String Identifications: NC(=O)N

... (attachments as defined above)

Example Substituted Ureas:

CAS No. Name SMILES Notation 330-54-1 Diuron O=C(N( C)C)Nc(ccc(c1Cl)Cl)c1 18691-97-9 Methabenzthiazuron CNC(=O)N(C)c2nc1ccccc1s2Sulfonyl Ureas The Sulfonyl Ureas class is ident ified by the following structure:

R1 and R2 - can be anything (no exclusions) In the current ECOSAR program, the Sulfony l Urea structure must meet the following criteria: (1) A sulfone group [S(=O)(=O)] is attac hed to the nitrogen atom of a urea function [NC(=O)N]. (2) The urea nitrogens or the sulf one group can have other attachments (no exclusions). SMILES String Identifications : NC(=O)NS(=O)(=O)

... (attachments as defined above)

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a gener al class having a CC(=O)N, NC(=O)N or S(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the ot her classes (such as Sulfonyl Ureas). The Vinyl/Allyl Sulfones class contains the -S(=O)(=O)- function which is the only other ECOSAR class containing the sulfone group.

Example Sulfonyl Ureas:

CAS No. Name SMILES Notation 82097-50-5 Triasulfuron ClCCOc1ccc cc1S(=O)(=O)NC(=O) Nc2nc(OC)nc(C)n2 74223-64-6 Metsulfuron-methyl COC(=O)c 1ccccc1S(=O)(=O)NC(= O)Nc2nc(OC)nc(C)n2 64902-72-3 Chlorsulfuron n1c(OC)nc (C)nc1NC(=O)NS(=O)(=O)c2ccccc2Cl 122931-48-0 Rimsulfuron CCS(=O)(=O)c1cccn c1S(=O)(=O)NC(=O)N c2nc(OC)cc(OC)n2ECOSAR Class Definition: Thiazolidinones / Benzothiazolidinones
The Thiazolidinone class is identif ied by the follo wing structures:

N S C O

N S C S N S C O

N S C S

In the current ECOSAR program, the Th iazolidinone structure meets the following criteria: (1) a five-member ring containing one carbonyl (or thiocarbonyl) attached to one aliphatic sulfur and one aliphatic nitrogen. The two carbon atoms in the ring can be either alkyl carbons or two arom atic carbons of a fused-ring. (2) The atoms in the thiazolidinone ring ca n have other attachments (no exclusions).
Notations: Currently, the thiazolidinone ring cannot contain two olefinic carbons with a double bond in place of the aromat ic carbons or alkyl carbons. SMILES String Identifications : O=C1SCCN1 S=C1SCCN1 In conjunction with a fused aromatic ring : O=C1Sc2ccccc2N1 S=C1Sc2ccccc2N1

Associated ECOSAR Class(s) :
Thiocarbamates & Dithiocarbamates - the order of the car bonyl (or thiocarbonyl) with attached sulfur and nitrogen is additionally cl assified by ECOSAR as one of these classes.
The Isothiazolone class ring also contains a car bonyl, one sulfur, one nitrogen and two carbon atoms, but in a different order.

Example Thiazolidinones / Benzothiazolidinones:

CAS No. Name SMILES Notation 25059-80-7 Benazolin-ethyl CC OC(=O)CN1C(=O) Sc2cccc(Cl)c12 96-53-7 2-Thiazolidinethione N(C(=S)SC1)C1 1908-87-8 2-Thiazolidinethione, 3-methyl- N(C(SC1)=S)(C1)C 2682-49-7 2-Thiazolidinone N1CCSC1=OECOSAR Class Definition: Thiazolidinones - Acids
The Thiazolidinones-Acid class is ident ified by the following structures:

N S C O

N S C S N S C O

N S C S



### + Acid Group

This class is identical to the Thiazolidi none-Benzothiazolidinone class with the addition of an acid function. In the current ECOSAR program, the Thiazo lidinone-Acid structur e meets the following criteria: (1) a five-member ring containing one carbonyl (or thiocarbonyl) attached to one aliphatic sulfur and one aliphatic nitrogen. The two carbon atoms in the ring can be either alkyl carbons or two arom atic carbons of a fused-ring. (2) an Acid group (carboxylic acid, sulfonic acid, phosphonic acid) exists anywhere in the structure. (3) The atoms in the thiazolidinone ring ca n have other attachments (no exclusions).
Notations: Currently, the thiazolidinone ring cannot contain two olefinic carbons with a double bond in place of the aromat ic carbons or alkyl carbons. SMILES String Identifications : O=C1SCCN1 S=C1SCCN1 In conjunction with a fused aromatic ring : O=C1Sc2ccccc2N1 S=C1Sc2ccccc2N1 Plus - an Acid group : Carboxylic Acid: C(=O)O ... equivalent to : C(=O)OH or C(=O)O[H] Phosphoric Acid: P(=O)(O) ... equivalent to : P(=O)(OH)OH Sulfonic Acid: S(=O)(=O)O ... equivalent to : S(=O)(=O)OH

Associated ECOSAR Class(s) :
Thiocarbamates & Dithiocarbamates - the order of the car bonyl (or thiocarbonyl) with attached sulfur and nitrogen is additionally cl assified by ECOSAR as one of these classes. Example Thiazolidinones / Benzothiazolidinones:

CAS No. Name SMILES Notation 3813-05-6 Benazalox (Metizolin) OC(=O)CN1C(=O) Sc2cccc(Cl)c12ECOSAR Class Definition: Thiocarbamate,Di (Free Acid) The Thiocarbamate,Di (Free Acid) class is identified by the following structures:



### N H 2 

### C S S R N C SH S R N H 2 

### C SH S

R - can be anything (no exclusions) In the current ECOSAR program, the Thio carbamate,Di (Free Acid) class meets the following criteria: (1) the core dithiocarbamate structure [N-C(=S)-S] occurs in the structure. (2) either (or both) the nitrogen or sulfur exists as free acid in the form of -NH2 or -SH. SMILES String Identifications : NC(=S)S ... equivalent to : [NH2]C(=S)S or N(H)(H)C(=S)S NC(=S)S ... equivalent to : NC(=S)SH or NC(=S)S[H] NC(=S)S ... equivalent to : [NH2]C(=S)SH or N(H)(H)C(=S)SH

... (attachments as defined above)

Associated ECOSAR Class(s) : Thiocarbamate, Di (Substituted) - both of the free acids are substituted.

Example Thiocarbamate,Di (Free Acid):

CAS No. Name SMILES Notation 29596-83-6 Acetic acid, [(aminothi oxomethyl)thio]- S=C(SCC(=O)O)N 99-00-3 Picadex N1CCN(C(=S)S)CC1 12656-69-8 Dithane SC(=S)NCCNC(S)=SECOSAR Class Definition: Thiocarbamate,Di (Substituted) The Thiocarbamate,Di (Substituted) class is identified by the following structures:



## N C S S R R

R - can be anything except hydrogen attached to the sulfur or two hydrogens (H2) attached the nitrogen. In the current ECOSAR program, the Thioca rbamate,Di (Substituted) class meets the following criteria: (1) the core dithiocarbamate structure [N-C(=S)-S] occurs in the structure. (2) both the nitrogen or sulfur have a hydr ogen substitution (excluding both as free acids). SMILES String Identifications : NC(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Thiocarbamate, Di (Free Acids) - either (or both) the nitrogen or sulfur exists as free acid in the form of -NH2 or -SH. Example Thiocarbamate,Di (Substituted):

CAS No. Name SMILES Notation 137-26-8 Thioperoxydicarbonic diamide,tetr amethyl- N(C(=S)SSC(N(C)C)=S)(C)C 95-06-7 Sulfallate CCN(CC)C(=S)SCC(Cl)=C 96-53-7 2-Thiazolidinethione N(C(=S)SC1)C1 533-74-4 Dazomet N(CSC(N1C)=S)(C1)CECOSAR Class Definition: Thiocarbamates, Mono The Thiocarbamates, Mono class is ident ified by the follo wing structures:



## N C S O R1 R2 N C O S R1 R3

R1 - can be anything except H2 (t wo hydrogens off the nitrogen).
R2 - can be anything (including hydrogen).
R3 - can be anything except hydrogen In the current ECOSAR program, the Thiocar bamates, Mono class meet s the criteria as shown in the structure above. SMILES String Identifications : NC(=O)S NC(=S)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Vinyl/Allyl Thiocarbamates - if the R3 substituent is viny l (-C=C) or allyl (-CC=C) group, ECOSAR will identify the st ructure as both Thiocarbamates, Mono and Vinyl/Allyl Thiocarbamates and report both classes. ECOSAR includes a variety of Di-Th iocarbamate ester classes.

Example Thiocarbamates, Mono:

CAS No. Name SMILES Notation 759-94-4 Eptam (EPTC) O=C(N(CCC)CCC)SCC 1114-71-2 Pebulate CCCCN(CC)C(=O)SCCC 2303-16-4 Diallate CC(C)N (C(C)C)C(=O) SCC(Cl)=CCl 42116-76-7 Carnidazole Cc1n cc(N(=O)(=O))n 1CCNC(=S)OC 88678-67-5 Pyributicarb n1c(OC)cccc1 N(C)C(=S)Oc2cc(C (C)(C)C)ccc2ECOSAR Class Definition: Thiocyanates/Isothiocyanates The Thiocyanates/Isothiocyanates class is identified by the following structure:



## R - N = C = S R S C N

R - can be aliphatic, alicyclic, arom atic, or hetercyclic, but not hydrogen. SMILES String Identifications : N=C=S N#CS Associated ECOSAR Class(s) : Isocyanates - the thiocyanate sulfur is replaced by an oxygen (R-N=C=O)

Example Thiocyanates/Isothiocyanates:

CAS No. Name SMILES Notation 57-06-7 Allyl isothiocyanate C=CCN=C=S 556-61-6 Methyl isothiocyanate CN=C=S 103-72-0 Phenyl isothiocyanate c1ccccc1N=C=S 6317-18-6 Methylene bis(thiocyanate) N#CSCSC#NECOSAR Class Definition: Thiols and Mercaptans The Thiols and Mercaptans class is i dentified by the fo llowing structure:



### Aliphatic Carbon SH

Aromatic Carbon SH SH SH (example)

(example)

In the current ECOSAR program, the Thiol-Me rcaptan structure must meet the following criteria: (1) A thiol-mercaptan function (-SH) is a ttached to an alkyl, olefinic, acetylenic or aromatic carbon atom. SMILES String Identifications : SC ... equivalent to : HSC or [H]SC SC=C ... equivalent to : HSC=C or [H]SC=C SC#C ... equivalent to : HSC#C or [H]SC#C Sc1ccccc1 ... equivalent to : HSc1ccccc1 or [H]Sc1ccccc1

Associated ECOSAR Class(s) : None specifically.

Example Thiols and Mercaptans:

CAS No. Name SMILES Notation 74-93-1 Methanethiol SC 111-31-9 1-Hexanethiol SCCCCCC 68-11-1 Mercapto acetic acid O=C(O)CS 1455-21-6 1-Nonanethiol SCCCCCCCCC 5331-91-9 Chloro-2-mercaptobenzothiazole S(C(S)=N1)c(ccc2Cl)c1c2ECOSAR Class Definition: Thiomethacrylates The Thiomethacrylates class is identified by the following structures:



### C C S O

C R1 CH 3 

### C C {O,S} S

C R1 CH 3

R1 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S} - can be either oxygen (-O-) or sulfur (-S-) Internally, the ECOSAR progr am initially detects a carb onyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefin ic attachment and one oxygen or sulfur attachment. The olefinic carbon attac hed to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a possible Thiomethacryla te to a possible Acrylate. The oxygen or sulfur must have either an alkyl carbon, olef inic carbon, acetylenic carbon or aromatic carbon attachment to be classified as ei ther a Thiomethacrylate or Acrylate. SMILES String Identifications : C=C(C)C(=O)S ... equivalent to : C=C(C(H)(H)H)C(=O)S or C=C([CH3])C(=S)S

.... Note : ECOSAR converts a SMILES entry of [ CH3] to C(H)(H)(H), then C only C=C(C)C(=S)O C=C(C)C(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Methacrylates are a class separate from either Thiomethacrylates or Acrylates

. Structures classified as Thiomethacrylates are also classified as Methacrylates. In addition, ECOSAR will classi fy Thiomethacrylates having the thiocarbonyl function [C(=S)] as Esters. Example Thiomethacrylates:

CAS No. Name SMILES Notation O-Methyl thiomethac rylate C=C(C)C(=S)OC S-Methyl thiomethac rylate C=C(C)C(=O)SC Methyl dithiomethacrylate C=C(C)C(=S)SCThiophenes The Thiophenes class is identified by t he occurrence following ring structure:



# S

ECOSAR identifies a Th iophene ring as follows: (1) a five-atom-member ring consisting of one sulfur atom and four carbon atoms (2) the ring is an aromatic ring; the SMIL ES designation for an unsubstituted ring is s1cccc1 ... if the SMILES entry into ECOSAR is S1C=CC=C1, it will be converted into s1cccc1 ... ECOSAR identifies the aromatic ring as a Thiophene (3) the Thiophene ring cannot be part of an aromatic fused-ring system (such as benzothiophene) ... the Thiophene ring can be fused to an aliphatic ring. SMILES String Identifications : s1cccc1 S1C=CC=C1

Associated ECOSAR Class(s) : None

Example Thiophenes:

CAS No. Name SMILES Notation 110

‐ 02

‐ 1 Thiophene S1C=CC=C1 [or] s1cccc1 872

‐ 31

‐ 1 3

‐ Bromothiophene C1=CC(Br)=CS1 554

‐ 14

‐ 3 2

‐ Methythiophene C1=C(C)SC=C1ECOSAR Class Definition: Thiophthalimides The Thiophthalimides class is iden tified by the following structure:

Substitutions can be anything (no exclusions). In the current ECOSAR program, the thiopht halimides structure contains a benzene ring bound to a 5-membered ring containing an aliphat ic nitrogen bound to a sulfur atom and surround by two carbonyl [C(=O)] groups (as depicted above). SMILES String Identifications: Thiophthalimides Group : C1cccc2c1C(=O)N(SC)C2=O

Associated ECOSAR Class(s): Imides - identified by C(=O)-N-C(=O).

Example Thiophthalimides:

CAS No. Name SMILES Notation
133-06-2 Captan O=C(N(SC(Cl)(Cl)Cl)C(=O)C1CC=CC2)C 12 133-07-3 Folpet O=C(N(SC(Cl)(Cl)Cl)C(=O)c1cccc2)c12
2939-80-2 Captafol O=C1N(C(=O)C2C1CC=CC2)SC(C(Cl)Cl) (Cl)ClECOSAR Class Definition: Thiotetrazoles
The Thiotetrazoles class is ident ified by the follo wing structures:



## N H

N N N S R S N

N N N

R - attachment to the sulfur can be anything in current ECOSAR program. In the current ECOSAR program, the Thiote trazole structure ident ification meets the following criteria: (1) The ECOSAR program looks for two aromatic rings with the following characteristics: (a) a five-member aromat ic ring containing one carbon atom (with an aliphatic sulfur attachment) and four nitrogen atoms (a tetraz ole ring) or (b) a fivemember aromatic ring containing one su lfur atom and four nitrogen atoms. (2) The [nH] in the tetrazole ring can hav e the hydrogen atom attachment replaced by another atom. (3) The tetrazole or thiotetrazole ring can be fused to additional aromatic ring(s). SMILES String Identifications : Sc1nnnn1 Sc1nnn[nH]1 SC1=NN=NN1 s1nnnn1 S1N=NN=N1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo.

Examples Thiotetrazoles:

CAS No. Name SMILES Notation

56610-79-8 1H-Tetrazole, 1-methyl-5- [(phenylmethyl)thio]- c1 ccccc1CSC2=NN=NN2C

133088-69-4 1H-Tetrazole, 5-(hexylsulfinyl)-1-(4- nitrophenyl)- CCCCCCS(=O)C1= NN=NN1c2ccc(N(=O)=O)cc2ECOSAR Class Definition: Thioureas
The Thioureas class is identifi ed by the following structure:



## C S

N N R2 R1

R1 and R2 - can be anything (no exclusions) In the current ECOSAR program, the Thi ourea structure must meet the following criteria: (1) A thiocarbonyl function [-C(=S)-] is atta ched to two aliphatic ni trogen atoms. If the thiocarbonyl is attached an aromatic nitrogen (such as a nitrogen in a pyrrole ring), the structure will not be classified as a Thiourea. (2) The nitrogen atoms can have other attachments (no exclusions). SMILES String Identifications : NC(=S)N

... (attachments as defined above)

Associated ECOSAR Class(s) : None specifically. Other urea classes (e.g. Substituted Ureas or Sufonyl Ureas) pertain to a carbonyl [C(=O)] urea as compared to the thioca rbonyl [C(=S)] urea of this class.

Example Thioureas:

62-56-6 Thiourea NC(=S)N 534-13-4 Thiourea, N,N'-d imethyl- N(C(=S)NC)C 5217-47-0 1,3-Diethyl-thiobarbituric acid O=C(N(C(N(C1 =O)CC)=S)CC)C1ECOSAR Class Definition: Triazines, Aliphatic The Triazines, Aliphatic class is identif ied by the following example structures:



## N N N

In the current ECOSAR program, the Triazine, Aliphatic structure is a six-member ring containing three aliphatic carbon atoms (car bonyls are not included) and three aliphatic nitrogen atoms in t he sim position . SMILES String Identifications: N1CNCNC1
Associated ECOSAR Class(s): Triazines, Aromatic- a six-me mber aromatic ring containi ng three aromatic nitrogen atoms and three aromatic car bon atoms or one aromatic ca rbon with two carbonyls or two aromatic carbons with one carbonyl Aliphatic Amines – defined in ECOSAR as any primary, secondary or tertiary aliphatic amine group. Since the Aliphatic Triazine cl ass does not take precedence over aliphatic amines, both classes are reported in ECOS AR for these chemicals – though aliphatic triazines yield higher toxicity profiles. Example Triazines:

CAS No. Name SMILES Notation 100-97-0 Hexamethylenetetrami ne N(CN(CN1CN23)C3)(C1)C2

7779-27-3 1,3,5-Triazine, 1,3,5- triethylhexahydro- N(CN(CN1CC)CC)(C1)CCECOSAR Class Definition: Triazines, Aromatic The Triazines, Aromatic class is identif ied by the following example structures:
Structure 1 Structure 2 Struct ure 3 Structure 4

N N

N R

R R

N N N O

R R

N N N O

R O

N N N O O

O

Triazine, aromatics consists of a six-memb er aromatic ring cont aining three aromatic nitrogen atoms in the sim-positio n in addition to either; 1) Three aromatic carbon atom s, 2) two aromatic carbons with one carbonyl; 3) one aromatic carbon with two carbonyls; or 4) three carbonyl groups (as shown above).
R can be anything except three prim ary or secondary nitrogen atoms.
If all R groups are primary or secondary ni trogen atoms, ECOSAR will identify the class as Melamine In structure 3 and 4 represented above containi ng at least 2 carbonyls, if there is a chlorine atom attached to the nitrogen between two carbonyls, the class will be identified at haloimides [( C(=O)NC(=O)] which present s higher toxicity concern presumably due to the presence of the halo gen based on analysis of similar chemicals. SMILES String Identifications: n1cnc(=O)nc1=O n1cncnc1 n1cnc(=O)nc1 n1c(=O)nc(=O)nc1=O
Example Triazines, Aromatic:

CAS No. Name SMILES Notation 101-05-3 Anilazine Clc2nc(Cl)nc(Nc1ccccc1Cl)n2 122-34-9 Simazine n(c(nc(n1)NCC)NCC)c1Cl 1912-24-9 Atrazine n(c( nc(n1)NC(C)C)NCC)c1ClECOSAR Class Definition: Tria zole Pyrimidines Sulfonamides Formerly refered to as the Triazole Pyri midines class, the Tr iazole Pyrimidine Sulfonamides class is entirely composed of chemicals with the following identifying structures:



## N N N

N S N O

O
The class was updated to include the CNS(=O )(=O) fragment since the entire training set for the class (which is a class of pes ticides) included this as part of the base fragment. Searches for toxicity patte rns for the former base fragm ent (c1nn2c(n1)ccnc2) yielded no results on toxicity profiles. It is suspec ted that due to the arom atic nature of the backbone this fragment alone would present mi nimal toxicity, unless substituted with reactive functional groups. In the current ECOSAR program, the Triazole Pyrimidines Sulfonamide is a sulfonamide bound to two fused aromatic rings (as depicted above) with the followin g characteristics: (a) a five-member aromatic ring containi ng two carbon atoms and three nitrogen atoms (a triazole ring), (b) a six-member aromat ic ring containing four carbon atoms and two nitrogen atoms, and (c) both rings contain one or more fused carbon atoms (meaning each ring is fused to another aromatic ring).
ALERT: Chemicals containing the large molecu lar fragment for triazole pyrimidine sulfonamides are likely designed to act as herbicides. If the query compound contains this structural fragment, it is likely to be most closely relate d to the training set chemicals in the triazole pyrimidine sulf onamides class – irrespective of the other classes reported. SMILES String Identifications: CNS(=O)(=O)c1nn2c(n1)ccnc2

