Metabolites of ortho-dichlorobenzene (o-DCB) were identified by gas chromatography (GC) and mass spectrometry (MS) in urine samples of exposed chemical factory workers. The three workers were exposed to 1 to 4 parts per million o-DCB used as a solvent. ... The GC total ion chromatograms of the urine samples contained peaks corresponding to the retention times of a standard containing 2,3-dichlorophenol, 3,4-dichlorophenol, 3,4-dichlorocatechol, and 4,5-dichlorocatechol...
Microsomes were prepared from livers obtained from male Wistar-rats pretreated with phenobarbital, 3-methylcholanthrene, isosafrole, or dexamethasone. Reversed phase high performance liquid chromatography analysis was performed to identify the metabolites of 1,2-dichlorobenzene (1,2-DICB) and 1,4-dichlorobenzene (1,4-DICB). Covalent binding of 1,2-DICB and 1,4-DICB to microsomal protein and DNA was determined, and molecular orbit computer calculations were conducted. The major metabolites of both dichlorobenzene isomers were dichlorophenols and dichlorohydroquinones. The metabolite 2,5-dichlorophenol was associated with 1,2-DICB, and the metabolites 2,3-dichlorophenol and 3,4-dichlorophenol were associated with 1,4-DICB. ... Covalent binding of 1,2-DICB and 1,4-DICB metabolites with protein was observed, while DNA binding occurred only to a very small extent. ....
1,2-Dichlorobenzene gave 3,4-dichlorophenol with smaller amounts of 2,3-dichlorophenol, 3,4- and 4,5-dichlorocatechol and 3,4-dichlorophenylmercapturic acid also observed; 1,3-dichlorobenzene gave 2,4-dichlorophenol as the major product with 3,5-dichlorophenol, 3,4-dichlorocatechol, and 2,4-dichlorophenylmercapturic acid also identified; 1,4-dichlorobenzene gave 2,5-dichlorophenol as the major metabolite with 2,5-dichlorquinol identified as a minor product.
... To investigate the relation between metabolism and toxicity of 1,2-dichlorobenzene (1,2-DCB), the biotransformation, tissue distribution, blood kinetics, and excretion at three different oral dose levels (5, 50 and 250 mg/kg) of the radiolabelled compound were investigated in the male Wistar rat. A toxic dose level (250 mg/kg...) was included. ... The concentration of parent chemical was essentially constant during 3 and 6 hr for the mid- and high-dose level respectively, and then declined. 1,2-DCB could only be detected in blood in the first 2 hr after administration of the 5-mg/kg dose. The major route of biotransformation was via the glutathione pathway and 60% of the urinary metabolites were mercapturic acids. In addition, the major metabolites in bile were conjugates of glutathione. Other major metabolites in urine were the sulfate conjugates of 2,3- and 3,4-dichlorophenol (DCP). No significant differences in metabolic profiles were observed between the different doses. Induction with phenobarbital resulted in the increased excretion of sulfate conjugates (30% in the induced rat, 20% in the control rat), mainly the conjugate of 3,4-DCP...
来源:Hazardous Substances Data Bank (HSDB)
代谢
2,3-二氯苯酚是1,2-二氯苯的人类已知代谢物。
2,3-dichlorophenol is a known human metabolite of 1,2-dichlorobenzene.
Neurotoxin - Other CNS neurotoxin
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.
Nephrotoxin - The chemical is potentially toxic to the kidneys in the occupational setting.
Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect
Other Poison - Uncoupler
Dermatotoxin - Skin burns.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Phenols and related compounds/
/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 necessary. 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 ... . Administer activated charcoal ... . Do not use emetics. Cover skin burns with dry, sterile dressings after decontamination ... . Maintain body temperature. /Phenols and related compounds/
/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 ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. DIRECT PHYSICIAN ORDER ONLY ... Treat seizures with diazepam or lorazepam. ... Use proparacaine hydrochloride to assist eye irrigation ... . /Phenols and related compounds/
/SIGNS AND SYMPTOMS/ SYMPTOMATOLOGY: Burning pain in mouth and throat. White necrotic lesions in mouth, esophagus and stomach. Abdominal pain, vomiting ... and bloody diarrhea. Pallor, sweating, weakness, headache, dizziness, tinnitus. Shock: Weak irregular pulse, hypotension, shallow respirations, cyanosis, pallor, and a profound fall in body temperature. Possibly fleeting excitement and confusion, followed by unconsciousness. ... Stentorous breathing, mucous rales, rhonchi, frothing at nose and mouth and other signs of pulmonary edema are sometimes seen. Characteristic odor of phenol on the breath. Scanty, dark-colored ... urine ... moderately severe renal insufficiency may appear. Methemoglobinemia, Heinz body hemolytic anemia and hyperbilirubinemia have been reported. ... Death from respiratory, circulatory or cardiac failure. If spilled on skin, pain is followed promptly by numbness. The skin becomes blanched, and a dry opaque eschar forms over the burn. When the eschar sloughs off, a brown stain remains. /Phenol/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
由于二氯酚类化合物具有高脂溶性和在生理pH下低离子化特性,因此预计在摄入后会被迅速吸收。/二氯酚/
Because of their high lipid solubility and low ionization at physiological pH, dichlorophenols would be expected to be readily absorbed following ingestion. /Dichlorophenols/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
二氯酚同分异构体通过皮肤和肠道被吸收。/二氯酚同分异构体/
Dichlorophenol isomers are absorbed through the skin and from the gut. /Dichlorophenol isomers/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
易于从胃肠道和注射部位吸收。/氯酚/
... Readily absorbed from the gastroenteric tract and from parenteral sites of injection. /Chlorophenols/
Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
申请人:Abbott Laboratories
公开号:US20040116518A1
公开(公告)日:2004-06-17
The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases and cerebral vasospasm, to pharmaceutical compositions containing these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
[EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
申请人:HANGZHOU DAC BIOTECH CO LTD
公开号:WO2017046658A1
公开(公告)日:2017-03-23
Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人:HANGZHOU DAC BIOTECH CO LTD
公开号:WO2020257998A1
公开(公告)日:2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人:HANGZHOU DAC BIOTECH CO LTD
公开号:WO2020006722A1
公开(公告)日:2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
[EN] NEW THIENOPYRIMIDINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX DÉRIVÉS DE THIÉNOPYRIMIDINE, PROCÉDÉ POUR LEUR PRÉPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
申请人:SERVIER LAB
公开号:WO2015097123A1
公开(公告)日:2015-07-02
Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R12, X, A and n are as defined in the description.