黄曲霉毒素 B1 | 1162-65-8

• 物质功能分类: 分析化学 - 标准品 - 食品和化妆品标准品
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 黄曲霉毒素 B1
• 中文别名: 黄曲霉毒素B1；黄曲霉素B1
• 英文名称: aflatoxin B1
• 英文别名: AFB1；alfatoxin B₁；(3S,7R)-11-methoxy-6,8,19-trioxapentacyclo[10.7.0.02,9.03,7.013,17]nonadeca-1,4,9,11,13(17)-pentaene-16,18-dione
• CAS: 1162-65-8
• 化学式: C₁₇H₁₂O₆
• 分子量: 312.279
• InChiKey: OQIQSTLJSLGHID-WNWIJWBNSA-N

物化性质

• 熔点：
  268-269 °C
• 比旋光度：
  D -558° (c = 0.1 in CHCl3); D -480° (c = 0.1 in DMF)
• 沸点：
  372.21°C (rough estimate)
• 密度：
  1.2810 (rough estimate)
• 闪点：
  2 °C
• 溶解度：
  DMF：20mg/mL； DMF:PBS(pH 7.2)(1:1)：0.5 mg/ml；二甲基亚砜：12mg/mL
• LogP：
  2.039 (est)
• 物理描述：
  Aflatoxin b-1 appears as colorless to pale yellow crystals or white powder. Exhibits blue fluorescence. (NTP, 1992)
• 颜色/状态：
  Crystals ... exhibits blue fluorescence
• 蒸汽压力：
  2.65X10-10 mm Hg at 25 °C (est)
• 稳定性/保质期：

  1. 如果遵照规格使用和储存，则不会分解，没有已知的危险反应，避免与氧化物接触。

  2. 吸入、口服或与皮肤接触均极其有毒，可能致癌。操作时应穿戴适当的防护服，避免暴露。

• 旋光度：
  Specific optical rotation (0.1 in chloroform): -558 deg/D; (0.1 in dimethylformamide): -480 deg at 25 °C/D
• 分解：
  When heated to decomposition it emits acrid smoke.
• 碰撞截面：
  161 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

ADMET

代谢

黄曲霉毒素预计会通过4种途径进行生物转化：（i）通过对两个融合呋喃环交界处碳原子的羟基化，黄曲霉毒素B1转化为黄曲霉毒素M1，这在哺乳动物肝脏中在一定程度上发生，（ii）通过氧化去甲基化单一芳香甲氧基取代基，产生黄曲霉毒素P1...（iii）通过醇醚双键的水合作用会形成半缩酮，黄曲霉毒素B1在豚鼠、小鼠和鸟类肝脏中转化为黄曲霉毒素半缩酮B2a，（iv）通过环戊烯酮环的还原，产生二氢黄曲霉毒素，但这种生物转化似乎仅限于鸟类，可能与哺乳动物无关。

Aflatoxins would be expected to undergo biotransformations by 4 routes: (i) by hydroxylation of carbon atom at junction of the two fused furan rings, aflatoxin B1 is converted into aflatoxin M1, & this occurs to some extent in mammalian liver, (ii) oxidative o-demethylation of single aromatic methoxy-substituent gives aflatoxin P1 ... (iii) hydration of vinyl ether double bond would afford hemiacetals, & aflatoxin B1 is ... converted into aflatoxin hemiacetal B2a in guinea pig, mouse, & avian livers, (iv) & by reduction of cyclopentenone ring, dihydroaflatoxicol, but this biotransformation seems to be confined to avian species, & may be irrelevant to mammals.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在恒河猴中，通过静脉注射...氯仿可溶的尿液排泄产物包括黄曲霉毒素M1（剂量的2.3%）以及至少3种其他未识别的...化合物，以及未改变的黄曲霉毒素B1（0.01-0.10%）。尿液中的氯仿不溶代谢物通过离子交换方法分离；主要亚组分由黄曲霉毒素P1-β-葡萄糖醛酸苷组成。尿液中的黄曲霉毒素P1-β-葡萄糖醛酸苷约占剂量的20%；其中17%为葡萄糖醛酸苷，3%为硫酸酯，1%为未结合的酚类。

