Benzocaine

165.18900

165.19

202-303-5

U3RSY48JW5

755909|41531|4688

DTXSID8021804

C28923

Rhombohedra from ether|Needles from water

C05AD03|C - Cardiovascular system|D - Dermatologicals|N - Nervous system|R - Respiratory system

2922499990

52.32000

1.9

DryPowder

1.17

92 °C

310 °C

> 110ºC

1.5502

soluble in ethanol, chloroform, ethyl ether and dilute acids. Sparingly soluble in water

0-6ºC

2.6X10-4 mm Hg at 25 deg C /Estimated/

LD50 oral in rat: 3042mg/kg

2.51(at 25 °C)

Henry's Law constant = 1.6X10-8 atm-cu m/mole at 25 °C /Estimated/

2.51 (at 25 °C)|pKa = 2.51 (conjugate acid)

148.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|145.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Stable in air|Hydroxyl radical reaction rate constant = 3.6X10-11 cu cm/molecule-sec at 25 °C /Estimated/

III

NONH for all modes of transport

2

R36/37/38; R43

S22; S24/25; S37/39; S26; S24

DG2450000

Xi

Stable. Combustible. Incompatible with strong oxidizing agents.

P260, P261, P264, P270, P272, P273, P280, P302+P352, P307+P311, P314, P321, P333+P313, P363, P391, P405, P501

H317

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 quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

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.

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 47 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H317 (98.82%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P264, P272, P280, P302+P352, P305+P351+P338, P321, P333+P313, P337+P313, P363, and P501|Aggregated GHS information provided by 207 companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.|Danger|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P260, P261, P264, P270, P272, P280, P302+P352, P307+P311, P314, P321, P333+P313, P363, P405, and P501

LD50=3040 mg/kg (rat, oral)

Benzocaine's production and use as a local anesthetic(1) may result in its release to the environment through various waste streams(SRC).

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).

The rate constant for the vapor-phase reaction of benzocaine with photochemically-produced hydroxyl radicals has been estimated as 3.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 11 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 2.4X10-9 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 91 yrs and 9 yrs at pH values of 7 and 8, respectively(2). The compound is one of the photodegradation products formed from ethyl N-phenyl-carbamate (EPC) using a high-pressure quartz mercury vapor lamp over a 5 hr time period; benzocaine further degrades to the azo and colored products, (i.e. diethyl 4,4'-azobenzenedicarboxylate) of EPC(3).

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.

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).

The Henry's Law constant for benzocaine is estimated as 1.6X10-8 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that benzocaine is expected to be essentially nonvolatile from water surfaces(2). 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(3).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 167,623 workers (146,838 of these are female) are potentially exposed to benzocaine in the US(1). Occupational exposure to benzocaine may occur through inhalation and dermal contact with this compound at workplaces where benzocaine is produced or used(SRC). The general population may be exposed to benzocaine via inhalation and dermal contact with products containing benzocaine(SRC).

For general use as a lubricant and topical anesthetic on esophagus, larynx, mouth, nasal cavity, rectum, respiratory tract or trachea, urinary tract, vagina. It is also used to suppress gag reflex.|Treatment of oropharyngeal pain|Treatment of haemorrhoidal disease

Indicated for the relief of: canker sores, cold sores, or fever blisters: benzocaine (gel and topical solution); gingival or oral mucosal pain (i.e., pain caused by mouth or gum irritation, inflammation, lesions, or minor dental procedures): benzocaine (gel, dental paste, lozenges, and topical solution); dental prosthetic pain (i.e., pain or irritation caused by dentures or other dental or orthodontic appliances): benzocaine (dental paste, gel ointment, and topical solution); teething pain: benzocaine (7.5% and 10% gel); and toothache: benzocaine (10% and 20% gel and topical solution).|Indicated to suppress the gag reflex and/or other laryngeal and esophageal reflexes to facilitate dental examination or procedures (including oral surgery), endoscopy, or intubation: benzocaine (gel, topical aerosol, and topical solution). /Included in US product labeling/|Indicated to provide topical anesthesia of accessible mucous membranes prior to examination, endoscopy or instrumentation, or other procedures involving the: esophagus: benzocaine (gel and topical solution)); larynx: benzocaine (gel and topical solution); mouth, In dental procedures and oral surgery: benzocaine (gel, topical aerosol, and topical solution); nasal cavity: benzocaine (gel); pharynx or throat: benzocaine (gel, topical aerosol, and topical solution); rectum: benzocaine (gel); respiratory tract or trachea: benzocaine (gel, topical aerosol, and topical solution); urinary tract: benzocaine (gel); and vagina: benzocaine (gel).|Anesthetic (local).|(VET): Local (usually surface) anesthetic.

