Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs?

This study considers the implications and research needs arising from anticancer (also referred to as antineoplastic) drugs being released into the aquatic environment, for the entire therapeutic classes used: cytotoxic, cytostatic and endocrine therapy drugs.A categorization approach, based on French consumption amounts, allowed to highlight parent molecules and several metabolites on which further occurrence and ecotoxicological studies should be conducted.Investigations of consumption trends at a national and a local scale show an increase in the use of anticancer drugs between 2004 and 2008, thus leading to increased levels released in the environment. It therefore appears necessary to continue surveying their presence in surface waters and in wastewater treatment plant (WWTP) effluents.Furthermore, due to the rise of anticancer home treatments, most of the prescribed molecules are now available in town pharmacies. Consequently, hospital effluents are no longer the main expected entry route of anticancer drugs into the aquatic environment.Concerning ecotoxicological risks, current knowledge remains insufficient to support a definitive conclusion. Risk posed by cytotoxic molecules is still not well documented and it is not possible to conclude on their long-term effects on non-target organisms. To date, ecotoxicological effects have been assessed using standardized or in vitro assays. Such tests however may not be suitable for anticancer drugs, and further work should focus on full-life cycle or even multigenerational tests.Environmental significance (i.e. occurrence and effects) of cytostatics (protein kinases inhibitors and monoclonal antibodies), if any, is not documented. Protein kinases inhibitors, in particular, deserve further investigation due to their universal mode of action.Finally, concerning endocrine therapy drugs, molecules such as antiestrogen Tamoxifen and its active metabolites, could be of concern.Overall, to accurately assess the ecotoxicological risk of anticancer drugs, we discuss the need to break away from tests on isolated molecules and to test effects of mixtures at the low ng.l^− 1 range.     

How accurately do semi-permeable membrane devices measure the bioavailability of polycyclic aromatic hydrocarbons to Daphnia magna?

Semi-permeable membrane devices (SPMDs) are passive samplers that have been designed to sample the bioavailable fractions of hydrophobic organic compounds in aquatic ecosystems. This study aims at evaluating the ability for SPMD to sample polycyclic aromatic hydrocarbons (fluoranthene, pyrene and benzo[a]pyrene) that are actually bioavailable to Daphnia magna. For that purpose, the SPMD-available fraction and the bioavailable fraction to D. magna are compared in controlled media with Dissolved Organic Matters (DOMs) from various origins and at different concentrations. The presence of all but one DOM reduces the accumulation of PAHs in SPMD or in D. magna. Moreover, this comparative laboratory study shows that in 10 cases on 13, the SPMD-available fraction is close to the available fraction to D. magna. When significant differences are observed between SPMD-available and bioavailable fractions, they remain less than 50% at DOM concentrations below 10 mg/l DOC, which corresponds to a maximum DOC concentration usually found in temperate rivers. This study confirms the suitability of the SPMD technique to monitor readily bioavailable hydrophobic contaminants in aquatic environments containing DOM from various origins and characteristics.     

Developing environmental quality standards for various pesticides and priority pollutants for French freshwaters

The French Ministry of the Environment and Water Agencies have derived environmental quality standards following the existing French framework called SEQ-Eau, for 28 pesticides and seven priority substances listed in the Water Framework Directive. Like other existing frameworks, SEQ-Eau relies upon the use of standard toxicity test results and assessment factors. This approach made it possible to derive the desired quality standards, but due to the lack of chronic toxicity data many of the standards are only provisional. In addition, emerging issues such as endocrine disruption should be taken into account in this framework. Depending on the available data, more flexible derivation approaches, such as the statistical distribution of NOECs, are recommended for future versions of SEQ-Eau. A comparison is made using SEQ-Eau and the methodology currently being discussed in Europe to develop environmental quality standards, showing that the European approach is more conservative. Conversely, the proposed approach under the Water Framework Directive does not cover the entire range of required quality classes.     

