QSARsfor Endocrine Disruption Priority Setting Database 2 The

QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model John D. Walkera *, Hong Fangb, Roger Perkinsb and Weida Tongc a b c TSCA Interagency Testing Committee (ITC), U.S. Environmental Protection Agency (M7401), Washington, DC 20460 Northrop Grumman Information Technology, Jefferson, Arkansas 72079 National Center for Toxicological Research (NCTR), Jefferson, Arkansas 72079 Abstract Version 2 of the Endocrine Disruption Priority Setting Database (EDPSD2) is a decision support tool developed by the U.S. Environmental Protection Agency. EDPSD2 is organized into 4 categories (exposure-related, effectsrelated, combined exposure-and effects-related and specially-targeted priorities) that are supported by several compartments and information sources. The effects-related category includes a Quantitative Structure Activity Relationship compartment that is supported by two models for predicting estrogen receptor binding affinities of chemicals in EDPSD2. This paper describes the categories and compartments of EDPSD2 and the use of the Integrated 4-Phase model to predict the estrogen receptor binding affinities of chemicals in EDPSD2. * To receive all correspondence: Phone: (202) 564-7526, Fax: (202) 564-7528, E-mail: walker.johnd@epa.gov Key words: QSARs, receptor binding, estrogen, EDPSD, Integrated 4-Phase Abbreviations: EDPSD ± Endocrine Disruption Priority Setting Database QSARs RBAs FQPA FIFRA U.S. EPA EDSTAC MDL ISIS SMILES HQSAR ER 2D 3D CAS CoMFA HSDB RTECS\R ATSDR EAFUS AQUIRE ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± Quantitative Structure Activity Relationships receptor binding affinities Food Quality Protection Act Federal Insecticide, Fungicide, and Rodenticide Act U.S. Environmental Protection Agency Endocrine Disruptors Screening and Testing Advisory Committee Molecular Design Limited Information Systems\9 Integrated Scientific Information System Simplified Molecular Input Line Entry System Hologram QSAR estrogen receptor 2 dimensional 3 dimensional Chemical Abstract Service Comparative Molecular Field Analysis Hazardous Substances Data Bank Registry of Toxic Effects of Chemical Substances Agency for Toxic Substances Disease Registry Everything Added to Food in the United States AQUatic toxicity Information REtrieval (AQUIRE) database Terrestrial Toxicity database Organization for Economic Cooperation and Development Screening Information Data Set International Council of Chemical Associations partial least squares 1 Introduction The 1996 Food Quality Protection Act (FQPA, 21 U.S.C. ßß201 ± 415) requires the U.S. Environmental Protection Agency (U.S. EPA) to implement programs for screening and testing of pesticide chemical active ingredients and ™inert∫ formulation ingredients for their ability to disrupt estrogen functions. In response, the U.S. EPA established the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC). The EDSTAC recommended that the U.S. EPA create an Endocrine Disruption Priority Setting Database (EDPSD) as a tool that could be used to assist rapid sorting and priority setting of chemicals for endocrine disruption screening and testing. EDPSD 1 was developed for and demonstrated to EDSTAC at a December 1997 public meeting [1]. Quantitative Structure Activity Relationships (QSARs) were not used for EDPSD1 [2]. Following the development of EDPSD1, the U.S. EPA developed EDPSD2 (http:/www.epa.gov/scipoly/oscpendo/ index.htm). EDPSD2 is a multi-user client/server application developed using Visual Basic 6.0 for the ™front end∫ screens and user interface, Microsoft Access97 for the ™back end∫ database, and Seagate Crystal Reports 7 for the reports (http:/www.erg.com/endocrine). The EDPSD2 QSAR compartment includes two independently-developed QSAR-based models for predicting 1 TERRETOX ± OECD ± SIDS ICCA PLS ± ± ± Quant. Struct.-Act. Relat., 22 (2003) ¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 0931-8771/03/010&-0001 $ 17.50+.50/0 J. D. Walker et al. estrogen receptor binding affinities (RBAs). The purpose of this paper is to discuss: 1) categories and compartments of EDPSD2, and 2) results from using the Integrated 4-Phase model to predict the estrogen RBAs of the 623 chemicals from EDPSD2. 2 Methods The Integrated 4-Phase model was developed at the U.S. Food and Drug Administration×s National Center for Toxicological Research (NCTR) by Drs. Hong Fang, Weida Tong, Roger Perkins and others [3, 4]. The Integrated 4Phase model is composed of four sequential phases (Figure 1). Phase I: Filtering ± Two rejection filters, molecular weight < 94 or > 1000 and no-ring structure, were used to significantly and with high confidence eliminate those chemicals extremely unlikely to bind to an estrogen receptor (ER) [3]. These two filters were validated on $ 2000 chemicals whose ER activities were available from the literature. Phase II: Active/Inactive Assignment ± The chemicals passing through Phase I were assigned as YES/NO for ER binding using three different methods, i.e., structural alerts, pharmacophore searching, and classification models. While structural alerts identify key 2D structural features associated with ER binding, pharmacophore searching identified 3D (3-dimensional) sub-structures important for ER binding. Classification models used pattern recognition to qualitatively categorize chemicals into active and inactive subsets on the basis of their similarity in physicochemical properties. In its current form, this Phase employs 11 models in parallel, 3 structural alerts [3], 7 pharmacophores [4] and 1 classification model [3], which are able to identify both strong and weak estrogens, some of these structures are not similar to estradiol, such as kepones [3]. These 11 models are complementary and were designed to distinguish active from inactive chemicals. Only chemicals identified as inactive by all 11 models were eliminated from further evaluation in Phase III. As would be expected from the application of 11 models, a chemical could be predicted to be active by none, a few, or many of these models. Since each model identifies specific structural attributes associated with activity, the number of models predicting that a chemical is active should tend to increase in direct proportion to its activity. To provide semiquantitative activity data for these 11 models, a consensusranking index was developed to provide a score for a chemical by summing the model×s concordance that predicts the chemical as active. The activities estimated by the consensus-ranking index correlated very well with the NCTR dataset of measured estrogen RBAs. Thus, this index was used to estimate semi-quantitatively the predicted log RBAs values in Phase II. Phase III: Quantitative Predictions ± In this Phase, 3D chemical structure assessments, or identification of bioactive conformers, and molecular alignments were used to develop a Comparative Molecular Field Analysis (CoMFA) model making a more accurate quantitative activity predictions for chemicals that passed Phase II [5]. Both putative bioactive conformers and proper molecular alignment in the model were determined based on the recently published 4 ligands-ER crystal structure. After alignment, the molecules in the training set were placed in a 3D cubic lattice and the steric and electrostatic descriptors at each mesh point were calculated based on the L-J (6 ± 12) and Coulombic potentials, respectively. About 600 descriptors were analyzed using the method of partial least-squares (PLS) regression to derive the CoMFA model. The model had r2 ˆ 0.91 in fitting and q2 ˆ 0.66 in a leave-one-out cross validation, indicating self-consistency and high predictivity. Chemicals with higher predicted binding affinity are given higher priority for further evaluation in Phase IV. The CoMFA model demonstrated good statistical reliability using both internal and external validation. Phase IV: Rule-Based Decision-Making System ± A knowledge-based system can be used to foster definitive decision making and facilitate priority assessments of chemicals with high predicted estrogen RBAs. This involves a multidisciplinary effort that includes computational chemists, toxicologists, and environmental and regulatory scientists from different agencies. The system is useful only after incorporating accumulated human knowledge and expertise (i.e., rules). The following information should be considered in the final decision making: 1. Information gained at each phase of the integrated computational approach. 