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Methapyrilen
Methaphenilene · a3322 · AH-42 · A 3322 · histase · Lulamin · Rest-On · Restryl
Identifikatoren & physikalische Daten
| CAS No. | 91-80-5 |
|---|---|
| Summenformel | C14H19N3S |
| Durchschnittliche Molmasse | 261,39 g/mol |
| Monoisotopische Masse | 261,12996861 g/mol |
| SMILES | CN(C)CCN(Cc1cccs1)c1ccccn1 |
| InChIKey | HNJJXZKZRAWDPF-UHFFFAOYSA-N |
| PubChem CID | 4098 |
| ChEMBL | CHEMBL1411979 |
| ChEBI | CHEBI:6820 |
| EC No. | 202-099-8 |
| DTXSID | DTXSID2023278 |
| Lokaler Name | Methapyrilen |
Chemische & physikalische Eigenschaften
| XLogP | 2,6 |
|---|---|
| Polarare Oberfläche (TPSA) | 47,6 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 6 |
| Schwere Atome | 18 |
| Formalladung | 0 |
| Komplexität | 235 |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15 |
| LogP (Verteilungskoeffizient) | 2.87 |
| Color/Form | LIQUID |
| Löslichkeit | WHITE CRYSTALLINE POWDERUSUALLY FAINT ODORSOL IN WATER & ALCOHOLPH (1 IN 20 SOLN) BETWEEN 3 & 4. /METHAPYRILENE FUMARATE/DMSO (Sparingly), Methanol (Slightly)601.2mg/L(30 ºC) |
| Human Drugs | Pharmaceuticals |
| Siedepunkt | 343 to 347 °F at 3 mmHg (NTP, 1992)173-175 °C at 3.00E+00 mm Hg173-175 °C @ 3 MM HGBP: 125-135 °C @ 0.45 MM HGbp0.45 125-135°bp3 173-175° |
| Schmelzpunkt | MP: 135-136 °C. /METHAPYRILENE FUMARATE/25°C |
| Dampfdruck | 7.0X10-4 mm Hg at 25 °C (extrapolated from vapor pressure data at higher temperatures, SRC) |
| Brechungsindex | INDEX OF REFRACTION: 1.5915 @ 20 °C/DMAX ABSORPTION (WATER): 238 NM (LOG E= 4.17), 304 NM (LOG E= 3.60)INDEX OF REFRACTION: 1.5842 @ 25 °C/D, 1.5835 @ 25 °C/DnD25 1.5842 (also reported as 1.5835) |
| Physical Description | Methapyrilene is a clear colorless liquid. (NTP, 1992) |
| Dissociation Constants | 8.85 (at 20 °C) |
| Collision Cross Section | 157.6 Ų [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID0020818]156.27 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Dichte | 1.1388 (rough estimate) |
| Lagerbedingungen | Refrigerator, under inert atmosphere |
| Aggregatzustand | Oil |
| pKa (Säurekonstante) | pKa 3.02 ± 0.058.24± 0.11(H2O,t undefined,I=0.30(NaCl)) (Uncertain) |
| Farbe | Colourless to Light Yellow |
| Henry-Konstante | 3.6×101 mol/(m3Pa) at 25℃, HSDB (2015) |
| Stabilität | Stable. Incompatible with strong oxidizing agents. |
| EPA chemische Informationen | Methapyrilene (91-80-5) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 38 reports by companies from 1 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatorische Informationen | 1,2-Ethanediamine, N,N-dimethyl-N'-2-pyridinyl-N'-(2-thienylmethyl)-: Does not have an individual approval but may be used under an appropriate group standard |
| DOT-Kennzeichnung | Poison |
| Brandgefahren | Flash point data for this chemical are not available, but it is probably combustible. (NTP, 1992) |
| Gesundheitsgefahren | ACUTE/CHRONIC HAZARDS: This material is highly toxic by ingestion. (NTP, 1992) |
| Gefahrenübersicht | The major hazards encountered in the use and handling of methapyrilene stem from its toxicologic properties. Primarily toxic by ingestion, exposure to this liquid may occur from its production or veterinary use (parenteral or topical application) on domestic animals to treat histamine associated allergies or hypersensitivities. Effects from exposure may include tachycardia, CNS depression, hallucinations, toxic psychosis, cerebral edema, deep coma, cardio-respiratory collapse, or death. |
| Reaktive Gruppe | Amines, Phosphines, and Pyridines |
| Special Reports | Lijinsky WChronic Toxicity Tests of Pyrilamine Maleate and Methapyrilene Hydrochloride in F344 ratsFood and Chemical Toxicology 22 (1): 27-30 (1984). |
| RCRA-Anforderungen | U155As stipulated in 40 CFR 261.33, when methapyrilene, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5). |
| Reactivity Profile | An amine, organosulfide. Organosulfides are incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. Reactions with these materials generate heat and in many cases hydrogen gas. Many of these compounds may liberate hydrogen sulfide upon decomposition or reaction with an acid. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides. |
