A new review article from Nick Plant (An Introduction to Systems Toxicology; Toxicology Research, 2014) provides an excellent overview of the need for systems toxicology, and the available approaches: covering relational databases, rule and structure alerts and modelling, ranging from small to multiscale and from qualitative to quantitaitve models.
Plant approaches this topic from the perspective of drug discovery, and links systems toxicology to the fascinating prospect of network drug targeting, in which drug discovery could in fact start with drug combinations, with each drug alone appearing minimally active. The risk would be that this ‘synergistic pharmacology’ might be accompanied by ‘synergistic toxicology’; however there are some encouraging signs that in fact combination therapies are generally more specific than single therapies.
The AOP-wiki is now public access, and should constitute an invaluable resource in terms of making the AOP concept more tangible, providing state-of-the-art AOP examples and allowing users to start thinking about the practical applications of AOPs and the wider implementation of the AOP concept.
The wiki is part of a wider knowledgebase and will fit with other components of the knowledgebase including Effectopedia (OECD), the AOP Xplorer (US Army Corps of Engineers – Engineering Research and Development Center) and the Intermediate Effects DB (EC JRC).
The US NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) held a workshop on AOPs: from Research to Regulation on 3-5th September 2014. The agenda and video casts of the plenary sessions are available online here.
An Adverse outcome pathways (AOP) describes causal Key Events (KEs) between a molecular initiating event (MIE) and an adverse outcome (AO). Events are linked by Key Event Relationships (KERs), which require a weight of evidence (WoE) assessment. AOPs may provide ways of presenting the weight of evidence for an effect, of identifying biomarkers and of identifying endpoints that require test development.
When I tried to describe what entities were covered by toxicology, I thought ‘that’s easy, it’s chemicals’! But it is very important to note that not all chemicals are ‘bad’, that the body is composed of chemicals, and we could not live without chemicals (as well as finding many chemicals useful and convenient). There are also different terms, some used interchangeably, some with important differences and meanings. This post will try and clarify the matter, and explore how these definitions affect toxicology. It is a work in progress!
Toxicology is the study of chemicals and similar items that can affect human health, or the environment.
The aim of this post is to describe the important aspects of toxicology, as they relate to an understanding of systems toxicology. Toxicology spans biology and chemistry, and can include politics, geography, economics, social science and much more. There are many good toxicology textbooks that describe this fascinating field in fuller detail. Continue reading
Systems Toxicology (systox) is the use of computational methods from the field of Systems Biology to do Toxicology, the aim of which is to protect human health and the environment from the adverse effects of chemicals (see ‘what is toxicology?’).