Entwicklung und Einsatz eines standardisierten Labortests für Dungkäfer (Aphodius constans) zur Prüfung der Ökotoxizität von Veterinärpharmaka

Goal, Scope, and Background

According to European legislation, an environmental risk assessment of veterinary pharmaceuticals for dung beetles is required if the substance is a parasiticide for the treatment of pasture animals. However, the demonstration of the environmental safety of those substances for dung beetles is strongly hampered by the fact that no standardized test system is available so far. Therefore, starting with recommendations from the SETAC advisory group DOTTS (Dung Organism Toxicity Test Standardization), a test system using the widespread temperate dung beetle species Aphodius constans was developed.

Methods

Using experiences gained at the University of Montpellier (e.g. in field studies) and in other terrestrial tests, details of culturing and testing of A. constans were investigated in a project sponsored by the German Environment Protection Agency (UBA). Basically, the survival of young larvae of A. constans exposed to the test substance spiked into formulated (i.e. dried, grounded and re-wetted) or fresh dung is measured over a period of three weeks. Using the model substance dimethoate (an insecticide required as positive control in tests with the predatory mite Hypoaspis aculeifer) the suitability of the new test was checked. Afterwards, the new test method was used to determine the toxicity of four common veterinary pharmaceuticals (ivermectin, dicyclanil, moxidectin, praziquantel) in formulated and fresh dung. Finally, the effects of ivermectin on the dung beetles were determined in a test using fresh dung from treated cattle.

Results and Conclusions

For Dmethoate LC₅₀-values were found in a range of 1–3 mg a.s./kg dung (dew.), depending on the dung type. Praziquantel did not show eirecis in the tested concentration range (i.e. up to 1000 mg a.s./kg Dung (DW). The LC₅₀-values of the other three pharmaceuticals were very low (<6 mg a.s./kg dung (DW)). With the exception of Dicyclanil no differences between formulated and fresh dung were identified. In the case of ivermectin the LC₅₀-value were even lower: about 0.5 mg a.s./kg dung (DW). No differences between the results of test in which the substance was spiked into dung and those tests which were performed with dung from treated cattle were found. These results prove the sensitivity as well as the robustness of this test method.

Recommendations and Perspectives

Based on the experiences reported here, it is recommended to standardize this test in an international ring test so that it can be incorporated in the risk assessment process for veterinary pharmaceuticals as described in the currently developed international registration guidelines.     

Pharmazeutische Wirkstoffe und Umweltschutz

On 26 April this year the German Environmental Advisory Council (SRU) published a statement on ‘Pharmaceuticals in the environment’ and pointed considerable need for action to understand and to reduce the risks from diffuse pharmaceutical inputs in the environment. On the one hand, it is urgently necessary to improve the database for environmental risk assessments; on the other hand measures should already be taken to minimize harmful inputs. Fortunately, the new regulations for an application for an authorization to market new pharmaceuticals require an environmental risk assessment. However, there is a lack of information on possible impacts from long time admitted medicines which may be responsible for harmful active substances detectable in the environment. To remove this data deficit, a European programme for risk evaluation of old pharmaceuticals should be established. It is necessary for an adequate risk assessment to look at all impacts of one active substance or all substances same-directed in their active potential summativ and to generate regularly consumption data in particular for the use of veterinary products. The hot spots of contamination are the introduction of large scale volumes of active pharmaceutical ingredients for human use like diclofenac and carbamazepin as well as hormones into surface waters, as well as the application of antibiotics-loaded economic fertilizers on soils. Not to be neglected is the application of antiparasitics in animals kept on pasture. With the assessment of the use of pharmaceuticals for all purposes special attention is needed on antibiotic resistance. For the mitigation of environmental exposures there are exposures measures necessary to reduce use of antibiotics in farming, for the application of new effective technologies in treatment sewage — as for example ozonation, filtration with activated carbon or membrane filtration — as well as for the labelling of environmentally harmful medicinal products.     

