Tricarboxylic Acid (TCA) Cycle

One of the latest technologies to emerge - metabolomics - is being used to create a snapshot of how environmental chemicals affect living organisms.

An added complication is the fact that the interaction between the environment and organism health is extremely complex, with chemical, biological, physical and geographical stressors each contributing to toxicological effects over time.

To what extent do living organisms absorb pollutants in our environment? Are particular ‘chemical cocktails’ more risky than others? Do current ecotoxicological risk assessment techniques adequately protect the environment? These are the sorts of questions that interest Drs Oliver Jones and Julian Griffin in the Department of Biochemistry, who are working as part of a Europe-wide integrated research project to develop better tools to evaluate the chemical risks we face in everyday life.


It is generally acknowledged that many organisms in the environment are exposed to a large variety of pollutants during their lifetime; a fact borne out by advances in analytical technology. For example, many people will have heard of the effects on fish populations caused by endocrine-disrupting compounds in sewage, whereby some male fish living downstream of sewage treatment plants were found to have developed female characteristics, leading to a reduction in their ability to reproduce. In recent years, a plethora of other anthropogenic contaminants such as pharmaceuticals, personal care products, pesticides and flame retardants, and the potential for these man-made products to work their way into the food chain, have also begun to be of concern to environmental chemists.

However, the majority of these pollutants are present at extremely low concentrations and so it is difficult to ascertain whether or not they have an overall effect on ecosystem health, especially if outward effects are minimal. An added complication is the fact that the interaction between the environment and organism health is extremely complex, with chemical, biological, physical and geographical stressors each contributing to toxicological effects over time.

It’s important therefore to develop methods for assessing the cumulative risks for a range of species that are being exposed to mixtures of pollutants at non-lethal levels. In this way, steps can be taken both to improve safety in the environment and to safeguard ecological health.


One technique that shows a great deal of promise in the area of ecotoxicology is metabolomics. This rapidly emerging discipline measures the thousands of naturally occurring small molecules (metabolites) such as sugars, organic acids, amino acids and lipids that are the products of cellular metabolism. An organism’s ‘metabolome’ is its full complement of metabolites, in the same way that its genome is its complete genetic content.

Why study metabolic changes? Well, these changes often happen much earlier in an organism than either tissue accumulation of pollutants or induced histopathological changes. The technique can be used to give a biochemical snapshot of a cell, tissue or indeed whole organism at a moment in time. When an organism is stressed or diseased, its metabolic pathways are perturbed. Advanced computer-assisted pattern recognition techniques can then be used to assess the differences in metabolic profiles between sample groups. Metabolomics therefore offers a particularly sensitive method to monitor changes in a biological system and is proving to be an outstanding tool for studying ecotoxicology.

No Miracle

The environmental research in Dr Griffin’s group in the Department of Biochemistry is part of a European Union (EU) research project involving 38 laboratories spread across 16 countries and is known as NoMiracle (for ‘Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe’). The project seeks to improve ecological and environmental risk assessment in the EU, and to help scientists gauge the impact of chemicals on the environment and human health.

The Cambridge team are developing analytical techniques based on high-throughput analysis of metabolites from organisms at different positions in the food chain, such as earthworms, nematodes, slime moulds, marine mussels and water fleas. Being able to study such a broad set of experimental species has been possible because of long-term collaborations with the Centre for Ecology and Hydrology (part of the UK Natural Environment Research Council), King’s College London, the University of Piemonte Orientale in Italy and the University of Antwerp in Belgium, all developed as part of the NoMiracle project.

Using state-of-the-art nuclear magnetic resonance spectroscopy and gas chromatography mass spectrometry, long-term studies are being run to establish a basal metabolic profile for each of these species, as well as how these profiles change in response to toxic insult. By looking at the different patterns of metabolic profiles between organisms, a comprehensive description is being built up of how each of them responds to stress and toxicity. One important finding has been that biochemical effects are often observed at lower chemical concentrations than were previously thought to cause any effect when assessed using traditional toxicology testing techniques.

Assessing the risks

Why is there a need for improved risk assessment in ecotoxicology? In current toxicity tests, an organism is typically exposed to a single chemical in a strictly controlled laboratory setting, over a relatively short period of time (typically days or weeks). Yet, in the environment, organisms will clearly be exposed to many different pollutants possibly throughout their entire life. An accurate risk assessment must take into account cumulative effects rather than just direct effects and single factors. Organisms are also often likely to be stressed by other factors not present in a laboratory setting. For instance, work within the NoMiracle project has demonstrated that organisms can be affected by pollutants at much lower levels than those predicted from traditional toxicity tests if they are also stressed by other factors such as co-exposure to pollutants, temperature extremes or food restriction.

The work in the Cambridge section of the NoMiracle project is moving into its third and final year. The research is showing that the accurate assessment of chemical mixtures is more complex than current testing regimes allow for and the aim now is to use these results to develop a new framework for assessing the effects of complex mixtures of pollutants. The ultimate goal of the NoMiracle partners is to change ecotoxicology policy in the whole of the EU, so that long-term, multi-stressor exposure testing is considered as standard. This will offer great improvements in understanding and mitigating the effects of cumulative pollution exposure on the health of our ecosystem.

For more information, please contact the authors Dr Oliver Jones ( or Dr Julian Griffin ( at the Department of Biochemistry.

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