松针汁的毒性及致突变性研究

对松针汁进行了毒性和致突变性实验。结果显示：松针汁急性毒性试验，ＬＤ５０〉１０ｇ／ｋｇｂｗ；在所示剂量范围内，Ａｍｅｓ试验加与不加Ｓ９活化系统，各剂量组平均回主率均〈２，小鼠骨髓细胞微核试验，各剂量组微核率与阴性对照组比较无明显差异，小鼠精子畸形试验，各剂量组精子畸形率与阴性对照组比较无明业差异，表明松针汁无毒，无致突变作用。     

Absence of genotoxicity of potato alkaloids alpha-chaconine, alpha-solanine and solanidine in the Ames Salmonella and adult and foetal erythrocyte micronucleus assays.

To assess whether reported toxicities of potato-derived glycoalkaloids could be the result of interactions with cellular DNA, the genotoxic effects of alpha-solanine, alpha-chaconine and solanidine were studied, using the Ames test (Salmonella strains TA98 and TA100), the mouse peripheral blood micronucleus test and the mouse transplacental micronucleus test. The Ames test for mutagenicity with alpha-solanine was weakly positive in TA100 with S-9 activation (29 revertants per millimole per plate). However, pooled data from duplicate tests gave a negative effect. Pooled data from two experiments with alpha-chaconine gave a weak positive response in TA98 without microsomes (17 revertants per millimole per plate). The micronucleus tests for clastogenicity using male mouse and foetal blood were negative. The absence of mutagenicity and clastogenicity suggests lack of damage to intracellular DNA for potato alkaloid toxicity.     

The toxicology and safety of apple polyphenol extract.

Apple polyphenol extract has strong antioxidant activity and various physiological functions, and is used in Japan as a food additive and nutritional supplements. Here, we tested the consumption safety of Applephenon, which is a polyphenol extract produced from unripe apples. The Ames test without S9 mixture revealed that Applephenon, had slight mutagenicity at a high concentration of 2500 microg/plate; however, both chromosomal aberration test and the micronucleus test found no significant mutagenicity. Furthermore, an acute oral-toxicity test, and a 90-day subchronic-toxicity test showed no significant hematological, clinical, chemical, histopathological, or urinary effects at a dose of 2000 mg/kg. These results confirm that Applephenon is safe and no toxic at average dietary level.     

N,N-diethylphenylacetamide, an insect repellent: absence of mutagenic response in the in vitro Ames test and in vivo mouse micronucleus test

N,N-diethylphenylacetamide (DEPA), a promising new insect repellent, was tested for mutagenicity in the in vitro Ames Salmonella/microsome mutagenicity test and the in vivo mouse micronucleus test. For the Ames test, DEPA was assayed both in the presence and absence of Aroclor 1254-induced rat-liver S-9 mix (5 and 20% S-9 fraction), using five tester strains of Salmonella typhimurium--TA97a, TA98, TA100, TA102 and TA104. For the micronucleus test, mice were exposed to DEPA through ip injection for 2 and 5 days in separate experiments, and bone marrow and peripheral blood were sampled 6 and 48 hr after the final injection, respectively. DEPA did not induce a mutagenic response in the Ames test, and mouse bone marrow and peripheral blood micronucleus tests. DEPA was not considered cytotoxic, as a depression of the percentage PCE was not observed at any dose in the range of 1 to 100 mg/kg body weight with either treatment protocol of the micronucleus test.     

赤苷脉通注射液的致突变研究

目的探讨中药制剂赤苷脉通注射液的致突变性。方法采用鼠伤寒沙门氏组氨酸营养缺陷型菌株回复突变实验(Ames实验)、中国仓鼠肺成纤维细胞(CHL)染色体畸变实验和小鼠骨髓微核实验来检测赤苷脉通注射液的致突变作用。结果 Ames实验中,赤苷脉通注射液在312.5～5 000μg.皿-1剂量范围内,无论加或不加S9,鼠伤寒沙门氏菌组氨酸缺陷型TA97,TA98,TA100,TA102和TA1535 5株菌的回复突变菌落数均未出现剂量依赖性的增加;染色体畸变实验中,非活化条件或代谢活化条件下,药物质量浓度为1 200,600和300μg.mL-1时,细胞的染色体畸变率均未出现剂量依赖性增加;微核实验中,在1 150,575和287.5mg.kg-1剂量组中均未见骨髓中含微核的嗜多染红细胞数增加。结论在该实验室条件下,Ames实验、CHL细胞染色体畸变实验和小鼠骨髓微核实验结果均为阴性,即中药制剂赤苷脉通注射液无潜在的遗传毒性。     