2. Information on human exposure, environmental fate and other effects, and chemical production volumes. 3. Chemical structure novelty, that is, when a structure is encountered that is dissimilar to all those that have been Quant. Struct.-Act. Relat., 22 (2003) Figure 1. The Integrated 4-Phase Model. 2 QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model used to train and test the models. For example, care should be taken to interpret prediction for chemicals containing metals, etc. Phase IV was not used for this paper. 3 Results The results from using the Integrated 4-Phase model to predict the estrogen RBAs of 623 EDPSD2 chemicals are summarized in Tables 1 and 2. One hundred eighty could not be screened for estrogen RBAs. The remaining 443 could be screened; 156 passed Phase I, but 287 did not (Table 1). The 156 that passed Phase I included 78 that passed Phase II and 78 that did not pass Phase II. Of the 78 that passed phase II, 35 passed Phase III and 43 did not (Table 1) Of the 78 chemicals that passed phase II, 59 had Phase II predicted log RBA ranges <À 2 (Table 2). Of these 59, 39 were predicted to be not active in Phase III (Table 2). Four (4) of the 12 Phase II chemicals that had predicted log RBA ranges of À 1$ 0, were predicted to be not active in Phase III (Table 2). None of the 7 Phase II chemicals that had predicted log RBA ranges > 0, were predicted to be not active in Phase III (Table 2). 4 Discussion 4.1 EDPSD2 The EDPSD2 characterizes the category-compartmentbased approach for priority setting that was recommended by the EDSTAC. Compartment refers to a group of chemicals that share a common source, i.e., common exposure, effects, exposure and effects or a special priority. EDPSD2 is organized into 4 categories: exposure-related, effects-related, combined exposure-and effects-related and specially-targeted priorities (Figure 2). Each category includes several compartments and information sources used to provide data for those compartments. The exposure category is the largest category; it contains 13 compartments and numerous combined and individual information sources (Figure 3). Exposure data are important because chemical exposures have caused adverse effects in the endocrine systems of humans, domestic animals, birds, fish, and wildlife. The exposure information sources represent a variety of media encountered by humans and other species including food, drinking water, surface water, sediment, soil, etc. Exposure-related information, such as persistence in the environment, bioaccumulation potential, release to the environment, and production volume provide an indirect indication of the likelihood of exposure. The effects-related category contains 7 compartments (Figure 4). For these 7 compartments there are 6 information sources (Hazardous Substances Data Bank (HSDB), Registry of Toxic Effects of Chemical Substances (RTECS¾), Agency for Toxic Substances Disease Registry (ATSDR) Toxicological Profiles, Everything Added to Food in the United States (EAFUS), AQUatic toxicity Information REtrieval (AQUIRE) database, Terrestrial Toxicity (TERRETOX) database) and 2 QSARs, the COREPA and the Integrated 4-Phase models (Figure 4). Detailed descriptions and reference sources for HSDB, RTECS¾, ATSDR, EAFUS, AQUIRE and TERRETOX were provided for EDPSD1 for which they were also used as data sources [1]. The combined exposure-and effects-related category is weighted toward identifying those chemicals for which there is both exposure effects related information (Figure 5). The specially-targeted priorities category includes mixtures and naturally-occurring non steroidal estrogens (Figure 6). Mixtures include those substances found in products, the environment, and human tissues and fluids, such as contaminants in human breast milk; phytoestrogens in soy-based infant formula; mixtures of chemicals commonly found at hazardous waste sites; pesticide and fertilizer mixtures; disinfection byproducts; and gasoline. Naturally occurring non-steroidal estrogens Table 2. Number of Phase II EDPSD2 chemicals and Phase III EDPSD2 chemicals associated with Phase II and Phase III predicted log RBA ranges Phase II EDPSD2 chemicals 4 3 12 Phase II predicted log RBA range > 1.0 0.0 $ 1.0 À 1.0 $ 0.0 Phase III EDPSD2 chemicals 3 1 2 1 1 4 3 4 3 5 2 20 1 1 8 19 Phase III predicted log RBA range À 2.0 $À 1.0 À 3.0 $À 2.0 À 3.0 $À 2.0 <À 3.0 À 2.0 $À 1.0 À 3.0 $À 2.0 <À 3.0 Not Active À 2.0 $À 1.0 À 3.0 $À 2.0 <À 3.0 Not Active À 2.0 $À 1.0 À 3.0 $À 2.0 <À 3.0 Not Active Table 1. Number of EDPSD2 chemicals that passed or did not pass Pre-Phase I and Phases I, II and III of the Integrated 4-Phase model Number of EDPSD2 chemicals Total Pre-Phase I Phase I Phase II Phase III 623 443 156 78 Pass 443 156 78 35 Not pass 180 287 78 43 29 <À 3.0 30 À 3.0 $À 2.0 Quant. Struct.-Act. Relat., 22 (2003) 3 J. D. Walker et al. Figure 2. Categories of the Endocrine Disruption Priority Setting Database version 2 (EDPSD 2). Figure 3. Compartments and information sources for the exposure category of the Endocrine Disruption Priority Setting Database version 2 (EDPSD 2). include natural products derived from plants (phytoestrogens) and fungi (mycotoxins). 4.2 Integrated 4-Phase Model Predicitions Binding to the estrogen receptor may be one process in a series of events proceeding through translation and transcription that could result in reproductive or other effects. However, because of the promiscuous nature of estrogen receptors [6] there may be some uncertainty when predicting estrogen RBAs. EDPSD2 chemicals that could not be screened for estrogen RBAs To predict estrogen RBAs, the Integrated 4-Phase QSAR-based model requires that chemicals be assigned SMILES notations [7 ± 9]. There were 180 EDPSD2 chemicals that could not be screened for estrogen RBAs (Table 1). SMILES could not be written for 166 of these EDPSD2 chemicals; the other 14 contained structures or heavy atoms that could not be modeled. Examples of chemicals for which SMILES could not be written included tallow, lard, petroleum resins, turpentine, linseed, corn, soybean, cottonseed, coconut, peanut and castor oils. Quant. Struct.-Act. Relat., 22 (2003) 4 QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model Figure 4. Compartments and information sources for the effects category of the Endocrine Disruption Priority Setting Database version 2 (EDPSD 2). Figure 5. Compartments and information sources for the exposure-effects category of the Endocrine Disruption Priority Setting Database version 2 (EDPSD 2). Phase I EDPSD2 chemicals Of the 443 EDPSD2 chemicals that could be screened by the Integrated 4-Phase model, 156 passed Phase I (Table 1). However, 287 did not pass Phase I because they did not contain a ring structure or had a molecular weight < 94 daltons. Quant. Struct.-Act. Relat., 22 (2003) Phase II EDPSD2 chemicals Of the 156 EDPSD2 chemicals that passed Phase I, 78 passed Phase II (Table 1). Seventy-eight (78) did not pass Phase II because they did not meet any of the requirements for the 3 structural alerts, 7 pharmacophore queries or the 5 J. D. Walker et al. Figure 6. Compartments and information sources for the special priorities category of the Endocrine Disruption Priority Setting Database version 2 (EDPSD 2). classification and regression tree model in Phase II. For the78 that passed Phase II qualitative estrogen RBAs were predicted (Table 2). Phase III EDPSD2 chemicals Thirty-five of the 78 EDPSD2 chemicals that passed Phase II also passed Phase III modeling so quantitative estrogen RBAs predictions could be made (Table 2). Fortythree of the 78 EDPSD2 chemicals that passed Phase II were not active in Phase III (Table 2). Comparison of Phase II and Phase III predicted log RBA ranges For the 29 Phase II EDPSD2 chemicals with predicted log RBAs < À 3, 27 had predicted log RBAs <À 3 or lower in Phase III (Table 2). For the 30 Phase II EDPSD2 chemicals with predicted log RBAs À 3.0 $À 2.0, 27 additional EDPSD2 chemicals had predicted log RBAs À 3.0 $À 2.0 or lower in Phase III. For the remaining 19 Phase II predictions, all of the Phase III predictions were lower than the Phase II predictions. These results suggested that the Phase III predictions were more conservative than the Phase II predictions. These comparisons became more conservative as the Phase II predicted log RBAs increased from À 1.0 $ 0.0 to > 1.0 (Table 2). Comparing predicted estrogen RBAs with experimental data To compare the predicted estrogen RBAs with experimental data, 3 data sources were reviewed: 1) rat estrogen RBA data from Blair et al. [10], 2) E-Screen data from Soto et al. [11, 