赭曲霉毒素 C | 4865-85-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 赭曲霉毒素及相关物质
• 中文名称: 赭曲霉毒素 C
• 中文别名: 赭曲霉毒素C
• 英文名称: ochratoxin C
• 英文别名: ethyl (2S)-2-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoate
• CAS: 4865-85-4
• 化学式: C₂₂H₂₂ClNO₆
• 分子量: 431.873
• InChiKey: BPZZWRPHVVDAPT-PXAZEXFGSA-N

物化性质

• 沸点：
  612.6±55.0 °C(Predicted)
• 密度：
  1.328±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：可溶； DMSO：可溶；乙醇：可溶；甲醇：可溶
• 颜色/状态：
  Amorphous solid
• 蒸汽压力：
  1.81X10-15 mm Hg at 25 °C (est)
• 解离常数：
  pKa1 = 8.2 (hydroxyl); pKa2 = 13.1 (amine) (est)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

ADMET

代谢

研究了在大鼠口服和静脉注射后，赭曲霉毒素C转化为赭曲霉毒素A的情况。在口服给予等量赭曲霉毒素C或赭曲霉毒素A后，血液中赭曲霉毒素A的浓度随时间的变化是相同的。给药后60分钟测得赭曲霉毒素A的最大浓度。静脉注射赭曲霉毒素C后，同样转化为赭曲霉毒素A，最大浓度在给药后90分钟达到。可以得出结论，无论是口服还是静脉注射，赭曲霉毒素C都很容易转化为赭曲霉毒素A。有理由相信，这两种毒素的相似毒性是基于这种转化，并且只有干扰生物转化机制可能会造成它们毒性的差异。

The conversion of ochratoxin C to ochratoxin A was studied in rats after oral and intravenous administration. The concentration of ochratoxin A in the blood as a function of time was the same after oral administration of equivalent amounts of either ochratoxin C or ochratoxin A. The maximum ochratoxin A concentrations were measured 60 min after administration. Given intravenously, ochratoxin C was also converted to ochratoxin A. Maximum concentrations were reached after 90 min. It is concluded that ochratoxin C is readily converted to ochratoxin A after both oral and intravenous administration. There is reason to believe that a comparable toxicity of the two toxins is based upon this conversion and that only interference with the biotransformation mechanisms may cause a difference in their toxicity.

来源:Hazardous Substances Data Bank (HSDB)

代谢

OA的代谢轮廓在大鼠和产生OA的赭曲霉培养物中进行了研究。从赭曲霉培养物中分离出ochratoxin alpha (O alpha)、ochratoxin beta (O beta)、4-R-羟基ochratoxin A (4-R-OH OA)、4-R-羟基ochratoxin B (4-R-OH OB)和10-羟基ochratoxin A (10-OH OA)，并通过1H核磁共振光谱、质谱和高压液相色谱对其结构进行了表征。4-R-OH OA和O alpha在真菌培养物中以及用OA和ochratoxin C (OC)处理的 rats 中始终产生，并且是主要的生物转化代谢物，而10-OH OA的形成在真菌系统中是有条件的。通过洗涤剂提取真菌培养物，然后进行冷醋酸沉淀和凝胶过滤，分离出绿色荧光生物大分子。荧光大分子的酸性水解导致释放出几种ochratoxins，包括O alpha (80%)、OA (2%)和OC (5%)，以及其他未识别的荧光化合物，但不是OB和O beta。OA的自然大分子结合物与抗OA多克隆抗体的交叉反应性研究表明，它们通过一个不同于羧基的基团与大分子共价连接。这些研究表明，真菌可以产生与大鼠相同的某些OA代谢物，并且O alpha、OA和OC可能与大分子共价连接。