Associated ECOSAR Class(s): Other ECOSAR classes containing a fused triazole ring: Benzotriazoles - a 1,2,3-triazole ring fused to another aromatic ring ECOSAR classes containing a non-fused triazole ring: Triazoles (Non-Fused) - a structure containing either a 1,2,4-triazole , 1,2,3-triazole or 1,3,4-triazole ring t hat is not fused to another aromatic ring. Examples Triazole Pyrimidines:

CAS No. Name SMILES Notation

145701-21-9 Diclosulam c1(n2c(cc(n1)F)nc(n2)S( =O)(=O)Nc1c(cccc1Cl)Cl)O CC 98967-40-9 Flumetsulam Fc1cccc(F) c1NS(=O)(=O)c2nc3nc(C)ccn3n2ECOSAR Class Definition: Triazoles (Non-Fused) The Triazoles (Non-Fused) class is i dentified by the following structures:



### N

N N N

N N N

N N

In the current ECOSAR program, the Triazo les (Non-Fused) structure identification meets the follo wing criteria: (1) The ECOSAR program identifies a five -member aromatic ring containing two carbon atoms and three nitrogen atoms (a triazole ring). (2) The position of the ni trogen atoms in the ring does not matter. The ring can be either 1,2,4-triazole, 1,2,3- triazole or 1,3,4-triazole. (3) The triazole ring cannot be fused to additional aromatic ring(s). SMILES String Identifications : n1cncn1 ... equivalent to : [nH]1cncn1 n1ccnn1 ... equivalent to : [nH]1ccnn1 n1cnnc1 ... equivalent to : [nH]1cnnc1 N1C=NC=N1 N1C=CN=N1 N1C=NN=C1

Associated ECOSAR Class(s) : None specific to a non-fused triazole ring. Other ECOSAR classes containing a fused triazole ring:
Benzotriazoles - a 1,2,3-triazole ring fu sed to another aromatic ring Triazole Pyrimidines - a triazole-pyrimidine fused ring structure

Examples Triazoles (Non-Fused):

CAS No. Name SMILES Notation 288-88-0 1H-1,2,4-Triazole n1ncnc1 76674-21-0 Flutriafol n1cncn1 CC(O)(c2ccc(F)cc2)c3ccccc3F 43121-43-3 Triadimefon CC(C)(C) C(=O)C(Oc1ccc(Cl)cc1)n2cncn2 83657-22-1 Uniconazole c1ncnn1C(C(O)C(C)(C)C)=Cc2ccc(Cl)cc2 79983-71-4 Hexaconazole Clc2c( ccc(c2)Cl)C(Cn1ncnc1)(O)CCCC 85509-19-9 Flusilazole c1cc(F) ccc1[Si](C)(c2ccc(F)cc2)Cn3ncnc3ECOSAR Class Definition: Vinyl/Allyl Alcohols The Vinyl/Allyl Alcohols class is i dentified by the following structures:



## C C OH C C C OH

In the current ECOSAR program, the Vinyl/A llyl Alcohols structur e meets the following criteria: (1) A hydroxy group (-OH) is attached to a vi nyl group (-C=C) or allyl group (-C-C=C). The single-bonded carbon on the allyl group is an alkyl carbon. SMILES String Identifications : C=CO ... equivalent to : C=COH or C=CO[H] C=CCO ... equivalent to : C=CCOH or C=CCO[H]

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of alcohol clas ses (such as Propargyl Alcohols, Benzyl Alcohols, Nitro Alcohols) and Vinyl/Allyl classes.

Example Vinyl/Allyl Alcohols:

CAS No. Name SMILES Notation 107-18-6 Allyl alcohol C=CCO 924-41-4 1,5-Hexadien-3-ol OC(CC=C)C=C 4798-44-1 1-Hexen-3-ol OC(C=C)CCC 66-76-2 Dicumarol O=C1Oc2ccccc2C(O)=C1CC3=C(O)c4ccccc4OC3=O 50-81-7 L-Ascorbic acid O1C(=O)C(O)=C(O)C1C(O)CO 557-75-5 Vinyl alcohol C=COECOSAR Class Definition: Vinyl/Allyl Aldehydes The Vinyl/Allyl Aldehydes class is i dentified by the following structures:



## H C C O C H C C O C C H C C O C

The Vinyl/Allyl Aldehyde class is identif ied when an aldehyde gr oup (HC(=O)-) is attached to a vinyl (C=C), allyl (-C -C=C) or acetylenic (-C#C) group. In the current ECOSAR program, if a stru cture contains more than one Vinyl/Allyll Aldehyde group (or one Vinyl/Allyl Aldehyde group plus additional Aldehyde functional groups), the structure will be classified as both Vinyl/Allyl Aldehydes and Aldehydes (Poly). Structures classified as Vinyl/Allyl Aldehydes are not classified as Aldehydes (Mono). SMILES String Identifications : O=CC=C ... equivalent to : O=C(H)C=C O=CCC=C ... equivalent to : O=C(H)CC=C O=CC#C ... equivalent to : O=C(H)C#C

Associated ECOSAR Class(s) : Aldehydes (Mono) - If the attachment to the aldehyde group (HC(=O)-) is an alkyl carbon, aromatic carbon, carbonyl or hydr ogen, the structure will be classified as an Aldehyde (Mono) Aldehydes (Poly) - the structure must contain two or more aldehyde functional groups. In the current ECOSAR program, a structur e can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes.

Example Vinyl/Allyl Aldehydes:

CAS No. Name SMILES Notation 107-02-8 Acrolein [or 2-Propenal] O=CC=C 5392-40-5 2,6-Octadienal, 3,7-di methyl- O=CC=C(CCC=C(C)C)C 6203-18-5 4-Dimethylaminocinnamal dehyde O=CC=Cc(ccc(N(C)C)c1)c1 7319-38-2 3-Butenal O=CCC=CECOSAR Class Definition: Vinyl/Allyl Esters The Vinyl/Allyl Esters class is i dentified by the following structures:



### C C O O Vinyl or Allyl



### C C S O Vinyl or Allyl 

### C C O S Vinyl or Allyl



### C C S S Vinyl or Allyl 

### O C O O Vinyl or Allyl



### S C S S Vinyl or Allyl

Vinyl/Allyl - Vinyl (-C=C) and Allyl (-C-C=C) In the current ECOSAR program, the Vinyl/A llyl Esters class meet s the criteria as shown in the structur e above and the following: (1) the carbon atom (to which t he carbonyl or thiocarbonyl is attached) must be an alkyl, olefinic, acetylenic or aromatic carbon. (2) carbonate and thiocarbonate esters can also be identified as Vinyl/Allyl Esters.

SMILES String Identifications : CC(=O)OC=C CC(=O)OCC=C CC(=S)OC=C CC(=S)OCC=C CC(=O)SC=C CC(=O)SCC=C CC(=S)SC=C CC(=S)SCC=C COC(=O)OC=C COC(=O)OCC=C

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is pr ogrammed to include the Ester class when the Vinyl/Allyl Esters class is reported.

Example Vinyl/Allyl Esters:

CAS No. Name SMILES Notation 105-38-4 Vinyl propionate O=C(OC=C)CC 123-20-6 Vinyl butyrate CCCC(=O)OC=C 123-68-2 Allyl caproa te O=C(OCC=C)CCCCCECOSAR Class Definition: Vinyl/Allyl Ethers The Vinyl/Allyl Ethers class is iden tified by the following structures:



## C O C C C O C C C

The ether function is identified as an ali phatic oxygen attached to two carbons atoms (alkyl, olefinic, acetylenic or aromatic carbon). In the current ECOSAR program, the Vinyl/ Allyl Ether structur e meets the following criteria: (1) one (or both) sides of t he ether function is a vinyl (-C=C) or allyl (-C-C=C) group. SMILES String Identifications : COC=C COCC=C C=COC=C C=COCC=C C#COC=C C#COCC=C c1ccccc1OC=C c1ccccc1OCC=C

Associated ECOSAR Class(s) : None specifically.
The ether function also occurs in the Halo Ether class.

Example Vinyl/Allyl Ethers:

CAS No. Name SMILES Notation 107-25-5 Methyl vinyl ether COC=C 557-40-4 Allyl ether O(CC=C)CC=C 83-79-4 Rotenone COc5cc4OCC3Oc2c1 CC(Oc1ccc2C(=O)C3c4cc5OC)C(C)=C 57-24-9 Strychnidin-10-one O=C(N(c(c(C1(C(N (C2)CC(C3C4C5OC6)=C6)C3)C2)ccc7)c7)C14)C5ECOSAR Class Definition: Vinyl/Allyl Halides The Vinyl/Allyl Halides class is id entified by the following structures:



## C C {Br,Cl,I} C C C {Br,Cl,I} C C {Br,Cl,I}

In the current ECOSAR program, the Vinyl/ Allyl Halides struct ure must meet the following criteria: (1) A halogen atom (bromine, chlorine or iodine; fluorine excluded) is attached to a vinyl group (-C=C), allyl group (-C-C=C) or ac etylenic group (-C#C). The single-bonded carbon on the allyl group is an alkyl carbon.
Notation: Fluorine has been excluded from this cla ss. In addition, the acetylenic group (which was included in the original program code) is still included. SMILES String Identifications : C=CBr or C=CCl or C=CI C=CCBr or C=CCCl or C=CCI C#CBr or C#CCl or C#CI

Associated ECOSAR Class(s) : Propargyl Halides - Vinyl/Allyl Halides identified with the acetylenic group (-C#C) are additionally classified as Pr opargyl Halides by ECOSAR. ECOSAR includes a variety of Vinyl/A llyl classes and Halo-Halide classes.

Example Vinyl/Allyl Halides:

CAS No. Name SMILES Notation 107-05-1 Allyl Chloride C=CCCl 79-01-6 Trichloroethy lene C(=CCl)(Cl)Cl 591-97-9 2-Butene, 1-chloro- C(=CC)CCl 78-88-6 1-Propene, 2,3-dichloro- C(=C)(CCl)Cl 127-18-4 Tetrachloroethyl ene C(=C(Cl)Cl)(Cl)ClECOSAR Class Definition: Vinyl/Allyl Ketones Vinyl/Allyl Ketones are identifi ed by the following structures:



## C C C O

C C O

C

To be classified as Vinyl/Allyl Ketones by the current ECOSAR pr ogram, the structure must meet the fo llowing criteria: (1) The basic ketone fragment is identified as carbonyl group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. To be classified as Vinyl/Allyl, one or both attachments to the carbonyl must be a vinyl group (-C=C) or an allyl group (-C-C=C). (2) The vinyl/allyl ketone fragment can be either cyclic or acyclic. SMILES String Identifications : CC(=O)C=C CC(=O)CC=C C=CC(=O)C=C C=CC(=O)CC=C C#CC(=O)C=C C#CC(=O)CC=C c1ccccc1C(=O)C=C c1ccccc1C(=O)CC=C
Associated ECOSAR Class(s) : In addition to the Vinyl/Allyl Ketones class, the ECOSAR program will add any of the classes below to the to the program output if identified in a structure.
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Vinyl/Allyl Ketones (e.g. SMILES: C=CC(=O)CC(=O)C). Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl
Halo Ketones (0-1 Free H) - a ketone with a -CH- Halogen (or -C-Halogen) attachment to a carbon atom at the alpha- or beta-position to the carbonyl Example Vinyl/Allyl Ketones:

CAS No. Name SMILES Notation 78-94-4 Vinyl methyl ketone C=CC(=O)C 78-59-1 Isophorone O=C(C=C(CC1(C)C)C)C1 141-79-7 Mesityl oxide O=C(C=C(C)C)CECOSAR Class Definition: Vinyl/Allyl Nitriles The Vinyl/Allyl Nitriles class is id entified by the following structures:



## C N C N

In the current ECOSAR program, the Vinyl/A llyl Nitrile structure must meet one of the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to a vinyl group (-C=C) or an allyl group (-C-C=C). (2) Two or more nitrile groups at tached to the same alkyl carbon. SMILES String Identifications : C=CC#N C=CCC#N

Associated ECOSAR Class(s) : Nitriles, Polyaliphatic - Two or more nitrile groups are attached to aliphatic atoms in the whole structure. When two or more nitrile groups are attached to the same alkyl or olefinic carbon, the structur e will be classified as both Viny l/Allyl Nitriles and Nitriles, Polyaliphatic.

Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Vinyl/Allyl Nitriles:

CAS No. Name SMILES Notation 109-75-1 Allyl cyanide N#CCC=C 107-13-1 2-Propenenitrile N#CC=CVinyl/Allyl Pyrazoles/Pyrroles The Vinyl/Allyl Pyrazoles/Pyrroles class is identified by the following structures:



### N R N N R

R = -C=C (vinyl) or –CC=C (allyl) In the current ECOSAR program, the Vi nyl/Allyl Pyrazoles/Pyrroles structure identification meets th e following criteria: (1) The ECOSAR program looks for an aromat ic ring with the following characteristics: (a) a five-member aromatic ring containing four carbon at oms and one nitrogen atom (a pyrrole ring) or (b) a five-member aromat ic ring containing th ree carbon atoms and two nitrogen atoms that are adjacent to each other (a pyrazole ring). (2) The [nH] in either the pyrazole ring or pyrrole ring can have the hydrogen atom attachment replaced by another atom. (3) Either ring can be fused to additional aromatic rings. SMILES String Identifications : Pyrrole : C=Cn1cccc1 C=CCn1cccc1 Pyrazole : C=Cn1nccc1 C=CCn1nccc1

Associated ECOSAR Class(s) : Pyrazoles/Pyrroles – A five-membered aromat ic ring containing either one or two nitrogens. Example Vinyl/Allyl Pyrazoles/Pyrroles:

CAS No. Name SMILES Notation 288-13-1 1H-Pyrazole N1N=CC=C1 109-97-7 1H-Pyrrole C1=CC=CN1 122453-73-0 Chlorfenapyr N#Cc1c(Br)c( C(F)(F)F)n(COCC) c1c2ccc(Cl)cc2 71561-11-0 Pyrazoxyfen Clc1cc(Cl)ccc1 C(=O)c2c(C)nn(C)c2 OCC(=O)c 3ccccc3 82692-44-2 Benzofenap c1cc(C)ccc1C(=O) COc2n(C)nc(C)c2C(= O)c3ccc(Cl)c(C)c3ClECOSAR Class Definition: Vinyl/Allyl Sulfones The Vinyl/Allyl Sulfones class is ident ified by the following structures:



### C S C O C C S C O C O C S C O C O C

C S C O C C
In the current ECOSAR program, the Vinyl/A llyl Sulfones structure must meet one of the following criteria: (1) A sulfone group [S(=O)(=O)] is attached to an alkyl, olefinic, acetylenic or aromatic carbon atom and the sulfone group is attached to a vinyl (-C=C) or allyl (-C-C=C) group. (2) A sulfoxide group [-S(=O)- ] is attached to an alkyl, olefinic, acetylenic or aromatic carbon atom and the sulfoxide group is attached to a vinyl (-C=C) or allyl (-C-C=C) group. SMILES String Identifications : C=CS(=O) C C=CCS(=O) C C=CS(=O)(=O) C C=CCS(=O)(=O) C

... (bolded C (carbon atom) can be alkyl (C), olef inic (C=C), acetylenic (C#C) or aromatic (c))

Associated ECOSAR Class(s) : None specifically. The Sulfonyl Ureas class contains the -N-C(=O)-N-S(= O)(=O)- function which is the only other ECOSAR class cont aining the sulfone group.
The Amides class contains a sulfoxide group as in: -N-S(=O)-

Example Vinyl/Allyl Sulfones:

CAS No. Name SMILES Notation 3680-02-2 Methyl vinyl sufone CS(=O)(=O)C=C 16212-05-8 Allyl phenyl sulfone S(=O)(=O)(c1ccccc1)CC=C 77-79-2 Thiophene, 2,5-dihydro-, 1,1-dioxide O=S(=O)(CC=C1)C1ECOSAR Class Definition: Diazoniums, Aromatic The Diazoniums, Aromatic class is i dentified by the following structure:



## [N+] A r omatic Rin g N

An aromatic ring is attached to a char ged nitrogen that is triple bonded to another nitrogen. The SMILES notation represent ing a diazonium func tion required by ECOSAR is either of the following: (1) [N+]#N ... as in c1ccccc1[N+]#N (2) N#N ... as in c1ccccc1N#N SMILES String Identifications : N#N [N+]#N

... (requires aromatic attachment)

Associated ECOSAR Class(s) :
Diazoniums - the Aromatic Ring attachment to t he charged nitrogen atom is replaced by an aliphatic atom attachment.
Azides - the Aromatic Ring attachment is re placed by a nitrogen double bonded to the charged nitrogen (which will no longer be charged).

Example Diazoniums, Aromatic:

CAS No. Name SMILES Notation 6087-56-5 Benzenediazonium,4-(dimethy lamino)- c1cc(N(C)C)ccc1[N+]#N 52572-38-0 4-Diazo-2-methylpyrrolidinobenze ne ZnCl N1(c2c(C)cc([N+]#N)cc2)CCCC1Diketones
The Diketones class is identifi ed by the following structure:

To be classified as Diketones by the current ECOSAR program, the st ructure must meet the following criteria: (1) The diketone fragment must be a 1,3-di ketone. The two carbonyl groups must be separated by one carbon atom; this carbon atom must be an alkyl or olefinic carbon. The carbon atoms on the ends of the diketone fragment must be alkyl, olefinic, acetylenic or aromatic carbons. (2) The diketone fragment must be acyclic. The carbon atom in the middle cannot occur in a ring. SMILES String Identifications : CC(=O)CC(=O)C CC(=O)CC(=O)C=C CC(=O)CC(=O)C#C CC(=O)CC(=O)c ... (aromatic attachment)

... full ring : CC(=O)CC(=O)c1ccccc1

... (attachments as defined above)

Associated ECOSAR Class(s) : In addition to the Diketones class, the EC OSAR program will add any of the classes below to the to the program output if identified in a structure. Vinyl/Allyl Ketones - a ketone with a vinyl (-C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl Halo Ketones (0-1 Free H) - a ketone with a -CH- Halogen (or -C-Halogen) attachment to a carbon atom at the alpha- or beta-position to the carbonyl

Example Diketones:

CAS No. Name SMILES Notation 123

‐ 54

‐ 6 2,4

‐ Pentanedione CC(=O)CC(=O)C 3002

‐ 24

‐ 2 2,4

‐ Hexanedione CC(=O)CC(=O)CC 69725

‐ 37

‐ 7 3,5

‐ Octanedione, 2,2,7

‐ trimethyl ‐ O=C(C(C)(C)C)CC(=O)CC(C)CECOSAR Class Definition: Epoxides, Mono The Epoxides, Mono class is identifi ed by the following ring structure:


# O

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system To be classified as Epoxides, Mono, a stru cture must contain only one epoxide ring. SMILES String Identifications : O1CC1 ... equivalent to : C1OC1 or C(O1)C1

Associated ECOSAR Class(s) : Epoxides, Poly - if a structure contains two or more epoxide rings, it will be classified as Epoxides, Poly instead of Epoxides, Mono Epoxides, Mono Acid Substituted - contains one epoxide ring plus an acid function. Structures classified as Epoxi des, Mono Acid Substituted are not additionally classified as Epoxides, Mono Halo Epoxides - structures containing an epoxide ri ng and a halogen attached directly to the ring or on an alkyl carbon attached to the ring). In the current ECOSAR program, structures identified as Halo Epoxides are not additionally classified as Epoxides, Mono.

Example Epoxides, Mono:

CAS No. Name SMILES Notation 75-21-8 Ethylene oxide O1CC1 3266-23-7 Oxirane, 2,3-dimethyl- O(C1C)C1C 122-60-1 Phenyl glycidyl ether O1CC1COc2ccccc2 72-20-8 Endrin ClC4=C(Cl)C5(Cl)C3C1CC(C2OC12)C3C4(Cl)C5(Cl)ClECOSAR Class Definition: Epoxides, Poly The Epoxides, Poly class is identified by more than one occurence the following ring structure:



# O

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system To be classified as Epoxides, Poly, a structur e must contain two or more epoxide rings. SMILES String Identifications : O1CC1 ... equivalent to : C1OC1 or C(O1)C1

Associated ECOSAR Class(s) : Epoxides, Mono - if a structure cont ains only one epoxide ring, it will be classified as Epoxides, Mono instead of Epoxides, Poly Epoxides, Mono Acid Substituted - contains one epoxide ring and an acid function Halo Epoxides - structures containing an epoxide ring and a halogen attached directly to the ring or on an alkyl carbon attached to the ring). In the current ECOSAR program, structures can be classified as both Halo Epoxides and Epoxides, Poly.

