Appendix
Table S1 Experimentalacute toxicity and lipophilicity values of different compounds considered for modeling
Sl. No. / CAS# / Smiles code / Name of the compounds / Toxicity value of different endpoints / Lipophilicity values usedRodent pLD50 (mol/kg) / Algae pLC50 (mol/L) / Daphnia pLC50 (mol/L) / Fish pLC50 (mol/L) / LOGKo/w / LOGKo/w2
Analgesics, Anti-inflammatory Drugs and Antipyretics (n=7)
28 / 50-78-2 / CC(=O)Oc1ccccc1C(O)=O / Aspirin / 2.954628 / NA / 3.106439 / 3.005238 / 1.1300 / 1.2769
76 / 15307-86-5 / OC(=O)Cc1ccccc1Nc1c(cccc1Cl)Cl / Diclofenac / 3.675635 / 4.310147 / 4.121267 / NA / 4.0200 / 16.1604
105 / 2135-17-3 / C[C@@H]1C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]2(C)[C@@]1(O)C(=O)CO / Flumethasone / 1.787193 / 3.613268 / 3.613268 / 3.613268 / 1.9400 / 3.7636
120 / 15687-27-1 / CC(C)Cc1ccc(cc1)[C@@H](C)C(O)=O / Ibuprofen / 2.511008 / 4.463207 / 4.355424 / 3.076419 / 3.9700 / 15.7609
123 / 22071-15-4 / C[C@@H](C(O)=O)c1cccc(c1)C(=O)c1ccccc1 / Ketoprofen / 3.610136 / NA / 3.599140 / NA / 3.0000 / 9.0000
154 / 22204-53-1 / COc1ccc2cc(ccc2c1)[C@H](C)C(O)=O / Naproxen / 2.634683 / 4.040004 / 3.794022 / 2.614036 / 3.1800 / 10.1124
176 / 103-90-2 / CC(=O)Nc1ccc(cc1)O / Paracetamol / 1.891648 / 3.052345 / 4.215662 / 2.601958 / 0.5100 / 0.2601
Anthelmintics (n=1)
17 / 54965-21-8 / CCCSc1ccc2nc([nH]c2c1)NC(=O)OC / Albendazole / 2.043574 / 3.724815 / 7.043574 / NA / 3.1400 / 9.8596
Antibacterials (n=28)
25 / 26787-78-0 / CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccc(cc3)O)C(=O)N2[C@H]1C(O)=O / Amoxicillin / 1.386681 / 5.220350 / NA / NA / 0.9700 / 0.9409
31 / 83905-01-5 / CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(C2O)N(C)C)C(C)(O)CC(C)CN(C)C(C)C(O)C1(C)O / Azithromycin / 2.573448 / NA / 3.795297 / NA / 4.0200 / 16.1604
51 / 78439-06-2 / CC(C)(O\N=C(/C(=O)NC1C2SCC(=C(N2C1=O)C(O)=O)C[n+]1ccccc1)\c1csc(n1)N)C(O)=O / Ceftazidime pentahydrate / 1.437417 / 7.340507 / 3.713141 / 3.713141 / -1.3600 / 1.8496
53 / 64544-07-6 / CO\N=C(/C(=O)N[C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)O[C@@H](C)OC(C)=O)COC(N)=O)\c1occc1 / Cefuroxime axetil / 1.707974 / 3.748933 / 2.707974 / 3.628793 / 0.1100 / 0.0121
56 / 56-75-7 / OCC(NC(=O)C(Cl)Cl)C(O)c1ccc(cc1)[N+]([O-])=O / Chloramphenicol / 2.111440 / NA / 3.025080 / 3.025080 / 1.1400 / 1.2996
61 / 57-62-5 / CN(C)[C@H]1[C@@H]2C[C@H]3C(=C(O)c4c(ccc(c4[C@@]3(C)O)Cl)O)C(=O)[C@]2(O)C(=O)\C(=C(\N)/O)\C1=O / Chlortetracycline / 2.203110 / NA / 3.573022 / NA / -0.6200 / 0.3844
65 / 85721-33-1 / OC(=O)C1=CN(C2CC2)c2cc(c(cc2C1=O)F)N1CCNCC1 / Ciprofloxacin / 2.219252 / 5.043160 / 3.742130 / NA / 0.0000 / 0.0000
68 / 81103-11-9 / CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(C2O)N(C)C)C(C)(CC(C)C(=O)C(C)C(O)C1(C)O)OC / Clarithromycin / 2.770076 / 8.572850 / 4.602038 / NA / 3.1800 / 10.1124
90 / 114-07-8 / CCC1OC(=O)C(C)C(OC2CC(C)(OC)C(O)C(C)O2)C(C)C(OC2OC(C)CC(C2O)N(C)C)C(C)(O)CC(C)C(=O)C(C)C(O)C1(C)O / Erythromycin base / 2.202900 / NA / 3.276826 / 3.322832 / 3.0600 / 9.3636
102 / 79660-72-3 / CN1CCN(CC1)c1c(cc2c(c1F)N(CCF)C=C(C(O)=O)C2=O)F / Fleroxacin / 1.965370 / 4.923977 / 3.567430 / 3.643150 / 1.0800 / 1.1664
104 / 42835-25-6 / C[C@@H]1CCc2cc(cc3c2N1C=C(C(O)=O)C3=O)F / Flumequine / 2.072668 / 1.718090 / 3.432983 / NA / 2.7000 / 7.2900
128 / 859-18-7 / CCC[C@@H]1C[C@H](N(C)C1)C(=O)N[C@H]([C@@H](C)O)[C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O / Lincomycin / 1.910129 / 6.764001 / 5.776591 / NA / 0.2900 / 0.0841
129 / 98079-51-7 / CCN1C=C(C(O)=O)C(=O)c2cc(c(c(c21)F)N1CCN[C@H](C)C1)F / Lomefloxacin / 1.965959 / 5.165531 / 3.431799 / 3.315294 / -0.3000 / 0.0900
