RTD info logoMagazine on European Research

N 40 - February 2004
  MEDICINES AND THE ENVIRONMENT  -  Taking the pollution out of health care

'The attention paid to date by governments and scientists to the impact of pharmaceutical products on the environment can be described as weak or negligible.' That is the verdict of Professor Roberto Andreozzi (University of Naples 'Federico II'), chemist, expert on oxidation, and coordinator of one of the three European research projects in the Pharma Cluster. The aim of this research is to make a detailed study of the toxicity of the principal persistent molecules found in waste of medicinal or para-medicinal origin, and to propose effective treatment solutions.

A number of parameters affect the effectiveness of water treatment plants, such as the nature of the products, time spent at the plant, slurry activation, etc. A European study carried out in four countries revealed the presence of various pharmaceutical agents at the plant outlet points.
A number of parameters affect the effectiveness of water treatment plants, such as the nature of the products, time spent at the plant, slurry activation, etc. A European study carried out in four countries revealed the presence of various pharmaceutical agents at the plant outlet points.
More than 3 000 pharmaceutical substances are used in the Union. A recent survey estimated that more than 100 tonnes of prescription drugs are issued every year in Germany alone. European consumption of antibiotics (used widely in veterinary medicine) is on the same scale as the production of certain pesticides – several thousand tonnes a year. Yet, unlike many other molecules which are commercially available, pharmaceuticals are designed specifically to have biological effects. They are often persistent and lipophillic, properties which aggravate their polluting potential.

Antibiotics: cautious optimism
Launched in 2000(1), the three research projects included in the Pharma Cluster are looking at the three main facets of the problem of waste of medicinal origin(2). The Eravmis project is concentrating on the impact of veterinary antibiotics. 'With production running at over 5 000 tonnes a year in Europe, these are by far the most widely used molecules,' explains project coordinator Alistair Boxall of the Cranfield Centre for Eco Chemistry (UK). The research has focused on three major antibiotics, members of the tetracycline, macrolide and sulphonamide families. ‘Along with our Dutch, Danish and Spanish partners, we had already acquired expertise in studying and detecting these substances, but this European co-operation has made it possible to draw on a pool of skills not possible at national level,' stresses the project coordinator.

Eravmis  tested the migration of these three classes of antibiotics into soils and groundwater, as well as their life expectancy in these environments. Researchers studied what happens to their metabolites and their impact on various families of living organisms – bacteria, of course, but also algae, aquatic plants, worms, freshwater invertebrates and fish cell lines. So, what did they find? Apart from aquatic plants, which proved sensitive to sulphonamides (whose structure is similar to certain pesticides), it is only bacteria that react to the concentrations generally found in the environment. As these products are, in fact, designed mainly to combat bacteria, this is hardly surprising.

For other living organisms, the first effects are only found at concentrations above 1 mg/kg. Even the most contaminated sites studied scarcely reached half this concentration.

Although a reassuring result, a word of caution must be sounded. 'Much remains to be done,' reports Boxall. 'Our studies were over short periods – three weeks at the most – and we know that some of these molecules remain in the environment for months. And as farm animals are treated regularly with antibiotics, some environments are subject to continuous exposure, the effects of which require further investigation.'

'Post-treatment' analysis
Around 140 000 tonnes of shampoo enter the water cycle every year in Germany alone. Soap, bubble baths and other PPCPs – pharmaceuticals and personal care products – also have an environmental impact which researchers are beginning to study very seriously.
Around 140 000 tonnes of shampoo enter the water cycle every year in Germany alone. Soap, bubble baths and other PPCPs – pharmaceuticals and personal care products – also have an environmental impact which researchers are beginning to study very seriously.
The Rempharmawater project looked at the impact of a wide range of human medicines at a key stage, i.e. the point of exit from sewage treatment plants. With the exception of accidental pollution or special cases, pharmaceutical products enter the environment after passing through the human body. They are present in the urine and faeces which enter the purification networks before ending up in the aquatic environment or being spread as slurry on the land. An initial study of the pharmaceutical molecules present at these sewage plant outlets was carried out in the four project partner countries (Italy, France, Greece and Sweden). The effectiveness of the treatment was shown to be highly variable with very different results, depending on the nature of the products, time spent at the plant, slurry activation, etc.

'In the effluent analysed we recorded the presence of 26 pharmaceutical agents belonging to six therapeutic classes: antibiotics, beta blockers, antiseptics, anti-inflammatories and lipid regulators,' explains project coordinator Roberto Andreozzi of the University of Naples ‘Federico II’. The researchers then scrutinised the behaviour of six of the most common such products: carbamazepine, clofibric acid, diclofenac, sulfamethoxazole, ofloxacin, and propanolol(3).