12], and 3) yeast two-hybrid assay data from Nishihara et al. [13]. The experimental rat estrogen RBA data developed by Blair et al. [10] were developed using the rat uterine cytosol estrogen receptor competitive binding assay. The E-Screen assay was developed to assess the estrogenicity of environmental chemicals using the proliferative effects of estrogens on MCF-7 cells as an endpoint [11, 12]. The Nishihara et al. yeast two-hybrid assay measures ER binding-dependent transcriptional and translational activities [13]. As expected, the experimental rat estrogen RBA data developed by Blair et al. [10] compared most favorably with the Phase III predicted log RBA ranges because these data were used to develop the Integrated 4-phase model (Table 3). Comparisons of experimental rat estrogen RBA data correlated with the E-Screen MCF-7 cell proliferation assay data [11, 12] and the yeast two-hybrid assay data [13], especially for the lower Phase III predicted log RBA ranges (Table 3). These findings suggest that estrogen receptor binding may be related to different levels of biological complexity, e.g., cell proliferation (E-Screen assay) and ER binding-dependent transcriptional and translational activities (yeast two-hybrid assay). Additional comparisons of these assays were described previously [14]. 5 Conclusions Including the QSAR-based Integrated 4-Phase model in EDPSD2 provided opportunities to predict estrogen RBAs. Estrogen RBA predictions from the Integrated 4-Phase model indicated that 50% of the EDPSD2 chemicals that passed Phase I, passed Phase II, but < 50% of those passed Phase III. Of the 35 EDPSD2 chemicals that passed Phase III, 17 had predicted log RBAs <À 3, suggesting their estrogen receptor binding affinity potential was very weak at best. The remaining18 EDPSD2 chemicals that passed Phase III had predicted log RBAs ranging from À 3 to À 1, suggesting that estrogen receptor binding affinity potential was only slightly stronger. Since SMILES, mole files or some other method for describing chemical structures are needed to develop QSARs, some other non-QSAR modeling approach will have to be used to screen the estrogen RBAs of the 166 EDPSD2 chemicals for which SMILES could not be written and the 14 EDPSD2 chemicals that could not be modeled. To provide other investigators with opportunities to measure or predict the RBAs of the 623 EDPSD2 chemicals the Table 3. Comparison of Phase III EDPSD2 chemicals predicted log RBA ranges with experimental data Phase III EDPSD2 chemicals 8 13 14 43 Phase III predicted log RBA range À 2.0 $À 1.0 À 3.0 $À 2.0 <À 3.0 Not Active Blair et al. [10] data 3/ 2/ 2/ 6/ À 1.5, À 2.1, À 3.4, À 4.5, À 1.8, À 2.3 À 3.6 NB 5NB Soto et al. [11, 12] data 2/ 1/ 1/ 3/ À 1.5, À 3.5 À 3.5 NB À 3.5, À 4.2, NB Nishihara et al. [13] data 2/ À 0.8, NB 3/ À 2.0, À 3.0, NB 1/ À 4.1 10/ À 4.0, À 4.2, 8NB 6 Quant. Struct.-Act. Relat., 22 (2003) Quant. Struct.-Act. Relat., 22 (2003) QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model Table 4. Chemical Abstract Service (CAS) number, chemical name, applicable Simplified Molecular Input Line Entry System (SMILES) and molecular weight (MW) of EDPSD2 chemicals for which estrogen receptor binding affinities were predicted using the Integrated 4-Phase model CAS No. 000050-00-0 000050-21-5 000050-70-4 000050-81-7 000050-99-7 000054-21-7 000056-81-5 000057-10-3 000057-11-4 000057-13-6 000057-50-1 000057-55-6 000059-67-6 000060-00-4 000060-12-8 000060-33-3 000062-54-4 000064-02-8 000064-17-5 000064-18-6 000064-19-7 000065-85-0 000067-56-1 000067-63-0 000067-64-1 000067-68-5 000068-04-2 000069-65-8 000069-72-7 000071-23-8 000071-36-3 000071-41-0 000071-55-6 000074-84-0 000074-86-2 000074-98-6 000075-00-3 000075-05-8 000075-28-5 000075-31-0 000075-37-6 000075-45-6 000075-52-5 000075-65-0 000075-68-3 000075-69-4 000075-71-8 000076-13-1 000077-71-4 000077-73-6 000077-86-1 000077-90-7 000077-92-9 000077-99-6 000078-40-0 000078-51-3 000078-59-1 000078-70-6 000078-78-4 000078-83-1 000078-92-2 000078-93-3 Chemical Name Formaldehyde Lactic acid Glucitol, DL-Ascorbic acid D-Glucose Sodium salicylate Glycerol Palmitic acid Stearic acid Urea Sucrose 1,2-Propanediol Nicotinic acid Acetic acid, (ethylenedinitrilo)tetraPhenethyl alcohol Linoleic acid Calcium acetate Acetic acid, (ethylenedinitrilo)tetra-, tetrasodium salt Ethyl alcohol Formic acid Acetic acid Benzoic acid Methanol Isopropyl alcohol Methyl ketone Methyl sulfoxide Citric acid, trisodium salt Mannitol, DSalicylic acid Propyl alcohol Butyl alcohol 1-Pentanol Ethane, 1,1,1-trichloro Ethane Ethyne Propane Ethane, chloroAcetonitrile Propane, 2-methyl2-Propanamine Ethane, 1,1-difluoroMethane, chlorodifluoroMethane, nitrotert-Butyl alcohol Ethane, 1-chloro-1,1-difluoroMethane, trichlorofluoroMethane, dichlorodifluoroEthane, 1,1,2-trichloro-1,2,2-trifluoroHydantoin, 5,5-dimethyl4,7-Methanoindene, 3a,4,7,7a ± tetrahydro1,3-Propanediol, 2-amino-2-(hydroxymethyl)Citric acid, tributyl ester, acetate Citric acid 1,3-Propanediol, 2-ethyl-2-(hydroxymethyl)Phosphoric acid, triethyl ester Ethanol, 2-butoxy-, phosphate (3:1) 2-Cyclohexen-1-one, 3,5,5-trimethyl1,6-Octadien-3-ol, 3,7-dimethylButane, 2-methyl1-Propanol, 2-methylsec-Butyl alcohol 2-Butanone SMILES OˆC OˆC( O )C( O )C OCC( O )C( O )C( O )C( O )CO O1C(ˆO )C( O )ˆC( O )C1C( O )CO OCC1C( O )C( O )C( O )C( O )O1 Oc1ccccc1C(ˆO )O[ Na] OCC( O )CO OˆC( O )CCCCCCCCCCCCCCC OˆC( O )CCCCCCCCCCCCCCCCC OˆC( N )N O( C( C( O )C( O )C1O )CO )C1OC( OC( C2O )CO )( C2O )CO OCC( O )C OˆC( O )c(cccn1)c1 OˆC( O )CN( CCN( CC(ˆO )O )CC(ˆO )O )CC(ˆO )O OCCc(cccc1)c1 OˆC( O )CCCCCCCCˆCCCˆCCCCCC [ Ca]( OC(ˆO )C )OC(ˆO )C [ Na]OC(ˆO )CN( CCN( CC( O[ Na])ˆO )CC( O[ Na])ˆO )CC( O[ Na])ˆO OCC OˆCO OˆC( O )C OˆC( O )c(cccc1)c1 OC OC( C )C OˆC( C )C OˆS(C )C [ Na]OC(ˆO )CC( O )( C(ˆO )O[ Na])CC(ˆO )O[ Na] OCC( O )C( O )C( O )C( O )CO OˆC( O )c(c( O )ccc1)c1 OCCC OCCCC OCCCCC C( Cl)( Cl)( Cl)C CC C#C C( C )C ClCC N#CC C( C )( C )C NC( C )C FC( F )C FC( F )Cl OˆN(ˆO )C OC( C )( C )C FC( F )( Cl)C FC( Cl)( Cl)Cl FC( F )( Cl)Cl FC( F )( C( F )( Cl)Cl)Cl OˆC( NC( C1ˆO )( C )C )N1 C( C( CˆCC12)C1)( C2CˆC3)C3 OCC( N )( CO )CO OˆC( OC( C(ˆO )OCCCC )( CC(ˆO )OCCCC )CC(ˆO )OCCCC )C OˆC( O )C( O )( CC(ˆO )O )CC(ˆO )O OCC( CC )( CO )CO OˆP(OCC )( OCC )OCC OˆP(OCCOCCCC )( OCCOCCCC )OCCOCCCC OˆC( CˆC( CC1( C )C )C )C1 OC( CˆC )( CCCˆC( C )C )C C( CC )( C )C OCC( C )C OC( CC )C OˆC( CC )C MW 30.03 90.08 182.17 176.13 180.16 160.11 92.1 256.43 284.49 60.06 342.3 76.1 123.11 292.25 122.17 280.45 158.17 380.17 46.07 46.03 60.05 122.12 32.04 60.1 58.08 78.13 258.07 182.17 138.12 60.1 74.12 88.15 133.41 30.07 26.04 44.1 64.52 41.05 58.12 59.11 66.05 86.47 61.04 74.12 100.5 137.37 120.91 187.38 128.13 132.21 121.14 402.49 192.13 134.18 182.16 398.48 138.21 154.25 72.15 74.12 74.12 72.11 7 Table 4. (cont.) CAS No. 000078-96-6 000079-09-4 000079-11-8 000079-14-1 000079-24-3 000079-34-5 000079-41-4 000080-05-7 000080-26-2 000080-56-8 000080-62-6 000081-07-2 000084-66-2 000084-74-2 000085-40-5 000085-41-6 000085-44-9 000085-68-7 000088-12-0 000089-65-6 000090-80-2 000091-20-3 000091-53-2 000093-83-4 000094-36-0 000095-14-7 000095-48-7 000095-49-8 000096-29-7 000096-48-0 000097-63-2 000097-64-3 000097-85-8 000097-88-1 000097-99-4 000098-54-4 000098-55-5 000098-82-8 000098-86-2 000098-94-2 000099-76-3 000100-02-7 000100-37-8 000100-41-4 000100-51-6 000100-52-7 000100-97-0 000101-02-0 000101-68-8 000101-86-0 000102-60-3 000102-71-6 000102-76-1 000103-11-7 000103-23-1 000103-24-2 000104-15-4 000104-46-1 000104-55-2 000104-76-7 000106-22-9 000106-24-1 000106-43-4 Chemical Name 2-Propanol, 1-aminoPropionic acid Acetic acid, chloroGlycolic acid Ethane, nitroEthane, 1,1,2,2-tetrachloroMethacrylic acid Phenol, 4,4'-isopropylidenedip-Menth-1-en-8-ol, acetate 2-Pinene Methacrylic acid methyl ester 1,2-Benzisothiazolin-3-one, 1,1-dioxide Phthalic acid, diethyl ester Phthalic acid, dibutyl ester 4-Cyclohexene-1,2-dicarboximide Phthalimide Phthalic anhydride Phthalic acid, benzyl butyl ester 2-Pyrrolidinone, 1-ethenylD-erythro-Hex-2-enonic acid, .gamma.-lactone Gluconic acid, .delta.-lactone, DNaphthalene Quinoline, 6-ethoxy-1,2-dihydro-2,2,4-trimethylOleamide, N,N-bis(2-hydroxyethyl)Benzoyl peroxide 1H-Benzotriazole o-Cresol Toluene, o-chloro2-Butanone, oxime 2(3H )-Furanone, dihydroMethacrylic acid, ethyl ester Lactic acid, ethyl ester Isobutyric acid, isobutyl ester Methacrylic acid, butyl ester Furfuryl alcohol, tetrahydroPhenol, p-tert-butylp-Menth-1-en-8-ol Cumene Acetophenone Cyclohexylamine, N,N-dimethylBenzoic acid, p-hydroxy-, methyl ester Phenol, p-nitroEthanol, 2-(diethylamino)Benzene, ethylBenzyl alcohol Benzaldehyde 1,3,5,7-Tetraazatricyclo[3.3.1.13,7]decane Phosphorous acid, triphenyl ester Isocyanic acid, methylenedi-p-phenylene ester Cinnamaldehyde, .alpha.