Priorisierung von bioziden Wirkstoffen aufgrund der potenziellen Gefährdung schweizerischer Oberflächengewässer

Background, Aim and Scope Active substances for use in biocidal products can potentially occur as micropollutants in natural waters. Biocides, which are used in Switzerland for non-agricultural applications, should be evaluated and prioritized with regard to their respective environmental risks. The following questions were emphasized: Which active substances are used for which purposes and in which amounts? Is there discharge to the aquatic environment? What are the environmental behaviours and ecotoxicological effects of these biocides? How can a prioritization be achieved? Which active substances should be suggested for further assessments? Methods Manufacturing firms, sales organisations, users and environmental experts were identified as key stakeholders for the issues of this project. Chemical identities, product compositions, used amounts, product types, ways and places of applications were elucidated. A database was established with information on approximately 1760 products with totally 277 active substances. A prioritization procedure was established, providing a distinction of the active substances. For priority setting, water pollution risks by biocides were evaluated based on potential environmental emissions as well as on environmental behaviour and ecotoxic effects. Results In the European Union 372 active substances were notified for biocidal products, which accounted for use of 7500 tons per year in Switzerland. More than 95?% of the total use bases on 30 active substances, of which seven are rapidly biodegradable. A group of experts determined 22 substances as candidates for an extended assessment. It became evident that many active biocidal substances are highly ecotoxic und could, therefore, cause an augmented environmental risk Discussion It could be shown which active substances are applied in Switzerland in substantial amounts. Although close to 300 active biocidal substances are used, only about 30 substances are employed in relevant amounts of more than 5000?kg per year. For 22 active substances with low biodegradability, a potential environmental risk for natural surface waters can be inferred. These active substances are used at amounts comparable to the pesticides.     

Entwicklung von ökotoxikologischen Instrumenten und ihre rechtliche Implementierung zur marinen ökologischen Risikobewertung von Chemikalien, Pestiziden und Baggergut

Background, aim, and scope The marine environment is often the final sink for pollutants, especially for persistent organic pollutants (POPs) and for persistent, bioaccumulative and toxic (PBT) substances. The body burden of marine top predators in the Baltic Sea, in the North Sea and also in the Arctic seas is alarming. Thus, the question was investigated if the European environmental law considers a prospective marine ecological risk assessment of chemicals, pesticides and dredged material before they are launched on the market or disposed to the sea. Results The analysis of European environmental law showed that the European environmental protection goals demand a good quality status of coastal waters until 2015 (Waterframework Directive) and a good quality status of European seas until 2020 (Marine Strategy Directive), but a specific marine ecological risk assessment of chemicals and pesticides is not sufficiently required in current European legislation. Discussion It was shown that the ecological risk assessment for freshwater ecosystems is, due to the pecularities of pollutant impacts in the marine environment, not adequate to predict marine effects and to protect the marine environment sufficiently. A statistical analysis of international databases on the relative toxicity of narcotics revealed that marine organisms can be significantly more sensitive than freshwater organisms towards substances with an unspecific mode of action (narcotics). Approximately 60?% of the industrial chemicals are classified as narcotics by their mode of action. Thus, this substance class is of environmental importance. Due to the hydrophobic properties and the low solubility of narcotics in seawater, the ecotoxicological assessment of marine sediments was of interest. An estuarine and marine bioassay test set was established and further developed to assess the ecotoxicological potential of brackish and seawater sediments. It was important that the test procedures were adapted to brackish and marine conditions and were harmonised between each other as well as on the international level. Conclusions Beside two bioassays for the ecotoxicological assessment of elutriates of marine and brackish sediments (bacteria bioluminescence test and marine algae test), the implementation and further development of the whole sediment bioassay with the marine amphipod Corophium volutator was important for enhancing the risk assessment. In order to gain a more standardised, all-season available test organism, the marine amphipod was for the first time reproduced under laboratory conditions the whole year round (also in winter), which is the essential basis for the urgently needed chronic whole sediment bioassay. The results of this investigation were implemented in the international (ISO), European (EN) and national (DIN) standardisations. Therefore, a standardised test set is ready for the implementation in the marine ecological risk assessment of chemicals, pesticides and dredged material in international, European and national legislation. Recommendations and perspectives Recommendations to improve the implementation of a marine risk assessment in European regulations are given with the goal to reach the internationally required objective of a sustainable development of the seas.     