146 / 443-48-1 / Cc1[n+H]cc(n1CCO)[N+]([O-])=O / Metronidazole / 1.756269 / 4.136481 / NA / 3.233391 / -0.1000 / 0.0100
164 / 67-20-9 / [O-][N+](=O)c1oc(cc1)\C=N\[N+H]1CC(=O)NC1=O / Nitrofurantion / 2.595830 / 3.721729 / 3.507636 / 4.376867 / -0.4700 / 0.2209
165 / 59-87-0 / NC(=O)N/N=C/c1oc(cc1)[N+]([O-])=O / Nitrofurazone / 2.526115 / 5.150839 / 3.839085 / 4.296967 / 0.2300 / 0.0529
168 / 85721-33-1 / C[C@@H]1COc2c(c(cc3c2N1C=C(C(O)=O)C3=O)F)N1CCN(C)CC1 / Ofloxacin / 2.002860 / 5.399592 / 4.317156 / NA / 0.0000 / 0.0000
175 / 79-57-2 / CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C(O)c4c(cccc4[C@@]3(C)O)O)C(=O)[C@]2(O)C(=O)\C(=C(\N)/O)\C1=O / Oxytetracycline (anhydrous) / 1.981931 / NA / NA / 3.663173 / -1.1200 / 1.2544
210 / 57-92-1 / CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@H]1[C@@H](O[C@@H](C)[C@]1(O)C=O)O[C@H]1[C@H](O)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]1N=C(N)N / Streptomycin / 1.810366 / 6.640757 / 3.077080 / NA / -7.5300 / 56.7009
211 / 68-35-9 / Nc1ccc(cc1)S(=O)(=O)Nc1ncccn1 / Sulfadiazine / 2.222326 / NA / 3.349199 / NA / -1.3000 / 1.6900
212 / 2447-57-6 / COc1ncnc(c1OC)NS(=O)(=O)c1ccc(cc1)N / Sulfadoxine / 1.775816 / 4.552300 / 3.491820 / NA / 0.7000 / 0.4900
213 / 127-69-5 / Cc1noc(c1C)NS(=O)(=O)c1ccc(cc1)N / Sulfafurazole / 1.427002 / NA / NA / 3.427002 / 1.0100 / 1.0201
214 / 127-79-7 / Cc1ccnc(n1)NS(=O)(=O)c1ccc(cc1)N / Sulfamerazine / 2.145638 / NA / NA / 3.422099 / 0.2100 / 0.0441
215 / 57-68-1 / Cc1cc(nc(n1)NS(=O)(=O)c1ccc(cc1)N)C / Sulfamethazine / 2.143527 / NA / NA / 3.444557 / 0.8900 / 0.7921
216 / 723-46-6 / Cc1onc(c1)NS(=O)(=O)c1ccc(cc1)N / Sulfamethoxazole / 1.611201 / 6.926471 / 4.403593 / NA / 0.8900 / 0.7921
219 / 60-54-8 / CN(C)[C@H]1[C@@H]2C[C@H]3C(=C(O)c4c(cccc4[C@@]3(C)O)O)C(=O)[C@]2(O)C(=O)\C(=C(\N)/O)\C1=O / Tetracycline / 2.740940 / 5.305391 / 6.430329 / 3.305391 / -1.3300 / 1.7689
236 / 738-70-5 / COc1cc(cc(c1OC)OC)Cc1cnc(nc1N)N / Trimethoprim / 3.161849 / 3.421486 / 3.462879 / 3.462879 / 0.6400 / 0.4096
239 / 1401-69-0 / CCC1OC(=O)CC(O)C(C)C(OC2OC(C)C(OC3CC(C)(O)C(O)C(C)O3)C(C2O)N(C)C)C(CC=O)CC(C)C(=O)C=CC(=CC1COC1OC(C)C(O)C(OC)C1OC)C / Tylosin / 2.262978 / NA / 3.129439 / NA / 1.0500 / 1.1025
Antidepressants (n=5)
22 / 50-48-6 / CN(C)CCC=C1c2ccccc2CCc2ccccc21 / Amitriptyline / 2.937970 / NA / 5.551025 / 5.551025 / 4.9500 / 24.5025
67 / 59729-33-8 / CN(C)CCC[C@]1(OCc2cc(ccc12)C#N)c1ccc(cc1)F / Citalopram / 3.258224 / NA / 4.920012 / NA / 3.7400 / 13.9876
109 / 54910-89-3 / CNCC[C@@H](Oc1ccc(cc1)C(F)(F)F)c1ccccc1 / Fluoxetine / 2.573969 / 7.110212 / 5.782853 / 5.645325 / 4.6500 / 21.6225
177 / 61869-08-7 / Fc1ccc(cc1)[C@@H]1CCNC[C@H]1COc1ccc2c(c1)OCO2 / Paroxetine / 2.818714 / NA / 5.754256 / 5.216654 / 3.9500 / 15.6025
200 / 79559-97-0 / CN[C@H]1CC[C@@H](c2ccc(c(c2)Cl)Cl)c2ccccc21 / Sertraline / 2.561774 / NA / 6.406872 / NA / 2.1800 / 4.7524
Antidiabetics (n=4)
9 / 56180-94-0 / C[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O[C@@H]2CO)O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1N[C@H]1C=C(CO)[C@@H](O)[C@H](O)[C@H]1O / Acarbose / 1.429759 / NA / 2.809971 / 2.809971 / -8.0800 / 65.2864
38 / 100-46-9 / NCc1ccccc1 / Benzylamine / 2.251860 / NA / 3.331042 / 3.687589 / 1.0900 / 1.1881
114 / 10238-21-8 / COc1ccc(cc1C(=O)NCCc1ccc(cc1)S(=O)(=O)NC(=O)NC1CCCCC1)Cl / Glibenclamide / 1.392701 / 3.693731 / 3.693731 / 3.693731 / 3.0000 / 9.0000
139 / 657-24-9 / CN(C)\C(=N)\N=C(N)N / Metformin / 1.949775 / NA / 1.982421 / NA / -2.6400 / 6.9696
Antiepiletics (n=4)