Example Epoxides, Poly:

CAS No. Name SMILES Notation 3568-29-4 Glycerin, 1,3-diglycidyl ether O(C1COCC(O)COCC(O2)C2)C1 54208-63-8 Bisphenol, diglycidyl ether O( C1COc(c(ccc2)Cc(c(OC C(O3)C3)ccc4)c4)c2)C1

### ECOSAR Class Definition: Esters ECOSAR includes a variety of structures ident ified in the Esters class. The various structures identified as Esters are listed below.

Esters (as Formic Acid Esters) Formic acid and thioformic acid esters are identified by the following structures



### H C O O C H C S O C

The carbon must be alkyl, olefinic , acetylenic or aromatic carbon. SMILES String Identifications : O=COC ... equivalent to : O=C(H)OC or O=C([H])OC O=CSC ... equivalent to : O=C(H)SC or O=C([H])SC ... (the carbon must be alkyl, ol efinic, acetylenic or aromatic): O=COC=C O=COC#C O=COc

Esters (as Carboxylic Acid Esters) Carboxylic acid esters and thiocarboxylic ac id esters [-C(=O)-S-] are identified by the following structures:



## R1 C O O
R2 R1 C S O
R2

R1 - must be alkyl, acetylenic, or aromatic carbon or a carbonyl;.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included); silicon allowed if attached to oxygen.
Notation: If R1 is olefinic (-C=C ), ECOSAR will classify the structure as an Acrylate (or Methacrylate), and the Esters class will be excluded from the ECOSAR report. SMILES String Identifications : C(=O)O or C(=O)S

... (attachments as defined above)

Esters (as Carbonates and Thiocarbonates)
Carbonic acid esters are identif ied by the following structures:

### O C O O
R R S C S O
R R O C S O
R R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included); silicon allowed if atta ched to oxygen. SMILES String Identifications : OC(=O)O or SC(=O)S or OC(=O)S

... (attachments as defined above)

Esters (as Carbamic Acid Esters)
Carbamic acid esters are ident ified by the follo wing structures:



### N C O O R1 R N C S O R1 R

R1 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included); silicon allowed if attached to oxygen.
R - attachments to th e nitrogen can be anything
Notation: ECOSAR will classify the structure as a Carbamate Ester or Thiocarbamate. SMILES String Identifications : NC(=O)O or NC(=O)S { equivalent to : N(H)(H)C(=O)O or N(H)(H)C(=O)S

... (attachments as defined above)

Esters (as Carbamimidic Acid Esters)
Carbamimidic acid esters are id entified by the following structures:



### N C O NH
R2 R1 N C O N R2 R3

R1

R1 and R3 - can be anything (no exclusions).
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : NC(=N)O

... (attachments as defined above)Esters (as Thioformic Acid Esters)



### H C O S R H C S S R

R - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : S=CO or S=CS { equivalent to : S=C(H)O or S=C(H)S

... (attachments as defined above)

Esters (as Thiocarboxylic Acid Esters)



### R1 C O S
R2 R1 C S S
R2

R1 - must be alkyl, acetylenic, or aromatic carbon or a carbonyl.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included).
Notation: If R1 is olefinic (-C=C ), ECOSAR will classify the structure as an Acrylate (or Methacrylate) in addition to the Esters class ... Note : this differs from the Carboxylic acid esters which are excluded from the ECOSAR report when Acrylates (or Methacrylates) are identified. SMILES String Identifications : C(=S)O or C(=S)S

... (attachments as defined above)

Esters (as Thiocarbamic Acid Esters)
Thiocarbamic acid esters are ident ified by the following structures:



### N H 2 

### C O S R N H 2 

### C S S R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included).
Notation: the amine (-NH2) must be -NH2 ... if a hydrogen is substituted by a carbon, ECOSAR will classify the structure as a Thiocarbamate or Dit hiocarbamate, and the Esters class will be excluded from the ECOSAR report. SMILES String Identifications : NC(=S)O or NC(=S)S { equivalent to : N(H)(H)C(=S)O or N(H)(H)C(=S)S

... (attachments as defined above)Esters (as Thiocarbonates [C(=S)] )
Thiocarbonate acid esters are id entified by the following structures:



### O C O S
R R S C S S
R R O C S S
R R

R - must be alkyl, olefinic, acetyl enic or aromatic carbon (carbonyl not included). In addition, R can be an aromatic nitrogen.
Notation: the carbonate and thiocarbonate Esters (where the carbonyl is C(=O) instead of C(=S)), do not allow the R attachment to be an aromatic nitrogen. SMILES String Identifications : OC(=S)O or SC(=S)S or OC(=S)S

... (attachments as defined above)

Esters (as Phosphate-type) Phosphate esters are identifi ed by the following structures:



### O P R3 O

R2 R1 S P R3 O

R2 R4

R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, a carbonyl, phosphorus, sulf ur, oxygen or nitrogen.
R2 and R3 - can be anything except a hydroxy group (-OH).
R4 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus
Notation: Esters (Phosphates) are a separate ECOSAR class. When identified, ECOSAR reports both Esters and Esters (Phosphates). SMILES String Identifications : P(=O)O or P(=O)S

... (attachments as defined above)

Esters (as Thiophosphate-type) Thiophosphate esters are identif ied by the following structure:



### S P R3 S

R2 R1R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus.
R2 and R3 - can be anything except oxygen.
Notation: Esters, Monothiophosphates and Este rs, Dithiophosphates are separate ECOSAR classes from Esters. When either of the two separate cl asses are identified ECOSAR excludes the Esters identification. SMILES String Identifications : P(=S)S

... (attachments as defined above)

Esters (as Sulfuric Acid or Sulfonate Esters)
Sulfonate and sulfuric acid esters are identified by the fo llowing structures:



### O S O O

O R1 R1 R2 S O O

O R1

R1 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). In addition, R1 can be silicon.
R2 - must be alkyl, olefinic, acetyleni c or aromatic carbon (carbonyl not included). SMILES String Identifications : OS(=O)(=O)O or S(=O)(=O)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Other ester classes reported in conjunction with the Esters class by ECOSAR: Esters (Phosphates) Vinyl/Allyl Esters
Ester classes that explicitly exclude the Esters class or ECOSAR generally does not report both if both are identified: Carbamate Esters Oxime Carbamate Esters Thiocarbamates ... (includes a vari ety of Thiocarbamate classes ... depending on structure, ECOSAR may report both). Beta-Halo Esters Propargyl Carbamates Acrylates Methacrylates Esters (imidic) Esters, Monothiophosphates Esters, (Phosphinates) Esters, DithiophosphatesExample Esters :

CAS No. Name SMILES Notation Formates 107-31-3 Methyl formate O=COC Carboxylates 141-78-6 Ethyl ac etate CC(=O)OCC 138-22-7 Butyl lactate O=C(OCCCC)C(O)C 131-11-3 Dimethyl phthalate O=C(OC)c(c(ccc 1)C(=O)OC)c1 Carbonates 105-58-8 Diethyl carb onate O=C(OCC)OCC Carbamic Acid Esters 51-79-6 Carbamic acid, ethyl ester O=C(OCC)N Carbamimidic Acid Esters 64037-23-6 Benzoxazoline, 5-chloro-2-imi no-3-methyl- c12N(C)C(=N)Oc1ccc(Cl)c2 Thioformic Acid Esters O-Methyl thioformate S=COC Thiocarboxylic Acid Esters 2168-84-5 Methyl dithioacetate CC(=S)SC Thiocarbonates 822-38-8 1,3-Dithiolane-2-thione S(C(SC1)=S)C1 Phosphates 78-40-0 Triethyl phosphate O=P(OCC)(OCC)OCC 62-73-7 Dichlorvos O=P(OC)(OC)OC=C(Cl)Cl Thiophosphates 996-05-4 Phosphonotrithioic acid, methyl-,dipropyl CCCSP(=S)(C)SCCC Sulfonates & Sulfuric acid esters 62-50-0 Methanesulfonic acid , ethyl ester O=S(=O)(OCC)C 515-46-8 Ethylbenzene sulfonate S(=O)(=O)(OCC)c(ccc1)cc1 64-67-5 Sulfuric acid, diet hyl ester O=S(=O)(OCC)OCCECOSAR Class Definition: Esters, Dithiophosphates The Esters, Dithiophosphates class is i dentified by the fo llowing structure:



## R1 P O S R3
S R2

R1 - can be anything except sulfur (additional sulfur s change the “dithio” class identification).
R2 - must be hydrogen, carbon (a lkyl, olefinic, acetylenic, aromatic, or carbonyl) or phosphorus.
R3 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur. In the current ECOSAR program, the Esters , Dithiophosphates class meets the criteria as shown in the structures above.
Notation : Currently, ECOSAR does not identify compounds having a structure such as P(=O)(S)(S) as a possible Dithiophosphate. SMILES String Identifications : S=P(S)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Esters, Monothiophosphates - contains the P(=S)-O- st ructure (only one sulfur bonded to the phosphorus).
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters, Dithiophosphates class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates) and Esters (Phosphinates)

. Example Esters, Dithiophosphates:

CAS No. Name SMILES Notation 000060-51-5 Dimethoate O=C(NC)CSP(OC)(OC)=S 121-75-5 Malathion CCOC(=O) CC(SP(=S)(OC)OC)C(=O)OCC 298-04-4 Disulfoton CCOP(=S)(OCC)SCCSCC 13071-79-9 Terbufos CCOP (=S)(OCC)SCS C(C)(C)CECOSAR Class Definition: Esters, Monothiophosphates The Esters, Monothiophosphates class is identified by the following structure:



## R1 P O S R3
R2

R1 and R2 - can be anything except sulfur (additional sulfurs change the “monothio” class identification).
R3 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur. In the current ECOSAR program, the Es ters, Monothiophosphates class meets the criteria as shown in the structures above.
Notation : Currently, ECOSAR does not identify compounds having a structure such as P(=O)S as a possibl e Monothiophosphate. SMILES String Identifications : S=P(O) ... ( attachments as defined above)

Associated ECOSAR Class(s) : Esters, Dithiophosphates - contains the P(=S)-S- structure.
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters, Monothiophosp hates class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates) and Esters (Phosphinates)

.

Example Esters, Monothiophosphates:

CAS No. Name SMILES Notation 115-90-2 Fensulfothion CCOP(= S)(OCC)Oc1ccc(cc1)S(C)=O 8000-97-3 Demeton S=P(OCC)(OCC)OCCSCC 333-41-5 Diazinon O(P(OCC)(O c(nc(nc1C)C(C)C)c1)=S)CC 2921-88-2 Chlorpyrifos CCOP(= S)(OCC)Oc1nc(Cl)c(Cl)cc1Cl 2104-64-5 EPN CCOP(=S)(Oc1cc c(cc1)N(=O)=O)c2ccccc2ECOSAR Class Definition: Esters, Phosphates The Esters, Phosphates class is identif ied by the following structures:



## O P R3 O

R2 R1 S P R3 O

R2 R4

R1 - can be alkyl carbon, olefinic carbon, acetylenic carbon, aromatic carbon, a carbonyl, phosphorus, sulf ur, oxygen or nitrogen.
R2 and R3 - can be anything except a hydroxy group (-OH.
R4 - can be alkyl carbon, olefinic carbon, acetylenic carbon, ar omatic carbon, or phosphorus. In the current ECOSAR program, the Esters , Phosphates class meets the criteria as shown in the structures above. SMILES String Identifications : O=P(O) O=P(S)

... (attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to report the Ester class whenever the Esters, Phosphates class is reported Other phosphorus esters classes in ECOS AR include Esters, Monothiophosphates
, Esters (Phosphinates) and Esters, Dithiophosphates ... the Esters, Phosphates class structure is not identified when these cl asses are identified.

Example Esters, Phosphates:

CAS No. Name SMILES Notation 512-56-1 Trimethyl phosp hate O=P(OC)(OC)OC 115-96-8 Tris(beta-chloroethyl) phosphate O=P(OCCCl)(OCCCl)OCCCl 1080-32-6 Diethyl benzylphosph onate O=P(OCC)(OCC)Cc(cccc1)c1 126-72-7 Tris(2,3-dibromopropyl)phosphat e O=P(OCC(Br)CBr)(O CC(Br)CBr)O CC(Br)CBrECOSAR Class Definition: Esters (Phosphinates) The Esters (Phosphinates) class is i dentified by the fo llowing structure:



## R1 P O O R2
Carbon

R1 - can be anything except oxygen.
R2 - must be hydrogen, carbon (alkyl, olefin ic, acetylenic, aromatic, or carbonyl), nitrogen, oxygen, phosphorus, or sulfur.
Carbon - alkyl, olefinic, acetylenic, or arom atic carbon (not including carbonyl). In the current ECOSAR program, the Esters (Phosphinates) class m eets the criteria as shown in the structure above. SMILES String Identifications : O=P(O)C ... ( attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Esters (Phosphinates) class is reported. Other phosphorus esters classes in ECOSAR include Esters (Phosphates)

.

Example Esters (Phosphinates):

CAS No. Name SMILES Notation 96-64-0 Soman CC(OP(C)(F)=O)C(C)(C)C 107-44-8 Sarin CC(C)OP(C)(F)=O 1224-64-2 Nibufin N(=O)(=O)c1ccc(OP (=O)(CCCC )CCCC)cc1 2511-09-3 Phosphinic acid,phenyl- ,ethyl ester O=P(c1ccccc1)OCCHaloacetamide: The haloacetamide class is identif ied by the following structure:

R1 and R2 - can be anything except a carbonyl group. If a carbonyl group is attached at R1 or R2, then ECOSAR will identify the class as imides In the current ECOSAR program, the haloacet amide structure must meet the following criteria: The carbonyl group has an aliphatic nitrogen and an alkyl carbon substituent, [NC(=O)C] and the alkyl carbon has one or more halogen substituents.
Notation: Currently, if alkyl carbon has two or more fluorine attach ments (and no other halogen attachments), the hal oacetamide identific ation is not counted by ECOSAR. SMILES String Identifications: NC(=O)CBr NC(=O)CCl NC(=O)CF NC(=O)CI

... (attachments as defined above)

Associated ECOSAR Class(s): Example haloacetamide:

CAS No. Name SMILES Notation 683-72-7 Acetamide, 2,2- dichloro- O=C(N)C(Cl)Cl 10222-01-2 Acetamide, 2,2-dibr omo-2-cyano- O=C( N)C(C#N)(Br)Br 15972-60-8 Alachlor CCc1cc cc(CC)c1N(CO C)C(=O)CClECOSAR Class Definition: Haloacids
The Haloacid class is identifi ed by the following structures:

C C OH O Halogen C C OH O Halogen

C C C O O Halogen { Na, K, Li }

In the current ECOSAR program, the Ha loacid structure m eets the following: (1) a carboxylic acid function [-C(=O)-OH] is attached to an alkyl or olefinic carbon atom. (2) the alkyl or olefinic carbon atom has an attached halogen (bromine, chlorine, fluorine or iodine). (3) the hydrogen atom in the carboxylic ac id function [-C(=O)-OH] can be substituted with a sodium, potassium or lithium atom.

SMILES String Identifications : OC(=O)CCl or OC(=O)CBr or OC(=O)CF or OC(=O)CI OC(=O)C(Br)=C [Na]OC(=O)CBr

... (halogen attachments can be Cl or Br or F or I)

Associated ECOSAR Class(s) : None specifically.

Example Haloacids:

CAS No. Name SMILES Notation 79-11-8 Monochloroacetic acid O=C(O)CCl 76-03-9 Trichloroacetic acid O=C(O)C(Cl)(Cl)Cl 75-99-0 2,2-Dichloropropionic acid O=C(O)C(Cl)(Cl)C 127-20-9 Dalapon CC(Cl)(Cl)C(O[Na])=OECOSAR Class Definition: Halo Alcohols
The Halo Alcohols class is identifi ed by the following ex ample structures:



### O H C {Br,Cl,I} C C O H {Br,Cl,I} C C O H C {Br,Cl,I}

In the current ECOSAR program, the Halo Al cohols structure meets one of the following criteria: (1) a single alkyl carbon atom has both an hydroxy attachment (-OH) and a halogen attachment. For all criteria here halogens are limited to bromine, chlorine and iodine (fluorine is excluded). (2) an alkyl carbon is attached to another alkyl carbon (or olefinic carbon). The halogen and hydroxy (-OH) are on different carbons. A maximum of thr ee carbon atoms can occur between the halogen and hydroxy (-OH). SMILES String Identifications : OCBr or OCCl or OCI OCCBr or OCCCl or OCCI OCCCBr or OCCCCl or OCCCI

... initial OC equivalent to : HOC or [H]OC

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other classes containing alcohol or halogens, but not in combination in the same class.

Example Halo Alcohols:

CAS No. Name SMILES Notation 107-07-3 2-Chloroethanol OCCCl 627-30-5 1-Propanol, 3-chloro- OCCCCl 96-13-9 1-Propanol, 2,3-dibromo- OCC(Br)CBr 115-20-8 Ethanol, 2,2,2-trichloro- OCC(Cl)(Cl)ClHalo Epoxides The Halo Epoxides class is identified by the occurrence following ring structure(s):

ECOSAR identifies an Epoxide ring as follows: (1) a three member aliphatic ring consisti ng of one aliphatic oxygen and two aliphatic carbons (2) the carbon atoms cannot have double or triple bonds (excludes olefinic and acetylenic carbons or carbons with bonds such as C=N) (3) the Epoxide ring can be part of a fused-ring system In addition to one or more epoxide rings, to be classified as Halo Epoxides, a structure must contain: a halogen at om (Br, Cl, F, I) attached directly to an epoxide ring or a halogen atom (Br, Cl, F, I) attached to an alkyl carbon that is attached directly to an epoxide ring. Halogen atoms further removed from the epoxide ring are not currently included in the Halo E poxide identification. SMILES String Identifications : O1CC1Br or O1CC1Cl or O1CC1F or O1CC1I O1CC1CBr or O1CC1CCl or O1CC1CF or O1CC1CI
Associated ECOSAR Class(s) : Epoxides, Mono - - if a structure cont ains one epoxide rings and no acid function, it will be classified as Epoxides, Mono. In the current ECOSAR program, a structure classified as Halo Epoxides cannot be additionally classified as Epoxides, Mono. Epoxides, Mono Acid Substituted - contains one epoxide ring and an acid function. In the current ECOSAR program , a structure classified as Halo Epoxides cannot be additionally classified as Epox ides, Mono Acid Subsituted. Epoxides, Poly - if a structure contains two or more epoxide rings, it will be classified as Epoxides. In the current EC OSAR program, a structure c an be classified as both Halo Epoxides and Epoxides, Poly Example Halo Epoxides :

CAS No. Name SMILES Notation 106

‐ 89

‐ 8 Epichlorohydrin O(C1CCl)C1 3132

‐ 64

‐ 7 Epibromohydrin O(C1CBr)C1ECOSAR Class Definition: Halo Esters
The Halo Esters class is identif ied by the following structures:



### C C O O Halogen R C O O R Halogen

R - must be alkyl, oelfinic, acetylenic or aromatic carbon (carbonyl not included). Halogen - bromine (Br), chlorine (Cl) , fluorine (F) or iodine (I). In the current ECOSAR program, the Halo Este rs class meets the criteria as shown in the structure above and the following: (1) the carbon atom (to whic h the Halogen is attached) mu st be an alkyl carbon (an olefinic carbon not currently a llowed). The halogen can be in either the alpha- or betapositions where the alpha-pos ition is direct attach ment to the carbonyl. (2) Fluorine was previously excluded, but is now included in this class. SMILES String Identifications : OC(=O)CBr or OC(=O)CCl or OC(=O)CI or OC(=O)F OC(=O)Br or OC(=O)Cl or OC(=O)CI or OC(=O)F

... (attachments as defined above)

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is programmed to exclude the Ester class when the Halo Esters class is reported.
Acid Halides - the Acid Halides class includes any structure with C(=O)-Halogen; ECOSAR reports both classes when present in a structure.

