Over the last few years, the presence in the environment of trace amounts of emerging substances, especially drug residues in water, has been a concern for public opinion, the scientific community and the health authorities. Numerous studies have indeed demonstrated the presence of therapeutic or diagnostic compounds in surface water or groundwater at concentrations ranging from a few nanograms to a few micrograms per litre. Some of these resources are then used for the production of water intended for human consumption, and drug residues have sometimes been identified in the public water supply in France. This therefore raises the issue of the potential health risks to users associated with the presence of these substances at the measured levels.
In this context, and despite the fact that no study has yet demonstrated any health risk associated with the presence of drug residues in water intended for human consumption, the Agency has been working on this topic since 2006, mainly at the request of the French Ministry of Health. Its work is part of the National Plan on Drug Residues in Water (PNRM) launched in 2011, and which followed the National Environmental Health Plans (PNSE 1 and PNSE 2).
A comprehensive approach to provide answers
In 2008, the Agency developed a prioritisation strategy to determine the most relevant human and veterinary drugs to be screened for in water intended for human consumption.
Based on this, it then developed analytical methods for these substances. In 2011, ANSES’s Nancy Laboratory for Hydrology published the results of a national campaign specifically on the detection of human and veterinary drug residues in resources used for the production of the drinking water supply and in treated water.
Pending the results of this campaign, ANSES and the French National Agency for Medicines and Health Products Safety (ANSM) were both formally requested to assess the health risks associated with the presence of drug residues in water intended for human consumption. This required defining a method for assessing such risks and testing its application on carbamazepine, a drug used in human medicine that, according to the bibliography, had a high probability of being found, and on a compound used in veterinary medicine, both of which were detected during the analysis campaign.
In June 2010, the Agency published the first part of this work, dedicated to assessment of exposure to drug residues via water intended for human consumption. The final results of this assessment are published today in the form of an opinion and report.
A general risk assessment method
Based on its previous work, the expert appraisal published today by the Agency proposes a general method for assessing the health risks associated with the presence of drug residues in water intended for human consumption. This method consists of eight steps dealing respectively with the compound’s characteristics, the identification of relevant drug metabolites and transformation products for the risk assessment, the assessment of human exposure via water intended for human consumption, the determination of the biological effects of the substances assessed, the determination of toxicity reference values, the development of a guideline value and, finally, the risk assessment.
As part of this work, the Agency applied this method to two drugs and two of their metabolites. Carbamazepine, a substance used in human medicine for its antiepileptic, neurotropic and psychotropic properties, with its metabolite 10,11-epoxycarbamazepine, and danofloxacin, an antibiotic of the class of fluoroquinolones used exclusively in veterinary medicine, with its metabolite desmethyldanofloxacin.
Agency’s conclusions and recommendations
The experts conclude that there is a negligible health risk following the ingestion of these compounds via water intended for human consumption, with the safety margins being adequate regardless of the assessment methods used and in view of the available analytical and toxicological data.
However, applying ANSES’s proposed method to these substances has brought to light a number of limitations. In terms of exposure, there are few available robust data on the contamination of water intended for human consumption in France by drug residues, and especially by their metabolites and transformation products. The study conducted by the Nancy Laboratory for Hydrology, which served to characterise French exposure to carbamazepine and danofloxacin, despite being of good quality, gives only a snapshot of the contamination of water intended for human consumption in France, and does not include spatial and temporal variations.
Moreover, assessing the chronic toxicity of the active ingredients is also hampered by a lack of data, mainly on drugs for human use, because they are either non-existent or inaccessible.
All of these limitations mean that a quantitative risk assessment is difficult. Thus, the Agency stresses the need for chronic toxicity studies on drug residues, but also on their relevant metabolites and transformation products.
More broadly, the issue of assessing the risks of such residues is also part of the general problem of taking into account the possible effects of mixtures of substances at low doses.
The Agency will continue its assessment work with the other substances screened for as part of the analysis campaign performed by the Nancy laboratory.