Evaluation of the genotoxic potential of sorbic acid and potassium sorbate.

The genotoxic potential of sorbic acid and potassium sorbate was investigated in vivo and in vitro. Oral administration of sorbic acid (up to 5000 mg/kg body weight) did not induce sister chromatid exchanges or the formation of micronuclei in bone marrow cells of mice. Intraperitoneal treatment of rats with 400-1200 mg potassium sorbate/kg body weight did not alter the elution profile of DNA from isolated liver cells in the in vivo alkaline elution assay. Sorbic acid did not induce DNA repair in cultured human A549 cells in the unscheduled DNA synthesis (UDS) assay. In vitro incubation of the cells with 1-1000 micrograms potassium sorbate/ml, in the absence or presence of rat liver homogenate, did not result in the formation of DNA single-strand breaks in the alkaline elution assay. These results demonstrate that sorbic acid and its potassium salt are not genotoxic in vivo or in vitro. In contrast to sorbic acid and potassium sorbate, sodium sorbate is very sensitive to oxidative degradation; the main oxidation product was identified to be 4,5-oxohexenoate, which was mutagenic in the Ames test.     

Toxicological evaluation of potassium sorbate added to cigarette tobacco.

Potassium sorbate (PS) may be incorporated in blended cigarette tobacco either as a mold growth inhibitor in processed tobacco sheet material, or as a preservative in flavor systems or paper adhesives. To evaluate the effect of PS addition, neat material pyrolysis studies, smoke chemistry and biological activity studies (bacterial mutagenicity, cytotoxicity, in vivo micronucleus, and 90-day nose-only rat inhalation) with mainstream smoke, or mainstream smoke preparations from cigarettes containing various measured levels of PS (0%, 0.15%, 1.6%, and 3.7%) were performed. At simulated tobacco burning temperatures up to 1000 degrees C, neat PS completely pyrolyzed to form aromatic ring materials including benzene, toluene, substituted benzenes, naphthalene, and substituted naphthalenes. Under machine smoking conditions (FTC/ISO), high levels of PS may alter the burning characteristics of the cigarette leading to decreased puff count, total particulate matter, carbon monoxide, hydrogen cyanide, 2-nitropropane, and tobacco specific nitrosamines yields in the smoke, while increasing the yield of nicotine, 1,3-butadiene, isoprene, and some PAHs. Biological studies indicated no relevant differences in the genotoxic or cytotoxic potential of either mainstream smoke from cigarettes with or without added PS. Rats exposed to mainstream cigarette smoke developed respiratory tract changes consistent with those seen in previous smoke inhalation studies, with no relevant histopathological differences between the control and the PS test cigarette groups. These studies demonstrated that high levels of PS could alter the burning rate of the tobacco leading to alteration in the smoke chemistry profile. Yet, based on the panel of biological endpoints monitored here, it appeared that added PS produced little relevant change in the overall toxicity profile of smoke.     

Evaluating the potential for genotoxic carcinogenicity of methyl isocyanate

The carcinogenicity prediction and battery selection method was used to predict the probability of carcinogenicity of methyl isocyanate (MIC) based upon the results of short-term tests. The analysis predicts that MIC has a significant potential for inducing cancer in rodents. However, the pattern of response suggests that the carcinogenic potency would be low. Obviously, the realization of the identified risk would be dependent upon level, duration, and mode of exposure.     

Determination of caffeine and potassium sorbate in a neonatal oral solution by HPLC

A reversed-phase HPLC method was developed and validated for the determination of caffeine and potassium sorbate in a neonatal oral solution. Chromatography was performed with a 100 × 4.5 mm Spherisorb 5 μm hexyl column with a mobile phase of 12% acetonitrile in 0.1 M sodium acetate buffer pH 4.5 and ultraviolet detection at 258 nm. The method is stability indicating and there was no interference from a number of common formultion ingredients, although benzoic acid did interfere.     

注射用炎琥宁与头孢呋辛钠配伍的稳定性考察

目的:考察注射用炎琥宁与注射用头孢呋辛钠在0.9%氯化钠注射液中的配伍稳定性.方法:采用高效液相色谱法,测定注射用炎琥宁与注射用头孢呋辛钠配伍后在室温下8 h内的含量变化,并观察和检测配伍液的外观及pH值变化.结果:配伍液pH值无明显变化,颜色随时间变化逐渐加深,头孢呋辛钠相对百分含量在5 h后降至95%以下,4 h后降解产物峰面积占总峰面积百分比超过1%.结论:注射用炎琥宁与注射用头孢呋辛钠在0.9%氯化钠注射液可配伍使用,但应在4 h内用完.     