Example Halo Esters:

CAS No. Name SMILES Notation 14064-10-9 Diethyl chloromal onate O=C(OCC)C( C(=O)OCC)Cl 105-39-5 Acetic acid, chloro -, ethyl ester O=C(OCC)CCl 599-99-5 Tribromoacetic acid, et hyl ester BrC(Br)(Br)C(=O)OCC 356-24-1 Butanoic acid, heptafluoro-, meth yl ester O=C(OC)C(F )(F)C(F)(F)C(F)(F)F 623-48-3 Acetic acid, iodo- , ethyl ester O=C(OCC)CIECOSAR Class Definition: Halo Ethers
The Halo Ethers class is identif ied by the following structures:



## C O C Halogen C O C C Halogen

The ether function is identified as an ali phatic oxygen attached to two carbons atoms (alkyl, olefinic, acetylenic or aromatic carbon).
Note: The oxygen may not be contained within a 3 member ring. If so, ECOSAR will classify that chemical as a halo epoxide In the current ECOSAR program, the Halo Ether structure must meet one of the following criteria: (1) an alkyl carbon of an ether function has a halogen attachment (Br, Cl, F or I). (2) an alkyl carbon (that is attached to an alkyl carbon of an et her function) has a halogen attachment (Br, Cl, F or I). In the current ECOSAR progr am, the halogen can be in eith er the alpha- or betaposition. SMILES String Identifications: COCBr or COCCl or COCF or COCI COCCBr or COCCCl or COCCF or COCCI

... (attachments as defined above)

Associated ECOSAR Class(s): None specifically.
The ether function also occurs in the Vinyl/Allyl Ether class.

Example Halo Ethers:

CAS No. Name SMILES Notation 3188-13-4 Chloromethyl ethyl ether CCOCCl 111-44-4 Bis(2-chloroet hyl)ether O(CCCl)CCCl 34723-82-5 (2-Bromomethyl)-t etrahaydropyra n BrCC1CCCCO1ECOSAR Class Definition: Haloimides

The Haloimides class is identified by the following structure:

R1 or R3 can be anythi ng (no exclusions). Please note that in the parent imide class R1 and R3 can not be a nitrogen atom , otherwise ECOSAR will identify the class as carbonyl ureas. But for this class there are many training set chemicals containing a nitrogen atom with a halogen attachment in the R1 or R3 position, and all are much more toxic to fish and d aphnid than the carbonyl urea estimates. It appears these halogen attachments are driving toxicity. Therefore we are not excluding these attachments so that the haloimides estimates will be provided displaying more accurate toxicity estimates based on an alogs.
R 2

- must be a Cl, Br, I or F Haloimides class does not currently have acute or chronic QSARs for Green Alg ae

. However, based on the fact that associated chemicals are used as herbicides, toxicity to green algae is expected to be significant.
In the current ECOSAR program, the Haloimides structure must meet the following criteria:
Notation: Currently, the halogen must be attached to the nitrogen

. SMILES String Identification s : Haloimide Group : C(=O)N(Cl, Br, or I)C(=O) C(=S)N(Cl, Br, or I)C(=S) C(=N)N(Cl, Br, or I)C(=N) ... equivalent to : C(=NH)NC(=NH)

... (or any combination of the various carbonyl

- types)

... (attachments as defined above)

Example Haloimides :

CAS No. Name SMILES Notation 77

- 48

- 5 2,4

- Imidazolidinedione, 1,3

- dibrom o
- 5,5

- dimethyl

- O=C(N(C(C1(=O))(C)C)Br)N1Br 118

- 52

- 5 1,3

- Dichloro

- 5,5

- dimethylhydantoin O=C(N(C(C1(=O))(C)C)Cl)N1Cl 126

- 06

- 7 3

- Bromo

- 1

- chloro

- 5,5

- dimethylhydantoin O=C(N(C(C1(=O))(C)C)Cl)N1BrECOSAR Class Definition: Halo Ketones (2 Free Hydrogens) Halo Ketones (2 Free H) are ident ified by the following structures:



## C 

## CH 2 

## Halogen 

## O

C 

## C O 

## CH 2 

## Halogen

To be classified as Halo Ketones (2 Free H) by the current ECOSAR program, the structure must meet the following criteria: (1) The basic ketone fragment is identified as a carbony l group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. To be classified as Halo Ketones (2 Free H), the Halogen atom (bromine, chlorine, fluorine or iodine) must be attached at an alpha- or beta-position carbon to the carbonyl. In addition, the Halogen must be attached to a CH2 alkyl carbon (two free hydrogens on the alkyl carbon). SMILES String Identifications: CC(=O)CBr or CC(=O)CCl or CC(=O)CF or CC(=O)CI CC(=O)CCBr or CC(=O)CCCl or CC(=O)CCF or CC(=O)CCI

... (attachments as defined above)

Associated ECOSAR Class(s): In addition to the Halo Ketones (2 Free H) class, the ECOSAR program will add any of the classes below to the to the progra m output if identified in a structure.
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Benzyl Ketones (e.g. SMILES: c1ccccc1CC(=O)CC(=O)CC). Vinyl/Allyl Ketones - a ketone with a vinyl (- C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aroma tic ring attachment to the carbonyl Example Halo Ketones (2 Free H):

CAS No. Name SMILES Notation 1204-21-3 Bromomethyl-2,5-dimethoxypheny l ketone COc1ccc(OC)c(c1)C(=O)CBr 78-95-5 2-Propanone, 1-chloro- O=C(CCl)CHalo Nitriles
The Halo Nitriles class is identif ied by the following structures:

In the current ECOSAR program, the Halo Nitr iles structure meets t he following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl carbon. (2) An alkyl carbon in the alpha- or beta- position to the nitrile has one (or more) halogen attachments (bromine, ch lorine, fluorine or iodine). (3) The alkyl carbons (alpha- or beta-posit ion) can have other a ttachments (no current exclusions).
Notations: Halogens attached to olefinic, acet ylenic or aromatic carbons are not currently included in the class identification. Halogens further re moved from a nitrile group are not included (further than alpha- or beta-position). SMILES String Identifications : BrCC#N or ClCC#N or FCC#N or ICC#N BrCCC#N or ClCCC#N or FCCC#N or ICCC#N

Associated ECOSAR Class(s) : None specifically.
Other SAR Nitrile classes include: Azoni triles, Nitrile Esters, Nitrile Alpha-OH, Phthalonitriles, Vinyl/Allyl Nitr iles, and Nitriles, Polyaliphatic.

Example Halo Nitriles:

CAS No. Name SMILES Notation 107-14-2 Acetonitrile, chloro- N#CCCl 3252-43-5 Acetonitrile, dibromo- N#CC(Br)Br 375-00-8 Butanenitrile, heptafluor o- N#CC(F)(F)C(F)(F)C(F)(F)FHalo Pyridines The Halo Pyridines class is ident ified by the follo wing structure:

In the current ECOSAR program, the Halo Py ridines structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aromatic ring containing five carbon atoms and one nitrogen atom (a pyridine ring). (2) The aromatic car bon atoms on the pyridine ring have one or more halogen attachments (halogens include bromine, chlorine, fluorine or iodine). (3) The pyridine ring can be fused to additional ring(s). SMILES String Identifications : n1ccccc1Br n1ccccc1Cl n1ccccc1F n1ccccc1I

... (the halogen can be attached to any of the aromatic carbons)

Associated ECOSAR Class(s) : Other ECOSAR classes specifica lly containing a Pyridine ring: Pyridine-alpha-Acid - a carboxylic acid group (-C(=O) -OH) is attached to the pyridine ring in an ortho-position to the nitrogen atom. A structure can be classified as both a Pyridine-alpha-Acid and a Halo Pyridine.
Notation: the Pyridine Thiones class does not contain an aromatic pyridine ring (the ring is an aliphatic thione ring wit h C(=S) as part of the ring).

Examples Halo Pyridines:

CAS No. Name SMILES Notation 109

‐ 09

‐ 1 2

‐ Chloropyridine n1ccccc1Cl 626

‐ 55

‐ 1 3

‐ Bromopyridine n1cccc(Br)c1 1929

‐ 82

‐ 4 Pyridine, 2

‐ chloro

‐ 6

‐ (trichloromethyl) ‐ n(c(ccc1)C(Cl)(Cl)Cl)c1Cl 2176

‐ 62

‐ 7 Pyridine, pentachloro ‐ n(c(c(c(c1Cl)Cl)Cl)Cl)c1ClECOSAR Class Definition: Hydrazines ECOSAR currently identifies several different types of structures as Hydrazines which are described separately below.

Common Hydrazines :



### N N R1

R2 R4 R3

Common hydrazines are identified by two aliphatic nitrogen atoms attached with a single-bond. At least one of the R1, R2, R3 or R4 s ubstituents muct be an alkyl, olefinic, acetylentic or aromatic carbon.
Notation: In the current ECOSAR program, the R1, R2, R3 and R4 substituents can be anything. SMILES String Identifications: NN

... (attachments as defined above)

Hydrazones as Hydrazines : 

### N N C C N N C R
The R substituent can be anything. SMILES String Identifications: C=NN=C C=NN

... (attachments as defined above)

Hydrazides, Semicarbazides and Thiosemicarbazides as Hydrazines :



### N N C R O N N C R S N N C C O

The R substituent can be anything. ECOSAR identifies various hydrazides, carbazides and carbazones as Hydrazines. SMILES String Identifications: C(=O)NN C(=S)NNC(=O)NN=C

... (attachments as defined above)

Notation : Azo Structures as Hydrazines : 

### N N R1 R2
In ECOSAR versions prior to v1.10, t he linear azo structure was identified as a Hydrazine. However, this azo struct ure is no longer identified as an ECOSAR Hydrazine.

Previously Associat ed ECOSAR Class(s): Semicarbazide (Aryl-Ortho), Semicarbazide (Aryl-Meta/Para), Semicarbazide (Akyl) - identified by N-N-C(=O)-N-R ... These previously identif ied classes (but no longer identified ECOSAR classes) do not have SAR equations. The Hydrazine class is identified and used by ECOSAR.

Example Hydrazines:

CAS No. Name SMILES Notation 302-01-2 Hydrazine NN 57-14-7 1,1-Dimethylhydrazine NN(C)C 122-66-7 Hydrazine, 1,2-dipheny l- N(Nc(cccc1)c1)c(cccc2)c2 79-19-6 Thiosemicarbazide NC(=S)NN 54-85-3 Isoniazid NNC(=O)c1ccncc1 537-47-3 4-Phenylsemicarbazide c1ccccc1NC(=O)NNECOSAR Class Definition: Hydroquinones The Hydroquinones class is identified by the following example structures:



### OH OH

In the current ECOSAR program, a hydr oquinone is a six-member aromatic ring (benzene or any other aromatic ring including hetero-aromatic rings) that has hydroxyl groups [-OH] in para-position. The arom atic ring can be fused to another ring. SMILES String Identifications : Oc1ccc(O)cc1
Associated ECOSAR Class(s) : Quinone – Under environmental conditions, a re versible reduction-oxidation (redox) change from hydroquinone to semiquino ne and to quinone may occur. Phenols, Poly - the hydroquinone identific ation is a more toxic sub-class of the Phenols, Poly class. ECOSAR reports both classes.

Example Hydroquinones:

CAS No. Name SMILES Notation 123-31-9 1,4-Hydroquinone Oc1ccc(O)cc1 58-27-5 2-Methyl-1,4-hydroquinone Oc1cc(C)c(O)cc1ECOSAR Class Definition: Imidazoles
The Imidazoles class is identif ied by the following structure:



# N

N

In the current ECOSAR program, the Imidaz oles structure must meet the following criteria: (1) The Imidazole ring is a five-member ar omatic ring with nitrogen atoms at the 1- and 3-positions. The 1-position is [NH] if uns ubstituted, but the hydrogen can be replaced by another substituent. (2) The imidazole ring can be fus ed to another ring (e.g. Benzimidazole) SMILES String Identifications : [nH]1cncc1 n1cncc1 c1ncnc1 c(n1)cnc1 N1C=NC=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Benzotriazoles, Triazoles, Tr iazole Pyrimidines and Thiazole, Benzo.

Examples Imidazoles:

CAS No. Name SMILES Notation 288-32-4 1H-Imidazole N1C=NC=C1 51-17-2 1H-Benzimidazole n(c(c(n1)ccc2)c2)c1 58-08-2 Caffeine CN1C(=O)N(C)c2ncn(C)c2C1(=O) 693-98-1 2-Methylimidazole N(C=CN1)=C1C 2034-22-2 2,4,5-Tribromoimid azole BrC1=NC(Br)=C(Br)N1ECOSAR Class Definition: Imides The Imides class is identified by the following example structures:



### N [S or N] O

R 1 

### R 2



### O [S or N] R 3

R1 and R3 can be anything except a nitrogen atom.
If R1 or R3 are a nitrogen atoms, ECOSAR wil l identify the class as carbonyl
ureas. Note that If R1 or R3 are an oxygen at oms, ECOSAR will also identify the class as carbamate, esters. At this time substitution of the oxygen atom is not being excluded because we do not have supporting evidence indicating which class has higher toxi city potential or if any chemicals actually contain a hybrid of both functional groups.
R2 can be anything except a halogen atom or a [C-aromatic] group:
If R2 is a halogen attachment, ECOSAR wi ll identify the class as haloimides
If R2 is a [C-aromatic] group, ECOSAR will identify the class as benzyl imides. A strict definition of “benzyl” implies the single alkyl carbon is a -CH2- group and the aromatic ring is a benzene ring. Howe ver, in the current ECOSAR program, the single alkyl carbon can be -CH2-, -CH< or >C< and the aromatic ring can be any aromatic ring including hetero-aromatic rings. The oxygen in the carbonyl(s) could be repl aced by sulfur or NH. The structure can have any combination of C=O, C=S or C=NH as long as the nitrogen has two such attachments. SMILES String Identifications: Imide Group : C(=O)NC(=O) C(=S)NC(=S) C(=N)NC(=N) ... equivalent to : C(=NH)NC(=NH)

... (or any combination of the various carbonyl-types)

... (attachments as defined above)

Example Imides:

CAS No. Name SMILES Notation 123-56-8 Succinimide O=C(NC(=O)C1)C1ECOSAR Class Definition: Thiazolones (Iso) or Isothiazolones
The Isothiazolone class is identif ied by the follo wing structures:



### N S C O

S N C O

N S C O

In the current ECOSAR program, the Is othiazolone structure meets the following criteria: (1) a five-member ring containing one ca rbonyl, one aliphatic sulfur, one aliphatic nitrogen and two carbon atoms. The two carbon atoms can be aromatic if the isothiazolone ring is fused to an aromatic ring. If there are no arom atic carbon atoms in the ring, the ring has one double bond. (2) the sulfur and nitrogen atoms in the ring are adjacent to each other. (3) The atoms in the ring can have other attachments (no exclusions). SMILES String Identifications : O=C 1NSC=C1 O=C1SNC=C1 O-C1C=NSC1

Associated ECOSAR Class(s) : None specifically.
The Thiazolidinone class ring also contains a carbony l, one sulfur, one nitrogen and two carbon atoms, but in a different order.

Example Isothiazolones:

CAS No. Name SMILES Notation 26530-20-1 3(2H)-Isothiazolone, 2-octyl- O=C1C=CSN1CCCCCCCC 2682-20-4 3(2H)-Isothiazolone, 2-methyl- S1N(C)C(=O)C=C1ECOSAR Class Definition: Ketone Alcohols (or a-,b-Ketone Alcohol)
The Ketone Alcohols class is ident ified by the following structures:



## C C C O OH C C C O C OH

To be classified as Ketone Alcohols by t he current ECOSAR program, the structure must meet the fo llowing criteria: (1) The basic ketone fragment is identified as a carbony l group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. (2) An hydroxy group (-OH) is attached to an alkyl carbon at an alpha- or beta-position to the ketone carbonyl. SMILES String Identifications : CC(=O)CO ... equivalent to : CC(=O)COH or CC(=O)CO[H] CC(=O)CCO ... equivalent to : CC(=O)CCOH or CC(=O)CCO[H]

Associated ECOSAR Class(s) :
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Benzyl Ketones (e.g. SMILES: c1ccccc1CC(=O)CC(=O)CC). Vinyl/Allyl Ketones - a ketone with a vinyl (-C=C) or allyl (-C-C=C) attachment to the carbonyl Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl

Example Ketone Alcohols:

CAS No. Name SMILES Notation

123-42-2 2-Pentanone, 4-hydroxy-4- methyl- O=C(CC(O)(C)C)C

50-02-2 Dexamethasone C1(=O)C=C2CCC3C4CC(C)C(O)(C(=O)CO)C4(C)CC(O)C3(F) C2(C)C=C1 50-22-6 Corticosterone CC34CC(O)C 1C(CCC2=CC(=O)CCC12C)C3CCC4C(=O)CO

96-26-4 2-Propanone, 1,3- dihydroxy- O=C(CO)COECOSAR Class Definition: Malonitriles
The Malonitrile class is characte rized by the following structure:



### C N
C C N C N
C C N

C
In the current ECOSAR program, the Malonitrile structure must have two or more nitrile groups (carbon triple-bonded to nitrogen; SMILES of C#N) attached to a single carbon in the structure. The carbon must be either an alkyl or olefinic carbon. SMILES String Identifications : N#CCC#N C=C(C#N)C#N

Associated ECOSAR Class(s) : Nitrile, Polyaliphatic - Malonitriles are a more to xic sub-class of the Nitriles, Polyaliphatic. In the Polyal iphatic, Nitriles class, the tw o or more cyano groups do not need to be attached to the same carbon. ECOSAR reports both classes when identified. Vinyl/Allyl Nitriles - basically, a vinyl (-C=C) or a llyl group (-C-C=C) is attached to one or more nitriles groups. When two or more ni trile groups are attached to the same alkyl or olefinic carbon, the stru cture will be classified as a Vi nyl/Allyl Nitriles and either a Nitriles, Polyaliphatic or a Malonitriles. Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Malonitriles:

CAS No. Name SMILES Notation 2698-41-1 O-Chlorobenzylidene malononi trile N#CC(C#N)=Cc(c(ccc1)Cl)c1 109-77-3 Malononitrile C(#N)CC(#N)Melamines
The Melamines class is identifi ed by the following structure:

R1
, R2 and R3 - can be hydrogen or any other single-bonded atom. In the current ECOSAR program, the Mela mine structure must meet the following criteria: (1) A six-member aromatic ring with three nitrogen atoms in sym-positions. The three carbon atoms have aliphatic nitrogen subsitiuents as either -NH2 or -NH- (the aliphatic nitrogen must have at least one hydrogen). Associated ECOSAR Class(s): Anilines (amino-meta) - this class current ly allows hetero-arom atic rings. Amino substituents in the meta-position (as Melami nes allows) are additionally classified by ECOSAR as Anilines (amino-meta). Example Melamines:

CAS No. Name SMILES Notation 108-78-1 Melamine Nc1nc(N)nc(N)n1 2827-46-5 2,4,6-Trimethylmelamine n1c(NC)nc(NC)nc1NC 66215-27-8 Cyromazine n1c(N)nc(N)nc1NC2CC2ECOSAR Class Definition: Methacrylates The Methacrylates class is identif ied by the follo wing structures:



### C C {O,S} O

C R2 CH 3 

### C C {O,S} S

C R2 CH 3

R2 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S} - can be either oxygen (-O-) or sulfur (-S-) Internally, the ECOSAR progr am initially detects a carb onyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefin ic attachment and one oxygen or sulfur attachment. The olefinic carbon attac hed to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a Methacrylate to an Acryla te. The oxygen or sulf ur must have either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon attachment to be classified as either a Me thacrylate or Acrylate. SMILES String Identifications : C=C(C)C(=O)O ... equivalent to : C=C(C(H)(H)H)C(=O)O C=C(C)C(=O)S C=C(C)C(=S)O C=C(C)C(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Acrylates - The olefinic carbon attached to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a Methac rylate to an Acrylate. Thiomethacrylates - Thiomethacrylates are methacry lates with having a thiocarbonyl or a sulfur attached to the carbonyl function. In the current ECOSAR program, structures classified as Thiomethacrylates are also classified as Methacrylates.

