Ethylene bis[3,3-bis(3-tert-butyl-4-hydroxyphenyl)butyrate]

Endpoint summary

Description of key information

no study available

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

There are no studies available in which the toxicokinetic properties of Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate]were investigated.

 

Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate](molecular weight: 795 g/mol) is a white crystalline solid, which is considered to be hydrolytically stable. Its water solubility is determined to be 0.5 mg/L at 20°C (see chapter 4.8). The octanol water partition coefficient (Log P_ow) value of > 6.5 was obtained for Ethylene bis[3,3-bis(3-tert-butyl-4-hydroxyphenyl)butyrate], using a HPLC method. (see chapter 4.7). Due to the relative high Log P_owof 13.66 in combination with only a slight hydrolysis of the substance (see chapter 5.1.2) a general low potential of bioaccumulation might be considered.

 

Absorption

With reference to the Log P_owof 13.66, the very limited water solubility and the molecular weight of 795 g/mol the absorption of Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate] is considered to be very poor (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, Table R.7.12-1, p. 152). Furthermore, the substance contains several hydroxyl 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. 150). Therefore, a large-scale absorption of Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate] might be excluded. This assumption is strengthened by the results of the acute oral toxicity studies in rats (LD₅₀> 15,000 mg/kg bw). However, since some (unspecific) effects were observed in the course of repeated dose studies at high doses a small 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. 150).

 

Distribution

Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate]is a very lipophilic substance with a high molecular weight. Therefore, it will tend to migrate into cells and concentrate in adipose tissues (please refer to Guidance on information requirements and chemical assessment, Chapter R.7c, pp. 159-160). The accumulation in milk also can not be excluded. This possible distribution pattern might explain the observations made in pups in the course of the reproductive toxicity studies while the lactation phase.

 

Metabolism

Taking into accountthe Log P_owof 13.66, the very limited water solubility and the molecular weight of 795 g/mol, an uptake of considerable amounts of this substance is very unlikely to occur. However, absorption of small amounts can not be excluded.

Studies on genotoxicity performed with theof Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate](Ames-Test; chromosome aberration test and HPRT 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 ofof Ethylene-bis[3,3-bis(3-tert.-butyl-4-hydroxyphenyl)butyrate] is supported by the proven low tendency to hydrolyze and the poor water solubility. However, a cleavage of the ester functions in the molecular center is thinkable.

 

Excretion

With reference to the high Log P_owand molecular weight 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. 161).