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Description of key information

There are no studies available in which the toxicokinetic properties of 2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]-henicosan-21-one / 2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]-henicosan-21-one were investigated.

 

The substance (molecular weight: 364 g/mol) is a white solid powder, which is considered to be hydrolytically stable. Its water solubility is determined to be 3 mg/L at 20°C (see chapter 4.8). The octanol water partition coefficient (Log Pow) value of 6.0 was obtained for Hostavin N 20, using a HPLC method (see chapter 4.7). Due to the relative high Log Powof 6 in combination with only a slight hydrolysis of the substance (see chapter 5.1.2) a general potential of bioaccumulation might be considered. However, a bioaccumulation study performed with the substance demonstrated that there is only a low potential for bioaccumulation (refer to chapter 5.3).

 

Absorption

With reference to the Log Powof 6, the very limited water solubility and its chemical structure the absorption of Hostavin N 20 is considered to be very limited (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, Table R.7.12-1, p. 168).Furthermore, the substance contains several amine functions which might be ionisable. Ionisation does not contribute to a readily diffusion across biological membranes (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, p. 167). Therefore, a large-scale absorption of Hostavin N 20 might be excluded. This assumption is strengthened by the results of the acute oral toxicity studies in rats (LD50> 2000 mg/kg bw). However, since systemic effects were observed in the course of repeated dose studies at doses at and above 250 mg/kg bw/d a considerable amount of the substance is proved to be bioavailable. The absorption of highly lipophilic substances might be by micellar solubilisation by bile salts and subsequent entering the circulation via the lymphatic system (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, p. 168).

 

Distribution

Hostavin N 20is a verylipophilic substance with a medium molecular weight. Therefore, it might tend to migrate into cells and concentrate in adipose tissues (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, pp. 176-177).

 

Metabolism

Taking into account the Log Powof 6, the very limited water solubility and the chemical structure, an uptake of excessive amounts of this substance might be unlikely to occur. However, absorption of particular amounts is proved by the systemic effects observed in the course of repeated dose studies.

Studies on genotoxicity performed with Hostavin N 20 (Ames-Test; chromosome aberration test and HGPRT test) were negative, i.e. there is no indication of a reactivity of the substance under the test conditions. The assumption of a very limited metabolism of Hostavin N20 is supported by the proven low tendency to hydrolyze and the poor water solubility. However, a cleavage of the amide function in the molecular center is thinkable.

 

 

 

Excretion

With reference to the highLog Powand molecular weight (> 300) the biliary excretion might be the considered as the most favorable excretion route. Therefore, enterohepatic recycling resulting in a prolonged biological half-life can not be excluded (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, p. 178).

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential

Additional information