Sub-lethal impacts of pharmaceuticals on aquatic animals

Updated: Jul 7

We have a problem that is proving difficult to solve in the fields of environmental chemistry and ecotoxicology — the constant emission of small concentrations of pollutants being moved into waterways. Compounding this are the effects of many different chemicals from many different sources being emitted or making their way into water, creating mixtures of chemicals to which organisms are chronically exposed.


Chemicals from many different sources and moving along many different pathways in soil, and water, and air, can end up mixed together in aquatic ecosystems. These chemicals aren’t just from industrial and commercial activities like agriculture and mining. Many of the pharmaceuticals and health products we use on a day-to-day basis in our homes are not being captured in sewage treatment plants and are discharged into rivers and estuaries. The animals associated with this water aren’t just dosed once but constantly, and for as long as they live, for as long as the chemicals are discharged, or for as long as the chemicals continue to stick around in their environment [1].


Measuring these chemicals is not a simple task and requires the specialised development of specific laboratory methods. Even if methods are developed which accurately and precisely measure chemical concentrations, assessing the impact of these chemicals is very difficult.


There’s been some research that was published recently that highlights the extent of the problem to some degree. A group of researchers lead by Erinn Richmond at Monash University set out to understand whether pharmaceutical chemicals used by people can be found in watercourses in the vicinity of Melbourne [2]. The researchers also wanted to understand the potential impact of these chemicals on ecosystems. They looked at 98 different pharmaceuticals in spiders and insects, collecting these animals from rivers ranging from a reference site ― that is one where there should be no occurrence of pharmaceuticals ― through to sewage outfalls where pharmaceutical concentrations can be assumed to be the highest.


What they found was that all insects assessed, including from the reference site, contained at least one pharmaceutical in measurable concentrations as a result of such discharges [2]. Sixty-nine different types of pharmaceuticals were found in invertebrate (both insects and spiders) samples collected for the study. The highest concentrations of pharmaceuticals occurred in organisms collected from beside the outfall of a sewage facility with tertiary treatment and disinfection. The most commonly detected compounds were mianserin (an anti-depressant), memantine (for alzheimers treatment), codeine (a painkiller), fluconazole (an anti-fungal), and clotrimazol (another anti-fungal).


An important discovery of Richmond et al.’s (2018) research was that the spiders which preyed on the aquatic insects contained pharmaceuticals at concentrations an order of magnitude higher than the insects themselves ― this means that the pharmaceuticals were increasing in concentration up through the food web [3]. The researchers also found that insectivorous species such as platypus and native brown trout were exposed to between one quarter and one half of a human dose of some pharmaceuticals a day. In addition, rather than just the one or two highly regulated drugs to which a human would be exposed, platypus were estimated to be consuming more than 1 mg/kg of 67 different drugs from 22 different therapeutic drug classes.




This leads to another important question in the field of ecotoxicology. What is the effect of even one of these chemicals on organisms? This is a really challenging question to answer. As a chemical risk assessor recently explained to me, different parts of an organism can be affected by a single chemical all at the same time. It’s then very hard to understand whether an organ is failing because of the chemical in question or because other parts of the organism’s body is affecting the organ. Sometimes a chemical can also be broken down by an organism into different compounds which may cause more damage than the chemical itself, but we may not even know to look for these chemicals in the animals. If we do know to look for them, we may not know how to measure their concentration. Thus, to study the effect of chemicals on animals in the environment (i.e. ecotoxicology) is a very challenging task. There have, however, been some developments in this area in recent years.


In one study, again lead by scientists from Monash University, the behaviour of mosquito fish after chronic exposure to fluoxetine ― an anti-depressant also found Richmond et al.’s (2018) research ― at environmentally relevant doses (that is concentrations known to occur as a result of pollution in the environment) was assessed. This research found that the mosquito fish did not avoid predatory behaviour as they normally would and instead moved into the zone where they could be predated [4]. This is an important sub-lethal effect, which could potentially reduce the fish’s population even though these pharmaceuticals are not causing disease. Other studies of the effects of anti-depressants on fish species have identified aggression, changed reproductive behaviour, altered sociality, altered feeding rate, and altered boldness occurs as a result of exposure [5].


Richmond et al. (2018) also found the azole anti-fungal fluconazole in many samples. Azole anti-fungals such as fluconazole and clotrimazol are known to decrease egg production, alter gonad morphology, and inhibit reproductive hormones in the fish species studied [6]. They also found the opioid codeine in many samples. Opioid analgesics appear to reduce pain in fish in some cases, enabling them to continue normal behaviour in cold temperatures where they otherwise wouldn’t [7]. This particular effect is disputed though, with different studies finding contradictory effects of opioids on fish [8].


