A mixture of: bis(2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-1,10-decanedioate; 1,8-bis[(2,2,6,6-tetramethyl-4-((2,2,6,6-tetramethyl-1-octyloxypiperidin-4-yl)-decan-1,10-dioyl)piperidin-1-yl)oxy]octane

Endpoint summary

Additional information

Assessment of the Toxicokinetic Behaviour (EC No. 406 -750 -9)

 

There were no studies available in which the toxicokinetic properties of the test item were investigated.

The test item is a yellow colored liquid mixture with a molecular weight of 685 Da (see chapter 1 general information). The test substance is of low volatility (see chapter 4.6), very low water solubility (< 6 mg/L at 20°C (see chapter 4.8 water solubility)) and has an n-octanol-water partition coefficient (log Pow) of >10 at 25 °C (see chapter 4.7 partition coefficient). The substance is not readily biodegradable. A general accumulation of the test substance in humans may be low because it’s a high lipophilic molecule and because of the sterically reasons.

 

Absorption

Slight effects were noted in the 28-day and 90-day repeated dose studies that were reversible after a subsequent four-week period without treatment. Therefore, bioavailability of the test substance to some degree is indicated after oral administration. Physico-chemical properties do not support a potential for systemic exposure of the test item.

In line with the low acute oral and dermal toxicity of the test substance are physico-chemical properties: as a highly lipophilic molecule the test substance might be poorly absorbed from the gastrointestinal tract and its bioavailability is expected to be low as indirectly proven by the absence of slight degree of toxicity. Due to the high molecular weight and the very low water solubility the dermal absorption is also considered as low.

The test item has a comparably low vapour pressure of 3.6E-4 Pa at 25°C (CIBA-Geigy, see chapter 4.6 vapour pressure); subsequently, the calculated vapour saturation threshold is ca. 0.00011 mg/L. Therefore, relevant human exposure of the substance via the inhalative route is not assumed.

 

Metabolism

Information about potential metabolites is not available. Genotoxicity studies did not reveal a difference in the results with or without application of the S9 -mix. The test item has very low water solubility (< 6 mg/L) but may not be hydrolytically resistant. Hydrolysis reactions are suggested under the conditions in the gastro-intestinal tract and cleavage products may be much better absorbed than the parent substance through the intestinal wall. Similar reactions are suggested to occur in the liver. Hydrolytic cleavage of the acyclic carboxylic esters is predicted, followed by glucuronidation and/or elimination.

Theoretically, an accumulation might occur in the lipid-rich tissues due to the high lipophility. However, the proportion of the substance that enters systemic circulation unchanged is considered as extremely low. Furthermore, it can only be concluded from the reversibility of the observed effects in the subacute and subchronic repeated dose studies that the test substance does not accumulate in the body.

 

Excretion

There is no information available about potential metabolites.

High molecular weight and the low water solubility indicate biliary excretion. The cleavage products however may be subject to urinary excretion.