HuagongsheHuagongshe Chemie-Druckbericht · Nur für Forschungszwecke
Benzocain
ETHYL 4-AMINOBENZOATE · Benzocaine base · ethyl aminobenzoate · ETHYL P-AMINOBENZOATE · 4-AMINOBENZOIC ACID ETHYL ESTER · Nitemazepam · 4-Carbethoxyaniline · Anestezin
Identifikatoren & physikalische Daten
| CAS No. | 94-09-7 |
|---|---|
| Summenformel | C9H11NO2 |
| Durchschnittliche Molmasse | 165,19 g/mol |
| Monoisotopische Masse | 165,07897859 g/mol |
| SMILES | CCOC(=O)c1ccc(N)cc1 |
| InChIKey | BLFLLBZGZJTVJG-UHFFFAOYSA-N |
| PubChem CID | 2337 |
| ChEMBL | CHEMBL278172 |
| ChEBI | CHEBI:116735 |
| EC No. | 202-303-5 |
| DTXSID | DTXSID8021804 |
| Lokaler Name | Benzocain |
Chemische & physikalische Eigenschaften
| XLogP | 1,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 52,3 |
| H-Brücken-Donoren | 1 |
| H-Brücken-Akzeptoren | 3 |
| Frei drehbare Bindungen | 3 |
| Schwere Atome | 12 |
| Formalladung | 0 |
| Komplexität | 151 |
| Stoffklassen | Other Uses -> Pharmaceuticals |
| Arzneimittel | PharmaceuticalsPharmaceuticals -> Listed in ZINC15 |
| SpringerMaterials Properties | 15N nuclear magnetic resonance spectrum |
| Pestizide | Biocide |
| LogP (Verteilungskoeffizient) | log Kow = 1.861.87 |
| Color/Form | Rhombohedra from etherNeedles from water |
| Löslichkeit | One gram dissolves in about 5 ml alcohol, 2 ml chloroform, in about 4 ml ether, and in 30 to 50 ml of expressed almond oil or olive oil. Also sol in dil acids.Soluble in acidIn water, 1,310 mg/L at 25 °C>24.8 [ug/mL] (The mean of the results at pH 7.4)alcohol: soluble1 gm in 5 mlSoluble in ethanol, chloroform, ethyl ether and dilute acids. Sparingly soluble in water |
| Human Drugs | Breast FeedingLactationAnesthetics, LocalPharmaceuticals |
| Animal Drugs | Pharmaceuticals -> UK Veterinary Medicines Directorate List |
| Siedepunkt | 310 °C172 °C (12.7517 mmHg) |
| Schmelzpunkt | 92 °C88-90 °C |
| Dampfdruck | 2.6X10-4 mm Hg at 25 °C /Estimated/ |
| Dichte | 1.17 |
| Brechungsindex | 1.5600 (estimate) |
| Flammpunkt | 172°C/13mm |
| Lagerbedingungen | 2-8°C |
| Aggregatzustand | Crystalline Powder |
| pKa (Säurekonstante) | 2.5(at 25℃) |
| Farbe | White |
| Geruch | odorless |
| Merck | 14,1086 |
| BRN | 638434 |
| Henry-Konstante | 6.2×102 mol/(m3Pa) at 25℃, HSDB (2015) |
| Stabilität | Stable. Combustible. Incompatible with strong oxidizing agents. |
| Kosmetik-Inhaltsstoffe Funktionen | UV ABSORBERORAL CARE |
| InChI | 1S/C9H11NO2/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6H,2,10H2,1H3 |
| InChIKey | BLFLLBZGZJTVJG-UHFFFAOYSA-N |
| SMILES | CCOC(=O)c1ccc(N)cc1 |
| LogP (Verteilungskoeffizient) | 1.860 |
| CAS Datenbank | 94-09-7(CAS DataBase Reference) |
| NIST chemische Informationen | Benzoic acid, 4-amino-, ethyl ester(94-09-7) |
| EPA chemische Informationen | Benzocaine (94-09-7) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 11.1% (39 of 351) of reports.DangerH317 (77.8%): May cause an allergic skin reaction [Warning Sensitization, Skin]P260, P261, P264, P270, P272, P273, P280, P302+P352, P308+P316, P321, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 351 reports by companies from 22 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H402: Harmful to aquatic life [Hazardous to the aquatic environment, acute hazard] |
|---|---|
| Regulatorische Informationen | Benzoic acid, 4-amino-, ethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzoic acid, 4-amino-, ethyl ester are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)Status: Active Update: 31-05-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/19637Benzocaine: Does not have an individual approval but may be used under an appropriate group standard |
| Weitere Sicherheitsinformationen | IMAP assessments - Benzoic acid, 4-amino-, ethyl ester: Environment tier I assessment |
| Gefahrenübersicht | Procaine allergy used to be a common skin sensitizer for dentists. There exists cross-reactivity between procaine, benzocaine, and tetracaine but not with lidocaine and other amide-type local anesthetics currently used. [Kanerva, p. 434] |
| FDA-Anforderungen | Anorectal drug products for over-the-counter human use. Local anesthetic active ingredients. The active ingredient of the product consists of any of the following when used in the concentration or within the concentration range established for each ingredient. Benzocaine 5 to 20 percent is included on this list.External analgesic drug products for over-the-counter human use. Analgesic, anesthetic, and antipruritic active ingredients. The active ingredient of the product consists of any of the following within the specified concentration established for each ingredient: Male genital desensitizers: benzocaine, 3 to 7.5 percent in a water-soluble base. |
| Hazard Classes and Categories | Skin Sens. 1 (77.8%)Skin sensitization - Category 1Hazardous to the aquatic environment (Acute) - Category 3 |