48 / 298-46-4 / NC(=O)N1c2ccccc2C=Cc2ccccc21 / Carbamazepine / 2.081823 / 3.847074 / 4.233534 / NA / 2.2500 / 5.0625
73 / 1622-61-3 / [O-][N+](=O)c1ccc2c(c1)C(=NCC(=O)N2)c1ccccc1Cl / Clonazepam / 1.323204 / NA / 4.022174 / 2.499296 / 2.4100 / 5.8081
111 / 60142-96-3 / NCC1(CCCCC1)CC(O)=O / Gabapentin / 1.330512 / NA / 2.192209 / NA / -1.1000 / 1.2100
180 / 50-06-6 / CCC1(C(=O)NC(=O)NC1=O)c1ccccc1 / Phenobarbital / 2.546390 / NA / 2.200690 / 2.681089 / 1.4700 / 2.1609
Antifungals (n=1)
117 / 126-07-8 / COc1cc(c2c(c1Cl)O[C@]1([C@H](C)CC(=O)C=C1OC)C2=O)OC / Griseofulvin (microsize) / 1.547493 / NA / 2.506100 / NA / 2.1800 / 4.7524
Antimalarial (n=1)
190 / 58-14-0 / CCc1nc(nc(c1c1ccc(cc1)Cl)N)N / Pyrimethamine / 2.752248 / 4.094671 / 4.714460 / 4.624849 / 2.4100 / 5.8081
Antimigraine (n=1)
13 / 50-78-2 / CC(=O)Oc1ccccc1C(O)=O / Acetylsalicylic acid / 2.954628 / 3.227493 / 3.311175 / 3.079567 / 1.1900 / 1.4161
Antineoplastics and Immunosuppressants (n=8)
44 / 55-98-1 / CS(=O)(=O)OCCCCOS(C)(=O)=O / Busulphan / 4.049029 / NA / 4.391452 / NA / -0.6800 / 0.4624
74 / 59865-13-3 / CCC1NC(=O)C(C(O)C(C)C\C=C\C)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O)C(C)C / Cyclosporine / 2.909869 / NA / 4.779100 / 4.080130 / 1.0000 / 1.0000
87 / 9/5/3094 / C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=C(F)C(=O)NC1=O / Doxifluridine / 1.861079 / 3.391279 / 3.391279 / 2.391279 / -1.4000 / 1.9600
108 / 51-21-8 / FC1=CNC(=O)NC1=O / Fluorouracil / 2.752477 / 6.072812 / 3.716265 / 2.114205 / -0.6900 / 0.4761
110 / 13311-84-7 / CC(C)C(=O)Nc1ccc(c(c1)C(F)(F)F)[N+]([O-])=O / Flutamide / 2.545272 / NA / 5.301368 / 2.441247 / 3.5100 / 12.3201
141 / 59-05-2 / CN(Cc1cnc2nc(nc(c2n1)N)N)c1ccc(cc1)C(=O)N[C@@H](CCC(O)=O)C(O)=O / Methotrexate / 3.527147 / 3.242507 / 2.657481 / 3.728062 / -1.2800 / 1.6384
223 / 154-42-7 / NC1=NC(=S)c2[nH]cnc2N1 / Thioguanine / 2.746084 / 7.691726 / 4.005721 / NA / -0.3100 / 0.0961
226 / 52-24-4 / S=P(N1CC1)(N1CC1)N1CC1 / Tiotepa / 3.915227 / NA / 2.539762 / NA / 0.6100 / 0.3721
Antivirals (n=5)
16 / 59277-89-3 / NC1=NC(=O)c2ncn(c2N1)COCCO / Acyclovir / 1.051551 / 3.356946 / 3.384098 / 3.374858 / -1.7000 / 2.8900
156 / 159989-64-7 / Cc1c(cccc1C(=O)N[C@@H](CSc1ccccc1)[C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)O / Nelfinavir / 2.055214 / 3.754184 / 3.754184 / 3.754184 / 4.1000 / 16.8100
197 / 127779-20-8 / CC(C)(C)NC(=O)C1CC2CCCCC2CN1CC(O)C(Cc1ccccc1)NC(=O)C(CC(N)=O)NC(=O)c1ccc2ccccc2n1 / Saquinavir amorphous (CS) / 2.127656 / 4.525596 / 4.270323 / 4.246842 / 3.3400 / 11.1556
209 / 3056-17-5 / CC1=CN([C@@H]2O[C@H](CO)C=C2)C(=O)NC1=O / Stavudine / 1.748606 / NA / 2.359440 / NA / -0.7900 / 0.6241
243 / 7481-89-2 / NC1=NC(=O)N(C=C1)[C@H]1CC[C@@H](CO)O1 / Zalcitabine / 2.023705 / NA / 2.071882 / NA / -1.7200 / 2.9584
Anxiolytic Sedative Hypnotics and Antipsychiotics (n=13)
24 / 57-43-2 / CCC1(CCC(C)C)C(=O)NC(=O)NC1=O / Amobarbital / 2.956696 / NA / NA / 3.423178 / 2.0000 / 4.0000
42 / 1812-30-2 / Brc1ccc2c(c1)C(=NCC(=O)N2)c1ccccn1 / Bromazepam / 2.209868 / NA / 3.499902 / 2.800932 / 1.9300 / 3.7249
55 / 302-17-0 / OC(O)C(Cl)(Cl)Cl / Chloral hydrate / 2.538209 / 4.771387 / 2.419204 / 1.983016 / 0.9900 / 0.9801
57 / 58-25-3 / CNC1=Nc2ccc(cc2C(=N(=O)C1)c1ccccc1)Cl / Chlordiazepoxide / 2.883486 / NA / NA / 3.663859 / 2.4400 / 5.9536
75 / 439-14-5 / CN1C(=O)CN=C(c2ccccc2)c2cc(ccc12)Cl / Diazepam / 2.603197 / 4.963094 / 4.820987 / 4.350652 / 2.5800 / 6.6564
106 / 1622-62-4 / CN1C(=O)C[N+H]=C(c2ccccc2F)c2cc(ccc12)[N+]([O-])=O / Flunitrazepam / 2.877895 / NA / NA / 3.571664 / 2.0600 / 4.2436