Evaluation of the mutagenic and genotoxic potential of ubiquinol

Ubiquinol (the reduced form of coenzyme Q(10)) is the two-electron reduction product of ubiquinone (the oxidized form of coenzyme Q(10)), and has been shown to be an integral part of living cells, where it functions as an antioxidant in both mitochondria and lipid membranes. To provide information to enable a Generally Regarded as Safe (GRAS) evaluation for the use of ubiquinol in selected foods, a series of Organisation of Economic Cooperation and Development (OECD) and good laboratory practice (GLP) toxicological studies was conducted to evaluate the mutagenic and genotoxic potential of Kaneka QH brand of ubiquinol. Ubiquinol did not induce reverse mutations in Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2uvrA at concentrations up to 5000 mu g/plate, in either the absence and presence of exogenous metabolic activation by rat liver S9. Likewise, ubiquinol did not induce chromosome aberrations in Chinese hamster lung fibroblast (CHL/IU) cells in short-term (6-h) tests with or without rat liver S9 at concentrations up to 5000 mu g/ml or in a continuous (24-h) treatment test at concentrations up to 1201 mu g/ml. Finally, no mortalities, no abnormal clinical signs, and no significant increase in chromosome damage were observed in an in vivo micronucleus test when administered orally at doses up to 2000 mg/kg/day. Thus, ubiquinol was evaluated as negative in the bacterial reverse mutation, chromosomal aberration, and rat bone marrow micronucleus tests under the conditions of these assays.     

Determination of indinavir, potassium sorbate, methylparaben, and propylparaben in aqueous pediatric suspensions

A gradient, reversed phase, HPLC method was developed for simultaneous analysis of potassium sorbate, methylparaben, propylparaben, and indinavir in aqueous suspensions that contain a proprietary orange flavoring and Magnasweet sweetener enhancer (MacSanrews and Forbes Company, Magnasweet product brochure). The chromatographic separation is performed on an Eclipse XDB-C8 column using a gradient run with an analysis time of 35 min. The mobile phase consists of acetonitrile and acetonitrile:citrate buffer, pH 4.0 (20:80 v/v). The method successfully separates the three preservatives, indinavir (active ingredient), the orange flavoring, the Magnasweet species, and the indinavir lactone degradate. Recovery, linearity, and precision results for the three preservatives and indinavir are described. The method applies to two types of formulations: Xanthan Gum suspension and NanoSystems suspension.     

Evaluation of genotoxic effects of sodium propionate, calcium propionate and potassium propionate on the root meristem cells of Allium cepa

The effects of different treatments with food preservatives, sodium propionate (SP), calcium propionate (CP) and potassium propionate (PP), on the cytology and DNA content of Allium cepa were investigated. Five concentrations of these additives – 1000, 1500, 2000, 2500, and 3000 ppm – were applied for 24, 48, and 72 h. All concentrations of these chemicals showed an inhibitory effect on cell division in root-tips of A. cepa and caused a decrease in mitotic index values. Additionally, all treatments changed the frequency of mitotic phases when compared with the control groups. These compounds increased chromosome abnormalities in test material. Among these abnormalities were C-mitosis, anaphase bridges, micronuclei, binucleated cells, stickiness, laggards, and chromosome breaks. The nuclear DNA contents decreased when compared with control groups.     

注射用阿莫西林钠克拉维酸钾的质量评价

摘要：目的 评价国产注射用阿莫西林钠克拉维酸钾的质量现状,并提出改进建议。方法 法定标准检验结合探索性研 究,对产品的杂质谱、克拉维酸聚合物及其他荧光杂质、复溶行为、成盐率、包材密封性等进行比较研究。结果 212批次样 品法定标准检验均符合规定;采用建立的杂质分析方法,对主要杂质的结构与来源进行确证;证明水分和温度易促进主成分 的降解;此外,应严格控制原料成盐过程中的工艺参数,控制成盐剂的残留量;并关注包材密封完整性对产品全生命周期的影 响。结论 注射用阿莫西林钠克拉维酸钾总体质量较好,现行质量标准有待提高。     

