The Agricultural Perspective on Water Contamination by Pharmaceuticals

The United States Environmental Protection Agency has recognized pharmaceuticals and personal care products (PPCPs) [1] to be part of a class of materials known as “emerging contaminants”. Emerging contaminants [2] can be either manmade or naturally occurring compounds that have recently been discovered to have a toxic, or otherwise demonstrably harmful effect on the living beings in their local environment.

Medicines have been commonplace since the time of the apothecaries in the middle ages, and arguably the first kind of wide-scale pharmaceutical market originated during the American civil war [3] as demand for antiseptics and painkillers sky-rocketed. With such a long history, it appears odd that PPCPs can be classed as emerging contaminants. The reality is that despite centuries of research into drug development, investigation into the environmental impact of pharmaceuticals is a much younger field.

The Environmental Risk of PPCPs

The polluting nature of PPCPs and the health risks associated with their use are still in the process of being understood fully. However, it is known that PPCPs can act as an endocrine disruptor to marine life [4] after prolonged low-level exposure, and is thought to have the potential to do the same in humans if the contaminant accumulates to high enough levels in the body. Ingestion of endocrine disruptors can lead to hormonal imbalance [5] which can cause problems such as infertility [6], ovarian or prostate cancers [7], and an increased risk of developing autoimmune diseases [8].

PPCPs can enter the environment in a number of ways [9]. The wastewater from the production plants that synthesize the pharmaceuticals is often contaminated with trace amounts of PPCP material. In addition, the water supply can also become contaminated through the excretions of the humans and animals who use PPCPs. Once these PPCPs are in the water supply they can be challenging to remove using traditional water treatment methods. If not treated effectively, there is the potential for PPCP contamination to affect the agriculture industry through the use of this contaminated water supply.

Pharmaceutical Contamination of Soils and Crops

Many countries across the world are regularly affected by periods of drought during their long summers. The water shortages that come with these droughts mean that it is becoming common practice to use treated wastewater to irrigate crops grown in those regions. Recognizing that PPCPs may still be present in treated wastewater, a research group from Sultan Qaboos University in Oman carried out a study [10] with the aim of assessing the extent to which soil and crops that are treated with PPCP-spiked wastewater are affected by the contaminants.

The group identified four commonly used pharmaceutical products in Oman (amoxicillin, sulfamethoxazole, trimethoprim, and ibuprofen) and spiked two water stores with them, one to a low concentration of 1 mg/l, and one to a significantly higher level of 5 mg/l. The water stores were then used to grow two batches of radishes. Two additional batches were grown using groundwater and industrially treated wastewater for comparison. The soil and the radish plant material were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to detect the presence of any of the pharmaceutical products.

The study found no indication of any of the pharmaceuticals in the soil samples taken from each of the four batches. This disappearance is thought to be down to degradation due to the pharmaceuticals’ short biological half-life in soil. Alternatively, the disappearance could be down to a mixture of the uptake of pharmaceuticals by the plants and the pharmaceuticals leaching beyond the sampling depth of the soil.

Outside of the LC-MS/MS testing, it was clear from a simple visual inspection of the four batches that the radish plants were being affected by the presence of the pharmaceuticals. Plants exposed to the pharmaceutical-spiked water had lost several of their mature leaves, and a small number of the plants did not survive to maturity. Two of the pharmaceuticals used in the spiked water, sulfamethoxazole and amoxicillin, were detected in the shoots and roots of the radish plants. Interestingly, the pharmaceuticals underwent a translocation to the leaves of the plant once enough of the drugs had accumulated in the roots of the plants.

Professor Mushtaque Ahmed, one of the authors of the study, believes that further investigation into the action of PPCPs in agricultural soil systems is necessary to determine if there is a significant health risk from the usage of PPCP-containing wastewater.

He explains, “I feel that for agricultural purposes, pharmaceuticals and personal care products in treated wastewater is not something that should be worrying us too much currently. However, it may be an issue if treated wastewater is used directly in hydroponic systems that do not use soil.”

“We need more research under various conditions, although there are challenges to this, such as our technical capabilities to measure small amounts of such PPCPs in water, soil and plants.”

Treatment of PPCP Contaminated Soils

Knowing that PPCPs can be spread to plant roots and leaves through the use of PPCP contaminated water, it is important that research is undertaken to establish how to best deal with this potential future health hazard. New research [11] led by scientists from the School of Medicine at Washington University in St Louis could lead to a potential method to the remediation of antibiotic pharmaceuticals in soil. Specifically, the team studied the metabolism of penicillin by proteobacteria in soil with the aim of creating a specialized bacterial strain for the clean-up of antibiotics. 