Example Methacrylates:

CAS No. Name SMILES Notation 80-62-6 Methyl methac rylate C=C(C)C(=O)OC 96-05-9 Allyl methacryla te C=C(C)C(=O)OCC=C 2495-37-6 Benzyl methacryla te C=C(C)C(=O)OCc1ccccc1O-Methyl thiomethac rylate C=C(C)C(=S)OC S-Methyl thiomethac rylate C=C(C)C(=O)SCECOSAR Class Definition: Neonicotinoids Neonicotinoids act as agonists of the nicoti nic acetylcholine receptor (nAChR) in a similar mechanism as nicotinoids; however, the presence of a elec tronegative nitro or cyano group attached to the aliphatic nitrogen in neonicotinoids alters the binding potential compared to nicotino ids and results in varied toxicity in mammals and insects (Tomizawa & Casida, 2003). Although toxicity of nicotinoids and neonicotinoids in aquatic organisms appear to differ based on a few available data points, insufficient information and data are available for aquatic organisms to make any firm conclusions. Additional uncertainties include the effe ct a halogen substitution has on the pyridine ring. Thus, further research is needed to confirm the separate classification of nicotinoids and neonicotinoids for aquatic toxicity.
Neonicotinoids are identified by the following structures:



### N N R N N R



### N N R N N R
R = an electronegative nitro or cyano group (e.g., -C=NC#N or -C=NT). In the current ECOSAR program, the Neonicoti noids class meets the criteria as shown in the structure above. Substitutions on t he pyridine or pyrrole ring are allowed. SMILES String Identifications :

Associated ECOSAR Class(s) :
Nicotinoids: Are neonicotinoids without an elec tronegative nitro or cyano substitution on the aliphatic nitrogen. Example Neonicotinoids:

CAS No. Name SMILES Notation 138261-41-3 Imidacloprid c1 cc(Cl)ncc1CN2CCNC2=NT 210880-92-5 Clothianidin c1nc(Cl)sc1CNC(=NT)NC 153719-23-4 Thiamethoxam c1nc (Cl)sc1CN2C(=NT)N(C)COC2 135410-20-7 Acetamiprid c1cc (Cl)ncc1cn(C)C(C)=NC#N 111988-49-9 Thiacloprid c1cc (Cl)ncc1CN2C(=NC#N)SCC2

References: Tomizawa M., Casida J.E. 2003. Selective toxicity of neoni cotinoids attributable to specificity of insect and mammalian nicotini c receptors. Annu. Rev. Entomol., 48:339- 64.ECOSAR Class Definition: Nereistoxin Analogues The Nereistoxin Analogues class is ident ified by the following sub-structure:



### N

S S
In the current ECOSAR program, the Nere istoxin Analogues structure meets the following criteria: (1) The structure as depicted above. The nitrogen cannot be aromatic. (2) Attachments to the thiol can be anything including hydrogen, sulfur, or carbons (alkyl, olefinic or acetylenic). SMILES String Identifications : CN(C)C(CS)CS
(attachments as defined above)

Associated ECOSAR Class(s) : Aliphatic Amines – Nitrogens with aliphatic carbon attachments (alkyl, olefinic or acetylenic carbon). Thiols & Mercaptans - A thiol-mercaptan functi on (-SH) attached to an alkyl, olefinic, acetylenic or arom atic carbon atom.

Example Nereistoxin Analogues:

CAS No. Name SMILES Notation 15263-53-3 Cartap CN(C )C(CSC(=O)N)CSC(=O)N 31895-21-3 Thiocyclam C1SSSCC1N(C)CECOSAR Class Definition: Neutral Organics

The following types of example classes are represented by the neutral organics class which assumes a simple non

- polar narcosis mechanism of action for s olvents and non
reactive, non

- ionizable organic compounds

1 . Alcohols 2. Acetals 3. Ketones 4. Ethers 5. Alkyl halides 6. Aryl halides 7. Aromatic hydrocarbons 8. Halogenated aromatic hydrocarbons 9. Halogenated aliphatic hydrocarbons 10. Sulfides and di

- sulfides 11. Sulfoxides and sulfones

Please note: If there are no positive identificat ions of any other associated SAR classes for the query chemical , ECOSAR reports the structure as a Neutral Organic (regardless of what chemical functions may occur in the structure). When this occurs, the user will be promoted with the following flag:

Example Neutral Organics from the SAR Sheet : CAS No. Name SMILES Notation 112

- 27

- 6 Triethylene glycol O(CCOCCO)CCO 67

- 68

- 5 Dimethyl sulfoxide CS(=O)C 67

- 64

- 1 Acetone O=C(C)C 110

- 86

- 1 Pyridine n1ccccc1 60

- 29

- 7 Diethyl ether CCOCC 110

- 00

- 9 Furan O1C=CC =C1 71

- 43

- 2 Benzene c1ccccc1 100

- 61

- 8 N

- Methylaniline CNc1ccccc1ECOSAR Class Definition: Nicotinoids Nicotinoids act as agonists of the nicotinic acetylcholine re ceptor (nAChR) in a similar mechanism as neonicotinoids; however, the absence of a electronegative nitro or cyano group attached to the aliphatic nitrogen in ni cotinoids alters the binding potential compared to neonicotinoids and results in va ried toxicity in mammals and insects (Tomizawa & Casida, 2003). Although toxicity of nicotinoids and neonicotinoids in aquatic organisms appear to differ based on a few available data points, insufficient information and data are available for aquatic organisms to make any firm conclusions. Additional uncertainties include the affe ct a halogen substitution has on the pyridine ring. Thus, further research is needed to confirm the separate classification of nicotinoids and neonicotinoids for aquatic toxicity. Nicotines are identified by the following structures:



### N N

N N



### N N N N
In the current ECOSAR program, the Nicotinoi ds class meets the cr iteria as shown in the structure above. Substitutions on the pyridine or pyrrole ring are allowed.

SMILES String Identifications :

Associated ECOSAR Class(s) :
Neonicotinoids: A sub-classification of nicotinoids with a substitution of an electronegative cyano or nitro group on the aliphatic nitrogen. Example Nicotines:

CAS No. Name SMILES Notation 140111-52-0 Epibatidine c1cc (Cl)ncc1C2C3NC(CC3)C2 54-11-5 Nicotine c1ccncc1C2N(C)CCC2 525-74-6 Dihydronicotyri ne c1ccncc1C2=CCCN2C 494-52-0 Anabasine c1ccncc1C2NCCCC2 494-97-3 Nornicotine c1ccncc1C2NCCC2

References: Tomizawa M., Casida J.E. 2003. Selective toxicity of neoni cotinoids attributable to specificity of insect and mammalian nicotini c receptors. Annu. Rev. Entomol., 48:339- 64.ECOSAR Class Definition: Nitrile Alpha-OH The Nitrile Alpha-OH class is iden tified by the following structures:



## C C N

OH C C N C

OH

In the current ECOSAR progr am, the Nitrile Alpha-OH st ructure meets the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to an alkyl or olefinic carbon. In addition, an hy droxyl group (-OH) is attached to the same alkyl or olefinic carbon. (2) The alkyl carbon can have other a ttachments (no curr ent exclusions). SMILES String Identifications : C(O)C#N ... equivalent to : C(OH)C#N or C(O[H])C#N C=C(O)C#N ... equivalent to : C=C(OH)C#N or C=C(O[H])C#N

... (attachment as defined above)

Associated ECOSAR Class(s) : None specifically.
Other SAR Nitrile classes include: Azoni triles, Nitrile Esters, Halo Nitriles, Phthalonitriles, Vinyl/Allyl Nitr iles, and Nitriles, Polyaliphatic.

Example Nitrile Alpha-OH:

CAS No. Name SMILES Notation 78-97-7 Lactonitrile N#CC(O)C 75-86-5 Acetone Cyanohydrin N#CC(O)(C)C 513-96-2 3,3,3-Trichlorolacto nitrile ClC(Cl)(Cl)C(O)C#N 532-28-5 Mandelonitrile N#CC(O)c(cccc1)c1ECOSAR Class Definition: Nitro Alcohols
The Nitro Alcohols class is identifi ed by the following ex ample structures:



### O H C NO 2 

### C C O H NO 2 

### C C O H C NO 2

In the current ECOSAR program, the Nitro Alc ohols structure meets one of the following criteria: (1) a single alkyl carbon atom has both an hydroxy attachment (-OH) and a nitro function attachment (NO 2 ). (2) an alkyl carbon is attached to another al kyl carbon (or olefinic carbon). The nitro function (NO 2 ) and hydroxy (-OH) are on different ca rbons. A maximum of three carbon atoms can occur between the nitro function (NO 2 ) and hydroxy (-OH). SMILES String Identifications : OCN(=O)(=O) ... equivalent to : HOCN(=O)(=O) or [H]OCN(=O)(=O) OCCN(=O)(=O) OCCCN(=O)(=O)

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) OC[N+](=O)([O-]) or OCC[N+](=O)([O-]) or OCCC[N+](=O)([O-])

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs OCT or OCCT or OCCCT

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of other classes containing alcohol or nitro functions, but not in combination in the same class.

Example Nitro Alcohols:

CAS No. Name SMILES Notation 52-51-7 1,3-Propanediol, 2-brom o-2-nitro- N(=O)(=O)C(Br)(CO)CO 760-40-7 3-Nitro-1,1,1-trichloro-2- propanol ClC(Cl)(Cl)C(O)CN(=O)=O 89167-84-0 2-Propanol, 1,1-dinitr o- N(=O)(=O)C(N(=O)(=O))C(O)CECOSAR Class Definition: Nitro-/Nitroso-Benzamides
The Nitro-/Nitroso-Benzamides class is i dentified by the following structures:

C N O R2 R1

NO 2 C N O R2 R1

N O

R1 an d R2 - must be either hydrogen or alkyl, olefinic, acetylenic or aromatic carbon (carbonyl not included). In the current ECOSAR program, the Nitro -/Nitroso-Benzamide structure meets the following criteria: (1) A six-member aromatic ring (benzene or any other aromatic ring including heteroaromatic rings) has both an amide-substit uent (as noted above in the structure) and either a nitro substituent (-NO2) or a nitros o substituent (-N=O). The positioning on the ring does not matter. (2) The aromatic ring can be fused to another ring. SMILES String Identifications : Nitrosobenzamide (ortho-isomer only SMILES) : O=Nc1ccccc1C(=O)N Nitrobenzamide (ortho-isomer only SMILES) : N(=O)(=O)c1ccccc1C(=O)N

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) [N+](=O)([O- ])c1ccccc1C(=O)N

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs Tc1ccccc1C(=O)N

... (attachments as defined above)

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a general class having a CC(=O)N or NC(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the other classes (as in Nitro-/Nitroso-Benzamides). Example Nitro-/Nitroso-Benzamides:

CAS No. Name SMILES Notation 619-80-7 4-Nitrobenzamide O= C(N)c(ccc(N(=O)(=O))c1)c1 144189-66-2 3-Nitrosobenzami de NC(=O)c1cc(N=O)ccc1 3011-89-0 Aklomide Clc1cc(N(=O)(=O))ccc1C(=O)N 13160-58-2 Pyridine, 4-(p-nitrobenzamido )- n1ccc(NC(=O)c2ccc(N(=O)=O)cc2)cc1ECOSAR Class Definition: Omadines
The Omadines class is identifi ed by the following structures:



### N S

O N S O N SH O

In the current ECOSAR program, the Om adine structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aliphatic ring cont aining four olefinic carbon atoms (and two double bonds), one nitrogen atom (as N=O) and one thiocarbonyl group [C(=S)]. (2) Also identified is an aromatic pyridi ne-N-oxide ring with a thiol [-SH] at an orthoposition. (3) The omadine ring can be fused to additional ring(s). SMILES String Identifications : S=C1C=CN(=O)C=C1 S=C1N(=O)C=CC=C1 O=n1c(S)cccc1

Associated ECOSAR Class(s) : None specifically related to the whole Omadine ring. Vinyl/Allyl Amines - both ring structures above are addi tionally classified as Vinyl/Allyl Amines Aliphatic Amines - the first ring structure above (nitrogen para-position to thiocarbonyl) is additionally classified as an Aliphatic Amine.

Example Omadines: None specifically. Experimental data is CBI (Confidential Business Information).ECOSAR Class Definition: Oxetanes
The Oxetanes class is identifi ed by the following structure:



### O

C
C C

In the current ECOSAR program, the Ox etane structure identification meets the following criteria: (1) The ECOSAR program identifies a f our-member ring containi ng three alkyl carbon atoms and one oxygen atom. (2) The alkyl carbon atoms can have any substituent attachments; the substituent attachments are not included in the Oxetane i dentification. (3) The Oxetane ring can be fused to additional ring(s). SMILES String Identifications : O1CCC1 C1OCC1 O(C1)CC1

Associated ECOSAR Class(s) :
None.

Examples Oxetanes:

CAS No. Name SMILES Notation 503-30-0 Oxetane O1CCC1 68797-60-4 Oxetane, dibr omo- BrC1C(CO1)Br 425-82-1 Hexafluoro oxetane O1C(F)(F)C(F)(F)C1(F)F 3047-32-3 3-Oxetanemethanol, 3-ethyl- O(CC1(CC)CO)C1ECOSAR Class Definition: Oxyamines The Oxyamines class is identifi ed by the following structure:



## R2 N O R3 R1

R1 and R2 - must be hydrogen.
R3 - attachments must be alkyl, olefinic, ac etylenic or aromatic carbon (hydrogen not included). In the current ECOSAR program, the Oxyamine structure meets the criteria as defined above. SMILES String Identifications : NOC NOC=C NOC#C NOc1ccccc1

... (nitrogen attachments as defined above)

Associated ECOSAR Class(s) : Aliphatic Amines - under the current identificat ion scheme, ECOSAR commonly classifies a structure as both Aliphatic Am ines and Oxyamines. ECOSAR reports both identifications.

Example Oxyamines:

CAS No. Name SMILES Notation 29812-79-1 o-Decylhyd roxylamine NOCCCCCCCCCCECOSAR Class Definition: Peroxy Acids The Peroxy Acids class is identif ied by the follo wing structure:



## R1 O O R2

R1 and R2 - In the current ECOSAR program, c an be anything with one exception. The exception is that either R1 or R2 is a carbonyl [C (=O)] and the other is not a hydrogen ... This exception identif ies the Peroxy Ester class. The ECOSAR program initially identifies any -O-O- stru cture as a Peroxy Acid. Whenever a Peroxy Ester class is identified, t he previous Peroxy Acid identification is negated to give precedence to the more specific Peroxy Ester class.

SMILES String Identifications : OO

... (attachments as defined above)

Associated ECOSAR Class(s) : Peroxy Esters - an Ester class identified by C(=O)- O-O-X (where X is anything except hydrogen).

Example Peroxy Acids:

CAS No. Name SMILES Notation 79-21-0 Peroxyacetic acid CC(=O)OO 628-37-5 Diethyl peroxide CCOOCC 29914-92-9 Dipropyl peroxide CCCOOCCCECOSAR Class Definition: Peroxy Esters The Peroxy Esters class is ident ified by the follo wing structure:



## O O R2 C R1 O

R1 - can be anything (no exclusions).
R2 - can be anything except hydrogen (hydr ogen would make it a Peroxy Acid). The ECOSAR program initially identifies any -O-O- stru cture as a Peroxy Acid. Whenever a Peroxy Ester class is identified, the previous Peroxy Acid identification is negated to give precedence to the more specific Peroxy Ester class.

SMILES String Identifications : C(=O)OO

... (attachments as defined above)

Associated ECOSAR Class(s) : Peroxy Acids - a peroxy class ident ified by -O-OExample Peroxy Esters:

CAS No. Name SMILES Notation 16066-38-9 Peroxydicarbonic acid, di propyl ester O=C(OC CC)OOC(=O)OCCC 3313-92-6 Peroxydicarbonic acid, disodium salt [Na]OC(=O)OOC(=O)O[Na] 110-22-5 Peroxide, diacetyl O=C(OOC(=O)C)CECOSAR Class Definition: Phenol Amines The Phenol Amines class is identified by the following structure combination:



### OH 

## + an Amine

[ Phenol ring can also be Hetero-Aromatic ]

The current ECOSAR program identifies the Phenol Amines class using identifications of other ECOSAR classes and the following logic: (1) First, the structure must already be classified as (a) Phenols, (b) Dinitrophenols or (c) Phenols, Poly. (2) If the first criteria is satisfied and the structure is addi tionally classified as any one of the ECOSAR Amine classes, then the structure is additiona lly classified as Phenol Amines. The ECOSAR Amine classes inclu de Aliphatic Amines, Anilines (Aromatic Amines), Dinitro Aromatic Amine, Ben zyl Amines, Propargyl Amines, Amides, and Vinyl/Allyl Ether Amines. SMILES String Identifications : c(O) or c1O ... full ring : c1ccccc1O ... equivalent to : c1ccccc1OH or c1ccccc1O[H]

... Plus any of the SAR Amine Classes listed above ( see the individual definition documents )

Associated ECOSAR Class(s) : See criteria (1) and (2) above.

Examples Phenol Amines:

CAS No. Name SMILES Notation 119-34-6 4-Amino-2-nitrophenol O=N(=O)c(c(O)ccc1N)c1 94-67-7 Salicyclaldoxime N(O)=Cc(c(O)ccc1)c1 133-11-9 Phenyl-4-aminosalicylat e Oc1cc(N)ccc1C(=O)Oc2ccccc2 123-30-8 4-Aminophenol Oc(ccc(N)c1)c1 103-90-2 Acetamide, N-(4-hydro xyphenyl)- O=C(Nc(ccc(O)c1)c1)C 591-27-5 3-Aminophenol Oc(cccc1N)c1ECOSAR Class Definition: Phenols, Poly The Phenols, Poly class is identif ied by the follo wing structures:



### OH

OH X O H OH

[ Rings can also be Hetero-Aromatics ]

X - can be either a direct connection of two rings or another fragment separating the rings In the current ECOSAR program, the Phenols, Poly structure must meet the following criteria: (1) More than one hydroxyl (-OH) group are attached to aromatic rings in the structure. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) The hydroxyl (-OH) groups attached to ar omatic ring(s) can either be on the same ring or separate rings. SMILES String Identifications : c(O) or c1O ... equivalent to : c(OH) or c(OH) or c(O[H]) or c1O[H]

... example complete ring : Oc1ccccc1O ... equivalent to : HOc1ccccc1OH Associated ECOSAR Class(s) :
Phenols - Only one hydroxyl group can be attached to aromatic rings in the structure. Dinitrophenols - Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group. Hydroquinone - the hydroquinone identific ation is a more toxic sub-class of the Phenols, Poly class. ECOSAR reports both classes.

Examples Phenols:

CAS No. Name SMILES Notation 80-05-7 Bisphenol A Oc(ccc(c 1)C(c(ccc(O)c2)c2)(C)C)c1 97-23-4 Phenol, 2,2'-methylenebis 4-chloro - Oc(c(cc(c1)Cl)Cc (c(O)ccc2Cl)c2)c1

79-95-8 Phenol, 4,4'-(1-methylethylidene)bis 2,6- dichloro- Oc(c(cc(c1)C(c(cc(c(O)c2Cl)Cl)c2)(C)C)Cl)c1Cl 70-30-4 Phenol, 2,2'-methylenebis 3,4,6-trichloro- Oc(c(c(c(c1)Cl)Cl)Cc(c(c (cc2Cl)Cl)Cl)c2O)c1ClECOSAR Class Definition: Phenols The Phenols class is identified by the following structures:



### OH

Hetero-Aromatic Ring OH

In the current ECOSAR program, the Phenols st ructure must meet t he following criteria: (1) An hydroxyl (-OH) group is attached to an aromatic ring. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) The structure can cont ain only one hydroxyl (-OH) gr oup attached to an aromatic ring. Multiple hydroxyl groups attached to aromatic rings changes the classification to Phenols, Poly. SMILES String Identifications : c(O) or c1O ... equivalent to : c(OH) or c(OH) or c(O[H]) or c1O[H]

... example complete ring : c1ccccc1O ... equivalent to : c1ccccc1OH

Associated ECOSAR Class(s) : Phenols, Poly - More than one hydroxyl groups are attached to aromatic rings in the structure. Dinitrophenols - Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group.

Examples Phenols:

CAS No. Name SMILES Notation 108

‐ 95

‐ 2 Phenol Oc1ccccc1 150

‐ 76

‐ 5 4

‐ Methoxyphenol Oc1ccc(OC)cc1 88

‐ 75

‐ 5 2

‐ Nitrophenol Oc1ccccc1N(=O)=O 95

‐ 48

‐ 7 o
‐ Cresol Oc1ccccc1C 90

‐ 15

‐ 3 1

‐ Naphthol Oc(c(c(ccc1)cc2)c1)c2ECOSAR Class Definition: Phosphine Oxide The Phosphine Oxide class is iden tified by the following structure:



# P O R3 R1 R2

R1
, R2 and R3 - must be hydrogen or an alkyl, olef inic, acetylenic or aromatic carbon. In the current ECOSAR program, the P hosphine Oxide structur e must meet the following criteria: (1) A P(=O) function is attached to hydrogen at oms or to alkyl, olefinic, acetylenic or aromatic carbon atoms. SMILES String Identifications : O=P or P(=O) ... (attachments atta chments as defined above) example string: O=P(C)(C) ... equivalent to : O=P(C)(C)H

Associated ECOSAR Class(s) : None specifically.

