chlordane | 57-74-9

• 物质功能分类: 分析化学 - 标准品 - 挥发性有机化合物(VOCs)
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 乙烯基卤化物
• 英文名称: chlordane
• 英文别名: Chlorindan；(1R,7S)-1,3,4,7,8,9,10,10-octachlorotricyclo[5.2.1.02,6]dec-8-ene
• CAS: 57-74-9；5103-71-9；5103-74-2
• 化学式: C₁₀H₆Cl₈
• 分子量: 409.782
• InChiKey: BIWJNBZANLAXMG-YQELWRJZSA-N

物化性质

• 熔点：
  106°C (estimate)
• 沸点：
  492.46°C (rough estimate)
• 密度：
  1.80
• 闪点：
  -18 °C
• 溶解度：
  与脂肪族和芳香族溶剂混溶 (Windholz et al., 1983)
• 物理描述：
  Chlordane (technical mixture and metabolites) appears as brown or amber very viscous liquid. Insoluble in water.
• 颜色/状态：
  Viscous, amber-colored liquid
• 气味：
  PENETRATING; AROMATIC; SLIGHTLY PUNGENT, LIKE CHLORINE
• 蒸汽密度：
  14.3 (NTP, 1992) (Relative to Air)
• 蒸汽压力：
  9.75X10-6 mm Hg @ 25 °C
• 亨利常数：
  2.93e-04 atm-m3/mole
• 稳定性/保质期：

  Dehydrohalogenates in presence of alkali

• 分解：
  Hazardous decomposition products: Toxic gases and vapors, such as hydrogen chloride, chlorine, phosgene, and carbon monoxide. ...
• 粘度：
  69 poises at 25 °C (about that of 95% glycerol); viscosity reduced by heating to 120-140 °F
• 燃烧热：
  -4,000 BTU/LB= -2,200 CAL/G= -93X10+5 JOULES/KG (EST)
• 表面张力：
  LIQUID SURFACE TENSION: 25 DYNES/CM= 0.025 N/M @ 20 °C (EST)
• 气味阈值：
  Odor low: 0.0084 mg/cu m; Odor high: 0.0419 mg/cu m
• 折光率：
  Index of refraction: 1.56-1.57 @ 25 °C/D

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

在连续28天每隔一天口服技术级氯丹的小鼠中，顺式和反式氯丹在第一天即在全身达到峰值水平，尽管反复给药，但随后降至较低水平；顺式和反式九氯和氧化氯丹在整个研究期间呈增加趋势。测试样本中顺式与反式氯丹的比例（分别为6:7）和顺式与反式九氯的比例（分别为1:4），以及实验结束时小鼠体内的比例（分别为5:3和1:7），表明反式氯丹比顺式氯丹更容易被代谢，顺式九氯比反式九氯更容易被代谢。随着反复给药，氯丹同分异构体的含量减少，而氧化氯丹的含量增加，这表明氯丹诱导了其自身的代谢。

In mice treated orally every other day for 28 days with technical chlordane, cis- and trans-chlordane reached peak levels in the whole body on the first day and declined to lower levels in spite of repeated dosing; cis- and trans-nonachlor and oxychlordane increased during the entire study period. The ratio of cis- to trans-chlordane and cis- to trans-nonachlor in the test sample (6:7 and 1:4, respectively) and in the mouse body at termination of the experiment (5:3 and 1:7, respectively) suggests that trans-chlordane is metabolized more readily than cis-chlordane and that cis-nonachlor is metabolized more readily than trans-nonachlor. The decreasing content of the chlordane isomers and the increasing content of oxychlordane with repeated dosing suggests that chlordane induces its own metabolism.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯化丹（chlordane）和氧化氯丹通过大鼠肝微粒体的代谢在体外进行了研究。从雄性Sprague-Dawley大鼠制备的肝微粒体与12.3纳米摩尔氯化丹在有无还原型NADPH生成系统的存在下，在空气或氮气或一氧化碳气氛中于37°C下孵化15分钟。大鼠肝微粒体与11.8纳米摩尔氧化氯丹在空气和NADPH的存在下，以及有无0.2 mM 1,1,1-三氯丙烯-2,3-氧化物的存在下于37°C下孵化15分钟。在NADPH存在和空气条件下，大约11%的氯化丹被代谢。当反应混合物中不存在NADPH时，不发生代谢。当氮气替代空气时，氯化丹的降解减少了67%。在一氧化碳气氛下，不发生氯化丹的代谢。当孵化混合物中不存在1,1,1-三氯丙烯-2,3-氧化物时，氧化氯丹被大量代谢。当其存在时，1,1,1-三氯丙烯-2,3-氧化物导致代谢的氧化氯丹量急剧减少。作者得出结论，氯化丹的氧化降解是由肝微粒体细胞色素P-450催化的。氧化氯丹是氯化丹的氧化代谢物，可被肝环氧化物水解酶进一步代谢。