3种促智药:石杉碱甲、茴拉西坦和吡乙酰胺的诱变作用和诱变协同作用

在鼠伤寒沙门菌/微粒体系统中测试了石杉碱甲、茴拉西坦和吡乙酸胺的诱变作用。结果表明,药物浓度从1μg-5mg/皿对TA97、TA98、TA100和TA1024个菌株,在无S_9代谢系统上所测的这3个药和有S_9代谢系统所测的石杉碱甲、茴拉西坦均未显示任何诱变作用。向拉西坦和吡乙酰胺在诱变协同实验中均不增加对-硝基喹啉在TA98上和甲基磺酸甲酯在TA100上诱发的回变数。ICR纯系小鼠骨髓微核试验,剂量高达1/2LD_(50)时不增加嗜多染红细胞的微核率,也无骨髓抑制作用.     

Safety evaluation of water extracts of Toona sinensis Roemor leaf.

The purposes of this study were to evaluate the safety of water extracts of Toona sinensis Roemor leaf (TSL-1). The mutagenic properties of TSL-1 was investigated using the Ames test, and no mutagenicity was found toward all tester strains (Salmonella typhimurium TA98, TA100, TA102 and TA1535). In the acute oral toxicity study, a single limit dose of 5000 mgTSL-1/kg bw was given to male and female ICR mice, then observed for a 14-day period. In the subacute study, TSL-1 was administered as oral daily dose of 1000 mg/kg bw/day for 28 days. The results showed no acute lethal effect at a maximal tested dose of 5000 mg/kg bw TSL-1 in male and female mice. The subacute toxicity showed the oral administration of 1000 mg/kg bw for consecutive 28 days was safe in male mice. TSL-1 treated female mice showed decreases of food intake and kidney relative weight in acute oral toxicity test, and decreases of body weight gain, food intake and lung relative weight in subacute toxicity trial. However, no remarked toxic effects were found in the biochemical and histopathological parameters of TSL-1 treated female mice. These effects whether related to the major components or other ingredients in TSL-1 need to elucidate in the further studies.     

油松花粉遗传毒性研究

目的 探讨油松花粉的遗传毒性,为其应用提供安全性毒理学评价依据.方法 用鼠伤寒沙门细菌营养缺陷型突变株TA97(a)、TA 98、TA 100和TA 102,采用平皿掺入法进行Ames实验,将实验分为加和不加代谢激活系统S9 2组平行实验.受实物设5个剂量组(0.008、0.040、0.200、1.000、5.000 mg/皿).应用小鼠骨髓嗜多染红细胞微核实验,检测小鼠骨髓嗜多染红细胞微核率;利用小鼠精子畸形实验,观察不同浓度的油松花粉致小鼠精子畸形的数目.结果 在Ames实验中,油松花粉各剂量组引起的回变菌落数未超过对照组自发回变菌落数的1倍以上;小鼠骨髓嗜多染红细胞微核实验显示,油松花粉3个剂量组的微核发生率均在正常范围内,与阴性对照组比较差异无显著性(P＞0.05),与阳性对照组比较差异显著(P＜0.05);小鼠精子畸形实验显示,油松花粉3个剂量组的精子畸形率均在正常范围内,与阴性对照组比较差异无显著性(P＞0.05),与阳性对照组比较差异显著(P＜0.05).结论 油松花粉对所实菌株、小鼠体细胞及生殖细胞无诱变性.     

