The safety of chemicals in the environment is assessed by conducting an environmental risk assessment. The approach requires the comparison of the concentration of a chemical which is expected to be present in the environment (the Predicted Environmental Concentration or PEC) with the concentration of the chemical which is not expected to produce an adverse impact on organisms in that environment (the Predicted No Effect Concentration or PNEC). This approach recognizes that whilst all chemicals have the potential to have adverse effects on organisms through one or a number of potential proposed modes of toxic action, whether this potential is ever realised is highly dependent on the exposure (e.g. chemical concentration, duration of exposure etc.).

Up to 70% of the most commonly used chemicals in industrial applications are thought to act by narcosis as their sole mode of toxic action in aquatic organisms. These chemicals act on fundamental cellular functions and can impact a wide range of species when they enter into the environment. However, the mechanistic details about how these chemicals elicit their toxicity on a molecular level are often either undefined or poorly understood. Consequently, it is difficult with current approaches to classify them with confidence, extrapolate between species and to understand their full potential as environmental toxicants.

The well-established chemical classification scheme of Verhaar et al. (1992) identifies two separate classes of narcotic chemicals, namely general narcotics and polar narcotics. There is, however, some evidence that other distinct classes of narcosis may exist, such as ester and amine narcosis.  Common to all narcotic-acting chemicals is a strong correlation between toxicity and hydrophobicity. This suggests that the lipid phase (including membranes) of the organism is a key target site. Due to this strong correlation between the potency of narcotic compounds and hydrophobicity, accurate predictions of acute effects (notably lethality) can often be made where a chemical can be positively classified as a narcotic. Sub-acute effects and other mechanisms of toxicity require further effort to make accurate predictions. Thus, if a chemical can be established with a high degree of confidence to act only by narcosis (i.e. having no additional more specific mechanisms of toxicity) across species then appropriate strategies for establishing hazard can be taken as part of the risk assessment approach to assess environmental safety.

A common theory with regards to the chemical mode of action for narcosis is that partitioning into lipid membranes leads to changes in membrane fluidity, which in turn disrupts signalling pathways. In fish this can lead to key events such as cardiovascular and respiratory failure.  Other organisms, however, have different physiological systems and may thus be subject to other key events in the narcosis mode of action.

The AOP approach has recently been suggested as a useful framework to help bridge the gaps between effects at the molecular, cellular, individual, population and community levels. We are currently using the AOP framework to develop case studies considering narcotic chemicals. Specifically we are investigating the use of a range of techniques including ‘omics and computation chemistry and toxicology approaches to better understand mechanisms of narcosis in a range of chemicals in several model species. The case studies will ultimately be applied as examples of how the AOP approach can improve our mechanistic understanding of the adverse effects of narcotic chemicals for future use in environmental risk assessment.

Latest Presentation

The role of 21st century toxicology in refining Environmental Risk Assessment

Potential Roles of Omics Data in the use of Adverse Outcome Pathways for Environmental Risk Assessment

A systems biological approach to understanding narcosis using Caenorhabditis Elegans and RTgill cell lines

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Geoff Hodges