The metabolism of trans-chlordane (chlordane) and oxychlordane by rat liver microsomes was studied in vitro. Liver microsomes prepared from male Sprague-Dawley rats were incubated with 12.3 nmol chlordane in the presence or absence of a reduced NADPH generating system under air or atmospheres of nitrogen or carbon monoxide for 15 min at 37 degrees C. Rat liver microsomes were incubated with 11.8 nmol oxychlordane in air with NADPH and in the presence or absence of 0.2 mM 1,1,1-trichloropropene-2,3-oxide for 15 min at 37 degrees C. Approximately 11% of the chlordane was metabolized in the presence of NADPH and under air. No metabolism occurred when NADPH was absent from the reaction mixture. Degradation of chlordane was decreased by 67% when nitrogen was substituted for air. No chlordane metabolism occurred under the carbon-monoxide atmosphere. Oxychlordane was metabolized to an appreciable extent when 1,1,1-trichloropropene-2,3-oxide was absent from the incubation mixture. When present, 1,1,1-trichloropropene-2,3-oxide caused a sharp decrease in the amount of oxychlordane that was metabolized. The authors conclude that oxidative degradation of chlordane is catalyzed by hepatic microsomal cytochrome P-450. Oxychlordane, an oxidized metabolite of chlordane, is metabolized further by hepatic epoxide-hydrolase.

来源:Hazardous Substances Data Bank (HSDB)

代谢

代谢过程似乎主要是氧化性的，涉及肝脏微粒体细胞色素P-450。环氧水合酶可能是参与进一步降解氧氯丹的主要酶，但这个过程在动物和人类中似乎进行得较慢。此外，还原脱卤作用，可能导致了活性自由基中间体的形成，这可能在氯丹的毒性中起着重要作用。

Metabolism appears to be largely oxidative, involving hepatic microsomal cytochrome P-450. Epoxide hydrolase is probably the predominant enzyme involved in further degradation of oxychlordane, but the process appears to be slow in animals and humans. In addition, reductive dehalogenation, probably resulting in the formation of reactive free radical intermediates, may be important in the toxicity of chlordane.

来源:Hazardous Substances Data Bank (HSDB)

代谢

氯丹分子的代谢涉及四条途径...第一种提出的代谢途径是从分子第三位羟基化开始，形成3-羟基氯丹。这一反应被认为是微粒体多功能氧化酶（MFO）系统介导的。3-羟基氯丹的脱水导致1,2-二氯氯代烯，并最终形成其他代谢物，如氧化氯丹和L-羟基-2-氯氯代烯。或者，3-羟基氯丹可能会经历氯原子被羟基取代，形成单氯二羟基和三羟基衍生物。第二条途径从脱氢氯化开始形成七氯。这一反应的机制尚未完全了解，但认为是细胞色素P-450系统或谷胱甘肽-S-转移酶型酶介导的。七氯的进一步代谢导致1-羟基氯代烯、七氯环氧或最终形成1-氯-2,3-二羟基二氢氯丹。第三条途径从氯丹的脱卤开始形成L-氯二氢氯丹，可能由微粒体MFO系统介导。进一步的反应可能涉及水解并与葡萄糖醛酸结合。第四条代谢途径可能是最不为人所知的，涉及水解去除一个氯原子，并用一个羟基取代，形成L-氯-2-羟基氯丹氯醇。这一产物可能会进一步代谢，形成二氢氯丹的单氯二羟基和三羟基衍生物。对大鼠肝微粒体的研究表明，细胞色素P-450可能是催化反式氯丹降解的最重要酶。环氧化物水解酶可能是催化氧化氯丹降解的主要酶。还原脱卤，产生自由基，在氯丹的毒性中也可能很重要。

Metabolism for the chlordane molecule involves four routes ... The first proposed metabolic route starts with hydroxylation at position three of the molecule to form 3-hydroxychlordane. This reaction is thought to be mediated by the microsomal mixed-function oxidase (MFO) system. Dehydration of 3-hydroxychlordane leads to 1,2-dichlorochlordene and eventually to other metabolites such as oxychlordane and l-hydroxy-2-chlorochlordene. Alternatively, 3-hydroxychlordane may undergo replacement of chlorines by hydroxyl groups to form monochlorodihydroxylated and -trihydroxylated derivatives. The second pathway starts with dehydrochlorination to form heptachlor. The mechanism of this reaction is not completely understood but is thought to be mediated by the cytochrome P-450 system and/or by glutathione-S-transferase type enzymes. Further metabolism of heptachlor leads to 1-hydroxychlordene, heptachlor epoxide, or eventually to 1-chloro-2,3-dihydroxydihydrochlordene. The third pathway starts with dehalogenation of chlordane to form l-chlorodihydrochlordene, probably mediated by microsomal MFO systems. Further reactions probably involve hydrolysis and conjugation with glucuronic acid. The fourth metabolic pathway, and probably the least understood, involves hydrolytic removal of a chlorine atom and its replacement by a hydroxyl group to form l-chloro-2-hydroxychlordene chlorohydrin. This product may undergo further metabolism to form monochlorodihydroxy- and trihydroxy- derivatives of dihydrochlordene. Studies with rat hepatic microsomes suggest that cytochrome P-450 may be the most important enzyme to catalyze degradation of trans-chlordane. Epoxide hydrolase is probably the predominant enzyme to catalyze degradation of oxychlordane. Reductive dehalogenation, with the production of free radicals, may also be important in the toxicity of chlordane.

