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.     

粉葛根腐病菌的生物学特性及防治研究

粉葛根腐病是粉葛生产上新发现的一种毁灭性土传病害。作者对病原作了人工分离和接菌试验，观测了温度、pH对病原菌菌丝体生长的影响；对防治药剂进行了筛选和试验，探讨了该病的有效防治药物及对策。     

北京市水环境中精神活性物质污染特征

为评价北京市水环境中精神活性物质的污染水平和生态环境风险,利用高效液相色谱-质谱联用法检测了该地区地表水和地下水中6种典型精神活性物质[甲基苯丙胺(METH)、苯丙胺(AMP)、氯胺酮(KET)、麻黄碱(EPH)、甲卡西酮(MC)和羟亚胺(HY)]的质量浓度.结果表明,北京市地表水中共检测出3种目标药物,其质量浓度范围为低于检出限n.d.~70.9ng·L~(-1).EPH的检出频率和质量浓度平均值最高,分别为42%和10.1 ng·L~(-1);其次为METH,检出频率为25%,质量浓度平均值为1.8 ng·L~(-1).地下水样品中只检测到了AMP,检出频率21%,质量浓度水平在n.d.~2.2 ng·L~(-1)之间.与国内外其他研究相比,北京市水环境中精神活性物质的污染浓度总体处于较低水平.METH和EPH浓度最高值均出现在北京市第二大排污河和南城主要污灌渠凉水河.风险评估结果显示,北京市地表水中6种目标药物的风险熵值均小于0.10,表明存在较低的环境风险,但考虑到精神活性物质具有较强的生物活性,它们对水生生态系统的长期和综合风险值得关注.     

在线固相萃取-液相色谱串联质谱法测定污水厂尾水中6种酸性药物

建立了大体积在线固相萃取-液相色谱串联质谱(Online-SPE-LC-MS)检测污水厂尾水中6种酸性药物的方法.10 mL水样采用0.45μm微孔滤膜过滤后经自动进样器直接在线上样,经Atlantis T3柱(100 mm×4.6 mm×3μm)富集,Atlantis T3柱(100 mm×2.1 mm×2.6μm)...     

Metabolism of aceclofenac in cattle to vulture‐killing diclofenac

The nonsteroidal anti‐inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures, and its recent widespread use in South Asia caused catastrophic declines in at least 3 scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds, and it is known to metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four‐fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful.     

Predominance of alcohol and illicit drugs among traffic accidents fatalities in an urban area of Brazil

Objective: The objective of this study was to determine the prevalence of alcohol and illicit drug use among victims of fatal traffic accidents in the Metropolitan Region of Vitória, Brazil, during the period 2011–2012.

Methods: Blood samples were collected and analyzed for the presence of drugs from 391 deceased victims of traffic crashes that occurred in the Metropolitan Region of Vitória, Brazil. The victims included drivers, passengers, and pedestrians. Sociodemographic variables such as age, gender, day of the week, and period of the year in which the accidents occurred were recorded. The analyses were performed by a gas chromatography–flame ionization method for alcohol and by a gas chromatography–mass spectrometry for amphetamines, cocaine, and cannabis.

Results: The results showed that 44.8% (n = 175) of all cases were positive for alcohol and/or illicit drugs. The detection of alcohol and/or drugs was more frequent in young males, aged 17 to 34, whose samples were positive in 46.8% of cases. Small differences among drivers, passengers, and pedestrians were observed (drivers = 45.9%, passengers = 46.4%, and pedestrians = 45.6%). In general, the most prevalent drug was alcohol, with 141 positive cases (36.1%), followed by cocaine, with 47 positive cases (12%). Amphetamines and cannabis had positivity rates of 4.1 and 4.3%, with 16 and 17 positive cases, respectively. The combined use of alcohol and other drugs was found in 36 cases (9.2%). Crack cocaine use was observed in 27.7% of the positive cases for cocaine.

Conclusions: For the effective reduction of traffic accidents related to driving under influence of drugs (DUID), we suggest the intensification of enforcement actions against the use of alcohol by drivers, the definition of which illicit drugs should be surveyed, as well the cutoff values, the promotion of changing legislation to oblige drivers to provide samples for toxicological testing, and the establishment of public information programs and specific actions aimed at young drivers to promote behavioral changes.     

