Mixed esters of fatty acids C16 and C16-C18 unsatd. with adipic acid and pentaerythritol

Endpoint summary

Additional information

The following remarks on the toxicokinetics of the substance are based on physicochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

The substance is a colourless, clear organic liquid (Currenta, 2009) with a low vapour pressure under normal ambient conditions (2.2 x 10exp-8 Pa at 25 °C, calculated value, Currenta, 2012). Inhalation exposure via vapour is therefore not to be expected. Absorption of the substance via skin or mucosa is assumed to be low due to the high average molecular weight of the substance (> 1000 g/mol), which actually is an UVCB according to REACH (“Substance of Unknown or Variable composition, Complex reaction product or Biological material”). Moreover, and consistent with structural composition (“esters with C16-22 fatty acids”, cf. CAS-Name), the substance has strong lipophilic properties (calculated log Pow >20; KOWWIN v 1.67 of the U.S. EPA) and is nearly insoluble in water (< 3 mg/L at 20 °C and pH 5.6, Currenta, 2011), both indicating that absorption via passive diffusion should not be favoured. If absorption at all occurs, the substance’s lipophilicity suggests an uptake by micellular solubilisation. 

No indications for systemic availability and thus for absorption could be observed after acute oral and dermal exposure to the substance, because no toxicological effects at all were observed (OECD TG 423 and 402, both Gillissen, 2009).

Indications for absorption could be derived from an oral repeated dose toxicity study (OECD TG 407, Schladt, 2010), in which a single adverse effect (mesenterial lymph nodes) and also adaptive effects (liver, thyroid) were reported. In this study the test substance-related adverse effect, led to NOAELs of 300 mg/kg bw for males and 100 mg/kg bw for females. In detail, foamy macrophage aggregates of minimal to moderate degree were found in the mesenterial lymph nodes of high dose animals and to a minimal in a single female of the mid dose group. A PAS stain (Periodic acid-Schiff stain: detecting carbohydrate macromolecules) was minimally to slightly positive in these areas. The effect might be attributed to intestinal absorption of the test article. No comparable effect was reported for distal lymph nodes (popliteal, mandibular), indicating that the presence of foamy macrophages is limited to gut draining lymph nodes only.

Additionally, a further repeated dose study (developmental toxicity study, OECD TG 414, Mueller, 2010) gave no indications for systemic toxicity and thus for absorption, because no substance related findings were observed (NOAEL 1000 mg/kg for maternal and developmental toxicity).

Certainly, the calculated log Pow (see above) indicates an accumulation potential for the substance. Anyhow, due to the limited systemic availability it is unlikely that accumulation is a protruding toxicokinetic property for the substance.

Since the water solubility of the substance is poor, hydrolysis of the substance will not occur to an appreciable amount. It could be assumed that most of the substance ingested will be excreted unchanged via faeces.

Based on the results of the genotoxicity tests in vivo and in vitro (OECD TG 471, Herbold, 2009; OECD TG 476, Entian, 2009; OECD TG 473, Nern, 2009) it could be concluded, that DNA-reactive metabolites most probably will not be generated in mammalian organisms due to hepatic biotransformation.