-hexyl2-Propanol, 1,1',1'',1'''-(ethylenedinitrilo)tetraEthanol, 2,2',2''-nitrilotrisAcetin, triAcrylic acid, 2-ethylhexyl ester Adipic acid, bis(2-ethylhexyl) ester Azelaic acid, bis(2-ethylhexyl) ester p-Toluenesulfonic acid Anisole, p-propenylCinnamaldehyde 1-Hexanol, 2-ethyl6-Octen-1-ol, 3,7-dimethyl2,6-Octadien-1-ol, 3,7-dimethyl-, ( E )Toluene, p-chloroSMILES OC( CN )C OˆC( O )CC OˆC( O )CCl OˆC( O )CO OˆN(ˆO )CC C( C( Cl)Cl)( Cl)Cl OˆC( O )C(ˆC )C Oc(ccc(c1)C(c(ccc( O )c2)c2)( C )C )c1 OˆC( OC( C( CCC(ˆC1)C )C1)( C )C )C C( C( CC1C2)C1( C )C )(ˆC2)C OˆC( OC )C(ˆC )C OˆC( NS(ˆO )(ˆO)c1cccc2)c12 OˆC( OCC )c(c(ccc1)C(ˆO )OCC )c1 OˆC( OCCCC )c(c(ccc1)C(ˆO )OCCCC )c1 OˆC( NC(ˆO )C1CCˆCC2)C12 OˆC( NC(ˆO )c1cccc2)c12 OˆC( OC(ˆO )c1cccc2)c12 OˆC( OCc(cccc1)c1)c(c(ccc2)C(ˆO )OCCCC )c2 OˆC( N( CˆC )CC1)C1 OCC( O )C1C( O )ˆC( O )C(ˆO )O1 OˆC( OC( C( O )C1O )CO )C1O c(c(ccc1)ccc2)(c1)c2 O(c(ccc( NC( CˆC1C )( C )C )c12)c2)CC OˆC( N( CCO )CCO )CCCCCCCCˆCCCCCCCCC OˆC( OOC(ˆO )c(cccc1)c1)c(cccc2)c2 c1ccc2nnnc2c1 Oc(c(ccc1)C )c1 c(c(ccc1)Cl)(c1)C N( O )ˆC( CC )C OˆC( OCC1)C1 OˆC( OCC )C(ˆC )C OˆC( OCC )C( O )C OˆC( OCC( C )C )C( C )C OˆC( OCCCC )C(ˆC )C O( C( CC1)CO )C1 Oc(ccc(c1)C( C )( C )C )c1 OC( C( CCC(ˆC1)C )C1)( C )C c(cccc1)(c1)C( C )C OˆC(c(cccc1)c1)C N( C( CCCC1)C1)( C )C OˆC( OC )c(ccc( O )c1)c1 OˆN(ˆO )c(ccc( O )c1)c1 OCCN( CC )CC c(cccc1)(c1)CC OCc(cccc1)c1 OˆCc(cccc1)c1 N( CN( CN1CN23)C3)( C1)C2 O(c(cccc1)c1)P( Oc(cccc2)c2)Oc(cccc3)c3 OˆCˆNc(ccc(c1)Cc(ccc( NˆCˆO )c2)c2)c1 OˆCC(ˆCc(cccc1)c1)CCCCCC OC( C )CN( CCN( CC( O )C )CC( O )C )CC( O )C OCCN( CCO )CCO OˆC( OCC( OC(ˆO )C )COC(ˆO )C )C OˆC( OCC( CCCC )CC )CˆC OˆC( OCC( CCCC )CC )CCCCC(ˆO )OCC( CCCC )CC OˆC( OCC( CCCC )CC )CCCCCCCC(ˆO )OCC( CCCC )CC OˆS(ˆO)( O )c(ccc(c1)C )c1 O(c(ccc(c1)CˆCC )c1)C OˆCCˆCc(cccc1)c1 OCC( CCCC )CC OCCC( CCCˆC( C )C )C OCCˆC( CCCˆC( C )C )C c(ccc(c1)Cl)(c1)C MW 75.11 74.08 94.5 76.05 75.07 167.85 86.09 228.29 196.29 136.24 100.12 183.18 222.24 278.35 151.17 147.13 148.12 312.37 111.14 176.13 178.14 128.18 217.31 369.59 242.23 119.13 108.14 126.59 87.12 86.09 114.15 118.13 144.22 142.2 102.13 150.22 154.25 120.2 120.15 127.23 152.15 139.11 117.19 106.17 108.14 106.13 140.19 310.29 250.26 216.33 292.42 149.19 218.21 184.28 370.58 412.66 172.2 148.21 132.16 130.23 156.27 154.25 126.59 8 Quant. Struct.-Act. Relat., 22 (2003) J. D. Walker et al. Table 4. (cont.) CAS No. 000106-44-5 000106-88-7 000106-97-8 000107-15-3 000107-18-6 000107-21-1 000107-22-2 000107-41-5 000107-64-2 000107-88-0 000107-92-6 000107-98-2 000108-10-1 000108-21-4 000108-24-7 000108-31-6 000108-32-7 000108-39-4 000108-46-3 000108-63-4 000108-65-6 000108-80-5 000108-83-8 000108-88-3 000108-93-0 000108-94-1 000108-95-2 000109-52-4 000109-89-7 000109-99-9 000110-05-4 000110-12-3 000110-16-7 000110-17-8 000110-19-0 000110-27-0 000110-30-5 000110-43-0 000110-44-1 000110-54-3 000110-63-4 000110-64-5 000110-80-5 000110-82-7 000110-91-8 000110-97-4 000111-27-3 000111-30-8 000111-40-0 000111-41-1 000111-42-2 000111-46-6 000111-60-4 000111-70-6 000111-76-2 000111-77-3 000111-82-0 000111-87-5 000111-90-0 000112-02-7 000112-05-0 000112-07-2 000112-24-3 Chemical Name p-Cresol Butane, 1,2-epoxyButane Ethylenediamine 2-Propen-1-ol Glycol Glyoxal 2,4-Pentanediol, 2-methylDimethyldioctadecylammonium chloride 1,3-Butanediol Butyric acid 2-Propanol, 1-methoxy2-Pentanone, 4-methylAcetic acid, isopropyl ester Acetic anhydride Maleic anhydride Carbonic acid, cyclic propylene ester Phenol, 3-methyl1,3-Benzenediol Adipic acid, bis(1-methylheptyl) ester 2-Propanol, 1-methoxy-, acetate 1,3,5-Triazine-2,4,6(1H,3H,5H )-trione 4-Heptanone, 2,6-dimethylToluene Cyclohexanol Cyclohexanone Phenol Pentanoic acid Diethylamine Furan, tetrahydrotert-Butyl peroxide 2-Hexanone, 5-methylMaleic acid Fumaric acid Acetic acid, isobutyl ester Myristic acid, isopropyl ester Octadecanamide, N,N'-ethylenebis2-Heptanone Sorbic acid Hexane 1,4-Butanediol 2-Butene-1,4-diol Ethanol, 2-ethoxyCyclohexane Morpholine 2-Propanol, 1,1'-iminodiHexyl alcohol Pentanedial Diethylenetriamine Ethanol, 2-[(2-aminoethyl)amino]Ethanol, 2,2'-iminodiEthanol, 2,2'-oxybisStearic acid, 2-hydroxyethyl ester Heptyl alcohol Ethanol, 2-butoxyEthanol, 2-(2-methoxyethoxy)Lauric acid, methyl ester Octyl alcohol Ethanol, 2-(2-ethoxyethoxy)Ammonium, hexadecyltrimethyl-, chloride Nonanoic acid Ethanol, 2-butoxy-, acetate Triethylenetetramine SMILES Oc(ccc(c1)C )c1 O( C1CC )C1 C( CC )C NCCN OCCˆC OCCO OˆCCˆO OC( CC( O )(C )C )C N( Cl)( C )( C )( CCCCCCCCCCCCCCCCCC )CCCCCCCCCCCCCCCCCC OCCC( O )C OˆC( O )CCC O( CC( O )C )C OˆC( CC( C )C )C OˆC( OC( C )C )C OˆC( OC(ˆO )C )C OˆC1OC(ˆO )CˆC1 OˆC( OCC1C )O1 Oc(cccc1C )c1 Oc(cccc1O )c1 OˆC( OC( CCCCCC )C )CCCCC(ˆO )OC( CCCCCC )C COCC( OC(ˆO )C )C n(c(nc(n1)O )O )c1O OˆC( CC( C )C )CC( C )C c(cccc1)(c1)C OC( CCCC1)C1 OˆC( CCCC1)C1 Oc(cccc1)c1 OˆC( O )CCCC N( CC )CC O( CCC1)C1 O( OC( C )( C )C )C( C )( C )C OˆC( CCC( C )C )C OˆC( O )CˆCC(ˆO )O OˆC( O )CˆCC(ˆO )O OˆC( OCC( C )C )C OˆC( OC( C )C )CCCCCCCCCCCCC OˆC( NCCNC(ˆO )CCCCCCCCCCCCCCCCC )CCCCCCCCCCCCCCCCC OˆC( CCCCC )C OˆC( O )CˆCCˆCC C( CCCC )C OCCCCO OCCˆCCO O( CCO )CC C( CCCC1)C1 O( CCNC1)C1 OC( C )CNCC( O )C OCCCCCC OˆCCCCCˆO N( CCN )CCN OCCNCCN OCCNCCO O( CCO )CCO OˆC( OCCO )CCCCCCCCCCCCCCCCC OCCCCCCC O( CCCC )CCO O( CCOC )CCO OˆC( OC )CCCCCCCCCCC OCCCCCCCC O( CCOCC )CCO CCCCCCCCCCCCCCCCN( Cl)( C )( C )C OˆC( O )CCCCCCCC OˆC( OCCOCCCC )C N( CCNCCN )CCN MW 108.14 72.11 58.12 60.1 58.08 62.07 58.04 118.18 586.52 90.12 88.11 90.12 100.16 102.13 102.09 98.06 102.09 108.14 110.11 370.58 132.16 129.08 142.24 92.14 100.16 98.15 94.11 102.13 73.14 72.11 146.23 114.19 116.07 116.07 116.16 270.46 593.04 114.19 112.13 86.18 90.12 88.11 90.12 84.16 87.12 133.19 102.18 100.12 103.17 104.15 105.14 106.12 328.54 116.21 118.18 120.15 214.35 130.23 134.18 320.01 158.24 160.21 146.24 Quant. Struct.-Act. Relat., 22 (2003) QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model 9 Table 4. (cont.) CAS No. 000112-27-6 000112-30-1 000112-34-5 000112-39-0 000112-53-8 000112-55-0 000112-57-2 000112-62-9 000112-69-6 000112-70-9 000112-80-1 000112-90-3 000112-92-5 000115-10-6 000115-77-5 000115-83-3 000115-95-7 000117-84-0 000118-58-1 000119-36-8 000119-47-1 000119-61-9 000120-40-1 000120-51-4 000121-33-5 000121-44-8 000121-91-5 000122-19-0 000122-20-3 000122-40-7 000123-17-1 000123-31-9 000123-38-6 000123-42-2 000123-77-3 000123-79-5 000123-86-4 000123-95-5 000124-04-9 000124-07-2 000124-10-7 000124-38-9 000124-40-3 000124-68-5 000126-30-7 000126-86-3 000126-92-1 000127-08-2 000127-09-3 000127-39-9 000128-37-0 000128-44-9 000131-11-3 000131-17-9 000131-57-7 000132-27-4 000135-19-3 000136-51-6 000136-53-8 000137-20-2 000137-40-6 000139-33-3 000139-89-9 Chemical Name Triethylene glycol 1-Decanol Ethanol, 2-(2-butoxyethoxy)Palmitic acid, methyl ester Dodecyl alcohol Dodecyl mercaptan Tetraethylenepentamine Oleic acid, methyl ester Hexadecylamine, N,N-dimethyl1-Tridecanol Oleic acid 9-Octadecenylamine, ( Z )1-Octadecanol Dimethyl ether Pentaerythritol Stearic acid, neopentanetetrayl ester 1,6-Octadien-3-ol, 3,7-dimethyl-, acetate Phthalic acid, dioctyl ester Salicylic acid, benzyl ester Salicylic acid, methyl ester p-Cresol, 2,2'-methylenebis[6-tert-butylBenzophenone Dodecanamide, N,N-bis(2-hydroxyethyl)Benzoic acid, benzyl ester Vanillin Triethylamine Isophthalic acid Ammonium, benzyldimethyloctadecyl-, chloride 2-Propanol, 1,1',1''-nitrilotriCinnamaldehyde, .alpha.