酸枣仁油的致突变作用的研究

目的对酸枣仁油进行毒理学试验,探讨酸枣仁油是否有致突变作用。方法①小鼠急性毒性试验:一次最大限量法。②Ames试验:选用经鉴定符合要求的鼠伤寒沙门氏组氨酸缺陷型TA97、TA98、TA100、TA102试验菌株,采用平板掺入法。③小鼠骨髓嗜多染红细胞微核试验。结果酸枣仁油对雌雄小鼠经口LD50均>10g/kg,为实际无毒级物质;骨髓嗜多染红细胞微核实验和Ames试验未发现破酸枣仁油对小鼠有致突变作用。结论从毒理学角度可以认为酸枣仁油作为保健食品用于人体是安全的。     

Acute, subacute toxicity and genotoxic effect of Bio-Quinone Q10 in mice and rats

In the present study, the acute, subacute and genetic toxicity of Coenzyme Q10 (CoQ10) in the form of Bio-Quinone (Pharma Nord, Denmark) was assessed. LD(50) of CoQ10 by oral treatment was greater than 20g/kg body weight in both female and male mice. Genotoxicity was assessed in mice by Ames test in Salmonella typhimurium strains TA97, TA98, TA100 and TA102, by bone marrow micronucleus test and sperm abnormality. Thirty-day subacute toxicity was conducted with oral daily dose at 0, 0.56, 1.13 and 2.25g/kg body weight in rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight, sperm abnormality, mutagenicity and micronucleus formation were observed and no clinical signs or adverse effects were detected by administration of CoQ10. These results support the safety of CoQ10 for oral consumption.     

Evaluation of genetic toxicity of 6-diazo-5-oxo-l-norleucine (DON)

DON (6-diazo-5-oxo-l-norleucine), a glutamine antagonist, was demonstrated to exhibit analgesic, antibacterial, antiviral and anticancer properties. The study was performed to characterize its in vitro and in vivo genetic toxicity potential. DON was tested in the bacterial reverse mutation assay (Ames test) using Salmonella typhimurium tester strains (TA98, TA100, TA1535 and TA1537) and Escherichia coli tester strain (WP2 uvrA) with and without S9 and also with reductive S9. In addition, DON was tested for the chromosome aberrations in Chinese hamster ovary (CHO) cells with or without S9 to evaluate the clastogenic potential. Furthermore, DON was also evaluated for its in vivo clastogenic activity by detecting micronuclei in polychromatic erythrocyte (PCE) cells in bone marrow collected from the male mice dosed intravenously with 500, 100, 10, 1 and 0.1?mg/kg at 24 and 48-h post-dose. The Ames mutagenicity assay showed no positive mutagenic responses. However, the in vitro chromosome aberration assay demonstrated dose dependent statistically positive increase in structural aberrations at 4 and 20-h exposure without S9 and also at 4-h exposure with S9. The in vivo micronucleus assay also revealed a statistically positive response for micronucleus formation at 500, 100 and 10?mg/kg at 24 and 48-h post-dose. Thus, DON appears to be negative in the Ames test but positive in the in vitro chromosome aberration assay and in the in vivo micronucleus assay. In conclusion, the results indicate DON is a genotoxic compound with a plausible epigenetic mechanism.     

Study of mutagenicities of phthalic acid and terephthalic acid using in vitro and in vivo genotoxicity tests

Genotoxicities of phthalic acid (PA) and terephthalic acid (TPA) were examined using three mutagenicity tests: Ames, chromosome aberration (CA), and micronucleus (MN). In the Ames test, these two agents did not produce any mutagenic responses in the absence or presence of S9 mix on the Salmonella typhimurium strains TA98, TA100, TA102, TA1535, or TA1537. The CA test also showed that PA and TPA exerted no significant cytogenetic effect on Chinese hamster ovary (CHO) cells. In the mouse MN test, no significant alteration in occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice ip administered any of these agents at doses of 0, 20, 100, 500, 2500 or 12,500 microM/kg. These results indicate that PA and TPA produced no mutagenic effects using these in vitro and in vivo mutagenic test systems.     

银参胶囊遗传毒性研究

目的探讨银参胶囊的遗传毒性。方法选用SPF级健康ICR小鼠,通过Ames试验、小鼠骨髓细胞微核试验、小鼠睾丸染色体畸变试验等遗传毒性试验验证银参胶囊的安全性。结果 Ames试验中,银参胶囊在8~5 000μg/皿剂量范围内,无论是否加入哺乳动物肝脏微粒体酶(S9),鼠伤寒沙门菌TA97,TA98,TA100,TA102等4株菌的回复突变菌落数均未出现剂量依赖性增加;微核试验中,2 500,5 000,10 000 mg/kg剂量组均未见骨髓中含微核的嗜多染红细胞数增加;小鼠睾丸染色体畸变试验中,药物质量分数为2 500,5 000,10 000 mg/kg时,细胞的染色体畸变率均未出现剂量依赖性增加。结论银参胶囊未显示致突变作用,可初步判定其在遗传毒性方面是安全的。     

