Pulmonary toxicity of indium arsenide and arsenic selenide following repeated intratracheal instillations to the lungs of hamsters

Chronic toxicity of indium arsenide (InAs) and arsenic selenide (As₂Se₃) was studied in male Syrian golden hamsters which received InAs or As₂Se₃ particles, each containing a total dose of 7.5 mg of arsenic, by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total lifespan, the cumulative body weight gain of the hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the As₂Se₃ group when compared with that in the control group. However, the survival rate for the InAs group was significantly higher compared with the control group, but not for the As₂Se₃ group when compared with the control group. During the animals' total lifespan, one lung adenoma was seen in the 27 hamsters in the InAs group and one lung adenoma in the 23 hamsters in the control group. No tumors of the lung were observed in the As₂Se₃ group. Malignant tumors outside the lung appeared in four hamsters in the InAs group and in two in the As₂Se₃ group. No non-lung malignant tumours were seen in the control group. Total tumor incidence rates were 25.9% (7/27) in the InAs group, 10.3% (3/29) in the As₂Se₃ group and 8.7% (2/23) in the control group. There were therefore no significant differences in tumor incidence between the InAs or the As₂Se₃ group, and the control group. Regarding histopathological findings in the lung, incidence rates of proteinosis-like lesions, pneumonia, metaplastic ossification and emphysema were seen only in the InAs group, and alveolar or bronchiolar cell hyperplasia observed in both the InAs and the As₂Se₃ groups were at significantly higher rates than those in the control group. From these results, it was concluded that InAs and As₂Se₃ particles could induce pulmonary toxicity when instilled intratracheally into hamsters. A great deal of attention should be paid to the toxicity of both InAs and As₂Se₃, even though in this study the adverse health effects of As₂Se₃ appeared to be less than those of InAs.     

The chemical form and acute toxicity of arsenic compounds in marine organisms

A method for the separation and identification of inorganic and methylated arsenic compounds in marine organisms was constructed by using a hydride generation/cold trap/gas chromatography mass spectrometry (HG/CT/GC MS) measurement system. The chemical form of arsenic compounds in marine organisms was examined by the HG/CT/GC MS system after alkaline digestion. It was observed that trimethylarsenic compounds were distributed mainly in the water-soluble fraction of muscle of carnivorous gastropods, crustaceans and fish. Also, dimethylated arsenic compounds were distributed in the water-soluble fraction of Phaeophyceae. It is thought that most of the trimethylated arsenic is likely to be arsenobetaine since this compound released trimethylarsine by alkaline digestion and subsequent reduction with sodium borohydride. The major arsenic compound isolated from the water-soluble fraction in the muscle and liver of sharks was identified as arsenobetaine from IR, FAB Ms data, NMR spectra and TLC behaviour. The acute toxicity of arsenobetaine was studied in male mice. The LD₅₀ value was higher than 10 g kg⁻¹. This compound was found in urine in the non-metabolized form. No particular toxic symptoms were observed following administration. These results suggest that arsenobetaine has low toxicity and is not metabolized in mice. The LD₅₀ values of other minor arsenicals in marine organisms, trimethylarsine oxide, arsenocholine and tetramethylarsonium salt, were also examined in mice.     

基于遗传算法的非线性映射预测硝基苯化合物的生物毒性

摘要: 非线性映射是一种降维处理技术,通过Sammon算法可以将多维分析问题转化为二维问题分析。应用该法的关键在于寻求二维空间的最佳投影点,这可以转化为一个复杂的非线性优化问题来进行解决。遗传算法是解决各类函数优化和非线性映射问题的一种有效算法。以硝基苯化合物的生物毒性的模式识别为例,编制基于误差函数的目标函数和遗传算法约束参数,应用基于MATLAB的遗传算法工具箱进行优化求解。结果表明:该工具箱在求解此类非线性优化问题上是有效的, 基于遗传算法的非线性映射的预测结果比其它方法要好些。     

Labelling,Fractionation and Toxicity of Scorpion (Leiurus quinquestriatus H and E) Venom,using 125I, 131I and Gel-Filtration Technique

Labelling the venom of scorpion was achieved by means of a technique previously published by the author. The radioisotopes, used were both ¹²⁵I and ¹³¹I in a nascent form. Fractionation was done by the use of Sephadex G-100. Both the radioactivity and the extinction curves denoted the presence of three well defined peaks. The toxicity of the first fraction was found to be the most lethal. While the second peak was in the magnitude of 20 percent of the first, the third peak proved to be nontoxic to mice up to a concentration of 6 mg/kg body weight.     

