reaction mass of bis(2-propylheptyl) hexanedioate and O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy)hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hexanedioate

Endpoint summary

Description of key information

The registered substance is a liquid multiconstituent substance. Its main component (80 %), bis(2-propylheptyl) hexanedioate (EC 940-510-9), has a molecular weight of 426.67 g/mol. 14.5 % of the reaction mass consists of the second component, O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy) hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hexanedioate(triester of trimethylolpropane with adipic adic mono (2-propylheptyl) ester) with a molecular weight above 800 g/mol.
The second component of the reaction mass, O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy) hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hexanedioate is a large molecule that will not be absorbed into the body based on its physicochemical properties and particularly based on the size of the molecule. Therefore, this substance is of no relevance with regard to the toxicological profile of the registered substance.
Physicochemical properties of the main compound bis(2-propylheptyl) adipate itself do not favour absorption into the body but acute toxicity data show that some absorption takes place. Based on the available toxikokinetic data it is assumed that the substance will first be metabolised in the liver and afterwards the metabolites can be distributed through the bloodstream. The main metabolite is adipate. No bioaccumulation is expected and excretion is supposed to be rapid and complete.  

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic assessment of the test substance

 

The registered substance is a liquid multiconstituent substance. Its main component (80 %), bis(2-propylheptyl) hexanedioate (EC 940-510-9), has a molecular weight of 426.67 g/mol. 14.5 % of the reaction mass consists of the second component, O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy) hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hexanedioate(triester of trimethylolpropane with adipic adic mono (2-propylheptyl) ester) with a molecular weight above 800 g/mol.

The reaction mass has a density of 0.9411 g/cm³, its’ freezing point was determined to be

< - 90 °C and the boiling point was found to be ca. 245 °C. Thermal decomposition was not observed at lower temperatures. The registered substance has a vapour pressure of ≤6.5 Pa at 20 °C and a log Pow of >3.5. The water solubility is very low (4.4 µg/L).

 

Relevant physicochemical parameters with regard to absorption, distribution, metabolism and excretion for the main component (EC 940-510-9) were obtained from the ECHA disseminated Dossier. The log Pow was determined to be >6.5. The water solubility was found to be <1 µg/L and the vapour pressure is very low (0-0.2 hPa). The boiling point was found to be between 377 and 388 °C.

 

 

Absorption

Generally, oral absorption is favoured for molecular weights below 500 g/mol, which is only the case for the main component. But, due to the extremely low water solubility oral absorption might be limited. As the compound is lipophilic (log Pow >6.5), it may thus be taken up by micellular solubilisation, but taken together the compound is most probably poorly absorbed via the oral route. The molecule will not directly enter the systemic circulation by passive diffusion. However acute oral toxicity data show that absorption takes place at least to a very small extent: The oral LD50 value was found to be greater than 5000 mg/kg bw in Wistar rats, but some clinical signs were noted (piloerection). No clinical signs were observed up to 2000 mg/kg bw. The second component of the reaction mass is unlikely to be absorbed via oral, inhalation and dermal route due to the high molecular weight.

 

Furthermore the reaction mass will hardly become available for inhalation because of the low vapour pressure.If the substance would reach the lungs in its vapour or gaseous state, absorption directly across the respiratory tract epithelium by passive diffusion is unlikely to occur due to its limited water solubility. In general a substance could be taken up by micellular solubilisation if it is lipophilic enough, which might be the case for the main component. But absorption via respiratory route was not confirmed by an acute inhalation toxicity study in Wistar rats with the read-across substance bis(2-ethylhexyl) adipate (EC 203-090-1), where the animals were exposed to the test substance as an aerosol at a high (limit) concentration of 5.7 mg/L air. No mortality occurred and no pathologic findings were recorded.

 

Similarly, based on physico–chemical properties of the compound, primarily water solubility, dermal uptake will be low. As mentioned above, the second component of the reaction mass (O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy)hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hex-anedioate) will not be able to penetrate skin based on the size of the molecule. Due to the high log Pow value, bis(2-propylheptyl) hexanedioate is unlikely to be taken up.Indeed, in an acute dermal toxicity study in Wistar rats the LD50 value was found to be above 5000 mg/kg bw and no local effects on the skin were observed.

Taken together, physico-chemical properties and experimental data indicate low bioavailability of the test substance via oral, dermal and inhalation route.

 

 

Distribution

Assuming that the test substance is absorbed into the body following oral intake, it may be distributed into the interior part of cells due to its lipophilic properties and in turn the intracellular concentration may be higher than the extracellular concentration particularly in adipose tissues. As mentioned above, the physico-chemical properties, especially the higher molecular weight and low water solubility, do not favour absorption, but clinical signs observed in the acute oral toxicity study indicate that systemic absorption has occurred at least to a small extend.

The read-across substance Bis(2-ethylhexyl) adipate was found to be distributed to the body fat, liver and kidneys. Besides that, the metabolites were also distributed into the foetus of pregnant mice. Little accumulation was observed in the foetus and in the amniotic fluid. In another (pharmacokinetic) study using Wistar rats no evidence of bioaccumulation was found (ECHA disseminated dossier of Bis(2-ethylhexyl) adipate).

 

 

Metabolism

In the ECHA disseminated Dossier of the main component Bis (2-propylheptyl) hexanedioate a study is described which was conducted similar to OECD Guideline 417 to investigate the metabolism of the read-across substance Bis(2-ethylhexyl) adipate in vivo in Fischer 344 rats. Metabolites present in the GI tract, liver and urine were identified. As a result, the substance was found to be metabolised to a large extend via oxidation reactions in the liver and glucoronidation of the metabolites. Other studies conducted with rats revealed that adipic acid was found to be the main urinary metabolite; which was also present in the digestive tract, blood and liver. A similar metabolism is expected for the registered substance.

 

 

Excretion

The read-across substance Bis(2-ethylhexyl) adipate was rapidly excreted via urine, feces and exhaled air. The substance was found to be excreted within 48 hours, predominantly via urine, in a toxikokinetic study conducted with male Wistar rats. A study conducted with monkeys confirmed the results, except for one female monkey showing a higher rate of renal excretion. In females the amounts of excretion products was similar. Excretion via exhaled air was less important. Excretion of the registered substance is thus expected to be similar.