Benzocaine

Benzocaine shares a common receptor with all other local anesthetics (LAs) in the voltage-gated Na+ channel, with an IC50 of 0.8 mM tested with a potential of +30 mV.

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Neurological Disease

IC50: 0.8 mM (Na+ channel)[1].

Benzocaine blocks μ1 wild-type Na+ currents in a dose-dependent Manner. The Benzocaine concentration that inhibits 50% of Na+ currents (IC50) is estimated to be about 0.8 mM when a test potential of +30 mV is applied. The slope of the h∞ curve is also significantly reduced by benzocaine (from 6.6 to 9.9 mV). Mutation of μ1-N1584A also significantly increases the potency of Benzocaine. At 1 mM, Benzocaine blocks about 55% of wild-type Na+ current but about 95% of μ1-N1584A mutant current. Benzocaine also appears to bind more strongly to its LA receptor in the N1584A mutant than in the wild type[1]. The inhibition of Ca2+ uptake occurres at lower Benzocaine concentration (IC50=40.3±1.2mM) than that affecting the enzymatic activity[2].

A common Benzocaine-containing anesthetic is topically applied to the following species: dogs, domestic shorthair cats, Long-Evans rats, Sprague-Dawley rats, ferrets, rhesus monkeys, cynomolgus monkeys, owl monkeys, New Zealand White rabbits, miniature pigs, ICR mice, C3H mice, and C57BL/10SnJ mice. All animals, except mice and rats, receive a 2-second spray to the mucous membranes of the nasopharynx for an estimated dose of 56 mg. A 2-second spray to rodents' oral mucous membranes delivers too great a volume of fluid for these animals. The study is repeated in dogs several months later to confirm low response. Response to Benzocaine spray is observed in most animals tested, with response peaking between 15 and 30 minutes after dosing[3].

[1]. Wang GK et al. A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels. Pflugers Arch. 1998 Jan;435(2):293-302.

[2]. Di Croce D et al. Drug action of benzocaine on the sarcoplasmic reticulum Ca-ATPase from fast-twitch skeletal muscle. Naunyn Schmiedebergs Arch Pharmacol. 2015 Nov;388(11):1163-70.

[3]. Davis JA, et al. Benzocaine-induced methemoglobinemia attributed to topical application of the anesthetic in several laboratory animal species. Am J Vet Res. 1993 Aug;54(8):1322-6.

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DATA ITEMS CITED :

12

MOLECULAR FORMULA :

C9-H11-N-O2

MOLECULAR WEIGHT :

165.21

WISWESSER LINE NOTATION :

ZR DVO2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - guinea pig

REFERENCE :

JSCCA5 Journal of the Society of Cosmetic Chemists. (Soc. of Cosmetic Chemists, 1995 Broadway, Suite 1701, New York, NY 10023) V.1- 1947- Volume(issue)/page/year: 28,357,1977 ** ACUTE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

12 mg/kg

TOXIC EFFECTS :

Blood - methemoglobinemia-carboxyhemoglobin

REFERENCE :

NEJMAG New England Journal of Medicine. (Massachusetts Medical Soc., 10 Shattuck St., Boston, MA 02115) V.198- 1928- Volume(issue)/page/year: 263,454,1960

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3042 mg/kg

TOXIC EFFECTS :

Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (2),34,1996

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2500 mg/kg

TOXIC EFFECTS :

Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (2),34,1996

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

216 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 17,900,1974

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

1150 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,33,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Bird - wild bird species

DOSE/DURATION :

56 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 21,315,1972 *** REVIEWS *** TOXICOLOGY REVIEW PHREA7 Physiological Reviews. (American Physiological Soc., 9650 Rockville Pike, Bethesda, MD 20814) V.1- 1921- Volume(issue)/page/year: 12,190,1932 *** U.S. STANDARDS AND REGULATIONS *** EPA FIFRA 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATION FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936- Volume(issue)/page/year: 54,7740,1989 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 81723 No. of Facilities: 293 (estimated) No. of Industries: 8 No. of Occupations: 7 No. of Employees: 2005 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 81723 No. of Facilities: 1499 (estimated) No. of Industries: 12 No. of Occupations: 17 No. of Employees: 167623 (estimated) No. of Female Employees: 146838 (estimated)