...The metabolic profile of ochratoxin A (OA) /was studied/ in rats and in a culture of OA-producing Aspergillus ochraceus. Ochratoxin alpha (O alpha), ochratoxin beta (O beta), 4-R-hydroxyochratoxin A (4-R-OH OA), 4-R-hydroxyochratoxin B (4-R-OH OB), and 10-hydroxyochratoxin A (10-OH OA) were isolated from a culture of A. ochraceus and structurally characterized by 1H nuclear magnetic resonance spectroscopy, mass spectrometry and high-pressure liquid chromatography. 4-R-OH OA and O alpha were consistently produced and were the dominant biotransformed metabolites in the fungal culture and in rats treated with OA and ochratoxin C (OC), while the formation of 10-OH OA was conditional in the fungal system. Green fluorescent biomacromolecules were isolated by detergent extraction of the fungal culture followed by cold-acetone precipitation and gel filtration. Acid hydrolysis of the fluorescent macromolecules resulted in the release of several ochratoxins, including O alpha (80%), OA (2%), and OC (5%), and other unidentified fluorescent compounds but not OB and O beta. Cross-reactivity studies of the natural macromolecule conjugates of OA with anti-OA polyclonal antibodies indicated that they were covalently linked to the macromolecules via a group other than the carboxyl group. These studies demonstrated that a fungus can produce some of the same metabolites of OA as the rat and that O alpha, OA, and OC may be covalently linked to fungal macromolecules.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

替代方法和体外测试：为了研究长期接触低浓度赭曲霉毒素A（OTA）或赭曲霉毒素C（OTC）对人类单核细胞系（THP-1）的影响，开发了一种体外模型。细胞在24孔细胞培养板中培养15天。在整个培养期间，细胞培养液中分别包含1 ng/mL浓度的OTA和OTC制剂。在暴露时间结束时，检查细胞活性和细胞功能的参数。经过15天的赭曲霉毒素暴露，THP-1细胞系的活性和功能发生了改变。所有真菌毒素制剂增加了线粒体活性和IL-6的产生。细胞膜完整性受到干扰，增殖以及TNF-a和IL-8的产生被抑制。这些参数在使用含有OTC的真菌毒素制剂时受到的影响最为严重。我们的结果显示，长期接触低浓度的OTA特别是OTC可以引起细胞活性和功能的微妙变化，这可能对人类和动物健康产生显著影响。在这种情况下，似乎有必要更深入地研究食物和饲料中OTC的污染。

/ALTERNATIVE and IN VITRO TESTS/ An in-vitro model was developed to study the effects of a long-term exposure with a low concentration of ochratoxin A (OTA) or ochratoxin C (OTC) on a human monocytic cell line (THP-1).Cells were propagated in 24-well cell culture plates for 15 days. OTA and OTC preparations, respectively, at a concentration of 1 ng/mL were included in the cell culture medium during the whole cultivation period. At the end of the exposure time, parameters of cell viability and cell function were examined.After 15 days of exposure to ochratoxins, viability and function of the THP-1 cell line were modulated. Mitochondrial activity and the production of IL-6 were increased by all mycotoxin preparations. Cell membrane integrity was disturbed, proliferation and the production of TNF-a and IL-8 were inhibited. These parameters were most severely affected by mycotoxin preparations containing OTC.Our results show that long term exposure to OTA and especially OTC in low concentrations can cause subtle alterations of cell viability and function which may have remarkable consequences for human and animal health. In this context it seems to be necessary to study the contamination of food and feed stuffs with OTC more intensively.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 2811

制备方法与用途

生物活性方面，Ochratoxin C 是 Ochratoxin A 的乙酯类似物，由 A. ochraceus 生成，是一种神经毒素（真菌毒素）。Ochratoxin C 是常见的一种食品污染物。

反应信息

• 作为产物：
  描述：

  赭曲霉毒素A 、 乙醇 在 氯化亚砜 作用下， 反应 3.0h， 生成 赭曲霉毒素 C
  参考文献：
  名称：

  Development of a Sensitive Enzyme-Linked Immunosorbent Assay for the Determination of Ochratoxin A

  摘要：

  Polyclonal antibodies for ochratoxin A (OTA) were generated from rabbits after the animals had been immunized with either OTA-gamma-globulin or OTA- keyhole limpet hemocyanin (KLH). A competitive direct enzyme-linked immunosorbent assay (cdELISA) and a competitive indirect ELISA (ciELISA) were used for the characterization of the antibodies and for analysis of OTA in various agricultural commodities. The antibody titers in the serum of rabbits immunized with OTA-gamma-globulin were considerably higher than those in rabbits immunized with OTA-KLH. The antibodies from the rabbits immunized with OTA-gamma-globulin were further characterized. In the cdELISA, the concentrations causing 50% inhibition (IC50) of binding of OTA-horseradish peroxidase to the antibodies by OTA, ochratoxin B (OTB), and ochratoxin C (OTC) were found to be 0.90, 110, and 0.54 ng/mL, respectively. When 10 to 250 ng/g of standard OTA was spiked to soybean samples and then extracted with 50% aqueous methanol, the recovery rate of OTA was found to be 85.9% in the cdELISA. Analysis of OTA in various agricultural commodities showed that 12 of the 20 examined samples were contaminated with OTA at levels from 16 to 160 ng/g. The efficacy of cdELISA was also confirmed by the high-performance liquid chromatography method.