135 / 12/6/2898 / CN1CCN=C(c2ccccc2)c2cc(ccc12)Cl / Medazepam / 2.478343 / NA / NA / 5.318643 / 4.4300 / 19.6249
143 / 115-19-5 / CC(C)(O)C#C / Methylbutinol / 1.634852 / 2.225917 / 2.225917 / 1.924887 / 0.3200 / 0.1024
147 / 59467-70-8 / Cc1ncc2n1c1ccc(cc1C(=NC2)c1ccccc1F)Cl / Midazolam (base) / 3.180476 / 4.456009 / 6.211884 / 4.879446 / 2.7300 / 7.4529
163 / 146-22-5 / [O-][N+](=O)c1ccc2c(c1)C(=[N+H]CC(=O)N2)c1ccccc1 / Nitrazepam / 2.532670 / NA / NA / 2.449124 / 2.2200 / 4.9284
178 / 76-74-4 / CCC[C@@H](C)C1(CC)C(=O)NC(=O)NC1=O / Pentobarbital / 3.282754 / NA / NA / 3.660031 / 2.0000 / 4.0000
195 / 106266-06-2 / CC1=C(CCN2CCC(CC2)c2noc3cc(ccc23)F)C(=O)N2CCCCC2=N1 / Risperidone / 3.860486 / NA / 4.835152 / 4.835152 / 3.4900 / 12.1801
199 / 76-73-3 / CCC[C@@H](C)C1(CC=C)C(=O)NC(=O)NC1=O / Secobarbital / 3.280188 / NA / NA / 4.004186 / 2.3600 / 5.5696
Brochiodilators and Antiasthma Drugs (n=1)
222 / 58-55-9 / CN1C(=O)N(C)c2nc[nH]c2C1=O / Theophylline / 2.903490 / NA / 2.571725 / 2.627283 / -0.3900 / 0.1521
Cardiovascular Drugs (n=26)
10 / 37517-30-9 / CCCC(=O)Nc1ccc(c(c1)C(C)=O)OC[C@H](O)CNC(C)C / Acebutolol / 3.650677 / NA / 3.819325 / NA / 1.1900 / 1.4161
29 / 29122-68-7 / CC(C)NC[C@@H](O)COc1ccc(cc1)CC(N)=O / Atenolol / 2.124405 / 2.633044 / 3.901689 / NA / -0.0300 / 0.0009
32 / 27589-33-9 / NS(=O)(=O)c1cc(c(cc1Cl)NCc1sccc1)c1n[nH]nn1 / Azosemide / 2.164342 / 3.569176 / 3.743101 / 3.629657 / 3.0000 / 9.0000
39 / 41859-67-0 / CC(C)(Oc1ccc(cc1)CCNC(=O)c1ccc(cc1)Cl)C(O)=O / Bezafibrate / 2.524270 / 3.558498 / 3.558498 / 3.558498 / 3.0000 / 9.0000
47 / 62571-86-2 / C[C@H](CS)C(=O)N1CCC[C@H]1C(O)=O / Captopril / 1.709147 / 3.111715 / 3.337025 / NA / 0.8400 / 0.7056
49 / 72956-09-3 / COc1ccccc1OCCNC[C@@H](O)COc1cccc2[nH]c3ccccc3c12 / Carvedilol / 1.705950 / 6.378591 / 5.131918 / 5.609040 / 4.1900 / 17.5561
63 / 92077-78-6 / CCOC(=O)C(CCc1ccccc1)NC1CCCN2CCCC(N2C1=O)C(O)=O / Cilazapril / 1.921691 / 3.620661 / 2.626343 / 3.620661 / 0.8000 / 0.6400
71 / 637-07-0 / CCOC(=O)C(C)(C)Oc1ccc(cc1)Cl / Clofibrate / 2.411945 / 4.305892 / 4.137100 / 4.498582 / 3.6200 / 13.1044
72 / 882-09-7 / CC(C)(Oc1ccc(cc1)Cl)C(O)=O / Clofibric acid / 2.378935 / 3.397229 / 3.474395 / 3.382337 / 2.8400 / 8.0656
82 / 71-63-6 / CC1OC(CC(O)C1O)OC1C(O)CC(OC1C)OC1C(O)CC(OC1C)OC1CCC2(C)C(CCC3C2CCC2(C)C(CCC32O)C2=CC(=O)OC2)C1 / Digitoxin / 4.507969 / 3.883632 / 3.883632 / 6.485692 / 1.8500 / 3.4225
83 / 20830-75-5 / CC1OC(CC(O)C1O)OC1C(O)CC(OC1C)OC1C(O)CC(OC1C)OC1CCC2(C)C(CCC3C2CC(O)C2(C)C(CCC32O)C2=CC(=O)OC2)C1 / Digoxin / 4.441296 / NA / 4.566286 / NA / 1.2600 / 1.5876
99 / 49562-28-9 / CC(C)OC(=O)C(C)(C)Oc1ccc(cc1)C(=O)c1ccc(cc1)Cl / Fenofibrate / 2.256280 / NA / 3.858340 / NA / 5.1900 / 26.9361
113 / 25812-30-0 / Cc1ccc(c(c1)OCCCC(C)(C)C(O)=O)C / Gemfibrozil / 2.248076 / NA / 3.398525 / NA / 4.7700 / 22.7529
144 / 22664-55-7 / CC(C)NC[C@@H](O)COc1cc(c(c(c1C)C)OC(C)=O)C / Metipranolol / 3.092587 / 5.092587 / 3.916495 / 4.490527 / 2.6600 / 7.0756
145 / 56392-17-7 / COCCc1ccc(cc1)OC[C@H](O)CNC(C)C / Metoprolol / 1.686746 / 4.563786 / 4.482626 / NA / 1.6900 / 2.8561
152 / 42200-33-9 / CC(C)(C)NC[C@H](O)COc1cccc2c1C[C@H](O)[C@H](O)C2 / Nadolol / 1.766251 / NA / 3.277275 / NA / 1.1700 / 1.3689
153 / 57149-07-2 / COc1ccccc1N1CCN(CC1)C[C@@H](O)COc1cccc2ccccc12 / Naftopidil / 1.894866 / 3.593836 / 3.593836 / 3.593836 / 3.9400 / 15.5236
162 / 63675-72-9 / COC(=O)C1=C(C)NC(=C(C1c1ccccc1[N+]([O-])=O)C(=O)OCC(C)C)C / Nisolfipine / 2.489966 / NA / 4.070787 / 5.112180 / 3.9000 / 15.2100
