Toxicological evaluation of mixtures of nonionic surfactants, alone and in combination with oil.
The toxicity to human bronchial (16-HBE14o-) epithelium cells of nonionic surfactants, polyoxyethylene-10-oleyl ether (C(18:1)E(10)), polyoxyethylene-10-dodecyl ether (C(12)E(10)), and N,N-dimethyl-dodecylamine-N-oxide (C(12)AO) alone or in combination with a range of pharmaceutically acceptable oils (namely, ethyl esters and triglyceride oils), was determined with the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Regardless of the presence of oil, all C(12)E(10)- and C(12)AO-containing systems were toxic at concentrations around or below their critical aggregation concentrations (as determined by surface tension measurements), suggesting that surfactant toxicity was due to the disruption caused by the partitioning of monomeric surfactant into the cell membrane. Systems prepared from C(18:1)E(10) alone or in combination with a low-molecular-weight oil, such as ethyl butyrate or tributyrin, were toxic above their critical aggregation concentration. In contrast, systems prepared from C(18:1)E(10) in combination with a high-molecular-volume oil (e.g., ethyl oleate, Miglyol 812, or soybean oil) were toxic only at concentrations significantly greater than their critical aggregation concentration, suggesting that in these cases surfactant toxicity was mediated by the aggregated form of the surfactant solubilizing components of the cell membrane. In the C(18:1)E(10)-stabilized system, it is proposed that toxicity was significantly reduced on incorporation of high-molecular-volume oils because these oils cause formation of a distinct oil core in the aggregates that leads to a reduction in the ability of the system to solubilize components of the cell membrane.
Warisnoicharoen
Warangkana
W
Pharmacy Department, King's College London, University of London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NN, United Kingdom.
Lansley
Alison B
AB
Lawrence
M Jayne
MJ
D001980:Bronchi / Q000166:cytology; D002087:Butyrates / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004123:Dimethylamines / Q000737:chemistry / Q000633:toxicity; D004339:Drug Compounding; D004655:Emulsions; D004848:Epithelium; D006801:Humans; D008823:Micelles; D009821:Oils / Q000737:chemistry / Q000633:toxicity*; D009829:Oleic Acids / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity*; D014280:Triglycerides / Q000737:chemistry / Q000633:toxicity
D002087:Butyrates; D004123:Dimethylamines; D004655:Emulsions; D008823:Micelles; D009821:Oils; D009829:Oleic Acids; D013501:Surface-Active Agents; D014280:Triglycerides; C478747:polyoxyethylene-10-dodecyl ether; C478746:polyoxyethylene-10-oleyl ether; D011092:Polyethylene Glycols; C014518:dodecyldimethylamine oxide; C045572:ethyl butyrate; C033180:ethyl oleate