Benzethonium

208.1 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID6023810]

209.09 Ų [M]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Danger

H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

P260, P264, P280, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P321, P363, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory.

R - Respiratory system

QR - Respiratory system

Benzethonium belongs to the family of compounds known as cationic detergents that act by disrupting lipid bilayers. It demonstrated antitumor activity against cancer cell lines in vitro. The effective dose required to decrease cell viability by 50% after 48 hours (ED50) of benzethonium for FaDu (hypopharyngeal squamous cancer) and C666-1 (nasopharyngeal cancer) cell lines were approximately 3.8 and 5.3 μmol/L, respectively.

While exact mechanism of benzethonium is not fully understood, it is proposed that benzethonium acts similarly to other structurally-related quaternary ammonium compounds in disrupting cytoplasmic and outer membrane lipid bilayers of microorganisms. The positively charged quaternary nitrogen associates with the polar head groups of acidic membrane phospholipids, followed by the hydrophobic tail interacting with the hydrophobic membrane core. Benzethonium is thought to form mixed-micelle aggregates with hydrophobic membrane components that solubilize membrane and lyse the cells, leading to leakage of cytoplasmic contents. Based on findings in vitro cell assays, its mode of action on cancer cells may involve cancer cell apoptosis via dysregulating mitochondria or rough endoplasmic reticulum (rER). It is proposed that intracellular cationic molecules such as benzethonium will create swelling of the rER and damage the organelle. Ultimately, there is a loss in cell membrane integrity and cytosolic Ca2+ levels increase. Dysregulation of mitochondria and rER leads to the activation of caspase-2, caspase-8, caspase-9, and caspase-3.