Environmental persistent pharmaceutical pollutant

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Environmental persistent pharmaceutical pollutants (EPPP) are a group of pollutants which can lead to water pollution, groundwater pollution or soil contamination. The term 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)[1] by the International Society of Doctors for the Environment (ISDE).

Pharmaceuticals are synthetic chemicals belonging to a wide group of different chemical families and may also react differently in the environment.

As there are thousands of different synthesized chemicals present at the same time in the environment, different interactions may occur and the result of these multiple exposure in human and nature are not sufficiently studied or understood.[medical citation needed]

Pharmaceutical drugs have various known and unknown effects on the environment.

Background[edit]

Pharmaceuticals comprise one of the few groups of chemicals that are specifically designed to act on living cells, which presents a special risk when they enter, persist and disseminate in the environment.

Pharmaceuticals chemicals, widely used globally by humans and for food production for an intended purpose, may enter and persist in the environment during their life cycle creating a new and emerging problem, and may pose a threat of important magnitude, with significant adverse effects on environment and human health and special impact in vulnerable populations.

As the world’s population is growing and aging, more people can afford medical treatment and new treatments are developed, the amounts of pharmaceuticals can be expected to increase rapidly. Pharmaceuticals chemicals entering the environment persist there and residues are presently found in drinking water. They are found in fish where they may accumulate. The presence of different pharmaceutical chemicals contributes to the increasing multiple chemical cocktail that today’s population is exposed to. Vulnerable populations are exposed, for example foetuses during the windows of development, with possible important consequences for life.

With exception for downstream sewage treatment plants, the concentration of pharmaceuticals in water is probably extremely low. However, the effect that the chronic exposure to environmental pharmaceuticals chemicals adds to the effects of other chemicals in the cocktail is still not studied. The different chemicals might be potentiating synergistic effects (1+1=3). 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, fish and mussels;
  • 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.[2]

Environmental classification of pharmaceuticals[edit]

In Sweden, the industry together with universities and health care sector has developed a method for environmental risk assessment and environmental classification of drugs.[3][4] 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 health care possibilities to make better choices when prescribing medicines.

Exposure[edit]

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).(ny 8 WHO) 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. The tendency of bio-accumulation in fish is alarming, as fish is an important nourishment.

Release into the environment[edit]

Pharmaceuticals reach the environment mainly in three ways:

  • They are excreted from humans and animals, intact or metabolized, 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.

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 for pharmaceutical industries. EPPPs from treated sewage sludge used as fertilizer are absorbed by soya, and antibiotics have been found in the leaves.

Drinking water[edit]

Which EPPPs are found in drinking water depends on what resources and detection methods are available. Atenolol (beta blocker), Citalopram (antidepressant drug), Diclofenac (analgesic), Ibuprofen (analgesic), Metoprolol (beta blocker), Naproxen (anti-inflammatory) and Trimetoprim (antibiotic) have been found in drinking water of Stockholm, Sweden. Fish caught downstream from the sewage treatment plants of Stockholm contain Citalopram (antidepressant drug) and Propoxyphene (narcotic/anesthetic).[citation needed]

Several broad-spectrum antibiotics in very high concentrations,[dubious ] as well as bacteria resistant to all known antibiotics, were found downstream from a sewage treatment plant in India. Also in Indian drinking water Cetirizine (antihistaminic), Ciprofloxacin (antibiotic), Enoxacin (antibiotic), Terbinafin (antimycotic), and Citalopram (antidepressant drug) were found.[citation needed] Up to 14 different pharmaceuticals have been found in the drinking water of big cities around the world. There also exist publications reporting the presence of cancer drugs in surface water in some countries.[citation needed]

Some of these environmental pharmaceuticals chemicals are well known to have serious genotoxic effects in humans.[medical citation needed] Half-life in nature varies depending on the environment (air, water, soil, sludge), but is more than one year for several compounds.[5][6][7]