来源:Hazardous Substances Data Bank (HSDB)

代谢

活体和体外大鼠研究表明，氯化丹存在多种生物转化途径，并且代谢物包括：顺式氯化丹、1,2-二氯氯化烯、氧化氯化丹、1-羟基-2-氯氯化烯、1-羟基-2-氯-2,3-环氧化氯化烯、氯化丹氯醇和1,2-顺式-二羟基二氢氯化丹，以及七氯的代谢物。体外研究表明，大鼠和人类的肝脏几乎具有相同的降解氯化丹的能力，不同的是人类肝脏将顺式九氯转化为顺式氯化丹的能力较弱。

In vivo and in vitro studies in rats have revealed /several/ routes of biotransformation of chlordane and shown that the metabolites include: trans-chlordane, 1,2-dichlorochlordene, oxychlordane, 1-hydroxy-2-chlorochlordene, 1-hydroxy-2-chloro-2,3-epoxy chlordene, chlordene chlorohydrin, and 1,2-trans-dihydroxy dihydrochlordene, as well as metabolites of heptachlor. In vitro studies showed that the liver of rat and man have almost identical capacity to degrade chlordane except that human liver has little capacity to convert trans-nonachlor to trans-chlordane.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：B2组可能的人类致癌物

Cancer Classification: Group B2 Probable Human Carcinogen

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

证据权重特征：根据1986年致癌风险评估指南，氯丹被归类为B2级，可能是人类致癌物。 ...人类致癌性数据：证据不足。动物致癌性数据：足够。

WEIGHT OF EVIDENCE CHARACTERIZATION: Chlordane is classified as B2, probable human carcinogen, using the 1986 Guidelines for Carcinogen Risk Assessment. ...HUMAN CARCINOGENICITY DATA: Inadequate evidence. ANIMAL CARCINOGENICITY DATA: Sufficient.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：对于氯丹和七氯对人类致癌性的证据不足。对于氯丹和七氯在实验动物中的致癌性有足够的证据。总体评估：氯丹和七氯可能对人类致癌（2B组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of chlordane and heptachlor. There is sufficient evidence in experimental animals for the carcinogenicity of chlordane and heptachlor. Overall evaluation: Chlordane and heptachlor are possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

A3; 已确认的动物致癌物，对人类的相关性未知。

A3; Confirmed animal carcinogen with unknown relevance to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

国际癌症研究机构2B类, 国立职业安全与健康研究所-致癌性, 阈限值-吸入危险, 环境保护局B2类

IARC-2B, NIOSH-Ca, TLV-A3, EPA-B2

来源:Occupational Safety and Health Administration (OSHA)

吸收、分配和排泄

通过皮肤吸收，更容易通过肺部，以及从胃肠道吸收。

...Absorbed through skin, more readily via the lungs, and from ... /gastrointestinal/ tract.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在儿童中，脂肪浓度在单次剂量后继续上升到摄入后的第8天，并且3个月后脂肪-血清分配比为1470:1。

In a child, fat concentration ... after single dose continued to rise through 8th post-ingestion day, and after 3 months fat-serum partition was 1470:1.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

主要排泄途径是胆汁，尽管几乎所有有机氯化合物都会产生可测量的尿液代谢物。许多未经代谢的杀虫剂被肠道有效重吸收（肠肝循环），大大减缓了粪便排泄。/固体有机氯杀虫剂/

The chief route of excretion is biliary, although nearly all organochlorines yield measurable urinary metabolites. ... Many of the unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic circulation) substantially retarding fecal excretion. /Solid organochlorine insecticides/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

... 接受静脉注射的Wistar大鼠 ... (14)C-α-氯丹显示，在60小时内，总注射活性的29%通过粪便排出，仅有1%通过尿液排出。/顺式异构体/

... Wistar rats that received iv ... (14)C-alpha-chlordane showed that 29% of total injected radioactivity was excreted within 60 hr in feces and only 1% was excreted in urine. /cis-isomer/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,N,Xi,F,T
• 安全说明：
  S16,S26,S33,S36,S36/37,S45,S60,S61,S7
• 危险类别码：
  R21/22,R11,R39/23/24/25,R40,R36/37/38,R50/53,R23/24/25
• WGK Germany：
  2
• 海关编码：
  29038200
• 危险品运输编号：
  2995
• RTECS号：
  PB9800000
• 包装等级：
  II
• 危险类别：
  6.1(b)

制备方法与用途

类别：农药
毒性分级：高毒
急性毒性：

• 口服-大鼠 LD50: 500 毫克/公斤
• 口服-小鼠 LD50: 125 毫克/公斤

可燃性危险特性：热分解排出有毒氯化物烟雾

储运特性：库房低温通风干燥，与食品原料分开存放

灭火剂：水、二氧化碳、泡沫、干粉