-pentyl4-Nonanol, 2,6,8-trimethylHydroquinone Propionaldehyde 2-Pentanone, 4-hydroxy-4-methylFormamide, 1,1'-azobisAdipic acid, dioctyl ester Acetic acid, butyl ester Stearic acid, butyl ester Adipic acid Octanoic acid Myristic acid, methyl ester Carbon dioxide Dimethylamine 1-Propanol, 2-amino-2-methyl1,3-Propanediol, 2,2-dimethyl5-Decyne-4,7-diol, 2,4,7,9-tetramethylSulfuric acid, mono(2-ethylhexyl) ester, sodium salt Potassium acetate Sodium acetate Succinic acid, sulfo-, 1,4-diisobutyl ester, sodium salt p-Cresol, 2,6-di-tert-butyl1,2-Benzisothiazolin-3-one, 1,1-dioxide, sodium salt Phthalic acid, dimethyl ester Phthalic acid, diallyl ester Benzophenone, 2-hydroxy-4-methoxy2-Biphenylol, sodium salt 2-Naphthol Hexanoic acid, 2-ethyl-, calcium salt Hexanoic acid, 2-ethyl-, zinc salt Taurine, N-methyl-N-oleoyl-, sodium salt Propionic acid, sodium salt Acetic acid, (ethylenedinitrilo)tetra-, disodium salt Glycine, N-(carboxymethyl)-N'-(2-hydroxyethyl)-N,N'-ethylenedi-, trisodium salt SMILES O( CCOCCO )CCO OCCCCCCCCCC O( CCOCCO )CCCC OˆC( OC )CCCCCCCCCCCCCCC OCCCCCCCCCCCC SCCCCCCCCCCCC N( CCNCCNCCN )CCN OˆC( OC )CCCCCCCCˆCCCCCCCCC N( CCCCCCCCCCCCCCCC )( C )C OCCCCCCCCCCCCC OˆC( O )CCCCCCCCˆCCCCCCCCC NCCCCCCCCCˆCCCCCCCCC OCCCCCCCCCCCCCCCCCC O( C )C OCC( CO )( CO )CO OˆC( OCC( COC(ˆO )CCCCCCCCCCCCCCCCC )(COC(ˆO )CCCCCCCCCCC OˆC( OC( CˆC )( CCCˆC( C )C )C )C OˆC( OCCCCCCCC )c(c(ccc1)C(ˆO )OCCCCCCCC )c1 OˆC( OCc(cccc1)c1)c(c( O )ccc2)c2 OˆC( OC )c(c( O )ccc1)c1 Oc(c(cc(c1)C )Cc(c( O )c(cc2C )C( C )(C )C )c2)c1C( C )( C )C OˆC(c(cccc1)c1)c(cccc2)c2 OˆC( N( CCO )CCO )CCCCCCCCCCC OˆC( OCc(cccc1)c1)c(cccc2)c2 OˆCc(ccc( O )c1OC )c1 N( CC )( CC )CC OˆC( O )c(cccc1C(ˆO )O )c1 CCCCCCCCCCCCCCCCCCN( Cl)(C )( C )Cc1ccccc1 OC( C )CN( CC( O )C )CC( O )C OˆCC(ˆCc(cccc1)c1)CCCCC OC( CC( CC( C )C )C )CC( C )C Oc(ccc( O )c1)c1 OˆCCC OˆC( CC( O )( C )C )C OˆC( NˆNC(ˆO )N )N OˆC( OCCCCCCCC )CCCCC(ˆO )OCCCCCCCC OˆC( OCCCC )C OˆC( OCCCC )CCCCCCCCCCCCCCCCC OˆC( O )CCCCC(ˆO )O OˆC( O )CCCCCCC OˆC( OC )CCCCCCCCCCCCC OˆCˆO N( C )C OCC( N )( C )C OCC( CO )( C )C OC( C#CC( O )( CC( C )C )C )( CC( C )C )C CCCCC( CC )COS( O[ Na])(ˆO )ˆO [ K]OC(ˆO )C CC( O[ Na])ˆO CC( C )COC(ˆO )C( S(ˆO )(ˆO )O[ Na])CC(ˆO )OCC( C )C Oc(c(cc(c1)C )C( C )( C )C )c1C( C )( C )C OˆC1N([ Na])S(ˆO )(ˆO )c2ccccc12 OˆC( OC )c(c(ccc1)C(ˆO )OC )c1 OˆC( OCCˆC )c(c(ccc1)C(ˆO )OCCˆC )c1 OˆC(c(cccc1)c1)c(c( O )cc( OC )c2)c2 [ Na]Oc1ccccc1c2ccccc2 Oc(ccc(c1ccc2)c2)c1 [ Ca]( OC(ˆO )C( CCCC )CC )OC(ˆO )C( CCCC )C [ Zn]( OC(ˆO )C( CC )CCCC )OC(ˆO )C( CC )CCCC CCCCCCCCCˆCCCCCCCCC(ˆO )N( C )CCS(ˆO )(ˆO )O[ Na] CCC(ˆO )O[ Na] OC(ˆO )CN( CCN( CC( O )ˆO )CC( O[ Na])ˆO )CC( O[ Na])ˆO [ Na]OC(ˆO )CN( CCO )CCN( CC(ˆO )O[ Na])CC(ˆO )O[ Na] MW 150.18 158.29 162.23 270.46 186.34 202.4 189.31 296.5 269.52 200.37 282.47 267.5 270.5 46.07 136.15 1202 196.29 390.57 228.25 152.15 340.51 182.22 287.45 212.25 152.15 101.19 166.13 424.16 191.27 202.3 186.34 110.11 58.08 116.16 116.08 370.58 116.16 340.6 146.14 144.22 242.41 44.01 45.08 89.14 104.15 226.36 232.27 98.14 82.03 332.35 220.36 205.16 194.19 246.27 228.25 192.19 144.17 312.47 351.81 425.61 96.06 336.21 344.21 10 Quant. Struct.-Act. Relat., 22 (2003) J. D. Walker et al. Table 4. (cont.) CAS No. 000139-96-8 000140-01-2 000140-11-4 000140-66-9 000141-32-2 000141-43-5 000141-78-6 000141-79-7 000141-97-9 000142-47-2 000142-78-9 000142-82-5 000142-91-6 000143-07-7 000143-18-0 000143-28-2 000144-62-7 000147-14-8 000149-30-4 000149-44-0 000149-57-5 000150-76-5 000151-21-3 000298-07-7 000300-92-5 000334-48-5 000461-58-5 000504-60-9 000506-93-4 000526-95-4 000527-07-1 000532-32-1 000533-74-4 000541-02-6 000544-63-8 000552-30-7 000555-31-7 000556-67-2 000557-04-0 000557-05-1 000577-11-7 000586-62-9 000593-81-7 000614-45-9 000627-83-8 000628-63-7 000631-61-8 000637-12-7 000763-69-9 000822-16-2 000872-50-4 001002-89-7 001047-16-1 001111-78-0 001241-94-7 001300-72-7 001319-77-3 001321-94-4 001328-53-6 001330-20-7 001333-86-4 001338-02-9 Chemical Name Sulfuric acid, monododecyl ester, compd. with 2,2',2''-nitrilotriethanol (1 : 1) Glycine, N,N-bis[2-[bis(carboxymethyl)amino]ethyl]-, pentasodium salt Acetic acid, benzyl ester Phenol, p-(1,1,3,3-tetramethylbutyl)Acrylic acid butyl ester Ethanol, 2-aminoAcetic acid ethyl ester 3-Penten-2-one, 4-methylAcetoacetic acid, ethyl ester Glutamic acid, monosodium salt, LDodecanamide, N-(2-hydroxyethyl)Heptane Palmitic acid, isopropyl ester Lauric acid Oleic acid, potassium salt 9-Octadecen-1-ol, ( Z )Oxalic acid Copper, [phthalocyaninato(2-)]2(3H )-Benzothiazolethione Sodium formaldehydesulfoxylate Hexanoic acid, 2-ethylPhenol, p-methoxySulfuric acid monododecyl ester sodium salt Phosphoric acid, bis(2-ethylhexyl) ester Aluminum, hydroxybis(stearato)Decanoic acid Guanidine, cyano1,3-Pentadiene Guanidine, mononitrate Gluconic acid, DGluconic acid, monosodium salt, DSodium benzoate 2H-1,3,5-Thiadiazine-2-thione, tetrahydro-3,5-dimethylCyclopentasiloxane, decamethylMyristic acid 1,2,4-Benzenetricarboxylic acid, cyclic 1,2-anhydride 2-Propanol, aluminum salt Cyclotetrasiloxane, octamethylMagnesium stearate Stearic acid, zinc salt Succinic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt p-Mentha-1,4(8)-diene Trimethylamine, hydrochloride Peroxybenzoic acid, tert-butyl ester Stearic acid, ethylene ester Acetic acid, pentyl ester Acetic acid, ammonium salt Aluminum stearate Propionic acid, 3-ethoxy-, ethyl ester Stearic acid, sodium salt 2-Pyrrolidinone, 1-methylStearic acid, ammonium salt Quino[2,3-b]acridine-7,14-dione, 5,12-dihydroAmmonium carbamate Phosphoric acid, 2-ethylhexyl diphenyl ester Xylenesulfonic acid, sodium salt Cresol Naphthalene, methylC.I. Pigment Green 7 Xylene Carbon black Naphthenic acids, copper salts SMILES CCCCCCCCCCCCOS( O )(ˆO )ˆO.OCCN( CCO )CCO [ Na]OC( CN( CCN( CCN( CC( O[ Na])ˆO )CC( O[ Na])ˆO )CC( O[ Na])ˆ OˆC( OCc(cccc1)c1)C Oc(ccc(c1)C( CC( C )( C )C )( C )C )c1 OˆC( OCCCC )CˆC OCCN OˆC( OCC )C OˆC( CˆC( C )C )C OˆC( OCC )CC(ˆO )C NC( CCC( O[ Na])ˆO )C( O )ˆO OˆC( NCCO )CCCCCCCCCCC C( CCCCC )C OˆC( OC( C )C )CCCCCCCCCCCCCCC OˆC( O )CCCCCCCCCCC [ K]OC(ˆO )CCCCCCCCˆCCCCCCCCC OCCCCCCCCCˆCCCCCCCCC OˆC( O )C(ˆO )O [ Cu]6N2C3ˆNc8nc(c0c8cccc0)ˆNc9c5ccccc5c(n69)Nˆc7nc(c N(c(c( S1)ccc2)c2)ˆC1S OCS( O[ Na])ˆO OˆC( O )C( CCCC )CC O(c(ccc( O )c1)c1)C CCCCCCCCCCCCOS(ˆO )(ˆO )O[ Na] OˆP(OCC( CCCC )CC )( OCC( CCCC )CC )O OˆC( O[ Al]( OC(ˆO )CCCCCCCCCCCCCCCCC )O )CCCCCCCCCCCCCCCC CCCCCCCCCC(ˆO )O NC(ˆNC(#N ))N C(ˆCCˆC )C OˆN(ˆO )ON( H )ˆC( N )N OˆC( O )C( O )C( O )C( O )C( O )CO [ Na]OC(ˆO )C( O )C( O )C( O )C( O )CO [ Na]OC(ˆO )c1ccccc1 N( CSC( N1C )ˆS )( C1)C C[ Si]1( C )O[ Si]( C )( C )O[ Si]( C )( C )O[ Si]( C )( C )O[ Si]( C )( C OˆC( O )CCCCCCCCCCCCC OˆC( OC(ˆO )c1ccc( C(ˆO )O )c2)c12 [ Al]( OC( C )C )( OC( C )C )OC( C )C C[ Si]1( C )O[ Si]( C )( C )O[ Si]( C )( C )O[ Si]( C )( C )O1 [ Mg]( OC(ˆO )CCCCCCCCCCCCCCCCC )OC(ˆO )CCCCCCCCCCCCCCCCC [ Zn]( OC(ˆO )CCCCCCCCCCCCCCCCC )OC(ˆO )CCCCCCCCCCCCCCCCC CCCCC( CC )COC(ˆO )CC( C(ˆO )OCC( CC )CCCC )S(ˆO )(ˆO )O C(ˆC( C )C )( CCC(ˆC1)C )C1 CN( H )( Cl)(C )C OˆC( OOC( C )( C )C )c(cccc1)c1 OˆC( OCCOC(ˆO )CCCCCCCCCCCCCCCCC )CCCCCCCCCCCCCCCCC OˆC( OCCCCC )C N( H )( H)( H )( H )OC(ˆO )C [ Al]( OC(ˆO )CCCCCCCCCCCCCCCCC )( OC(ˆO )CCCCCCCCCCCCCCCC OˆC( OCC )CCOCC [ Na]OC(ˆO )CCCCCCCCCCCCCCCCC OˆC1CCCN1C N( H )( H)( H )( H )OC(ˆO )CCCCCCCCCCCCCCCCC Oc(c(c(nc1cc(c(nc(c2ccc3)c3)c4)c2O )ccc5)c5)c14 NC(ˆO )ON( H)( H )( H )H OˆP(Oc1ccccc1)( Oc2ccccc2)OCC( CC )CCCC [ Na]OS(ˆO )(ˆO )c1ccc(cc1C )C Oc1ccccc1C Cc1cccc2ccccc12 [ Cu]763[ N ‡ ]2ˆC8c1c(c(c(c(c1Cl)Cl)Cl)Cl)C2ˆNc4n3c(c5c4c(c(c(c5Cl)Cl)Cl)Cl)NˆC%11[ N ‡ ]6ˆC( N ˆC9N7C(ˆN8)c%10c9c(c(c(c%10Cl)Cl)Cl)Cl)c%12c%11c(c(c(c%12Cl)Cl)Cl)Cl Cc1ccccc1C C(ˆO )( O[ Cu])CCCCCCC1CC( CC1)C MW 415.66 503.26 150.18 206.33 128.17 61.08 88.11 98.15 130.14 169.11 243.39 100.21 298.51 200.32 320.56 268.49 90.04 578.1 167.24 118.08 144.22 124.14 288.38 322.43 610.95 172.27 84.08 68.12 121.08 196.16 218.14 144.11 162.27 370.78 228.38 192.13 204.25 296.62 591.26 632.35 422.58 136.24 95.57 194.23 595.01 130.19 77.08 877.42 146.19 306.47 99.13 301.52 312.33 78.07 362.41 208.21 108.14 142.2 Quant. Struct.-Act. Relat., 22 (2003) QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model 106.17 274.87 11 Table 4. (cont.) CAS No. 001338-24-5 001338-39-2 001338-41-6 001338-43-8 001401-55-4 001560-69-6 001569-01-3 001592-23-0 001643-20-5 001675-54-3 001806-26-4 001843-05-6 001934-21-0 001948-33-0 001984-06-1 002050-08-0 002082-79-3 002235-54-3 002440-22-4 002492-26-4 002530-87-2 002717-15-9 002783-94-0 002786-76-7 002807-30-9 002809-21-4 002915-53-9 003147-75-9 003164-85-0 003319-31-1 003468-63-1 003687-46-5 003710-84-7 003844-45-9 003926-62-3 004075-81-4 004080-31-3 004316-73-8 004404-43-7 005064-31-3 005131-66-8 005281-04-9 005324-84-5 005392-40-5 005466-77-3 005989-27-5 006104-30-9 006358-31-2 006381-77-7 006419-19-8 006846-50-0 006915-15-7 006938-94-9 007023-61-2 007173-62-8 007440-44-0 007580-31-6 008001-20-5 008001-22-7 008001-26-1 008001-29-4 008001-30-7 008001-31-8 Chemical Name Naphthenic acids Sorbitan, monolaurate Sorbitan, monostearate Sorbitan, monooleate Tannins Propionic acid, cobalt(2 ‡ ) salt 2-Propanol, 1-propoxyStearic acid, calcium salt Dodecylamine, N,N-dimethyl-, N-oxide Propane, 2,2-bis[p-(2,3-epoxypropoxy)phenyl]Phenol, p-octylBenzophenone, 2-hydroxy-4-(octyloxy)C.I. Acid Yellow 23 Hydroquinone, tert-butylOctanoic acid, sodium salt Salicylic acid, pentyl ester Hydrocinnamic acid, 3,5-di-tert-butyl-4-hydroxy-, octadecyl ester Sulfuric acid, monododecyl ester, ammonium salt p-Cresol, 2-(2H-benzotriazol-2-yl)2(3H )-Benzothiazolethione, sodium salt Silane, (3-chloropropyl)trimethoxyOleic acid, compd. with 2,2',2''-nitrilotriethanol (1 : 1) Sunset Yellow FCF 2-Naphtho-o-phenetidide, 4-[(p-carbamoylphenyl)azo]-3-hydroxyEthanol, 2-propoxyPhosphonic acid, (1-hydroxyethylidene)diMaleic acid, dioctyl ester Phenol, 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)Hexanoic acid, 2-ethyl-, potassium salt 1,2,4-Benzenetricarboxylic acid, tris(2-ethylhexyl) ester C.I. Pigment Orange 5 Oleic acid, decyl ester Ethanamine, N-ethyl-N-hydroxyC.I. Acid Blue 9, disodium salt Acetic acid, chloro-, sodium salt Propionic acid, calcium salt 3,5,7-Triaza-1-azoniaadamantane, 1-(3-chloroallyl)-, chloride Sarcosine, monosodium salt C.I. Fluorescent Brightening Agent 28 Acetic acid, nitrilotri-, trisodium salt 2-Propanol, 1-butoxyC.I. Pigment Red 57, calcium salt (1:1) 1-Octanesulfonic acid, sodium salt 2,6-Octadienal, 3,7-dimethyl2-Propenoic acid, 3-(4-methoxyphenyl)-, 2-ethylhexyl ester p-Mentha-1,8-diene, ( R )-(‡)Urea, 1,1'-isobutylidenediC.I. Pigment Yellow 74 D-erythro-Hex-2-enonic acid, .gamma.