防污漆中活性物质海洋环境风险评估关键技术探讨

防污漆中的活性物质对海洋生态环境和人类健康造成的潜在风险受到日益广泛的关注,一些发达国家已建立了针对活性物质海洋环境风险评估的技术体系,但我国相关研究目前尚属空白。综述了防污漆活性物质海洋环境风险评估的研究背景、相关法规、技术标准和发展现状,针对环境风险评估的2个重要组成部分(危害性评估和暴露评估)中的关键技术进行了探讨。在危害性评估中,重点分析和比较了受试生物物种的选择原则、生态毒理数据的要求以及预测无效应浓度的推导方法和应用范围;在暴露评估中,系统阐述了活性物质在水环境中释放速率的计算及修正方法、环境浓度的预测模型、现有的暴露场景及其局限性等。本文以期为我国开展防污漆活性物质海洋环境风险评估提供研究基础和科学依据,并提出了今后的研究重点和方向。     

Humanarzneimittel im aquatischen Ökosystem

Goal

In the Brandenburg State Office for the Environment an approach to assess the potential risk of drug residues in aquatic ecosystems has been developed based on an investigation of the consumption amounts in 1999 to identify or to exclude a potential environmental risk of important human drugs and further to define priority substances for monitoring programs in Brandenburg in the future.

Method

This assessment approach tested with 60 drug agents is based on an exposure estimation considering the main path for the entry human—waste water—sewage plant—surface water, on a substance specific analysis of effects and on an analysis of the environmental fate as compartment distribution, bioaccumulation and persistence.

Results

In Brandenburg surface waters the drug agent concentration for eight of the considered substances is supposed to be greater than 1 μg/l and for at least 13 of the considered substanoes the PNEC in aquatic ecosystems is assumed to be lower than 1 μg/l. A potential risk for the environment can be seen for the antibiotics Ciprofloxacin-HCl and Clarithromycin, the disinfectants Benzalkonium Chloride, Cocospropylendiaminguaniacetat, Glucoprotamine, Laurylpropylenediamine and Polyvidone-iodine, the sexual hormon Ethinylestradiol, the antidiabetic Metformin-HCl, the antiepileptic Carbamazepine and the lipid regulator Clofibrinic acid on the basis of effects because their PEC:PNEC-relation is about 1 or higher. For further 19 drug agents an environmental risk is to be assumed because of their environmental behaviour without support by ecotoxicological data at present.

Conclusion

Although there is only a small base of valid ecotoxicological data, this risk assessment shows that adverse effects in the aquatic environment by some drug agents cannot be excluded. However, it should be noted that this first assessment gives only a crude orientation. Appropriate test data are necessary to refine the assessment in future.     

Antibiotika als Umweltkontaminanten — Effekte auf Bodenbakterien

Goal and scope

Among the human and veterinary pharmaceuticals, antibiotics form an important group. Recent research addressed the environmental ‘side effects’ of antibiotics. Evidence for environmental effects of antibiotics has for example been found for the respiratory activity of soil microorganisms. In the present contribution, results of studies on the ecotoxicology of antibiotics that are based on the utilization of carbon substrates in so-called Biolog plates are summarized.

Methods, Results and Conclusions

The method of pollution-induced community tolerance (PICT) takes centre stage. PICT is based on the changes in community composition of environmental communities brought about by a toxicant, which lead to an overall increase in community tolerance to this toxicant. The suitability of such an increase in community tolerance as ecotoxicological endpoint had been the subject of several experiments. It was shown that effect testing of antibiotics requires supplementation of the communities with nutrients, and that the PICT method reveals antibiotic effects with a high specificity. In an application of PICT, effects of three classes of antibacterial compounds were investigated. Dose-response relationships were obtained for all substances, and effect concentrations were partly in the range of expected environmental concentrations. The possible risks of antibiotic use for an increase in the occurrence of antibiotic resistance genes in the environment are also touched upon, including the extent of natural resistance.

Outlook

Due to its specificity, the PICT method has shown to be a suitable ecotoxicological assay. Due to possible effects of tetracyclines on the structure of the soil microbial community, it is advised to use veterinary antibiotics with caution. The risks of an increase in the occurrence of antibiotic resistance in the environment should be investigated in more detail.     

