The presence of human pharmaceuticals in the environment is not a new issue; their presence in the aquatic environment in North America was highlighted several decades ago (Stumm-Zollinger and Fair, 1965, Tabak and Bunch, 1970; Garrison et al., 1975). In Europe, the first reports of human pharmaceuticals in the environment were published a little later (eg Aherne and Briggs, 1989). These early reports from Europe were very far-sighted in that they identified sex steroids, and in particular oestrogens, as being present in the aquatic environment, and likely to affect reproduction of fish if concentrations were high enough. Research progressed steadily during the 1980’s and 1990’s, and this progress was summarized a decade ago in two influential reviews by primarily European chemists who had been studying the presence of pharmaceuticals and personal care products in the environment (Halling-Sorensen et al., 1998; Daughton and Ternes, 1999).
Since, an increasing interest in this area resulted in an “explosion” in the number of references (Roig, 2010). However, all this research merely documented the presence, fate and behaviour of human pharmaceuticals in the environment; it did little to address the issue of whether or not their presence constituted a hazard to either wildlife (especially aquatic organisms) and humans drinking water containing minute quantities of these pharmaceuticals.
According to the literature review, it appears that most pharmaceuticals do not pose a threat to the environment, but a small number do, and that none appear likely to pose a significant threat to human health (via environmental exposure). These conclusions are supported by the most recent and detailed human health risk assessment (Cunningham et al., 2009). However, this apparent certainty that there is no human health risk posed by the presence of human pharmaceuticals in the environment is not supported by deeper thinking. For example, the apparently reassuring risk assessments of Cunningham et al (2009) are based on potential risks to healthy adults: the more sensitive and hence vulnerable foetus, child elderly and infirm were not considered. The real situation is that, currently, there are many more uncertainties than certainties, which leaves the public and the press still unconvinced that drinking water containing a tiny quantity of a pharmaceutical is completely harmless. Thus, the key objective of this proposal is to significantly advance the science, so that the risks to the environment and public health can be more accurately defined. An additional key point of the proposal is to include the main transformation products (metabolites, degradation and treatment by products) with the target molecules. The characterisation of such risk has to be unquestionable, robust and reliable. Furthermore, for decision makers and also for the general public, it is important to make this science easily understandable and available.
However, with thousands, of different pharmaceuticals present in the environment, it will obviously be impractical to study them all, or even a reasonable proportion of them, hence the choice of target pharmaceuticals is a necessity to perform the right research. The wisest strategy is to focus on the group, or groups, of pharmaceuticals considered most likely to be a threat to the environment and/or human health. We concur with Cunningham et al (2009) that these are anticancer drugs and antibiotics (see selection of target pharmaceuticals below). The anticancer drugs can be cytotoxic, genotoxic, mutagenic and teratogenic, and it is generally accepted that no threshold of safety can be given for some of them. Moreover, they represent a group of pharmaceuticals that has been studied very little, yet are obviously of high importance. Concerning the second group, the antibiotics, although their presence in the environment has already been well studied, the extent to which they are responsible for the induction of genetic resistance is still not well understood.
In this context, and in order to move science in this area forward, PHARMAS project will pursue the following aims:
1. PHARMAS will determine the human and animal exposure to the target molecules by measuring and modelling the concentrations found from the resource (mainly surface water) to the tap (drinking water). This will be done for all EU 27 countries. It will provide accurate, reliable exposure data (concentration and scenario of exposure) without which risk assessments are not possible.
2. PHARMAS will provide the missing data on ecotoxicological and toxicological thresholds of concern, i.e. the lowest concentrations/doses that still cause effects on wild animals, plants, microorganisms and humans. This will be achieved by the implementation of targeted ecotoxicological experiments and the compilation of all available literature to determine the minimum dose of selected drugs of potential concern that cause measurable effects on human health.
3. PHARMAS will determine if embryos/newborns are more susceptible than adults to adverse effects of pharmaceuticals, allowing us to state whether (as some suggest), risk assessments should be focused on the unborn/newborn.
4. PHARMAS will go beyond the typical substance-by-substance risk assessments by investigating the toxicity of realistic mixtures involving antibiotics and anti-cancer drugs in several dedicated case studies.
5. PHARMAS will produce probabilistic estimates of the risk caused by the exposure of wildlife and humans to the selected pharmaceuticals by analyzing the uncertainty and variability in the exposure estimates.
6. PHARMAS will evaluate the usefulness of ecological effect data for the assessment of human effects. These will be evaluated based on a comparison of the toxicokinetic and toxicodynamic processes involved.
7. PHARMAS will explore options to develop a common effect endpoint for human and ecological risks.
8. PHARMAS will identify stable transformation products of the drugs of interest and will investigate their concentrations and (eco)toxicology in the environment.
9. PHARMAS will explore the needs and contents, as well as the scientific and socio-economic impact, of a pan-European classification system. Based on the Swedish experience, PHARMAS will develop a web-based prototype classification system primarily designed as an easily accessible (web-based) decision support tool for practitioners (e.g. physicians and pharmacists) providing straightforward action alternatives
10. As “Pharmaceuticals in the Environment” is an issue receiving growing attention, from scientists, the media and the public, with a current inability to answer many of the key questions, PHARMAS will help the public to make an assessment of whether or not it should be worried by the presence of pharmaceuticals in the environment and in drinking water.
11. PHARMAS will stimulate discussion by all stakeholders and beneficiaries of the work by supporting communication and collaboration between scientists and regulators.
12. PHARMAS will contribute to an evolution of the regulation and EU policies by distilling the policy-relevant information, products and conclusions of the project for the relevant policy fields.
13. PHARMAS will promote the results of the project by the organisation of an international conference in month 24, the edition of newsletters and policy brief and the implementation of a web site.