Amides, C16-18, N-[3-(dimethylamino)propyl]

Endpoint summary

Description of key information

Experimental toxicokinetic studies are not available for C16-18 DMAPA amidoamine.
The log Kow and the molecular weight are suggestive of oral absorption from gastro-intestinal tract, by dermal route or from the lungs. The substance is protonated to a large extent (>99%) at pH<7. It is generally thought that ionised substances do not readily diffuse across biological membranes. However, due to the lack of experimental data, 100% absorption by all routes is assumed as worst case default for chemical safety assessment.
Based on physicochemical properties, no potential for bioaccumulation is to be expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Experimental toxicokinetic studies are not available for C16-18 DMAPA amidoamine. Thus, the assessment of toxicokinetics is based on physicochemical properties:

molecular weight range: 340.59 to 368.64 g/mol

water solubility: 3.65 mg/L at 23°C

log Kow at pH 4, 7 and 9: 2.00, 2.01 and 2.57, respectively

The substance is a surfactant showing a complex solubility behaviour due to aggregation. The concentration reaches a limiting value at the critical micelle concentration (the limit above which virtually all additional surfactant molecules form micelles) remaining approximately constant when the total concentration is further increased.

Moreover, the substance is protonated to a large extent at pH<7. As it is generally thought that ionised substances do not readily diffuse across biological membranes, this will also be taken into account for the assessment of toxikokinetics.

 

	free amine [%]	protonated amine [%]
pH 9	26.2	73.8
pH 7	0.4	99.6
pH 4	0	100

 

 

Oral absorption

The physicochemical properties of C16-18 DMAPA amidoamine (log Kow in the range of 2.00 to 2.57 depending on pH) and the molecular weight range of 340.59 to 368.64 g/mol are in a range suggestive of absorption from the gastro-intestinal tract subsequent to oral ingestion.

For chemical safety assessment an oral absorption rate of 100% is assumed as a worst case default value in the absence of other data.

 

Dermal absorption

The physicochemical data are in a range suggestive of dermal absorption. Although it is generally thought that ionised substances do not readily diffuse across biological membranes, in a study according to OECD guideline 414 with dermal application of the substance systemic effects (lower body weight and lower food consumption) were noted. Thus, in the absence of detailed dermal penetration data it has to be assumed that dermal penetration may occur.

For chemical safety assessment a dermal absorption rate of 100% is assumed as a worst case default value based on the physicochemical properties and on experimental toxicological data.

 

Inhalative absorption

For chemical safety assessment an inhalative absorption rate of 100% is assumed as a worst case default value in the absence of other data.

 

Distribution

As a small molecule a wide distribution can be expected. No information on potential target organs are available. However, as an ionised molecule, the substance is thought to not readily diffuse across biological membranes.

 

Metabolism

It is very difficult to predict the metabolic changes a substance may undergo on the basis of physico-chemical information alone.

Based on the structure, the substance is likely to undergo hydrolysis by amidases, which in general have a broad substrate specificity. Hydrolysis of C16-18 DMAPA amidoamine would result in Stearic acid, Palmitic acid and 3-Aminopropyldimethylamine. Stearic acid as well as Palmitic acid is likely to enter the normal fatty acid metabolism and may be broken down to carbon dioxide or two carbon fragments, or be re-esterified to triacylglycerols and either metabolised for energy or stored in adipose tissue.

In general, lower primary aliphatic amines are metabolised to the corresponding carboxylic acid and urea. The tertiary site would be expected to undergo oxidation mediated by cytochrome P-450 or mixed function amine oxidases.

 

Elimination

The major routes of excretion for substances from the systemic circulation are the urine and/or the faeces.

Stearic acid and Palmitic acid as major metabolites would enter the regular fatty acid metabolism and be indistinguishable from fatty acids from other sources including diet. Thus, further considerations are not considered necessary.

The amine metabolite is likely to be excreted via the urine. Favourable physicochemical properties for urinary excretion are good water-solubility and low molecular weight (< 300 g/mol; mostly anionic and cationic compounds). 

 

Bioaccumulation

Based on the log Kow <3 (2.00 to 2.57 in the pH range of 4 to 9) the substance is unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace.