This study reports timely and original results of the mechanistic toxicity assessment of 4-MCHM and its metabolites via a newly developed quantitative toxicogenomics approach, employing proteomics analysis in yeast cells and transcriptional analysis in human cells. These results suggested that, although 4-MCHM is considered only moderately toxic based on the previous limited acute toxicity evaluation, 4-MCHM metabolites were likely more toxic than 4-MCHM in both yeast and human cells, with different toxicity profiles and potential mechanisms. In the yeast library, 4-MCHM mainly induced chemical stress related to transmembrane transport and transporter activity, while 4-MCHM metabolites of S9 mainly induced oxidative stress related to antioxidant activity and oxidoreductase activity.
IDENTIFICATION AND USE: 4-Methylcyclohexanemethanol (MCHM) is a clear, colorless liquid, which is reported to smell like licorice. It is used in a coal industry in the separation of usable coal from rocks, debris and cold dust. HUMAN EXPOSURE AND TOXICITY: Symptoms of MCHM exposure include: nausea, vomiting, dizziness, headaches, diarrhea, reddened skin, itching, and rashes. In the days immediately following January 9, 2014, the West Virginia Poison Center received calls from over 1,900 patients reporting chemical exposures related to the drinking water. Most reported symptoms included mild rashes and reddened skin from dermal exposure, or GI distress (nausea, vomiting and/or diarrhea) from ingesting contaminated water. The symptoms tended to be mild and self-limiting. It was possible that the symptoms reported to be caused by exposure to MCHM could have been caused by other mild clinical illness such as colds or flu or other viral infections. Results of laboratory tests done in the Emergency Department did not indicate any people had new kidney or liver damage. With human A549 cells, MCHM mainly induced DNA damage-related biomarkers. ANIMAL STUDIES: Rats dosed with 800 mg/kg of MCHM showed signs of CNS depression resulting in decreased activity levels and ataxia. Administration of 400 mg/kg/day of the test article to rats by gavage for four weeks was associated with erythropoietic, kidney, and liver effects. The no-observed-effect level for this subacute toxicity study was 100 mg/kg/day. MCHM was a strong skin irritant in guinea pigs and moderate eye irritant in rabbits. NTP mouse study found MCHM is a skin irritant; however, it did not induce hypersensitivity unlike crude MCHM. An acute dermal toxicity study was conducted in male and female rats administered a single limit dose of 2000 mg/kg of the test substance topically. Two female rats died (on Day 1 and Day 3); the cause of death was not determined. For female rats, clinical sign observed included prostration, stumbling, transient weakness, and skin abnormalities (erythema, desquamation, and induration). Additionally, lack of feces, red urine, and inguinal hair wet with urine was observed for the female rats. For male rats, clinical signs observed were limited to erythema and desquamation of the skin at the site of application. All animals which survived to scheduled necropsy gained weight during the study. Treatment-related gross or microscopic changes were observed only for female rats. For the two female rats which died, treatment-related gross lesions included distention of the urinary bladder with red urine, and/or hemorrhage in the glandular gastric mucosa; darker than normal spleens were also observed in these rats. The lesions observed in the glandular gastric mucosa may have been due to consumption of test substance during grooming or may have been due to stress. Microscopic lesions consisted of atrophy and congestion of the splenic red pulp and/or atrophy and necrosis of the splenic white pulp. The white pulp atrophy may have been secondary to stress and the red pulp atrophy and congestion may have been related to stress and/or hemorrhage. In addition, splenic effects have not been associated with wrapping, and therefore, may be associated with test substance toxicity. Treatment-related lesions observed for one of the female rats that survived the 14-day observation period consisted of desquamation and minor induration of the skin at the application site grossly and consisted of focal necrosis and eschar formation on the skin at the application site microscopically. The test substance was a dermal irritant as evidenced by focal necrosis and eschar formation on the skin at the application site. In prenatal developmental toxicity study in rats NTP found that MCHM decreased fetal weight and induced malformations in fetuses (400 mg/kg/day). A small decrease in fetal weight was also observed (200 mg/kg/day). In zebrafish studies, MCMH did not have effects on embryonic and larval development and behavior, but it affected zebrafish photomotor response. In the yeast library, MCHM induced chemical stress related to transmembrane transport and transporter activity, while MCHM metabolites induced oxidative stress related to antioxidant activity and oxidoreductase activity. In the mutagenicity study with Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA (pKM101) MCHM was not active with or without metabolic activation. MCHM was negative in the in vivo rat micronucleus assay conducted by NTP. ECOTOXICITY STUDIES: LC50; Fathead minnow; Conditions: freshwater, static; Concentration 54.7 mg/L for 96 hr. EC50; Species: Daphnia magna (Water flea); Conditions: freshwater, static; Concentration: 98.1 mg/L for 48 hr; effect: stress and immobility. Others reported EC50 for Daphnia magna approximately 50 mg/L for 48 hr.
