N,N-dimethyldodecanamide

Endpoint summary

Description of key information

The bioavailability of the substance can be confirmed through different routes. Possible uptake routes are dermal, oral and inhalative. Further it can be assume that the substance is wide distributed, metabolised via phase 1 and 2 enzymes (via N-demethylase or/and P450) and extreted via urine. Accumulation seems unlikely.

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

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the N,N-dimethyldodecanamide were investigated.

 

N,N-dimethyldodecanamide having a molecular weight of ~227,38 g/mol is a liquid with a water solubility of 0.028 g/L. It has a very low volatility of < 0.17 Pa (20°C) and has a strong lipophilic character (log Pow = 5.2). The structure shows ionic elements.

 

The expected toxicokinetic behaviour is derived from the physicochemical properties, the results from the available toxicological studies and the available literature following the information given in guidance document 7c.

Please note that the real behaviour may be different but can only be determined with ADME studies, which are not justified based on the very low toxicity of the substance. Additionally a few information are derived from acute or repeated dose studies of a N,N-dimethyloctan-1-amide / N,N-dimethyldecan-1-amide – mixture.

 

Oral and GI absorption:

Based on the phys. Chem. data, it can be expected that substance is ionisable and therefore do not readily diffuse across biological membranes. Due to the high hydrophilic properties passive diffusion may be less relevant in absorption, nevertheless it can be expected, that absorption happens via micellular solubilisation but that due to the highly lipophilic properties substance has a limited ability to dissolve into GI fluids. Based on this it can be expected that the substance can be absorbed and that the major fraction is parent compound or parent compound metabolites. As acute toxicity studies for close homologues (with shorter carbon chain length) show low toxicity (decreasing in toxicity with increasing carbon chain length) but indicate some effects at 5000mg/kg bw. (see BASF 1997 for CAS 14433-76-2) the oral bioavailability of the test material is indicated. Further, a 90 day feeding study (Bayer 2000) with beagle conducted with a close homologue indicate also the systemic availability of the substance.

 

Inhalative absorption:

The substance itself has a low vapour pressure, therefore inhalation of vapours is expected not to reach sufficient amount for any effects. Nevertheless if sprays are generated and inhaled possible higher amounts may reach the lower respiratory region. Due to the high hydrophilic properties and the low water solubility the substance may be taken up be micellular solubilisation also partly a direct absorption may be possible. But results from a close homologue show no toxicity (despite irriation) if the highest attainable dose is inhaled (see acute inhalation study C8/C10 mixture (Bayer 1991, LC50= 3551 mg/m3) and an repeated dose sighting inhalation study where 111.2mg/m3 C8/C10 aerosol were tolerated (Bayer 1992; 5x6h)).

In summary mist may be reach the lower respiratory region an may also be absorbed but expected toxic are low despite irritation.

 

 

Dermal absorption:Due to the physicochemical information of the substance absorption via skin is anticipated to be low due to its low solubility. Further N,N-dimethyldodecanamide has a limited rate of penetration due to its lipophilic character, but small uptake into the epidermis can not fully be excluded. Nevertheless due to lipophilic character the substance may readily penetrate the lipid rich stratum corneum but in summary is not well absorbed systemically. An in-vitro study (BASF, 2014) revealed a skin irritation potential of N,N-dimethyldodecanamide and due to this damage, the substance can possible enhance skin penetration. In addition, literature indicated that a maximum skin penetration enhancing effect is measured for C8 and C10 dimethylalkylamides.

 

Distribution:The physicochemical information points due to the small molecule size to a wide distribution of the substance but less diffusion through aqueous pores and channels because of its lipophilic character. Further it can be assumed that the substance is likely distributed into cells, especially in fatty tissue (log P>0). Im summary a wide distribution can be assumed.

 

Accumulative potential:Due to the water solubility and distribution an accumulation in general is unlikely. Nevertheless, if accumulation happens the main site of accumulation is assumed to be the adipose tissue. Lipophilic substances will tend to concentrate in adipose tissue and may accumulate, if the interval between exposure is less than 4 times of the whole body half-life of the substance. Furthermore highly lipophilic substances can readily penetrate the lipid rich stratum corneum but are not well absorbed systemically. Although the may persist in the stratum corneum, they will eventually be cleared as the stratum corneum is sloughed off. No accumulation in bone or in lung is predicted.

 

Metabolism:

No detail information is available concerning the metabolism. Based on the general structure of the molecule itcan be assumed that metabolisation (via N-demethylase or/and P450) appears, degrading the substance, further the metabolites may be conjugated via phase II enzymes creating molecules with molecular masses preferred for kidney elimination.

 

Reactivity:

Available studies on genotoxicity with N,N-dimethyloctan-1-amide / N,N-dimethyldecan-1-amide were negative, i. e. there is no indication of a reactivity against DNA of homologe dimethylamides in genotoxicity assays are observed.

 

Excretion:

Based on the molecular weight and water solubility it can be assumed that the substance or its metabolites are mainly excreted via urine. Nevertheless due to the lipophilic character of the parent substance these molecular maybe also found in the bile. Metabolites will have more hydrophilic properties and therefore be excreted via urine. If dermal application appears also a portion of the substance could be eliminated via exfoliation.

 

Due to a assumed metabolism the main route of excretion is expected to be via kidney but small portions maybe also found in the bile.

 

In summary:The bioavailability of the substance can be confirmed through different routes. Possible uptake routes are dermal, oral and inhalative. Further it can be assume that the substance is wide distributed, metabolised via phase 1 and 2 enzymes (via N-demethylase or/and P450) and extreted via urine. Accumulation seems unlikely.

In a worst case assumption full absorption via all routes are assumed as the substance penetrates thru skin.