Example Phosphine Oxides:

CAS No. Name SMILES Notation 791-28-6 Triphenylphosphine oxide O= P(c(cccc1)c1 )(c(cccc2)c2)c(cccc3)c3 1638-75-1 Phosphine oxide, (chlor omethyl)dimethyl- O=P(CCl)(C)C 14717-29-4 Phosphine oxide, dicycl ohexyl- P(=O)(C(CCC1) CC1)C(CCC2)CC2ECOSAR Class Definition: Phthalonitriles
The Phthalonitriles class is identif ied by the following structure:



## C

C N

N

In the current ECOSAR program, the Pht halonitriles structure meets the following criteria: (1) Two nitrile groups (carbon triple-bonded to nitrogen; SMILES of C#N) are attached to an aromatic ring in ort ho-positions to each other. (2) The aromatic ring must be six-member aromatic ring. The ring can be a benzene ring or a hetero-aromatic ring (such as pyridine). SMILES String Identifications : N#Cc1ccccc1C#N c1cc(C#N)c(C#N)cc1 c(c1C#N)cccc1C#N

Associated ECOSAR Class(s) : None specifically. Other SAR Nitrile classes include: Azonitriles, Nitrile Esters, Halo Nitriles, Vinyl/Allyl Nitriles, Nitriles Alpha-OH, and Nitriles, Polyaliphatic.

Example Phthalonitriles:

CAS No. Name SMILES Notation 91-15-6 1,2-Benzenedicarbonitrile C(#N)c(c(C(#N))ccc1)c1 712-74-3 Tetracyanobenzene N# Cc1c(C#N)cc(C# N)c(C#N)c1 1835-65-0 Tetrafluorophthalonitrile Fc(c(F)c(F)c1C#N)c(F)c1C#N 1953-99-7 Tetrachlorophthalonitrile Clc(c(Cl)c(Cl)c1C#N)c(Cl)c1C#NECOSAR Class Definition: Nitriles, Polyaliphatic The Nitriles, Polyaliphatic class is c haracterized by the following structure:



### C N C N Structure
(2 or more cyano groups attached to aliphatic atoms)

In the current ECOSAR program , the Nitriles, Polyaliphati c structure must meet the following criteria: (1) Two or more nitrile groups (carbon tr iple-bonded to nitrogen; SMILES of C#N) are attached to aliphatic atoms in the structure. The aliphatic atoms include alkyl carbon, olefinic carbon, acetylenic carbon, nitr ogen, sulfur and phosphorus . Other aliphatic atoms are not currently included (e.g. oxygen). SMILES String Identifications : CC#N C=CC#N C#CC#N NC#N SC#N PC#N

... (two or more of these cyano [C#N] attachments required)

Associated ECOSAR Class(s) :
Malonitriles - Malonitriles are a more toxic sub-cl ass of the Nitriles, Polyaliphatic class that consist of 2 cyano groups separated by a single carbon. Vinyl/Allyl Nitriles - basically, a vinyl (-C=C) or a llyl group (-C-C=C) is attached to one or more nitriles groups. When two or more ni trile groups are attached to the same alkyl or olefinic carbon, the stru cture will be classified as a Vi nyl/Allyl Nitriles and either a Nitriles, Polyaliphatic or Malonitriles. Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Vinyl/Allyl Nitriles:

CAS No. Name SMILES Notation 2698-41-1 O-Chlorobenzylidene malononi trile N#CC(C#N)=Cc(c(ccc1)Cl)c1 109-77-3 Malononitrile C(#N)CC(#N) 110-61-2 Butanedinitrile C(#N)CCC(#N) 111-69-3 Hexanedinitrile C(#N)CCCCC(#N)ECOSAR Class Definition: Polynitroan ilines (Polynitro Aromatic Amine) The Polynitroanilines class is iden tified by the following structure:


### NH 2



### NO 2 

### O 2 

### N

In the current ECOSAR program, the Poly nitroaniline structure meets the following criteria: (1) A benzene ring (or any other aromatic ri ng including hetero-aromatic rings) has one (or more) amine substituent (a s -NH2) and two (or more) ni tro substituents (-NO2). (2) The aromatic ring can be fused to another ring.
Notation: the amine substituent must be -NH2 ... an amine substituent as -NH- or -N< is not identified as an amine for this class. SMILES String Identifications: Nc1c(N(=O)(=O))cccc1N(=O)=O Nc1c([N+](=O)([O-] ))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Nc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs
Associated ECOSAR Class(s): Anilines (Unhindered) - An aromatic ring has an amine substituent (-NH2) that is not hindered by specific ortho-substituents. If the Polynitroanilines class is identified, ECOSAR reports both identifications. Anilines (Hindered) - An ar omatic ring has an amine substi tuent (-NH2) that is hindered by specific ortho-substituent s. If the Polynitroanilines cl ass is identified, ECOSAR reports both identifications Dinitrobenzenes - An aromatic ring has two (or more) -NO2 substituents. If the Polynitroanilines class is identified, ECOSAR excludes the Polynitrobenzene identification. Anilines (amino-ortho), Anilines (amino-meta ), Anilines (amino-para) - These classes are identified when a six-member aromatic ring has two -NH2 substituents in either an ortho-, meta- or para-position. When identified in conjunction with Polynitroanilines, they are also reported by ECOSAR. Example Polynitroanilines:

CAS No. Name SMILES Notation 97-02-9 2,4-Dinitroaniline N(=O )(=O)c(ccc(N)c1N(=O)(=O))c1 96-91-3 Picramic acid Nc1cc(cc(N(=O)=O)c1O)N(=O)=O 489-98-5 2,4,6-Trinitroaniline Nc1c (cc(cc1N(=O)=O)N (=O)=O)N(=O)=OECOSAR Class Definition: Polynitrobenzenes The Polynitrobenzenes class is identif ied by the following structures: 

### NO 2



### NO 2 or ... Hetero-Aromatic Ring with two or more -NO2

In the current ECOSAR program, the Poly nitrobenzenes structure identification meets the following criteria: (1) The ECOSAR program looks for an arom atic ring (either a benzene or any heteroaromatic ring) with two or more nitro groups (-NO2) attached to t he same ring. The position of the NO2 groups on the ring does not matter. (2) The aromatic ring can not additionally have the following attachments: -OH or an amine (NH2). The presence of thes e groups changes the current ECOSAR classification to Polyni trophenols or Polynitroanilines. (3) The aromatic ring can be fus ed to one additional aromatic ring. SMILES String Identifications: c1c(N(=O)(=O))cccc1N(=O)=O c1c([N+](=O)([O-]))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Nc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs Associated ECOSAR Class(s): Polynitroanilines - an aromatic ring containing two or more nitro substituents (NO2) plus an amine substituent (e.g. -NH2). In the current ECOSAR program, an aromatic ring will not be classified as both Dinitrobenz ene and Dinitroaniline (t he Amine is given precedence). Polynitrophenols - an aromatic ring containing tw o or more nitro substituents (NO2) plus an hydroxyl (-OH) substituent. In the current ECOSAR pr ogram, an aromatic ring will not be classified as both Polynitrobenz enes and Polynitrophenols (the phenol is given precedence).

Example Polynitrobenzenes:

CAS No. Name SMILES Notation 100-25-4 1,4-Dinitrobenzene N( =O)(=O)c(ccc(N(=O)(=O))c1)c1 528-29-0 1,2-Dinitrobenzene O=N(=O)c1ccccc1N(=O)=O 121-14-2 Benzene, 1-methyl-2,4-dinit ro- N(=O)(=O)c(ccc (c1N(=O)(=O))C)c1 3698-83-7 Benzene, 1,5-dichloro-2,4-dinit ro- O=N(=O)c(c(cc(c1 N(=O)=O)Cl)Cl)c1ECOSAR Class Definition: Polynitrophenols The Polynitrophenols class is identifi ed by the following structures:



### OH

NO 2 

### O 2 

### N

[ Ring can also be Hetero-Aromatic ]

In the current ECOSAR program, the Polyni trophenols structure must meet the following criteria: (1) One or more hydroxyl (-O H) groups are attached to an ar omatic ring. The aromatic ring can be either a phenyl ring or any other aromatic ring unit including heterocyclic aromatic rings. (2) Two or more nitro (-NO2) groups must be attached to the same aromatic ring as the hydroxyl (-OH) group. SMILES String Identifications: Oc1c(N(=O)(=O))cccc1N(=O)=O Oc1c([N+](=O)([O-] ))cccc1[N+]([O-])=O

... nitro function (NO2) can be either N(=O)(=O) or [N+](=O)([O-]) Oc1cc(T)ccc1T

... nitro function (NO2) can entered as T ... this is unique to all EPI Suite programs

Associated ECOSAR Class(s): Phenols - Only one hydroxyl group can be attac hed to aromatic rings in the structure. Phenols, Poly - More than one hydroxyl groups are attached to aromatic rings in the entire structure.

Examples Polynitrophenols:

CAS No. Name SMILES Notation 51-28-5 2,4-Dinitrophenol N(=O )(=O)c(ccc(O)c1N(=O)(=O))c1 88-89-1 2,4,6-Trinitrophenol N(=O)(=O )c(cc(N(=O)( =O))c(O)c1N( =O)(=O))c1 534-52-1 4,6-Dinitro-o-cresol N(=O )(=O)c(cc(N(=O)( =O))c(O)c1C)c1Propargyl Alcohols-Hindered The Propargyl Alcohols-Hindered class is identified by the following structures:



### C C C OH
R R
C C C C OH
R R R

R

R - is attached to alkyl carbons. These al kyl carbons can have two attachments each; the combination R attachments that i dentify Propargyl Alcoho ls-Hindered are noted below. In the current ECOSAR program, the hy droxy group (-OH) can be attached to the propargyl function (C#C-C-) at either an alpha- or beta-position. The Propargyl AlcoholHindered structure meets one of the following criteria: (1) In the first structure abov e, the hydroxyl group (-OH) is attached to an alkyl carbon that attached directly to an acetylenic carb on (alpha-position) . Neither of the Rsubstituents can be hydrogen (if either R is hydrogen, the structure is identified as a Propargyl Alcohol). (2) In the second structur e above, an hydroxyl group (-OH) is attached at the betaposition. If both R-substituents off the beta-carbon are not hydrogen, then the Propargyl Alcohol-Hindered class is ident ified (regardless of the alpha-carbon subs tituents). If either substituent off the alpha-carbon is not hydrogen, then the Propargyl AlcoholHindered class is identified (regardless of the beta-carbon substituents).
Notation: The ECOSAR classification changes from Propargyl Alcohols-Hindered to Propargyl Alcohols when the basic structure is identified, but the R-substituents do not meet the criteria above.. SMILES String Identifications : C#CCO ... equivalent to : C#CCOH or C#CCO[H] C#CCCO ... equivalent to : C#CCCOH or C#CCCO[H]

... (attachments as defined above)

Associated ECOSAR Class(s) : Propargyl Alcohols - see notation above.

Example Propargyl Al cohols-Hindered:

CAS No. Name SMILES Notation 115-19-5 3-Butyn-2-ol, 2-methyl- OC(C#C)(C)C 77-75-8 1-Pentyn-3-ol, 3-methyl- OC(C#C)(CC)C 127-66-2 2-Phenyl-3-butyn-2 -ol OC(C#C)(c(cccc1)c1)CPropargyl Alcohols The Propargyl Alcohols class is identified by the following structures:



### C C CH OH R 

### C C CH 2 

### CH OH R

R - can be anything (no exclusions) In the current ECOSAR program , the Propargyl Alcohol struct ure is identified as shown above. The hydroxy group (-OH) can be atta ched to the propargyl function (C#C-C-) at either an alpha- or beta-position.
Notation: The Propargyl Alcohols class is dist inguished from the Propargyl AlcoholsHindered class in that the hydroxyl (-OH) is at tached to a straight-chain alkyl carbon. In the first structure above, the -OH is attached to a -CH- (with only o ne substituent). In the second structure (beta- position), the chain must be -CH2-CH- (with only one substituent off the second carbon) ... If t he alkyl carbons have additional substituents replacing the designated hydrogens, then the Propargyl Alcohols-Hin dered class will be identified. SMILES String Identifications : C#CCO ... equivalent to : C#CCOH or C#CCO[H] C#CCCO ... equivalent to : C#CCCOH or C#CCCO[H] C#CC(O)C ... equivalent to : C#CC(OH)C or C#CC(O[H])C

... (attachments as defined above)

Associated ECOSAR Class(s) : Propargyl Alc ohol-Hindered - see notation above.

Example Propargyl Alcohols:

CAS No. Name SMILES Notation 107-19-7 Propargyl alcohol OCC#C 110-65-6 2-Butyne-1, 4-diol OCC#CCO 927-74-2 3-Butyn-1-ol OCCC#C 764-01-2 2-Butyn-1-ol CC#CCO 4117-14-0 2-Decyn- 1-ol OCC#CCCCCCCCECOSAR Class Definition: Propargyl Ethers The Propargyl Ethers class is identi fied by the following structure:



## C C C O Carbon

In the current ECOSAR program, the Propar gyl Ether structure meets the following criteria: (1) An ether oxygen is attached to an alkyl carbon that is attached to an acetylenic carbon. (2) The “Carbon” in the structure above can be alkyl, olefinic, acetylenic or aromatic carbon. SMILES String Identifications : C#CCOC C#CCOC=C C#CCOC#C C#CCOc1ccccc1

Associated ECOSAR Class(s) : None specifically. Vinyl/Allyl Ethers - the propargyl group (C#C-C-O-C ) is replaced by an allyl group (C=C-C-O-C)

Example Propargyl Ethers:

CAS No. Name SMILES Notation 6921-27-3 Dipropargyl ether O(CC#C)CC#C 53135-64-1 1-Propyne, 3-propoxy- CCCOCC#CECOSAR Class Definition: Propargyl Halides The Propargyl Halides class is identif ied by the following structures:



## C C Halogen C C C Halogen

In the current ECOSAR program, the Propar gyl Halides structur e meets one of the following criteria: (1) A halogen atom (Br, Cl, F, or I) is attached directly to an acetylenic carbon. (2) A halogen atom (Br, Cl, F, or I) is attached to an alkyl carbon that is attached directly to an acetylenic carbon.
Notation: In the current ECOSAR program, t he first criteria above overlaps with a criteria used by the Vinyl/Ally Halides cl ass. ECOSAR identif ies and reports both classes for a compound such as bromoacetylene (BrC#C). SMILES String Identifications : C#CBr or C#CCl or C#CF or C#CI C#CCBr or C#CCCl or C#CCF or C#CCI

Associated ECOSAR Class(s) : Vinyl/Allyl Halides - the propargyl group (C#C-C-) is r eplaced by a vinyl group (-C=C) or an allyl group (C=C-C-).

Example Propargyl Halides:

CAS No. Name SMILES Notation 624-65-7 Propargyl chloride C(#C)CC 106-96-7 1-Propyne, 3-bromo- C(#C)CBr 7572-29-4 Dichloroacetylene ClC#CClPyrazoles/Pyrroles The Pyrazoles/Pyrroles class is ident ified by the following structures:



## N H N H
N

In the current ECOSAR program, the Pyrazo les/Pyrroles structure identification meets the following criteria: (1) The ECOSAR program looks for an aromat ic ring with the followin g characteristics: (a) a five-member aromatic ring containing four carbon at oms and one nitrogen atom (a pyrrole ring) or (b) a five-member aromat ic ring containing th ree carbon atoms and two nitrogen atoms that are adjacent to each other (a pyrazole ring). (2) The [nH] in either the pyrazole ring or pyrrole ring can have the hydrogen atom attachment replaced by another atom. (3) Either ring can be fused to one additional aromatic ring. SMILES String Identifications : Pyrrole : n1cccc1 Hn1cccc1 [nH]1cccc1 N1C=CC=C1 Pyrazole : n1nccc1 Hn1nccc1 [nH]1nccc1 N1N=CC=C1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo.

Example Pyrazoles/Pyrroles:

CAS No. Name SMILES Notation 288-13-1 1H-Pyrazole N1N=CC=C1 109-97-7 1H-Pyrrole C1=CC=CN1 122453-73-0 Chlorfenapyr N#Cc1c(Br)c( C(F)(F)F)n(COCC) c1c2ccc(Cl)cc2 71561-11-0 Pyrazoxyfen Clc1cc(Cl)ccc1 C(=O)c2c(C)nn(C)c2 OCC(=O)c 3ccccc3 82692-44-2 Benzofenap c1cc(C)ccc1C(=O) COc2n(C)nc(C)c2C(= O)c3ccc(Cl)c(C)c3ClECOSAR Class Definition: Pyrethroids The Pyrethroids class is identifi ed by the following base structures:



### C H 3 

### CH 3



### C O C C C

O Aromatic/Aliphatic Ring

O O C N O CH 3


### C H 3

Attachments can be anything (no exclusions) In the current ECOSAR program, the Pyrethro id structure must me et either of the structures depicted above.
Notation: The structures are explicit for Pyreth roid identification. For example, the CH3 groups must be CH3 groups and the vinyl group on the fi rst structure (C=C) must be a vinyl group.

Associated ECOSAR Class(s) : None specifically.

Example Pyrethroids:

CAS No. Name SMILES Notation 70124-77-5 Flucythrinate CC(C)C(C(=O)OC(C #N)c2cccc(Oc1ccccc1) c2)c3ccc(OC(F)F)cc3 10453-86-8 Resmethrin CC(C)=CC3C(C (=O)OCc2coc(Cc1c cccc1)c2)C3(C)C 52918-63-5 Deltamethrin CC 1(C)C(C=C(Br)Br)C1 C(=O)OC(C#N)c3cccc(Oc2ccccc2)c3 52315-07-8 Cypermethrin ClC(Cl)=CC1C(C)( C)C1C(=O)OC(C#N)c2cccc(Oc3ccccc3)c2ECOSAR Class Definition: Pyridine-alpha-Acid The Pyridine-alpha-Acid class is i dentified by the following structure:



## N OH 

## O

In the current ECOSAR program, the Pyridi ne-alpha-Acid structure identification meets the following criteria: (1) The ECOSAR program identifies a six-me mber aromatic ring containing five carbon atoms and one nitrogen atom (a pyridine ring). (2) A carboxylic acid gr oup (-C(=O)-OH) is attached to the pyridine ring in an orthoposition to the nitrogen atom. (3) The pyridine ring can be fused to additional ring(s). SMILES String Identifications : n1ccccc1C(=O)O ... equivalent to : n1ccccc1C(=O)OH or n1ccccc1C(=O)O[H] N1=CC=CC=C1C(=O)O

Associated ECOSAR Class(s) : Other ECOSAR classes specifica lly containing a Pyridine ring: Halo Pyridines - one or more halogen atoms are attached to a pyridine ring. A structure can be classified as both a Pyridine-alpha-Acid and a Halo Pyridine.

Notation: the Pyridine Thiones class does not contain an aromatic pyridine ring (the ring is an aliphatic thione ring wit h C(=S) as part of the ring).

Examples Pyridine-alpha-Acid:

CAS No. Name SMILES Notation 98-98-6 2-Pyridinecarboxylic acid O=C(O)c(nccc1)c1 10469-09-7 2-Pyridinecarboxylic acid, 3,4,5, 6-tetrachloro- O=C(O) c(nc(c(c1Cl)Cl)Cl)c1Cl 499-83-2 2,6-Pyridinedicarboxylic acid O=C(O)c(nc(cc1)C(=O)O)c1ECOSAR Class Definition: Quinones The Quinones/Hydroquinones class is ident ified by the following example structures:

C C O

O C C O

O C C O

O
In the current ECOSAR program, the Qui nones structure meets one of the following criteria: (1) A six-member aliphatic ring with two car bonyls [C(=O)] at para-positions. The other four ring members (that are not carbonyl) must be either (a) four olefinic carbons with two double-bonds, (b) two olefinic car bons with a double-bond and two aromatic carbons as part of a fused ring, or (c) four aromatic carbons as part of a fused ring. SMILES String Identifications : O=C1C=CC(=O)C=C1 O=C1C=CC(=O)c2ccccc2c1 c1ccc2C(=O)c3ccccc3C(=O)c2c1

Associated ECOSAR Class(s) : Vinyl/Allyl Ketones - a Quinone ring (with olefinic carbon s) also fits the identification of the Vinyl/Allyl Ketone class ... However, ECOSAR currently excludes the ketone identification when a Quinon e ring is identified.