Polyethylene sebacate: Genotoxicity,mutagenicity evaluation and application in periodontal drug delivery system

The objective of the present study is to evaluate Polyethylene sebacate (PES) for its toxicity profile including oral toxicity, genotoxicity and mutagenicity. PES was synthesised, and characterised by gel permeation chromatography, FTIR, ¹H-NMR, differential scanning calorimetry and X-ray diffraction. Oral toxicity studies revealed PES to be nontoxic up to 3000 mg/kg body weight with no significant changes in serum biochemistry. The standard battery of genotoxicity tests including micronucleus test, chromosomal aberration and comet assay revealed PES as nongenotoxic. Mutagenicity of PES was evaluated using the Ames microplate format mutagenicity assay sample kit using TA98 and TA100 strains of Salmonella typhimurium, both in presence and absence of Aroclor 1254 induced rat liver S9. Ames assay confirmed PES to be nonmutagenic. Periodontal implants of PES of varying roxithromycin/PES ratios and different diameter were prepared. A decrease in in vitro drug release was seen with increase in diameter of the implants. Release rates, however, increased with increase in PES concentration, and were attributed to decreased crystallinity of roxithromycin, confirmed by the DSC thermographs and XRD spectra. Roxithromycin release from the implants followed Higuchi kinetics and exhibited controlled release. The results suggest PES as a safe polymer for biomedical and pharmaceutical applications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4781–4795, 2009     

中药复方藿莲香Ⅰ号的遗传毒理学研究

目的：根据前期藿莲香Ⅰ号药效学研究结果,进一步研究该复方的急性毒性和致突变作用,为其进一步应用的安全性提供理论依据。方法应用急性毒性实验、小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验检测该组分配伍复方的急性毒性和致突变性。结果急性经口毒性试验：雌性、雄性小鼠经口MTD均大于10g＆#183;kg-1,属实际无毒。致突变实验：小鼠骨髓嗜多染红细胞微核试验、小鼠骨髓细胞染色体畸变试验和Ames试验结果均为阴性,显示在本实验条件下,该中药复方未见有致突变性作用。结论中药复方藿莲香Ⅰ号未见有明显的急性毒性和致突变作用,表明该药物安全性良好。     

Disposition of [14C]2,3-dichloropropene in Fischer-344 rats after oral or intraperitoneal administration

The genotoxicity of indigo has been assessed by two short-term tests. The mutagenicity of natural indigo was compared with that of synthetic indigo. Both chemicals were tested using the standard procedure of the Salmonella/microsome mutagenicity test as described by Ames. The substance exhibits mutagenicity towards strains TA1538 and TA98 when S9 preparations of rat liver induced with Aroclor 1254 were present in the medium. The clastogenic potential was evaluated by the micronucleus test in the bone marrow of male mice. The test compound was administered twice with an interval of 24 h, the animals were killed 30 h and 54 h after the first treatment. When the test compound was given by oral gavage as two equal dosages of 0.1, 1 and 1.2 g/kg body weight, no statistically significant increase in the percentage of polychromatic erythrocytes with micronuclei was observed for any group treated with natural indigo.     

百草胶囊的毒性研究

目的　研究百草胶囊的毒性。方法　采用最大耐受剂量 (MTD)试验 ,小鼠骨髓嗜多染红细胞微核试验 ,小鼠精子畸形试验 ,Ames试验和大鼠 30d喂养试验 ,分别观察百草胶囊的急性毒性 ,遗传毒性和亚急性毒性。结果　百草胶囊对小鼠经口MTD大于 16 0 0 0mg/kg ;对小鼠骨髓嗜多染红细胞微核试验无诱发微核增多作用 ;小鼠精子畸形试验未见导致精子畸形和畸形率增高 ;Ames试验在加与不加S9的条件下均无致突变性 ;大鼠 30d喂养试验未观察到中毒表现 ,百草胶囊各剂量组动物体重 ,食物利用率 ,血液学和血液生化学指标值 ,各脏器的脏 /体比值与空白对照组比较差异均无显著意义 (P >0 0 5 )。主要脏器在外观形态和组织学上均无异常变化。结论　百草胶囊对动物的生长发育、造血功能、肝肾功能、器官组织均无明显毒性。     