In rhesus monkeys, injected ip ... the chloroform soluble urinary excretory products included aflatoxin M1 (2.3% of dose) & at least 3 other, unidentified ... compounds, as well as unchanged aflatoxin B1 (0.01-0.10%). Chloroform insoluble metabolites in urine were separated by ion exchange methods; major sub fraction consisted of aflatoxin P1 beta-glucuronide. Urinary aflatoxin P1 beta glucuronide represented about 20% of the dose; 17% as glucuronide, 3% as sulfate ester, & 1% as unconjugated phenol.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类肝脏匀浆体外代谢黄曲霉毒素B1的研究表明，黄曲霉毒素B1-2,3环氧物被产生。

Investigations of the in vitro metabolism of aflatoxin B1 by liver homogenates from humans ... indicate that aflatoxin B1-2,3 epoxide is produced ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

黄曲霉毒素B1的代谢在虹鳟鱼肝细胞中被研究。细胞内DNA加合物的形成与黄曲霉毒素B1剂量线性相关，并且与体内形成的加合物在性质上相似。在最初的小时内，加合物积累的代谢速率是恒定的，之后速率逐渐增加并逐渐降低。主要未结合的黄曲霉毒素B1代谢产物，包括黄曲霉毒素醇、黄曲霉毒素M1和极性共轭物的产生速率在前一个小时内保持恒定，但随后随着DNA结合的变化而变化。

Metabolism of Aflatoxin B1 was examined in isolated hepatocytes from rainbow trout. Intracellular DNA adduct formation was linearly related to aflatoxin B1 dose, & qualitatively similar to adducts formed in vivo. The rate of metabolism of adduct accumulation was constant during the first hr, after which an increased & gradual decrease in rate routinely occurred. Relative rates of production of the major unbound aflatoxin B1 metabolites aflatoxicol, aflatoxin M1 & polar conjugates, also remained constant over the 1st hr of preparation age, but subsequently changed in manner consistent with the changes in DNA binding.

来源:Hazardous Substances Data Bank (HSDB)

代谢

黄曲霉毒素B1已知的人类代谢物包括黄曲霉毒素B1-外-8,9-氧化物、黄曲霉毒素M1和黄曲霉毒素Q1。

Aflatoxin b1 has known human metabolites that include Aflatoxin B1- exo-8,9-oxide, Aflatoxin M1, and Aflatoxin Q1.

来源:NORMAN Suspect List Exchange

毒理性

• 致癌性证据

评估：有足够的人类证据证明自然发生的黄曲霉毒素混合物具有致癌性。有足够的人类证据证明黄曲霉毒素B1具有致癌性。有足够的实验动物证据证明自然发生的黄曲霉毒素混合物以及黄曲霉毒素B1、G1和M1具有致癌性。总体评估：自然发生的黄曲霉毒素对人类具有致癌性（第1组）。/自然发生的黄曲霉毒素/

Evaluation: There is sufficient evidence in humans for the carcinogenicity of naturally occurring mixtures of aflatoxins. There is sufficient evidence in humans for the carcinogenicity of aflatoxin B1. There is sufficient evidence in experimental animals for the carcinogenicity of naturally occurring mixtures of aflatoxins and aflatoxins B1, G1 and M1. Overall evaluation: Naturally occurring aflatoxins are carcinogenic to humans (Group 1). /Naturally occurring aflatoxins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

黄曲霉毒素：已知的人类致癌物。

Aflatoxins: known to be human carcinogens. /Aflatoxins/

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

• 相互作用

胡椒碱已知会改变药物的生物转化。已经描述了胡椒碱对大鼠体内(3)H-黄曲霉毒素B1的代谢激活和分布的影响。胡椒碱在体外以剂量依赖性方式显著抑制了肝微粒体催化的(3)H AFB1与牛胸腺DNA的结合。与对照组相比，预先用胡椒碱处理的 rats 在血浆和检查的组织中积累了相当多的(3)H AFB1放射性。然而，胡椒碱对体内肝脏(3)H AFB1-DNA结合没有影响，这可能是由于胡椒碱对肝脏细胞质谷胱甘肽S-转移酶活性的无效影响。胡椒碱处理的 rats 肝微粒体显示出在体内增强(3)H AFB1与牛胸腺DNA结合的趋势。因此，胡椒碱对AFB1代谢的影响与SKF 525-A对外源化合物生物转化的作用模式非常相似。