Penicillin was one of the earliest mass-produced pharmaceutical drugs, but due to increasing antibiotic resistance it is used much more rarely now. Related compounds, such as amoxicillin and ampicillin, are still frequently used and so understanding the metabolism of penicillin is still industrially important. 

By examining the behavior of the proteobacteria when exposed to penicillin versus sugar, the team found three sets of genes, belonging to the β-lactamase families, which became active when the proteobacteria “ate” the penicillin, but that remained dormant on the sugar diet. Each of these gene sets corresponded to a different step in the three-step metabolic pathway that was established for penicillin in the study. 

It was noted that the proteobacteria used in the study were not particularly robust or stable bacteria to work with, and so the researchers also endeavored to create a more industrially useful penicillin-metabolizing bacteria strain that could be used in practical applications. To do this, the team genetically engineered a strain of Escherichia coli (E. Coli), a far more stable and tractable bacterium, which contained the genetic material needed to metabolize penicillin instead of its usual sugar diet. 

Dr Terence Crofts, the first author on the research paper, explains, “With limited further engineering, these strains could be developed as tools for in situ bioremediation of antibiotic-contaminated soils or environments, such as those located near pharmaceutical manufacturers. These environments are important drivers of antibiotic resistance development, and their remediation could help prevent the spread of resistance.”

Concerning the release of E. coli, which is commonly perceived by the public as a dangerous bacterium, into the environment, Dr Crofts explains, “The benefits of any such future bioremediation program would of course need to be weighed against the risk of releasing a genetically modified bacterium into the environment.” The research group hopes that future research into similar metabolic pathways of other PPCPs could lead to the development of simple bioremediation systems that can be used safely and cheaply by farmers to counteract the effects of PPCP contamination.

The Outlook for Agriculture 

With the classification of PPCPs as an emerging contaminant, further research into their routes of contamination, associated health risks, and potential remedies to their pollution will remain a high priority in the scientific community. Work such as that shown above, demonstrates the research already being done in the field of PPCP identification and treatment. It is hoped that this work can one day be used in conjunction with better water treatment systems for the effective removal of PPCP contaminants from our water, our agriculture, and the wider environment.

References

[1] U.S. EPA, Contaminants of Emerging Concern including Pharmaceuticals and Personal Care Products, https://www.epa.gov/wqc/contaminants-emerging-concern-including-pharmaceuticals-and-personal-care-products, (accessed August 2018).

[2] S. Sauvé and M. Desrosiers, A review of what is an emerging contaminant., Chem. Cent. J., 2014, 8, 15.

[3] pharmaphorum.com, A History of the Pharmaceutical Industry, https://pharmaphorum.com/articles/a_history_of_the_pharmaceutical_industry/, (accessed August 2018).

[4] A. J. Ebele, M. Abou-Elwafa Abdallah and S. Harrad, Pharmaceuticals and personal care products (PPCPs) in the freshwater aquatic environment, Emerg. Contam., 2017, 3, 1–16.

[5] National Institute of Environmental Health Sciences, Endocrine Disruptors Fact Sheet, 2010.

[6] A. Marques-Pinto and D. Carvalho, Human infertility: are endocrine disruptors to blame?, Endocr. Connect., 2013, 2, R15-29.

[7] H. Rochefort, Endocrine disruptors (EDs) and hormone-dependent cancers: Correlation or causal relationship?, C. R. Biol., 2017, 340, 439–445.

[8] 1 C.-H. Kuo, S.-N. Yang, P.-L. Kuo and C.-H. Hung, Immunomodulatory effects of environmental endocrine disrupting chemicals, Kaohsiung J. Med. Sci., 2012, 28, S37–S42.

[9] istc.illinois.edu, PPCPs in the Environment, https://www.istc.illinois.edu/cms/one.aspx?pageId=446307, (accessed 5 August 2018).

[10] R. Al-Farsi, M. Ahmed, A. Al-Busaidi and B. S. Choudri, Assessing the presence of pharmaceuticals in soil and plants irrigated with treated wastewater in Oman, Int. J. Recycl. Org. Waste Agric., 2018, 7, 165–172.

[11] T. S. Crofts, B. Wang, A. Spivak, T. A. Gianoulis, K. J. Forsberg, M. K. Gibson, L. A. Johnsky, S. M. Broomall, C. N. Rosenzweig, E. W. Skowronski, H. S. Gibbons, M. O. A. Sommer and G. Dantas, Shared strategies for β-lactam catabolism in the soil microbiome, Nat. Chem. Biol., 2018, 14, 556–564.