A REVIEW OF THE EFFECTS OF PHARMACEUTICAL WASTE ON THE ENVIRONMENT AND HUMAN HEALTH

Felicia Manole^1,2, Paula Marian^2,3*, Gabriel Mihai Mekeres^2,3, Andrei Nicolae Csep^2,4

ABSTRACT

Pharmaceutical wastes include a wide range of antibiotics, painkillers, and cancer drugs that cause environmental pollution and disrupt the natural functioning of ecosystems. In this review study, the effects of pharmaceutical waste on the environment and human health were investigated. The results obtained from the review of various studies showed that pharmaceutical waste has environmental risks and destructive effects. The review of various studies showed the negative effects of pharmaceutical waste on human health, including mortality, the prevalence of respiratory and lung diseases, cancer, and negative effects on the soil of agricultural products and water. Research evidence showed the harmful environmental effects of pharmaceutical waste on surface and underground water, soil plants, and agricultural and aquatic products, serious damage to people's health, respiratory diseases, cancer, neurological disorders, and transmission to food chains. However, this evidence requires a more detailed and comprehensive evaluation so that the results can be interpreted more confidently.

Keywords: Environment, Human health, Pharmaceutical waste, Pollution

Introduction

Medicines play an important role in the treatment and prevention of diseases in animals and humans [1, 2]. But pharmaceutical residues may have unwanted effects on animals and microorganisms in the environment [3, 4]. Although the side effects of drugs on human and animal health are usually fully investigated in safety and toxicology studies, the potential environmental effects of drug residues have been less studied. Some pharmaceutical residues, including painkillers, antidepressants, and antibiotics, can affect humans and animals [5, 6]. Many researches show that one of the effects of the industrialization of societies is the pollution of soil and underground water and hazardous pharmaceutical waste all over the world [7, 8].

Medicines are known as hazardous waste whose generic or chemical name is included in part 33 of the list of wastes published by the United States Environmental Protection Agency under the title of hazardous waste in 40CFR261 [9, 10] and also has characteristics of flammability, corrosiveness, reaction acceptability, and toxicity that are given in the same list (40CFR261) [11, 12].

In European countries in 2014, according to estimates, 342,000 landfills of contaminated pharmaceutical waste were identified (5.7 per 10,000 population) [13, 14]. According to the data collected from 33 countries in 2011, the most pollutants that lead to soil and surface and underground water pollution were hazardous waste [15, 16], including urban and industrial waste and industrial and commercial activities, and pollution caused by pharmaceutical waste and hospital waste [17]. In seven Asian countries, 679 areas were identified as places contaminated with pharmaceutical and chemical waste [18]. According to the report of the World Health Organization, one-third of the disease burden in Africa is related to environmental risk factors [19, 20]. Environmental pollution by pharmaceutical waste is reaching an alarming level, and the burden of diseases related to the effects of waste in low-income countries is increasing and is not sufficiently recognized [21]. A wide variety of human drugs, including antibiotics, statins, or cytotoxins used in cancer treatment, as well as large amounts of veterinary drugs such as antibacterials, antifungals, and antiseptics, reach the environment through various pathways [22, 23] and lead to soil, surface water, and agricultural land pollution.

After being released into the environment, pharmaceutical wastes are deposited in surface water and rivers, air, soil, and agricultural lands. A wide range of other factors such as physical properties and chemical compounds and characteristics of the receiving environment affect their distribution in the environment [24]. Adsorption coefficients of pharmaceutical residues in soil for several veterinary drugs have been reported from 1 liter per kilogram to more than 6000 liters per kilogram [25]. In addition, the degradation of pharmaceutical residues varies significantly depending on the chemistry, biology, and weather conditions. For example, the half-life in winter conditions is six times higher than in summer, and this compound is absorbed faster in loamy sandy soils [26]. Recent studies have measured a wide range of drugs, including hormones, steroids, and antibiotics, with small amounts in different soil, surface, and underground water samples, and the effects of these pharmaceutical residues on environmental organisms and human health are worrisome [27]. A wide range of harmful effects of pharmaceutical residues, including physiological effects, inhibition or stimulation of growth in aquatic plants and algae species, and effects on the fertility and growth of fish, reptiles, and aquatic invertebrates have been identified [28]. In addition to the structure and function of DNA in tumor cells, anticancer drugs and chemotherapy or cytostatic drugs directly or indirectly affect non-target cells and tissues in living organisms [29]. Considering the above contents and the need to investigate the role of pharmaceutical waste as a dangerous environmental pollutant, our main goal in this research is to investigate the effects of pharmaceutical waste on the environment and human health.