Clofibric acid, a metabolite of the lipid-lowering agent Clofibrate, can still be found in surface as well as well water, although Clofibrate long ago has been withdrawn.[citation needed] Concentrations of EPPPs can vary from 1 ng to 1 mg per litre (2). Serious effects of EPPPs on water-living organisms, especially on reproductive systems, have been already shown, as well as on microbial communities.[7][8][9][10][page needed]

This would be of much less concern if the population 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[edit]

  • 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 (2, 8). 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 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 the vulnerable population exposure for example during the period of development.
  • Aquatic organisms may bio-concentrate and bio-accumulate lipid-soluble chemicals, including pharmaceuticals. It is well known that certain fish species, like Herring, may contain very high concentrations of the persistent and lipophilic chemicals DDT (dichlorodiphenyl-trichloroethane, an insecticide) and PCBs (Polychlorinated biphenyls, a group of industry chemicals earlier used in e.g. building materials). The same mechanism may also be applied for chemicals synthesized for pharmaceutical uses. Bioaccumulation of citalopram (SSRI, antidepressant) and Propoxyphene (painkiller) has been found in Perche in the Baltic Sea.[citation needed][dubious ] Therapeutic levels of Levonorgestrel (a sex hormone) has been found in Rainbow trout downstream a sewage treatment plant.[11]
  • Pharmaceutical chemicals are not thought or designed to enter in the environment and persist there but for a clear pharmaceutical purpose. When a new medicine is developed, its pharmacological and toxicological effects are tested in acute trials, before being accepted for marketing. However, clinical test procedures are not entirely sufficient to completely guarantee that a new pharmaceutical is devoid of unacceptable side effects when used in large cohorts of patients for a long time. Furthermore, there are currently no test methods to assess whether such effects may occur after long-term use in human, during periods of development, on aquatic microorganisms or how they may affect other animals. Based on this, the persistent and diffuse exposure to low doses of pharmaceutical synthetic chemicals, for long periods of time, is not currently well known or studied.
  • The diffuse dissemination of the EPPP in the environment may indiscriminately expose vulnerable populations: embryos/foetuses, children and adolescents, men and women of reproductive age, and elderly or weak persons. Some of the pharmaceuticals found in surface water are prescribed to patients under special controlled conditions for short periods of time due the risk of side effects. Others are prohibited from prescription to pregnant women or children. These chemicals were not synthesized to expose the general population in a diffuse manner. This presents a new and emerging issue under the chemical safety global pollution.
  • It can be assumed that a large portion of excreted or disposed medicines reach the public sewage treatment plants (STP’s) . Today, the sewage treatment plants do not have the capacity to clean the water from pharmaceutical chemicals. This is sometimes also the case for the industries’ own sewage treatment plants. In many parts of the world, the sewage treatment plant water is reused as drinking water, not always after cleaning treatment. To add a step for cleaning sewage water from pharmaceuticals means more energy, more chemicals and higher costs. - Alternatively, the sewage is directly let out into various surface waters like rivers, lakes, streams or the open sea. - Detection and monitoring at global scale of EPPPs in drinking and surface water as in animals and plants is necessary to understand the magnitude of the problem. The first step is to recognize EPPP as an emerging issue to be able to invest the necessary human and financial resources and develop effective environmental detection methods.

Laws and regulations[edit]

Environmental Pharmaceutical Persistent Pollutants, EPPP, are insufficiently addressed as not covered by other international or regional agreements or arrangements.

Pharmaceuticals differ from other anthropogenic chemicals with respect to legal requirements. They are regularly 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 is much less documented, in comparison to other consumer chemicals.

In the European Union, the new directive for human pharmaceuticals explicitly requires that all member states should establish collection systems for unused or expired medicines. Such systems were already in use in several member countries at the time the new legislation went into action in 2004. Nevertheless, the extent to which such systems have been established and made publicly known, varies between regions. Furthermore, the directive does not regulate how the collected pharmaceuticals should be handled. Disposal into the sewage system is still a legally accepted route of elimination. However, incineration at high temperature (1200°C) is a preferred alternative to avoid environmental pollution.