Piperine is known to modify the biotransformation of drugs. The effect of piperine on the metabolic activation and distribution of (3)H-aflatoxin B1 in rats has been described. Piperine markedly inhibited liver microsome catalysed (3)H AFB1 binding to calf thymus DNA in vitro, in a dose dependent manner. Rats pretreated with piperine accumulated considerable (3)H AFB1 radioactivity in plasma and in the tissues examined as compared to the controls. However, piperine had no influence on hepatic (3)H AFB1-DNA binding in vivo, which could possibly be due to the null effect of piperine on liver cytosolic glutathione 5-transferase activity. Piperine treated rat liver microsomes demonstrated a tendency to enhance (3)H AFB1 binding to calf thymus DNA in vivo. The effect of piperine on AFB1 metabolism thus closely resembles the mode of action of SKF 525-A on biotransformation of foreign compounds.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

北京鸭模型被用来研究先天鸭乙型肝炎病毒感染和黄曲霉毒素B1（AFB1）暴露在诱导和发展肝癌中的作用。AFB1以两种剂量（0.08和0.02 mg/kg）通过每周一次的腹腔注射给感染或未感染鸭乙型肝炎病毒的鸭子，从孵化后第三个月开始直到它们被宰杀（2.3年后）。有两个未用AFB1处理的对照组鸭子（其中一组感染了鸭乙型肝炎病毒）被观察了相同的时间。每个实验组包括13-16只鸭子。与未感染病毒仅用AFB1处理的鸭子和其他对照组鸭子相比，感染了鸭乙型肝炎病毒并用AFB1处理的鸭子观察到更高的死亡率。在未感染病毒但用高剂量和低剂量AFB1处理的鸭子中，分别有10只中的3只和2只发展出了肝癌；在高剂量AFB1处理的感染鸭子中，6只中有3只观察到肝癌，而在低剂量AFB1处理的感染鸭子中没有肝癌。两个对照组中没有观察到肝癌。感染了鸭乙型肝炎病毒并用AFB1处理的鸭子与其他组相比，显示出更明显的门脉周围炎症变化、纤维化和局部坏死。所有携带鸭乙型肝炎病毒的鸭子在整个观察期间持续带毒。与仅感染的对照组相比，AFB1处理的动物在肝脏和血清中的病毒DNA滴度升高是常见现象。尽管在一个AFB1处理的鸭子的肝细胞癌中检测到了病毒多聚体DNA形式的积累，但没有观察到鸭乙型肝炎病毒DNA整合到宿主基因组中。

...A Pekin duck model /was used/ to examine the effect of congenital duck hepatitis B virus infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to duck hepatitis B virus infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by ip injection once a wk from the third month posthatch until they were sacrificed (2.3 yr later). Two control groups of ducks not treated with AFB1 (one of which was infected with duck hepatitis B virus) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with duck hepatitis B virus and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with duck hepatitis B virus and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All duck hepatitis B virus carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No duck hepatitis B virus DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

注射到猴子体内四天后，剂量的5.6%仍然被肝脏保留，主要与肝蛋白结合。在口服黄曲霉毒素B1后，恒河猴在头四天内以黄曲霉毒素M1的形式排出了大约20%；未改变的黄曲霉毒素B1仅占很小一部分，而黄曲霉毒素B1β-葡萄糖苷酸占5%（其中3.3%为葡萄糖苷酸形式，1.2%为硫酸盐结合物）。另外5%的剂量以黄曲霉毒素B1和黄曲霉毒素M1的形式随粪便排出。

Four days after /IP/ injection into monkeys, 5.6% of the dose was still retained by the liver, principally bound to liver proteins. After oral dose of aflatoxin B1, rhesus monkeys excreted about 20% as aflatoxin M1 during days 1-4; unchanged aflatoxin B1 accounted only for a small proportion & aflatoxin B1 beta-glucuronide accounted for 5% (3.3% as glucuronide & 1.2% as sulfate conjugate). Another 5% of the dose was excreted as aflatoxin B1 & aflatoxin M1 in the feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

黄曲霉毒素醇、黄曲霉毒素B1和M1在喂食了估计的B1半数致死剂量（0.1毫克/千克体重）的大肠杆菌中发现了，这些大肠杆菌是通过黄曲霉米培养物提供的，以及喂食了自然污染的饲料，饲料中含有400纳克/克的黄曲霉毒素B1，持续喂食了14天。在大肠杆菌中，B1和M1被发现时，除了肾脏外，所有组织的水平都大致相同，在肾脏中，M1是最主要的黄曲霉毒素。

