No exposure limit has been set for this com pound. Carcinogenicity: Animal Sufficient
Evidence, Human Limited Evidence (IARC).
物理描述：
Hexachlorobenzene appears as a white crystalline substance. Insoluble in water and denser than water. Contact may irritate skin, eyes and mucous membranes. May be toxic by ingestion. Used to make other chemicals.
After ip and oral admin of (14)C hexachlorobenzene in rats was dose-dependent ... major urinary metabolites were ... pentachlorophenol, tetrachlorohydroquinone, and pentachlorothiophenol. Other urinary metabolites were tetrachlorobenzene, pentachlorobenzene, 2,4,5- & 2,4,6-trichlorophenols ... 2,3,4,6- and 2,3,5,6-tetrachlorophenols; 2,3,4-trichlorophenol and other tetrachlorophenols were present in traces. These metabolites were excreted as conjugates or in free form in urine. Unchanged hexachlorobenzene was found in the feces and in fat.
When 110 ug/day (14)C-hexachlorobenzene was given orally to macaca mulatta monkeys for 11-15 months, 50% of radioactivity found in urine was pentachlorophenol and 25% pentachlorobenzene, the remainder was unidentified metabolites and unchanged hexachlorobenzene. In feces, 99% of radioactivity was unchanged HCB.
Hexachlorobenzene (HCB) was metabolized by phenobarbital induced liver microsomes from male rats to pentachlorobenzene, pentachlorophenol, tetrachloro-1,2-benzenediol, and tetrachloro-1,4-benzenediol (1:88:2:9). Metabolites were identified and quantified by electron capture gas-liquid chromatography. Structures were confirmed by selective ion monitoring gas-liquid chromatography/mass spectrometry. The formation of pentachlorophenol was dependent on the presence of NADPH and oxygen and inhibited by carbon monoxide SKF 525A, and metyrapone. Conversion of HCB to pentachlorophenol was stimulated by pretreatment of rats with phenobarbital but not by 3-methylcholanthrene, or 2,3,7,8-tetrachlorodibenzo-p-dioxin. In contrast, the conversion of pentachlorophenol to tetrachloro-1,4-benzenediol was markedly induced by 3-methylcholanthrene but poorly by phenobarbital. HCB, Aroclor 1254, and isosafrole stimulated both hydroxylations. The cytochrome p450 inhibitor 9-hydroxyellipticine inhibited conversion of pentachlorophenol to tetrachlorobenzenediols by HCB and beta-naphthoflavone induced micrsomes. In addition to hydroxylation reactions, evidence was obtained for the conjugaton of HBC with glutathione catalyzed by a microsomal glutathione transferase. Radioactivity from (14)carbon HCB was bound to microsomal protein during aerobic incubations. Binding was inhibited by GSH and N-acetyl-cysteine.
The induction by organochloride pesticides of rat hepatic microsomal monooxygenases which hydroxylate benzo(a)pyrene and testosterone was compared with that of phenobarbital, in order to investigate their activity as inducers of different cytochrome p450 isozymes. Long Evans rats were administered intraperitoneal injections of 400 umol/kg phenobarbital for 4 consecutive days and were sacrificed the following day, or were administered single doses of heptachlor, chlordane, hexachlorobenzene, toxaphene, dieldrin, lindane, or p,p'-DDT and were sacrificed 4 days later. Microsomal liver fractions were analyzed for benzo(a)pyrene and testosterone metabolism. All the compounds tested except lindane induced both benzo(a)pyrene and testosterone hydroxylases. Hexachlorobenzene induced formation of benzo(a)pyrene 9,10-dihydrodiol and 7,8-dihydrodiol metabolites. A different combination of testosterone hydroxylases was induced by each of the chemicals. Phenobarbital induced the activities of the 15-beta, 16-alpha, and 16-beta testosterone hydroxylases. With the exception of lindane, all of the pesticides tested induced the 16-alpha and 16-beta testosterone hydroxylases.
