Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia

Endpoint summary

Description of key information

The bioavailability of the substance can be confirmed through different routes. But the uptake may be limited due to the phys-chem. behaviour. Possible uptake routes are dermal, oral and inhalation, whereas via dermal and inhalation route the absorption is expected to be lower. It can be assumed that the substance is not wide distributed and unlikely to accumulate. A main route of elimination could not be concluded, but renal and bile excretion may be the main path for excretion. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia were investigated.

 

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 aren’t justified based on the very low toxicity of the substance.

 

Reaction product of fatty acids C14-18/C16-18 unsaturated with dihydrogendioxide and Ammonia having a molecular weight of ~ 333 g/mol is a pastose (handle as liquid solutions) with a water solubility of 0.34g/l . It has a low volatility of < 11 Pa and a hydrophilic character (log Pow = 1.48). The structure shows ionisable elements and the hydrolysis test shows hydrolysis stability at all tested temperature. The surface tension is 42.9 mN/m.

 

Oral and GI absorption:

Based on the physicochemical data the substance is suspected to be less dissolvable in GI and absorbed via passive diffusion. As the substance is hydrolytically stable an increased hydrolysis in the gastric fluid is not expected (due to phy-chem. parameter, enzymatic hydrolysis may possible) and the parent compound may represent the major compartment. Low toxicity seen in acute and long term test point to low systemic toxicity. Partly the substance may be dissociating and ions may be thereafter more easily be taken up. In summary due to the molecular weight and phys-chem. behaviour the substance may be absorbed orally / via GI tract. But the amount may be limited.

 

Inhalation absorption:

Derived from the physicochemical data the substance has a less volatility is therefore only inhaled in very low concentration. No dust may be occurring as the substance is pastose or handle as dilutions. Absorption, if the substance is inhaled, may happen in the mucosa via passive diffusion. Nevertheless due to less hydrophilic character the substance may also reach lower respiratory regions. Nevertheless the substance may partly dissociate and the dissociated components may be more retained in the upper mucosa due to the higher hydrophilic properties. As no hydrolysis of the substance in biological fluids is expected (excluding enzymatic), absorptions (if happened) of the parent component is expected.

In summary only very limited inhalation absorption is expected, due to the low exposure and absorption of the substance in the upper mucosa.

 

Dermal absorption:

Triggered by the physicochemical data the following dermal absorption behaviour is expected but not confirmed: Due to pastose state of the substance it can be easily distributed on the skin surface. The low vapour pressure increases the dermal contact time. But the low water solubility and log pow are strongly limiting the dermal absorption. As there also no or only slight effects seen in dermal contact tests, no increased absorption due to skin damage is expected. Nevertheless as the substance has the ability to dissociate, the ions may be more up taken due to the higher solubility. In summary a low dermal absorption is expected, but dermal absorption cannot fully exclude.

Second it is known for cosmetic ingredients having a MW below 300 g/mol and a log pow between -1 and 5 that an dermal absorption of 10% can be expected (Kroes et al., Food Chem Toxicol 2007 Dec; 45(12): 2533-62). As there are structural similarities between the substance and few cosmetic ingredients, hence for exposition calculation 10% dermal absorption is used as assumption.

 

Distribution:

Based on the physicochemical data the substance is expected to be less distributed in the organism due to their low water solubility. The molecular mass may also limit the distribution and the absence of systemic effects in repeated dose studies questions the systemic availability. Special targets for distribution could not be identified. Nevertheless all this behaviour is estimated, detailed information can only be obtained by ADME investigations.

 

Accumulative potential:

Based on the available data the substance accumulation of the substance is not expected.

 

Metabolism:

No detail information can be derived concerning the metabolism.

 

Reactivity:Available studies on genotoxicity were negative, i. e. there is no indication of a reactivity under the test conditions.

 

Excretion:

Based on the available information the expected behaviour of the substance is estimated: The ionic character may shift excretion to urine whereas the high molecular mass points to an excretion via bile. Nevertheless both routes are expected. If the substance is partly excreted via bile and is glucoronidated a reabsorption in the GI may be possible (enterohepatic circulation). As the substance is expected to not wide distributed, less amount in breast milk or saliva are expected. This expected behaviour is only estimated based on the few availalbe phys-chem. information, only detailed ADME investigation can confirm these behaviour. But based on the toxicological profile further investigation are not necessary as the substance has a very low (non) toxicity

 

In summary:The bioavailability of the substance can be confirmed through different routes. But the uptake may be limited due to the phys-chem. behaviour. Possible uptake routes are dermal, oral and inhalation, whereas via dermal and inhalation route the absorption is expected to be lower. It can be assumed that the substance is not wide distributed and unlikely to accumulate. A main route of elimination could not be concluded, but renal and bile excretion may be the main path for excretion.