Example Quinones:

CAS No. Name SMILES Notation 106-51-4 1,4-Benzoquinone C1(=O)C=CC(=O)C=C1 58-27-5 1,4-Naphthalenedione, 2-meth yl- c1cc2C(=O)C= C(C)C(=O)c2cc1 84-65-1 Anthraquinone O=C(c(c(C(=O)c1cccc2)ccc3)c3)c12ECOSAR Class Definition: Rosins The Rosins class is identified by the following example structures:

O OH O OH O OH

Abietic Acid Pimaric Acid

The primary constituents of ro sin are resins acids of t he abietic and pimaric types having a phenanthrene- shaped ring nucleus. In the current ECOSAR program, the Rosi n structure meets th e following criteria: (1) the structure contains a fused three-ri ng unit comprised of th ree six-member rings having all carbon atoms. The rings are positioned in a phenanthrene-shaped configuration. (2) At least two of the rings must be primarily aliphatic in nature (comprised mostly of aliphatic carbons) ... only one ring can be aromatic (a benzene ring). (3) The structure must contain one (or more ) carboxylic acid groups [-C(=O)OH]. The carboxylic acid group can be loca ted anywhere in the structure. SMILES String Identifications : Abietic acid ring unit : C1CCC2CC=C3C=CCCC3C2C1 Pimaric acid ring unit : C1CCC2CCC3=CCCCC3C2C1 Ring unit with one aromatic ring : C1CCC2CCc3ccccc3C2C1 Plus a Carboxylic Acid: C(=O)O ... equivalent to : C(=O)OH or C(=O)O[H]

Associated ECOSAR Class(s) : None specifically. Example Rosins:

CAS No. Name SMILES Notation 1740-19-8 Dehydroabietic acid O=C(O)C(C( C(c(c(cc(c1)C( C)C)C2)c1)(CC3)C)C2)(C3)C 514-10-3 Abietic acid O=C( O)C(C(C(C(C(=C1)C=C(C2)C (C)C)C2)(CC3)C)C1)(C3)C 5835-26-7 Isopimaric acid CC3(CCC1C( =CCC2C1(C)CCCC2(C) C(=O)(O))C3)C=C 471-77-2 Neoabietic acid C(C(CC1)=C(C )C)=C(CCC2C(C3)(C(=O)O)C)C1C2(CC3)CECOSAR Class Definition: Schiff Bases-Azomethine
The Schiff Bases class is identif ied by the follo wing structure:



### C N R3 R2 R1

R1 and R2 - must be hydrogen or alkyl, olefinic, ac etylenic or aromatic carbon atoms (no other atoms allowed).
R3 - cannot be hydrogen In the current ECOSAR program , the Schiff Base structure m eets the following criteria: (1) The structure as depicted ab ove. The C=N fragment cannot be part of a ring structure. SMILES String Identifications : C=N

... (attachments as defined above)

Associated ECOSAR Class(s) : None specifically.

Example Schiff Bases:

CAS No. Name SMILES Notation

64611-40-1 Methanamine, Nethylidene-, (Z)- CC=NC

104-71-2 1,2-Ethanediamine, N,N'- bis(phenylmethylene)- N(CCN= Cc(cccc1)c1)=Cc(cccc2)c2 92-29-5 Hydrobenzamide c1ccccc1C=NC(c2ccccc2)N=Cc3ccccc3ECOSAR Class Definition: Substituted Ureas
The Substituted Ureas class is ident ified by the following structure:



## N O

N R 1



## R 2 

## R 4 

## R 3

In the current ECOSAR program, the Subs tituted Ureas struct ure must meet the following criteria:
R1 and R2 can be either a hydrogen or oxygen atom or alkyl, olefinic, acetylenic or aromatic carbon atoms, but at least one attachment mu st be to a carbon atom.
R3 and R4 can be anything except a carbonyl group.
If R3 or R4 contain a carbonyl group, then EC OSAR will identify the class as carbonyl ureas. SMILES String Identifications: NC(=O)N

... (attachments as defined above)

Example Substituted Ureas:

CAS No. Name SMILES Notation 330-54-1 Diuron O=C(N( C)C)Nc(ccc(c1Cl)Cl)c1 18691-97-9 Methabenzthiazuron CNC(=O)N(C)c2nc1ccccc1s2Sulfonyl Ureas The Sulfonyl Ureas class is ident ified by the following structure:

R1 and R2 - can be anything (no exclusions) In the current ECOSAR program, the Sulfony l Urea structure must meet the following criteria: (1) A sulfone group [S(=O)(=O)] is attac hed to the nitrogen atom of a urea function [NC(=O)N]. (2) The urea nitrogens or the sulf one group can have other attachments (no exclusions). SMILES String Identifications : NC(=O)NS(=O)(=O)

... (attachments as defined above)

Associated ECOSAR Class(s) :
Amides - the ECOSAR Amides class is a gener al class having a CC(=O)N, NC(=O)N or S(=O)N group that occurs in other ECOSAR classes. In general, the Amides class is reported by ECOSAR in addition to the ot her classes (such as Sulfonyl Ureas). The Vinyl/Allyl Sulfones class contains the -S(=O)(=O)- function which is the only other ECOSAR class containing the sulfone group.

Example Sulfonyl Ureas:

CAS No. Name SMILES Notation 82097-50-5 Triasulfuron ClCCOc1ccc cc1S(=O)(=O)NC(=O) Nc2nc(OC)nc(C)n2 74223-64-6 Metsulfuron-methyl COC(=O)c 1ccccc1S(=O)(=O)NC(= O)Nc2nc(OC)nc(C)n2 64902-72-3 Chlorsulfuron n1c(OC)nc (C)nc1NC(=O)NS(=O)(=O)c2ccccc2Cl 122931-48-0 Rimsulfuron CCS(=O)(=O)c1cccn c1S(=O)(=O)NC(=O)N c2nc(OC)cc(OC)n2ECOSAR Class Definition: Thiazolidinones / Benzothiazolidinones
The Thiazolidinone class is identif ied by the follo wing structures:

N S C O

N S C S N S C O

N S C S

In the current ECOSAR program, the Th iazolidinone structure meets the following criteria: (1) a five-member ring containing one carbonyl (or thiocarbonyl) attached to one aliphatic sulfur and one aliphatic nitrogen. The two carbon atoms in the ring can be either alkyl carbons or two arom atic carbons of a fused-ring. (2) The atoms in the thiazolidinone ring ca n have other attachments (no exclusions).
Notations: Currently, the thiazolidinone ring cannot contain two olefinic carbons with a double bond in place of the aromat ic carbons or alkyl carbons. SMILES String Identifications : O=C1SCCN1 S=C1SCCN1 In conjunction with a fused aromatic ring : O=C1Sc2ccccc2N1 S=C1Sc2ccccc2N1

Associated ECOSAR Class(s) :
Thiocarbamates & Dithiocarbamates - the order of the car bonyl (or thiocarbonyl) with attached sulfur and nitrogen is additionally cl assified by ECOSAR as one of these classes.
The Isothiazolone class ring also contains a car bonyl, one sulfur, one nitrogen and two carbon atoms, but in a different order.

Example Thiazolidinones / Benzothiazolidinones:

CAS No. Name SMILES Notation 25059-80-7 Benazolin-ethyl CC OC(=O)CN1C(=O) Sc2cccc(Cl)c12 96-53-7 2-Thiazolidinethione N(C(=S)SC1)C1 1908-87-8 2-Thiazolidinethione, 3-methyl- N(C(SC1)=S)(C1)C 2682-49-7 2-Thiazolidinone N1CCSC1=OECOSAR Class Definition: Thiazolidinones - Acids
The Thiazolidinones-Acid class is ident ified by the following structures:

N S C O

N S C S N S C O

N S C S



### + Acid Group

This class is identical to the Thiazolidi none-Benzothiazolidinone class with the addition of an acid function. In the current ECOSAR program, the Thiazo lidinone-Acid structur e meets the following criteria: (1) a five-member ring containing one carbonyl (or thiocarbonyl) attached to one aliphatic sulfur and one aliphatic nitrogen. The two carbon atoms in the ring can be either alkyl carbons or two arom atic carbons of a fused-ring. (2) an Acid group (carboxylic acid, sulfonic acid, phosphonic acid) exists anywhere in the structure. (3) The atoms in the thiazolidinone ring ca n have other attachments (no exclusions).
Notations: Currently, the thiazolidinone ring cannot contain two olefinic carbons with a double bond in place of the aromat ic carbons or alkyl carbons. SMILES String Identifications : O=C1SCCN1 S=C1SCCN1 In conjunction with a fused aromatic ring : O=C1Sc2ccccc2N1 S=C1Sc2ccccc2N1 Plus - an Acid group : Carboxylic Acid: C(=O)O ... equivalent to : C(=O)OH or C(=O)O[H] Phosphoric Acid: P(=O)(O) ... equivalent to : P(=O)(OH)OH Sulfonic Acid: S(=O)(=O)O ... equivalent to : S(=O)(=O)OH

Associated ECOSAR Class(s) :
Thiocarbamates & Dithiocarbamates - the order of the car bonyl (or thiocarbonyl) with attached sulfur and nitrogen is additionally cl assified by ECOSAR as one of these classes. Example Thiazolidinones / Benzothiazolidinones:

CAS No. Name SMILES Notation 3813-05-6 Benazalox (Metizolin) OC(=O)CN1C(=O) Sc2cccc(Cl)c12ECOSAR Class Definition: Thiocarbamate,Di (Free Acid) The Thiocarbamate,Di (Free Acid) class is identified by the following structures:



### N H 2 

### C S S R N C SH S R N H 2 

### C SH S

R - can be anything (no exclusions) In the current ECOSAR program, the Thio carbamate,Di (Free Acid) class meets the following criteria: (1) the core dithiocarbamate structure [N-C(=S)-S] occurs in the structure. (2) either (or both) the nitrogen or sulfur exists as free acid in the form of -NH2 or -SH. SMILES String Identifications : NC(=S)S ... equivalent to : [NH2]C(=S)S or N(H)(H)C(=S)S NC(=S)S ... equivalent to : NC(=S)SH or NC(=S)S[H] NC(=S)S ... equivalent to : [NH2]C(=S)SH or N(H)(H)C(=S)SH

... (attachments as defined above)

Associated ECOSAR Class(s) : Thiocarbamate, Di (Substituted) - both of the free acids are substituted.

Example Thiocarbamate,Di (Free Acid):

CAS No. Name SMILES Notation 29596-83-6 Acetic acid, [(aminothi oxomethyl)thio]- S=C(SCC(=O)O)N 99-00-3 Picadex N1CCN(C(=S)S)CC1 12656-69-8 Dithane SC(=S)NCCNC(S)=SECOSAR Class Definition: Thiocarbamate,Di (Substituted) The Thiocarbamate,Di (Substituted) class is identified by the following structures:



## N C S S R R

R - can be anything except hydrogen attached to the sulfur or two hydrogens (H2) attached the nitrogen. In the current ECOSAR program, the Thioca rbamate,Di (Substituted) class meets the following criteria: (1) the core dithiocarbamate structure [N-C(=S)-S] occurs in the structure. (2) both the nitrogen or sulfur have a hydr ogen substitution (excluding both as free acids). SMILES String Identifications : NC(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Thiocarbamate, Di (Free Acids) - either (or both) the nitrogen or sulfur exists as free acid in the form of -NH2 or -SH. Example Thiocarbamate,Di (Substituted):

CAS No. Name SMILES Notation 137-26-8 Thioperoxydicarbonic diamide,tetr amethyl- N(C(=S)SSC(N(C)C)=S)(C)C 95-06-7 Sulfallate CCN(CC)C(=S)SCC(Cl)=C 96-53-7 2-Thiazolidinethione N(C(=S)SC1)C1 533-74-4 Dazomet N(CSC(N1C)=S)(C1)CECOSAR Class Definition: Thiocarbamates, Mono The Thiocarbamates, Mono class is ident ified by the follo wing structures:



## N C S O R1 R2 N C O S R1 R3

R1 - can be anything except H2 (t wo hydrogens off the nitrogen).
R2 - can be anything (including hydrogen).
R3 - can be anything except hydrogen In the current ECOSAR program, the Thiocar bamates, Mono class meet s the criteria as shown in the structure above. SMILES String Identifications : NC(=O)S NC(=S)O

... (attachments as defined above)

Associated ECOSAR Class(s) : Vinyl/Allyl Thiocarbamates - if the R3 substituent is viny l (-C=C) or allyl (-CC=C) group, ECOSAR will identify the st ructure as both Thiocarbamates, Mono and Vinyl/Allyl Thiocarbamates and report both classes. ECOSAR includes a variety of Di-Th iocarbamate ester classes.

Example Thiocarbamates, Mono:

CAS No. Name SMILES Notation 759-94-4 Eptam (EPTC) O=C(N(CCC)CCC)SCC 1114-71-2 Pebulate CCCCN(CC)C(=O)SCCC 2303-16-4 Diallate CC(C)N (C(C)C)C(=O) SCC(Cl)=CCl 42116-76-7 Carnidazole Cc1n cc(N(=O)(=O))n 1CCNC(=S)OC 88678-67-5 Pyributicarb n1c(OC)cccc1 N(C)C(=S)Oc2cc(C (C)(C)C)ccc2ECOSAR Class Definition: Thiocyanates/Isothiocyanates The Thiocyanates/Isothiocyanates class is identified by the following structure:



## R - N = C = S R S C N

R - can be aliphatic, alicyclic, arom atic, or hetercyclic, but not hydrogen. SMILES String Identifications : N=C=S N#CS Associated ECOSAR Class(s) : Isocyanates - the thiocyanate sulfur is replaced by an oxygen (R-N=C=O)

Example Thiocyanates/Isothiocyanates:

CAS No. Name SMILES Notation 57-06-7 Allyl isothiocyanate C=CCN=C=S 556-61-6 Methyl isothiocyanate CN=C=S 103-72-0 Phenyl isothiocyanate c1ccccc1N=C=S 6317-18-6 Methylene bis(thiocyanate) N#CSCSC#NECOSAR Class Definition: Thiols and Mercaptans The Thiols and Mercaptans class is i dentified by the fo llowing structure:



### Aliphatic Carbon SH

Aromatic Carbon SH SH SH (example)

(example)

In the current ECOSAR program, the Thiol-Me rcaptan structure must meet the following criteria: (1) A thiol-mercaptan function (-SH) is a ttached to an alkyl, olefinic, acetylenic or aromatic carbon atom. SMILES String Identifications : SC ... equivalent to : HSC or [H]SC SC=C ... equivalent to : HSC=C or [H]SC=C SC#C ... equivalent to : HSC#C or [H]SC#C Sc1ccccc1 ... equivalent to : HSc1ccccc1 or [H]Sc1ccccc1

Associated ECOSAR Class(s) : None specifically.

Example Thiols and Mercaptans:

CAS No. Name SMILES Notation 74-93-1 Methanethiol SC 111-31-9 1-Hexanethiol SCCCCCC 68-11-1 Mercapto acetic acid O=C(O)CS 1455-21-6 1-Nonanethiol SCCCCCCCCC 5331-91-9 Chloro-2-mercaptobenzothiazole S(C(S)=N1)c(ccc2Cl)c1c2ECOSAR Class Definition: Thiomethacrylates The Thiomethacrylates class is identified by the following structures:



### C C S O

C R1 CH 3 

### C C {O,S} S

C R1 CH 3

R1 - attachment must be either an alkyl carbon, olefinic carbon, acetylenic carbon or aromatic carbon. {O,S} - can be either oxygen (-O-) or sulfur (-S-) Internally, the ECOSAR progr am initially detects a carb onyl function [C(=O)] or a thiocarbonyl function [C(=S)] with one olefin ic attachment and one oxygen or sulfur attachment. The olefinic carbon attac hed to the carbonyl (or thiocarbonyl) must have a methyl (CH3) attachment (anything other than a methyl group (CH3) changes the classification from a possible Thiomethacryla te to a possible Acrylate. The oxygen or sulfur must have either an alkyl carbon, olef inic carbon, acetylenic carbon or aromatic carbon attachment to be classified as ei ther a Thiomethacrylate or Acrylate. SMILES String Identifications : C=C(C)C(=O)S ... equivalent to : C=C(C(H)(H)H)C(=O)S or C=C([CH3])C(=S)S

.... Note : ECOSAR converts a SMILES entry of [ CH3] to C(H)(H)(H), then C only C=C(C)C(=S)O C=C(C)C(=S)S

... (attachments as defined above)

Associated ECOSAR Class(s) : Methacrylates are a class separate from either Thiomethacrylates or Acrylates

. Structures classified as Thiomethacrylates are also classified as Methacrylates. In addition, ECOSAR will classi fy Thiomethacrylates having the thiocarbonyl function [C(=S)] as Esters. Example Thiomethacrylates:

CAS No. Name SMILES Notation O-Methyl thiomethac rylate C=C(C)C(=S)OC S-Methyl thiomethac rylate C=C(C)C(=O)SC Methyl dithiomethacrylate C=C(C)C(=S)SCThiophenes The Thiophenes class is identified by t he occurrence following ring structure:



# S

ECOSAR identifies a Th iophene ring as follows: (1) a five-atom-member ring consisting of one sulfur atom and four carbon atoms (2) the ring is an aromatic ring; the SMIL ES designation for an unsubstituted ring is s1cccc1 ... if the SMILES entry into ECOSAR is S1C=CC=C1, it will be converted into s1cccc1 ... ECOSAR identifies the aromatic ring as a Thiophene (3) the Thiophene ring cannot be part of an aromatic fused-ring system (such as benzothiophene) ... the Thiophene ring can be fused to an aliphatic ring. SMILES String Identifications : s1cccc1 S1C=CC=C1

Associated ECOSAR Class(s) : None

Example Thiophenes:

CAS No. Name SMILES Notation 110

‐ 02

‐ 1 Thiophene S1C=CC=C1 [or] s1cccc1 872

‐ 31

‐ 1 3

‐ Bromothiophene C1=CC(Br)=CS1 554

‐ 14

‐ 3 2

‐ Methythiophene C1=C(C)SC=C1ECOSAR Class Definition: Thiophthalimides The Thiophthalimides class is iden tified by the following structure:

Substitutions can be anything (no exclusions). In the current ECOSAR program, the thiopht halimides structure contains a benzene ring bound to a 5-membered ring containing an aliphat ic nitrogen bound to a sulfur atom and surround by two carbonyl [C(=O)] groups (as depicted above). SMILES String Identifications: Thiophthalimides Group : C1cccc2c1C(=O)N(SC)C2=O

Associated ECOSAR Class(s): Imides - identified by C(=O)-N-C(=O).

Example Thiophthalimides:

CAS No. Name SMILES Notation
133-06-2 Captan O=C(N(SC(Cl)(Cl)Cl)C(=O)C1CC=CC2)C 12 133-07-3 Folpet O=C(N(SC(Cl)(Cl)Cl)C(=O)c1cccc2)c12
2939-80-2 Captafol O=C1N(C(=O)C2C1CC=CC2)SC(C(Cl)Cl) (Cl)ClECOSAR Class Definition: Thiotetrazoles
The Thiotetrazoles class is ident ified by the follo wing structures:



## N H

N N N S R S N

N N N

R - attachment to the sulfur can be anything in current ECOSAR program. In the current ECOSAR program, the Thiote trazole structure ident ification meets the following criteria: (1) The ECOSAR program looks for two aromatic rings with the following characteristics: (a) a five-member aromat ic ring containing one carbon atom (with an aliphatic sulfur attachment) and four nitrogen atoms (a tetraz ole ring) or (b) a fivemember aromatic ring containing one su lfur atom and four nitrogen atoms. (2) The [nH] in the tetrazole ring can hav e the hydrogen atom attachment replaced by another atom. (3) The tetrazole or thiotetrazole ring can be fused to additional aromatic ring(s). SMILES String Identifications : Sc1nnnn1 Sc1nnn[nH]1 SC1=NN=NN1 s1nnnn1 S1N=NN=N1

Associated ECOSAR Class(s) : None specifically. However, ECOSAR includes other “ring structure” classes such as Triazines, Imidazoles, Triazoles (Non-Fuse d), Triazole Pyrimidines and Thiazole, Benzo.

Examples Thiotetrazoles:

CAS No. Name SMILES Notation

56610-79-8 1H-Tetrazole, 1-methyl-5- [(phenylmethyl)thio]- c1 ccccc1CSC2=NN=NN2C

133088-69-4 1H-Tetrazole, 5-(hexylsulfinyl)-1-(4- nitrophenyl)- CCCCCCS(=O)C1= NN=NN1c2ccc(N(=O)=O)cc2ECOSAR Class Definition: Thioureas
The Thioureas class is identifi ed by the following structure:



## C S

N N R2 R1

R1 and R2 - can be anything (no exclusions) In the current ECOSAR program, the Thi ourea structure must meet the following criteria: (1) A thiocarbonyl function [-C(=S)-] is atta ched to two aliphatic ni trogen atoms. If the thiocarbonyl is attached an aromatic nitrogen (such as a nitrogen in a pyrrole ring), the structure will not be classified as a Thiourea. (2) The nitrogen atoms can have other attachments (no exclusions). SMILES String Identifications : NC(=S)N

... (attachments as defined above)

Associated ECOSAR Class(s) : None specifically. Other urea classes (e.g. Substituted Ureas or Sufonyl Ureas) pertain to a carbonyl [C(=O)] urea as compared to the thioca rbonyl [C(=S)] urea of this class.

