Evaluation of bioanalytical assays for toxicity assessment and mode of toxic action classification of reactive chemicals

The toxicity of electrqphiles, including reactive organochlorines, epoxides, and compounds with an activated double bond was investigated. A set of different bioanalytical assays based on genetically modified Escherichia coli strains was set up to quantify cytotoxicity and specific reactivity toward the important biological nucleophiles DNA and glutathione (GSH). The significance of GSH for detoxification was assessed by cellular GSH depletion as well as by growth inhibition of a GSH-deficient strain. Tests for DNA damage comprised the measurement of induction of DNA repair systems, DNA fragmentation, and growth inhibition of a strain deficient in major DNA repair mechanisms. The most suitable assays for detection of mechanisms that underlie the observable cytotoxicity of the tested electrophiles were two sets of strains either lacking GSH or DNA repair in combination with their corresponding parent strains. Comparison of toxicity observed in those strains suggests three clearly distinguishable modes of toxic action for electrophilic chemicals: "DNA damage", "GSH depletion-related toxicity", and "unspecific reactivity". The class of chemicals causing DNA damage includes the epoxides 1,2-epoxybutane, (2,3-epoxypropyl)benzene, and styrene oxide. The class of chemicals with GSH depletion-related toxicity includes compounds with an activated double bond, like acrylates and acrolein. All reactive organochlorines and some epoxides were classified as unspecifically reactive because their toxicity is initiated by reactions with both biological nucleophiles. The work presented here is a contribution for an alternative hazard and effect assessment of organic pollutants based on mode of toxic action classification.     

食源性内分泌干扰物联合效应研究进展

食源性内分泌干扰物(endocrine disrupting chemicals,EDCs)因具有相似的作用终点,低剂量下混合暴露可能产生大于单一暴露的联合效应,已成为影响食品安全的一类重要风险因子,国际上已开始关注低剂量下混合暴露所引起的联合效应问题。本文首先对食源性EDCs的污染现状和检测技术(包括前处理技术和高通量检测技术)进行了梳理分析,基于气相色谱-质谱、液相色谱-质谱的分析技术已经成为EDCs的主流分析技术。随后,探讨了模式生物和毒性替代测试在联合效应研究中的研究现状,最后从浓度相加模型、独立作用模型和相互作用模型等3个方面介绍了联合效应评价方法的研究进展。基于毒性测试替代技术的联合效应研究将为科学评价食源性EDCs的联合效应,揭示联合效应产生的分子机制,修订食源性EDCs的安全限量标准提供依据。     

Screening for PBT chemicals among the "existing" and "new" chemicals of the EU

Under the European chemicals legislation, REACH, industrial chemicals that are imported or manufactured at more than 10 t/yr need to be evaluated with respect to their persistence (P), bioaccumulation potential (B), and toxicity (T). This assessment has to be conducted for several 10,000 of chemicals but, at the same time, empirical data on degradability, bioaccumulation potential and toxicity of industrial chemicals are still scarce. Therefore, the identification of PBT chemicals among all chemicals on the market remains a challenge. We present a PBT screening of approximately 95,000 chemicals based on a comparison of estimated P, B, and T properties of each chemical with the P, B, and T thresholds defined under REACH. We also apply this screening procedure to a set of 2576 high production volume chemicals and a set of 2781 chemicals from the EU's former list of "new chemicals" (ELINCS). In the set of 95,000 chemicals, the fraction of potential PBT chemicals is around 3%, but in the ELINCS chemicals it reaches 5%. We identify the most common structural elements among the potential PBT chemicals. Analysis of the P, B, and T data for all chemicals considered here shows that the uncertainty in persistence data contributes most to the uncertainty in the number of potential PBT chemicals.     

