Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters

Endpoint summary

Additional information

Assessment of the Toxicokinetic Behaviour

There were no studies available on the toxicokinetic properties of Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters (CAS 68440-06-2).

Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters (CAS 68440-06-2) is an organic liquid with a molecular weight of 789.34 g/mol. The measured water solubility was smaller than 1 mg/L at 21 ºC. The log Po/w was calculated to be 18.79 (EPIWIN calculation, see IUCLID section 4.7).

In an acute oral toxicity study with Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters (CAS 68440-06 -2) performed according to OECD TG 423 (acute toxic class method), a LD50 value of 5000 mg/kg bw was estimated.

In an acute inhalation toxicity study with the read across substance Fatty acids, C18-unsaturated dimers, 2-ethylhexyl esters (CAS 68334-05-4) performed according to OECD TG 436 (acute toxic class method, limit test), a LC50 value greater than 5.3 mg/L was found for rats.

Given the size of the molecules, their relative insolubility in water and their lipophilic nature, the bioavailability of esters of 2-ethylhexanol and unsaturated fatty acids (e. g. dimers or hydrogenated dimers) is only little (Lipinski et al. 2001; "rule of five"). Therefore, systemic adverse effects are assumed to be low or even negligible. If absorption occurs (assumed to be < 1%), the esters will be hydrolysed to unsaturated fatty acid dimers and 2‑ethylhexanol. For these substances, there are sufficient data available for mammalian toxicity endpoints.

In support of this, a toxicokinetic study with dimeric fatty acids was available, in which low absorption rates were measured in rats (Hsieh and Perkins, 1976). Upon oral administration only ca. 0.4% of the 14C-labeled dimeric fatty acid methyl esters given by gastric intubation were absorbed within 12 h. Ca. 1% of the labeled material was excreted via urine and ca. 2% as CO2. Ca. 80% of the radioactivity was recovered in the gastrointestinal tract and the feces. About 0.115% of the administered test material was incorporated in the liver and metabolized to different lipid classes.

 

The metabolism of 2-ethylhexanol (CAS 104-76-7) was studied in rats (Deisinger, 1994). Upon oral application, 2-ethylhexanol was absorbed effectively by the gastrointestinal tract. The major portion of the dose was excreted within 24 h, primarily in the urine. Smaller amounts of the dose were excreted in the feces primarily within 24 h. A mean of 11% of the dose was recovered as 14CO2, but only a fraction of a percent of the dose was recovered from the breath as [14C] volatile organics.

Upon dermal application, only a small portion of the dose was absorbed, which was eliminated primarily in the urine, with smaller amounts eliminated in the feces, and as 14CO, in the breath.

 

Dermal absorption

There is no information available on the dermal absorption of Fatty acids, C18-unsatd., dimers, hydrogenated, 2-ethylhexyl esters (CAS 68440-06-2). However, due to the physicochemical properties, the skin penetration potential is expected to be very low. Penetration of the stratum corneum is facilitated by high lipophilicity, but because of the very low solubility in water, transfer into the epidermis and hence dermal uptake is likely to be low. In addition, due to the large molecular weight (> 600), dermal absorption can be regarded as negligible.

In support of this, available data for several fatty acids indicate that the skin penetration both in vivo (rat) and in vitro (rats and human) decreases with increasing chain length. Thus, after 24 h exposure about 0.14% and 0.04% of C16 and C18 soap solutions are absorbed through human epidermis applied in vitro at 217.95 µg C16/cm² and 230.77 µg C18/cm². At 22.27 µg C16/cm² and 24.53 µg C18/cm², about 0.3% of both C16 and C18 soap solutions is absorbed through rat skin after 6 h exposure in vivo (see IUCLID section 7.1.2, Howes, 1975).