Results and Discussion

Pharmaceutical residues in the environment usually appear as complex compounds, and therefore even if the concentration of a compound is low, it may be important for environmental toxicity [30]. In the study of Mishik et al. investigating the genotoxic properties of anticancer drugs, it was found that even low concentrations of these drugs have toxic effects on the ecosystem [31]. The concentration of medicinal compounds has been observed several times higher than the predicted concentration in the environment, so these results suggest the possibility of adverse effects of medicinal residues in plants [32]. Kennedy et al. reported that compared to the effective concentrations of a binary compound, a combination of pharmaceutical waste drugs, including anticancer drugs, can pose a serious risk to the environment. Because their effects occur in very low concentrations, which are in the range of concentrations encountered in aquatic systems. According to Al-Rashak et al.'s reports, the effects of some pharmaceutical residues are synergistic even at low concentrations.

In addition, the previous study of the double combination of anticancer drugs showed that algae are more sensitive than cyanobacteria and these compounds can have their own cooperative or antagonistic effects [33]. In the studies of Kovács et al. [34], Pichler et al. [35], Gajski et al. [36], Novak et al. [37], and Larsson et al. [38], the harmful environmental effects of pharmaceutical wastes on surface and underground water, plants, soil, and serious harm to health People at risk of these pollutants have been identified. In addition to this review, various studies show that pharmaceuticals are not the only dangerous environmental pollutants, but living and aquatic organisms are at risk, from a combination of drugs and other substances, including pesticides, agricultural toxins, and industrial chemicals [39]. Many countries do not routinely monitor the presence of drugs, including antibiotics, in drinking water due to high costs. Studies conducted in Southeast Asia have reported the presence of several types of antibiotics in hospital wastewater. Studies conducted in Bangladesh, India, Indonesia, and Thailand have reported antibiotic residues in aquatic products [40]. Therefore, when wastewaters containing untreated antibiotics enter open water or soil, antibiotics, and their metabolites can enter the human food chain and endanger the health of humans and other living organisms.

The review of various studies in this research showed that indirect exposure to pharmaceutical substances through surface water, soil, and agricultural products is considered a risk for humans. A comparison of the data obtained from previous studies showed that the concentration of medicinal compounds in the groundwater levels is very low. However, the possibility of transmission from other methods, such as soil absorption by crops and biomagnification through the food chain, has not been sufficiently calculated and the possibility of transmission cannot be completely ruled out [41]. Evaluating the environmental effects of pharmaceutical waste is very difficult and complex. Since 1980, the US Food and Drug Administration (FDA) has evaluated the environmental risks of human and veterinary drugs and their effects on aquatic and terrestrial organisms before they are placed on the market. However, the harmful effects of most drugs remain unknown and there is a need for evidence-based studies [42]. Various studies have shown the environmental effects and potential negative effects of pharmaceutical residues on fish, algae, bacteria, earthworms, plants, and invertebrates [43].

However, there is a fundamental question regarding the real value of these studies; Based on the fact that in evaluating the risks of medicinal substances, they usually use standard biotoxicity tests, which are often short-term and focus mainly on mortality or respiratory diseases and cancer as the endpoint. In addition, evaluation tests focus on pharmaceutical substances remaining in surface waters and do not pay attention to pharmaceutical substances that are present in sediments [44]. The observed effects of pharmaceutical effects in the laboratory are at much higher concentrations than those which are measured in the natural environment, so the more subtle effects of pharmaceutical residues in the environment may remain unknown [45]. In addition, many organisms that affect human and animal health and are targeted by drugs play a vital role in the functioning of ecosystems [46]. While many of these observations are seen in realistic environmental concentrations and their importance in environmental health has not yet been determined; In fact, the fact that some drugs indirectly have adaptive environmental effects will be one of the research challenges in the coming years. Also, the environmental behavior of a substance may change in the presence of other substances. For example, antibacterials act on soil microbes, which play an important role in reducing pesticides [41].

