- ACD/Labs ToxSuite. Advanced Chemistry
Development Inc., Toronto, Canada. Soft-
ware available atwww.acdlabs.com - Martin T Toxicity Estimation Software Tool
(TEST). Software available atwww.epa.gov/
nrmrl/std/qsar/qsar.html - TOxicity Prediction by Komputer Assisted
Technology (TOPKAT). Accelrys Inc., San
Diego, USA. Software available athttp://
accelrys.com - ADMET Predictor. Simulations Plus Inc.,
Lancaster, USA. Software available atwww.
simulationsplus.com - TerraQSAR. TerraBase Inc., Hamilton,
Canada. Software available atwww.terrabase-
inc.com - Gonella Diaza R, Manganelli S, Esposito A,
Roncaglioni A, Manganaro A, Benfenati E
(2015) Comparison of in silico tools for eval-
uating rat oral acute toxicity. SAR QSAR
Environ Res 26(1):1–27.https://doi.org/
10.1080/1062936x.2014.977819 - Drwal MN, Banerjee P, Dunkel M, Wettig
MR, Preissner R (2014) ProTox: a web server
for the in silico prediction of rodent oral tox-
icity. Nucleic Acids Res 42(Web Server issue):
W53–W58. https://doi.org/10.1093/nar/
gku401.nar/gku401 - Muller L, Kikuchi Y, Probst G, Schechtman L,
Shimada H, Sofuni T, Tweats D (1999)
ICH-harmonised guidances on genotoxicity
testing of pharmaceuticals: evolution,
reasoning and impact. Mutat Res 436
(3):195–225. https://doi.org/10.1016/
s1383-5742(99)00004-6 - Lagunin AA, Dearden JC, Filimonov DA,
Poroikov VV (2005) Computer-aided rodent
carcinogenicity prediction. Mutat Res 586
(2):138–146. https://doi.org/10.1016/j.
mrgentox.2005.06.005 - Benigni R (2005) Structure-activity relation-
ship studies of chemical mutagens and carci-
nogens: mechanistic investigations and
prediction approaches. Chem Rev 105
(5):1767–1800. https://doi.org/10.1021/
cr030049y - Sato S, Tomita I (2001) Short-term screening
method for the prediction of carcinogenicity
of chemical substances: current status and
problem of an in vivo rodent micronucleus
assay. J Health Sci 47(1):1–8.https://doi.
org/10.1248/jhs.47.1 - Benfenati E, Benigni R, Demarini DM,
Helma C, Kirkland D, Martin TM,
Mazzatorta P, Ouedraogo-Arras G, Richard
AM, Schilter B, Schoonen WG, Snyder RD,
Yang C (2009) Predictive models for
carcinogenicity and mutagenicity: frame-
works, state-of-the-art, and perspectives. J
Environ Sci Health C Environ Carcinog Eco-
toxicol Rev 27(2):57–90. https://doi.org/
10.1080/10590500902885593
- Kruhlak NL, Contrera JF, Benz RD, Mat-
thews EJ (2007) Progress in QSAR toxicity
screening of pharmaceutical impurities and
other FDA regulated products. Adv Drug
Deliv Rev 59(1):43–55.https://doi.org/10.
1016/j.addr.2006.10.008 - Ashby J (1985) Fundamental structural alerts
to potential carcinogenicity or noncarcino-
genicity. Environ Mutagen 7(6):919–921.
https://doi.org/10.1002/em.2860070613 - Bailey AB, Chanderbhan R, Collazo-Braier N,
Cheeseman MA, Twaroski ML (2005) The
use of structure-activity relationship analysis
in the food contact notification program.
Regul Toxicol Pharmacol 42(2):225–235.
https://doi.org/10.1016/j.yrtph.2005.04.
006 - Munro IC, Ford RA, Kennepohl E, Sprenger
JG (1996) Thresholds of toxicological con-
cern based on structure-activity relationships.
Drug Metab Rev 28(1–2):209–217.https://
doi.org/10.3109/03602539608994000 - Kazius J, McGuire R, Bursi R (2005) Deriva-
tion and validation of toxicophores for muta-
genicity prediction. J Med Chem 48
(1):312–320. https://doi.org/10.1021/
jm040835a - Kazius J, Nijssen S, Kok J, Back T, Ijzerman
AP (2006) Substructure mining using elabo-
rate chemical representation. J Chem Inf
Model 46(2):597–605.https://doi.org/10.
1021/ci0503715 - Benigni R, Bossa C (2008) Structure alerts for
carcinogenicity, and the Salmonella assay sys-
tem: a novel insight through the chemical
relational databases technology. Mutat Res
659(3):248–261.https://doi.org/10.1016/
j.mrrev.2008.05.003 - Wang Y, Lu J, Wang F, Shen Q, Zheng M,
Luo X, Zhu W, Jiang H, Chen K (2012)
Estimation of carcinogenicity using molecular
fragments tree. J Chem Inf Model 52
(8):1994–2003. https://doi.org/10.1021/
ci300266p - Kalgutkar AS, Didiuk MT (2009) Structural
alerts, reactive metabolites, and protein cova-
lent binding: how reliable are these attributes
as predictors of drug toxicity? Chem Biodivers
6(11):2115–2137 - Benigni R, Bossa C, Tcheremenskaia O
(2013) Nongenotoxic carcinogenicity of che-
micals: mechanisms of action and early
262 Jing Lu et al.