2
R. Kusko and H. Hong
CYP
Cytochrome P450 enzyme
DA
Department of Agriculture
DILI
Drug-induced liver injury
EDC
Endocrine disrupting chemical
EDSP
Endocrine disruptor screening program
EPA
Environment Protection Agency
FDA
Food and Drug Administration
ML
Machine learning
MD
Molecular dynamics
MDDT Medical Device Development Tools
MOA
Mechanism of Action
MoA
Mode of Action
NCATS National Center for Advancing Translational Sciences
NIEHS National Institute of Environmental Health Sciences
NN
Neural Networks
POD
Point of Departure
QSAR Quantitative structure–activity relationship
REACH Registration, Evaluation, Authorisation and Restriction of Chemicals
TsTKB Target-specific Toxicity Knowledgebase
US
United States
1.1 Computational Toxicology
Toxicology as a broad field seeks to predict and eliminate substances which may cause
a living body harm, including pharmaceuticals, natural products, food products, and
environmental substances. Toxicology has been performed since the ancient Greeks
and Chinese [1]. It is currently a major field of study around the world. The study of
toxicology is of importance not only to governmental regulatory agencies, but also
to the pharmaceutical/biotech industry, the veterinary industry, food manufacturers, and academics. Toxicology also spans many sub-disciplines as it must consider
the entire path of a potential toxicant, including exposure, absorption, distribution,
metabolism, excretion, as well as interactions with cellular machinery throughout
this entire pathway (Fig. 1.1). Pinpointing the exact mechanism or mode of toxicity
as a potential toxicant interacts with a living organism is paramount. Adding to an
already complex system, nearly any known substance can be toxic at a high enough
exposure. Moreover, toxicity is dependent on an array of other factors including
organism size, species, age, sex, genetics, diet, combination with other chemicals,
overall health, and/or environmental context.
Toxicological methods can be classed into experimental and computational [2].
Experimental methods consist of two types: in vivo and in vitro experiments indicated
by the blue arrows in Fig. 1.1. Traditional experiments in toxicology are conducted
on non-human animals such and mice and rats [3]. Though in vivo experiments are
generally treated as the gold standard method in toxicological studies and remain as
R. Kusko and H. Hong
CYP
Cytochrome P450 enzyme
DA
Department of Agriculture
DILI
Drug-induced liver injury
EDC
Endocrine disrupting chemical
EDSP
Endocrine disruptor screening program
EPA
Environment Protection Agency
FDA
Food and Drug Administration
ML
Machine learning
MD
Molecular dynamics
MDDT Medical Device Development Tools
MOA
Mechanism of Action
MoA
Mode of Action
NCATS National Center for Advancing Translational Sciences
NIEHS National Institute of Environmental Health Sciences
NN
Neural Networks
POD
Point of Departure
QSAR Quantitative structure–activity relationship
REACH Registration, Evaluation, Authorisation and Restriction of Chemicals
TsTKB Target-specific Toxicity Knowledgebase
US
United States
1.1 Computational Toxicology
Toxicology as a broad field seeks to predict and eliminate substances which may cause
a living body harm, including pharmaceuticals, natural products, food products, and
environmental substances. Toxicology has been performed since the ancient Greeks
and Chinese [1]. It is currently a major field of study around the world. The study of
toxicology is of importance not only to governmental regulatory agencies, but also
to the pharmaceutical/biotech industry, the veterinary industry, food manufacturers, and academics. Toxicology also spans many sub-disciplines as it must consider
the entire path of a potential toxicant, including exposure, absorption, distribution,
metabolism, excretion, as well as interactions with cellular machinery throughout
this entire pathway (Fig. 1.1). Pinpointing the exact mechanism or mode of toxicity
as a potential toxicant interacts with a living organism is paramount. Adding to an
already complex system, nearly any known substance can be toxic at a high enough
exposure. Moreover, toxicity is dependent on an array of other factors including
organism size, species, age, sex, genetics, diet, combination with other chemicals,
overall health, and/or environmental context.
Toxicological methods can be classed into experimental and computational [2].
Experimental methods consist of two types: in vivo and in vitro experiments indicated
by the blue arrows in Fig. 1.1. Traditional experiments in toxicology are conducted
on non-human animals such and mice and rats [3]. Though in vivo experiments are
generally treated as the gold standard method in toxicological studies and remain as