| Air and Water Reactions | No rapid reaction with air. No rapid reaction with water. |
| EPA Hazardous Waste Number | U155A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or manufacturing chemical intermediate. |
| CERCLA-Meldepflichtmengen | Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5,000 lb or 2270 kg. The toll free telephone number of the NRC is (800) 424-8802in the Washington metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.6 (see section IV. D.3.b). |
| Brandbekämpfung | Fires involving this compound should be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992) |
| Erste Hilfe | EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. |
| Freisetung ohne Brand | Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]: |
| Entsorgungsverfahren | Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U155, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. |
| Isolation and Evacuation | Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]: |
| Personal Protective Equipment (PPE) | RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992) |
| Körperbelastung | Methapyrilene was found in the blood of 16 persons who died of non-drug related causes in Maryland between 1975 and 1980 at concn ranging from 0.1 to 7.2 mg/l and at an avg concn of 1.8 mg/l(1). It also was found in the blood of 2 persons who had apparently committed suicide by ingesting unknown amounts of methapyrilenethe range of concn found in these suicide victims was 0.5-9.8 mg/l and the average concn was 5.2 mg/l(1). |
| Wechselwirkungen | A CASE OF FATAL POISONING WITH SOMINEX (METHAPYRILENE HYDROCHLORIDE, COMBINATION, SCOPOLAMINE AMINOXIDE HYDROBROMIDE & SALICYLAMIDE) CAPSULES IS REPORTED. |
| Umweltverhalten | TERRESTRIAL FATE: If methapyrilene is released to soil, it will be expected to exhibit low mobility in soil(1,SRC) based upon an estimated Koc of 737(2-3,SRC). Methapyrilene, therefore, may very slowly leach through soil to groundwater(3,SRC). It should not hydrolyze in moist soil(2). Based upon an estimated Henry's Law constant of 2.74X10-7 atm-cu m/mole (which was calculated from an estimated water solubility(2-3,SRC) and an extrapolated vapor pressure(4,SRC), volatilization of methapyrilene from moist near-surface soil should not be significant(2,SRC). It is not known whether methapyrilene biodegrades in soil(SRC).AQUATIC FATE: If methapyrilene is released to water, it may be susceptible to direct photolysis in the atmosphere since the compound absorbs light at wavelengths >290 nm(1). It should not hydrolyze(2), bioconcentrate signficantly in aquatic organisms(2-3,SRC), or strongly adsorb to sediment or suspended sediments(2-3,SRC). Based upon an estimated Henry's Law constant of 2.74X10-7 atm-cu m/mole (which was calculated from an estimated water solubility(2-3,SRC) an an extrapolated vapor pressure(4,SRC), volatilization of methapyrilene from water should not be significant(2,SRC). It is not known whether methapyrilene biodegrades in natural water(SRC).ATMOSPHERIC FATE: If methapyrilene is released to the atmosphere, it will be expected to exist in both vapor and particulate phases, based upon(2) a vapor pressure of 7.0X10-4 mm Hg at 25 °C which was extrapolated from vapor pressure data at higher temperatures(4,SRC). It may be susceptible to direct photolysis in the atmosphere since the compound absorbs light at wavelengths >290 nm(1). It should react rapidly with photochemically produced hydroxyl radicals based upon an estimated rate constant for this process of 185X10-12 cu cm/molecule-sec at 25 °C which corresponds to an atmospheric half-life of 2.1 hr at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(2,SRC). |
| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Methapyrilene hydrochloride/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=135-23-9] |
| Soil Adsorption/Mobility | An estimated Koc of 737 can be calculated(2,SRC) from an estimated log Kow of 2.74(1) using a recommended regression equation(2,SRC). Based upon this estimated Koc, methapyrilene will be expected to exhibit low mobility in soil(3,SRC). |