/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 if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the 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. /Poisons A and B/
/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 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 0.9% saline (NS) 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 ... . /Poisons A and B/
/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 ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
4-Methyl-1-cyclohexanemethanol (cis- and trans- Revision number: 5 mixture) SAFETY DATA SHEET Section 1. IDENTIFICATION Product name: 4-Methyl-1-cyclohexanemethanol (cis- and trans- mixture)
Revision number: 5 Section 2. HAZARDS IDENTIFICATION GHS classification PHYSICAL HAZARDS Category 4 Flammable liquids HEALTH HAZARDS Not classified Not classified ENVIRONMENTAL HAZARDS GHS label elements, including precautionary statements Pictograms or hazard symbols None Signal word Warning Hazard statements Combustible liquid Precautionary statements: [Prevention] Keep away from flames and hot surfaces. Wear protective gloves and eye/face protection. [Storage] Store in a well-ventilated place. Keep cool. [Disposal] Dispose of contents/container through a waste management company authorized by the local government. Section 3. COMPOSITION/INFORMATION ON INGREDIENTS Substance Substance/mixture: Components: 4-Methyl-1-cyclohexanemethanol (cis- and trans- mixture) >98.0%(GC) Percent: CAS Number: 34885-03-5 Synonyms: 1-(Hydroxymethyl)-4-methylcyclohexane Chemical Formula: C8H16O Section 4. FIRST AID MEASURES Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing. Get medical advice/attention if you feel unwell. Skin contact: Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower. If skin irritation or rash occurs: Get medical advice/attention. Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. If eye irritation persists: Get medical advice/attention. Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth. Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air- tight goggles. 4-Methyl-1-cyclohexanemethanol (cis- and trans- mixture) Section 5. FIRE-FIGHTING MEASURES Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide. media: Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing method according to the surrounding situation is used. Uninvolved persons should evacuate to a safe place. In case of fire in the surroundings: Remove movable containers if safe to do so. Special protective When extinguishing fire, be sure to wear personal protective equipment. equipment for firefighters: Section 6. ACCIDENTAL RELEASE MEASURES Use personal protective equipment. Keep people away from and upwind of spill/leak. Personal precautions, protective equipment and Ensure adequate ventilation. Entry to non-involved personnel should be controlled emergency procedures: around the leakage area by roping off, etc. Environmental precautions: Prevent product from entering drains. Methods and materials for Absorb spilled material in a suitable absorbent (e.g. rag, dry sand, earth, saw-dust). containment and cleaning In case of large amount of spillage, contain a spill by bunding. Adhered or collected up: material should be promptly disposed of, in accordance with appropriate laws and regulations. Prevention of secondary Remove all sources of ignition. Fire-extinguishing devices should be prepared in hazards: case of a fire. Use spark-proof tools and explosion-proof equipment. Section 7. HANDLING AND STORAGE Precautions for safe handling Technical measures: Handling is performed in a well ventilated place. Wear suitable protective equipment. Prevent generation of vapour or mist. Keep away from flames and hot surfaces. Take measures to prevent the build up of electrostatic charge. Use explosion-proof equipment. Wash hands and face thoroughly after handling. Use a closed system, ventilation. Advice on safe handling: Avoid contact with skin, eyes and clothing. Conditions for safe storage, including any incompatibilities Storage conditions: Keep container tightly closed. Store in a cool, dark and well-ventilated place. Store away from incompatible materials such as oxidizing agents. Comply with laws. Packaging material: Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION Engineering controls: Install a closed system or local exhaust as possible so that workers should not be exposed directly. Also install safety shower and eye bath. Personal protective equipment Respiratory protection: Vapor respirator. Follow local and national regulations. Hand protection: Protective gloves. Safety glasses. A face-shield, if the situation requires. Eye protection: Skin and body protection: Protective clothing. Protective boots, if the situation requires. Section 9. PHYSICAL AND CHEMICAL PROPERTIES Physical state (20°C): Liquid Clear