Aflatoxicol & aflatoxin B1 & M1 were found in tissues of kidney, liver, & muscle of feeder pigs fed estimated LD50 dose of B1 (0.1 mg/kg body wt) provided as rice culture of aspergillus flavus & of market wt pigs, fed naturally contaminated feed containing aflatoxin B1 at level of 400 ng/g from corn for 14 days. B1 & M1, when found in the feeding experiment, were at about the same levels in all tissues except the kidney, in which M1 was the most dominant aflatoxin.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

黄曲霉毒素以代谢物黄曲霉毒素M1的形式从哺乳动物的乳汁中排出。在给予单次口服黄曲霉毒素的牛中，牛奶和尿液中检测到的总量的85%是在处理后的前48小时内发现的。四天后牛奶中没有了，六天后尿液或粪便中也没有了。牛奶中发现的黄曲霉毒素总量是摄入量的0.39%。……给予的黄曲霉毒素B1小于0.6%通过牛奶排出。牛奶中排出的黄曲霉毒素量与产奶量无关，而且在停止喂食有毒饲料的三到四天后，它会从牛奶中消失。

Aflatoxin is excreted in the form of its metabolite aflatoxin M1 in the milk of lactating animals. In cattle given a single oral dose of aflatoxin, 85% of the total amount found in the milk and urine were detected in the first 48 hours after treatment. There was none in the milk after four days, nor in the urine or feces after six days. The total aflatoxin found in the milk was 0.39% of that ingested. ... Less than 0.6% of administered aflatoxin B1 was excreted in the milk. The amount of aflatoxin excreted in milk is unrelated to milk yield, and it disappears from the milk three to four days after the feeding of toxic meal is discontinued.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

使用黄曲霉毒素B1，环标记或甲氧基标记的碳-14已显示出大鼠在24小时内排出了单次腹腔注射剂量的70-80%。

Using aflatoxin B1, ring-labelled or methoxy-labelled with (14)carbon have shown that rats excrete 70-80% of a single ip dose within 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+,T,Xn,F
• 安全说明：
  S16,S24,S26,S36,S45,S53,S7
• 危险类别码：
  R20/21/22,R36/38,R36,R26/27/28,R45,R48/23/24/25,R11,R23/24/25,R39/23/24/25,R65,R46
• WGK Germany：
  3
• 海关编码：
  29322090
• 危险品运输编号：
  UN 3462 6.1/PG 1
• 储存条件：
  密封于0°C至4°C之间保存。

SDS

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模块 1. 化学品
1.1 产品标识符
: 黄曲霉素 B1 来源于黄曲霉
产品名称
1.2 鉴别的其他方法
无数据资料
1.3 有关的确定了的物质或混合物的用途和建议不适合的用途
仅用于研发。不作为药品、家庭或其它用途。

---

模块 2. 危险性概述
2.1 GHS-分类
急性毒性, 经口 (类别 1)
急性毒性, 吸入 (类别 2)
急性毒性, 经皮 (类别 1)
致癌性 (类别 1B)
2.2 GHS 标记要素，包括预防性的陈述
象形图
警示词 危险
危险申明
H300 吞咽致命。
H310 皮肤接触致命。
H330 吸入致命。
H350 可能致癌。
警告申明
预防
P201 在使用前获取特别指示。
P202 在读懂所有安全防范措施之前切勿操作。
P260 不要吸入粉尘/ 烟/ 气体/ 烟雾/ 蒸汽/ 喷雾。
P262 严防进入眼中、接触皮肤或衣服。
P264 操作后彻底清洁皮肤。
P270 使用本产品时不要进食、饮水或吸烟。
P271 只能在室外或通风良好之处使用。
P280 穿戴防护手套/ 防护服。
P284 戴呼吸防护装置。
响应
P301 + P310 如果吞下去了: 立即呼救解毒中心或医生。
P302 + P350 如果在皮肤上: 仔细地用大量肥皂和水洗。
P304 + P340 如吸入: 将患者移到新鲜空气处休息，并保持呼吸舒畅的姿势。
P310 立即呼叫中毒控制中心或医生.
P320 紧急具体治疗(见本标签上提供的急救指导)。
P330 漱口。
P361 立即去除/脱掉所有沾染的衣服。
P363 沾染的衣服清洗后方可重新使用。
储存
P403 + P233 存放于通风良的地方。 保持容器密闭。
P405 存放处须加锁。
处置
P501 将内容物/