Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, isotridecyl ester

Endpoint summary

Description of key information

Expert statement: C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate has a minor potential for bioaccumulation. The relevant absorption rates can be estimated by expert judgement to 50% (oral, including metabolites and hydrolysis products), 50% (dermal) and 25% (inhalation).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

25

Additional information

In order to assess the toxicokinetic behaviour of C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, the available toxicological and physico-chemical data were evaluated.

The substance, i.e. the unchanged parent compound, is expected to be rather poorly absorbed via the oral route. With a molecular weight of 460.7 g/mol, absorption in general can be considered as possible. However, taking into account the Log Pow of Log Pow = 3.56 (at 25°C), might indicate a beginning slightly hindered absorption e.g. by diffusion, and also, only water-soluble substances will readily dissolve into the gastrointestinal fluids and hence be available for absorption, which limits the absorption of the poorly soluble compound. The presence of absorption is indicated by some effects observed in animal studies.

Based on the chemical structure of the substance, a hydrolysis of the parent compounds needs to be taken into account, which are most likely 3,5-Di-tert-butyl-4-hydroxyphenylpropionic acid and isotridecanol.In general, the low molecular weight of the hydrolysis products makes them favourable for absorption. The uptake of the long-chain alcohols seems to be limited due to their low water solubility and high Log Pow and is also not toxicologically relevant due to their non-toxicity. Similar considerations with regard to absorption apply to 3,5-Di-tert-butyl-4-hydroxyphenylpropionic acid, however, without information on the toxicological relevance.

It is also unknown to which extent the absorption of the hydrolysis products needs to be regarded. As the oral absorption of the parent compound can be considered as limited, the oral absorption rate can be estimated to approx. 25%. Since hydrolysis is nevertheless a very likely scenario, the degradation products and their uptake should be considered, too. This leads to the estimation of a precautionary absorption rate of approx. 50% due to the similarly hindered absorption as the parent compound, probably overestimating the actual oral absorption.

C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (data from EC 413-750-2) has a rather low vapour pressure (e.g. 166 Pa at 20°C, 430 Pa at 40°C) and a boiling point of 220-245°C at 101.3 kPa, showing that the inhalative absorption as a gas does not have to be regarded, which is supported by the fact that it is liquid at room temperature, i.e. no particles of an inhalable size are present. Thinking of a possible, but very unlikely inhalation of an aerosol and considering the available phys.-chem. data, the absorption of the parent compound as well as possible hydrolysis products can be neglected and since the concretehydrolysis rate is not available, a precautionary absorption rate of up to 25% can be estimated.

In case of C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, neither evaporation after skin contact nor very remarkable additional absorption-enhancing effects due to corrosivity need to be regarded. Taking into account the molecular weight, high Log Pow and low water solubility, a passage of the parent compound and similarly the possible hydrolysis products through the stratum corneum is unlikely, but cannot be completely excluded. Due to uncertainty issues, a precautionary absorption rate of 50% should be taken into account.

Taking into account the molecular weight of 460.7 g/mol, the rather lipophilic character and poor water solubility, the absolute systemic bioavailability is rather low and expected to be more extensive in fat tissues than in other tissues. Similar considerations apply to the potential hydrolysis products, although their bioavailability, if occurring, might be slightly enhanced compared to the parent compound. As, after first pass metabolism, more hydrophilic metabolites are expected to occur, and a rather minor absorption of C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, no relevant peak exposure, AUC and prolonged bioavailability will occur.

Since C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate is not considered especially hydrolytically or metabolically stable, a prolonged, extensive accumulation is not expected. After metabolism, the excretion of the metabolites, either as such or after Phase 2 metabolism, will occur rather fast, as well as the unchanged hydrolysis products and their metabolites would, an accumulation is not very likely, too. The sites of metabolism of the parent compound as well as hydrolysis products were identified as the aliphatic moieties. Summarising, it is most likely that the substance of interest and its hydrolysis products will be subject to metabolism by cytochrome P450 enzymes and subsequent conjugation.

In conclusion, C13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate has a minor potential for bioaccumulation in its non-metabolised form, and will be excreted rapidly after hydrolysis and accompanying / subsequent metabolism.

The present expert statement covers all relevant toxicokinetic parameters to assess the behaviour ofC13-(branched)-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionatein the body, the available information is well-investigated and sufficient to enable one to perform a proper risk assessment. The tonnage-driven data requirement under REACH are fully met and hence, no further information needs to be gathered and further studies can be omitted due to animal welfare.