  DOI：

  10.1021/jf0513922

文献信息

• Method for producing purified and/or concentrated analytes, use and kit
  申请人：AOKIN AG

  公开号：EP2026068A1

  公开（公告）日：2009-02-18

  The present invention relates to a method for producing purified and/or concentrated analytes of interest from a sample of biological sources, said method comprising or consisting of the following steps: a) providing an affinity column capable of being centrifuged, the column comprising or consisting of: (i) a centrifugation column, (ii) optionally one, two or more separators, and (iii) an affinity matrix comprising a matrix and one or more, the same or different binding moieties, wherein the binding moieties are attached to the matrix in such a way, that the binding moieties are capable of binding to the analytes of interest to form a binding moiety-analyte-complex so that the analytes of interest are not eluted from the column, b) optionally washing the affinity column with a washing solvent, c) adding the sample comprising the analytes of interest to and filtering the sample through the affinity column, so that at least part of the analytes of interest of the sample form the binding moiety-analyte-complex, d) optionally washing the affinity column comprising the binding moiety-analyte-complexes with a washing solvent, e) adding an incubating solvent to said affinity column comprising the binding moiety-analyte-complexes, f) incubating the incubation solvent on the affinity column comprising the binding moiety-analyte-complexes, so that at least part of the binding moiety-analyte-complexes are destroyed and g) eluting the analytes of interest from the affinity column by way centrifugation, a use of an affinity column capable for being centrifuged, a kit comprising an affinity column and an affinity column.

  本发明涉及一种从生物源样品中制备纯化和/或浓缩的相关分析物的方法，所述方法包括或由以下步骤组成： a) 提供可离心的亲和柱，该亲和柱包括或由以下部分组成： (i) 离心柱、 (ii) 可选的一个、两个或多个分离器，以及 (iii) 由基质和一个或多个相同或不同的结合分子组成的亲和基质，其中结合分子以这样 的方式附着在基质上，即结合分子能够与感兴趣的分析物结合形成结合分子-分析物-复合物， 从而使感兴趣的分析物不会从柱中洗脱出来、 b) 用洗涤溶剂清洗亲和柱、 c) 将包含相关分析物的样品加入亲和柱并通过亲和柱过滤样品，使样品中的至少一部分相关分析物形成结合莫伊--分析物--络合物、 d) 选择性地用洗涤溶剂清洗亲和柱，亲和柱中包括结合莫伊-分析物-复合物、 e) 将孵育溶剂加入到所述亲和柱中，亲和柱中包含结合莫伊-分析物络合物、 f) 在亲和柱上孵育孵育溶剂，使至少部分结合莫伊耶-分析物复合物被破坏，以及 g) 通过离心从亲和柱中洗脱出感兴趣的分析物、 使用可离心的亲和柱、包括亲和柱和亲和柱的试剂盒。
• Method of determining a concentration of analytes of interest in a sample
  申请人：Aokin AG

  公开号：EP2048500A1

  公开（公告）日：2009-04-15

  Summary: The present invention relates to a method of determining a concentration of analytes of interest in a sample reaction mixture, which includes or is suspected to include the analytes of interest, comprising or consisting of the following steps: a) Measuring or providing intensities of the polarized fluorescence of one, two, three, four, five or more comparative reaction mixtures with differing concentrations of analytes of interest in vertical and horizontal direction over a given time period of the reaction, b) Measuring an intensity of the polarized fluorescence of a sample reaction mixture in vertical and horizontal direction over a given time period of the reaction, c) Determining preliminary concentrations of the analytes of interest in the sample reaction mixture by comparing the measured intensities of the sample reaction mixture at two, three, four, five or more time points of the reaction (tn = t0s + xn) with the intensities of the first, second, third, fourth, fifth and further comparative reaction mixture at the same time points of the reaction (tn = t0c + xn), d) Determining the margin of error for the preliminary concentration of the analytes of interest in the sample reaction mixture in step c) at the given time points (tn) and e) Determining the concentration of the analytes of interest in the sample reaction mixture by comparing the preliminary concentrations and the respective margin of error at the given time points (tn) and selecting the appropriate preliminary concentration or a mean value of preliminary concentrations to be the concentration of analytes of interest in the sample reaction mixture.

