Octylamine

Endpoint summary

Description of key information

Following i.v. injection of very small doses of octylamine hydrochloride elevated levels were seen in the lungs (only for 15), liver, and kidneys. The substance is metabolised via oxidative deamination by MAO (monoamine oxidase) to NH3 and octanal which is subsequently metabolised by reactions of aldehyde dehydrogenase and ß-oxidation. The potential for bioaccumualtion is low. 
The velocity of MAO is, however, limited and may be the limiting step at elevated dose levels that are generally used in toxicity testing (approx. 10 to 1000 mg/kg bw). The organ distribution and metabolism rates may therefore be different under such conditions.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The organ distribution and metabolism of octylamine (and other primary alkylamines) was extensively examined in a series of studies using a [¹¹C]-or [¹³N]-labeled test substance of extremely high specific activities without unlabeled material. This resulted in extremely low octylamine doses (Fowler 1976 a, Fowler 1976b; Gallagher 1977, Tominaga 1987). This technique allowed to examine distribution, metabolism and excretion of octylamine hydrochloride immediately after intravenous injection until 20 minutes thereafter. The results confirmed that the MAO reaction is the initial step in the metabolism, and that there are differences between alkylamines of differing chain lengths. It was also suggested that the lung concentrates octylamine (and other alkylamines with more than C8 chains), but that held only true for few minutes. High levels persisted in the liver and in the kidney; MAO is remarkably low in the kidney.

 

MAO is present in many tissues, but the velocity (V_max) is reportedly relatively low compared to other enzymes. It is therefore questionable whether the organ distribution and metabolic rates described in the above low-dose studies hold true for situations with elevated doses in the 10- 1000 mg/kg bw range. MAO is likely saturated under such conditions, and organ distribution may be altered.

 

It should be mentioned that octylamine may bind to P₄₅₀ and inhibit the metabolism of other xenobiotics. It may prevent the electron transfer from the (NADPH)-reduced flavoprotein to P₄₅₀. A 50% inhibition was seen at approx. 0.3 mM with mouse liver microsomes in vitro.

 

Toxicokinetic investigations are mainly performed with the RA-substance n-octylamine hydrochloride. Investigations on dermal absorption with n-octylamine or its hydrochloride are missing, only results from dodecylamine are available. Taken these data into account as well as the results of the acute toxicity studies it can be concluded that n-octylamine is absorbed after oral, inhalation and dermal application, but no quantitative figures can be provided.