The term environmental persistent pharmaceutical pollutants (EPPP) was first suggested in the nomination in 2010 of pharmaceuticals and environment as an emerging issue in a Strategic Approach to International Chemicals Management (SAICM)Strategic Approach to International Chemicals Management by the International Society of Doctors for the Environment (ISDE). The occurring problems from EPPPs are in parallel explained under environmental impact of pharmaceuticals and personal care products (PPCP). The European Union summarizes pharmaceutical residues with the potential of contamination of water and soil together with other micropollutants under "priority substances".DIRECTIVE 2013/39/EU of 12 August 2013 amending Directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy
Background Pharmaceuticals comprise one of the few groups of chemicals that are specifically designed to act on living cells. They present a special risk when they persist in the environment.
With the exception of watercourses downstream of sewage treatment plants, the concentration of pharmaceuticals in surface and ground water is generally low. Concentrations in sewage sludge and in landfill leachate may be substantially higher and provide alternative routes for EPPPs to enter the human and animal food-chain.
However, even at very low environmental concentrations (often ug/L or ng/L), the chronic exposure to environmental pharmaceuticals chemicals can add to the effects of other chemicals in the cocktail is still not studied. The different chemicals might be potentiating synergistic effects (higher than additive effects). An extremely sensitive group in this respect are foetuses.
EPPPs are already found in water all over the world. The diffuse exposure might contribute to extinction of species and imbalance of sensible ecosystems, as many EPPPs affect the reproductive systems of for example frogs, mussels, and fish; genetic, developmental, immune and hormonal health effects to humans and other species, in the same way as e.g. oestrogen-like chemicals; development of microbes resistant to antibiotics, as is found in India.
Environmental classification of pharmaceuticals In Sweden, industry together with universities and the health care sector has developed a method for environmental risk assessment and environmental classification of drugs.Gunnarsson B, Wennmalm Å. (2006) Environmental risk assessment and environmental classification of drugs. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB, 2006Environmentally Classified Pharmaceuticals 2011 . Stockholm: Stockholm County Council, 2011 Environmental risk refers to the risk of toxicity to the aquatic environment. It is based on the ratio between predicted environmental concentration of the substance (PEC) and the highest concentration of the substance that does not have a harmful effect in the environment (PNEC).
Environmental hazard expresses the inherent environmentally damaging characteristics of the substance in terms of persistence, bioaccumulation and toxicity. The toxicity tests used are acute toxicity of fish, acute toxicity of Daphnia sp. and growth inhibition test of algae. Most medications on the Swedish market are now classified. This gives the healthcare sector the possibility to make better choices when prescribing medicines.
Exposure Concentrations in surface waters, groundwater and partially treated water are typically less than 0.1 μg/L (or 100 ng/L), and concentrations in treated water are generally below 0.05 μg/L (or 50 ng/L). However, all water on the earth is part of the same stable pool, and as larger amounts of pharmaceuticals are consumed, there is a risk that the concentration of pharmaceuticals in drinking water will increase.
Release into the environment Pharmaceuticals reach the environment and cause water pollution mainly in three ways: They are excreted from humans and animals, intact or metabolised, mainly into the urine, passing on to the environment directly or via sewage treatment plants. Unused pharmaceuticals reach the environment either via household wastewater or via urban solid garbage handling. Manufacturing plants producing the active substances might unintentionally release pharmaceuticals into the environment.
Due to improved measurement methods, pharmaceuticals may be detected today in concentrations that probably have been present already for decades but could not be measured before. Many pharmaceuticals are (after consumption) excreted or washed off: investigations have shown excretion rates between 30% and 70% of orally taken substancesEco-directed sustainable prescribing: feasibility for reducing water contamination by drugs, 2014 and even higher rates considering externally applied ointments or gel.BIO Intelligence Service (2013), Study on the environmental risks of medicinal products, Final Report prepared for Executive Agency for Health and Consumers"
Some pharmaceuticals are degraded to various extents in sewage treatment plants, but others leave the plant in active forms. Active residues of pharmaceuticals have been detected in surface water, and they may persist in the environment for long periods of time. Large amounts of antibiotics and other pharmaceuticals have been found downstream from sewage treatment plants in sub catchments where the discharge of hospital wastewater plays a major role noPILLS in waters, 2015 or in catchments with pharmaceutical industries. EPPPs from treated sewage sludge used as fertilizer are absorbed by soya, and antibiotics have been found in the leaves.