  摘要： 本发明涉及一种确定样品反应混合物中相关分析物浓度的方法，该混合物包括或疑似包括相关分析物，该方法包括或由以下步骤组成： a) 在反应的给定时间段内，测量或提供一种、两种、三种、四种、五种或更多种具有不同浓度的相关分析物的比较反应混合物在垂直和水平方向上的偏振荧光强度、 b) 在反应的给定时间段内，测量样品反应混合物在垂直和水平方向上的偏振荧光强度、 c) 将样品反应混合物在反应的两个、三个、四个、五个或更多时间点（tn = t0s + xn）的测量强度与第一、第二、第三、第四、第五和更多比较反应混合物在反应的相同时间点（tn = t0c + xn）的强度进行比较，确定样品反应混合物中相关分析物的初步浓度、 d) 在给定的时间点（tn），确定步骤 c）中样品反应混合物中相关分析物初步浓度的误差范围，以及 e) 通过比较给定时间点（tn）的初步浓度和各自的误差范围，确定样品反应混合物中相关分析物的浓度，并选择适当的初步浓度或初步浓度的平均值作为样品反应混合物中相关分析物的浓度。
• BIOLOGICAL DEGRADATION OF OCHRATOXIN A INTO OCHRATOXIN
  申请人：Centro di Ricerca per l'Enologia (CRA-ENO)

  公开号：EP2599876A1

  公开（公告）日：2013-06-05

  The invention relates to the use of a microorganism of the genus Brevibacterium for the biological degradation of ochratoxin A, in which the microorganism is preferably Brevibacterium casei, Brevibacterium linens, Brevibacterium iodinum or Brevibacterium epidermidis. In addition, the invention relates to a method for the production of ochratoxin α using said microorganism.

  本发明涉及使用乳杆菌属微生物对赭曲霉毒素 A 进行生物降解，其中的微生物最好是干酪乳杆菌、亚麻乳杆菌、碘乳杆菌或表皮乳杆菌。此外，本发明还涉及一种利用上述微生物生产赭曲霉毒素 α 的方法。
• Biological degradation of ochratoxin A into ochratoxin α
  申请人：Muñoz Moreno María Rosario

  公开号：US10004251B2

  公开（公告）日：2018-06-26

  The invention relates to the use of a microorganism of the genus Brevibacterium for the biological degradation of ochratoxin A, in which the microorganism is preferably Brevibacterium casei, Brevibacterium linens, Brevibacterium iodinum or Brevibacterium epidermidis. In addition, the invention relates to a method for the production of ochratoxin α using said microorganism.

  本发明涉及使用乳杆菌属微生物对赭曲霉毒素 A 进行生物降解，其中的微生物最好是干酪乳杆菌、亚麻乳杆菌、碘乳杆菌或表皮乳杆菌。此外，本发明还涉及一种利用上述微生物生产赭曲霉毒素 α 的方法。
• Fungicide for the treatment of fungal pathogens causing mycotoxins
  申请人：AGRONATURALIS LTD

  公开号：US10897906B2

  公开（公告）日：2021-01-26

  Fungal diseases and resulting mycotoxins are reduced or eliminated from plant tissues during crop growth or post-harvest during storage by treatment with an aqueous spray solution prepared from a fungicide composition of a bicarbonate salt containing a surfactant system to reduce the surface tension and contact angle of the spray solution on the plant surface thereby controlling the crystal size of the bicarbonate and re-distribution and adherence of the crystals to the crop vegetation and/or grains.

  在作物生长过程中或收获后贮藏过程中，使用由含有表面活性剂系统的碳酸氢盐杀真菌剂组合物制备的水喷雾溶液处理植物组织，可减少或消除真菌疾病和由此产生的霉菌毒素，从而降低喷雾溶液在植物表面的表面张力和接触角，从而控制碳酸氢盐晶体的大小以及晶体在作物植被和/或谷物上的再分布和附着。