Infants and the elderly were more likely to develop toxic methemoglobinemia after benzocaine exposure. Other risk factors included genetic reductase deficiencies, exposure to high doses of anesthetic, and presence of denuded skin and mucous membranes. Because of the potential for severe complications, methemoglobinemia should be corrected promptly in compromised patients and those with toxic benzocaine concentrations. The possibility of masking symptoms during general anesthesia carries special risk of use of this agent in the preanesthesia setting.|Use of otic anesthetics may mask symptoms of a fulminating middle ear infection (acute otitis media). Otic solutions containing benzocaine should not be used in the presence of a perforated tympanic membrane.|When applied topically as recommended, benzocaine is relatively nontoxic, however, sensitization may occur.|When used as a male genital desensitizer, benzocaine generally does not adversely affect orgasm in female sexual partners and does not appear to anesthetize the clitoris or vagina.|For more Drug Warnings (Complete) data for BENZOCAINE (9 total), please visit the HSDB record page.

Benzocaine is a local anesthetic commonly used as a topical pain reliever. It is the active ingredient in many over-the-counter analgesic ointments. It is also indicated for general use as a lubricant and topical anesthetic on intratracheal catheters and pharyngeal and nasal airways to obtund the pharyngeal and tracheal reflexes; on nasogastric and endoscopic tubes; urinary catheters; laryngoscopes; proctoscopes; sigmoidoscopes and vaginal specula.

Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. (See all compounds classified as Anesthetics, Local.)

Branchial and urinary elimination of benzocaine residues was evaluated in adult rainbow trout, Oncorhynchus mykiss, given a single dorsal aortic dose of 14(C)-benzocaine hydrochloride. Branchial elimination of benzocaine residues was rapid and accounted for 59.2% of the dose during the first 3 h after dosing. Renal elimination of radioactivity was considerably slower; the kidney excreted 2.7% dose within 3 h and 9.0% within 24 hr. Gallbladder bile contained 2.0% dose 24 hr after injection. Of the radioactivity in radiochromatograms from water taken 3 min after injection, 87.3% was benzocaine and 12.7% was N-acetylated benzocaine. After 60 min, 32.7% was benzocaine and 67.3% was N-acetylated benzocaine. Of the radioactivity in radiochromatograms from urine taken 1 hr after dosing, 7.6% was para-aminobenzoic acid, 59.7% was N-acetylated para-aminobenzoic acid, 19.5% was benzocaine, and 8.0% was N-acetylated benzocaine. The proportion of the radioactivity in urine changed with time so that by 20 hr, 1.0% was para-aminobenzoic acid and 96.6% was N-acetylated para-aminobenzoic acid. Benzocaine and a more hydrophobic metabolite, N-acetylated benzocaine, were eliminated primarily through the gills; renal and biliary pathways were less significant elimination routes for benzocaine residues.

The effect of dose and enzymatic inhibition on the percutaneous absorption and metabolism of benzocaine was studied in vitro in the hairless guinea pig. At the dose level of 2 ug/sq cm, benzocaine was rapidly absorbed and extensively metabolized (80%) by acetyltransferase. As the applied dose of benzocaine was increased to 40 and 200 ug/sq cm, N-acetylation of benzocaine decreased to 44 and 34%, respectively, suggesting saturation of the acetyltransferase system. Total 14(C) absorption after benzocaine application was not significantly different between control and enzyme-inhibited skin and therefore does not appear to be affected by the extent of benzocaine metabolism during percutaneous penetration. Skin provides a significant first-pass metabolic effect for therapeutic doses of percutaneously absorbed benzocaine, and the primary metabolite formed, acetylbenzocaine, is biologically active.

Benzocaine 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.|Benzocaine reversibly stabilizes the neuronal membrane with decreases its permeability to sodium ions. Depolarization of the neuronal membrane is inhibited thereby blocking the initiation and conduction of nerve impulses.

... The cases of 2 patients who developed benzocaine-induced methemoglobinemia after the administration of benzocaine as premedication for transesophageal echocardiography /are described/. The use of intravenous methylene blue resolved the cyanosis in both patients.|Emergency and supportive measures; 1. Maintain an open airway and assist ventilation if necessary. 3. Treat coma, seizures, hypotension, arrhythmias, and anaphylaxis if they occur. Extracorporeal circulatory assistance (eg, balloon pump or partial cardiopulmonary bypass) has been used for short-term support for patients with acute massive overdose with 20% lidocaine solution. 3. Monitor vital signs and ECG for at least 6 hours /anesthetics, local/.|Decontamination; 1. Parenteral exposure. Decontamination is not feasible. 2. Ingestion. a. Prehospital. Administer activated charcoal if available. Do not induce vomiting because of the risk of abrupt onset of seizures. b. Hospital. Administer activated charcoal. Consider gastric lavage only for large recent ingestion /anesthetics, local/.|Enhanced Elimination; Because lidocaine has a moderate volume of distribution, hemoperfusion is potentially beneficial, particularly after a massive overdose or when metabolic elimination is impaired because of circulatory collapse or severe liver disease /anesthetics, local/.