Drinking water There are various pathways how pharmaceutical substances may enter drinking water. Predominantly, drinking water procurement comes from drinking water reservoirs, groundwater and bank filtration. If treated wastewater is discharged in catchments with drinking water procurement, the not eliminated pharmaceutical substances may be detected in the drinking water. The Netherlands for example gain 37% of their drinking water from surface water, mainly from bank filtration at Rhine and Meuse. Here certain attention is paid to pharmaceutical residues.
In German drinking water catchments and rivers, EPPPs have been detected already, especially radiocontrast agents. Moreover, pharmaceutical residues here partly have their origin in agriculture.Bayerisches Landesamt für Umwelt An evaluation of the German Federal Environment Agency of regional investigations carried out between 2009 and 2011 showed in total 27 different pharmaceutical substances in concentrations of more than 0.1 microgram per litre in German surface waters and up to 150 substances have been detected in total. Besides the radiocontrast agents, the painkiller diclofenac showed relevant concentrations.Hintergrundpapier des Umweltbundesamtes, 2014 For many micropollutants such as pharmaceuticals no threshold values in drinking water purification or waste water treatment are obligatory by now as the knowledge about effects is lacking or insufficiently proven.German Federal Environment Agency "Arzneimittel und Umwelt"
Some of these environmental pharmaceutical chemicals are well known to have serious genotoxic effects in humans. Half-life in nature varies depends on the environment (air, water, soil, sludge), but is more than one year for several compounds.Tysklind M et al. (2006) The spread of drugs in soil and water. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB.Westerlund E. (2007) Screening of pharmaceuticals in Skåne . Länstyrelsen i Skåne län. [In Swedish]
Concentrations of EPPPs can vary from 1 ng per litre to 1 mg per litre (2). Serious effects of EPPPs on water-living organisms, especially on reproductive systems, and on microbial communities have been already shown.Larsson J et al. (2006) Hormones and endocrine-disrupting substances in the environment. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB.Pharmaceuticals in the environment. Results of an EEA workshop. (2010) Luxembourg: Office for Official Publications of the European Communities.
This would be of much less concern if the populations were to keep their excrement out of the wastewater via the use of the urine-diverting dry toilet or systems that recycle treated blackwater to flush toilets again indefinitely.
Assessment Pharmaceuticals are special kinds of chemicals. They are manufactured to be biologically active in living organisms. The levels of pharmaceuticals in surface or drinking water are generally below 1 mg per litre, often measured in ng per litre. This low concentration might appear to guarantee that they hardly pose any problem to public health. Assuming a concentration of 100 ng/L of a pharmaceutical that in humans has a DDD (defined daily dose) of 10 mg implies that a volume of 100,000 litres would be required to make up one single DDD. Such calculation does not take into account vulnerable population exposure for example during the period of development. Therapeutic levels of levonorgestrel (a sex hormone) have been found in rainbow trout downstream a sewage treatment plant.
Laws and regulations Environmental persistent pharmaceutical pollutants (EPPP) have to be looked at in their entirety of the product chain.Dutch National Institute for Health and the Environment: Pharmaceutical product chain Pharmaceutical residues may enter the environment in various phases and therefore the influence or impact regarding environmental effects can be regulated on different levels: on the scientific and industrial level of development and production, on the governmental and administrative level of authorization, market regulation and legislation, on the level of health insurance and its influence on production and consumption, on the distribution level with physicians and their prescriptions respectively in pharmacies and stores, on the level of patients with individual consumption pattern, disposal behavior etc. and finally in the field of waste management, waste water treatment and drinking water supply. Pharmaceuticals differ from other anthropogenic chemicals with respect to legal requirements and depending on the countries and cultural frame. Partly they are excluded in laws and regulations which control manufacture, marketing, use, and disposal of other consumer products of a chemical character (solvents, paints, glues etc.). As a consequence the possible negative environmental impact of pharmaceuticals may be less documented, in comparison to other consumer chemicals.
Laws and regulations in the European Union In the European Union (EU) today, more than 3,000 pharmaceutical substances are approved. In 2013 the EU started initiatives to address to the task of pharmaceutical residues in the water cycle. Here the commission was proposing to add 15 chemicals to the watch list of substances in the Water Framework Directive (WFD) that are monitored and controlled in EU surface waters, including 3 pharmaceuticals (besides industrial chemicals, substances used in biocides and plant protection products): "The contamination of water and soil with pharmaceutical residues is an emerging environmental concern. In evaluating and controlling the risk to, or via, the aquatic environment from medicinal products, adequate attention should be paid to Union environmental objectives. In order to address that concern, the Commission should study the risks of environmental effects from medicinal products and provide an analysis of the relevance and effectiveness of the current legislative framework in protecting the aquatic environment and human health via the aquatic environment."