Form: Colour: Colorless - Almost colorless No data available Odour: pH: No data available Melting point/freezing point:No data available Boiling point/range: No data available Flash point: No data available Flammability or explosive limits: Lower: No data available 4-Methyl-1-cyclohexanemethanol (cis- and trans- mixture) Section 9. PHYSICAL AND CHEMICAL PROPERTIES Upper: No data available Relative density: No data available Solubility(ies): No data available [Water] [Other solvents] No data available Section 10. STABILITY AND REACTIVITY Chemical stability: Stable under proper conditions. Possibility of hazardous No special reactivity has been reported. reactions: Conditions to avoid: Open flame Incompatible materials: Oxidizing agents Hazardous decomposition Carbon monoxide, Carbon dioxide products: Section 11. TOXICOLOGICAL INFORMATION No data available Acute Toxicity: Skin corrosion/irritation: No data available No data available Serious eye damage/irritation: Germ cell mutagenicity: No data available Carcinogenicity: No data available IARC = NTP = No data available No data available Reproductive toxicity: Section 12. ECOLOGICAL INFORMATION Ecotoxicity: Fish: No data available Crustacea: No data available Algae: No data available Persistence / degradability: No data available Bioaccumulative No data available potential(BCF): Mobility in soil Log Pow: No data available Soil adsorption (Koc): No data available Henry's Law No data available constant(PaM3/mol): Section 13. DISPOSAL CONSIDERATIONS Recycle to process, if possible. Consult your local regional authorities. You may be able to burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section 14. TRANSPORT INFORMATION Hazards Class: Does not correspond to the classification standard of the United Nations UN-No: Not listed Section 15. REGULATORY INFORMATION Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002 and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport, loading and unloading were prescribed. 4-Methyl-1-cyclohexanemethanol (cis- and trans- mixture)
[EN] PROCESS FOR THE PREPARATION OF 1,4-CYCLOHEXANEDIMETHANOL FROM TEREPHTHALIC ACID [FR] PROCÉDÉ DE PRÉPARATION DE 1,4-CYCLOHEXANEDIMÉTHANOL À PARTIR D'ACIDE TÉRÉPHTALIQUE
[EN] NITRILE COMPOUND AND ITS USE IN PEST CONTROL<br/>[FR] COMPOSE NITRILE ET SON UTILISATION POUR LE CONTROLE DES INSECTES ET ANIMAUX NUISIBLES
申请人：SUMITOMO CHEMICAL CO
公开号：WO2005063694A1
公开（公告）日：2005-07-14
The present invention provides a nitrile compound represented by the formula (I): wherein R represents C1-C4 fluoroalkyl, Q represents halogen, C1-C11 alkyl optionally substituted with halogen, C2-C6 alkenyl group optionally substituted with halogen, C2-C6 alkynyl optionally substituted with halogen, C3-C7 cycloalkyl optionally substituted with halogen or (C3-C7 cycloalkyl optionally substituted with halogen)C1-C4 alkyl, which has excellent control effect against pests.
[EN] FUNCTIONALISED AMINE DERIVATIVES AS IL-17 MODULATORS<br/>[FR] DÉRIVÉS D'AMINE FONCTIONNALISÉS UTILES EN TANT QUE MODULATEURS D'IL-17
申请人：UCB BIOPHARMA SRL
公开号：WO2020120141A1
公开（公告）日：2020-06-18
A series of functionalised amine derivatives of formula (I) as defined herein, being potent modulators of human IL-17 activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including inflammatory and autoimmune disorders.
Tuning the chemoselective hydrogenation of aromatic ketones, aromatic aldehydes and quinolines catalyzed by phosphine functionalized ionic liquid stabilized ruthenium nanoparticles
作者：He-yan Jiang、Xu-xu Zheng
DOI：10.1039/c5cy00293a
日期：——
Rutheniumnanoparticles (Ru NPs) stabilized by phosphine-functionalized ionic liquids (PFILs) were synthesized in an imidazolium-based ionic liquid using H2 as a reductant. Characterization showed well-dispersed particles of about 2.2 nm (TEM) and confirmed the PFIL stabilization of the Ru NPs (NMR). The Ru NPs stabilized by PFILs exhibited excellent activity and switchable chemoselectivity in the
[EN] ATX MODULATING AGENTS<br/>[FR] AGENTS DE MODULATION D'ATX
申请人：BIOGEN MA INC
公开号：WO2015188051A1
公开（公告）日：2015-12-10
Compounds of formula (I) can modulate the activity of autotaxin (ATX).
式(I)的化合物可以调节自体税肽酶（ATX）的活性。
[EN] 3, 4-DISUBSTITUTED 1H-PYRAZOLE COMPOUNDS AND THEIR USE AS CYCLIN DEPENDENT KINASES (CDK) AND GLYCOGEN SYNTHASE KINASE-3 (GSK-3) MODULATORS<br/>[FR] COMPOSES 1H-PYRAZOLE 3,4-DISUBSTITUES ET LEUR UTILISATION EN TANT QUE KINASES DEPENDANT DES CYCLINES (CDK) ET MODULATEURS DE LA GLYCOGENE SYNTHASE KINASE-3 (GSK-3)
申请人：ASTEX TECHNOLOGY LTD
公开号：WO2005012256A1
公开（公告）日：2005-02-10
The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. Formula (0). In formula (0): X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, S02, C=O, NRg(C=O) or O(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from 0, S, NH, SO, S02; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).
