Effect of 2-N-mono- and 2-N-diethylaminoethanol on normal and choline-deficient rats.

-In rats, the acute oral LDs0 value of neutralized 2-N-monoethylaminoethanol (MEAE) was found to be 1 "0 (0.68-1 35) g/kg. The acute oral toxicity of MEAE, but not that of 2-N-diethylammoethanol (DEAE) could be largely reversed by simultaneous or subsequent ingestion of choline. MEAE partially prevented the development of fatty hver in chohnedeficmnt rats. No reversal of depressed growth rate was noted m choline-deficient ammals whose diets were supplemented with either MEAE or DEAE. INTRODUCTION The N-substituted aminoethanols (ethanolamines) are excellent curing agents, flotation agents, dispersants and emulsifiers. As such, they find wide application in the manufacture of cosmetics, shampoos, waxes, polishes, lubricants, resins and other related materials. The continuous inhalation toxicity of the parent compound, 2-aminoethanol was the subject of a report by Weeks, Downing, Musselman, Carson & Groff (1960) and two Nsubstituted aminoethanols, 2-N-monoethylaminoethanol (MEAE) and 2-N-diethylaminoethanol (DEAE), are the subjects of the present paper. The biological activity of N-ethylaminoethanols is of considerable interest because of their possible action as antimetabolites due to the structural relationship of these compounds to choline (N-trimethylaminoethanol). Choline has vitamin-like activity in animals and deficiencies may result in fatty liver, anaemia and hypoproteinaemia. Moyer & du Vigneaud (1942) demonstrated that N,N-dimethylethylaminoethanol functioned as choline in promoting the growth of rats on a diet deficient in choline and supplemented with homocysteine. N,N-Diethylmethylaminoethanol was quite toxic. Both these two choline analogues could be formed by the in vivo methylation of MEAE and DEAE. Thus, if the acute toxicities of MEAE and DEAE a r e related to their rapid conversion to N,N-dimethylethyland N,N-diethylmethylaminoethanol respectively, one would anticipate, on the basis of the work by Moyer & du Vigneaud (I 942), that DEAE would be considerably more toxic than MEAE. N-Triethylaminoethanol has been extensively investigated (Stekol & Weiss, 1950). It is lipotropic and prevents renal haemorrhage in young choline-deficient rats. However, animals also exhibit muscular weakness and convulsions. These toxic signs can be prevented by the simultaneous consumption of equivalent amounts of choline. Thus, N-triethylaminoethanol appears to substitute for choline as a lipotropic agent but by other mechanisms also produces a toxic effect. Hence, there is considerable evidence to indicate that N-ethyl analogues of choline may interfere with the normal metabolism of choline. The present studies were undertaken to determine the relationship of MEAE and DEAE toxicity to metabolic functions of choline. The LDso and 95~o confidence level of neutralized DEAE (5-6 (3.5-9.1) g/kg) has been previously reported (Cornish, 1965).