2 Background, Tasks, Modeling Methods …
17
QSAR
Quantitative structure–activity relationship
REACH
Registration, evaluation, authorization and restriction of chemicals
RNA
Ribonucleic acid
SE
Semi-empirical
SEURAT
Safety Evaluation Ultimately Replacing Animal Testing
SMILES
Simplified molecular-input line-entry system
SOC
Semi-volatile organic compound
US
United States
2.1 Background for Computational Toxicology
Environmental chemicals (e.g., industrial chemicals, pesticides, pharmaceuticals,
personal care products, flame retardants, etc.) constitute a major risk of affecting
human and ecological health [1, 2]. To solve problems caused by the pollution of
chemicals, it is necessary to assess/predict the exposure, hazard, and risk of chemicals before their entrance into the market, and to restrict the use of chemicals that are
of high concern [3]. Such a preventive perception of risk management has brought
about the most rigorous regulation in the history of humanity—the registration, evaluation, authorization, and restriction of chemicals (REACH) by the European Union
(EU) [4], which has profoundly reshaped the global chemicals management system.
Chemicals risk assessment itself, however, has encountered a bottleneck. Since
the twentieth century, the core discipline for assessing toxic effects of chemicals,
toxicology, has barely developed. The discipline has relied heavily on in vivo animal
tests for a long time, which may violate the replacement, reduction, and refinement
principles (3R principles) for animal tests. Besides, conventional in vivo tests have
to deal with uncertainties from conservative extrapolations between distinct dose
levels or different species. Based only on traditional in vivo tests, it will definitely
be difficult to accurately predict the toxicological effect of chemicals on human and
ecological health. On the other hand, an unprecedented number of chemicals are
awaiting comprehensive assessment. According to the statistics by REACH, there
are more than 140,000 chemicals registered in the European markets, among which
80% lack the safety data required [5, 6]. It is estimated that around 500–1000 new
chemicals are introduced into the market per year, which is much faster than the speed
of traditional chemicals risk assessment (ca. 2–3 years per chemical). Therefore, if the
assessment is to be merely based on conventional experiments, application of novel
chemicals as well as alternatives of legacy chemicals could be severely impeded due
to the inefficiency of the traditional risk assessment process.
In the recent decade, with the acknowledgement of the above-mentioned challenges, chemical toxicity test methodology has been going through a radical revolution [7]. In the report “Toxicity test in 21st century: A vision and strategy” published
in 2007 by the United States (US) National Research Council [8], toxicity pathway was emphasized and a paradigm shift from traditionally descriptive toxicology
17
QSAR
Quantitative structure–activity relationship
REACH
Registration, evaluation, authorization and restriction of chemicals
RNA
Ribonucleic acid
SE
Semi-empirical
SEURAT
Safety Evaluation Ultimately Replacing Animal Testing
SMILES
Simplified molecular-input line-entry system
SOC
Semi-volatile organic compound
US
United States
2.1 Background for Computational Toxicology
Environmental chemicals (e.g., industrial chemicals, pesticides, pharmaceuticals,
personal care products, flame retardants, etc.) constitute a major risk of affecting
human and ecological health [1, 2]. To solve problems caused by the pollution of
chemicals, it is necessary to assess/predict the exposure, hazard, and risk of chemicals before their entrance into the market, and to restrict the use of chemicals that are
of high concern [3]. Such a preventive perception of risk management has brought
about the most rigorous regulation in the history of humanity—the registration, evaluation, authorization, and restriction of chemicals (REACH) by the European Union
(EU) [4], which has profoundly reshaped the global chemicals management system.
Chemicals risk assessment itself, however, has encountered a bottleneck. Since
the twentieth century, the core discipline for assessing toxic effects of chemicals,
toxicology, has barely developed. The discipline has relied heavily on in vivo animal
tests for a long time, which may violate the replacement, reduction, and refinement
principles (3R principles) for animal tests. Besides, conventional in vivo tests have
to deal with uncertainties from conservative extrapolations between distinct dose
levels or different species. Based only on traditional in vivo tests, it will definitely
be difficult to accurately predict the toxicological effect of chemicals on human and
ecological health. On the other hand, an unprecedented number of chemicals are
awaiting comprehensive assessment. According to the statistics by REACH, there
are more than 140,000 chemicals registered in the European markets, among which
80% lack the safety data required [5, 6]. It is estimated that around 500–1000 new
chemicals are introduced into the market per year, which is much faster than the speed
of traditional chemicals risk assessment (ca. 2–3 years per chemical). Therefore, if the
assessment is to be merely based on conventional experiments, application of novel
chemicals as well as alternatives of legacy chemicals could be severely impeded due
to the inefficiency of the traditional risk assessment process.
In the recent decade, with the acknowledgement of the above-mentioned challenges, chemical toxicity test methodology has been going through a radical revolution [7]. In the report “Toxicity test in 21st century: A vision and strategy” published
in 2007 by the United States (US) National Research Council [8], toxicity pathway was emphasized and a paradigm shift from traditionally descriptive toxicology