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In Silico Testing

In silico, is an expression known as computer simulation. Various types of in silico methods are developed to characterize and predict toxic outcomes in humans and environments. In silico testing gives these results in a fraction of the time required for trials. In silico testing has provided data to build various forms of studies and models to gain more information about individual, animals, and the environment.

Subjects

In silico subjects are based on real individuals and observed variability of key parameters in general population. When the set of equations are defining in silico subjects are displayed, in silico cohort is created by generating parameter vectors spanning the parameter space observed. in silico subjects with widely distributed metabolic parameters represent well the intersubject variability observed in vivo.

Sensor

In silico sensors are developed on the basis of analysis of sensor errors. When a sensor simulation is initialized, the corresponding output should be set of sensor error with a distribution of a real sensor. The sensor simulation model provides knowledge of any errors, and the data is distributed to the real sensor to have a control trial. The simulated and observed distributions cover all possible error values.

Toxicology

In silico toxicology is the integration of modern computing and information technology with molecular biology to improve agency prioritization of data requirement and risk assessment of chemicals. In silico toxicology is toxicology research and risk assessment that occupy in silico components. In silico toxicology develops and stores data through computerized programs. In silico toxicology allows research to have access to different types of information.

Toxicokinetics

Toxicokinetics is a part of an in vivo study, when developing an alternative approach base on in vitro study. Toxicokinetic modeling is the most sufficient approach to simulate the fate of compounds in the human body, yet high-quality data is needed as input for the model. Toxicokinetic models are ideally suited for the integration of data produced from in vitro or in silico methods into a biological framework, and for the extrapolation to in vivo condition.

Pharmacokinetics

an example of the PBPK model

Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion. A fundamental concept in pharmacokinetics is drug clearance, the elimination of drugs from the body. Pharmacokinetics recognized the impact certain drugs can have an individual. Pharmacokinetics research have create models and data that assist in silico studies.

Physiologically based pharmacokinetics modelling

Physiologically based pharmacokinetics modelling has become a core approach to organize and combine input from in vivo, in vitro, and in silico studies. PBPK models are evolved compartmental models which try to use realistic biological descriptions of the determinants of the disposition of a chemical compound in the body. These models are usually used to estimate the concentration in a particular tissue, given a external exposure pattern, or an effective toxic concentration determined in a relevant in vitro system. in silico predictions are not used in isolation, they already constitute as a part of the integrated testing strategy.

Generic Applications

Inter-individual extrapolations, refers to the fact that a given exposure may induce different effects to the individuals of a population and that the same individual may respond differently to the same exposure at different times in his/her lifetime. These extrapolations are performed by setting parameter values to those of a subpopulation or an individual of interest, and are mainly used to predict the differential effects of chemicals on sensitive populations.

Inter-dose extrapolation

These extrapolations are achieved by capturing both the linear and non-linear steps of the biological processes known to govern the kinetics of the chemical of interest.

Inter-route of exposure extrapolation

Any route of exposure can be described either in isolation or in combination.

Specific Applications

A approach for pure predictions of toxicity, PBTK models can be used in a step by step approach. PBTK models can incorporate the results of specific in vitro estimates of pharmacokinetic parameters. PBTK modelling has been used primarily for the estimation of internal exposures in the studies,anf characterizing the toxicity of a chemical.

Non-Testing Methods

Non-testing data can be generated by three main approaches: grouping approaches, which include read-across and chemical category formation; structure–activity relationship (SAR) and quantitative SAR (QSAR), and expert systems. In more general terms, non-testing methods can be divided into two main classes, comprehensive global and specific local ones.

Quantitative SAR

(Q)SAR is a mathematical model that correlates a quantitative measure of chemical structure to either a physical property or a biological effect. (Q)SAR models are available for repeated dose toxicity, the latter often being considered as a far too heterogeneous and complex endpoint to be encoded in a single predictive model. While (Q)SARs could have an important role to play, they may need to be more focused on specific mechanisms, and a suite of (Q)SARs will probably be necessary for most endpoints. It is worth also noting that most of these (Q)SARs have been developed to serve pharmaceutical needs. In silico models are best used in an integrated testing strategy and not as individual isolated tools.