Drug pollution – an aquatic time bomb?

Dr Alex Ford discusses the effects of pharmaceuticals, like antidepressants, on aquatic wildlife The concept that minute amounts of antidepressants present in our rivers and estuaries maybe affecting aquatic life is sometimes met with shock, some scepticism and degree of humour. The general public were first alerted to the fact that pharmaceuticals in the environment may impact our fish through studies which investigated whether synthetic oestrogens feminised male fish in the early 1990s¹. The answer was overwhelmingly, yes, and at incredibly low concentrations (ng/L). This generated fears that similar problems maybe impacting human fertility² although conclusions relating to the latter have been more difficult to determine. The idea that chemicals at surprisingly low concentrations might dramatically alter the physiology of aquatic organisms isn’t that new. Back in the 1980s scientists were aware that concentrations even below 10ng/L of tributyltin or TBT (a compound used in paints to stop fouling on boats) would stimulate female marine snails to grow a penis³. This imposition of the male reproductive system resulted in catastrophic reproductive failure in females and not only wiped out snail populations internationally around coasts but also impacted the local ecosystems through knock-on effects in the food chain. More recently, an unusual story emerged highlighting the effects of another pharmaceutical, dichlofenac, which is a non-steroidal anti-inflammatory drug (NSAID). In this instance the drug was administered to lame cattle in India and Pakistan. What resulted shocked a lot of people and highlighted to need to consider the toxicological impacts of human and veterinary drugs on non-target wildlife. Whilst this drug is considered relatively harmless to mammals, what was not predicted was that vultures preying on dead cattle would suffer catastrophic renal failure which resulted in a ~90% drop in their populations^4,5. Some scientists have gone further to suggest that the impact of reduced vulture populations has resulted on a boom in feral dog populations passing rabies to the human population. So, what is the evidence for antidepressants impacting our aquatic wildlife? Studies around the world have suggested that rivers receiving sewage effluent can have antidepressants at concentrations up to around 1µg/L (=1000ng/L) although most rivers the concentrations recorded are considerably less (~1-20ng/L). However, there is now growing evidence that lower concentrations (<1-100ng/L) can impact a wide range of biological systems in aquatic life. Many antidepressants were designed to modulate serotonin. Serotonin is a hormone that although commonly associated with controlling behaviour is found throughout the animal kingdom and known to have additional biological functions including controlling growth, metabolism, reproduction, colour physiology and the immune system⁶. At the Institute of Marine Sciences in the University of Portsmouth we published an article back in 2010⁷ which demonstrated the role of serotonin in controlling a small crustacean’s (amphipods) preference for light vs dark areas. An increasing concentration of serotonin led to an increased preference for light areas which set the platform to ask whether antidepressants such as the selective serotonin re-uptake inhibitors (SSRIs) like fluoxetine (Prozac) could also affect their preference to light. We observed that a few weeks exposure to these drugs resulted in a five times greater preference for light at around 10-100ng/L fluoxetine; therefore, just hovering above that normally found in urbanised river catchments. New evidence published in a special edition of the journal Aquatic Toxicology has pooled together a range of studies focusing on the effects of antidepressants in the aquatic environment⁸. The most striking data suggest that there are multiple species ranging from fish, snails, bivalves, cuttlefish and crustaceans that are impacted at concentrations at or below 100ng/L (i.e. environmentally relevant). However, there appears to be considerable variability between the species affected and the effects observed range from swimming and activity patterns, locomotion, immune function, reproduction, colour change, feeding and predator behaviour through to gene expression. One of the problems facing ecotoxicologists is addressing whether these drugs are impacting fish and invertebrates in the wild. Whilst it was relatively easy to retrospectively determine whether a fish has had past exposure to an estrogenic chemical, it is currently very difficult to determine whether abnormal behaviour may have, or maybe currently occurring in aquatic species. In the field it is very difficult to measure altered