Hexetidine

339.6

339.60

161071

205-513-5

852A84Y8LS

757394|17764

DTXSID1045297

Liquid

A01AB12|A - Alimentary tract and metabolism|G - Genito urinary system and sex hormones

2933599090

32.5

5.7

0.8889 g/cm³ @ Temp: 20 °C

<25 °C

160 °C

70°C

1.4649

Not miscible or difficult to mix in water.acetone: soluble (lit.)

Hexetidine is stable and should be stored in a well-closed container in a cool, dry place. Brass and copper equipment should not be used for the handling or storage of hexetidine.

1.54X10-5 mm Hg at 25 deg C (est)

Henry's Law constant = 2.42X10-8 atm-cu m/mol at 25 °C (est)

pKa = 8.3

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

Good thermal stability|Hydroxyl radical reaction rate constant = 2.95X10-10 cu cm/molec-sec at 25 °C (est)

3

36/38-36/37/38

26-36

Xi

Hexetidine is stable and should be stored in a well-closed container in a cool, dry place. Brass and copper equipment should not be used for the handling or storage of hexetidine.

P305 + P351 + P338

H315-H319-H335

SRP: 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.

Hexetidine is incompatible with strong oxidizing agents. Salts are formed with mineral and organic acids; strong acids cause opening of the hexahydropyrimidine ring, releasing formaldehyde.

|Warning|H302 (12.5%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P322, P330, P332+P313, P337+P313, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 48 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P280, P301+P312, P302+P352, P305+P351+P338, P310, P321, P330, P332+P313, P362, and P501

Eye protection and gloves are recommended. When significant quantities are being handled, the use of a respirator with an appropriate gas filter is recommended.

... Cause strong primary irritations ...

LD50 Rat oral 610-1,430 mg/kg|LD50 Mouse oral 1,520 mg/kg|LD50 Rat ip 30-85 mg/kg bw|LD50 Mouse ip 142 mg/kg|For more Non-Human Toxicity Values (Complete) data for Hexetidine (8 total), please visit the HSDB record page.

Hexetidine's production and use as an antiseptic(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 1.2X10+5(SRC), determined from a structure estimation method(2), indicates that hexetidine is expected to be immobile in soil(SRC). The pKa of hexetidine is 8.3(3), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the base exists as a cation and cations do not volatilize. Hexetidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.54X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2010).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.2X10+5(SRC), determined from a structure estimation method(2), indicates that hexetidine is expected to adsorb to suspended solids and sediment(SRC). A pKa of 8.3(3) indicates hexetidine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(4). According to a classification scheme(5), an estimated BCF of 58(SRC), from an estimated log Kow of 5.26(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate, provided the compound is not metabolized by the organism(SRC). Biodegradation data in water were not available(SRC, 2010).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), hexetidine, which has an estimated vapor pressure of 1.54X10-5 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 hexetidine 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 1.3 hours(SRC), calculated from its rate constant of 2.95X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase hexetidine may be removed from the air by wet or dry deposition(SRC). Hexetidine does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of hexetidine with photochemically-produced hydroxyl radicals has been estimated as 2.95X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolysis is not expected to be an important environmental fate process since this compound does not contain functional groups that hydrolyze under environmental conditions(3). Hexetidine does not contain chromophores that absorb at wavelengths >290 nm(3), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 58 was calculated in fish for hexetidine(SRC), using an estimated log Kow of 5.26(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate, provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of hexetidine can be estimated to be 1.2X10+5(SRC). According to a classification scheme(2), this estimated Koc value suggests that hexetidine is expected to be immobile in soil. The pKa of hexetidine is 8.3(3), indicating that this compound will almost entirely exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

A pKa of 8.3(1) indicates hexetidine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(2). Hexetidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.54X10-5 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to hexetidine may occur through inhalation and dermal contact with this compound at workplaces where hexetidine is produced or used. Use data indicate that the general population may be exposed to hexetidine via ingestion of and dermal contact with consumer products containing this compound. (SRC)