-lactone, monosodium salt Phosphonic acid, [nitrilotris(methylene)]triIsobutyric acid, 1-isopropyl-2,2-dimethyltrimethylene ester Malic acid Adipic acid, diisopropyl ester C.I. Pigment Red 48, calcium salt (1:1) 1,3-Propanediamine, N-9-octadecenyl-, ( Z )Carbon Hexanoic acid, 2-ethyl-, nickel salt Tung oil Soybean oil Linseed oil Cottonseed oil Corn oil Coconut oil SMILES OˆC( OCC( C1OCC( C1O )O )O )CCCCCCCCCCC O( CC1O )C( C1O )C( O )COC(ˆO )CCCCCCCCCCCCCCCCC O( CC1O )C( C1O )C( O )COC(ˆO )CCCCCCCCˆCCCCCCCCC OˆC( C1( CˆC( O )C( O )ˆC( O )Cˆ1))OC4( C( O )C( OC(ˆO )C2(ˆCC( O ) CCC(ˆO )O[ Co]OC(ˆO)CC O( CC( O )C )CCC CCCCCCCCCCCCCCCCCC(ˆO )O[ Ca]OC(ˆO )CCCCCCCCCCCCCCCCC OˆN( CCCCCCCCCCCC )( C )C O( C1COc(ccc(c2)C(c(ccc( OCC( O3)C3)c4)c4)( C )C )c2)C1 Oc(ccc(c1)CCCCCCCC )c1 OˆC(c(cccc1)c1)c(c( O )cc( OCCCCCCCC )c2)c2 [ Na]Oc2c( NˆNc1ccc(cc1)S( O[ Na])(ˆO )ˆO )c(nn2c3ccc(cc3) Oc(c(cc( O )c1)C( C )( C )C )c1 [ Na]OC(ˆO )CCCCCCC OˆC( OCCCCC )c(c( O )ccc1)c1 OˆC( OCCCCCCCCCCCCCCCCCC )CCc(cc(c( O )c1C( C )( C )C )C( C )( C S(ˆO )(ˆO )( O )OCCCCCCCCCCCC Oc1ccc( C )cc1n2nc3ccccc3n2 c12NˆC( S[ Na])Sc1cccc2 CO[ Si]( CCCCl)( OC )OC N( H )( CCO )( CCO )( CCO )OC(ˆO )CCCCCCCCˆCCCCCCCCC Oc2ccc1cc(ccc1c2NˆNc3ccc(cc3)S( O[ Na])(ˆO )ˆO )S( O[ Na]) OˆC( Nc(c( OCC )ccc1)c1)c(c( O )c( NˆNc(ccc( C(ˆO )N )c2)c2)c O( CCO )CCC OˆP(O )( O )C( O )( P(ˆO )( O )O )C OˆC( OCCCCCCCC )CˆCC(ˆO )OCCCCCCCC Oc(c(n(nc(c1ccc2)c2)n1)cc(c3)C( CC( C )( C )C )( C )C )c3 [ K]OC(ˆO )C( CCCC )CC OˆC( OCC( CCCC )CC )c(ccc(c1C(ˆO )OCC( CCCC )CC )C(ˆO )OCC( CC OˆN(ˆO )c(c( NˆNc(c(c(ccc1)cc2)c1)c2O )ccc3N(ˆO )ˆO )c3 OˆC( OCCCCCCCCCC )CCCCCCCCˆCCCCCCCCC ON( CC )CC [ Na]OS(ˆO )(ˆO )c2ccccc2C(c3ccc(cc3)N( Cc4cccc(c4)S(ˆO ) [ Na]OC(ˆO )CCl [ Ca]( OC(ˆO )CC )OC(ˆO )CC ClCˆCCN( Cl)( CN( C1)C2)( CN1C3)CN32 [ Na]OC(ˆO )CNC [ Na]OS(ˆO )(ˆO )c2c(ccc(c2)Nc3nc(nc(n3)N( CCO )CCO )Nc4cc [ Na]OC(ˆO )CN( CC( O[ Na])ˆO )CC( O[ Na])ˆO O( CC( O )C )CCCC c12c( NˆNc3c( S(ˆO )(ˆO )O )cc( C )cc3)c( O )c( C(ˆO )O )cc1cccc CCCCCCCCS( O[ Na])(ˆO )ˆO OˆCCˆC( CCCˆC( C )C )C OˆC( OCC( CCCC )CC )CˆCc(ccc( OC )c1)c1 C(ˆCCC( C(ˆC )C )C1)( C1)C OˆC( NC( NC(ˆO )N )C( C )C )N OˆC( Nc(c( OC )ccc1)c1)C( NˆNc(c( OC )cc( N(ˆO )ˆO )c2)c2)C(ˆ OCC( O )C1OC(ˆO )C(ˆC1O )O[ Na] OˆP(O )( O )CN( CP(ˆO )( O )O )CP(ˆO )( O )O OˆC( OCC( C )( C )C( OC(ˆO )C( C )C )C( C )C )C( C )C OˆC( O )CC( O )C(ˆO )O OˆC( OC( C )C )CCCCC(ˆO )OC( C )C c12c( NˆNc3cc( Cl)c( C )cc3S(ˆO )(ˆO )O[ Ca]5)c( O )c( C(ˆO )O5 N( CCCCCCCCCˆCCCCCCCCC )CCCN OˆC( C( CC )CCCC )O[ Ni]OC(ˆO )C( CC )CCCC MW 346.47 430.63 428.61 636.48 205.08 118.18 607.04 229.41 340.42 206.33 326.44 556.34 166.22 166.2 208.26 530.88 266.4 225.25 189.23 198.72 431.66 452.37 454.49 104.15 206.03 340.51 323.44 182.31 546.79 338.28 422.74 89.14 794.87 116.48 186.22 251.16 111.08 960.95 257.09 132.2 386.38 216.27 152.24 290.41 136.24 174.2 386.37 198.11 299.05 286.42 134.09 230.31 458.89 324.6 12.01 345.11 12 Quant. Struct.-Act. Relat., 22 (2003) J. D. Walker et al. Table 4. (cont.) CAS No. 008001-78-3 008001-79-4 008002-03-7 008002-09-3 008002-13-9 008002-26-4 008002-43-5 008002-50-4 008002-74-2 008006-54-0 008006-64-2 008007-43-0 008007-45-2 008008-20-6 008008-57-9 008009-03-8 008013-07-8 008016-11-3 008016-70-4 008029-43-4 008030-30-6 008030-76-0 008030-78-2 008032-32-4 008042-47-5 008050-09-7 008050-15-5 008050-31-5 008052-10-6 008052-41-3 008052-42-4 008052-48-0 008061-52-7 009004-77-7 009004-82-4 009004-96-0 009004-98-2 009004-99-3 009005-00-9 009005-07-6 009005-67-8 009005-90-7 009016-45-9 009046-01-9 012001-85-3 012068-03-0 015708-41-5 015956-58-8 018479-58-8 020324-32-7 020324-33-8 020824-56-0 021245-02-3 022464-99-9 024634-61-5 024800-44-0 025013-15-4 025013-16-5 025154-52-3 025155-30-0 025265-71-8 025265-77-4 025321-41-9 Chemical Name Castor oil, hydrogenated Castor oil Peanut oil Oils, pine Rape oil Tall oil Lecithins Fats and Glyceridic oils, menhaden Paraffin waxes and Hydrocarbon waxes Lanolin Turpentine, oil Sorbitan, sesquioleate Tar, coal Kerosine, (petroleum) Oils, orange, sweet Petrolatum Soybean oil, epoxidized Linseed oil, epoxidized Soybean oil, hydrogenated Syrups, hydrolyzed starch Naphtha Lecithins, soya Quaternary ammonium compounds, trimethyltallow alkyl, chlorides Ligroine White mineral oil, (petroleum) Rosin Resin acids and Rosin acids, hydrogenated, Me esters Resin acids and Rosin acids, esters with glycerol Tall-oil rosin Stoddard solvent Asphalt Fatty acids, tallow, sodium salts Lignosulfonic acid, calcium salt Poly(oxy-1,2-ethanediyl), .alpha.-butyl-.omega.-hydroxyGlycols, polyethylene, mono(hydrogen sulfate), dodecyl ether, sodium salt Glycols, polyethylene, monooleate Glycols, polyethylene, mono-9-octadecenyl ether, ( Z )Glycols, polyethylene, monostearate Poly(oxy-1,2-ethanediyl), .alpha.-octadecyl-.omega.-hydroxyGlycols, polyethylene, dioleate Sorbitan, monostearate, polyoxyethylene derivs. Turpentine Poly(oxy-1,2-ethanediyl), .alpha.-(nonylphenyl)-.omega.-hydroxyPoly(oxy-1,2-ethanediyl), .alpha.-tridecyl-.omega.-hydroxy-, phosphate Naphthenic acids, zinc salts ar-Toluenesulfonic acid, sodium salt Ferrate(1-), [(ethylenedinitrilo)tetraacetato]-, sodium Hexanoic acid, 2-ethyl-, manganese salt 7-Octen-2-ol, 2,6-dimethyl2-Propanol, 1-(2-methoxy-1-methylethoxy)2-Propanol, 1-[2-(2-methoxy-1-methylethoxy)-1-methylethoxy]Acetic acid, (ethylenedinitrilo)tetra-, diammonium salt Benzoic acid, p-(dimethylamino)-, 2-ethylhexyl ester Hexanoic acid, 2-ethyl-, zirconium salt Sorbic acid, potassium salt Tripropylene glycol Styrene, ar-methylPhenol, tert-butyl-4-methoxyPhenol, nonylBenzenesulfonic acid, dodecyl-, sodium salt Propanol, oxybisPropanoic acid, 2-methyl-, monoester with 2,2,4-trimethyl-1,3-pentanediol Benzenesulfonic acid, dimethylSMILES MW Quant. Struct.-Act. Relat., 22 (2003) QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model [ Ca]OS(ˆO )(ˆO )CC( Oc3c(cc(cc3)CCCS(ˆO)(ˆO )O )OC )Cc1c(c OCCOCCOCCCC [ Na]OS(ˆO )(ˆO )OCˆCOCˆCOCCCCCCCCCCCC C(ˆCCCCCCCCC )CCCCCCCCO C(ˆCCCCCCCCC )CCCCCCCCO 530.62 162.23 372.46 268.49 314.56 c1(ccc(cc1)CCCCCCCCC )OCCO [ Na]OS(ˆO )(ˆO )c1ccc(cc1)C [ Na ‡ ].Fe].OC(ˆO)CN( CCN( CC( O )ˆO)CC( O )ˆO )CC( O )ˆO [ Mn]( OC(ˆO )C( CCCC )CC )OC(ˆO )C( CCCC )CC OC( CCCC( CˆC )C )( C )C O( CC( OCC( O )C )C )C O( CC( OCC( OCC( O )C )C )C )C OC(ˆO )CN( CC(ˆO)O )CCN( CC(ˆO )O )CC(ˆO )O OˆC( OCC( CCCC )CC )c(ccc( N( C )C )c1)c1 [ Zr]( OC(ˆO )C( CCCC )CC )OC(ˆO )C( CCCC )CC [ K]OC(ˆO )CˆCCˆCC CC( O )COC( C )COC( C )CO c(ccc1C(ˆC )C )cc1 COc1ccc( O )c(c1)C( C )( C )C Oc1ccc(cc1)CCCCCCCCC [ Na]OS(ˆO )(ˆO )c1ccc(cc1)CCCCCCCCCCCC CC( O )COCC( O )C OˆC( OCC( C( C( C )C )O )( C )C )C( C )C OˆS(ˆO)(c1ccc(cc1C )C )O 264.41 194.18 334.25 341.35 156.27 148.2 206.28 292.25 277.41 377.64 150.22 192.26 118.18 180.25 220.36 348.48 134.18 216.32 186.23 13 Table 4. (cont.) CAS No. 025322-68-3 025322-69-4 025339-17-7 025496-72-4 025498-49-1 025550-98-5 025956-17-6 025973-55-1 026183-52-8 026264-05-1 026264-06-2 026266-57-9 026266-58-0 026401-27-4 026447-10-9 026523-78-4 026544-23-0 026635-93-8 026761-40-0 027138-31-4 027176-87-0 027177-77-1 027193-28-8 027193-86-8 027251-75-8 027253-31-2 027323-41-7 028188-24-1 028348-53-0 028519-02-0 028553-12-0 028987-17-9 029385-43-1 029761-21-5 029806-73-3 029911-28-2 031566-31-1 032687-78-8 034590-94-8 036445-71-3 036653-82-4 037220-82-9 037764-25-3 037971-36-1 039464-70-5 051274-00-1 051811-79-1 052829-07-9 052836-31-4 053980-88-4 055406-53-6 061788-44-1 061788-47-4 061788-59-8 061788-89-4 061789-01-3 061789-30-8 061789-31-9 061789-40-0 061789-51-3 061789-65-9 061789-72-8 061789-73-9 Chemical Name Glycols, polyethylene Glycols, polypropylene Isodecyl alcohol Olein, monoTripropylene glycol monomethyl ether Phosphorous acid, diisodecyl phenyl ester 2-Naphthalenesulfonic acid, 6-hydroxy-5-[(2-methoxy-5-methyl-4-sulfophenyl)azo]-, disodium salt Phenol, 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylPoly(oxy-1,2-ethanediyl), .alpha.