丹参注射液单次给药的毒性及遗传毒性研究

目的研究丹参注射液的单次给药毒性及遗传毒性,为评价其安全性提供毒理学依据。方法采用一次性给予丹参注射液,观察ICR小鼠产生的毒性反应;用体外细菌回复突变(Ames)实验、中国仓鼠肺成纤维细胞(CHL)体外染色体畸变实验、小鼠骨髓嗜多染红细胞微核实验进行丹参注射液的遗传毒性研究。结果在单次给药毒性中,5个剂量组动物死亡数分别为9,7,4,3和0只;Ames实验中,丹参注射液剂量分别为5 000,2 000,500,50和5μg·皿-1,无论加或不加哺乳动物肝脏微粒体酶(S9),各剂量组的回复突变菌落数均未出现剂量依赖性的增加,结果为阴性;在染色体畸变实验中,非活化条件或代谢活化条件下,细胞的染色体畸变率均未出现剂量依赖性增加;在微核实验中,与溶媒对照组比较,丹参注射液各剂量组中的微核率均无显著性差异。结论在本实验条件下,单次给药毒性研究中,丹参注射液小鼠静脉注射给药的LD50为68.72g·kg-1,95%可信限为66.92~70.58g·kg-1,其对小鼠的急性毒性可能靶器官组织为肺脏。遗传毒性实验结果均为阴性,即中药制剂丹参注射液无潜在的致突变性。     

In vitro bioactivity of combustion products from 12 tobacco constituents.

Twelve chemical components of tobacco leaf, representing 50% of its dry weight, were individually combusted and the bioactivities of their combustion products i.e. total particulate matter (TPM) were assayed using three in vitro tests. These components included carbohydrates, amino acids, proteins, polyphenols and carboxylic acids. The mutagenic potencies were assessed with the Salmonella mutagenicity assay (S. typhimurium TA98 and TA100). The induction of chromosomal damage, determined with the micronucleus test (IVMNT), and the neutral red uptake cytotoxicity test (NRU), were conducted on V79 hamster lung fibroblast cells. The Salmonella mutagenicity test and IVMNT were conducted with and without rat liver microsomal S9 fraction. Salmonella mutagenicity data confirmed the mutagenicity of TPM samples obtained from nitrogenous compounds (amino acids and proteins). The IVMNT showed that precursors of phenols in smoke (i.e. polyphenols) exhibited significantly higher levels of toxicity compared to other tobacco components. While S9 activation amplified the Salmonella mutagenicity response to combustion products, it significantly inhibited the toxicity measured with the IVMNT. NRU data demonstrated the increasing cytotoxicity induced following longer exposure time to TPM samples from nitrogenous and phenolic components. This study is the first to characterize the toxicity of the combustion products of major tobacco constituents. Our data suggest different mechanisms of toxicity and underline the relevance of using various bioassays.     

Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily

Steroidal saponin DT-13 (25 (R, S)-ruscogenin-1-O-[β-d-glucopyranosyl - (1 → 2)] [β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside) is the main active component of the tube of Liriope muscari (Decne.) Baily and has been studied as a candidate drug for cancer metastasis. The objective of this study was to evaluate the safety of DT-13 systematically by genotoxicity and acute oral toxicity and subchronic 90-day oral gavage toxicity. Results of Ames test confirmed that DT-13 did not induce mutations in histidine auxotrophs Salmonella typhimurium (TA 97, TA 98, TA 100 and TA 102) both in the presence and absence of metabolic activation system at the doses of 0.05-500 μg/plate. Meanwhile, DT-13 did not induce clastogenicity at doses of 1250, 2500 and 5000 mg/kg in mouse micronucleus test. And the single oral dose of DT-13 at 5000 mg/kg did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of mice. In subchronic toxicity study, DT-13 was administrated to Sprague-Dawley rats via oral gavage at doses of 10, 60 and 360 mg/kg for 90 days. Necropsy, hematological and biochemical analysis, and histopathological examination did not reveal any remarkable and treatment related changes. In conclusion, DT-13 is of low toxicity at the tested doses.