Arzneimittel in der aquatischen Umwelt

The German Environmental Advisory Council evaluated German water protection policies in its last environmental report (2004) concluded that despite some great successes in this area there is still considerable need for action. Specifically, diffuse nutrient and chemical substances inputs remain an unsolved problem. The contamination of surface and groundwater with pharmaceuticals has been identified as an environmental risk increasing in pertinence. Pharmaceuticals and their metabolites are being detected in the whole aquatic environment, which they enter through sewage, soil contamination by agriculture, and waste storage facilities. Different pharmaceuticals have been tested for acute toxicity on various aquatic organisms, but almost nothing is known about chronic toxicity of these contaminants. This knowledge, however, is essential for estimating the ecotoxicological potential of pharmaceutical residues. In the opinion of the Environmental Council different strategies are necessary, to reduce the contamination of the environment with pharmaceuticals. Farmers should refrain from using pharmaceuticals for prophylactic purposes or from using hormonally or antibiotically active substances in livestock feed additives, so as to reduce inputs of veterinary drugs. As regards human medications, packaging should better correspond to appropriate dosage amounts, and environmentally responsible disposal measures should be followed. Still under discussion are a programme for the risk evaluation of existing pharmaceuticals and a ban on the use of sewage sludge in agriculture. In the future, improvement of sewage treatment facilities, for instances through membrane technologies, will offer further potential to reduce inputs of hazardous substances.     

In vitro Screening von Pflanzenschutzmittel-Wirkstoffen auf östrogene Aktivität

Over the last years, the obviously increasing, hormone-dependent impairments observed in humans and animals, as well as the increased occurrence of hormone-dependent types of cancer, are sometimes associated with environmental chemicals which are suspected to imitate or block the effects of natural hormones. For a variety of environmental chemicals an endocrine efficacy could already be demonstrated. Little is known, however, about a possible hormonal activity of plant protection agents which are at present certificated in the Federal Republic of Germany. The aim of the present study was the in vitro testing of at least 57 active ingredients of pesticides and growth regulators certificated in the Federal Republic of Germany, for their possible estrogenic activity. The E-Screen-Assay based on the human breast cancer cell line MCF-7 was used as the suitable test system. For at least 8 of the tested substances, an receptor-mediated estrogenic activity could be shown in vitro. With the exception of one substance, 7 active ingredients displayed a very weak affinity for the human estrogen receptor. Their ability to displace 17β-estradiol from the receptor was low. Only the herbicide Pendimethalin is to be classified as a full estrogen receptor agonist; it is able to displace 17β-estradiol almost completely from the receptor. Howeverm the estrogenic potency of Pendimethalin, in comparison to 17β-estradiol, was seen to be as small as the estrogenic potency of the other 7 substances tested positively in the E-Screen-Assay. Among this 7 substances, two could not be classified as estrogenically active anymore, because their affinity to the human estrogen receptor was too weak. The relevance of the available results for livng organisms should be clarified in further in vivo investigations.     

新型污染物及其生态和环境健康效应

近年来,随着现代分析手段的改进和发展,各种污染物检测能力的提高,以及新的毒作用模式的发现、新合成化合物的制造和使用等,一些物质成为广受国内外关注的新型污染物.新型污染物已在世界范围内对环境和生态系统造成了污染,对生态系统中包括人类在内的各种生物均构成了潜在的危害.目前,人们关注较多的新型污染物主要有全氟有机化合物、人用与兽用药物、饮用水消毒副产物、遮光剂/滤紫外线剂、人造纳米材料、汽油添加剂、溴化阻燃剂等.论文在总结国内外相关研究基础上,对一些重点新型污染物的生态效应及其潜在健康影响进行了简要综述,为我国开展这方面的研究提供了一定的参考.     

Effects of clotrimazole and amiodarone on early development of amphibian (Xenopus tropicalis)

Pharmaceuticals have been recognized as a continuing threat to environmental stability. Few experimental data are available for the effects of clotrimazole and amiodarone on the ecological environment. An acute test with embryos and a chronic test with larvae of amphibian (Xenopus tropicalis) were thus conducted to determine the influence of clotrimazole or amiodarone on early amphibian development. In acute test, % survival and the body length were numerically decreased by both pharmaceuticals treatments compared to control. In chronic test, the cumulative mortality was 22.2% with 0.1?µg?L^?1 clotrimazole treatment and 21.7% with 1?µg?L^?1 amiodarone. The whole body length and the biomass were significantly decreased and developmental stages significantly delayed by both pharmaceuticals. The results of our study suggest that clotrimazole exerted adverse effects on larvae of X. tropicalis at environmentally relevant concentrations.     