166 / 55-63-0 / [O-][N+](=O)OC(CO[N+]([O-])=O)CO[N+]([O-])=O / Nitroglycerin / 3.335003 / NA / 3.648622 / 4.879071 / 1.6200 / 2.6244
170 / 96829-58-2 / CCCCCCCCCCCC(CC1OC(=O)C1CCCCCC)OC(=O)C(CC(C)C)NC=O / Orlistat / 1.996285 / 5.416502 / 4.850157 / 4.428083 / 3.0000 / 9.0000
186 / 525-66-6 / CC(C)NC[C@H](O)COc1cccc2ccccc12 / Propranolol / 2.594338 / 5.568784 / 5.510792 / 5.142040 / 2.6000 / 6.7600
207 / 3930-20-9 / CC(C)NC[C@H](O)c1ccc(cc1)NS(C)(=O)=O / Sotalol / 2.537519 / NA / 2.958025 / NA / 0.3700 / 0.1369
230 / 56211-40-6 / CC(C)NC(=O)NS(=O)(=O)c1cnccc1Nc1cccc(c1)C / Torasemide / 1.843132 / 3.542102 / 3.542102 / 3.542102 / 2.3000 / 5.2900
233 / 396-01-0 / Nc1nc(c2nc(c(nc2n1)N)c1ccccc1)N / Triamterene / 2.801517 / 4.257449 / 4.403577 / 4.289633 / 0.8000 / 0.6400
240 / 152-11-4 / COc1ccc(cc1OC)CCN(C)CCC[C@@](C#N)(C(C)C)c1ccc(c(c1)OC)OC / Verapamil / 3.624214 / NA / 4.812539 / 4.865246 / 3.4500 / 11.9025
241 / 129-06-6 / CC(=O)C[C@@H](c1ccccc1)C1=C(O)Oc2ccccc2C1=O / Warfarin / 5.284900 / NA / 4.258571 / 4.233748 / -0.8400 / 0.7056
Colouring Agent (n=6)
7 / 371-40-4 / Nc1ccc(cc1)F / 4-Fluoroaniline / 2.425650 / NA / NA / 4.647846 / 1.1500 / 1.3225
26 / 62-53-3 / Nc1ccccc1 / Aniline / 2.571140 / 3.690327 / 5.491959 / 3.943774 / 0.9100 / 0.8281
85 / 1141-88-4 / Nc1ccccc1SSc1ccccc1N / Dithiodianiline / 3.144662 / NA / 6.531759 / 6.670806 / 3.0000 / 9.0000
149 / 108-45-2 / Nc1cccc(c1)N / m-Phenylenediamine / 2.586839 / 4.653786 / 4.263145 / 1.829877 / -0.3100 / 0.0961
150 / 121-69-7 / CN(C)c1ccccc1 / N.N’-Dimethylaniline / 2.105256 / 2.551958 / 4.384467 / 3.564923 / 2.6200 / 6.8644
151 / 91-66-7 / CCN(CC)c1ccccc1 / N.N-Diethylaniline / 2.550622 / 4.726713 / 3.324452 / 4.385703 / 3.2400 / 10.4976
Contrat media (n=1)
121 / 73334-07-3 / COCC(=O)Nc1c(c(c(c(c1[I])C(=O)N(C)CC(O)CO)[I])C(=O)NCC(O)CO)[I] / Iopromide / 1.567766 / 3.761520 / 2.891347 / 2.915065 / -2.4900 / 6.2001
Corticosteriods (n=3)
43 / 51333-22-3 / CCC[C@@H]1O[C@@H]2C[C@H]3[C@@H]4CCC5=CC(=O)C=C[C@]5(C)[C@H]4[C@@H](O)C[C@]3(C)[C@@]2(O1)C(=O)CO / Budesonide / 2.128864 / NA / 4.332984 / 4.355260 / 2.1800 / 4.7524
81 / 59198-70-8 / CCCCC(=O)OCC(=O)[C@H]1[C@H](C)C[C@H]2[C@@H]3C[C@H](F)C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21C / Diflucortolone valerate / 2.188588 / NA / 5.638558 / NA / 4.5000 / 20.2500
107 / 67-73-2 / CC1(C)O[C@@H]2C[C@H]3[C@@H]4C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@@]2(O1)C(=O)CO / Fluocinolone acetonide / 2.053553 / 3.655613 / 3.655613 / 3.655613 / 2.4800 / 6.1504
Disinfectants and Preservatives (n=6)
34 / 65-85-0 / OC(=O)c1ccccc1 / Benzoic acid / 1.856349 / NA / 3.086798 / 2.831526 / 1.8800 / 3.5344
40 / 25013-16-5 / COc1ccc(c(c1)C(C)(C)C)O / BHA / 1.954836 / 4.255866 / 4.750716 / 4.913443 / 3.5000 / 12.2500
41 / 128-37-0 / Cc1cc(c(c(c1)C(C)(C)C)O)C(C)(C)C / BHT / 2.393731 / NA / 5.184758 / NA / 5.0300 / 25.3009
92 / 91-53-2 / CCOc1ccc2c(c1)C(=CC(C)(C)N2)C / Ethoxyquin / 2.433990 / NA / 5.036050 / 4.081808 / 3.8700 / 14.9769
115 / 111-30-8 / O=CCCCC=O / Glutaraldehyde / 2.873403 / NA / 3.788320 / 3.951290 / -0.1800 / 0.0324
234 / 3380-34-5 / Oc1cc(ccc1Oc1ccc(cc1Cl)Cl)Cl / Triclosan / 1.893514 / 7.808504 / 6.347773 / 6.046743 / 4.6600 / 21.7156
Dopaminergics (n=2)
127 / 59-92-7 / N[C@@H](Cc1ccc(c(c1)O)O)C(O)=O / Levodopa / 2.044465 / 5.118794 / 3.294885 / 3.294885 / -2.2400 / 5.0176
229 / 134308-13-7 / Cc1ccc(cc1)C(=O)c1cc(c(c(c1)[N+]([O-])=O)O)O / Tolcapone milled / 2.135522 / 5.477510 / 4.139886 / 5.260460 / 0.2000 / 0.0400
Gastrointestinal Drugs (n=6)
64 / 51481-61-9 / C\N=C(\NCCSCc1nc[nH]c1C)/NC#N / Cimetidine / 1.703010 / NA / 2.532749 / 2.401980 / 0.4000 / 0.1600
