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.     

DIFFERENTIAL EFFECTS OF THE HERBICIDES BENSULFURON AND CINOSULFURON ON SOIL MICROORGANISMS

Bensulfuron toxicity on soil microbes was evaluated by the methods used in a previous study on cinosulfuron; the effects of the two sulfonylureas were compared. Cinosulfuron and bensulfuron, at the normal field application rate and 100 times higher, had no effect on the total number of bacteria and nitrifiers, or on the respiration activity in the soil, but they did decrease the nitrification activity. In vitro toxicity tests carried out on representative soil microbial strains using bensulfuron at 50 mg l^?1 showed some inhibition of three of the 17 bacterial strains and strong inhibition of almost all the 12 fungal strains; cinosulfuron had had no effect on any of these strains in the previous study. It is concluded that, compared with cinosulfuron, bensulfuron is potentially more toxic on soil heterotrophic microorganisms, but only at very high concentrations that are nearly impossible to reach with the usual agricultural use of the herbicides. However, autotrophic nitrifiers were more sensitive to both sulfonylureas than the other microorganisms.     

Integrated testing and intelligent assessment—new challenges under REACH

BACKGROUND, AIM AND SCOPE: Due to a number of drawbacks associated with the previous regime for the assessment of new and existing chemicals, the European Union established a new regulation concerning the registration, evaluation, authorisation and restriction of chemicals (REACH). All relevant industrial chemicals must now be assessed. Instead of the authorities, industry itself is responsible for the risk assessment. To achieve better and more efficient assessments while reducing animal testing, all information-standard, non-standard and non-testing-has to be used in an integrated manner. To meet these challenges, the current technical guidance documents for risk assessment of new and existing chemicals had to be updated and extended considerably. This was done by experts in a number of REACH Implementation Projects. This paper presents the most relevant results of the expert Endpoint Working Group on Aquatic Toxicity in order to illustrate the change of paradigm in the future assessment of hazards to the aquatic environment by chemical substances. MAIN FEATURES AND CHALLENGES: REACH sets certain minimum data requirements in order to achieve a high level of protection for human health and the environment. It encourages the assessor to use alternative information instead of or in addition to standard one. This information has to be equivalent to the standard information requirement and adequate to draw overall conclusions with respect to the regulatory endpoints classification and labelling, persistent, bioaccumulative and toxic (PBT) assessment and predicted no-effect concentrations (PNEC) derivation. The main task of the expert working group was to develop guidance on how to evaluate the toxicity of a substance based on integration of information from different sources and of various degrees of uncertainty in a weight of evidence approach. INTEGRATED TESTING AND INTELLIGENT ASSESSMENT: In order to verify the equivalence and adequacy of different types of information, a flexible sequence of steps was proposed, covering characterisation of the substance, analysis of modes of action, identification of possible analogues, evaluation of existing in vivo and in vitro testing data as well as of QSAR results. Finally, all available data from the different steps have to be integrated to come to an overall conclusion on the toxicity of the substance. This weight of evidence approach is the basis for the development of integrated testing strategies (ITS), in that the available evidence can help to determine subsequent testing steps and is essential for an optimal assessment. Its flexibility helps to meet the different requirements for drawing conclusions on the endpoints classification and labelling, PNEC derivation as well as PBT assessment. The integration of all kinds of additional information in a multi-criteria assessment reduces the uncertainties involved with extrapolation to the ecosystem level. The weight of evidence approach is illustrated by practical examples. CONCLUSIONS AND PERSPECTIVES: REACH leads to higher challenges in order to make sound decisions with fewer resources, i.e. to move away from extensive standard testing to an intelligent substance-tailored approach. Expert judgement and integrated thinking are key elements of the weight of evidence concept and ITS, potentially leading to better risk assessments. Important sub-lethal effects such as endocrine disruption, which are not covered by the current procedure, can be considered. Conclusions have to be fully substantiated: Risk communication will be an important aspect of future assessments.     

Toxicity testing with luminescent bacteria – Characterization of an automated method for the combined assessment of acute and chronic effects