Weight of evidence analysis for assessing the genotoxic potential of carbon nanotubes

Carbon nanotube (CNT) is a nanomaterial that has received interest because of its high-tensile strength and low weight. Although CNTs differ substantially in physico-chemical properties, they share high aspect ratio which resembles that of asbestos and other fibers causing lung cancer and mesothelioma. One type of multi-walled CNTs (i.e. MWCNT-7) has been classified as possibly carcinogenic to humans by IARC (Group 2B) based on experimental animal data, whereas other types of MWCNTs and single-walled CNTs (SWCNT) could not be classified due to lack of data from epidemiologic studies and insufficient mechanistic evidence. Damage to DNA is considered to be a key mechanistic step in the development of fiber-induced cancer. Thus, the genotoxic potential can be a cornerstone in the evaluation of hazards of CNTs. The present study used a weight of evidence (WoE) analysis to evaluate the genotoxicity of different types of CNTs. Genotoxicity endpoints close to cancer (mutations and chromosome aberrations) and animal models had highest weight in the WoE analysis. Eight CNT materials out of 130, which had been assessed in several studies, were evaluated in the WoE analysis. The results demonstrated that MWCNT-7 has strongest WoE for a genotoxic hazard among the MWCNTs. Two types of SWCNTs have a similar WoE for genotoxicity as MWCNT-7. Several reference materials from the Joint Research Centre have less WoE for genotoxicity. The WoE analysis demonstrates a difference in genotoxicity for CNTs, but further research is required to unravel the physico-chemical characteristics that govern the differences in genotoxic hazard.     

Comparative toxicity of physiological and biochemical parameters in Euglena gracilis to short-term exposure to potassium sorbate

Ecotoxicology - Potassium sorbate is the potassium salt of sorbic acid, is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions...     

Evaluation of genotoxic potential of synthetic progestin chlormadinone acetate

The genotoxicity study of a synthetic progestin chlormadinone acetate, was carried out on mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameter, chlormadinone acetate was studied at three different doses, i.e. 5.62, 11.25 and 22.50 mg/kg body weight and was found to be non-genotoxic at 5.62 mg/kg body weight. But at 11.25 and 22.50 mg/kg of body weight chlormadinone acetate increases SCE (P < 0.001) and CA (P < 0.01) at significant level compared to normal control. The results suggests a genotoxic and cytotoxic effect of chlormadinone acetate in mouse bone marrow cells.     

HPLC测定炎琥宁的原料及其制剂的含量

目的:建立HPLC法测定炎琥宁原料及其制剂的含量.方法:采用Waters XTerraRRP18(150 nm×4.6 mm,5μm),以0.05%磷酸二氢钾(用磷酸调pH至2.5±0.05)-甲醇(3∶7)为流动相,检测波长251 nm.结果:脱水穿心莲内酯琥珀酸半酯在0.02～1.0 mg·mL-1范围内线性关系良好;回归方程:A=7415C 1098(r=0.9999),平均回收率为100.41%,RSD为0.79%(n=9).结论:该方法简便、灵敏,可作为炎琥宁原料及其制剂的质量控制标准.     

注射用阿莫西林钠/克拉维酸钾的细菌内毒素检查

目的:探讨注射用阿莫西林钠/克拉维酸钾的细菌内毒素检查法.方法:按照2000年版<中国药典(二部)>收载的细菌内毒素检查法的要求进行.结果:对于注射用阿莫西林钠/克拉维酸钾,可用灵敏度为0.5 EU/mL的鲎试剂进行细菌内毒素检查.结论:鲎试剂可用于注射用阿莫西林钠/克拉维酸钾的细菌内毒素检查.     

电感耦合等离子体发射光谱法测定炎琥宁原料中的钠与钾

目的采用电感耦合等离子体发射光谱测定炎琥宁原料中钠、钾的含量及摩尔比。方法等离子体功率12 kW,工作气体为高纯氩,气体流速14 L·min^-1,矩管为高盐矩管,检测波长钠330.232 nm、钾769.896 nm。结果炎琥宁中钠、钾分别为5～50、5～100μg·mL^-1时与峰面积呈良好的线性关系,平均回收率分别为102.60%(RSD=1.70%)、97.50%(RSD=1.30%)。结论所用方法简便、快速、经济,可快速准确检测出炎琥宁原料药中钠、钾的含量及摩尔比,为其质量控制提供了可靠的检测依据。     