For pharmaceuticals approved for marketing in EU before 1995, there are no requirements for documentation of environmental effects. Hence, pharmaceuticals which have been on the market for decades may have serious environmental effects that have not been detected.

Effects of pharmaceuticals in the environment[edit]

Estradiol (estrogen, synthetic hormone)[edit]

Concentrations in surface water alone are not sufficient to assess the risk of negative environmental effects in the aquatic environment. Synthetic hormones are endocrine disruptors. Thus, estrogenic compounds like ethinyl-estradiol (estrogen hormone) at concentrations < 1 ng per litre may cause both vitellogenin production (a frequently used index for feminization of male fish), and structural change in their sex organs. It has also been demonstrated that fish exposed to sewage treatment plant (STP) effluent can take up and concentrate estrogenic compounds, including ethinyl-estradiol, to very high internal levels. These observations on feminization of fish by estrogenic compounds in STP effluents have been observed in many countries, and have also been observed in other species, like frogs, alligators and molluscs.

Cardiovascular medicines[edit]

Other examples of environmental impact in the aquatic environment of human medication concern both cardiovascular and neuro-psychiatric medicines. The non-selective beta-blocking agent Propanolol was found to cause a significant decrease in egg production in Medaka fish, at a concentration close to that demonstrated in the sewage treatment plants (STP) effluents.[citation needed] Gemfibrozil (cholesterol and triglycerides lowering drug) often appears in the effluent from STPs. At concentrations close to those reported in STP effluent, Gemfibrozil lowers the blood levels of testosterone in fish.[citation needed]

Citalopram / Fluoxetine (serotonin reuptake inhibitor anti depressants, SSRI’s)[edit]

Some SSRI’s have been shown to accumulate in exposed fish.[citation needed][dubious ] Citalopram has been detected in liver from wild perch in low µg per kg levels, and fluoxetine affects the serotonin system in the same way that it does in humans. Fluoxetine has also been shown to affect swimming activity in shellfish; whether this is linked to a disturbance of serotonin function in the brain is still unknown.

Antibiotics[edit]

High levels of antibiotics in the water are a cause for alarm as there is an increased risk of selecting resistant bacteria, an issue of global concern. This can lead to some highly effective antibiotics becoming ineffective. There are several examples: In India, bacteria resistant to ciprofloxacin have been found downstream pharmaceutical plants, genes for multi resistance were found in drinking water, and multi resistant Salmonella in water sprayed on vegetables. From Europe we know about the epidemic with multi resistant EHEC in summer 2011, originating from water sprayed vegetables.

The term "eco-shadow" has been introduced to describe the ecological impact of antibiotics. Antibiotics with a wide spectrum that are also stable will have a greater impact on the bacterial flora (a long eco-shadow) than those with a narrow antibacterial spectrum which disintegrates more rapidly (a short eco-shadow).

The ecological effects of tetracyclines and quinolones have been observed. They are not metabolized in the human body and are therefore excreted unmodified. When entered into the environment they are poorly degraded. They can be toxic to other animals, affecting particularly microorganism and fish. In the effluent from a sewage treatment plant in India, several broad spectrum antibiotics were found in concentrations toxic to bacteria and plants. In the sewage treatment plant itself, there were enterococcae resistant to all known antibiotics.

The development of resistant bacteria in sewage treatment plants is stimulated by high concentration of antibiotics (e.g. in plant sewage), large amounts of bacteria (e.g. from human sewage water that is added in plant sewage), and selection of Information that can be used to assess the nominated issue have been observed.

Gaps in knowledge[edit]

Effective environmental detection methods have to be developed and global detection strategy applied to map the current global situation.

There are currently no test methods to assess whether negative effects may occur after long-term environmental diffuse exposure in humans, during the vulnerable periods of development, on aquatic micro-organism or how it may affect other animals. Therefore the precautionary principle must be guiding.