The luminescent bacteria test according to EN ISO 11348 is frequently applied in (eco) toxicity testing and is applicable for a huge variety of environmental and industrial samples. A big disadvantage of this method is the very short exposure time, which is expressed in a low sensitivity in regard to substances with a delayed effect. Chronic effects, i.e. interference with cell growth, cannot be assessed with this conventional standard method. The goal of this research was to develop an automated testing system for long term toxicity towards the luminescent bacteria Vibrio fischeri by implementing microtitration-based instrumentation. The optimized method, hereinafter referred to as “kinetic luminescent bacteria test”, can be described as a miniaturized combination of the conventional short-term luminescence inhibition test according to EN ISO 11348 and the Photobacterium phosphoreum growth inhibition test (DIN 38412-37). The validation procedure included the evaluation of six reference compounds (3,4-Dichloroaniline, 3,5-Dichlorophenol, Chloramphenicol, Streptomycin sulfate, Potassium dichromate, Zinc sulfate heptahydrate) and three different endpoints that are acute luminescence inhibition (acute LI) after 30 min, chronic luminescence inhibition (chronic LI) after 24 h and growth inhibition (GI) after 14 h. The optimized method allows the assessment of acute and chronic effects within one test, by what a misinterpretation of the toxicity of substances with delayed bacterial toxicity can be prevented, without abandoning most of the advantages of the conventional short-term test. Therefore, the kinetic luminescent bacteria test is exceptional as an initial screening test for environmental samples or substances with unknown (eco) toxicological characteristics.     

Preliminary study of physico-chemical treatment options for hospital wastewater

Hospital effluents are loaded with pathogenic microorganisms, partially metabolized pharmaceutical substances, radioactive elements, and other toxic substances. Such effluents if not treated properly can damage the natural environment and create a biological imbalance. This paper points out the areas of concern for hospital wastewater disposal and reports the findings of a limited physico-chemical study of treatment options for hospital effluents conducted at Christian Medical College and Hospital, Vellore, Tamil Nadu. The effluent collected was checked for conventional parameters and subjected to coagulation experiments. The raw and settled effluents were coagulated with FeCl(3), filtered and disinfected. Physico-chemical treatment seems to be an attractive option for the cost-effective disposal of hospital effluents. The results of this study call for further detailed study in this area.     

基于自然环境中优选药物的毒性和生态毒理风险研究

在如今超过1 500种在用原料药中,环境中发现几率明确和对环境影响明确的原料药所占比例很小。由于很难监管所有在用原料药,众多先前的研究提议将原料药按照受关注程度排序,从而可以将研究资源集中于那些最受瞩目的药物。然而这些研究都存在局限性,本文从之前优先性方法的实践经验出发,提出了一种更为全面的原料药排序方法。该方法基于对水生生物、土壤生物、鸟类、野生哺乳动物和人类的风险,综合考虑了食物链顶端存在的生态毒理学研究终点和由这些治疗性药物作用机制带来的非顶端效果。对于在英国社区以及医院设置中使用的146种活性药物的分析可以更为详细地说明该方法的运用。根据这一方法,我们将16种化合物列为优先考虑的药物。这些药物包括了抗生素、抗抑郁药、抗炎药、抗糖尿病药、抗肥胖药、雌激素类化合物以及相关的代谢产物。我们建议这种优先性方法在将来可以更广泛地应用于世界上不同的地区。
精选自Jiahua Guo, Chris J. Sinclair, Katherine Selby, Alistair B.A. Boxall. Toxicological and ecotoxicological risk based prioritisation of pharmaceuticals in the natural environment. Environmental Toxicology and Chemistry: Volume 35, Issue 7, pages 1550–1559, July 2016. DOI: 10.1002/etc.3319
详情请见http://onlinelibrary.wiley.com/doi/10.1002/etc.3319/full
     

The water-soluble fraction of potentially toxic elements in contaminated soils: relationships between ecotoxicity, solubility and geochemical reactivity

To better understand the impacts posed by soil contamination to aquatic ecosystems it is crucial to characterise the links between ecotoxicity, chemical availability and geochemical reactivity of potentially toxic elements (PTE’s) in soils. We evaluated the adverse effects of water extracts obtained from soils contaminated by chemical industry and mining, using a test battery including organisms from different trophic levels (bacteria, algae and daphnids). These tests provided a quick assessment of the ecotoxicity of soils with respect to possible adverse effects on aquatic organisms although the ecotoxicological responses could be related to the solubility of PTE’s only to a limited extent.The analysis of results of bioassays together with the chemical characterisation of water extracts provided additional relevant insight into the role of conductivity, pH, Al, Fe, and Mn of soil extracts on toxicity to organisms. Furthermore, an important conclusion of this study was that the toxicity of extracts to the aquatic organisms could also be related to the soil properties (pH, Org C and Fe_ox) and to the reactivity of PTE’s in soils which in fact control the soluble fraction of the contaminants.The combined assessment of ecotoxicity in water fractions, solubility and geochemical reactivity of PTE’s in soils provided a more comprehensive understanding of the bioavailability of inorganic contaminants than ecotoxicological or chemical studies alone and can therefore be most useful for environmental risks assessment of contaminated soils.     

