A mixture of: 2,2,6,6-tetramethylpiperidin-4-yl-hexadecanoate; 2,2,6,6-tetramethylpiperidin-4-yl-octadecanoate

Endpoint summary

Description of key information

Expert statement: 'Reaction mass of 2,2,6,6-tetramethylpiperidin-4-yl-hexadecanoate and 2,2,6,6-tetramethylpiperidin-4-yl-octadecanoate' has no potential for bioaccumulation. The relevant absorption rates can be estimated by expert judgement to 80% (oral, including metabolites and hydrolysis products), 30% (dermal) and 30% (inhalation).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

80

Absorption rate - dermal (%):

30

Absorption rate - inhalation (%):

30

Additional information

In order to assess the toxicokinetic behaviour of SABOSTAB UV-91, 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 395.67 g/mol resp. 423.73 g/mol, it is generally favourable for absorption. However, taking into account the Log Pow of > 6.5 (at 40°C and pH7), the absorption e.g. by diffusion might be hindered, 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. Hence, an oral absorption rate of 25% or less can be estimated for the parent compound.

Based on the chemical structure of the substance and the results of the water solubility study, a hydrolysis of the parent compounds needs to be taken into account, which would lead to the formation of 2,2,6,6-Tetramethylpiperidin-4-ol and the fatty acids palmitic acid resp. stearic acid. The fatty acids are also regularly fed for nutrition and will be subjected to the naturally present process of the fatty acid metabolism. Consequently, these two substances do not need to be regarded further.The low molecular weight of 2,2,6,6-Tetramethylpiperidin-4-ol, its rather high water solubility and Log Pow of 0.94, however, make it very favourable for oral absorption.Taking the hydrolysis products also into account leads to the estimation of a precautionary absorption rate of approx. 80%, probably overestimating the actual oral absorption.

SABOSTAB UV-91 has a very low vapour pressure and a boiling point of 246°C at 39 kPa, clearly showing that the inhalative absorption as a gas does not have to be regarded, which is supported by its physical state, a waxy solid, which is not able to be inhaled. Thinking of a possible inhalation of an aerosol with the solved hydrolysis product 2,2,6,6-Tetramethylpiperidin-4-ol, however, a precautionary absorption rate of up to 30% can be estimated.

In case of SABOSTAB UV-91, neither an evaporation after skin contact nor very remarkable additional absorption-enhancing effects due to corrosivity need to be regarded. Taking into account its molecular weight, high Log Pow and low water solubility, a passage of the parent compound through the stratum corneum is unlikely. 2,2,6,6-Tetramethylpiperidin-4-ol, on the other hand, has a molecular weight of 157.25, a high water solubility (> 100 g/L at 25°C), and a Log Pow of 0.24 (at 25°C), enabling it in generally to be absorbed through the skin. Hence, the absorption rate of SABOSTAB UV-91 including its toxicologically more relevant hydrolysis product 2,2,6,6-Tetramethylpiperidin-4-ol is most likely in the range of 30%.

Taking into account the medium molecular weight of 395.67 g/mol resp. 423.73 g/mol of the unchanged SABOSTAB UV-91, its lipophilicity and poor water solubility, the absolute systemic bioavailablility is rather low and expected to be more extensive in fat tissues than in other tissues.

Considering the most likely occurring hydrolysis, however, the systemic bioavailability of the hydrolysis products, especially 2,2,6,6-Tetramethylpiperidin-4-ol, is rather high, leading toa certain peak exposure of both the hydrolysis products and their metabolites. Due to the high water solubility of 2,2,6,6-Tetramethylpiperidin-4-ol and the furthermore expected high solubility of the metabolites because of their hydroxyl groups, a rapid distribution in the aqueous compartments of the body is expected as well as a rapid excretion.

Since SABOSTAB UV-91 is not considered hydrolytically 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.

Since an at least partial hydrolysis of the ether bonds may occur in the acidic, aqueous environment of the stomach, metabolism of the hydrolysis products is a relevant issue to be considered. Besides Amine hydroxylation and Aliphatic hydroxylation of the parent compound being subject to further hydrolysis, the most like metabolizing processes for 2,2,6,6-Tetramethylpiperidin-4-ol were identified byToxtree estimation asAmine hydroxylation, Alcohol oxidation (resulting in2,2,6,6-Tetramethyl-4-piperidone) and Aliphatic hydroxylation. In general, it is hence unlikely that the parent substance will be excreted unchanged, the metabolites however will, based on the relevant available functional groups, i.e. ketone or hydroxyl groups, be excreted rather fast either unchanged or as Phase 2 conjugated metabolites via the urine.

In conclusion, SABOSTAB UV-91 has a minor potential for bioaccumulation in its non-metabolized 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 of 'Reaction mass of 2,2,6,6-tetramethylpiperidin-4-yl-hexadecanoate and 2,2,6,6-tetramethylpiperidin-4-yl-octadecanoate' in 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.