Concentrations in surface water alone are not sufficient to assess the risk of negative environmental effects of these synthetic chemicals. Consideration must be taken to bio-accumulation in fish and other aquatic food used by humans, as well as to additive and synergetic effects between pharmaceutical and other chemicals in the contaminated water.

In a small study, several pharmaceuticals were found in milk of goat, cow and human.[12] More research is needed to find out how common this is, the concentrations and the sources.

The industry must be invited to actively work on reducing pharmaceuticals in the environment. Emission of pharmaceuticals should be included in GMP.[according to whom?]

See also[edit]

References[edit]

  1. ^ Strategic Approach to International Chemicals Management
  2. ^ Kristiansson, Erik; Fick, Jerker; Janzon, Anders; Grabic, Roman; Rutgersson, Carolin; Weijdegård, Birgitta; Söderström, Hanna; Larsson, D. G. Joakim (2011). Rodriguez-Valera, Francisco, ed. "Pyrosequencing of Antibiotic-Contaminated River Sediments Reveals High Levels of Resistance and Gene Transfer Elements". PLoS ONE 6 (2): e17038. doi:10.1371/journal.pone.0017038. PMC 3040208. PMID 21359229. 
  3. ^ Gunnarsson B, Wennmalm Å. (2006) Environmental risk assessment and environmental classification of drugs. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB, 2006
  4. ^ Environmentally Classified Pharmaceuticals 2011. Stockholm: Stockholm County Council, 2011
  5. ^ Tysklind M et al. (2006) The spread of drugs in soil and water. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB.
  6. ^ Westerlund E. (2007) Screening of pharmaceuticals in Skåne. Länstyrelsen i Skåne län. [In Swedish]
  7. ^ a b Larsson J et al. (2006) Hormones and endocrine-disrupting substances in the environment. In: Environment and Pharmaceuticals. Stockholm: Apoteket AB.
  8. ^ Tyler, Charles; Williams, Richard; Thorpe, Karen; Burn, Robert W.; Jobling, Susan (2009). "Statistical Modelling Suggests That Anti-Androgens in Wastewater Treatment Works Effluents are Contributing Causes of Widespread Sexual Disruption in Fish Living in English Rivers". Environmental Health Perspectives. doi:10.1289/ehp.0800197. 
  9. ^ Pharmaceuticals in the environment. Results of an EEA workshop. (2010) Luxembourg: Office for Official Publications of the European Communities.
  10. ^ Brosché, Sara (2010). Effects of pharmaceuticals on natural microbial communities. Tolerance development, mixture toxicity, and synergistic interactions (PDF) (PhD thesis). University of Gothenburg. ISBN 978-91-85529-42-1. 
  11. ^ Fick, Jerker; Lindberg, Richard H.; Parkkonen, Jari; Arvidsson, Björn; Tysklind, Mats; Larsson, D. G. Joakim (2010). "Therapeutic Levels of Levonorgestrel Detected in Blood Plasma of Fish: Results from Screening Rainbow Trout Exposed to Treated Sewage Effluents". Environmental Science & Technology 44 (7): 2661–6. doi:10.1021/es903440m. PMID 20222725. 
  12. ^ Azzouz, Abdelmonaim; Jurado-SáNchez, Beatriz; Souhail, Badredine; Ballesteros, Evaristo (2011). "Simultaneous Determination of 20 Pharmacologically Active Substances in Cow's Milk, Goat's Milk, and Human Breast Milk by Gas Chromatography–Mass Spectrometry". Journal of Agricultural and Food Chemistry 59 (9): 5125–32. doi:10.1021/jf200364w. PMID 21469656. 

Further reading[edit]

Updated list of references is found at Swedish Doctors for the Environment (partly in Swedish). The site Pharmaceuticals as pollutants is solely in English.

Articles[edit]

Reports[edit]

External links[edit]