1,2,3-Propanetriol, homopolymer, docosanoate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Polyglycerintribehenate (CAS 64366-79-6; EC-No. 613-583-7) is a mixture of Di-, Tri-, Tetra-, Pentamers and higher oligomers of Glycerin where all free OH groups are esterified with the carboxylic groups of linear C22-acid. The main toxicokinetic properties of Polyglycerintribehenate are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance. Substance specific toxicokinetic or dermal absorption studies are not available.

Relevant physico-chemical properties

Moleculare weight distribution: Mn = 1700 g/mol, MW = 2300 g/mol

Physical state: brownish solidified melt at room temperature

Boiling point: 375°C at 1013,25 hPa

logPow: > 6.5 at 23°C / pH = 6.2

Water solubility: 3 - 4 mg/l at 20°C

pKa: not applicable (the substance does not contain any ionic structure)

Vapour pressure: < 0.000001 hPa at 20°C

Hydrolysis: considered to be stable in water

Surface tension: Based on chemical structure, no surface activity is predicted.

Absorption:

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2008).

 

Oral absorption

The high mean molecular weight of Polyglycerintribehenate (2500 g/mol) does not favour oral absorption. However, highly lipophilic compounds (log Pow > 4; applies for Polyglycerintribehenate) may be taken up by micellar solubilisation by bile salts. This mechanism may be of particular importance for compounds that are poorly soluble in water (≤ 1 mg/L; does not apply for Polyglycerintribehenate) which would otherwise be poorly absorbed (Aungst and Chen, 1986; ECHA, 2008). Oral absorption is probably limited by the fact that the substance is still a solid at a body temperature of 37 °C.

Following repeated oral gavage administration, Polyglycerintribehenate did not cause adverse effects concerning general, systemic toxicity indicative for a low oral absorption. In conclusion, the available information, the physicochemical properties and mean molecular weight of Polyglycerintribehenate suggest low oral absorption.

 

Dermal absorption

The high mean molecular weight of Polyglycerintribehenate (2500 g/mol) does not favour dermal absorption. Based on the rather low water solubility of Polyglycerintribehenate dermal uptake is anticipated to be low to moderate. The high log Pow value of Polyglycerintribehenate (> 6.5) indicates a limited uptake into the stratum corneum and a low rate of transfer from the stratum corneum to the epidermis, thus limiting dermal absorption (ECHA, 2008). The absorption rate of Polyglycerintribehenate may be further be limited by the fact that the substance is a solid at room temperature. In conclusion, dermal absorption of Polyglycerintribehenate is anticipated to be low.

 

Inhalation absorption

The very low volatility (vapour pressure < 0.000001 hPa at 20 °C) indicates that a vapour inhalation exposure is negligible. If exposure to respirable aerosol occurs, the mean molecular weight, log Pow and water solubility of Polyglycerintribehenate are suggestive of a possible absorption across the respiratory tract epithelium by micellar solubilisation. Overall, it can be concluded that inhalation absorption is low. A similar rate of inhalation absorption compared with oral absorption can be assumed.

Distribution/Metabolism:

Distribution of a compound within the body depends on the physicochemical properties of the substance, especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider the distribution. As Polyglycerintribehenate is lipophilic, it is likely to distribute into cells after absorption, and the intracellular concentration may be higher than extracellular concentration, particularly in fatty tissues (ECHA, 2008). Distribution to the central nervous system and testis is likely to be restricted by the blood-brain and blood-testis barriers.

It can be assumed that enzymatic hydrolysation (deesterification) of Polyglycerintribehenate to (poly)glycerol and behenic acid occurs. The conversion of Polyglycerintribehenate into metabolites that were more cytotoxic or more genotoxic than the parent substance was not noted when comparing in vitro test results with metabolic activation to in vitro test results without metobolic activation system (genetic toxicity tests). Based on this, an indication is not given that the formation of cytotoxic metabolites is likely.

Excretion:

Due to the poor solubility in water and the high molecular weight of Polyglycerintribehenate, it is assumed that excretion takes place mainly via the biliary route, with the faeces, but also with breast milk. Furthermore, based on the obtained results from various calculation models and the molecular properties, Polyglycerintribehenate is not expected to significantly accumulate in organisms.

 

References

Aungst B. and Shen D.D. (1986). Gastrointestinal absorption of toxic agents. In Rozman K.K. and Hanninen O. Gastrointestinal Toxicology. Elsevier, New York, US.

ECHA (2008). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.