兽药类环境内分泌干扰效应及评价研究进展

兽药在保障动物健康、提高畜禽产品质量尤其在畜牧业集约化发展等方面起着至关重要的作用,然而兽药和饲料添加剂的大量使用成为生态环境污染和人体健康损害的一个重要因素。研究表明许多抗生素类和激素类兽药是典型的环境内分泌干扰物,通过多种方式干扰生物体雄激素、雌激素、甲状腺激素等内分泌过程,产生内分泌干扰效应。本文介绍了典型兽药的污染现状及其内分泌干扰效应研究最新进展;以环境内分泌干扰物的最新研究方法为基础,较全面地评述了可用于兽药类内分泌干扰物的快速筛选、检测及评价方法,并对该领域未来研究提出了展望和建议,以期为环境和农业等管理部门制定兽药的使用、排放、管理政策提供科学依据。     

兽药类环境内分泌干扰效应及评价研究进展

兽药在保障动物健康、提高畜禽产品质量尤其在畜牧业集约化发展等方面起着至关重要的作用,然而兽药和饲料添加剂的大量使用成为生态环境污染和人体健康损害的一个重要因素。研究表明许多抗生素类和激素类兽药是典型的环境内分泌干扰物,通过多种方式干扰生物体雄激素、雌激素、甲状腺激素等内分泌过程,产生内分泌干扰效应。本文介绍了典型兽药的污染现状及其内分泌干扰效应研究最新进展;以环境内分泌干扰物的最新研究方法为基础,较全面地评述了可用于兽药类内分泌干扰物的快速筛选、检测及评价方法,并对该领域未来研究提出了展望和建议,以期为环境和农业等管理部门制定兽药的使用、排放、管理政策提供科学依据。     

Humanpharmakawirkstoffe in der Umwelt: Einträge, Vorkommen und der Versuch einer Bestandsaufnahme

Background

The presence of a large spectrum of pharmaceutical agents has been reported for aquatic environments (surface—and groundwater) and other aquatic media (influents and effluents of sewage treatment plants) in Germany and beyond, including their occurrence in drinking water. Considering the large number of pharmaceuticals produced for human use and released into the environment, various authors (Sattelberger 1999, Hanisch et al. 2004, Castiglioni et al. 2006, IWW 2006, Stockholm County Council 2006) tried to compile ‘priority lists’ focusing on those substances with environmental relevance. The following agents are included in all lists: ciprofloxacine, clarythromycine (antibiotics), carbamazepine (anti-epileptic agent), bezafibrate (lipid reducer), clofibric acid (lipid reducer metabolite), ethinylestradiol (sex hormone) and cylophosfamide (cytostatic agent). The agents erythromycine and sulfamethoxazole (antibiotics), ibuprofen, indometacine, propyphenazone (analgesics), atenolol (beta-blocker) and ifosfamide (cytostatic agent) can be found in three of four priority lists.

Results

Pharmaceuticals mainly enter the aquatic environment via effluent water, coming from wastewater treatment plants (including hospital and household sewerage), untreated discharges (e.g, secondary transfer of active agents into ground- and surface waters via sewage sludge application in agriculture and via landfill leachate) and leakages in the municipal sewer network.

Discussion

Potential activities towards a reduced release of pharmaceuticals into the environment should consider primarily the origin of the exposure to allow a separation of drug containing flows already at the source. Following the latter it would be possible to minimize the contamination of spring-, ground- and surface waters which serve as raw water resources for drinking water supply. However, considering the actual water pollution with pharmaceuticals and other substances, ‘end-of pipe’ techniques in the sewage and drinking water treatment are absolutely essential.

Conclusions

Sustainability criteria (e.g. protection of drinking water resources, habitats and biocoenoses, recycling and economizing use of resources) and economic aspects of modern sewage disposal concepts require a useful choice and combination of technical measures as components of centralized and decentralized sewage and drinking water treatment methods. It is though not realistic to cover and eliminate all pharmaceutical agents of environmental relevance equally effective even if a catalogue of potential technical treatment methods is elaborated thoroughly. Therefore, a concentration of efforts on selected drug agents, at least following initially some of the priority lists, is recommended.

Recommendations and Perspectives

The contamination of the water cycle with pharmaceuticals is nevertheless not exclusively to be solved via the application of technical methods. The BMBF (Federal Ministry for Education and Research) funded project start (Management Strategies for Pharmaceuticals in Drinking Water, www.start-project.de) therefore tries by implementation of a transdisciplinary approach to integrate technical-, behavioral-, and agent-orientated management strategies towards a more comprehensive and sustainable problem solution.     