Due to the limitations of the research conducted so far, only a small part of the currently used drugs has been investigated, and there is a need to understand how other drugs affect the environment. Traditional standard tests may be inappropriate for evaluating the effects of many drugs [47]. Although they showed unpleasant effects after exposure to drugs in realistic environmental concentrations. However, the function and ecological effects of medicinal substances should be determined precisely [44]. Drugs are unlikely to affect the environment individually. Therefore, it is necessary to examine the effects of pharmaceutical residues in combination with other substances. Therefore, future research should focus on understanding the basic biological processes including the release fate and effects of drug residues [39].

Such research should lead to the development of new modeling methods, for example, Hoggett et al. have proposed an adaptive plasma concentration model that can connect mammalian and fish species and provide useful information about the possible effects of drugs on Offer fish. Other modeling approaches, such as quantitative and structure-activity relationships, can help us estimate the environmental effects of drugs from their chemical structure and better understand the effects of drug residues on human health and the environment. Among the limitations of this research is the lack of sufficient and evidence-based studies to determine the absorption of pharmaceutical residues in soil, surface water, and agricultural products and their transfer to the food chain. Therefore, it is necessary to conduct quantitative studies to determine the indirect effects of pharmaceutical residues on the environment and human health. Due to the complexity and difficulty of determining the effects of pharmaceutical residues in the ecological cycle, the harmful and adverse consequences of most drugs in the environment remain unknown. Also, it is difficult to evaluate the effect of a drug alone, and the effects of other dangerous chemical substances, such as electronic waste, industrial and petroleum materials, may have synergistic effects on the negative consequences of pharmaceutical waste disposal in the environment. Therefore, future research should focus on understanding the biological processes of pharmaceutical waste based on its release and fate in the environment.

Conclusion

According to the results of reviewing various studies, pharmaceutical and chemical wastes as destructive factors have harmful effects on the environment and human health. In all these studies, the mortality rate, the incidence of respiratory diseases and cancer, the prevalence of hepatitis C, poisoning, and the risk of congenital malformations in people who lived near chemical waste disposal sites and pharmaceutical waste were significantly high. Research evidence showed the harmful environmental effects of pharmaceutical waste on surface and underground water, soil plants, and agricultural and aquatic products, serious damage to people's health, respiratory diseases, cancer, neurological disorders, and transmission to food chains. However, this evidence requires a more detailed and comprehensive evaluation so that the results can be interpreted more confidently.