behaviour and some behavioural effects maybe transient in time. Some scientists have also expressed caution suggesting that these studies must be repeated at other laboratories and rigorous measurements must be taken on the exposure concentrations used in the laboratory experiments⁹. This is especially important when results of studies can impact public opinions and policy. The topic very often invites what I’ll call ‘media over-interpretation’ of these ecotoxicological results. For example, our previous study⁷ recorded increased preference for light under exposure to serotonin or serotonin modulating drugs such as antidepressants. Some of the crustaceans we studied also carry parasites which have evolved to alter their host’s serotonin so that they swim in open areas thus making them more vulnerable to predation (the crustacean is an intermediate host for the parasite and requires its host to be eaten to complete its lifecycle). This does not prove that antidepressants cause suicide in humans as has been stated by some articles. The crustaceans don’t deliberately swim into open areas consciously trying to get eaten. The media should also try to express extreme caution when interpreting ‘human’ behaviour from latest studies into the effects of antidepressants on behaviour of aquatic wildlife. What can we as a society do about the problem? Well firstly, this isn’t just a problem about antidepressants. We consume hundreds of different types of medication every day and they all appear to a larger or lesser degree in sewage effluent. We certainly as a society aren’t going to stop taking our medicines (in some circumstances, lifesaving medicines!) therefore we must look to other solutions. Perhaps technology has the answer, however, the most up-to-date sewage treatment processes are very costly and still aren’t able to filter out all chemical contaminants. In some instances the location of sewage treatment plants where effluent is discharged into the largest available flow aiding dilution may help. However, this is not always possible in some landlocked states/countries with limited water supplies. Large numbers of drugs are not used and sit in draws and cupboards well past their use by dates. In some countries the public are obliged to return their unused medication to their pharmacy for disposal. Who pays for this collection and disposal of unwanted medication (pharmaceutical industry vs public tax payer) is currently hotly debated in the USA. The question of greener pharmaceuticals that break down more readily has been suggested by some, however they may prove incredibly difficult to manufacture especially given they have been designed to work optimally in the human or animal body. I expect the next few years will strengthen the evidence that these biological active compounds (antidepressants) are a pollutant of concern. An intriguing set of questions we must address in parallel is whether industrial pollutants can also impact the neuro-hormones such as serotonin in ways that alter an organism’s normal physiology. References

1. Sumpter, John P., and Susan Jobling. "Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment." Environmental health perspectives 103.Suppl 7 (1995): 173.
2. Colborn T, vom Saal FS, Soto AM (1993). Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 101 (5): 378–84.doi:10.2307/3431890
3. Gibbs, P. E., and G. W. Bryan. "Reproductive failure in populations of the dog-whelk, Nucella lapillus, caused by imposex induced by tributyltin from antifouling paints." Journal of the Marine Biological Association of the United Kingdom 66.04 (1986): 767-777.
4. Oaks, J. Lindsay, Martin Gilbert, Munir Z. Virani, Richard T. Watson, Carol U. Meteyer, Bruce A. Rideout, H. L. Shivaprasad et al. "Diclofenac residues as the cause of vulture population decline in Pakistan." Nature 427, no. 6975 (2004): 630-633.
5. Shultz, Susanne, Hem Sagar Baral, Sheonaidh Charman, Andrew A. Cunningham, DevojitDas, G. R. Ghalsasi, Mallikarjun S. Goudar et al. "Diclofenac poisoning is widespread in declining vulture populations across the Indian subcontinent." Proceedings of the Royal Society of London. Series B: Biological Sciences 271, no. Suppl 6 (2004): S458-S460.
6. Fong, P.P., Ford, A.T., 2014. The biological effects of antidepressants on the molluscs and crustaceans: a review. Aquatic Toxicology 151, 4–13.
7. Guler Y., Ford A., 2010. Anti-depressants make amphipods see the light. Aquat Tox-icol(Amst) 99 (3):397-404. http://dx.doi.org/10.1016/j.aquatox.2010.05.019
8. Ford, A.T. (2014) From gender benders to brain benders (and beyond!). Aquat. Toxicol. 151, 1-3.
9. Sumpter, J.P., Donnachie, R.L., Johnson, A.C., 2014. The apparently very variablepotency of the anti-depressant fluoxetine. Aquatic Toxicology 151, 57–60.