Effects of the parasiticide ivermectin on the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata

Although widely used for the treatment of endo- and ectoparasites in livestock and pets, very few data on chronic effects on aquatic organisms are available for the parasiticide ivermectin. In the present study, toxicity of ivermectin to two freshwater organisms, the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata was investigated. For D. magna, a mean LC(50) 48 h of 5.7 ngl(-1) was derived from 10 acute tests. Chronic toxicity of ivermectin to D. magna was extremely high: with 0.001 and 0.0003 ngl(-1), respectively, nominal LOEC and NOEC based on growth and reproduction were far below the analytical limit of detection for this compound. P. subcapitata was considerably less sensitive to ivermectin than D. magna. For both growth rate and yield, EC(50) was >4,000 microgl(-1), LOEC was 1,250 microgl(-1) and NOEC 391microgl(-1). In view of the high toxicity to D. magna, the use of ivermectin might pose a risk to local aquatic ecosystems. Further studies should be carried out to investigate the effects of ivermectin and its degradation products on pelagic and benthic freshwater invertebrates.     

Fluoxetine effects assessment on the life cycle of aquatic invertebrates

Fluoxetine is a serotonin re-uptake inhibitor, generally used as an antidepressant. It is suspected to provoke substantial effects in the aquatic environment. This study reports the effects of fluoxetine on the life cycle of four invertebrate species, Daphnia magna, Hyalella azteca and the snail Potamopyrgus antipodarum exposed to fluoxetine spiked-water and the midge Chironomus riparius exposed to fluoxetine-spiked sediments. For D. magna, a multi-generational study was performed with exposition of newborns from exposed organisms. Effects of fluoxetine could be found at low measured concentrations (around 10mugl(-1)), especially for parthenogenetic reproduction of D. magna and P. antipodarum. For daphnids, newborns length was impacted by fluoxetine and the second generation of exposed individuals showed much more pronounced effects than the first one, with a NOEC of 8.9mugl(-1). For P. antipodarum, significant decrease of reproduction was found for concentrations around 10mugl(-1). In contrast, we found no effect on the reproduction of H. azteca but a significant effect on growth, which resulted in a NOEC of 33mugl(-1), expressed in nominal concentration. No effect on C. riparius could be found for measured concentrations up to 59.5mgkg(-1). General mechanistic energy-based models showed poor relevance for data analysis, which suggests that fluoxetine targets specific mechanisms of reproduction.     

Development of rearing and testing protocols for a new freshwater sediment test species: the gastropod Valvata piscinalis

This paper aimed at proposing rearing and testing protocols for Valvata piscinalis, a new potential species for sediment toxicity testing. Such tests were developed since this species reliably represents the bio/ecological characteristics of other gastropods. It may thus be representative of their sensitivity to chemicals. V. piscinalis was successfully cultured in our laboratory for six generations. Cultures provided a high productivity for a low working time and low costs. The tests conditions we proposed seemed to be relevant for the development of reliable tests with this species. Indeed, hatching probability of egg-capsules, as well as embryo, newborn and juvenile survival rates, were close to 100%. Moreover, growth rates and fecundity were significantly higher than in field and in other laboratory studies. Partial life-cycle tests on clean sediments were achieved for various feeding levels to determine survival, growth and reproduction patterns, ad libitum feeding level and life cycle parameters values. Ad libitum feeding levels for newborn, juveniles and adults were 0.1, 0.4 and 0.8 mg Tetramin/individual/working day. Growth tests with zinc-spiked sediments provided a no-effect concentration and a lowest effect concentration of respectively 200 and 624 mg zinc/kg dry sediment. Other growth tests on spiked sediments we ran at our laboratory with second, third and fourth instars larvae of Chironomus riparius pointed out that V. piscinalis was more sensible to zinc than the chironomid, which is a routine test species in ecotoxicology. According to these results, V. piscinalis is a promising candidate species for sediment toxicity testing.     

The EU-project ERAPharm. Incentives for the further development of guidance documents?

- Triggered by the detection of a large variety of pharmaceuticals in surface waters, soils and groundwaters across the world (e.g. Halling- Sørensen et al. 1998, Daughton & Ternes 1999, Jones et al. 2001, Heberer 2002) and the widespread occurrence of endocrine active compounds and related effects in the environment (e.g. Purdom et al. 1994, Tyler et al. 1998, Vethaak et al. 2002), pharmaceuticals in the environment have become an issue for both the scientific and the public community. During the last few years, our understanding of the fate and effects of pharmaceuticals in the environment has progressed significantly. However, there are still a number of uncertainties concerning the effects of pharmaceuticals on the environment and the assessment of potential exposure (e.g. Hanisch et al. 2004, Salomon 2005). These uncertainties will be addressed by the EU-project ‘Environmental risk assessment of pharmaceuticals’ (ERAPharm). This project, a specific targeted research project, is carried out within the priority ‘Global change and ecosystems’ of the 6th framework programme of the European Union. ERAPharm has started on 1st October 2004; the project duration is three years.     