A bactericidal and fungicidal antiseptic. It is used as a 0.1% mouthwash for local infections and oral hygiene.|MEDICATION (VET): Hexetidine is a cationic antiseptic with a wide spectrum of actions against Gram-positive and Gram-negative bacteria, as well as some fungi and parasites. In veterinary medicine, it is indicated for use in horses as a shampoo, at low concentrations, for topical application to the skin. The use of hexetidine as teat disinfectant, both as teat dip and teat spray, is also known.|Hexetidine is a nonantibiotic antimicrobial agent that possesses broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi such as Candida albicans. Several studies have identified the antiplaque activity of hexetidine. Hexetidine has been shown to be effective against isolates of Staphylococcus aureus and Pseudomonas aeruginosa in planktonic form and against biofilms of the same microorganisms on PVC. Hexetidine has also been reported to reduce the adherence of Candida albicans to human buccal epithelial cells in vitro. Hexetidine has been shown to be a promising candidate antimalarial agent with IC50 values being comparable with those of quinine chlorohydrate and chloroquine sulfate.|This examiner-blind, parallel group, controlled clinical study examined the effectiveness of a hexetidine (0.1%) mouthwash both in inhibiting the development of supragingival plaque and in reducing gingivitis. One hundred and thirty-four adult subjects completed the 2-week experimental gingivitis model study. Following baseline examinations, which included plaque index, modified gingival index and gingival bleeding index, subjects received a full dental prophylaxis. Subjects were randomly assigned to one of three mouthwashes (hexetidine 0.1%, chlorhexidine 0.12% (positive control) or a 5% hydroalcohol negative control) and commenced three times daily supervised rinsing as their sole method of oral hygiene. All indices were rescored after 2 weeks. Compared to the negative control group, the hexetidine group demonstrated a statistically significant inhibition and reduction of supragingival plaque and gingival inflammation with reductions of 6.3%, 33.5% and 56% for gingivitis, plaque and gingival bleeding, respectively. The results of the chlorhexidine group were used to validate the study. The study confirms the efficacy of a hexetidine rinse in reducing supragingival plaque and gingival inflammation.|For more Therapeutic Uses (Complete) data for Hexetidine (8 total), please visit the HSDB record page.

Oral disinfectants containing chlorhexidine or hexetidine are able to produce disturbances of taste, as demonstrated by Krarup's electrogustometric method and the gustometric method of Harris and Kalmus. Hypo- and dysgeusia are characterized by dissociated disturbances, the most prominent of which concerns the sweet perception. The bitter taste is least affected, whereas the effects on salty and acidic tastes range between that for sweet and bitter. Taste disturbances which include ageusia for 48 hr were observed when the tongue was touched with a 20% solution of chlorhexidine. Not only the disinfectants themselves provoked dysgeusia but also other "taste improving" agents (particularly, the volatile /oils/). In addition to dysgeusia, the authors found disturbances of the mucous membrane sensitivity caused by the test substances.|The study in situ measured enamel erosion by acidified sodium chlorite, essential oil and hexetidine mouthrinses over 15-day study periods. The study was a 5 treatment, single blind cross over design involving 15 healthy subjects using orange juice, as a drink, and water, as a rinse, as positive and negative controls respectively. 2 enamel specimens from unerupted human third molar teeth were placed in the palatal area of upper removable acrylic appliances which were worn from 9 a.m. to 5 p.m., Monday to Friday for 3 weeks. Rinses were used 2x daily and 250 ml volumes of orange juice were imbibed 4x daily. Enamel loss was determined by profilometry on days 5, 10 and 15. The study in vitro involved immersing specimens in the 4 test solutions together with a reduced acid acidified sodium chlorite formulation for a period of 4 hr under constant stirring; Enamel loss was measured by profilometry every hour. Enamel loss was in situ progressive over time with the 3 rinses and orange juice but negligible with water. Acidified sodium chlorite produced similar erosion to orange juice and significantly more than the two proprietary rinses and water. The essential oil and hexetidine rinses produced similar erosion and significantly more than water. Enamel loss in vitro was progressive over time, and the order from low to high erosion was reduced acid acidified sodium chlorite, acidified sodium chlorite, Essential oil, and hexetidine mouthrinses and orange juice. Based on the study in situ, it is recommended that low pH mouthrinses should not be considered for long term or continuous use and never as pre-brushing rinses. In view of the plaque inhibitory efficacy of acidified sodium chlorite, short- to medium-term applications similar to those of chlorhexidine would be envisaged.|Hexetidine has been used in human medicine as an antiseptic agent for over 40 years. Although, mild buccal irritation has been reported on rare occasions, there is no evidence of any significant toxic effect from hexetidine in man (eg, if swallowed when being used as a mouthwash).|In a few individuals mild irritation (described as sore mouth, burning or itching) of the tongue and/or buccal tissues has been reported. Other side effects which are reported very rarely include transient anesthesia and taste impairment.|It is not known whether hexetidine is excreted in human breast milk, however, in view of the negligible amount of hexetidine which could be predicted to be systemically absorbed, it is unlikely that concentrations of hexetidine in the milk will present any risk to the neonate/infant.

Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. (See all compounds classified as Antifungal Agents.)|Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects. (See all compounds classified as Anti-Infective Agents, Local.)

Because of its cationic nature, hexetidine is absorbed to the mucous membranes and dental plaque after oral administration and is not easily removed. Studies in human beings with radiolabeled hexetidine have shown that it is retained on buccal tissues for 8 to 10 hours after a single oral rinse and it has been possible to detect the continued presence of it on the oral tissues for as long as 65 hours after application.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ Two hundred twenty human subjects were patch tested on the forearm with an ointment containing 1% hexetidine; 48 hours later 212 subjects were available for re-examination. None showed evidence of dermatitis or irritation at the contact site of the test material. Two weeks later 168 of these subjects were available for retesting and the original sites were again used for the repeated patch test. There was no evidence of primary irritation or sensitization.|/SIGNS AND SYMPTOMS/ Allergic contact dermatitis and altered olfactory and taste perception have occasionally been reported ... Toxic when administered intravenously. Solutions of hexetidine in oil at concentrations of 5-10% w/v cause strong primary irritations without sensitization in humans.|/ALTERNATIVE and IN VITRO TESTS/ Cell cultures were established from small samples of buccal tissue, using a 3T3 fibroblast feeder-layer technique. After exposure to increasing dilutions of three proprietary oral rinses for 22 hr or 2 hr, the effects upon cell proliferation were studied by measurement of [3H]-thymidine incorporation into cellular DNA. Cell membrane damage was assessed by measurement of lactate dehydrogenase content. Cultures exposed to hexetidine-containing ... rinses for 22 hr at dilutions of 250-fold or lower showed almost complete inhibition of [3H]-thymidine incorporation. ... Exposure to the same dilutions of hexetidine-....containing rinses for 2 hr resulted in 65% and 20% inhibition of incorporation, respectively. Lactate dehydrogenase content decreased to negligible levels after exposure to the rinse containing hexetidine at a 250-fold dilution ... . Thus dividing buccal epithelial cells in vitro may be adversely affected by exposure to certain commercial oral rinses.

Bactidol

Glypesin|Hexigel|Hexocil|Hexoral|For more Formulations/Preparations (Complete) data for Hexetidine (9 total), please visit the HSDB record page.

5-Pyrimidinamine, 1,3-bis(2-ethylhexyl)hexahydro-5-methyl-: ACTIVE|The acidic nitrosation of hexetidine and hexedine, common antimicrobial agents and drug constituents, leads to a mixture of nitrosamines. The major nitrosamine product, "HEXNO", forms rapidly in yields as high as 60% over the pH range 1-4.8 at incubation times of 1 hr at 37 degrees C with 40 mM NO2- and 10 mM hexetidine. On the basis of extensive spectroscopic characterization and independent synthesis HEXNO has been assigned the structure of 1-(2-ethylhexyl)-3-nitroso-4-methyl-4-[[N-(2-ethylhexyl)-N- nitrosoamino]methyl]imidazolidine ... The rapid formation of HEXNO from hexetidine and hexedine supports the hypothesis that tertiary geminal diamines will produce nitrosamines rapidly by a mechanism which involves the cleavage of a nitrosammonium ion with the assistance of the neighboring nitrogen atom. This process is deemed to be of possible importance in the endogenous production of potentially carcinogenic nitrosamines because of its low nitrite requirement and high nitrosation rate. The available data suggest the probable formation of HEXNO and other nitrosamines from hexetidine under conditions of its use.|Five new nitrosamines were identified as nitrosation products of N1,N3-bis(2-ethylhexyl)-2-methyl-1,2,3-propantriamine, a hydrolysis product usually found in preparations of the antimicrobial drug hexetidine. All nitrosamines are formed after deamination of the primary amino group by nitrosation of one of the two secondary amino groups. The propantriamine derivative is very easily nitrosatable, with total nitrosamine yields in the upper range of a comparative scale of drug nitrosatability.

Hexetidine has been quantitatively determined in both commercial formulations and saliva using a reversed-phase HPLC method ... .

Cosmetics -> Preservative; Solvent