66 / 81098-60-4 / CO[C@@H]1CN(CCCOc2ccc(cc2)F)CC[C@@H]1NC(=O)c1cc(c(cc1OC)N)Cl / Cisapride / 2.048621 / NA / 2.668340 / 2.668340 / 3.0900 / 9.5481
98 / 76824-35-6 / NC(N)=Nc1scc(n1)CSCC/C(/N)=N/S(N)(=O)=O / Famotidine / 1.920839 / NA / 2.928303 / 2.695678 / -0.6400 / 0.4096
125 / 103577-45-3 / Cc1c(nccc1OCC(F)(F)F)CS(=O)c1[nH]c2ccccc2n1 / Lansoprazole / 1.868481 / NA / 4.225028 / 4.312178 / 2.3800 / 5.6644
169 / 73590-58-6 / COc1ccc2nc([nH]c2c1)S(=O)Cc1ncc(c(c1C)OC)C / Omeprazole / 2.193949 / NA / 3.593859 / NA / 2.2000 / 4.8400
194 / 66357-35-5 / CN/C(/NCCSCc1oc(cc1)CN(C)C)=C\[N+]([O-])=O / Ranitidine / 1.798515 / NA / 2.684572 / NA / 0.2900 / 0.0841
General Anaesthetics (n=1)
224 / 76-75-5 / CCC[C@@H](C)C1(CC)C(=O)NC(=S)NC1=O / Thiopental / 3.305236 / NA / NA / 3.966116 / 2.8700 / 8.2369
Muscle Relaxants (n=1)
138 / 1665-48-1 / Cc1cc(cc(c1)OC[C@H]1CNC(=O)O1)C / Metaxalone / 2.455592 / 3.344894 / 3.469833 / 3.913530 / 2.0000 / 4.0000
Nutritional Agents and Vitamines (n=2)
157 / 98-92-0 / NC(=O)c1cccnc1 / Niacinamide 100% DC / 1.542741 / 2.086809 / 2.086809 / 2.086809 / -0.3800 / 0.1444
161 / 59-67-6 / OC(=O)c1cccnc1 / Nicotinic Acid/Niacin / 1.245199 / NA / NA / 4.090297 / 0.3600 / 0.1296
Organic Solvents (n=6)
2 / 107-98-2 / COC[C@@H](C)O / 1-Methoxy-2-propanol / 0.398527 / 1.954830 / 0.593102 / 1.292072 / -0.4700 / 0.2209
27 / 100-66-3 / COc1ccccc1 / Anisol / 1.465783 / NA / 3.431925 / 2.954804 / 2.1100 / 4.4521
80 / 95-92-1 / CCOC(=O)C(=O)OCC / Diethyl oxalate / 2.562717 / NA / 2.393925 / NA / 0.4000 / 0.1600
142 / 74-89-5 / CN / Methylamin / 2.492162 / 3.890102 / 1.810921 / 3.492162 / -0.6400 / 0.4096
181 / 110-89-4 / C1CCNCC1 / Piperidine / 2.328118 / NA / 3.930178 / 3.267420 / 0.6700 / 0.4489
221 / 119-64-2 / C1CCc2ccccc2C1 / Tetralin / 4.911732 / 4.276149 / 4.741036 / 3.799028 / 3.8000 / 14.4400
Paraffins and Similar Bases (n=1)
54 / 36653-82-4 / CCCCCCCCCCCCCCCCO / Cetyl alcohol / 1.685641 / 2.554665 / NA / NA / 6.6500 / 44.2225
Pesticides and Repellents (n=2)
1 / 106-93-4 / BrCCBr / 1.2-Dibromoethane / 3.240414 / NA / 4.018566 / 3.570547 / 2.1000 / 4.4100
100 / 67306-00-7 / C[C@H](CN1CCCCC1)Cc1ccc(cc1)C(C)(C)C / Fenpropidin / 2.276426 / 7.681020 / 5.704501 / 5.021921 / 2.5900 / 6.7081
Sex Hormones (n=8)
91 / 57-63-6 / C[C@@]12CC[C@H]3[C@@H](CCc4cc(ccc34)O)[C@@H]2CC[C@@]1(O)C#C / Ethinylestradiol / 2.170861 / 5.547611 / 4.716016 / 5.267771 / 4.2000 / 17.6400
101 / 98319-26-7 / CC(C)(C)NC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4NC(=O)C=C[C@]4(C)[C@H]3CC[C@@]21C / Finasteride / 2.950008 / NA / 4.248965 / 4.270154 / 3.2000 / 10.2400
137 / 72-33-3 / COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@@]2(C)[C@H]1CC[C@@]2(O)C#C / Mestranol / 1.491971 / 3.491971 / 3.491971 / 3.491971 / 4.7500 / 22.5625
167 / 68-22-4 / CC12CCC3C(CCC4=CC(=O)CCC34)C2CCC1(O)C#C / Norethindrone / 1.696683 / 5.331819 / 3.474834 / NA / 2.9700 / 8.8209
173 / 434-07-1 / C[C@]1(O)CC[C@H]2[C@@H]3CC[C@H]4CC(=O)/C(/C[C@]4(C)[C@H]3CC[C@@]21C)=C\O / Oxymetholone / 2.521768 / 4.461070 / 4.534996 / NA / 3.0000 / 9.0000
217 / 58-22-0 / C[C@@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@]34C)[C@@H]2CC[C@@H]1O / Testosterone / 1.761069 / NA / 5.170004 / NA / 3.2700 / 10.6929
218 / 57-85-2 / CCC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C / Testosterone propionate / 2.537180 / 4.946116 / 3.537180 / 4.236150 / 4.5000 / 20.2500
232 / 10161-34-9 / CC(=O)O[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CCC4=C3C=C[C@]12C / Trenbolone acetate / 1.795752 / 3.723870 / 5.540479 / 5.318631 / 3.7700 / 14.2129