Toxic ratio as an indicator of the intrinsic toxicity in the assessment of persistent, bioaccumulative, and toxic chemicals

Persistence, bioconcentration, and toxicity (PBT) are important hazardous properties of organic chemicals. In PBT assessments, it is desirable that the three criteria P, B, and T are independent. However, this requirement is not fulfilled if an aqueous lethal concentration (LC50) is used as T indicator because LC50 includes both bioconcentration and intrinsic toxicity. Indicators for intrinsic toxicity such asthe internal lethal concentration (ILC) are independent of a chemical's bioconcentration potential. However, ILC50 data are scarce and difficult to measure. Therefore, the toxic ratio (TR) is proposed here as an alternative. TR is defined as the ratio of a chemical's LC50 estimated from a QSAR for baseline toxicity and the experimental LC50 value. TR can also be interpreted as a measure of the ILC relative to the ILC for baseline toxicity. A TR of 10 separates specifically toxic chemicals from baseline toxicants. With some 800 chemicals, the practicability of classifying chemicals in terms of TR is demonstrated. Employing TR as toxicity indicator leads to different T scores for 30% of the chemicals studied. The baseline toxicity of hydrophobic compounds with TR < 10 does not receive a high T score but is still indicated by a high B score. The toxicity of specifically toxic hydrophilic substances is given additional emphasis by high TR values. These classification changes require that the interpretation of the B and T dimensions in PBT assessments is redefined.     

Mixture toxicity of reactive chemicals by using two bacterial growth assays as indicators of protein and DNA damage

The mixture toxicity of reactive chemicals was investigated with a set of bioanalytical tests that quantify not only the toxic effects but also allow the identification of the preferred target of reactive chemicals in bacterial cells. Softer electrophiles such as acrylates react preferentially with thiol groups in proteins and peptides, and harder electrophiles such as epoxides preferentially attack DNA. In addition, some compounds, e.g., benzyl chloride, have no preference for a biological target and damage both DNA and proteins. A thiophenol was used as a model compound representing nucleophiles. We explored if the paradigms of mixture toxicity also hold true for reactive chemicals. Compounds with the same targets and the same modes of action should act concentration additive in mixtures, and compounds with different modes of action should act according to the concept of independent action. In addition, we investigated the potential for interaction of compounds of mixtures of electrophiles or electrophiles plus nucleophiles, which might lead to synergistic or antagonistic effects. The toxicity of mixtures of electrophiles with a single preferred target was consistent with the prediction for concentration addition. Unfortunately, the predictions for independent action did not differ much from those for concentration addition; therefore it was not possible to differentiate between these two models. Mixtures of two groups with different preferred target sites clearly showed concentration addition. In contrast, mixtures of compounds with multiple targets, i.e., compounds that show nonspecific reactivity toward any biological nucleophile, exhibited effects that lay distinctly between the predictions for concentration addition and independent action. We observed neither synergism (higher toxicity than predicted by concentration addition) nor antagonism (lower toxicity than predicted by independent action) for mixtures of electrophiles. Binary combinations of different electrophiles with the nucleophile 4-chlorothiophenol yielded smaller effects than those expected from the prediction for independent action. The degree of antagonism was correlated with the reaction rate constant of the electrophile with the thiol group of glutathione, which indicates that the interaction between the mixture components occur in the toxicokinetic phase and is purely a result of chemical reactivity between the mixture components. Overall, we conclude that the concepts of mixture toxicity apply not only for baseline toxicity and receptor-mediated mechanisms, as has been shown in a large number of studies, but also for reactive mechanisms of toxicity, provided that one has checked beforehand that no chemical reactions occur between the mixture components.     

服装用仿皮革面料的质量检测

根据现有的相关标准对仿皮革面料的组成材质、耐折牢度、耐寒性能、耐碱液水解牢度、剥离负荷、透湿性、色牢度等性能,从测定意义、测试方法的选择以及不同标准之间测试方法的异同等方面进行了介绍,并提出了一些建议,建议应建立具体的企业标准,重视生态环保要求考核.     

化学品快速生物降解性标准体系

生物降解性作为评价有机化学品环境友好性的重要标志之一已得到普遍认可,文中阐述了国内外化学品快速生物降解性标准体系,包括经济合作与发展组织(OECD)及我国关于化学品快速生物降解性经典方法,重点介绍OECD 301系列标准提供的6种测试化学品快速生物降解性的方法,及其适用性和技术关键.     