| Lagerbedingungen | Benzocaine topical creams and ointments should be stored in tight containers and protected from lightprolonged exposure to temperatures greater than 30 °C should be avoided.Benzocaine topical aersols and solutions should be stored at a temperature less than 40 °C, preferably between 15-30 °Cfreezing should be avoided. Because the contents of benzocaine aerosols are under pressure, the aerosol container should not be punctured, used or stored near heat or an open flame, exposed to temperatures greater than 49 °C, or placed into a fire or incinerator for disposal. |
| Entsorgungsverfahren | SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations. |
| Treatment | Treatment is primarily symptomatic and supportivetermination of anesthesia by pneumatic tourniquet inflation should be attempted when the agent is administered by infiltration or regional injection. Methemoglobinemia may be treated with methylene blue, 1-2 mg/kg I.V. infused over several minutes. Seizures commonly respond to diazepam, while hypotension responds to I.V. fluids and Trendelenburg positioning. Bradyarrhythmias (when the heart rate is <60) can be treated with I.V., I.M., or SubQ atropine 15 mcg/kg. With the development of metabolic acidosis, I.V. sodium bicarbonate 0.5-2 mEq/kg and ventilatory assistance should be instituted. (L1861) |
| Gesundheitliche Auswirkungen | Allergic reactions occur with ester local anaesthetics (like benzocaine) because of the PABA structure. Benzocaine also is a well-known cause of methemoglobinemia. [Wikipedia]. Methemoglobinemia has been reported with benzocaine in oral overdose. (L1861) |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 250(SRC), determined from a log Kow of 1.86(2) and a regression-derived equation(3), indicates that benzocaine is expected to have moderate mobility in soil(SRC). Volatilization of benzocaine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.6X10-8 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Benzocaine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.6X10-4 mm Hg(SRC), determined from a fragment constant method(5). Benzocaine was classified as biodegradable in a procedure using an acclimated sludge inoculum(6), indicating that biodegradation may be an important fate process in the terrestrial environment(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 250(SRC), determined from a log Kow of 1.86(2) and a regression-derived equation(3), indicates that benzocaine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.6X10-8 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 5(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). An estimated base-catalyzed second-order hydrolysis rate constant of 2.4X10-9 L/mole-sec corresponds to half-lives of 91 yrs and 9 yrs at pH values of 7 and 8, respectively(7). Benzocaine was classified as biodegradable in a procedure using an acclimated sludge inoculum(6), indicating that biodegradation may be an important fate process in the aquatic environment(SRC).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), benzocaine, which has an estimated vapor pressure of 2.6X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase benzocaine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 11 hrs(SRC), calculated from its rate constant of 3.6X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase benzocaine may be removed from the air by wet and dry deposition(SRC). Benzocaine is susceptible to direct photolysis as indicated by formation of this compound from photodegradation of ethyl N-phenyl-carbamate (EPC), and further degradation of benzocaine to the azo and colored products of EPC(4). |
| Unerwünschte Wirkungen | Skin Sensitizer - An agent that can induce an allergic reaction in the skin.Benzocaine is relatively safe and low-risk when applied topically. However, 1 of the more life-threatening adverse effects is methemoglobinemia, which is characterized by cyanosis, hypoxia, and dyspnea that do not improve with oxygen administration. This effect occurs due to benzocaine's ability to metabolize into nitrobenzene, which reduces hemoglobin's oxygen-binding capacity by oxidizing iron (Fe2+ to Fe3+). Other adverse effects include hypotension, bradycardia, cardiac arrest, convulsions, drowsiness, dizziness, edema, and allergic reactions. Benzocaine topical spray is dosed for ages 12 and older as needed, a maximum of 4 times daily. A case involving a 14-year-old transgender male revealed vulvar changes and labial enlargement attributed to chronic use of a topical product containing benzocaine. This underscores the potential risks associated with off-the-shelf products and emphasizes the need for healthcare providers to inquire about such product use in adolescents with vulvovaginal concerns. Benzocaine is featured in the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) List due to the associated risk of methemoglobinemia. Avoiding benzocaine use in infants, especially for conditions like teething or pharyngitis. |
| Expositionspfade | Topicaloral |
| Toxizitätsübersicht | Signs and Symptoms of OverdoseBenzocaine binds to sodium channels and reversibly stabilizes the neuronal membrane which decreases its permeability to sodium ions. Depolarization of the neuronal membrane is inhibited thereby blocking the initiation and conduction of nerve impulses. |