Stimulants and Anoeretics (n=2)
45 / 58-08-2 / Cn1cnc2c1C(=O)N(C)C(=O)N2C / Caffeine / 3.004931 / NA / 3.028161 / 3.348713 / -0.0900 / 0.0081
159 / 54-11-5 / CN1CCC[C@H]1c1cccnc1 / Nicotine / 3.511172 / NA / 4.733021 / 4.608082 / 1.0000 / 1.0000
Supplementary. intermediates. and misc. drugs (n=42)
3 / 120-78-5 / S(Sc1sc2ccccc2n1)c1sc2ccccc2n1 / 2.2’-Dithiobisbenzothiazole / 1.442572 / 3.919693 / 3.618663 / 3.702209 / 4.5000 / 20.2500
4 / 2416-94-6 / Cc1ccc(c(c1C)O)C / 2.3.6-Trimethylphenol / 1.988027 / 3.855402 / 4.179913 / 3.930035 / 2.7200 / 7.3984
5 / 504-29-0 / Nc1ccccn1 / 2-Aminopyridine / 2.672633 / NA / NA / 3.973663 / 0.4800 / 0.2304
6 / 104-90-5 / CCc1ccc(nc1)C / 2-Methyl-5-ethylpyridine / 4.969493 / 3.592075 / 3.481377 / NA / 2.3900 / 5.7121
8 / 4083-64-1 / Cc1ccc(cc1)S(=O)(=O)N=C=O / 4-Tosyl isocyanate / 1.945842 / NA / NA / 2.518951 / 2.3400 / 5.4756
11 / 64-19-7 / CC(O)=O / Acetic acid glacial / 1.258702 / NA / 2.800807 / 2.165747 / -0.3100 / 0.0961
12 / 108-24-7 / CC(=O)OC(C)=O / Acetic anhydride / 1.758562 / 1.477503 / 3.268619 / 2.585736 / -0.3000 / 0.0900
14 / 107-02-8 / C=CC=O / Acroleine / 3.333711 / 5.963354 / 6.406261 / 6.544564 / -0.1000 / 0.0100
15 / 60046-50-6 / CCCCCCCCCCCCOCCO / Actinol / 1.549550 / NA / NA / 3.362463 / 1.1000 / 1.2100
20 / 5329-14-6 / NS(O)(=O)=O / Amidosulfonic acid / 1.487481 / NA / NA / 3.140213 / -4.3400 / 18.8356
21 / 156-87-6 / NCCCO / Aminopropanol / 4.423912 / 3.062786 / 2.176729 / 2.875699 / -1.0400 / 1.0816
33 / 100-52-7 / O=Cc1ccccc1 / Benzaldehyde / 1.911869 / NA / NA / 4.144999 / 5.0000 / 25.0000
35 / 98-88-4 / ClC(=O)c1ccccc1 / Benzoyl chloride / 1.869136 / NA / NA / 4.272828 / 1.4400 / 2.0736
37 / 501-53-1 / ClC(=O)OCc1ccccc1 / Benzyl chloroformiate / 1.754845 / NA / NA / 4.231967 / 1.8400 / 3.3856
46 / 66-25-1 / CCCCCC=O / Capronaldehyde / 1.311386 / NA / NA / 3.854567 / 1.8000 / 3.2400
58 / 79-11-8 / OC(=O)CCl / Chloroacetic acid / 3.094607 / 7.130322 / 3.088930 / 2.470270 / 0.0000 / 0.0000
59 / 79-04-9 / ClCC(Cl)=O / Chloroacetyl chloride / 2.734797 / NA / 3.508792 / 4.450800 / -0.2200 / 0.0484
78 / 111-42-2 / OCCNCCO / Diethanolamine / 5.229361 / 3.146692 / 2.766481 / 2.118663 / -1.8000 / 3.2400
79 / 105-58-8 / CCOC(=O)OCC / Diethyl carbonate / 0.896277 / NA / NA / 2.373398 / 1.2100 / 1.4641
84 / 108-01-0 / CN(C)CCO / Dimethylethanolamine / 1.649028 / 3.405990 / 2.958832 / 2.950058 / -0.5500 / 0.3025
86 / 112-54-9 / CCCCCCCCCCCC=O / Dodecanal / 0.903847 / NA / NA / 4.850601 / 5.1000 / 26.0100
88 / 106-89-8 / ClC[C@@H]1CO1 / Epichlorohydrin / 3.012016 / NA / 3.586047 / 3.481959 / 0.4500 / 0.2025
93 / 74-96-4 / CCBr / Ethyl bromide / 1.906955 / 2.841389 / 2.745033 / 2.763131 / 1.6100 / 2.5921
94 / 105-37-3 / CCOC(=O)CC / Ethyl propionate / 1.068151 / 3.863037 / 2.013530 / 3.260977 / 1.2100 / 1.4641
95 / 75-21-8 / C1CO1 / Ethylene oxide / 2.786643 / NA / 2.507255 / 2.719696 / 0.5200 / 0.2704
96 / 107-15-3 / NCCN / Ethylenediamine / 1.699683 / 2.927606 / 4.834382 / 2.456645 / -1.2000 / 1.4400
97 / 2809-21-4 / CC(O)(P(O)(O)=O)P(O)(O)=O / Etidronic acid / 2.058655 / 4.836806 / 2.592117 / 3.012897 / -0.8100 / 0.6561
103 / 78755-81-4 / CCOC(=O)c1ncn2c1CN(C)C(=O)c1cc(ccc21)F / Flumazenil / 1.858612 / NA / NA / 2.782891 / 1.1000 / 1.2100
119 / 999-97-3 / C[Si](C)(C)N[Si](C)(C)C / Hexamethyldisilazane / 2.278468 / NA / 2.940715 / 2.985170 / 2.6200 / 6.8644
122 / 5417-35-6 / CC(C)C1OCC=CCO1 / Isopropyldioxepen / 2.223473 / NA / 2.272078 / NA / 1.7900 / 3.2041
132 / 110-16-7 / OC(=O)\C=C/C(O)=O / Maleic acid / 2.214699 / NA / 2.763702 / 3.064732 / -0.3000 / 0.0900