/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 department; 8 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.

4-Aminobenzoic Acid Ethyl Ester

Oral: Lozenges 5 mg Vicks Chloraseptic Children's Sore Throat Lozenges, (Procter & Gamble); 10 mg Cepacol Anesthetic Lozenges (with cetylpyridinium chloride), (Williams JB), S[ec-TThroat Lozenges, (Bristol-Myers); 15 mg Mycinettes, (Pfeiffer).|Otic: Solution: 20% Americaine-Otic (with benzethonium chloride), (Celltech), Otocain, (Abana).|Topical: Aerosol: 20% Hurricaine Spray (with or without disposable extension tube), (Beutlich). Gel: 6.3% Anbesol Regular Strength (with alcohol 70% and phenol), (Wyeth); 7.5% Anbesol Baby, (Wyeth), Orabase Baby (alcohol free), (Colgate), Orajel Baby Regular, (Del); 10% Orajel Baby Nighttime, (Del), Orajel Regular Strength, (Del), Orajel Denture (with eugenol and propylene glycol), (Del), Zilactin-B Medicated Gel with Benzocaine, (Zila); 15% Orabase Gel (with alcohol), (Colgate); 20% Americaine Anesthetic Lubricant (with benzethonium chloride), (Celltech), Anbesol Maximum Strength (with alcohol 60%), (Wyeth), Hurricaine, (Beutlich), Orajel Maximum Strength, (Del), Orajel Mouth-Aid (with benzalkonium chloride povidone propylene glycol and zinc chloride), (Del). Paste: 20% Orabase-B with Benzocaine, (Colgate-Hoyt). Solution: 2.5% Babee Teething Lotion (with alcohol 20% cetalkonium chloride and propylene glycol), (Pfeiffer), 6.3% Anbesol Regular Strength (with alcohol 70% phenol and povidone-iodine yielding 0.04% iodine), (Wyeth); 20% Anbesol Maximum Strength (with alcohol 60%), (Wyeth), Hurricaine, (Beutich), Kank-a (with alcohol 0.5% aspartame benzyl alcohol and propylene glycol), (Blistex), Orajel Mouth-Aid Liquid (with alcohol 70% cetylpyridinium chloride povidone and tartrazine), (Del).|Topical: Aerosol 5% Foille Medicated First Aid (with benzyl alcohol and chloroxylenol 0.1%), (Blistex); 20% Dermoplast (with menthol 0.5% and methylparaben), (Medtech), Solarcaine (with isopropyl alcohol 35% w/w and triclosan 0.13%), (Schering-Plough). Cream: 1% Solarcaine (with trilosan 0.2%), (Schering-Plough); 5% Benzocaine Cream, (CMC, Rugby), Benzocol, (Hauck), Ivarest (with calamine 14% and propylene glycol), (Blistex), Rhulicream (with calamine 3% and camphor 0.3%), (Rhydelle); 6% BiCOZENE (with resorcinol 1.67%), (Novartis). Gel: 20% Americaine Anesthetic Lubricant, (Celltech), Detane, (Del). Lotion: 0.5% Solarcaine (with triclosan 0.2%), (Schering-Plough); 5% Ivarest (with calamine 14% and propylene glycol), (Blistex). Ointment: 2% Chiggerex, (Scherer), 5% Foille Medicated First Aid (with chloroxylenol 0.1%), (Blistex); 10% Anacaine (with boric acid), (Gordon). Solution: 2.1% Chiggertox (with benzyl benzoate 21.4%), (Scherer); 20% Outgro, (MedTech).|Trade Names: Anaesthesin (Ritsert, Germany); Hurricaine (Beutlich, USA)

All other basic organic chemical manufacturing|Benzoic acid, 4-amino-, ethyl ester: ACTIVE

Method: AOAC 968.40; Procedure: colorimetric method; Analyte: benzocaine; Matrix: drugs; Detection Level: not provided.[|Method: AOAC 968.42; Procedure: spectrophotometric method; Analyte: benzocaine; Matrix: drugs; Detection Level: not provided. Applicable in presence of glycerol and propylene glycol bases.[

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