Butyl 4-aminobenzoate

193.24

193.24

202-317-1

EFW857872Q

757433|128464

DTXSID7022417

Crystals from alc|White powder|White, amorphous powder

2922499990

52.3

2.9

N-butyl-p-aminobenzoate is a yellow powder. Insoluble in water. (NTP, 1992)

1.1±0.1 g/cm3

58 °C

173-174 °C @ Press: 8 Torr

184.6±17.9 °C

1.540

Very slightly soluble in water.

Odorless

Tasteless

2.472None

2.472|pKa= 2.47 (conjugate acid)

159.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydrolyzed slowly when boiled with water|ALKALI HYDROXIDES ACCELERATE HYDROLYSIS

May be sensitive to light and air. Insoluble in water. Slowly hydrolyzed when boiled in water. Also will hydrolyze under high and low pH conditions (NTP, 1992).

Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

N-BUTYL-P-AMINOBENZOATE is an aminophenyl ester derivative. 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. Esters react with acids to liberate heat along with alcohols and acids. Strong oxidizing acids may cause a vigorous reaction that is sufficiently exothermic to ignite the reaction products. Heat is also generated by the interaction of esters with caustic solutions. Flammable hydrogen is generated by mixing esters with alkali metals and hydrides.

NONH for all modes of transport

3

R36/37/38;R43

S26-S36/37

DG1530000

Xi:Irritant;

P261-P280-P305 + P351 + P338

H315-H317-H319-H335

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P272, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P333+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 42 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

A fire in your laboratory involving this chemical should be extinguished with a dry chemical, carbon dioxide or halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, you should dampen the solid spill material with alcohol, then transfer the dampened material to a suitable container. Use absorbent paper dampened with alcohol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with alcohol followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should keep this material in a tightly closed container under an inert atmosphere, and store it at refrigerated temperatures. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Combustible when exposed to heat or flame.

In studies, the most common effect was related to the generation of a prolonged effect. It was also shown in preclinical trials to produce tissue necrosis and neuritis. The LD50 of butamben is registered to be of 67 mg/kg.

These agents /cholinesterase inhibitors such as antimyasthenics; cyclophosphamide; demecarium; echothiophate; neurotoxic insecticides, possibly including large quantities of topical malathion; isoflurophate; thiotepa/ may inhibit metabolism of ester derivatives; absorption of significant quantities of ester derivatives in patients receiving a cholinesterase inhibitor may lead to increased risk of toxicity. /Topical anesthetics/|Metabolites of PABA-derivative topical anesthetics may antagonize antibacterial activity of sulfonamides, especially if the anesthetics are absorbed in significant quantities over prolonged periods of time. /Topical anesthetics/

LD50 Mouse ip 67 mg/kg

As all other local anesthetics, it is thought that butamben will be highly bound to plasma proteins, mainly to alpha-1-acid glycoprotein.

Butamben was indicated for the treatment of chronic pain due to its long-duration effect. It is also indicated as a surface anesthetic for skin a mucous membrane and for the relief of pain and pruritus associated with anorectal disorders.

Anesthetics, Local|... POORLY SOL IN WATER &, CONSEQUENTLY, TOO SLOWLY ABSORBED TO BE TOXIC. THEY CAN BE APPLIED DIRECTLY TO WOUNDS & ULCERATED SURFACES WHERE THEY REMAIN LOCALIZED FOR LONG PERIODS OF TIME ... ACCOUNTS FOR SUSTAINED ANESTHETIC ACTION. ... MOST IMPORTANT MEMBERS OF SERIES ARE ... BUTAMBEN, USP (BUTYL AMINOBENZOATE, BUTESIN).|MEDICATION (VET): TOPICALLY, AS SPRAY OR IN OINTMENTS (1-2%). ...PARENTERAL USE IN OIL HAS PROVIDED ANESTHESIA FOR UP TO 1 OR 2 DAYS & IS OCCASIONALLY USED IN DEEP PERIANAL INJECTIONS (OR WITH PROCAINE BASE & BENZYL ALC) WHERE PROLONGED PROTECTION AGAINST STRAINING IS DESIRED.|Topical anesthetics are indicated to relieve pain, pruritus, and inflammation associated with minor skin disorders, including: burns, minor, including sunburn; bites (or stings), insect; dermatitis, contact, including poison ivy, poison oak, or poison sumac; wounds, minor such as cuts and scratches. /Included in US product labeling; Topical anesthetics/

Butamben has been shown to selectively inhibit dorsal root pain signal transmission for periods of months when administered as epidural suspensions. The effect of butamben is not related to any significant loss of motor function which indicates that it targets specifically the pain-sensing C fibers of the dorsal root. When administered topically, butamben produced anesthesia by accumulating in the nerve cell membrane causing it to expand and lose its ability to depolarize and blocking the impulse transmission.

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.)

When butamben is administered epidurally in a suspension form, the physical characteristics of butamben allow a very slow release. When administered topically, butamben is also reported to have a very low systemic absorption which allows for a longer duration of action.|The metabolites found in plasma after cholinesterase processing are disposed of in the urine.|This pharmacokinetic property has not been determined.|Clearance is flow-limited and it highly depends on the state of protein-bound form.

The metabolic pathway of butamben follows the same pattern of other local anesthetics and it is driven mainly by the hydrolysis via cholinesterase for the formation of inert metabolites.

The effective half-life of unencapsulated butamben is registered to be of 90 minutes. Some efforts were made to prepare D, L-lactic acid capsules which increased the half-life of butamben to even 400 hours.

Butamben acts by inhibiting the voltage-gated calcium channels in dorsal root ganglion neurons. The modification in this channels is thought to cause a disturbance of the channel kinetics acceleration. It is reported as well that butamben is an inhibitor of the sodium channels and a delayed rectifier of potassium currents. All the effects of butamben are performed in the root ganglion neurons which suggests that the related anesthetic effect may be caused by the reduced electrical excitability.|...ACTION IS TO INTERFERE WITH INITIATION & TRANSMISSION OF NERVE IMPULSE. PRESENT THEORY HOLDS THAT LOCAL ANESTHETICS PREVENT DEPOLARIZATION OF NERVE MEMBRANE &, HENCE, PROPAGATION OF IMPULSE. ...THOUGHT TO BE DUE TO INTERFERENCE WITH MUTUAL EXCHANGE OF SODIUM & POTASSIUM IONS ACROSS MEMBRANE. /LOCAL ANESTHETICS/

SYMPTOMS: Symptoms of exposure to this compound may include sensitivity dermatitis, nausea, vomiting and methemoglobinemia. ACUTE/CHRONIC HAZARDS: This compound is an allergic sensitizer. (NTP, 1992)

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

butamben

ESSENTIALLY 100% AS AN ANESTHETIC

... MAY BE APPLIED AS DUSTING POWDERS, UNDIL OR DIL WITH STERILE TALC. THEY ARE SOL IN OIL & MAY BE INC IN OILY SOLN, OINTMENTS, & SUPPOSITORIES. /ANESTHETICS OF LOW SOLUBILITY/|Grade: NF

Benzoic acid, 4-amino-, butyl ester: ACTIVE|Available in the United States as a surface anesthetic in the form of a picrate.

METHOD IS PRESENTED FOR IDENTIFICATION & DETERMINATION BY THIN LAYER & GAS CHROMATOGRAPHY OF ESTERS OF P-AMINOBENZOIC ACID WITH FREE AMINE FUNCTION & LOCAL ANESTHETICS.