Representing inequities in the distribution of socio-economic benefits and environmental risk

There is currently no standard methodfor analyzing claims of environmental inequity. Neitheris there a database of statistics on the extent ofrelationship between regional indicators ofenvironmental quality, likely sources of pollution, andthe demographic characteristics of affectedpopulations. The resolution of environmental disputesis often hampered by inadequate communication betweenstakeholder groups about their perceptions andprioritization of the issues in dispute and bydifferential access to information about the issues byeach stakeholder group. This paper describes a web-based tool, ICEP, that uses multi-layered GIS maps toestablish a standard method for analyzing claims ofenvironmental inequity and establish a database ofcorrelation coefficients between environmentalindicators, industry type by SIC code, and demographiccharacteristics of the population in proximity tonoxious facilities. The maps are generated fromstakeholder reports of environmental quality and aredesigned to be accessible via the Internet. Thisprovides stakeholders with direct access to graphicaldisplays of the perceptions of their co-stakeholdersand provides all groups with links to relevantinformation sources about the issues in dispute. ICEPenhances existing community environmental websites likeScorecard and Envirofacts by providingdisplays of median household income as a measure of thedistribution of benefits accrued within an area.     

Cholinesterase activities as potential biomarkers: characterization in two freshwater snails, Potamopyrgus antipodarum (Mollusca, Hydrobiidae, Smith 1889) and Valvata piscinalis (Mollusca, Valvatidae, Müller 1774)

Anti-cholinesterase insecticides constitute a major portion of modern synthetic pesticides and the assessment of cholinesterase (ChE) inhibition is widely used as a specific biomarker for evaluating the exposure of non-target organisms to these pollutants. However, most studies on this biomarker were developed on vertebrates and among invertebrates, gastropod mollusks are rarely used. Gastropods are important members of aquatic habitats and therefore present a high ecological relevance for freshwater ecosystems. In this context, ChE activities were characterized in two freshwater gastropod mollusks, Potamopyrgus antipodarum and Valvata piscinalis, in order to ascertain their value as sentinel species. Firstly, characterization of ChE activities was performed using different substrates (acetylcholine iodide, butyrylcholine iodide and propionylcholine iodide) and specific inhibitors (eserine, iso-OMPA and BW284c51). Secondly, in vivo effect of a widely used organophosphate insecticide, chlorpyrifos, was tested on ChE activity in both species. Results suggested that P. antipodarum possesses two isoforms of cholinesterases, one isoform which properties are intermediate between an acetyl and a propionyl ChE, and one minor isoform which correspond to a butyryl ChE, while V. piscinalis seems to possess only one isoform which displays typical properties of an acetyl ChE. Chlorpyrifos induced no effect on V. piscinalis ChE. In contrast, P. antipodarum activity was significantly decreased by environmental realistic chlorpyrifos concentrations (2.86 and 14.2 nM) after seven days of contact. The present study suggests that P. antipodarum may be employed as a biological indicator for assessing pesticide contamination.     

Towards a renewed research agenda in ecotoxicology

New concerns about biodiversity, ecosystem services and human health triggered several new regulations increasing the need for sound ecotoxicological risk assessment. The PEER network aims to share its view on the research issues that this challenges. PEER scientists call for an improved biologically relevant exposure assessment. They promote comprehensive effect assessment at several biological levels. Biological traits should be used for Environmental risk assessment (ERA) as promising tools to better understand relationships between structure and functioning of ecosystems. The use of modern high throughput methods could also enhance the amount of data for a better risk assessment. Improved models coping with multiple stressors or biological levels are necessary to answer for a more scientifically based risk assessment. Those methods must be embedded within life cycle analysis or economical models for efficient regulations. Joint research programmes involving humanities with ecological sciences should be developed for a sound risk management.