While Regulatory Toxicology is a requirement, we have chosen to make Systems Toxicology an inherent part of the scientific assessment of our smoke-free products. Systems Toxicology addresses the questions why and how a substance is toxic.
What is Systems Toxicology?
The Institute for Health and Consumer Protection (IHCP) from the European Commission defines Systems Toxicology as a branch of science that aims to quantitatively understand, model, and predict the response of cells to external stimuli and expand this to model organ and body systems.
Within the context of chemical exposure measurements and a causal succession of molecular events linking exposures with toxicity and eventual disease outcome, Systems Toxicology allows us to build a detailed understanding of the mechanisms by which biological systems respond to toxicants, and to use this understanding to assess the risk of chemicals, drugs and consumer products.
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Why is Systems Toxicology important?
• Systems Toxicology can be used to predict the impact of external stimuli on the global cell machinery of the exposed biological systems
• Systems Toxicology allows us to gain a detailed understanding of the mechanisms by which biological systems respond to toxicants
• Systems Toxicology provides us with the means to use this understanding to assess how chemicals, and consumer products may influence the risk of developing diseases
The 3R principles
Advancing methods in toxicology
What is our Systems Toxicology approach?
Our in-house quantitative systems-based approach provides a robust impact assessment tool for RRPs.
Hoeng, J., et al. (2012). "A network-based approach to quantifying the impact of biologically active substances." Drug Discov Today 17(9): 413-418.
Design and conduct a Systems Biology experiment
A well-designed experiment begins with the choice of the appropriate experimental system and exposure method. It is very important to properly characterize the exposure of the system by measuring how much of the aerosol or smoke has been absorbed by the system during the exposure. During this stage, samples are harvested and a very comprehensive set of measurements is performed. This includes omics profiling as well as other endpoints.
Calculate Systems Response Profile
The data obtained in the first steps undergoes quality control and statistical analysis to generate an unbiased list of changes (the systems response profile) between exposed and unexposed samples.
Identify the biological mechanisms that are affected by the exposure and represent them as networks of molecules and their interactions.
Quantify the perturbations of individual networks by computing the Network Perturbation Amplitude (NPA) scores.
Quantify the overall perturbation induced by exposure by aggregating the NPA scores into a Biological Impact Factor (BIF) for one stimulus or a set of stimuli.
Defining exposure and experimental setup
In Vitro Systems, In Vivo Systems, Clinical Systems, Whole Smoke/Aerosol Exposure
Measuring biological impact
Cellular and tissue phenotypic screening; mechanistic, biological and omics endpoints
Assessing biological impact qualitatively and quantitatively
Computational biology, bioinformatics, biostatistics, causal biological network modeling
Our sbv IMPROVER project uses a crowd-sourcing approach to verify our methods, studies and results. sbv IMPROVER stands for systems biology verification: Industrial Methodology for PROcess VErification in Research and has demonstrated that crowd sourcing is a viable strategy to verify scientific methodology and results in an industrial context and to build strong methodological foundations in systems biology.
Understanding how biological systems respond to toxicants and how to use this to assess the risk of RRPs.
Years of biological research have already yielded a lot of data about what biological changes precede smoking-related diseases. The research has demonstrated that these biological changes occur at a molecular level, often well before disease symptoms appear. Therefore, Systems Toxicology studies can help us understand the potential effect that our smoke-free products may have on the development of smoking-related diseases in smokers who completely switched to them.