Toxicity of Selected Pharmaceuticals to the Anostracan Crustacean Thamnocephalus platyurus - Comparison of Sublethal and Lethal Effect Levels with the 1h Rapidtoxkit and the 24h Thamnotoxkit Microbiotests

- DOI: http://dx.doi.org/10.1065/espr2006.01.005 Background, Aims and Scope In view of the limited amount of information on the potential hazard of the ever increasing amounts of drugs in surface waters to aquatic biota, a study was undertaken to determine the effect levels of 28 selected pharmaceuticals to the crustacean test species Thamnocephalus platyurus. The drugs belong to 5 different groups: non steroidal anti-inflammatory agents, biocides, cardiovascular compounds, nervous system drugs and purine alkaloids. Methods Toxicity tests were carried out with the 1h Rapidtoxkit and the 24h Thamnotoxkit microbiotests in order to make a comparison of sublethal effects (visible as stress through absence of feeding) measured after a very short time of exposure (1h) and lethal effects after prolonged exposure (24h). Dilution series starting at 200 mg l–1 were prepared and applied, and median effects levels were calculated and transformed into Toxic Units (TU) for easy data comparison. Results and Discussion The toxic effects found have been ranked into 4 arbitrary toxicity classes: not toxic (TU<0.2), low toxicity (0.2<TU<1.0), toxic (1.0<TU<10) and very toxic (TU>10). The toxicity levels noted ranged from virtually no effects for a few of the pharmaceuticals, at the highest concentration tested out, to LC50's below 1 mg l–1 (>100 TU) for 3 nervous system drugs (Amitryptiline, Thioridazine and Chlorpromazine). According to the toxicity classification, 17 of the 28 compounds (i.e. 67%), belong to the same class for the lethal and the sublethal tests. More pronounced differences in effect levels between the two assays were observed mainly for the pharmaceuticals which were either not toxic or only slightly toxic at the 200 mg l–1 level. For 90% of the toxic drugs the ratio between the toxicity values for both tests is below 5. Conclusion An overall correlation coefficient of 0.96 was found between the 2 microbiotests, confirming the good predictive potential of the 1h stress-based Rapidtoxkit in revealing important biological effects (mortality) after more prolonged exposure of the crustacean test species to chemical compounds. Recommendation and Outlook The present study clearly shows that new microbiotests such as the 1h Rapidtoxkit and the 24h Thamnotoxkit are attractive tools for rapid cost-effective screening of 'new' pollutants such as drugs which may threaten the biological communities of the aquatic environment.     

污水中常见违禁药物分析方法优化及验证

违禁药物作为一种新型污染物得到了环境科学界的广泛关注.本文根据国内外已有研究,比较了污水样的前处理条件如SPE柱和水样pH值、冲洗、酸化及复溶过程.结果表明,对实际污水样的前处理应将样品pH值调为2,选用Oasis MCX柱,无需除杂质的冲洗和氮吹过程的酸化步骤,因两种上机测定方法 HILIC-UPLC-MS/MS和C18-UPLC-MS/MS不同而分别选择200μL乙腈和100μL乙腈+100μL 5 mmol·L~(-1)乙酸铵复溶.通过比较HILIC法和C18法的保留时间及检出限、定量限、回收率和基质效应等方法评价指标,确定污水样的测定应选用C18-UPLC-MS/MS.最后,将优化后的测定方法用于分析北京市12家污水处理厂的进、出水样,验证了方法的可靠性,为违禁药物的污水流行病学研究和环境风险评价奠定了基础.     

Mass spectral studies of 6‐n‐propyl‐2‐thiouracil,its oxygen,selenium and fluorinated congeners∗

The electron ionization mass spectra of the clinically used antithyroid agent 6‐n‐propyl‐2‐thiouracil (la), its minor metabolite, 6‐n‐propyluracil (lb) and their synthetic selenium and fluorinated analogs (1c and d) have been examined. The fragmentation pattern of these thiouracil and selenouracil studied bear strong similarities with those previously derived from a study of uracil analogs. Thus, the first step in the fragmentation is a retro Diel‐Alder decomposition with the loss of HCNX (X=O, S or Se) and the production of an ion radical which undergoes further fragmentation pathways which are discussed. 6‐n‐Propyl‐2‐selenouracil (1c) did show more complicated spectra due to the six natural isotopic abundance exhibited by the selenium atom. While the fluorinated analogs (1d) did substantiate the fact that the fragmentation pattern of these derivatives proceed through fragmentation between C₂ and N₃ bond since this produces the more resonance stabilized ion.