133 / 108-31-6 / O=C1OC(=O)C=C1 / Maleic anhydride / 2.389423 / NA / NA / 2.815392 / 1.6200 / 2.6244
134 / 105-53-3 / CCOC(=O)CC(=O)OCC / Malonic acid diethylester / 4.031393 / 2.498716 / 2.899228 / 3.341257 / 0.9600 / 0.9216
148 / 110-91-8 / C1COCCN1 / Morpholine / 1.778756 / 4.327340 / 2.940124 / 2.684851 / -2.5500 / 6.5025
172 / 149-73-5 / COC(OC)OC / Orthoformic acid trimethylester / 1.530258 / NA / NA / 2.400490 / 0.0900 / 0.0081
182 / 3282-30-2 / CC(C)(C)C(Cl)=O / Pivaloyl chloride / 2.117482 / NA / 2.576120 / 2.604149 / 0.8900 / 0.7921
185 / 123-38-6 / CCC=O / Propionaldehyde / 1.614806 / 2.349052 / 2.814635 / 3.617897 / 0.5900 / 0.3481
188 / 51-52-5 / CCCC1=CC(=O)NC(=S)N1 / Propylthiouracil / 2.134123 / 4.231033 / 4.189640 / 3.193607 / 1.5000 / 2.2500
191 / 8/3/2144 / Oc1ccc(c(c1O)O)C=O / Pyrogallolaldehyde / 1.846430 / 3.937445 / 3.669351 / NA / 1.5000 / 2.2500
201 / 138-59-0 / O[C@@H]1CC(=C[C@@H](O)[C@H]1O)C(O)=O / Shikimic acid / 2.240931 / 3.240931 / 3.176473 / 3.240931 / -1.5000 / 2.2500
237 / 935-92-2 / CC1=CC(=O)C(=C(C)C1=O)C / Trimethylquinone / 2.875573 / 4.176603 / 5.000512 / 5.176603 / 1.9300 / 3.7249
238 / 603-35-0 / c1ccc(cc1)P(c1ccccc1)c1ccccc1 / Triphenylphosphine / 2.573684 / 4.719812 / 4.719812 / 2.418782 / 2.6000 / 6.7600
Table S2Serial numbers of training and test set compounds used in developing the reported models (Eq. 1)
Description of developed model / Eq. no. / Ntotal / No. of Compounds after division / Sl. nos. of training set compounds / Sl. nos. of test set compoundsNtraining / Ntest
Rodent toxicity modeling / Whole class of compounds / 1 / 136 / 102 / 34 / 4, 5, 7, 12, 13, 17, 20, 22, 24, 28, 31, 32, 33, 35, 37, 39, 40, 42, 43, 53, 55, 56, 63, 65, 67, 68, 71, 72, 74, 75, 80, 81, 82, 83, 84, 85, 87, 88, 90, 92, 93, 95, 98, 99, 100, 102, 104, 105, 106, 107, 108, 109, 110, 113, 115, 122, 125, 127, 132, 133, 135, 139, 142, 146, 150, 151, 152, 153, 156, 162, 164, 165, 167, 169, 170, 173, 175, 181, 182, 185, 186, 188, 191, 197, 200, 201, 210, 212, 214, 215, 216, 218, 219, 222, 223, 230, 234, 236, 237, 238, 239, 243 / 8, 26, 29, 34, 38, 41, 45, 48, 57, 61, 66, 91, 101, 119, 120, 128, 129, 138, 143, 147, 149, 154, 163, 168, 176, 180, 190, 194, 209, 211, 213, 217, 229, 233
Antibacterials / 2 / 27 / − / − / 25, 31, 51, 53, 56, 61, 65, 68, 90, 102, 104, 128, 129, 164, 165, 168, 175, 210, 211, 212, 213, 214, 215, 216, 219, 236, 239
Psychopharmacological agents / 3 / 13 / − / − / 24, 42, 55, 57, 75, 106, 135, 143, 147, 163, 178, 195, 199
Cardiovascular drugs / 4 / 26 / − / − / 10, 29, 32, 39, 47, 49, 63, 71, 72, 82, 83, 99, 113, 144, 145, 152, 153, 162, 166, 170, 186, 207, 230, 233, 240, 241
Daphnia-algae inter species correlation modeling / 5 / 65 / 24 / 3, 4, 6, 12, 13, 16, 21, 26, 29, 32, 39, 40, 49, 51, 53, 58, 65, 68, 72, 75, 82, 87, 93, 97, 100, 102, 105, 108, 109, 120, 127, 129, 134, 138, 141, 142, 144, 145, 148, 149, 150, 151, 157, 164, 165, 167, 168, 170, 176, 190, 191, 197, 201, 210, 212, 216, 218, 221, 223, 232, 233, 234, 236, 237, 238 / 47, 48, 55, 63, 71, 76, 78, 84, 91, 104, 107, 114, 121, 137, 143, 153, 154, 156, 173, 185, 186, 188, 229, 230
Fish-algae inter species correlation model / 6 / 50 / 22 / 2, 4, 12, 13, 16, 32, 39, 40, 55, 63, 72, 75, 82, 84, 87, 91, 93, 94, 96, 97, 100, 102, 105, 107, 108, 109, 134, 137, 141, 142, 144, 146, 150, 151, 153, 156, 165, 170, 185, 186, 190, 218, 219, 221, 229, 230, 232, 233, 237, 238 / 21, 26, 49, 51, 53, 71, 78, 114, 120, 127, 129, 138, 143, 147, 148, 157, 164, 176, 188, 197, 234, 236