| Soil Adsorption/Mobility | The Koc of benzocaine is estimated as 250(SRC), using a log Kow of 1.86(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that benzocaine is expected to have moderate mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils(SRC). |
| Human Toxicity Excerpts | /CASE REPORTS/ A 27-year-old man with a history of cocaine abuse ingested a large quantity of street cocaine in an apparent suicide attempt. Shortly thereafter, he developed tonic-clonic seizures and became cyanotic. An arterial blood gas sample, collected in the emergency department, appeared chocolate-brown and showed pO2 279 mmHg, pCO2 53 mmHg, and pH 7.15. Hemoglobin spectral analysis revealed significant methemoglobinemia (37%). Subsequent gas-chromatographic and mass-spectral analysis of urine confirmed the presence of cocaine (106 mg/L), benzoylecgonine (94 mg/L), and other metabolites. Further testing revealed the presence of benzocaine, a compound known to produce methemoglobinemia. A powder submitted as the "cutting" substance was shown to be benzocaine. When confronted with a possible cocaine overdose (particularly by ingestion), the physician should consider the possible clinical effects of adulterants, especially local anesthetics such as benzocaine./CASE REPORTS/ On rare occasions benzocaine has produced methemoglobinemia from oral, rectal and dermal exposures. There is disagreement whether this is an idiosyncratic event or a dose-related event. To gain a better perspective on this problem cases at 4 large regional poison centers of children <18-y of age from 1993-1996 /were retrospectively reviewed/. One hundred and eighty-eight benzocaine exposures were reported. Mean and median ingested dosage were 86.8 (+/- 89.5) mg/kg and 50 mg/kg, respectively. Fifty-eight patients (30%) were managed in the emergency department8 patients had methemoglobin levels determined. One child had a methemoglobin level of 19%all others were <1%. One hundred and seventy-three patients (92%) remained asymptomatic. Other symptoms were minor: oral numbness (8), vomiting (3), and 1 each of oral irritation, dizziness and nausea. In this series of accidental ingestions of benzocaine-containing products cyanosis was rare and apparently not dose related. These cases may be safely managed at home with telephone follow up for at least 2 hr. If there is evidence of cyanosis, dusky pallor, shortness of breath, or change in mental status direct medical evaluation should be recommended. |
| Artificial Pollution Sources | Benzocaine's production and use as a local anesthetic(1) may result in its release to the environment through various waste streams(SRC). |
| Environmental Biodegradation | AEROBIC: Benzocaine was classified as biodegradable in a procedure using an acclimated sludge inoculum and a 5 day test period(1). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Environmental Bioconcentration | An estimated BCF of 5 was calculated for benzocaine(SRC), using a log Kow of 1.86(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC), provided the compound is not altered physically or chemically once released into the environment. |
| Wassergefährdungsklasse (WGK) | 2 |
| TSCA-Inventar-Status | TSCA listed |
| UN-Transportnummer | 3077 |
| Zollcode | 29224995 |
| RTECS-Nr. | DG2450000 |
| R-Sätze (R) | 43-36/37/38-39/23/24/25-23/24/25-11 |
| Toxizität | LD50 oral in rat: 3042mg/kg |
| Gefahrensymbole | Xi,T,F |
| Sicherheitshinweise (S) | 22-24/25-37/39-26-24-45-36/37-16-7 |
| Gefahrenklasse | 9Skin Sens. 1 |
| Verpackungsgruppe | III |
| Lagerklasse | 11 - Combustible Solids |
| Gefahrstoffdaten | 94-09-7(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Benzocaine (ethyl p-aminobenzoate) is used topically by itself or in combination with menthol or phenol in nonprescription dosage forms such as gels, creams, ointments, lotions, aerosols, and lozenges to relieve pain or irritation caused by such conditions as sunburn, insect bites, toothache, teething, cold sores or canker sores in or around the mouth, and fever blisters. Benzocaine is a lipophilic local anesthetic agent with a short duration of action. Like most amino ester-type local anesthetics, it is easily hydrolyzed by plasma cholinesterase. Because of its low pKa, however, it is un-ionized under most physiological conditions and, therefore, can only bind to the lipid side of the local anesthetic receptor. It also can easily cross membranes into systemic circulation to cause systemic toxicities. Furthermore, being a PABA derivative, it has similar allergenic properties to procaine and is contraindicated with sulfonamide antibacterial agents.
Verwenden
Benzocaine is used as an anesthetic (Local and topical) that in products such as burn and sunburn remedies, hemorrhoidal creams, suppositories, creams for treatment of poison ivy, oral and gingival products, sore-throat sprays/lozenges, astringents, appetite suppressants, callus and wart remedies, athlete's-foot remedies, toothache- and denture-irritation products.