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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 but able to accumulate. Nevertheless metabolites may be not accumulated therefore accumulative potential stays unclear as it can be not confirmed that parent substance may adipose tissues.  The main route of elimination is expected to be via bile/faeces and to small extend via other lipophilic routes. 

Key value for chemical safety assessment

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of the Fatty acids, C18-unsatd., dimers, ethoxylated 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.

 

Fatty acids, C18-unsatd., dimers, ethoxylated having a molecular weight of 648-652 g/mol

is viscose yellow liquid with a water solubility of 0.5mg/L. It has a low volatility (vapour pressure 0.4 Pa and a lipophilic character (log Pow = 14.84). The structure shows no ionisable elements and the hydrolysis test shows could be not conducted based on the low solubility. The surface tension is 42.9 mN/m.

 

Oral and GI absorption:

The substance has a molecular weight above 500 g/mol leading to a low absorption. Nevertheless as the molecular weight is below 1000 g/mol absorption can be possible. A further limiting factor for absorption may be the poor solubility (0.5mg/L) and the hydrophobicity (log Pow = 14.84) which makes a dissolving in GI fluid unlikely. Nevertheless based on the lipophilic character absorption may be possible via miscellular solubilisation. No systemic toxicity can be observed in short and long term studies (LD50>2000mg/kg oral, LD50>5000mg/kg dermal, subacute NOAEL = 1000 mg/kg, but increase liver weight) leading to a low systemic toxicity and/or a very poor absorption. Summarizing based on the available information the substance is expected to be absorbed in small amount and/or has a very low systemic toxicity. 

 

Inhalation absorption:

In general based on the low vapour pressure inhalation of vapours is not expected (extreme low volatile substance). Only spray application may be of interest but also be limited as the droplet size must be quiet defined. As spray uses are not the predominant use the favourite route for exposition is expected to be oral and dermal. Nevertheless if droplets below 15µm are generated the substance may reach alveolar region as due to low hydrophilicity a retaining in the upper mucosa area is less expected. In the respiratory system the uptake may take place by micellular solubilisation as the substance is highly hydrophilic (Log Pow = 14.84). Nevertheless as the substance shows a very low toxicity in short and long term studies (LD50>2000mg/kg oral, LD50>5000mg/kg dermal, subacute NOAEL = 1000 mg/kg, but increase liver weight) this could be a result of a low systemic toxicity or a very poor absorption. Based on the available information there are also no hints for irritation to skin or eye. Therefore also no respiratory irritation is expected. Summarising the substance may be inhaled if the right droplet size is generated and may also be absorbed, but low toxicity and negliable irritating character limiting the effect of an intoxication or respiratory irritation.

 

Dermal absorption:

The molecular weight (above 500g/mol) of the substance does not favor dermal absorption. Also it can be expected, based on the low water solubility and low hydrophilicity, that the substance will be only very slow transported thru hydrophilic barriers. Hence the transfer between strateum corneum and epidermis is expected to be quiet slow. Also the uptake in strateum corneum may be also slow. Contrary the substance may stay long on the skin due to the low vapor pressure which increases the possibility of dermal absorption. But as there are no signs of systemic toxicity in dermal acute toxicity test and the substance is not irritation or sensitizing an uptake is assumed to be not increased by these factors.

Second it is known for cosmetic ingredients having a MW > 300 g/mol and a log pow >5 that an default 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 a maximum dermal absorption of 10% is expected and used as assumption.

Summarising the substance is expected to be less absorbed via skin and/or the low toxicity of the substance and negliable irritating character limiting the effect of an intoxication.

 

Distribution:

The substance is expected to be less wide distributed based on the large molecular weight. The low water solubility reduces further a distribution as the molecule may be not able to pass thru aqueous pores. On the other hand the substance may easily distributed into cells based on the high lipophilic character and may reach higher concentration inside especially in adipose tissues. Increase liver weights observed in a long term study may be a hint that the substance reaches the liver and is conclusive may be distributed. But as no further organs show any effects the distribution is assumed to be limited and/or the substance is in general of very low toxicity. Effects on the CNS are not observed. Summarising the substance is expected to be systemic available but less wide distributed and/or the low toxicity of the substance is limiting the effect of an intoxication. Nevertheless all this behaviour is assumed, detailed information can only be obtained by ADME investigations.

 

Accumulative potential:

Based on the phy-chem. data and the structure of the substance the substance may not accumulate in lung or bone as it is a liquid containing no metal ions. Nevertheless due to the high lipophilicity the substance may be accumulating in adipose tissues and strateum corneum. But the amount reaching these regions may be limited and stays unclear. No further information can be derived for the available information; in general there is no hint for an accumulation. These may be explained by the metabolism of the substance which do lead to non-accumulative breakdown products.

 

Metabolism:

Based on the structure of the substance, which contains alkyl chains and esterified carbonyl function with ethylenoxide it can be expected that ß-oxidation of alkyl chain may happen and that the alcohol may be oxidized via alcohol/aldehyde dehydrogenase. Nevertheless this degradation may only happen if the substance is absorpted. But absorption may be limited based on the available information. Additionally also phase 2 metabolism may be possible leading to conjugated molecule and extending the water solubility.

 

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

 

Excretion:

The substance may be excreted mainly via bile due to high molecular weight (above 500 g/mol) and the non-ionic lipophilic character. Exhalation via lung of the major parent compound is not expected as the vapour pressure is too low. Nevertheless degradation products of metabolism may be carbon dioxide which is afterwards exhaled. Due to the lipophilic character an excretion via bile is expected and if phase II metabolites are build enterohepatic circulation may happen to some extent. Further derived from the lipophilicity a concentration in breast milk and excretion via salvia/sweat may be possible as well as exfoliation as dermal applied substance may reach strateum corneum. As the substance is no metal ion excretion via hair and nails is very unlikely. Summarising the substance is expected to be excreted via bile / feces as predominant route. Small amounts may be also excreted via lipophilic routes like breast milk, salvia, sweat and exfoliation. Metabolic degradation products, like CO2, may be exhaled if build.

 

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 but able to accumulate. Nevertheless metabolites may be not accumulated therefore accumulative potential stays unclear as it can be not confirmed that parent substance may adipose tissues. The main route of elimination is expected to be via bile/faeces and to small extend via other lipophilic routes.