| Human Toxicity Excerpts | SIMILAR TO OTHER ANTIHISTAMINICS IN ACUTE TOXICITY. OVERDOSES PRODUCE EXCITEMENT, CONVULSIONS, HYPERPYREXIA, CEREBRAL EDEMA, DEPRESSION, & OCCASIONALLY RENAL TUBULAR NECROSIS. DEATH HAS BEEN REPORTED FROM ORAL DOSE AS SMALL AS 12 MG/KG, BUT OTHERS HAVE SURVIVED AFTER 80 MG/KG. /METHAPYRILENE HYDROCHLORIDE/OVER THE COUNTER HYPNOTIC PREPN CONTAINING METHAPYRILENE IMPLICATED IN 21 CASES OF PSYCHOTROPIC DRUG OVERDOSE. 10 PATIENTS SHOWED CENTRAL ANTICHOLINERGIC TOXICITY: HALLUCINATIONS, DELIRIUM & CONFUSION. CONCLUDED THAT THE PREPN PRODUCES TOXIC PSYCHOSIS WHICH IS TEMPORARY & BENIGN.METHAPYRILENE TOXIC PSYCHOSIS MIMICKING ECLAMPSIA.FATALITY DUE TO METHAPYRILENE IN 38-YR-OLD WOMAN IS DESCRIBED.7 CASES OF METHAPYRILENE OVERDOSE, 5 OF WHICH PROVED FATAL, ARE PRESENTED & EXTRACTION & ASSAY FROM BIOL FLUIDS ARE REPORTED. IN 5 CASES, MULTIPLE DRUG INGESTION INCL ETHANOL WAS DIAGNOSED. |
| Artificial Pollution Sources | The hydrochloride and fumarate salts of methapyrilene have been used in the past as an antihistamine(1). The compound may no longer be used as a drug based upon a report that it was being withdrawn due to possible carcinogenicity(1). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)methapyrileneDILI PositiveDOI:10.1016/j.drudis.2019.09.022 |
| Environmental Bioconcentration | An estimated BCF of 71 can be calculated(2,SRC) from an estimated log Kow of 2.74(1) using a recommended regression equation(2,SRC). Based upon this estimated BCF, methapyrilene will not be expected to significantly bioconcentrate in aquatic organisms (SRC). |
| Volatilization from Water/Soil | Based upon an estimated water solubility of 879 mg/l(1,3,SRC) and a vapor pressure of 7.0X10-4 mm Hg at 25 °C which was extrapolated from vapor pressure data at higher temperatures(2,SRC), the Henry's Law Constant for methapyrilene has been calculated to be 2.74X10-7 atm-cu m/mole(SRC). Volatilization of methapyrilene from water and moist soil should not be significant based upon the low value for the Henry's Law constant(3,SRC). |
| Non-Human Toxicity Excerpts | TESTED SOLN OF SEVERAL ANTIHISTAMINIC CMPD ON ... RABBIT EYES TO DETERMINE RELATIONSHIP OF CONCN TO DISCOMFORT & CORNEAL INJURY. MAX CONCN WHICH COULD BE APPLIED AS SINGLE DROP TO RABBIT EYES WITHOUT INJURING CORNEA WERE ... METHAPYRILENE HYDROCHLORIDE, 5% ... . /METHAPYRILENE CHLORIDE/METHAPYRILENE HYDROCHLORIDE FED @ CONCN OF 1% TO MALE & FEMALE FISCHER RATS. ALMOST ALL DEVELOPED LIVER NEOPLASMS, MAINLY HEPATOCELLULAR CARCINOMAS & CHOLANGIOCARCINOMAS. OVER 50% HAD METASTASES FROM LIVER CARCINOMAS TO DISTANT ORGANS. /METHAPYRILENE HYDROCHLORIDE/METHAPYRILENE, 40 MG/KG, WAS ADMIN TO MALE MONGREL DOGS RESULTING IN BOTH CENTRAL & PERIPHERAL ANTICHOLINERGIC EFFECTS.Methapyrilene is negative in most short-term tests for genotoxicity, but some positive results have been noted. An unusual finding, as yet unexplained, is the considerable increase in the number of mitochondria in liver cells of rats given this drug.For more Non-Human Toxicity Excerpts (Complete) data for METHAPYRILENE (11 total), please visit the HSDB record page. |
| Environmental Abiotic Degradation | Methapyrilene may be susceptible to direct photolysis since the compound absorbs light at wavelength >290 nm(1). The rate constant for the vapor-phase reaction of methapyrilene with photochemically produced hydroxyl radicals has been estimated to be 185X10-12 cu cm/molecule-sec at 25 °C which corresponds to an atmospheric half-life of 2 hr at an atmospheric concentration of 5X10+5 hdyroxyl radicals per cu cm(2,SRC). Hydrolysis is not expected to be significant under normal environmental conditions (pH 5-9)(3). |
| UN-Transportnummer | 1851 |
| Toxizität | LD50 in mice, guinea pigs (mg/kg): 182.2 ±12.8, 374.9 ±34.5 orallyin mice (mg/kg): 19.85 ±0.69 i.v. (Lee) |
| Gefahrenklasse | 6.1(b) |
| Verpackungsgruppe | III |
| Gefahrstoffdaten | 91-80-5(Hazardous Substances Data) |
Anwendungen & Verwendung
Verwenden
Methapyrilene is an intermediate in the synthesis of Methapyrilene Hydrochloride (M259970). Methapyrilene is used as antihistaminic agent.