来源:Hazardous Substances Data Bank (HSDB)
代谢
六氯苯已知的人类代谢物包括五氯酚。
HEXACHLOROBENZENE has known human metabolites that include Pentachlorophenol.
Based on representative levels of hexachlorobenzene in air, water, and food, the total intake of hexachlorobenzene by adults in the general population ... is predominantly from the diet. ... Hexachlorobenzene is readily absorbed by the oral route in experimental animals and poorly via the skin. ... In animals and humans, hexachlorobenzene accumulates in lipid-rich tissues, such as adipose tissue, adrenal cortex, bone marrow, skin and some endocrine tissues, and can be transferred to offspring both across the placenta and via mothers' milk. Hexachlorobenzene undergoes limited metabolism, yielding pentachlorophenol, tetrachlorohydroquinone and pentachlorothiophenol as the major metabolites in urine.... The acute toxicity of hexachlorobenzene to experimental animals is low ... In animal studies, hexachlorobenzene is not a skin or eye irritant ... The available data on the systemic toxicity of hexachlorobenzene indicate that the pathway for the biosynthesis of heme is a major target of hexachlorobenzene toxicity. Elevated levels of porphyrin and/or porphyrin precursors have been found in the liver, other tissues and excreta of several species of laboratory mammals ... Porphyria has been reported in a number of studies in rats with subchronic or chronic oral exposure ... Repeated exposure to hexachlorobenzene has also been shown to affect a wide range of organ systems (including the liver, lungs, kidneys, thyroid, skin and nervous and immune systems) although these have been reported less frequently than porphyria. Hexachlorobenzene is a mixed-type cytochrome P-450-inducing compound, with phenobarbital-inducible and 3-methylcholanthrene-inducible properties. It is known to bind to the Ah receptor. ... The carcinogenicity of hexachlorobenzene has been assessed in several adequate bioassays on rodents. ... There were increases in the incidence of liver cell tumors (hepatoma) ... hemangioendotheliomas of the liver ... adenomas of the thyroid ... neoplastic liver nodules and adrenal pheochromocytomas ... parathyroid adenomas ... renal cell adenomas ... hepatocellular carcinomas, bile duct adenomas/carcinomas ... and adrenal cortical adenomas. ... Hexachlorobenzene has little capability to induce directly gene mutation, chromosomal damage and DNA repair. It exhibited weak mutagenic activity ... There is also some evidence of low-level binding to DNA in vitro and in vivo, but at levels well below those expected for genotoxic carcinogens. In studies of reproduction .... /suggest/ specificity of hexachlorobenzene within the site of the ovary. ... The results of a number of studies have indicated that hexachlorobenzene affects the immune system .... Most data on the effects of hexachlorobenzene on humans originate from accidental poisonings that took place in Turkey in 1955-1959, in which more than 600 cases of porphyria cutanea tarda were identified. In this incident, disturbances in porphyrin metabolism, dermatological lesions, hyperpigmentation, hypertrichosis, enlarged liver, enlargement of the thyroid gland and lymph nodes, and (in roughly half the cases) osteoporosis or arthritis were observed, primarily in children. Breast-fed infants of mothers exposed to hexachlorobenzene in this incident developed a disorder called pembe yara (pink sore) and most died within a year. There is also limited evidence that porphyria cutanea tarda occurs in humans with relatively high exposure to hexachlorobenzene in the workplace or in the general environment. The few available epidemiological studies of cancer ... are insufficient to assess the carcinogenicity of hexachlorobenzene to humans. ... There are few experimental studies on which an environmental risk assessment can be made. ... However, hexachlorobenzene concentrations ... /suggest/ that hexachlorobenzene has the potential to harm embryos of sensitive bird species ... /and/ to cause adverse effects in ... fish-eating mammals..
