Isatidine is not converted into pyrrolic metabolites by isolated rat liver microsomes. It is, However, reduced to retrorsine in the intestinal tract of rats, possibly by the gut flora, thus accounting for the large increase in toxicity when isatidine is administered by mouth rather than parenterally.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
没有关于人类的数据。动物致癌性的证据有限。总体评估：第3组：该物质对人类致癌性无法分类。
No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.
Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/
Presentation depends on the active toxic agent. In most cases, vomiting, abdominal pain, and diarrhea occur within 60 to 90 minutes of significant ingestion. With some toxins, severe gastroenteritis may result in massive fluid and electrolyte loss. ... Maintain open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat coma, seizures, arrhythmias, and hypotension if they occur. Replace fluid loss caused by gastroenteritis with intravenous crystalloid solutions. ... Administer activated charcoal if available ... Gastric emptying is not necessary if activated charcoal is given promptly. /Plants and Herbal Medicines: Group 1/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
人类毒性摘录
人类暴露研究/报告指出，人类摄入吡咯烷生物碱类中毒的两个主要来源是：食用了被含有生物碱的杂草污染的谷物和使用含有生物碱的草药进行药用和饮食目的。...在 South Asia 发生的三大疾病爆发中有两个发生在 central India 的同一地点，另一个发生在 North-West Afghanistan。第一次在印度的爆发发生在 central India 的 5 个部落村庄，时间是 1972-73 年。...在这些村庄的 2060 名总人口中，调查了 71 户家庭，共 366 名成员。在这些成员中，在调查开始前有 39 例病例发生，其中 19 例已经死亡。发病率是 1.1%，病死率是 50%。所有病例都发生在 20 户家庭中。在许多家庭中，有多个成员受到影响。在一户家庭中，5 例中有 4 例死亡。...尽管认为是由吡咯烷生物碱类污染引起的，但这次疫情的原因尚未确定。1975 年，同一地点再次爆发疫情...。共有 486 人受到影响，报告了 67 例病例，其中 28 例（46%）死亡。有很强的家族病史...。在后来的调查中，研究了 108 名患者，估计病死率为 63%。这一次，确定疫情的原因是植物 Crotalaria nana Burm，这种植物在他们主食作物小米（Panicum miliare）的田地里生长。在收获过程中，这种植物的种子与谷物混合在一起。这些有毒种子含有被确认为与单绿原碱非常相似的吡咯烷生物碱大环酯。估计总生物碱含量为 5.3 g/kg，以单绿原碱表示。报告指出，未受影响家庭的小米种子污染水平为 0-3.4 g/kg，受影响家庭的污染水平为 0-19 g/kg...。/吡咯烷生物碱/
/HUMAN EXPOSURE STUDIES/ The two main sources of pyrrolizidine alkaloid poisoning reported in human beings are the consumption of cereal grain contaminated by weeds containing the alkaloids and the use of alkaloid-containing herbs for medicinal and dietary purposes. ...Three of the largest outbreaks of the disease have been reported from South Asia, two from the same site in central India and one from North-West Afghanistan. The first Indian outbreak... occurred in a group of 5 tribal villages in central India in 1972-73. ...Out of a total population of 2,060 in these villages, 71 households with 366 members were investigated. Among these, 39 cases had developed and 19 had died before commencement of the investigations. The incidence rate was 1.1% and the case fatality rate was 50%. All cases occurred among 20 households. In many households, several members were affected. In one household, 4 out of 5 cases died. ...The etiological factor of this outbreak was not established, though dietary contamination with pyrrolizidine alkaloids was considered. A second outbreak occurred at the same site in 1975... . A total population of 486 was affected, 67 cases were reported, of whom 28 (46%) had died. There was a strong family history... . In a later survey, 108 patients were studied and the mortality rate was estimated to be 63%. This time the etiological factor was identified as the plant Crotalaria nana Burm, which had been growing in the fields of millet (Panicum miliare), their staple food crop. The seeds of this plant became mixed with the cereal grain during harvesting. The toxic seeds contained pyrrolizidine alkaloids that were identified as a macrocyclic ester closely similar to monocrotaline. The total alkaloid content was estimated to be 5.3 g/kg of seed, expressed as monocrotaline. The levels of contamination of the millet with seeds were reported to be 0-3.4 g/kg in the unaffected and 0-19 g/kg in the affected households... . /Pyrrolizidine alkaloids/