Model intercomparison for the uptake of organic chemicals by plants

Currently, a variety of models are available for predicting the uptake, translocation, and elimination of organic contaminants by plants. These models range from simple deterministic risk assessment screening tools to more complex models that consider physical, chemical, and biological processes in a mechanistic manner. This study evaluates the performance of a range of such models and model types against experimental data sets. Three dynamic, three regression-based, and three steady-state and equilibrium models have been selected for evaluation. These models differ in terms of their scope, methodological approach, and complexity. Data from nine published experiments were used to create scenarios to test model performance. These experiments consider plant contamination via both soil and aerial exposure pathways. A total of 19 different organic chemicals were used in the experiments along with 7 different plant species. Model predictions of chemical concentrations in the relevant plant compartments were compared with the experimentally recorded values. The results indicate that dynamic models offer performance advantages for acute exposure durations and for rapidly changing environmental media. Equilibrium/steady-state and regression-based models perform better for chronic exposure durations, where stable conditions are more likely to exist. The selection of an appropriate plant uptake model will therefore be dependent on the requirements of the assessment, the nature of the environmental media, and the duration of the source term. The results generated by the regression-based models suggest that in their current form these models are unsuitable for evaluating the uptake of organic chemicals from the air into plants.     

Baseline toxicity (narcosis) of organic chemicals determined by in vitro membrane potential measurements in energy-transducing membranes

Baseline toxicity of a selection of industrial chemicals and pharmaceuticals is determined experimentally with a new in vitro test system (Kinspec) using membrane vesicles isolated from a photosynthetic bacterium, Rhodobacter sphaeroides. This test system is selective and more sensitive than other mechanistic test systems for baseline toxicity. The only concomitantly determined mechanism is uncoupling, which can be distinguished from baseline toxicity by pH-dependent measurements. Because the tests system contains only the target site for baseline toxicants, the biological membrane, effective target site concentrations can be directly related to observed effects by combining the in vitro test with membrane-water partition experiments. No differences were found between the effective membrane concentrations of nonpolar and polar compounds, confirming the earlier hypothesis that differences in lethal body burdens are primarily caused by unequal distribution of the compounds between target and nontarget lipids and not by different mechanisms. A selection of pharmaceuticals with various specific modes of toxic action exhibited the same constant effective membrane concentrations as found for pure baseline toxicants. In mixtures of four to six components, the pharmaceuticals were concentration-additive with each other and with the pure baseline toxicants. A potential application of the proposed test system lies, therefore, in assessing the cumulative baseline toxicity in complex environmental mixtures.     

含氯苯酚在纺织品中的安全限量要求

含氯苯酚作为一种常用的防腐、防霉、防蛀剂成分,存在于纺织产业链所用的各种助剂和化学品中,有较大的风险。介绍了含氯苯酚的化学结构、物理特性、用途、危害性、检测方法以及REACH法规、最新版Oeko-Tex 100标准、欧盟部分成员国对五氯苯酚的安全限量要求。最后以南山纺织面料的含氯苯酚检测结果为例,说明了含氯苯酚在纺织品中的安全可控性。     

蛋白质疏水性测定方法的相关性及适用性

针对蛋白质的疏水性,以食品中常用的蛋白质如大豆分离蛋白(SPI) 及其水解物和乳清蛋白为对象,研究不同疏水性测定方法的相关性及适用性。结果表明：ANS荧光探针法对各种蛋白质及其水解物(DH＜23)疏水性的测定均比较合适;CPA荧光探针法不适合于测定疏水性较弱的蛋白质;反相高效液相色谱法较适合测定疏水性适中及较强的蛋白质;表面张力法中如采用气液界面参数进行表征,则其线性存在一定的缺陷。     

革的品种与皮化材料的配套

众所周知 ,几乎所有大型动物的皮都能制革 ,特别是家畜的皮。即使是同一种动物的皮 ,也可制成不同品种的革 (如黄牛皮 )。这就使革的品种 ,不象裘皮那样受皮种的束缚 ,可以无限的发展。但是 ,随着时间的推移 ,这些革品种也在慢慢地变化。一些品种消失了 ,一些品种扩大了 ,一些品种诞生了。 2 0世纪 70年代 ,当时的革品种经粗略计算有下列类别 :1轻革类 ,即以成品革的面积计价的叫轻革 ,其中包括鞋面革、服装革、体育用品革、衬里革、部分工业用革等等 ;2重革类 ,成品革以重量计价 ,叫重革 ,其中包括外底革、内底革、皮带革、部分工业革、装…     

