Preliminary studies of the toxic effects of non-ionic surfactants derived from lysine.
The toxic effects of new synthetic monodisperse non-ionic long-chain N alpha, N epsilon-diacyl lysine polyoxyethylene glycol amide compounds with a structural resemblance to natural lecithin phospholipids were studied by the haemolytic method and the test of the chorioallantoic membrane of the hen's egg (HET-CAM). The following compounds were tested: symmetrical N alpha,N epsilon-diacyl lysine homologues (N alpha,N epsilon-dihexanoyl, N alpha,N epsilon-dioctanoyl and N alpha,N epsilon-didecanoyl lysine) with one methyl ether polyoxyethylene glycol chain of different oxyethylene units (dioxyethylene glycol, tetraoxyethylene glycol and hexaoxyethylene glycol) as headgroup; symmetrical N alpha,N epsilon-diacyl lysine homologues with two methyl ether dioxyethylene glycol chains and the asymmetrical N alpha-butanoyl, N epsilon-dodecyl lysine with two hydrophilic methyl ether dioxyethylene glycol chains as headgroup. A commercial (polydisperse) oleoyl polyoxyethylene glycol diethanolamide with an average of eight units of ethylene oxide was used as control. All the synthesized tested compounds appeared to be less haemolytic and less irritant than the control. The synthesized products were studied with regard to their hydrophobic and hydrophilic chains in order to evaluate the influence of their structure on their haemolytic and irritative action. The results of this study show that the acyl chain distribution of these compounds greatly influence toxic effects: the asymmetrical compound N alpha-butanoyl,N epsilon-dodecyl lysine-bis[methyl ether diethylene glycol]amide was found to be the most haemolytic and irritating compound. Among the symmetrical homologues, the shortest-chain compounds N alpha,N epsilon-dihexanoyl lysine methyl ether polyoxyethylene glycol amides present the least haemolytic and irritating activity, independently of the number and length of the hydrophilic methyl ether polyoxyethylene glycol chains. Taking into account their surface activity properties and their less haemolytic and irritant action, the compound N alpha,N epsilon-dioctanoyl lysine-bis[methyl ether diethylene glycol]amide would be the most suitable for practical purposes.
Macián
M
M
Department of Human Physiological Sciences and Nutrition, Faculty of Pharmacy, University of Barcelona, Spain.
Seguer
J
J
Infante
M R
MR
Selve
C
C
Vinardell
M P
MP
D000482:Allantois / Q000187:drug effects; D000826:Animal Testing Alternatives; D000818:Animals; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D007509:Irritants / Q000633:toxicity; D008239:Lysine / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity*; D018675:Toxicity Tests
D005227:Fatty Acids; D007509:Irritants; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D008239:Lysine