A new ecotoxicological test method for genetically modified plants and other stressors in soil with the black fungus gnat <Emphasis Type="Italic">Bradysia impatiens</Emphasis> (Diptera): current status of test development and dietary effects of azadirachtin on larval development and emergence rate

Background

Few suitable and standardized test methods are currently available to test the effects of genetically modified plants (GMP) on non-target organisms. To fill this gap and improve ecotoxicological testing for GMP, we developed a new soil ecotoxicological test method using sciarid larvae as test organisms.

Results

Bradysia impatiens was identified as a candidate species. Species of the genus Bradysia occur in high numbers in European agroecosystems and B. impatiens can be reared in the laboratory in continuous culture. A functional basic test design was successfully developed. Newly hatched larvae were used as the initial life stage to cover most of the life cycle of the species during the test. Azadirachtin was identified as a suitable reference substance. In several tests, the effects of this substance on development time and emergence rate varied for different temperatures and test substrates. The toxicity was higher at 25 °C compared to 20 °C and in tropical artificial soil compared to coconut fiber substrate.

Conclusions and outlook

Results suggest that the developed test system is suitable to enter a full standardization process, e.g., via the Organisation for Economic Co-operation and Development. Such a standardization would not only assist the risk assessment of GMP, but could include other stressors such as systemic pesticides or veterinary pharmaceuticals reaching the soil, e.g., via spreading manure. The use of sciarid flies as test organisms supports recommendations of EFSA, which stressed the ecological role of flies and encouraged including Diptera into test batteries.

     

Arzneimittelentwicklung: Die Reduzierung von Umweltbelastungen durch gezieltes Moleküldesign

Results of the study In a long-term perspective innovations which are directed towards the principles of sustainable active pharmaceutical ingredients (APIs) will result in substituting problematic substances with other ones which are therapeutically effective as well as degradable in an environmentally compatible way. The substitution leads to a considerable decrease in water pollution with respect to the influx of APIs. The article summarizes the standard of knowledge considering measures with which such innovations and the consequent water improvement can be achieved. Discussion With an adequate promotion of research within this field and a modified scientific education the appliance of specific molecular designs could be established in the pharmaceutical sciences and industry. Examples will show that this, as a first step, may result in effective structures (model structures, which are already comprising synthetic substances) being modified so as to achieve a good degradability. By providing a list with evaluated and successfully established practical examples the basic practicability of this approach can convincingly be demonstrated. Especially within a changed political framework it will on this basis be possible as a second step to show that the approach also works in a systematic way when it comes to a broader development of new substances. With the help of advertising efforts the swift establishment of those innovations within the pharmaceutical market can be achieved thus supporting an accelerated environmental relief. Conclusions There is an option to develop a method of resolution, which will bring forward a trans-formation within the pharmaceutical industry with respect to a sustainable development. Those new methods furthering an improved degradability of pharmaceutical substances will result in an important reduction of influx into the environment and they will at the same time be able to improve the pharmaceutically relevant properties. Recommendations and perspectives The hereby suggested strategic approach is also applicable for environmentally relevant chemicals, i.?e. not for pharmaceuticals only.     

Pharmaceutical compounds in aquatic environment in China: locally screening and environmental risk assessment

An environmental risk assessment was performed for pharmaceutical compounds present in the aquatic environment of China. Predicted environmental concentration (PEC) of the compounds were calculated according to European Medicines Evaluation Agency (EMEA) guidelines. Available ecotoxicological data compromised by applying a very conservative assessment factor (AF) were employed to calculate the predicted no-effect concentration (PNEC). The screening principle and the risk assessment were based on risk quotient (RQ), which derived from the PEC and related PNEC values. PEC results indicated that all the compounds except sulfadimethoxine and levocarnitine, should carry out phase II risk assessment in EMEA guideline. RQ values suggested that more than 36 pharmaceuticals may be imposed health threats to the aquatic environment; especially the antibiotic therapeutic class including amoxicillin, sulfasalazine, trimethoprim, oxytetracycline and erythromycin showed high RQ values. These substances with high RQ value (RQ≥1) were regarded as top-priority pharmaceuticals for control in the aquatic environment of China. However, the antibiotic substances which had low risk quotient (RQ <1), should be reassessed by its potentially induced resistance under low concentration in future.