Acknowledgments: None

Conflict of interest: None

Financial support: None

Ethics statement: None

1. World Health Organization. World Health organization guidelines for indoor air quality: household fuel combustion: World Health Organization; 2015.
2. Yousaf M, Khan MM, Paracha AT. Leading professionally diverse workgroups of healthcare professionals for improving the quality of care. J Organ Behav Res. 2021;6(1):106-19.
3. Landrigan PJ, Wright RO, Cordero JF, Eaton DL, Goldstein BD, Hennig B, et al. The NIEHS superfund research program: 25 years of translational research for public health. Environ Health Perspect. 2015;123(10):909. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590764/
4. Karatas KS, Karatas Y, Telatar TG. Assessment of burnout syndrome and smartphone addiction in healthcare workers actively working during the Covid-19 pandemic. J Organ Behav Res. 2022;7(1):156-69.
5. McCormack VA, Schüz J. Africa’s growing cancer burden: Environmental and occupational contributions. Cancer Epidemiol. 2012;36(1):1-7.
6. Homauni A, Mosadeghrad AM, Jaafaripooyan E. Employee performance appraisal in health care organizations: A systematic review search. J Organ Behav Res. 2021;6(2):109-21.
7. Karpov VY, Medvedev IN, Komarov MN, Dorontsev AV, Kumantsova ES, Mikhailova OD. Possibilities of students' health improvement through physical training in the aquatic environment. J Biochem Technol. 2021;12(4):67-71.
8. Nweke OC, Sanders III WH. Modern environmental health hazards: A public health issue of increasing significance in Africa. Environ Health Perspect. 2009;117(6):863.
9. Perkins DN, Drisse MNB, Nxele T, Sly PD. E-waste: A global hazard. Ann Glob Health. 2014;80(4):286-95.
10. Perez-Nava J, Hernandez-Aldana F, Martinez-Valenzuela C, Rivera A. Pseudomonas sp isolated from wastewater and their interaction with microalgae. J Biochem Technol. 2021;12(2):1-5.
11. Inglezakis VJ, Moustakas K. Household hazardous waste management: A review. J Environ Manag. 2015;150:310-21.
12. Barman I, Hazarika S, Gogoi J, Talukdar N. A systematic review on enzyme extraction from organic wastes and its application. J Biochem Technol. 2022;13(3):32-7.
13. Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, et al. The navigation guide—evidence-based medicine meets environmental health: A systematic review of human evidence for PFOA effects on fetal growth. Environ Health Perspect. 2014;122(10):1028.
14. Alsaffar BH, Daghistani DK, Alshakhouri MH, Alqarni AA, Al Ghamdi MS, Adnan A, et al. Review on fixed prosthesis and its influence on periodontal health, literature review. Int J Pharm Res Allied Sci. 2021;10(3):89-93.
15. World Health Organization. World Health Organization. Handbook for guideline development: World Health Organization; 2014.
16. AlZahrani SG. Healthy schools framework in Saudi Arabia: A narrative review. Int J Pharm Res Allied Sci. 2023;12(1):110-5.
17. Cancer IAfRo, Humans IWGotEoCRt. IARC monographs on the evaluation of carcinogenic risks to humans: World Health Organization; 2007.
18. Cancer IAfRo. List of classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 118. Lyon, France: IARC. Available from: http://monographs iarc fr/ENG/Classification/Table4 pdf (accessed April 6, 2017).
19. EPA U. Support of Summary Information on the Integrated Risk Information System (IRIS); 2012.
20. Attar AA. The disaster preparedness among health care workers in holy mosques at Makkah and Madinah, Saudi Arabia. Int J Pharm Res Allied Sci. 2022;11(4):41-51.
21. Prasse C, Schlüsener MP, Schulz R, Ternes TA. Antiviral drugs in wastewater and surface waters: A new pharmaceutical class of environmental relevance? Environ Sci Technol. 2010;44(5):1728-35.
22. Sim WJ, Lee JW, Lee ES, Shin SK, Hwang SR, Oh JE. Occurrence and distribution of pharmaceuticals in wastewater from households, livestock farms, hospitals, and pharmaceutical manufacturers. Chemosphere. 2011;82(2):179-86.
23. Zagade H, Varma S, Suragimath G, Zope S. Knowledge, awareness, and practices of oral health for debilitated patients, among nursing staff of krishna hospital. Int J Pharm Res Allied Sci. 2022;11(2):73-80.
24. Collado N, Rodriguez-Mozaz S, Gros M, Rubirola A, Barceló D, Comas J, et al. Pharmaceuticals occurrence in a WWTP with significant industrial contribution and its input into the river system. Environ Pollut. 2014;185:202-12.