And finally, Alzheimers drugs like the memantine found by Richmond et al. (2018) are known to alter the way animals control their muscles (i.e. their motor response), and reduces the normal movement of animals like zooplankton away from light [9]. Habituation is the process animals undertake to learn what stimulus in an environment is associated with harm and which with benefits. Faria et al. (2019) also found that the habituation response was decreased in zebrafish exposed to memantine [10].


Richmond et al. (2018) only assessed 98 different drugs in their study of waterways near Melbourne. They pointed out that over 900 drugs are subsidised by the Australian Government, with the potential for many more drugs to be occurring in the environment. The presence of these pharmaceuticals in rivers is in fact now recognised as a typical feature of rivers in developed countries [8,11,12]. With the complexity of ecotoxicology and our difficulty understanding the effects of all these drugs on our aquatic animals, what to do about all this pollution is unclear [8].


As stated in the previous blog post, it can seem like the effects of small concentrations of pollutants are not worth worrying about and that sub-lethal effects are not of consequence to species. Yet there are clear cases where sub-lethal effects are worth worrying about. The crash of insect populations around the world has been linked most strongly with changes in behaviour as a result of light pollution [13]. This sub-lethal effect is in turn having catastrophic impacts on all the birds and mammals ― including humans ― which depend upon these insects for food and a fully functioning environment.


Addressing the problems presented in this blog is no easy task, with agreement about what some of the effects of pharmaceuticals on aquatic environments not yet well constrained [8]. Perhaps the use of a whole-of-life cycle assessment approach to any chemicals which might enter our waterways, including drugs, personal care products, and industrial chemicals, will go a long way to preventing this pollution. Such an approach would mean that the introduction of a new drug or chemical can only happen once we are sure where in the environment it will end up, and that when it gets there, it will either not cause environmental problems or these problems can be managed. Whatever the solution, we need to act to reduce the concentration of all pollutants, pharmaceuticals and otherwise, as fast as we can.


References

1. Gaw, S. et al. Towards sustainable environmental quality: Priority research questions for the Australasian region of Oceania. Integr. Environ. Assess. Manag. 15, 917–935 (2019).


2. Richmond, E. K. et al. A diverse suite of pharmaceuticals contaminates stream and riparian food webs. Nat. Commun. 9, 1–9 (2018).


3. Chiron, F., Chargé, R., Jiguet, F., Julliard, R. & Muratet, A. Agriculture, ecosystems and environment pesticide doses, landscape structure and their relative effects on farmland birds. Agric. Ecosyst. Environ. 185, 153–160 (2014).


4. Martin, J. et al. The psychoactive pollutant fluoxetine compromises antipredator behaviour in fish. Environ. Pollut. 222, 592–599 (2017).


5. Brodin, T. et al. Ecological effects of pharmaceuticals in aquatic systems—impacts through behavioural alterations. Philos. Trans. R. Soc. B Biol. Sci. 369, (2014).


6. Corcoran, J., Winter, M. J. & Tyler, C. R. Pharmaceuticals in the aquatic environment: A critical review of the evidence for health effects in fish. Crit. Rev. Toxicol. 40, 287–304 (2010).


7. Lopez-Luna, J., Al-Jubouri, Q., Al-Niaumy, W. & Sneddon, L. U. Impact of analgesic drugs on the behavioural responses of larval zebrafish to potentially noxious temperatures. Appl. Anim. Behav. Sci. 188, 97–105 (2015).


8. Tanoue, R. et al. Protecting the environment from psychoactive drugs: problems fro regulators illustrated by the possible effects of tremadol on fish behaviour. Sci. Total Environ. 664, 915–926 (2019).


9. Bedrossiantz, J. et al. A high-throughput assay for screening environmental pollutans and drugs impairing predator avoidance in Daphnia magna. Sci. Total Environ. XX, XX (2020).


10. Faria, M. et al. Development of a vibrational startle response assay for screening environmental pollutants and drugs impairing predator avoidance. Sci. Total Environ. 650, 87–96 (2019).


11. Baker, D. R. & Kasprzyk-Hordern, B. Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: New developments. Sci. Total Environ. 454455, 442–456 (2013).


12. Palmiotto, M. et al. Personal care products in surface, ground and wastewater of a complex aquifer system, a potential planning tool for contemporary settings. J. Environ. Manage. 214, 76–85 (2018).


13. Owens, A. C. S., Cochard, P., Durrant, J., Farnworth, B., Perkin, E. K. & Seymoure, B. Light pollution is a driver of insect declines. Biol. Conserv. 241, 108259 (2020).

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