Medicines in the environment. Implications and perspectives

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Pharmaceutical medicines, and in particular antibiotics, are useful tools to treat and prevent human and animal diseases. However, after their administration a significant fraction of the drug is not retained by the body mass, but is excreted in urine and faeces (1). In addition, recent surveys report that people, in the everyday practice, do not properly dispose expired and unused pharmaceuticals, discharging them via the sink or toilet (2). This, along with (i) the widespread wastewater treatment plants which are not always appropriate in the disposal of medicines, (ii) the direct release to soils from animals at pasture and (iii) the common agricultural practices which involve the application of manure and slurry to lands, represents some of the most representative pathways through which drugs can reach the environment (3).

The presence of pharmaceuticals in surface/ground waters and arable soils has been frequently observed, causing great concern in the scientific community about the possible consequences on ecosystem and human health. In fact, due to their chemical-physical characteristics, numerous molecules appear fairly degradable, thus persisting even up to several months.

With regard to the Italian situation, Zuccato et al. (4) reported the presence of some of the most used antibiotics by Italians, such as penicillins and sulfonamides, in many rivers of the Northern regions, demonstrating their insufficient removal by current wastewater treatment plants. These analyses permitted to estimate that up to 10-20% of the substances consumed at a national scale was discharged into the environment after use.

As a result, biologically active compounds, although present at very low concentrations once in the environment, may affect non-target organisms causing significant changes in the biosphere stability (5). Generally, the most visible damages can occur on microorganisms, such as soil bacteria and enzymes. In fact, the impact on the structure of soil microbial communities, necessary for the maintenance of nutrient cycling and the organic matter decomposition, has been frequently documented.

However, two articles recently published on Nature highlighted some harmful, and sometimes lethal, consequences associated to drug exposure even in the case of superior organisms, such as vertebrates. The first one reported a significant decline in three vulture species observed in the Indian subcontinent, because of renal failure and visceral gout caused by the veterinary use of the anti-inflammatory diclofenac in cattle, whose carcasses represent the basis of the vulture diet (6). The second manuscript (7) testified the feminization of male fishes as a result of the entrance of contraceptive pill residues into rivers, estuaries and lakes, from female urine.

Nevertheless, the most alarming consequence of the presence of antibiotics in the environment is probably the development of resistant pathogenic bacteria. Indeed, a recent survey highlighted the impact of low amounts of veterinary antibiotics on relevant soil bacteria strains, such as Pseudomonas, suggesting the origin of resistant forms (8). Furthermore, if resistant pathogens develop in the proximity of croplands the risk of human exposure may increase. As if that was not enough, scientists pointed out that most likely more than one substance may be present in the environment at the same time and the effects of drug combinations could be greater than that of the single substance (9).

To have an idea of the antibiotic consumption magnitude, it is sufficient to consider that in several European countries the active molecule sales, in 2007, have been approximately 3500 and 3350 tons for veterinary and human use, respectively (10). Nevertheless, considering that low-cost drugs are raising accessibility to the worldwide population, which is expected to exceed 8 billion in 2050 and to get older – and elderly persons usually require significant medical care – these numbers are likely to increase (11).

Faced with such a scenario, which is the response of the scientific community? An example of awareness comes from the European Environment Agency (2), which has recently suggested some main guidelines to limit the anthropogenic input of medicines in the environment. Despite its economical limitations, the preferential recommendation concerns the development of more efficient wastewater treatment systems, for instance through the implementation of the current technologies with sorbents (e.g. activated carbon, minerals and molecular imprinted polymers), advanced oxidation processes and/or UV lamps.

A second approach regards the field of “green” pharmacy, where great progress has been made, such as the use of less hazardous solvents, new synthesis routes and more degradable medicines after use. Moreover, a recent report proposed the implementation of taxes and incentives to make “green” medicines more attractive to pharmaceutical companies than conventional ones (9).

Always the European Environment Agency strongly encourages a proper information and education of medical specialists, pharmacists, drug producers and patients on a more environmental friendly way to manage medicines in the health care system. In fact, the awareness of the ecological risks of pharmaceuticals could help to limit the input of drugs and their residues into the environment by improving the daily habits.

A good example is given by the currently running Swedish model, a voluntary system that informs the general public on the potential environmental hazard of pharmaceuticals through information available on websites and in information booklets (9). As a consequence to this educational initiative, the attention among doctors is grown and, at present, most of the medical specialists are taking action when prescribing medicines to patients to contain the drug residue release. In addition, over the past twenty years, various medicine disposal programs have been set up in many countries around the world. A valid example comes from Portugal, where nearly all pharmacies are members of the return medicine disposal network called Valormed (http://www.valormed.pt/), created in 2001 by pharmacists, pharmaceutical companies and wholesalers’ associations (12).

Finally, considering the modern agricultural practices as another major source of antibiotics and, in some countries, growth hormones as well, researchers of international relevance argue that changes in manure/sludge application rates and timings, development of recommendations on where and when manure and biosolids are not applicable (e.g. too steep fields), and specification of buffer zones to protect water bodies, could limit such a contamination (13).

To conclude, it is worth remembering that the scientific community continuously emphasizes and endorses both laboratory and field investigations in order to understand the implications of medicines on the ecosystem biodiversity and human health.

References

1) Sarmah AK, Meyer MT, Boxall ABA (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65:725-759

2) EEA (2010) Pharmaceuticals in the environment. Results of an EEA workshop. EEA Technical report No 1/2010

3) Jorgensen SE, Halling-Sorensen B (2000) Drugs in the environment. Chemosphere 40:691-699

4) Zuccato E, Castiglioni S, Bagnati R, Melis M, Fanelli R (2010) Source, occurrence and fate of antibiotics in the Italian aquatic environment. J Hazard Mater 179:1042-1048

5) Henschel KP, Wenzel A, Diedrich M, Fliedner A (1997) Environmental hazard assessment of pharmaceuticals. Regul Toxicol Pharm 25:220-225

6) Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU (2004) Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 427, 630-633

7) Owen R, Jobling S (2012) The hidden costs of flexible fertility. Nature 485, 441

8) Michelini L, Reichel R, Ghisi R, Thiele-Bruhn S (2012) Willow and maize root associated soil microbial community composition and enzyme activities in the presence of the antibiotic sulfadiazine. AECT- under review

9) Boxall ABA (2012) New and emerging water pollutants arising from agriculture, OECD Publishing 1-48

10) ECDC – European Centre for Disease Prevention and Control; European Food Safety Authority (EFSA), European Medicines Agency (EMEA); European Commission’s Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) (2009) Joint Opinion on antimicrobial resistance (AMR) focused on zoonotic infections. EFSA J 7:1372

11) Depledge M (2011) Pharmaceuticals: Reduce drug waste in the environment. Nature 478, 36

12) Kümmerer K (2008) Pharmaceuticals in the environment. Sources, fate, effects and risks. Third edition. Springer ed., Berlin 1-521

13) Pope L, Boxall A, Corsing C, Halling-Sorensen B, Tait A, Topp E (2009) Exposure assessment of veterinary medicines in terrestrial systems. In Crane M, Boxall ABA, Barrett K (Eds) Veterinary medicines in the environment. CRC Press, Boca Raton129-153

Lucia Michelini has a degree in Sciences and Technologies for Environment and Territory. She is currently completing her studies at the PhD School in Territory, Environment, Resources and Health at the University of Padova.

Picture from: Depledge M., Nature, 2011