-decyl-.omega.-hydroxyBenzenesulfonic acid, dodecyl-, compd. with isopropylamine (1:1) Benzenesulfonic acid, dodecyl-, calcium salt Sorbitan, monopalmitate Sorbitan, trioleate Phosphorous acid, isooctyl diphenyl ester Xylenesulfonic acid, ammonium salt Phenol, nonyl-, phosphite (3:1) Phosphorous acid, isodecyl diphenyl ester Glycols, polyethylene, (9-octadecenylimino)diethylene ether, ( Z )Phthalic acid, diisodecyl ester Dipropylene glycol, dibenzoate Benzenesulfonic acid, dodecylBenzenesulfonic acid, dodecyl-, potassium salt Phenol, octylPhenol, dodecyl1,2,4-Benzenetricarboxylic acid, triisooctyl ester Neodecanoic acid, cobalt salt Benzenesulfonic acid, dodecyl-, compd. with 2,2',2''-nitrilotris[ethanol] (1:1) Stearic acid, triester with pentaerythritol ar-Cumenesulfonic acid, sodium salt Benzenesulfonic acid, dodecyloxydi-, disodium salt Phthalic acid, diisononyl ester Phenol, nonyl-, barium salt 1H-Benzotriazole, methylPhosphoric acid, isodecyl diphenyl ester Palmitic acid, 2-ethylhexyl ester 2-Propanol, 1-(2-butoxy-1-methylethoxy)Octadecanoic acid, monoester with 1,2,3-propanetriol Hydrazine, 1,2-bis(3,5-di-tert-butyl-4-hydroxyhydrocinnamoyl)Dipropylene glycol monomethyl ether Benzenesulfonic acid, decyl(sulfophenoxy)-, disodium salt 1-Hexadecanol 9-Octadecenoic acid ( Z )-, ester with 1,2,3-propanetriol Acetamide, 2,2-dichloro-N,N-di-2-propenyl1,2,4-Butanetricarboxylic acid, 2-phosphonoPoly(oxy-1,2-ethanediyl), .alpha.-phenyl-.omega.-hydroxy-, phosphate C.I. Pigment Yellow 42 Poly(oxy-1,2-ethanediyl), .alpha.-(nonylphenyl)-.omega.-hydroxy-, phosphate Decanedioic acid, bis(2,2,6,6-tetramethyl-4-piperidinyl) ester Oxazolidine, 3-(dichloroacetyl)-2,2,5-trimethyl2-Cyclohexene-1-octanoic acid, 5(or 6)-carboxy-4-hexylCarbamic acid, butyl-, 3-iodo-2-propynyl ester Phenol, styrenated Fatty acids, coco Fatty acids, coco, Me esters Fatty acids, C18-unsatd., dimers Fatty acids, tall-oil, epoxidized, 2-ethylhexyl esters Fatty acids, coco, potassium salts Fatty acids, coco, sodium salts 1-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acyl derivs., inner salts Naphthenic acids, cobalt salts Resin acids and Rosin acids, aluminum salts Quaternary ammonium compounds, benzyl(hydrogenated tallow alkyl)dimethyl, chlorides Quaternary ammonium compounds, benzylbis(hydrogenated tallow alkyl)methyl, chlorides SMILES OC( COC( CO )C )C OCCCCCCCC( C )C OˆC( OCC( O )CO )CCCCCCCCˆCCCCCCCCC OCC( OC( COC( COC )C )C )C OˆP(c1ccccc1)( OCCCCCCCC( C )C )OCCCCCCCC( C )C COc1cc(c( C )cc1NˆNc2c( O )ccc3cc(ccc23)S( O[ Na])(ˆO )ˆO )S Oc(c(cc(c1)C( CC )( C )C )C( CC )( C )C )c1n(nc(c2ccc3)c3)n2 CCCCCCCCCCCCc1ccc( S(ˆO )(ˆO )O[ Ca]OS(ˆO )(ˆO )c2ccc( CCCC OˆC( OCC( C( C( C( O )CO )O )O )O )CCCCCCCCCCCCCCC OCC( C( C( C( COC(ˆO )CCCCCCCCˆCCCCCCCCC )OC(ˆO )CCCCCCCCˆC OˆP(Oc1ccccc1)( Oc2ccccc2)CCCCCC( C )C Cc1cc( S(ˆO )(ˆO )ON( H )( H )( H )H )cc( C )c1 CCCCCCCCCc1ccc(cc1)OP( Oc2cccc(c2)CCCCCCCCC )Oc3ccc(cc CC( CCCCCCCOP( Oc1ccccc1)Oc2ccccc2)C CC( C )CCCCCCCOC(ˆO )c1ccccc1C(ˆO )OCCCCCCCC( C )C OˆC(c1ccccc1)OCC( OC( COC(ˆO )c2ccccc2)C )C OˆS(ˆO)(c1ccc(cc1)CCCCCCCCCCCC )O OˆS(ˆO)(c1ccc(cc1)CCCCCCCCCCCC )O[ K] Oc(ccc1CCCCCCCC )cc1 Oc1cccc(c1)CCCCCCCCCCCC OˆC(c1cc(ccc1C(ˆO )OCCCCCC( C )C )C(ˆO )OCCCCCC( C )C )OCCCC [ Co]( OC(ˆO )CC( C )( C )CC( C )( C )C )OC(ˆO )CC( C )( C )CC( C )( C )C OˆC( CCCCCCCCCCCCCCCCC )OCC( COC(ˆO )CCCCCCCCCCCCCCCCC )( [ Na]OS(ˆO )(ˆO )c1ccc(cc1)C( C )C c1cc( S(ˆO )(ˆO )O[ Na])cc(c1)Oc2cc( S(ˆO )(ˆO )O[ Na])cc( CC OˆC(c1ccccc1C(ˆO )OCCCCCCC( C )C )OCCCCCCC( C )C [ Ba]( Oc2cc(ccc2)CCCCCCCCC )Oc1cc(ccc1)CCCCCCCCC Cc1cccc2c1NˆNN2 OˆP(Oc1ccccc1)( Oc2ccccc2)OCCCCCCCC( C )C OˆC( OCC( CCCC )CC )CCCCCCCCCCCCCCC O( CC( OCC( O )C )C )CCCC OCC( O )COC(ˆO )CCCCCCCCCCCCCCCCC OˆC( NNC(ˆO)CCc(cc(c( O )c1C( C )( C )C )C( C )( C )C )c1)CCc(cc( COC( C )COCC( C )O OCCCCCCCCCCCCCCCC CCCCCCCCCˆCCCCCCCCC(ˆO )OCC( CO )O OˆC( N( CCˆC )CCˆC )C( Cl)Cl OˆC( O )C( P(ˆO )( O )O )(CC(ˆO )O )CCC(ˆO )O OP(ˆO )( OCCOc1ccccc1)O P(ˆO )( Oc1ccc(cc1)CCCCCCCCC )( OCC( O )CO )O OˆC( OC( CC( NC1( C )C )(C )C )C1)CCCCCCCCC(ˆO)OC( CC( NC2( C )C OˆC( N( CC( O1)C )C1( C )C )C( Cl)Cl OˆC( C1CC( CCC1CCCCCCCC(ˆO )O )CCCCCC )O OˆC( OCC#CI )NCCCC Oc1c(cccc1)CˆC OˆC( CˆCCCCCCCCCCCCCCˆCC(ˆO )O )O MW 14 Quant. Struct.-Act. Relat., 22 (2003) 158.29 356.55 206.28 438.64 496.42 351.5 691.06 420.59 1504.5 346.41 203.26 689.02 374.46 446.68 342.39 326.5 364.59 206.33 262.44 546.79 401.46 935.56 222.24 542.62 418.62 576.03 133.15 390.46 368.65 190.29 358.57 552.8 148.2 242.45 356.55 208.09 270.13 218.15 374.42 480.74 226.1 354.53 281.09 120.15 310.44 J. D. Walker et al. Table 4. (cont.) CAS No. 061789-77-3 061789-81-9 061789-86-4 061789-97-7 061789-99-9 061790-12-3 061790-50-9 061790-51-0 061790-63-4 061791-01-3 061791-31-9 061791-47-7 061791-48-8 063231-60-7 063449-39-8 064147-40-6 064365-17-9 064665-57-2 064741-41-9 064741-50-0 064741-51-1 064741-52-2 064741-53-3 064741-59-9 064741-65-7 064741-67-9 064742-14-9 064742-16-1 064742-42-3 064742-43-4 064742-46-7 064742-47-8 064742-51-4 064742-54-7 064742-55-8 064742-56-9 064742-61-6 064742-65-0 064742-81-0 064742-88-7 064742-89-8 064742-94-5 064742-95-6 064742-96-7 064743-02-8 064771-72-8 065997-06-0 067701-05-7 067701-09-1 067701-10-4 067762-27-0 067891-79-6 067891-80-9 068081-81-2 068122-86-1 068139-30-0 068140-00-1 068153-22-0 068154-36-9 068155-09-9 068171-29-9 068187-51-9 Chemical Name Quaternary ammonium compounds, dicoco alkyldimethyl, chlorides Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, Me sulfates Sulfonic acids, petroleum, calcium salts Tallow Lard Fatty acids, tall-oil Resin acids and Rosin acids, potassium salts Resin acids and Rosin acids, sodium salts Fatty acids, coco, compds. with diethanolamine Fatty acids, tall-oil, diesters with polyethylene glycol Ethanol, 2,2'-iminobis-, N-coco alkyl derivs. Ethanol, 2,2'-iminobis-, N-coco alkyl derivs., N-oxides Fatty acids, tall-oil, monoesters with sorbitan Paraffin waxes and Hydrocarbon waxes, microcryst. Paraffin waxes and Hydrocarbon waxes, chloro Castor oil, dehydrated Resin acids and Rosin acids, hydrogenated, esters with pentaerythritol 1H-Benzotriazole, 4(or 5)-methyl-, sodium salt Naphtha, (petroleum), heavy straight-run Distillates, (petroleum), light paraffinic Distillates, (petroleum), heavy paraffinic Distillates, (petroleum), light naphthenic Distillates, (petroleum), heavy naphthenic Distillates, (petroleum), light catalytic cracked Naphtha, (petroleum), heavy alkylate Residues, (petroleum), catalytic reformer fractionator Distillates, (petroleum), acid-treated light Petroleum resins Hydrocarbon waxes, (petroleum), clay-treated microcryst. Paraffin waxes, (petroleum), clay-treated Distillates, (petroleum), hydrotreated middle Distillates, (petroleum), hydrotreated light Paraffin waxes, (petroleum), hydrotreated Distillates, (petroleum), hydrotreated heavy paraffinic Distillates, (petroleum), hydrotreated light paraffinic Distillates, (petroleum), solvent-dewaxed light paraffinic Slack wax, (petroleum) Distillates, (petroleum), solvent-dewaxed heavy paraffinic Kerosine, (petroleum), hydrodesulfurized Solvent naphtha, (petroleum), medium aliph. Solvent naphtha, (petroleum), light aliph. Solvent naphtha, (petroleum), heavy arom. Solvent naphtha, (petroleum), light arom. Solvent naphtha, (petroleum), heavy aliph. Alkenes, C > 10 .alpha.Paraffins, (petroleum), normal C5-20 Rosin, hydrogenated Fatty acids, C8-18 and C18-unsatd. Fatty acids, C8-18 and C18-unsatd., potassium salts Fatty acids, C8-18 and C18-unsatd., sodium salts Alcohols, C16-18 Distillates, (petroleum), heavy arom. Distillates, (petroleum), light arom. Benzenesulfonic acid, mono-C10-16-alkyl derivs., sodium salts Imidazolium compounds, 4,5-dihydro-1-methyl-2-nortallow alkyl-1-(2-tallow amidoethyl), Me sulfates 1-Propanaminium, N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-3-sulfo-, N-coco acyl derivs., hydroxides, inner salts Amides, coco, N-(hydroxyethyl) Paraffin waxes and Hydrocarbon waxes, oxidized Fatty acids, coco, monoesters with sorbitan Amides, coco, N-[3-(dimethylamino)propyl], N-oxides Ethanol, 2,2',2''-nitrilotris-, tris(dihydrogen phosphate) (ester), sodium salt C.I. Pigment Yellow 119 SMILES MW Quant. Struct.