The comparative formation of chlorophenol metabolites of hexachlorocyclohexane was investigated in rats and mice. Male Swiss mice and female Wistar rats were fed a diet containing 500 ppm hexachlorocyclohexane. Circulating concentrations of chlorophenols were determined after 24 hr in Wistar rats and Swiss mice given a single 200 mg/kg ip injection of hexachlorocyclohexane. Chlorophenol metabolites identified included 2,3,4,5-tetrachlorophenol. Species differences in the rate of chlorophenol metabolite formation in vitro were also measured in hepatic microsome fractions prepared from Aroclor 1254 pretreated animals.
The comparative formation of chlorophenol metabolites of hexachlorocyclohexane was investigated in rats and mice. Male Swiss mice and female Wistar rats were fed a diet containing 500 parts per million hexachlorocyclohexane. Animals were killed after 2 months and hepatic chlorophenol metabolites were determined using hig performance liquid chromatography. Circulating concentrations of chlorophenols were determined in Wistar rats and Swiss mice given a single 200 mg/kg intraperitoneal injection of hexachlorocyclohexane. After 24 hours blood was collected by heart puncture and chlorophenols assayed chromatographically. Species differences in the rate of chlorophenol metabolite formation in vitro were also measured in hepatic microsome fractions prepared from Aroclor 1254 pretreated animals. Chlorophenol metabolites identified were 2,6-dichlorophenol, 2,3,5-trichlorophenol, 2,3,6-trichlorophenol, 2,4,6-trichlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,5,6-tetrachlorophenol, and pentachlorophenol. No qualitative species difference was detected in chromatographic profiles of chlorophenols extracted from mouse and rat liver after continuous 2 month administration of hexachlorocyclohexane. Only 2,6-dichlorophenol was significantly higher in mouse live than that observed in rat liver: 1292.5 ng/g in mouse and 140.0 ng/g in rat. No qualitative difference was observed in the chlorophenols of blood of mice and rats. However, the concentration of 2,6-dichlorophenol was 11.52 ug/ml compared to 1.65 ug/ml in mouse blood. In vitro, 647 picomoles/mg/hour 2,4,6-trichlorophenol were formed by rat liver microsomes, compared to 219 picomoles/mg/hour by mouse liver microsomes. It was concluded that hexachlorocyclohexane may be a tumor promoting agent which acts by facilitating the development of latent initiated cells of unknown origin. Differential plasma clearance of 2,6-dichlorophenol may account for species differences in its concentration; however it is unlikely that it plays a major role in the induction of liver tumors in mice.
The metabolism of tetrachlorobenzenes was investigated in the squirrel monkey and a comparison made of the interspecies metabolism of such compounds. Three groups of four male monkeys were given orally single doses of one of three tetrachlorobenzene isomers in corn oil twice per week for 3 weeks. The dose levels for 1,2,3,4-tetrachlorobenzene and 1,2,3,5-tetrachlorobenzene were 100 mg/kg, and the dose level for 1,2,4,5-tetrachlorobenzene was 50 mg/kg. Respective levels of fecal excretion at 48 hours were 38, 36, and 18% of the initial doses. No metabolism occurred for 1,2,4,5-tetrachlorobenzene in the squirrel monkey. Fecal metabolites of 1,2,3,5-tetrachlorobenzene included 2,3,4,5-tetrachlorophenol (2% of dose), 2,3,4,6-tetrachlorophenol (14%), 2,3,5,6-tetrachlorophenol (9%), and 2,3,5,6-tetrachlorophenyl-sulfinic-acid (15%). For animals dosed with either 1,2,3,4-tetrachlorobenzene or 1,2,3,5-tetrachlorobenzene, the fecal radioactivity demonstrated elimination of at least 50% unchanged compound. Fecal metabolites in monkeys dosed with 1,2,3,4-tetrachlorobenzene included 1,2,4,5-tetrachlorophenol (22 %), N-acetyl-S-(2,3,4,5-tetrachlorophenyl)cysteine (18%), 2,3,4,5-tetrachlorophenyl sulfinic acid (3%), 2,3,4-trichlorophenyl-methyl sulfide (0.6%), and 2,3,4,5-tetrachlorophenyl-methyl sulfide (0.2%). Different metabolic pathways were briefly compared for the squirrel monkey, the rat, and the rabbit. The authors conclude that the tetrachlorobenzenes studied are metabolized differently in different species and that different isomers are metabolized by different pathways.
Tetrachlorophenols are rapidly absorbed and excreted following occupational exposure, which involves both the inhalation and dermal routes. Most of the 2,3,4,5-tetrachlorophenol is excreted unchanged in the urine; trichlorohydroquinone has been identified as one of its metabolites. (L159)
Tetrachlorophenols decrease or block ATP production without blocking the electron transport chain. Thus the poisons uncouple phosphorylation from oxidation. Free energy from the electron transport chain then converts to more body heat. As body temp rises, heat-dissipating mechanisms are overcome and metabolism is speeded. More ADP and other substrates accumulate, and these substrates stimulate the electron transport chain further. The electron transport chain responds by using up more and more available oxygen (increasing oxygen demand) in an effort to produce ATP, but much of the free energy generated is liberated as still more body heat. Oxygen demand quickly overcomes oxygen supply, and energy reserves become depleted. (A541)
Not directly listed by IARC, but related polychlorophenols are discussed, and combined exposures to polychlorophenols or to their sodium salts are classified as possibly carcinogenic to humans (Group 2B). (L135)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
皮肤接触可导致腐蚀性皮肤损伤。
Dermal exposure can cause corrosive skin damage. (L159)
Dust has been found irritating to the nose and throat. Skin or eye contact can cause irritation of the exposed surface. Clinical signs preceding death for all tetrachlorophenol isomers included initial hyperactivity followed by hypoactivity, neuromuscular weakness, and convulsions. Headache can also result from exposure to 2,3,4,5-tetrachlorophenol. (L159)
来源:Toxin and Toxin Target Database (T3DB)
吸收、分配和排泄
化合物容易从胃肠道和注射部位被吸收。/氯酚/
The compounds are readily absorbed from the gastroenteric tract and from parenteral sites of injection. /Chlorophenols/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
氯酚容易被各种途径吸收，包括经皮和吸入。/氯酚/
Chlorophenols ... are readily absorbed from all routes including percutaneous and inhalation. /Chlorophenols/
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.
式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
[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] MICROBIOCIDAL QUINOLINE (THIO)CARBOXAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS MICROBIOCIDES DE QUINOLÉINE (THIO)CARBOXAMIDE
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2019053010A1
公开（公告）日：2019-03-21
Compounds of the formula (I) wherein the subsitiuents are as defined in claim 1. Furthermore, the present invention relates to agrochemical compositions which comprise compounds of formula (I), to preparation of these compositions, and to the use of the compounds or compositions in agriculture or horticulture for combating, preventing or controlling infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi.