Hexachlorobenzene causes porphyria by modifying sulfhydryl groups in the catalytic or substrate-binding sites of uroporphyrinogen decarboxylase. This inhibits uroporphyrinogen decarboxylase, resulting in a deficiency of the decarboxylation of uroporphyrinogen III and accumulation of uroporphyrins in the liver. In addition, metabolism of hexachlorobenzene by the cytochrome P-450 enzymes is believed to produce reactive electrophilic metabolites that covalently bind to cellular proteins and DNA, causing irreversible damage. Exposure to hexochlorobenzene also causes macrophages to be attracted to organs such as the spleen, lungs, and skin, where they become activated by the hexochlorobenzene. This leads to a cascade of reactions involving innate immune cells. The gene expression profiles provide evidence for the importance of macrophages and granulocytes and mediators released by these cells in the adverse inflammatory response against hexochlorobenzene. In this way, co-stimulatory or danger signals are generated that could polyclonally activate T cells. Hexachlorobenzene is a weak agonist for aryl hydrocarbon receptor and may exhibit some of its toxic effects by activating the gene-regulatory properties of this protein, possibly inducing cytochome P-450 enzymes. It may also act at certain endocrine receptors. (A14, L225, A156, A157, A60)
Evaluation: There is inadequate evidence in humans for the carcinogenicity of hexachlorobenzene. There is sufficient evidence in experimental animals for the carcinogenicity of hexachlorobenzene. Overall evaluation: Hexachlorobenzene is possibly carcinogenic to humans (Group 2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Hexachlorobenzene, when administered orally, has been shown to induce tumors in the liver, thyroid, and kidney in three rodent species. HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
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.
... In rats over a 53 week period ... /hexachlorobenzene/ was given orally every other day ... 9 weeks after start of treatment an equilibrium was reached between intake and elimination of the compound and its metabolites.
... Male wistar rats, fed by stomach tube 8 mg /hexachlorobenzene/ ... per kg (in sunflower oil) for 19 days. Tissue concentration at termination of treatment period were for body fat, 82 ppm; muscle, 17 ppm; total liver, 125 ug; total kidney, 21 ug; total spleen, 9 ug; total heart, 1.5 ug; and adrenal, 0.5 ug each.
... With labeled hexachlorobenzene ... four weeks after administration, 7% of radioactivity was excreted in rats via kidneys and 27% with feces. Nearly the total in urine was contained in metabolites of hexachlorobenzene, and 69% ... in feces was ... unchanged drug.
... Cd-1 mice ... treated with hexachlorobenzene by gastric intubation at ... 10, 50, or 100 mg/kg/day. Concentration in fetuses ranged from 0.76 ppm to ... 19.09 ppm and appeared ... related to level of dose received by mother. Fetal ... levels were higher in mice treated before implantation than in those treated on days 6-11 of gestation. ...
Reaction of Hexachlorobenzene and (Pentachlorophenyl)lithium with .alpha.-Arylacetonitriles
摘要：
(Pentachlorophenyl)lithium (2) reacts with alpha-lithio-alpha-arylacetonitriles (4) at -70 degrees C to room temperature to supply alpha-aryl-alpha-(2,3,5,6-tetrachlorophenyl)ace a. Small amounts of 1,2,4,5-tetrachlorobenzene (8) and trans-1,2-dicyano-1,2-diarylethylenes 9 are also obtained; however, no alpha-tetrachloroarylated nitriles 6 from 3,4,5,6-tetrachlorobenzyne were detected. Similar treatment of hexachlorobenzene (1) and 4 afforded alpha-aryl-alpha-(2,3,4,5,6-pentachlorophenyl)acetonitriles 10. The addition of 2 to 4 at tetrachlorobenzyne-generating temperatures (0-20 degrees C) gave a complex mixture containing mainly dimeric and polymeric materials; 6 was not found. A mechanism is proposed for the reaction of 2 and 4 which suggests that nitriles 7 are formed by the condensation of 2 and 4 via a four-centered transition state and that alkenes 9 are supplied by a base-mediated dimerization of alpha-chloro-alpha-arylacetonitriles 13, formed by a lithium-chlorine exchange between 2 and 4. Nitriles 10 most likely are provided from the reaction of 1 and 4 by the usual aromatic nucleophilic substitution pathway.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
[EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
申请人：BASF SE
公开号：WO2014206910A1
公开（公告）日：2014-12-31
The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
