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Description of key information

No toxicokinetics studies of the substance are available. However, based on its high molecular weight, very low water solubility and very high log Kow, oral bioavailability of the substance is expected to be low.

Key value for chemical safety assessment

Additional information

The substance has a high molecular weight of 1078–1190g (see IUCLID Section 1.1), a very low water solubility of <1 microgram per litre (see IUCLID Section 4.8), and a very high log Kow of >6.5 (see IUCLID Section 4.7).

 

These properties suggest that the oral (and dermal) bioavailability of the substance will likely be very low.

 

Six in vivo toxicity studies are available in which the substance was administered via the oral route (in each case, to rats): the acute oral toxicity study (see IUCLID Section 7.2.1); the 14 day range-finder and the 28-day oral toxicity study (see IUCLID Section 7.5.1); the 90 -day oral toxicity study (see IUCLID section 7.5.1) the reproduction / developmental toxicity screening study (see IUCLID Section 7.8) and the prenatal development study (IUCLID Section 7.8.2). No adverse treatment-related systemic effects were seen in these studies. There was evidence of some minor amounts of absorption:

The acute oral study consisted of a single dose at the limit of 2000 mg/kg/day. The only remarkable effects were changes to the stool, but there was no mortality for any of the animals. The changes in the stool and lower defecation were indicators that some amounts of material were absorbed.

The 14-day range-finder study had some minor, dose related findings only for females. Differences were observed with liver, spleen and thymus in the dosed animals relative to the controls. A dose-response effect was seen in those organs whether as actual weight or normalized to 100g body weight. The findings were within the range of historic control values for the laboratory conducting the work. Even though the responses were within bounds of historic controls, those responses do demonstrate that there was some degree of material uptake/absorption. 

 

Three in vivo toxicity studies are available in which the substance was administered via the dermal route: the acute dermal toxicity study in rats (see IUCLID Section 7.2.3); the skin irritation study in rabbits (see IUCLID Section 7.3.1); and the skin sensitisation study in mice (see IUCLID Section 7.4.1). No treatment-related signs of adverse systemic toxicity were seen in any of these studies.

 

No studies are available in which the substance has been administered via inhalation.

 

The available toxicity data, therefore, offer little insights into the relative absorption / bioavailability of the substance across the different routes of exposure. The results of the skin sensitisation study, though, in which the Stimulation Indices of the mice treated with the test substance were greater than those of the control animals, suggests that there was some absorption of the substance through the skin. The minor effects noted in the acute oral and 14 day rangefinder studies suggests some absorption is occurring across the GI tract.

 

The only empirical data that offer any insight into the potential fate of the substance should it enter in the body are the log Kow study and the ready biodegradation study. The partition coefficient study (see IUCLID Section 4.7) concluded the log Kow to be greater than 6.5 (the log Kow for the highest reference substance in the test). This would suggest that, if the substance is absorbed into the body, it would preferentially partition to fat and lipid-rich tissues. The ready biodegradation study (see IUCLID Section 5.2.1) found the substance to be readily biodegradable with over 60% degradation within 10 days. It might be expected, therefore, that the substance would undergo metabolic conversions in the body.