Example Thioureas:

62-56-6 Thiourea NC(=S)N 534-13-4 Thiourea, N,N'-d imethyl- N(C(=S)NC)C 5217-47-0 1,3-Diethyl-thiobarbituric acid O=C(N(C(N(C1 =O)CC)=S)CC)C1ECOSAR Class Definition: Triazines, Aliphatic The Triazines, Aliphatic class is identif ied by the following example structures:



## N N N

In the current ECOSAR program, the Triazine, Aliphatic structure is a six-member ring containing three aliphatic carbon atoms (car bonyls are not included) and three aliphatic nitrogen atoms in t he sim position . SMILES String Identifications: N1CNCNC1
Associated ECOSAR Class(s): Triazines, Aromatic- a six-me mber aromatic ring containi ng three aromatic nitrogen atoms and three aromatic car bon atoms or one aromatic ca rbon with two carbonyls or two aromatic carbons with one carbonyl Aliphatic Amines – defined in ECOSAR as any primary, secondary or tertiary aliphatic amine group. Since the Aliphatic Triazine cl ass does not take precedence over aliphatic amines, both classes are reported in ECOS AR for these chemicals – though aliphatic triazines yield higher toxicity profiles. Example Triazines:

CAS No. Name SMILES Notation 100-97-0 Hexamethylenetetrami ne N(CN(CN1CN23)C3)(C1)C2

7779-27-3 1,3,5-Triazine, 1,3,5- triethylhexahydro- N(CN(CN1CC)CC)(C1)CCECOSAR Class Definition: Triazines, Aromatic The Triazines, Aromatic class is identif ied by the following example structures:
Structure 1 Structure 2 Struct ure 3 Structure 4

N N

N R

R R

N N N O

R R

N N N O

R O

N N N O O

O

Triazine, aromatics consists of a six-memb er aromatic ring cont aining three aromatic nitrogen atoms in the sim-positio n in addition to either; 1) Three aromatic carbon atom s, 2) two aromatic carbons with one carbonyl; 3) one aromatic carbon with two carbonyls; or 4) three carbonyl groups (as shown above).
R can be anything except three prim ary or secondary nitrogen atoms.
If all R groups are primary or secondary ni trogen atoms, ECOSAR will identify the class as Melamine In structure 3 and 4 represented above containi ng at least 2 carbonyls, if there is a chlorine atom attached to the nitrogen between two carbonyls, the class will be identified at haloimides [( C(=O)NC(=O)] which present s higher toxicity concern presumably due to the presence of the halo gen based on analysis of similar chemicals. SMILES String Identifications: n1cnc(=O)nc1=O n1cncnc1 n1cnc(=O)nc1 n1c(=O)nc(=O)nc1=O
Example Triazines, Aromatic:

CAS No. Name SMILES Notation 101-05-3 Anilazine Clc2nc(Cl)nc(Nc1ccccc1Cl)n2 122-34-9 Simazine n(c(nc(n1)NCC)NCC)c1Cl 1912-24-9 Atrazine n(c( nc(n1)NC(C)C)NCC)c1ClECOSAR Class Definition: Tria zole Pyrimidines Sulfonamides Formerly refered to as the Triazole Pyri midines class, the Tr iazole Pyrimidine Sulfonamides class is entirely composed of chemicals with the following identifying structures:



## N N N

N S N O

O
The class was updated to include the CNS(=O )(=O) fragment since the entire training set for the class (which is a class of pes ticides) included this as part of the base fragment. Searches for toxicity patte rns for the former base fragm ent (c1nn2c(n1)ccnc2) yielded no results on toxicity profiles. It is suspec ted that due to the arom atic nature of the backbone this fragment alone would present mi nimal toxicity, unless substituted with reactive functional groups. In the current ECOSAR program, the Triazole Pyrimidines Sulfonamide is a sulfonamide bound to two fused aromatic rings (as depicted above) with the followin g characteristics: (a) a five-member aromatic ring containi ng two carbon atoms and three nitrogen atoms (a triazole ring), (b) a six-member aromat ic ring containing four carbon atoms and two nitrogen atoms, and (c) both rings contain one or more fused carbon atoms (meaning each ring is fused to another aromatic ring).
ALERT: Chemicals containing the large molecu lar fragment for triazole pyrimidine sulfonamides are likely designed to act as herbicides. If the query compound contains this structural fragment, it is likely to be most closely relate d to the training set chemicals in the triazole pyrimidine sulf onamides class – irrespective of the other classes reported. SMILES String Identifications: CNS(=O)(=O)c1nn2c(n1)ccnc2

Associated ECOSAR Class(s): Other ECOSAR classes containing a fused triazole ring: Benzotriazoles - a 1,2,3-triazole ring fused to another aromatic ring ECOSAR classes containing a non-fused triazole ring: Triazoles (Non-Fused) - a structure containing either a 1,2,4-triazole , 1,2,3-triazole or 1,3,4-triazole ring t hat is not fused to another aromatic ring. Examples Triazole Pyrimidines:

CAS No. Name SMILES Notation

145701-21-9 Diclosulam c1(n2c(cc(n1)F)nc(n2)S( =O)(=O)Nc1c(cccc1Cl)Cl)O CC 98967-40-9 Flumetsulam Fc1cccc(F) c1NS(=O)(=O)c2nc3nc(C)ccn3n2ECOSAR Class Definition: Triazoles (Non-Fused) The Triazoles (Non-Fused) class is i dentified by the following structures:



### N

N N N

N N N

N N

In the current ECOSAR program, the Triazo les (Non-Fused) structure identification meets the follo wing criteria: (1) The ECOSAR program identifies a five -member aromatic ring containing two carbon atoms and three nitrogen atoms (a triazole ring). (2) The position of the ni trogen atoms in the ring does not matter. The ring can be either 1,2,4-triazole, 1,2,3- triazole or 1,3,4-triazole. (3) The triazole ring cannot be fused to additional aromatic ring(s). SMILES String Identifications : n1cncn1 ... equivalent to : [nH]1cncn1 n1ccnn1 ... equivalent to : [nH]1ccnn1 n1cnnc1 ... equivalent to : [nH]1cnnc1 N1C=NC=N1 N1C=CN=N1 N1C=NN=C1

Associated ECOSAR Class(s) : None specific to a non-fused triazole ring. Other ECOSAR classes containing a fused triazole ring:
Benzotriazoles - a 1,2,3-triazole ring fu sed to another aromatic ring Triazole Pyrimidines - a triazole-pyrimidine fused ring structure

Examples Triazoles (Non-Fused):

CAS No. Name SMILES Notation 288-88-0 1H-1,2,4-Triazole n1ncnc1 76674-21-0 Flutriafol n1cncn1 CC(O)(c2ccc(F)cc2)c3ccccc3F 43121-43-3 Triadimefon CC(C)(C) C(=O)C(Oc1ccc(Cl)cc1)n2cncn2 83657-22-1 Uniconazole c1ncnn1C(C(O)C(C)(C)C)=Cc2ccc(Cl)cc2 79983-71-4 Hexaconazole Clc2c( ccc(c2)Cl)C(Cn1ncnc1)(O)CCCC 85509-19-9 Flusilazole c1cc(F) ccc1[Si](C)(c2ccc(F)cc2)Cn3ncnc3ECOSAR Class Definition: Vinyl/Allyl Alcohols The Vinyl/Allyl Alcohols class is i dentified by the following structures:



## C C OH C C C OH

In the current ECOSAR program, the Vinyl/A llyl Alcohols structur e meets the following criteria: (1) A hydroxy group (-OH) is attached to a vi nyl group (-C=C) or allyl group (-C-C=C). The single-bonded carbon on the allyl group is an alkyl carbon. SMILES String Identifications : C=CO ... equivalent to : C=COH or C=CO[H] C=CCO ... equivalent to : C=CCOH or C=CCO[H]

Associated ECOSAR Class(s) : None specifically. ECOSAR includes a variety of alcohol clas ses (such as Propargyl Alcohols, Benzyl Alcohols, Nitro Alcohols) and Vinyl/Allyl classes.

Example Vinyl/Allyl Alcohols:

CAS No. Name SMILES Notation 107-18-6 Allyl alcohol C=CCO 924-41-4 1,5-Hexadien-3-ol OC(CC=C)C=C 4798-44-1 1-Hexen-3-ol OC(C=C)CCC 66-76-2 Dicumarol O=C1Oc2ccccc2C(O)=C1CC3=C(O)c4ccccc4OC3=O 50-81-7 L-Ascorbic acid O1C(=O)C(O)=C(O)C1C(O)CO 557-75-5 Vinyl alcohol C=COECOSAR Class Definition: Vinyl/Allyl Aldehydes The Vinyl/Allyl Aldehydes class is i dentified by the following structures:



## H C C O C H C C O C C H C C O C

The Vinyl/Allyl Aldehyde class is identif ied when an aldehyde gr oup (HC(=O)-) is attached to a vinyl (C=C), allyl (-C -C=C) or acetylenic (-C#C) group. In the current ECOSAR program, if a stru cture contains more than one Vinyl/Allyll Aldehyde group (or one Vinyl/Allyl Aldehyde group plus additional Aldehyde functional groups), the structure will be classified as both Vinyl/Allyl Aldehydes and Aldehydes (Poly). Structures classified as Vinyl/Allyl Aldehydes are not classified as Aldehydes (Mono). SMILES String Identifications : O=CC=C ... equivalent to : O=C(H)C=C O=CCC=C ... equivalent to : O=C(H)CC=C O=CC#C ... equivalent to : O=C(H)C#C

Associated ECOSAR Class(s) : Aldehydes (Mono) - If the attachment to the aldehyde group (HC(=O)-) is an alkyl carbon, aromatic carbon, carbonyl or hydr ogen, the structure will be classified as an Aldehyde (Mono) Aldehydes (Poly) - the structure must contain two or more aldehyde functional groups. In the current ECOSAR program, a structur e can be classified as both Aldehydes (Poly) and Vinyl/Allyl Aldehydes.

Example Vinyl/Allyl Aldehydes:

CAS No. Name SMILES Notation 107-02-8 Acrolein [or 2-Propenal] O=CC=C 5392-40-5 2,6-Octadienal, 3,7-di methyl- O=CC=C(CCC=C(C)C)C 6203-18-5 4-Dimethylaminocinnamal dehyde O=CC=Cc(ccc(N(C)C)c1)c1 7319-38-2 3-Butenal O=CCC=CECOSAR Class Definition: Vinyl/Allyl Esters The Vinyl/Allyl Esters class is i dentified by the following structures:



### C C O O Vinyl or Allyl



### C C S O Vinyl or Allyl 

### C C O S Vinyl or Allyl



### C C S S Vinyl or Allyl 

### O C O O Vinyl or Allyl



### S C S S Vinyl or Allyl

Vinyl/Allyl - Vinyl (-C=C) and Allyl (-C-C=C) In the current ECOSAR program, the Vinyl/A llyl Esters class meet s the criteria as shown in the structur e above and the following: (1) the carbon atom (to which t he carbonyl or thiocarbonyl is attached) must be an alkyl, olefinic, acetylenic or aromatic carbon. (2) carbonate and thiocarbonate esters can also be identified as Vinyl/Allyl Esters.

SMILES String Identifications : CC(=O)OC=C CC(=O)OCC=C CC(=S)OC=C CC(=S)OCC=C CC(=O)SC=C CC(=O)SCC=C CC(=S)SC=C CC(=S)SCC=C COC(=O)OC=C COC(=O)OCC=C

Associated ECOSAR Class(s) :
Esters - the Esters class includes a wide variety of organic ester types including various phosphorus esters. Currently, ECOSAR is pr ogrammed to include the Ester class when the Vinyl/Allyl Esters class is reported.

Example Vinyl/Allyl Esters:

CAS No. Name SMILES Notation 105-38-4 Vinyl propionate O=C(OC=C)CC 123-20-6 Vinyl butyrate CCCC(=O)OC=C 123-68-2 Allyl caproa te O=C(OCC=C)CCCCCECOSAR Class Definition: Vinyl/Allyl Ethers The Vinyl/Allyl Ethers class is iden tified by the following structures:



## C O C C C O C C C

The ether function is identified as an ali phatic oxygen attached to two carbons atoms (alkyl, olefinic, acetylenic or aromatic carbon). In the current ECOSAR program, the Vinyl/ Allyl Ether structur e meets the following criteria: (1) one (or both) sides of t he ether function is a vinyl (-C=C) or allyl (-C-C=C) group. SMILES String Identifications : COC=C COCC=C C=COC=C C=COCC=C C#COC=C C#COCC=C c1ccccc1OC=C c1ccccc1OCC=C

Associated ECOSAR Class(s) : None specifically.
The ether function also occurs in the Halo Ether class.

Example Vinyl/Allyl Ethers:

CAS No. Name SMILES Notation 107-25-5 Methyl vinyl ether COC=C 557-40-4 Allyl ether O(CC=C)CC=C 83-79-4 Rotenone COc5cc4OCC3Oc2c1 CC(Oc1ccc2C(=O)C3c4cc5OC)C(C)=C 57-24-9 Strychnidin-10-one O=C(N(c(c(C1(C(N (C2)CC(C3C4C5OC6)=C6)C3)C2)ccc7)c7)C14)C5ECOSAR Class Definition: Vinyl/Allyl Halides The Vinyl/Allyl Halides class is id entified by the following structures:



## C C {Br,Cl,I} C C C {Br,Cl,I} C C {Br,Cl,I}

In the current ECOSAR program, the Vinyl/ Allyl Halides struct ure must meet the following criteria: (1) A halogen atom (bromine, chlorine or iodine; fluorine excluded) is attached to a vinyl group (-C=C), allyl group (-C-C=C) or ac etylenic group (-C#C). The single-bonded carbon on the allyl group is an alkyl carbon.
Notation: Fluorine has been excluded from this cla ss. In addition, the acetylenic group (which was included in the original program code) is still included. SMILES String Identifications : C=CBr or C=CCl or C=CI C=CCBr or C=CCCl or C=CCI C#CBr or C#CCl or C#CI

Associated ECOSAR Class(s) : Propargyl Halides - Vinyl/Allyl Halides identified with the acetylenic group (-C#C) are additionally classified as Pr opargyl Halides by ECOSAR. ECOSAR includes a variety of Vinyl/A llyl classes and Halo-Halide classes.

Example Vinyl/Allyl Halides:

CAS No. Name SMILES Notation 107-05-1 Allyl Chloride C=CCCl 79-01-6 Trichloroethy lene C(=CCl)(Cl)Cl 591-97-9 2-Butene, 1-chloro- C(=CC)CCl 78-88-6 1-Propene, 2,3-dichloro- C(=C)(CCl)Cl 127-18-4 Tetrachloroethyl ene C(=C(Cl)Cl)(Cl)ClECOSAR Class Definition: Vinyl/Allyl Ketones Vinyl/Allyl Ketones are identifi ed by the following structures:



## C C C O

C C O

C

To be classified as Vinyl/Allyl Ketones by the current ECOSAR pr ogram, the structure must meet the fo llowing criteria: (1) The basic ketone fragment is identified as carbonyl group attached to carbon atoms on both sides where the carbon atoms must be an alkyl, olefinic, acetylenic or aromatic carbon. To be classified as Vinyl/Allyl, one or both attachments to the carbonyl must be a vinyl group (-C=C) or an allyl group (-C-C=C). (2) The vinyl/allyl ketone fragment can be either cyclic or acyclic. SMILES String Identifications : CC(=O)C=C CC(=O)CC=C C=CC(=O)C=C C=CC(=O)CC=C C#CC(=O)C=C C#CC(=O)CC=C c1ccccc1C(=O)C=C c1ccccc1C(=O)CC=C
Associated ECOSAR Class(s) : In addition to the Vinyl/Allyl Ketones class, the ECOSAR program will add any of the classes below to the to the program output if identified in a structure.
Diketones - Diketones have two ketone functions at 1,3-positions. A structure can be classified as both Diketones and Vinyl/Allyl Ketones (e.g. SMILES: C=CC(=O)CC(=O)C). Benzyl Ketones - a ketone with -C-aromatic ri ng attachment to the carbonyl
Halo Ketones (2 Free H) - a ketone with a -CH2-Hal ogen attachment to a carbon atom at the alpha- or beta-pos ition to the carbonyl
Halo Ketones (0-1 Free H) - a ketone with a -CH- Halogen (or -C-Halogen) attachment to a carbon atom at the alpha- or beta-position to the carbonyl Example Vinyl/Allyl Ketones:

CAS No. Name SMILES Notation 78-94-4 Vinyl methyl ketone C=CC(=O)C 78-59-1 Isophorone O=C(C=C(CC1(C)C)C)C1 141-79-7 Mesityl oxide O=C(C=C(C)C)CECOSAR Class Definition: Vinyl/Allyl Nitriles The Vinyl/Allyl Nitriles class is id entified by the following structures:



## C N C N

In the current ECOSAR program, the Vinyl/A llyl Nitrile structure must meet one of the following criteria: (1) A nitrile group (carbon triple-bonded to ni trogen; SMILES of C#N) is attached to a vinyl group (-C=C) or an allyl group (-C-C=C). (2) Two or more nitrile groups at tached to the same alkyl carbon. SMILES String Identifications : C=CC#N C=CCC#N

Associated ECOSAR Class(s) : Nitriles, Polyaliphatic - Two or more nitrile groups are attached to aliphatic atoms in the whole structure. When two or more nitrile groups are attached to the same alkyl or olefinic carbon, the structur e will be classified as both Viny l/Allyl Nitriles and Nitriles, Polyaliphatic.

Other SAR Nitrile classes include: Azonitriles, Halo Nitriles, Nitrile Esters, Nitrile AlphaOH, and Phthalonitriles.

Example Vinyl/Allyl Nitriles:

CAS No. Name SMILES Notation 109-75-1 Allyl cyanide N#CCC=C 107-13-1 2-Propenenitrile N#CC=CVinyl/Allyl Pyrazoles/Pyrroles The Vinyl/Allyl Pyrazoles/Pyrroles class is identified by the following structures:



### N R N N R

R = -C=C (vinyl) or –CC=C (allyl) In the current ECOSAR program, the Vi nyl/Allyl Pyrazoles/Pyrroles structure identification meets th e following criteria: (1) The ECOSAR program looks for an aromat ic ring with the following characteristics: (a) a five-member aromatic ring containing four carbon at oms and one nitrogen atom (a pyrrole ring) or (b) a five-member aromat ic ring containing th ree carbon atoms and two nitrogen atoms that are adjacent to each other (a pyrazole ring). (2) The [nH] in either the pyrazole ring or pyrrole ring can have the hydrogen atom attachment replaced by another atom. (3) Either ring can be fused to additional aromatic rings. SMILES String Identifications : Pyrrole : C=Cn1cccc1 C=CCn1cccc1 Pyrazole : C=Cn1nccc1 C=CCn1nccc1

Associated ECOSAR Class(s) : Pyrazoles/Pyrroles – A five-membered aromat ic ring containing either one or two nitrogens. Example Vinyl/Allyl Pyrazoles/Pyrroles:

CAS No. Name SMILES Notation 288-13-1 1H-Pyrazole N1N=CC=C1 109-97-7 1H-Pyrrole C1=CC=CN1 122453-73-0 Chlorfenapyr N#Cc1c(Br)c( C(F)(F)F)n(COCC) c1c2ccc(Cl)cc2 71561-11-0 Pyrazoxyfen Clc1cc(Cl)ccc1 C(=O)c2c(C)nn(C)c2 OCC(=O)c 3ccccc3 82692-44-2 Benzofenap c1cc(C)ccc1C(=O) COc2n(C)nc(C)c2C(= O)c3ccc(Cl)c(C)c3ClECOSAR Class Definition: Vinyl/Allyl Sulfones The Vinyl/Allyl Sulfones class is ident ified by the following structures:



### C S C O C C S C O C O C S C O C O C

C S C O C C
In the current ECOSAR program, the Vinyl/A llyl Sulfones structure must meet one of the following criteria: (1) A sulfone group [S(=O)(=O)] is attached to an alkyl, olefinic, acetylenic or aromatic carbon atom and the sulfone group is attached to a vinyl (-C=C) or allyl (-C-C=C) group. (2) A sulfoxide group [-S(=O)- ] is attached to an alkyl, olefinic, acetylenic or aromatic carbon atom and the sulfoxide group is attached to a vinyl (-C=C) or allyl (-C-C=C) group. SMILES String Identifications : C=CS(=O) C C=CCS(=O) C C=CS(=O)(=O) C C=CCS(=O)(=O) C

... (bolded C (carbon atom) can be alkyl (C), olef inic (C=C), acetylenic (C#C) or aromatic (c))

Associated ECOSAR Class(s) : None specifically. The Sulfonyl Ureas class contains the -N-C(=O)-N-S(= O)(=O)- function which is the only other ECOSAR class cont aining the sulfone group.
The Amides class contains a sulfoxide group as in: -N-S(=O)-

Example Vinyl/Allyl Sulfones:

CAS No. Name SMILES Notation 3680-02-2 Methyl vinyl sufone CS(=O)(=O)C=C 16212-05-8 Allyl phenyl sulfone S(=O)(=O)(c1ccccc1)CC=C 77-79-2 Thiophene, 2,5-dihydro-, 1,1-dioxide O=S(=O)(CC=C1)C1