25. Region A, Region S-EA, Region EM, Region WP. Global action plan on antimicrobial resistance. Available from: http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_24-en.pdf
26. Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, et al. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Perspect. 2013;121(9):993.
27. Rehman MSU, Rashid N, Ashfaq M, Saif A, Ahmad N, Han JI. Global risk of pharmaceutical contamination from highly populated developing countries. Chemosphere. 2015;138:1045-55.
28. Sinthuchai D, Boontanon SK, Boontanon N, Polprasert C. Evaluation of removal efficiency of human antibiotics in wastewater treatment plants in Bangkok, Thailand. Water Sci Technol. 2016;73(1):182-91.
29. Pukkala E, Pönkä A. Increased incidence of cancer and asthma in houses built on a former dump area. Environ Health Perspect. 2001;109(11):1121.
30. Mišík M, Filipic M, Nersesyan A, Mišíková K, Knasmueller S, Kundi M. Analyses of combined effects of cytostatic drugs on micronucleus formation in the Tradescantia. Environ Sci Pollut Res. 2016;23(15):14762-70.
31. Mišík M, Pichler C, Rainer B, Filipic M, Nersesyan A, Knasmueller S. Acute toxic and genotoxic activities of widely used cytostatic drugs in higher plants: Possible impact on the environment. Environ Res. 2014;135:196-203.
32. Kundi M, Parrella A, Lavorgna M, Criscuolo E, Russo C, Isidori M. Prediction and assessment of ecogenotoxicity of antineoplastic drugs in binary mixtures. Environ Sci Pollut Res. 2016;23(15):14771-9.
33. Česen M, Kosjek T, Busetti F, Kompare B, Heath E. Human metabolites and transformation products of cyclophosphamide and ifosfamide: analysis, occurrence, and formation during abiotic treatments. Environ Sci Pollut Res. 2016;23(11):11209-23.
34. Kovács R, Bakos K, Urbányi B, Kövesi J, Gazsi G, Csepeli A, et al. Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish. Environ Sci Pollut Res. 2016;23(15):14718-29.
35. Pichler C, Filipič M, Kundi M, Rainer B, Knasmueller S, Mišík M. Assessment of genotoxicity and acute toxic effect of the imatinib mesylate in plant bioassays. Chemosphere. 2014;115:54-8.
36. Gajski G, Gerić M, Žegura B, Novak M, Nunić J, Bajrektarević D, et al. Genotoxic potential of selected cytostatic drugs in human and zebrafish cells. Environ Sci Pollut Res. 2016;23(15):14739-50.
37. Novak M, Žegura B, Baebler Š, Štern A, Rotter A, Stare K, et al. Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells. Environ Sci Pollut Res. 2016;23(15):14751-61.
38. Larsson DJ. Release of active pharmaceutical ingredients from manufacturing sites—need for new management strategies. Integr Environ Assess Manag. 2010;6(1):184-6.
39. Roos V, Gunnarsson L, Fick J, Larsson D, Rudén C. Prioritising pharmaceuticals for environmental risk assessment: Towards adequate and feasible first-tier selection. Sci Total Environ. 2012;421:102-10.
40. Murray-Smith RJ, Coombe VT, Grönlund MH, Waern F, Baird JA. Managing emissions of active pharmaceutical ingredients from manufacturing facilities: an environmental quality standard approach. Integr Environ Assess Manag. 2012;8(2):320-30.
41. Gissler M, Laursen TM, Ösby U, Nordentoft M, Wahlbeck K. Patterns in mortality among people with severe mental disorders across birth cohorts: A register-based study of Denmark and Finland in 1982–2006. BMC Public Health. 2013;13(1):834.
42. Ternes TA, Joss A, Siegrist H. Peer reviewed: Scrutinizing pharmaceuticals and personal care products in wastewater treatment. ACS Publications; 2004.
43. Castelló A, Río I, García-Pérez J, Fernández-Navarro P, Waller LA, Clennon JA, et al. Adverse birth outcomes in the vicinity of industrial installations in Spain 2004–2008. Environ Sci Pollut Res. 2013;20(7):4933-46.
44. Foster WG, Evans JA, Little J, Arbour L, Moore A, Sauve R, et al. Human exposure to environmental contaminants and congenital anomalies: a critical review. Crit Rev Toxicol. 2017;47(1):59-84.
45. García-Pérez J, Fernández-Navarro P, Castelló A, López-Cima MF, Ramis R, Boldo E, et al. Cancer mortality in towns in the vicinity of incinerators and installations for the recovery or disposal of hazardous waste. Environ Int. 2013;51:31-44.
46. Health UDo, Services H. The health consequences of smoking—50 years of progress: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014;17.
47. Dongo K, Tiembré I, Koné BA, Zurbrügg C, Odermatt P, Tanner M, et al. Exposure to toxic waste containing high concentrations of hydrogen sulfide illegally dumped in Abidjan, Côte d’Ivoire. Environ Sci Pollut Res. 2012;19(8):3192-9.