Having established their half-life (the time required for half their molecules to break down naturally) in the laboratory they found themselves facing some very worrying results: for the first two compounds, this half-life was 1 712 and 600 days respectively – or almost five years in the case of carbamazepine. 'Although tests carried out on algae, fish and invertebrates showed that these products generally only produce an effect at concentrations higher than those found in the environment, it must be stressed that such tests, especially those using algae, are not able to reproduce the real conditions of their potential activity. Additional research and evaluations are therefore needed to define the risks posed by these molecules, as well as by other similar products.'

There is one note of optimism, however. The researchers also made an evaluation of how this pharmaceutical residue behaved when exposed to the latest treatment, in particular exposure to powerful oxidants such as ozone or hydrogen peroxide. To do so, they concocted a concentrated cocktail of their six molecules, subjected it to oxidation, then administered it to the alga S. Leopolensis, known to be particularly sensitive to pollutants. The alga showed no adverse affects, indicating that such treatment effectively combats toxicity.

Kind to body and environment
Poseidon(4), the third project in the cluster, concentrated on studying the different water treatment technologies currently available. This involved scrutinising the results achieved in the case of pollution by both medicines and by pharmaceutical and personal care products – PPCPs for short. The latter – with over 8 000 preparations currently available over the counter at shops across Europe – represent a huge volume, with 140 000 tonnes of shampoo products alone entering the water cycle every year in Germany.

Thomas Ternes of the Bundesanstalt für Gewaesserkunde (BFG Koblenz, DE), the project coordinator, explains that 'we have identified many possible avenues for improvement. In some cases, we can collect and treat urine separately, considerably reducing contamination at the treatment plant outlet. Also, simply increasing the retention time, by using modern waste-water treatments, makes it possible to effectively eliminate all the hormones. Finally, if ozonation is added to these methods, all pharmaceutical products are rendered biologically inactive, at least as far as we can detect at present.'

As regards drinking water, Poseidon has served to establish that we have the technology (active carbon filtration, nanofiltration, oxidation) to eliminate all the products studied – although at a price, of course. Researchers recommend creating an ecological label as an incentive to industrialists to make available products which are kindest to the ecosystem.

(1) The key action Sustainable management and quality of water under the Fifth Framework Programme.
(2) The results of these studies will form the basis for regulations under the Reach legislative initiative. Proposed by the Commission, this aims to regulate the impact of chemical products on the environment (see In brief [ news_en.html ]).
(3) The principal prescriptions for these products are as follows: carbamazepine: epilepsy; clofibric acid: anticholesterol; diclofenac: anti-inflammatory; sulfamethoxazole: antibiotic; ofloxacin: urogenital infections; and propanolol: Parkinson's disease.
(4) Poseidon brought together eight partners, in Germany (2), Switzerland, Austria, Finland, France, Spain and Poland.

  From identification to risk analysis  
  The Envirpharma conference – organised in Lyons (FR) in April 2003 by Cemagref, a partner in the Rempharmawater project – took initial stock of the Pharma Cluster results. 'To date we have identified many substances which we know enter the environment,' explained Jeanne Garric (Cemagref). 'But we know little about their impact. We must develop the biological tools to carry out a genuine risk analysis, especially at very low doses.' 

Scientists must also look at the problem of mixes, as none of the molecules identified is present in isolation. Antibiotics, for example, are often administered directly in the form of a 'cocktail' by a veterinary surgeon. In the natural environment, pharmaceutical products are also present alongside pesticides and other compounds likely to reinforce or alter their action, create synergies, etc. Although these are not easy processes to study, this is a vital area of research which has been earmarked for funding under the Sixth Framework Programme. 


  Veterinary products: the need to investigate  
  Although antibiotics are the most commonly used molecules in veterinary care, they are not necessarily the most active. A number of European studies have stressed the worrying impact of certain anthelmintics (vermifuges) which contaminate the environment through animal excrement. 'Laboratory tests show that these substances are toxic at low concentrations,' stresses Alistair Boxall. 'Research is necessary to assess their real impact in the environment.' 

An article that appeared in the journal Environmental Science and Technology, published in connection with the Eravmis project, in co-operation with a US researcher, reviews the current state of knowledge on this question. The authors give a long list of other suspect veterinary products, especially antifungals, hormones, growth promoters, anaesthetics, and anti-coccidiosis drugs.


  Spreading the knowledge  
  An important function of the coming together of the Eravmis, Rempharmawater and Poseidon projects under the umbrella of the Pharma Cluster is to permit the exchange of data collected and the dissemination of the research results. The Commission is supporting this ambition through a new project called Triton. This aims to communicate new knowledge about product toxicity and technologies to cleanup pollution to young PhDs and doctors active in this area. In this way it will also contribute to the harmonisation of practices at European level.

Triton offers seminars and intensive distance training modules on analytical chemistry, the evaluation and management of environmental risks, and advanced technology for water treatment, organised by five university centres (FI, DE, ES, PL, AU).