-Act. Relat., 22 (2003) QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model Cc1cc2N([ Na])NˆNc2cc1 155.14 CCCCCCCCCˆC OˆC( CˆCCˆCCˆCCˆCCˆC )O 140.27 176.22 CCCCCCCCCCCCCCCCO 242.45 OˆP(OCCN( CCOP(ˆO )( O )O )CCOP(ˆO )( O )O[ Na])( O )O 411.11 15 Table 4. (cont.) CAS No. 068187-76-8 068187-84-8 068308-53-2 068308-74-7 068334-00-9 068334-30-5 068391-01-5 068409-75-6 068410-69-5 068424-85-1 068425-47-8 068439-57-6 068439-70-3 068476-30-2 068476-31-3 068476-33-5 068476-40-4 068476-78-8 068476-80-2 068477-31-6 068477-33-8 068514-74-9 068515-49-1 068526-82-9 068527-23-1 068551-07-5 068551-19-9 068553-00-4 068584-22-5 068584-25-8 068585-34-2 068602-80-2 068603-15-6 068603-18-9 068603-42-9 068608-26-4 068611-44-9 068611-55-2 068647-72-3 068650-39-5 068783-78-8 068891-38-3 068920-06-9 068937-83-7 068938-15-8 068953-36-6 068955-64-6 068990-53-4 069009-90-1 069012-32-4 070131-50-9 070592-80-2 071011-27-3 078491-02-8 088230-35-7 090438-79-2 097676-23-8 098730-04-2 119345-04-9 Chemical Name Castor oil, sulfated, sodium salt Castor oil, oxidized Fatty acids, soya Amides, tall-oil fatty, N,N-di-Me Cottonseed oil, hydrogenated Fuels, diesel Quaternary ammonium compounds, benzyl-C12-18-alkyldimethyl, chlorides Bone meal Poly(oxy-1,2-ethanediyl), .alpha.-[2-[bis(2-aminoethyl)methylammonio]ethyl]-.omega.-hydroxy-, N,N'-ditallow acyl derivs., Me sulfates (salts) Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides Amides, soya, N,N-bis(hydroxyethyl) Sulfonic acids, C14-16-alkane hydroxy and C14-16-alkene, sodium salts Amines, C12-16-alkyldimethyl Fuel oil, no. 2 Fuel oil, no. 4 Fuel oil, residual Hydrocarbons, C3-4 Molasses Fats and Glyceridic oils, vegetable, deodorizer distillates Distillates, (petroleum), catalytic reformer fractionator residue, low-boiling Gases, (petroleum), C3-4, isobutane-rich Palm oil, hydrogenated 1,2-Benzenedicarboxylic acid, di-C9-11-branched alkyl esters, C10-rich Alkenes, C6-10, hydroformylation products, high-boiling Naphtha, (petroleum), light steam-cracked arom. Alcohols, C8-18 Alkanes, C12-14-isoFuel oil, no. 6 Benzenesulfonic acid, C10-16-alkyl derivs. Benzenesulfonic acid, C10-16-alkyl derivs., compds. with triethanolamine Poly(oxy-1,2-ethanediyl), .alpha.-sulfo-.omega.-hydroxy-, C10-16-alkyl ethers, sodium salts Distillates, (petroleum), C12-30-arom. Alcohols, C6-12 Alcohols, C10-16, distn. residues Amides, coco, N,N-bis(hydroxyethyl) Sulfonic acids, petroleum, sodium salts Silane, dichlorodimethyl-, reaction products with silica Sulfuric acid, mono-C10-16-alkyl esters Terpenes and Terpenoids, sweet orange-oil Imidazolium compounds, 1-[2-(carboxymethoxy)ethyl]-1-(carboxymethyl)-4,5-dihydro-2-norcoco alkyl, hydroxides, inner salts, disodium salts Quaternary ammonium compounds, dimethylditallow alkyl, chlorides Poly(oxy-1,2-ethanediyl), .alpha.-sulfo-.omega.-hydroxy-, C12-14-alkyl ethers, sodium salts Hydrocarbons, C7-9 Fatty acids, C6-10, Me esters Fatty acids, coco, hydrogenated Fatty acids, tall-oil, reaction products with tetraethylenepentamine Hexanedinitrile, hydrogenated, high-boiling fraction, phosphonomethylated Glycerides, C14-22 mono1,1'-Biphenyl, bis(1-methylethyl)Slags, phosphorus-manufg. Bentonite, acid-leached Amines, C10-16-alkyldimethyl, N-oxides Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, salts with hectorite Urea, N-[1,3-bis(hydroxymethyl)-2,5-dioxo-4-imidazolidinyl]-N,N'-bis(hydroxymethyl)Hexanol, acetate, branched and linear Acetic acid, C6-8-branched alkyl esters Oils, licorice 2H-1,4-Benzoxazine, 4-(dichloroacetyl)-3,4-dihydro-3-methylBenzene, 1,1'-oxybis-, tetrapropylene derivs., sulfonated, sodium salts SMILES MW 16 Quant. Struct.-Act. Relat., 22 (2003) CN( CCCCCCCCCCCCCC )C 241.46 CCC 44.1 OˆC(c1ccccc1C(ˆO )OCCCCCCC( C )(C )C )OCCCCCCC( C )( C )C 446.68 OCCCCCCCCCCCCC CC( CCCCCCCCCC )C OˆS(ˆO)(c1ccc(cc1)CCCCCCCCCC )O 200.37 184.37 298.44 OCCCCCC 102.18 OˆC( OC )CCCCCCC 158.24 OˆC( C( C( OC(ˆO )CCCCCCCCCC )O )O )O CC(c1ccc(cc1)c2ccc(cc2)C( C )C )C CCCCCCCCCCN(ˆO )( C )C OˆC( NCO )N( C1N( C(ˆO )N( C1(ˆO ))CO )CO )CO CCCCCCOC(ˆO )C OˆC( OCCCCCCC )C c1ccc2N( C(ˆO )C( Cl)Cl)C( C )COc2c1 290.36 238.38 201.36 J. D. Walker et al. 278.22 144.22 158.24 260.12 QSARs for Endocrine Disruption Priority Setting Database 2: The Integrated 4-Phase Model Chemical Abstract Service (CAS) number, name, SMILES and molecular weights (if available) for these chemicals are listed in Table 4. Disclaimer Reference herein to any specific commercial product, process, or service by trademark, manufacturer, or otherwise, does not necessarily constitute its endorsement, recommendation or favoring by the Toxic Substances Control Act (TSCA) Interagency Testing Committee (ITC) or any of the 16 U.S. Government organizations represented on the ITC, including the U.S. Environmental Protection Agency (U.S. EPA). Views expressed in this paper do not necessarily reflect policies of the ITC or any of the U.S. Government organizations represented on the ITC, including the U.S. EPA. Acknowldgments The authors thank Norma Williams for formatting and proofing the manuscript and Gary Timm from the U.S. EPA×s Office of Science Coordination and Policy for reviewing the manuscript. References [1] Walker, J. D., Waller, C., and Kane, S., The Endocrine Disruption Priority Setting Database (EDPSD): A tool to rapidly sort and prioritize chemicals for endocrine disruption screening and testing, Chapter 4, in: Walker J. D. (Ed.), QSARs for Predicting Biological Activities Related to Endocrine Disruption and Environmental-Human Health Interactions, SETAC Press, Pensacola (Florida), 2003. [2] Schmieder, P., Ankley, G., Mekenyan, O., Walker, J. D., and Bradbury, S., QSARs for predicting estrogen receptor binding affinity of structurally diverse chemicals, Environ. Toxicol. Chem. 22, In Press (2003). [3] Shi, L., Tong, W., Fang, H., Perkins, R., Wu, J., Tu, M., Blair, R. M., Branham, W. S., Waller, C., Walker, J. D., and Sheehan, D. M., An Integrated ™4-Phase∫ Approach for Setting Endocrine Disruption Screening Priorities ± Phase I and II Predictions of Estrogen Receptor Binding Affinities, SAR QSAR Environ. Res. 13, 69 ± 88 (2002). [4] Hong, H., Tong ,W., Fang, H., Shi, L., Xie, R. Q., Wu, J., Perkins, R., Walker, J. D., Branham, W. S., and Sheehan, D. M., Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts, Environ. Health Perspect. 110, 29 ± 36. (2002). [5] Shi, L. M., Fang, H., Tong, W., Wu, J., Perkins, R., Blair, R., Branham, W. and Sheehan, D, QSAR models using a large diverse set of estrogens, J. Chem. Inf. Comput. Sci. 41, 186 ± 195 (2001). [6] Elsby, R., Ashby, J., Sumpter, J. P., Brooks, A. N., Pennie, W. D, Maggs, J. L., Lefevre, P. A., Odum, J., Beresford, N., Paton, D., Park, B. K., Obstacles to the prediction of estrogenicity from chemical structure: Assay-mediated metabolic transformation and apparent promiscuous nature of the estrogen receptor, Biochem. Pharmacol. 60, 1519 ± 1530 (2000). [7] Anderson, E., Veith, G. D., and Weininger, D., SMILES: A line notation and computerized interpreter for chemical structure, EPA/600/M-87-021, Technical Report, U.S. Environmental Protection Agency, Duluth (Minnesota) 1987. [8] Weininger, D., SMILES, A Chemical Language and Information System. 1. Introduction to Methodology and Encoding Rules, J. Chem. Inf. Comput. Sci. 28, 31 ± 36 (1988). [9] Weininger, D., Weininger, A., and Weininger, J. L., SMILES. 2. Algorithm for generation of unique SMILES notation, J. Chem. Inf. Comput. Sci. 29, 97 ± 101 (1989). [10] Blair, R., Fang, H., Branham, W. S., Hass, B., Dial, S. L., Moland, C. L., Tong, W., Shi, L., Perkins, R., and Sheehan, D. M., Estrogen Receptor Relative Binding Affinities of 188 Natural and Xenochemicals: Structural Diversity of Ligands, Toxicol. Sci. 54, 138 ± 153 (2000). [11] Soto, A. M., Justicia, H., Wray, J. W., and Sonnenschein, C., pNonylphenol: an estrogenic xenobiotic released from ™modified∫ polystyrene, Environ. Health Perspect. 92, 167 ± 173 (1991). [12] Soto, A. M., Sonnenschein, C., Chung, K. L., Fernandez, M. F., Olea, N., and Serrano, F. O., The E-SCREEN Assay as a Tool to Identify Estrogens: an update on Estrogenic Environmental Pollutants, Environ. Health Perspect. 103, Suppl. 7, 113 ± 122 (1995). [13] Nishihara, T., Nishikawa, J., Kanayama, T., Dakeyama, F., Saito, K., Imagawa, M., Takatori, S., Kitagawa, Y., Hori, S., and Utsumi, H., Estrogenic activities of 517 chemicals by yeast two-hybrid assay, J. Health Sci. 46, 282 ± 298 (2000). [14] Fang, H., Tong, W., Perkins, R., Soto, A., Prechtl, N., and Sheehan, D. M., Quantitative comparison of in vitro assays for estrogenic activity, Environ. Health Perspect. 108, 723 ± 729 (2000). Received on &; Quant. Struct.-Act. Relat., 22 (2003) 17