Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris
Introduction
Pharmaceuticals are designed to interact with biological systems in order to bring about beneficial effects principally in man but also in domestic and farm animals. In the UK there are currently 19 835 Marketing Authorisations for medicinal products covering 5091 active ingredients (Medicines Control Agency, pers. commun.). These target about 500 distinct biochemical receptors (Daughton and Ternes, 1999) and are available as either over the counter or prescription only medicines. Although they have been designed largely for specific effects in man, drugs could potentially bring about changes in other animals which may be exposed. Environmental problems may arise when excreted drugs (and those disposed of unused) enter water as the parent compound or a metabolite, via sewage effluent from domestic dwellings and hospitals or from landfill leachates. There are increasing demands from both the scientific communities and the popular press (Raloff, 1998; Pearce, 1999) for information on the potential toxicity of pharmaceuticals in water, yet there is an almost complete lack of data concerning their effects on aquatic fauna, particularly the invertebrates which play a major role in the structure and functioning of freshwater ecosystems. Hence it is important that we understand the extent to which invertebrates may be affected by the presence of active pharmaceutical agents. New drugs are added annually to the British National Formulary (BMA and RPS, 2001) but for most there are no available data on environmental fate, transformation or effects and there is still no approved environmental risk assessment (ERA) procedure for pharmaceuticals used in human therapy in Europe although several draft documents have been discussed. To determine a realistic ERA, chronic toxicity data for key species are ideally required (Girling et al., 2000). It is this information which is currently lacking and which can only be obtained through chronic, sub-lethal toxicity studies.
Many pharmaceuticals have already been detected (generally at ng l−1 or low μg l−1 concentrations) in sewage effluent and other environmental samples including surface, ground and even drinking water (Halling-Sørensen et al., 1998; Ternes, 1998). The available toxicity data for pharmaceuticals, much of which generally relate to acute lethal responses determined in the water flea Daphnia sp. (Lilius et al., 1995; Henschel et al., 1997; Wollenberger et al., 2000) indicate that high, environmentally unrealistic concentrations are needed to cause acute toxicity. However, to date, the chronic, sub-lethal effects of only ethinylestradiol (EE2) on aquatic species have been investigated. EE2, which is prescribed as a female contraceptive, has been identified as a potent endocrine disrupter which causes an increase in plasma vitellogenin in fish in the field (Purdom et al., 1994) and inhibits testicular growth in laboratory fish maintained at concentrations as low as 2 ng l−1 (Jobling et al., 1996). We have recently demonstrated (Watts et al., 2002) that concentrations as low as 100 ng l−1 EE2 caused increased juvenile recruitment in populations of the amphipod Gammarus pulex and a change in sex ratio from approximately 1:1 to 2:1 (female:male). In addition studies with the insect Chironomus riparius revealed deformities in the mouthparts following chronic exposure to EE2 at concentrations as low as 10 ng l−1 (Watts et al., in press).
These results suggest that invertebrates as well as fish are at risk from long-term, low level EE2 exposure, despite low acute toxicity e.g. the 96 h LC50 for G. pulex is 1.7 mg l−1 (Watts et al., 2001) and for C. riparius 9.5 mg l−1 (Segner et al., in press). This consequently raises the possibility that other pharmaceuticals could exhibit similar effects, i.e. lethal only at very high environmentally unrealistic concentrations but damaging at very low concentrations over long exposure times. The lack of data clearly indicates that the ecotoxicity of pharmaceuticals at environmentally relevant concentrations is a major unaddressed area (Daughton and Ternes, 1999).
The purpose of this study was to determine if common pharmaceuticals entering freshwater adversely effect the survival and life history characteristics of freshwater invertebrates to the extent that population structure could be modified. The investigation was carried out with the sedentary cnidarian Hydra which occurs in many freshwaters (Campbell and Bode, 1983) and is widely used for studying freshwater pollutants (Benson and Boush, 1983; Hyne et al., 1993; Beach and Pascoe, 1998; Pollino and Holdway, 1999; Karntanut and Pascoe, 2000) and in screening tests to assess the teratogenic potential of drugs (Wilby and Tesh, 1990). The pharmaceuticals were selected from lists of the most widely prescribed drugs, compiled in recent studies in the UK, including Wales (personal communication Dr. D. John, Welsh School of Pharmacy), Germany (Ternes, 1998) and Denmark (Stuer-Lauridsen et al., 2000) and taking into account the amounts produced and where available, their actual concentrations in sewage effluent/surface water as well as information relating to fate, biodegradability and persistence. Although it is unlikely that freshwater invertebrates would ever be exposed to drug concentrations causing acute lethal toxicity it was considered important for comparative purposes to assess acute effects before progressing to chronic studies at environmentally relevant concentrations.
Section snippets
Culture of test organism
Hydra vulgaris were cultured in Hydra medium (Lenhoff, 1983) at 20±1 °C with a 16:8 h light: dark regime using separate glass aquaria (33×24×21 cm) and following the procedure described by Beach and Pascoe (1998).
Test chemicals
The following 10 pharmaceuticals were examined: ibuprofen (non-steroidal anti-inflammatory, antipyretic and analgesic); paracetamol (acetamidophenol an analgesic–antipyretic); aspirin (acetylsalicylic acid, a non-steroidal anti-inflammatory, antipyretic and analgesic); amoxicillin
Water quality and drug concentration
Water quality parameters recorded for the Hydra medium during the study were hardness (207.6 mg l−1 as CaCO3), conductivity (445 μS cm−1), pH (7.6) and DO (7.2 mg l−1). Concentrations of all drug solutions were found to be within 10% of nominal and so the nominal concentrations were used in all data presentations and analyses. The toxicity data obtained with cadmium controls were in line with those seen in earlier experiments providing confidence in the validity of the results for the drug tests.
Acute toxicity––effects on polyp structure
Discussion
Pharmaceuticals differ from other pollutants entering water in two key respects; (i) they are actually designed to have effects upon biological systems by modification of physiological/biochemical function, and (ii) unlike many other pollutants, e.g. agrochemicals, which are discharged or released sporadically, pharmaceuticals are continuously introduced into surface waters causing life cycle exposures of the biota.
It is unlikely that freshwater invertebrates would ever be exposed to drug
Conclusion
Acute and chronic exposures of the cnidarian H. vulgaris to 10 commonly prescribed pharmaceuticals indicate that these substances do not present an acute lethal risk or adversely affect feeding or bud formation at concentrations up to 1.0 mg l−1. However, three of the drugs examined i.e. diazepam, digoxin and amlodipine did inhibit polyp regeneration at 10 μg l−1.
Acknowledgements
We gratefully acknowledge the supply of Amlodipine besylate by Pfizer Limited, Global Research and Development, Sandwich, Kent, UK. Dr. D. John of the Welsh School of Pharmacy provided information on drug usage in Wales and the Medicines Control Agency advised on medicinal product use in the UK. Wanchamai Karntanut is sponsored by the Royal Thai government.
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