富锌排铅咀嚼片安全性毒理学评价

对富锌排铅咀嚼片(RZLR)进行了急性毒性试验、Ames试验、骨髓微核试验、精子畸形试验和30 d喂养试验。结果表明,小鼠急性毒性LD50(BW)>21 500 mg/kg,属无毒级;Ames试验、小鼠骨髓微核试验、精子畸形试验和30 d喂养试验结果均为阴性;30 d喂养试验也未显示明显毒性。本研究证实RZLR是一种安全、无毒副作用的保健食品。     

QSAR models for biocides: The example of the prediction of Daphnia magna acute toxicity

ABSTRACT

Biocides are multi-component products used to control undesired and harmful organisms able to affect human or animal health or to damage natural and manufactured products. Because of their widespread use, aquatic and terrestrial ecosystems could be contaminated by biocides. The environmental impact of biocides is evaluated through eco-toxicological studies with model organisms of terrestrial and aquatic ecosystems. We focused on the development of in silico models for the evaluation of the acute toxicity (EC₅₀) of a set of biocides collected from different sources on the freshwater crustacean Daphnia magna, one of the most widely used model organisms in aquatic toxicology. Toxicological data specific for biocides are limited, so we developed three models for daphnid toxicity using different strategies (linear regression, random forest, Monte Carlo (CORAL)) to overcome this limitation. All models gave satisfactory results in our datasets: the random forest model showed the best results with a determination coefficient r² = 0.97 and 0.89, respectively, for the training (TS) and the validation sets (VS) while linear regression model and the CORAL model had similar but lower performance (r² = 0.83 and 0.75, respectively, for TS and VS in the linear regression model and r² = 0.74 and 0.75 for the CORAL model).     

Development of an information-intensive structure–activity relationship model and its application to human respiratory chemical sensitizers

Structure–activity relationship (SAR) models are recognized as powerful tools to predict the toxicologic potential of new or untested chemicals and also provide insight into possible mechanisms of toxicity. Models have been based on physicochemical attributes and structural features of chemicals. We describe herein the development of a new SAR modeling algorithm called cat-SAR that is capable of analyzing and predicting chemical activity from divergent biological response data. The cat-SAR program develops chemical fragment-based SAR models from categorical biological response data (e.g. toxicologically active and inactive compounds). The database selected for model development was a published set of chemicals documented to cause respiratory hypersensitivity in humans. Two models were generated that differed only in that one model included explicate hydrogen containing fragments. The predictive abilities of the models were tested using leave-one-out cross-validation tests. One model had a sensitivity of 0.94 and specificity of 0.87 yielding an overall correct prediction of 91%. The second model had a sensitivity of 0.89, specificity of 0.95 and overall correct prediction of 92%. The demonstrated predictive capabilities of the cat-SAR approach, together with its modeling flexibility and design transparency, suggest the potential for its widespread applicability to toxicity prediction and for deriving mechanistic insight into toxicologic effects.     

Evolution of the international workshops on quantitative structure-activity relationships (QSARs) in environmental toxicology†

This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method in understanding the properties and effects of chemicals on the environment and human health. From substances that only affect cell membranes to those that bind strongly to a specific enzyme, QSARs provides insight into the biological effects and chemical and physical properties of substances. QSARs are useful for delineating the quantitative changes in biological effects resulting from minor but systematic variations of the structure of a compound with a specific mode of action. In addition, more holistic approaches are being devised that result in our ability to predict the effects of structurally unrelated compounds with (potentially) different modes of action. Research in QSAR environmental toxicology has led to many improvements in the manufacturing, use, and disposal of chemicals. Furthermore, it has led to national policies and international agreements, from use restrictions or outright bans of compounds, such as polychlorinated biphenyls (PCBs), mirex, and highly chlorinated pesticides (e.g. DDT, dieldrin) for the protection of avian predators, to alternatives for ozone-depleting compounds, to better waste treatment systems, to more powerful and specific acting drugs. Most of the recent advances in drug development could not have been achieved without the use of QSARs in one form or another. The pace of such developments is rapid and QSARs are the keystone to that progress. These workshops have contributed to this progress and will continue to do so in the future.     

Screening for exogenous androgen anabolic steroids in human hair by liquid chromatography/orbitrap-high resolution mass spectrometry

A method for the screening of various anabolic steroids and their esters in human hair, based on liquid-chromatography–high resolution mass spectrometry using an Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This method involved methanolic incubation of 30 mg of hair and analysis of the relevant extract in HPLC using a C18 column. The mass detector, with nominal resolving power of 100,000, operated in full scan mode in APCI under positive ionization mode. Analytes were identified by exact mass, correspondence of isotopic cluster and retention times.     

Application of ultrasound‐assisted liquid–liquid microextraction coupled with gas chromatography and mass spectrometry for the rapid determination of synthetic cannabinoids and metabolites in biological samples

The constant emergence of new psychoactive substances is a challenge to clinical and forensic toxicologists who need to constantly update analytical techniques to detect them. A large portion of these substances are synthetic cannabinoids. The aim of this study was to develop a rapid and simple method for the determination of synthetic cannabinoids and their metabolites in urine and blood using gas chromatography–mass spectrometry. The method involves an ultrasound‐assisted dispersive liquid–liquid microextraction that implies a rapid procedure, giving excellent extraction efficiencies with minimal use of toxic solvents. This is followed by silylation and analysis with gas chromatography–mass spectrometry. The chromatographic method allows for the separation and identification of 29 selected synthetic cannabinoids and some metabolites. The method was validated on urine and blood samples with the ability to detect and quantify all analytes with satisfactory limits of detection (from 1 to 5 ng/mL), limits of quantification (5 ng/mL), and selectivity and linearity (in the range of 5–200 ng/mL). The developed assay is highly applicable to laboratories with limited instrumental availability, due to the use of efficient and low‐cost sample preparation and instrumental equipment. The latter may contribute to enhance the detection of new psychoactive substances in clinical and forensic toxicology laboratories.     

生物检材中芬太尼类物质检测方法研究进展

就芬太尼类物质的代谢及近年来对常见生物检材中此类物质的前处理方法及检测方法进行了综述.常见的生物检材有血液、尿液、毛发,这几种检材都具有各自的检测优势和不足.毒品在血液中代谢速度快,代谢产物浓度高,但对检测时效性要求较高;尿液检测前处理简单,代谢产物易检测,但存在易污染、造假的问题;毛发检测不受其他药物影响,可追溯半年...