革的品种与皮化材料的配套(续)

(上接 2 0 0 2年 9月第 17期 )1.3　沙发革及汽车座垫革黄牛沙发革、水牛沙发革、猪沙发革以及汽车座垫革 ,虽然有时风格各异 ,却属同一类型的革。黄牛沙发革与水牛沙发革成品较为一致 ,猪沙发革却倾向于猪正面服装革。但汽车座垫革要求严 ,标准也高。例如 :除一般的铬含量、油含量、灰分含量等化学指标 ,以及抗张强度、撕裂强度等物性指标外 ,还要求硬度、耐汗性、雾化值、气味、热老化性、迁移性等特殊的指标。如果严格按照德国某汽车公司的要求生产座垫革 ,国内外的大部分皮化材料都将不适用。而沙发革的要求就低得多了。以生产水牛沙发…     

Cholesterotropic and cuprotropic chemicals

A dozen or so chemicals modify both cholesterol and copper metabolism. Ascorbic acid and cadmium, etc., inhibit copper metabolism and raise cholesterol. Calcium and clofibrate, etc., enhance copper and lower cholesterol. Perhaps the doses of dietary cholesterol and fructose in this experiment were too severe to permit fenofibrate to lower cholesterol in a manner similar to clofibrate. © 2020 Society of Chemical Industry     

Potential of degradable organic chemicals for absolute and relative enrichment in the Arctic

Model simulations of the fate of numerous hypothetical substances in the global environment can provide considerable insight into how an organic chemical's degradability and partitioning properties influence its absolute and relative Arctic enrichment behavior, as quantified by the Arctic Contamination Potential. For substances that degrade faster in water than in soil, but are quite persistent in the atmosphere, highest Arctic contamination is expected to occur if the substances have intermediate volatility and high hydrophobicity. Organic substances that are degradable in the atmosphere can still accumulate in the Arctic if they are soluble and highly persistent in water. These latter substances, which reach the Arctic in the ocean, also show the highest potential for relative enrichment in the Arctic, i.e., high amounts in northern high latitudes relative to the amounts in the total global environment. Beyond a threshold persistence in surface media of the order of several months to a year, chemical degradability leads to further relative enrichment. This is because only chemicals that are sufficiently long-lived get transferred to polar regions and once there can persist longer than at lower latitudes. The model simulations can inform the search for new potential Arctic contaminants, and can highlight combinations of properties which should be avoided in high production volume chemicals with the potential for environmental release. Three categories of organic substances are singled out for troublesome combinations of persistence, distribution, and potential bioaccumulation characteristics, only one of which contains "classical" Arctic POPs. Examples of potential Arctic contaminants within each of these categories are named.     

Applicability of protein estimation methods for assaying glycomacropeptide

Glycomacropeptide (GMP) is a nutraceutical additive, which is released during cheese preparation. In this study, the protein content in a laboratory GMP preparation and two commercial GMP samples, which was estimated by the Bradford, biuret, Lowry and bicinchoninic acid (BCA) assays, were compared using the Kjeldahl method. There were apparent differences in the values of estimated proteins using the different methods. An absence of dose response in the Bradford method and a low dose response using the Lowry method indicated the unsuitability of both these methods. Absorbance in the biuret and BCA methods linearly increased with increasing GMP content. The BCA method was the most sensitive of these methods.     

纺织品前处理剂的生态问题和取代品

阐述了纺织品环保型前处理剂的生态要求，分析了目前使用的各种前处理剂（经纱上浆剂、退浆剂和退浆助剂、精练剂、漂白剂和净洗剂）的生态问题，指出了禁用和限用的前处理剂及其取代品。     

氟碳防水防油剂的研发进程

概述了氟碳防水防油剂的发展历程,以及近年国内外的研发现状;针对我国氟碳防水防油剂产业的特点,提出了研发C8替代物、含硅氟、含氧等杂原子的氟碳防水防油剂,研究相关检测技术,以及研究复配增效技术等应对建议.