Runoff rates,chemical speciation and bioavailability of copper released from naturally patinated copper

The release of copper, induced by atmospheric corrosion, from naturally patinated copper of varying age (0 and 30 years) has been investigated together with its potential ecotoxic effect. Results were generated in an interdisciplinary research effort in which corrosion science and ecotoxicology aspects were combined. The aim of the investigation was to elucidate the situation when copper-containing rainwater leaves a roof in terms of runoff rate, chemical speciation, bioavailability and ecotoxicity effects. Data have been collected during a three-year field exposure conducted in the urban environment of Stockholm, Sweden. The potential environmental effects have been evaluated using a combination of a copper specific biosensor test with the bacterium Alcaligenes eutrophus and the conventional 72-h growth inhibition test with the green alga Raphidocelis subcapitata. The results show annual runoff rates between 1.0 and 1.5 g/m2 year for naturally patinated copper of varying age. The runoff rate increased slightly with patina age, which mainly is attributed to the enhanced first flush effect observed on thicker patina layers. The total copper concentration in investigated runoff samplings ranged from 0.9 to 9.7 mg/l. Both computer modeling and experimental studies revealed that the majority (60-100%) of released copper was present as the free hydrated cupric ion, Cu(H2O)6(2+), the most bioavailable copper species. However, other copper species in the runoff water, such as, e.g. Cu(OH)+ and Cu2(OH)2(2+), were also bioavailable. The copper-containing runoff water, sampled directly after release from the roof, caused significant reduction in growth rate of the green alga. It should be emphasized that the results describe the runoff situation immediately after release from the copper roof and not the real environmental ecotoxicity. Therefore the data should only be used as an initial assessment of the potential environmental effect of copper runoff from building applications. Future risk assessments should also consider dilution effects of copper, changes in its chemical speciation and bioavailability during environmental entry, and type and sensitivity of the receiving ecosystem.     

An ecotoxicological evaluation of aged bottom ash for use in constructions

Municipal and Industrial Solid Waste Incineration (MISWI) bottom ash is mainly deposited in landfills, but natural resources and energy could be saved if these ash materials would be used in geotechnical constructions. To enable such usage, knowledge is needed on their potential environmental impact. The aim of this study was to evaluate the ecotoxicity of leachates from MISWI bottom ash, aged for five years, in an environmental relevant way using a sequential batch leaching method at the Liquid/Solid-ratio interval 1–3, and to test the leachates in a (sub)chronic ecotoxicity test. Also, the leachates were characterized chemically and with the technique of diffusive gradients in thin films (DGTs). By comparing established ecotoxicity data for each element with chemically analysed and labile concentrations in the leachates, potentially problematic elements were identified by calculating Hazard Quotients (HQ). Overall, our results show that the ecotoxicity was in general low and decreased with increased leaching. A strong correspondence between calculated HQs and observed toxicity over the full L/S range was observed for K. However, K will likely not be problematic from a long-term environmental perspective when using the ash, since it is a naturally occurring essential macro element which is not classified as ecotoxic in the chemical legislation. Although Cu was measured in total concentrations close to where a toxic response is expected, even at L/S 3, the DGT-analysis showed that less than 50% was present in a labile fraction, indicating that Cu is complexed by organic ligands which reduce its bioavailability.     

Chloroform in the environment: occurrence,sources, sinks and effects

The chloroform flux through the environment is apparently constant at some 660±220 Gg yr⁻¹ (±1σ) and about 90% of the emissions are natural in origin: the largest single source being in offshore sea water (contributing 360±90 Gg yr⁻¹), with soil processes the next most important (220±100 Gg yr⁻¹). Other natural sources, mainly volcanic and geological, account for less than 20 Gg yr⁻¹. The non-natural sources total 66±23 Gg yr⁻¹ and are much better characterised than the natural sources. They are predominantly the result of using strong oxidising agent on organic material in the presence of chloride ion, a direct parallel with the natural processes occurring in soils.

Chloroform partitions preferentially into the atmosphere; the equilibrium distribution is greater than 99% and the average global atmospheric concentration has been calculated to be 18.5 pmol mol⁻¹. Atmospheric oxidation, the principal removal process, is approximately in balance with the identified source fluxes. Chloroform is widely dispersed in the aquatic environment (even naturally present in some mineral waters). Consequently, it is also widely dispersed in the tissue of living creatures and in foodstuffs but there is little evidence of bioaccumulation and the quantities in foodstuffs and drinking water are not problematical for human ingestion at the highest concentrations found. Definitive studies have shown that current environmental concentrations of chloroform do not present an ecotoxicological risk, even to fish at the embryonic and larval stages when they are most susceptible.

By virtue of the very small amounts that actually become transported to the stratosphere, chloroform does not deplete ozone materially, nor is it a photochemically active volatile organic compound (VOC). It has a global warming potential that is less than that of the photochemically active VOCs and is not classed as a greenhouse gas.