注射用炎琥宁细菌内毒素检查法

目的:建立注射用炎琥宁细菌内毒素检查(BET)方法。方法:按中国药典[1]2005年版附录细菌内毒素检查法要求进行试验。结果:注射用炎琥宁(C=1.6mg/mL)稀释10倍(0.16mg/mL)后采用灵敏度0.125EU/mL的鲎试剂经干扰实验无增强、抑制作用。结论:细菌内毒素检查法适用于检测注射用炎琥宁中的内毒素。     

Bioassays for evaluating the water-extractable genotoxic and toxic potential of soils polluted by metal smelters

Physicochemical analyses of polluted soils are limited in their ability to determine all hazardous compounds, their bioavailability, and their combined effects on living organisms. Bioassays, on the other hand, can evaluate environmental quality more accurately. This study assesses the genotoxic potential of water extracts from soil polluted with metals (Pb, Cd, and Zn) by the former lead smelter in zerjav, Slovenia using comet assay with Tetrahymena thermophila and human hepatoma cells (HepG2). In addition, the toxicity of soil samples and their extracts was evaluated using Vibrio fischeri and delayed fluorescence of Lemna minor. Chemical analyses of metals using atomic absorption spectrophotometry (AAS) was performed for comparison. Measurements of the total metal concentrations showed that four of five plots near the former lead smelter were highly contaminated with Pb, Cd, and Zn, but the amount of metals in water/soil extracts was low at all the sampling plots. Genotoxicity was demonstrated using T. thermophila for the majority of the extracts, and HepG2 cells for only some of the extracts. Whereas V. fischeri indicated a gradual decrease in soil toxicity with greater distance from the smelter, the toxicity of extracts did not correlate with proximity. Low concentrations of metals in water extracts stimulated L. minor growth. The results indicate that comet assay with T. thermophila and HepG2 cells and the BSPT with V. fischeri are suitable protocols for screening the genotoxic and toxic potential of water/soil extracts by comet assay, whereas chemical analyses of total metal concentrations in soil do not solely suffice for evaluating metal pollution in the environment. Biological assays are thus crucial for risk assessment.     

Evaluation of the toxic and genotoxic potential of landfill leachates using bioassays

Landfill leachates are liquid effluents with elevated concentrations of chemical compounds that can cause serious environmental pollution. In the south of the state of Santa Catarina, Brazil, a sanitary landfill was installed that employs a system of anaerobic/facultative lagoons for the treatment of its leachate. The present work examined the toxic and genotoxic potential of untreated and treated landfill leachates using bioassays. The chemical, toxic, genotoxic and mutagenic properties of the untreated leachate and the treated leachate were determined. Examination of the chemical properties showed a marked decrease in parameters after treatment, as well as in toxicity towards all the organisms tested. The results of the comet assay demonstrated that both leachates showed genotoxicity in all of the organisms tested, indicating the persistence of genotoxic substances even after treatment. A significant decrease in micronucleated cells was detected in Geophagus brasiliensis exposed to the treated leachate compared to untreated.     

β-七叶皂苷钠抗大鼠主动脉血管形成作用及机制初探*

目的:研究β-七叶皂苷钠对血管形成的作用及其作用机制。方法:采用大鼠主动脉片96孔板培养,检测β-七叶皂苷钠对体外血管形成的影响;采用MTT法研究β-七叶皂苷钠对ECV-304细胞增殖的影响;采用免疫组织化学法研究β-七叶皂苷钠对小鼠S180肉瘤内血管内皮生长因子(VEGF)表达的影响。结果:β-七叶皂苷钠50μg.mL-1组在d1～d5对大鼠主动脉片血管出芽发生率有明显的抑制作用,抑制率均>39.0%;在d2～d6大鼠主动脉片血管相对面积明显小于阴性对照组,抑制率均>68.9%。MTT实验证明β-七叶皂苷钠对ECV-304细胞增殖具有明显抑制作用:100μg.mL-1抑制率为70.3%,50μg.mL-1抑制率为53.6%;免疫组织化学实验β-七叶皂苷钠1.4和2.8mg.kg-1组VEGF表达量均明显少于生理氯化钠溶液对照组。结论:β-七叶皂苷钠具有抑制血管形成的作用,其发挥作用的可能机制是抑制血管发生、内皮细胞的增殖及VEGF的表达。