Study on the Joint Toxicity of BPZ,BPS, BPC and BPF to Zebrafish

Bisphenol Z (BPZ), bisphenol S (BPS), bisphenol C (BPC), and bisphenol F (BPF) had been widely used as alternatives to bisphenol A (BPA), but the toxicity data of these bisphenol analogues were very limited. In this study, the joint toxicity of BPZ, BPS, BPC, and BPF to zebrafish (Danio rerio) was investigated. The median half lethal concentrations (LC50) of BPZ, BPS, BPC, and BPF to zebrafish for 96 h were 6.9 × 10⁵ µM, 3.9 × 10⁷ µM, 7.1 × 10⁵ µM, and1.6 × 10⁶ µM, respectively. The joint toxicity effect of BPF–BPC (7.7 × 10⁵–3.4 × 10⁵µM) and BPZ–BPC (3.4 × 10⁵–3.5 × 10⁵µM) with the same toxic ratio showed a synergistic effect, which may be attributed to enzyme inhibition or induction theory. While the toxicity effect of the other two bisphenol analogue combined groups and multi-joint pairs showed an antagonistic effect due to the competition site, other causes need to be further explored. Meanwhile, the expression levels of the estrogen receptor genes (ERα, ERβ1) and antioxidant enzyme genes (SOD, CAT, GPX) were analyzed using a quantitative real-time polymerase chain reaction in zebrafish exposure to LC₅₀ of BPZ, BPS, BPC, and BPF collected at 24, 48, 72, and 96 h. Relative expression of CAT, GPX, and ERβ1 mRNA declined significantly compared to the blank control, which might be a major cause of oxidant injury of antioxidant systems and the disruption of the endocrine systems in zebrafish.     

Photostability study of agomelatine using UHPLC-DAD-MS/MS method. Kinetics,identification of the transformation products and in silico evaluation of toxicity

Photostability of an antidepressant agomelatine under the simulated solar radiation was studied. Quantitative and qualitative analysis of this process was performed with the use of UHPLC-DAD system coupled with a high resolution hybrid ESI-Q-TOF mass spectrometer. In contrast to the foregoing studies agomelatine turned out to be relatively photolabile compound. During the experiment six transformation products were formed, and their structures were elucidated on the basis of MS/MS fragmentation spectra. Four of these photoproducts were found to be a result of aromatic and aliphatic hydroxylation. Additionally, identified products were submitted to the in silico toxicity evaluation, which showed that some of them could be more mutagenic or toxic to rodents than the parent compound.     

Effect of Sulfation Route and Subsequent Oxidation on Derivatization Degree and Biocompatibility of Cellulose Sulfates

Sulfated cellulose (CS) represents an interesting biopolymer due to bioactivity comparable to heparin. However, use of CS for making surface coatings or hydrogels requires the presence of reactive groups for covalent reactions. Here, an approach is presented to oxidize cellulose sulfates for subsequent cross‐linking reactions with amino groups to form imine bonds. Cellulose is sulfated by direct sulfation or acetosulfation, followed by a M alaprade oxidation. The CS obtained is characterized by elemental analysis and ¹³C‐NMR spectroscopy. The resulting oxidized cellulose sulfates (oxCS) have different degrees of sulfation ranging from 0.79 to 1.13 and oxidation degrees from 0.18 to 0.34, but also different mass average molecular mass (M_W). Toxicity studies are carried out with mouse 3T3 fibroblasts exposed to aqueous solutions of oxCS. The results show that all oxCS are non‐toxic at lower concentrations (0.5 mg mL^?1), but with both increasing degree of oxidation and concentrations, toxic effects are observed particularly for acetosulfated and lesser for direct sulfated oxCS, which is related to a decrease in the M_W of the products. It is concluded that oxCS obtained by direct sulfation with M_W above 70 kDa may represent a biocompatible material for the applications suggested above.     

LC–DAD/ESI–MS/MS characterization of phenolic constituents in Rosa canina L. and its protective effect in cells

In an aim to prove the efficiency of polyphenols of Rosa canina fruits in promoting human health. A methanolic extract of R. canina fruits was prepared by successive maceration with solvents of increasing polarity. The polyphenol composition was analyzed by HPLC–DAD–ESI–MS. The biological activity of this extract on SH-SY5Y cells and HepG2 cells was then studied. The antioxidant activity was tested by various in vitro tests such as DPPH-radical-scavenging activity, FRAP assay, hydroxyl radical scavenging assay and total antioxidant capacity. The subacute toxicity of R. canina was tested on female rats by repeated intraperitoneal administration of various doses. The phenolic profiles showed 25 antioxidants distributed into three classes of phenolic compounds: glycosylated and agglomerated flavonoids/isoflavonoids, tannins and phenanthrenes. Qualitative phytochemical analyses showed that this extract lacks alkaloids. The methanolic extract of R. canina fruits has a total antioxidant capacity of 82.69 ± 1.18 μg EAA/mg of methanol extract and the IC₅₀ of the methods used is in the following increasing order: FRAP assay (61.88 μg/ml), then hydroxyl radical scavenging assay (67.45 μg/ml) and then DPPH radical-scavenging activity (129.81 μg/ml). The extract of R. canina did not cause any phenotypic signs of toxicity or mortality during and after treatment. The LD₅₀ was >5,000 mg/kg, hence, R. canina was considered nontoxic. An in vivo study proved the protective effect of R. canina against cardiac and hepato-renal toxicities. These results drew the importance of a healthy diet, where diets rich in R. canina fruits can be used as a rich natural source of antioxidants and anticarcinogenic phenolic compounds.     

Introducing tox-Profiles of Chemical Reactions

In this Essay, we present a critical analysis of two common practices in modern chemistry—that is, of using speculations about the “greenness” and “nontoxicity” of developed synthesis procedures and of a priori labelling various compounds derived from natural sources as being environmentally safe. We note that every organic molecule that contains functional groups should be biologically active. Thus, analysis of the particular greenness and the potential environmental impact of a given chemical process should account for the biological activity of all its components in a measureable (rather than empirical) way. We highlight the necessity of clarifying discussions on biological activity and toxicity and propose possible ways of introducing tox-Profiles as a reliable overview of the overall toxicity of chemical reactions.