Reaction mass of (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl palmitate and (9-acetoxy-3,8,10-triethyl-7,8,10-trimethyl-1,5-dioxa-9-azaspiro[5.5]undec-3-yl)methyl stearate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Assessment of the toxicokinetic behavior of test substance:

The test substance is a multi-constituent. The main components can be distinguished by their side chains. Component (1) is esterified with a stearic acid (molecular weight of 638 g/mol) and component (2) is esterified with palmitic acid (molecular weight of 606.9 g/mol). The multi-constituent is a clear, colorless to slightly yellowish liquid (BASF, 2012) with a log Pow of 12 at 25°C for the carboxylic acid esters with C17 alkyl chain and with a log Pow of 11 at 25°C of the carboxylic acid esters with C15 alkyl chain (BASF, calculation EPISuite, 2018). The water solubility of the multi-constituent was 12.1 mg/L at 20°C (BASF, 2012) and the vapour pressure is < 0.00001 at 25°C (BASF, calculated SPARC, 2011).

 

Absorption

Generally, the smaller the molecule, the more easily it may be taken up. Molecular weights below 500 g/mol are favorable for absorption; molecular weights above 1000 g/mol do not favor absorption (ECHA GD 7c, 2008). Based on the molecular weight of the main components at least a slow absorption is suggested.

This is further supported by an available reproductive/developmental screening study in Wistar rats (ERBC, 2022. EC 936-831-9), which was performed at dose levels of 100, 300 and 1000 mg/kg bw/day. The test substance was administered by oral route. As shown by adaptive liver changes, absorption of the source substance through the GI tract does occur.

Dermal absorption might occur to some extent. The molecular weight of the test substance is > 500 g/mol, which may be too large for dermal absorption. In addition, for substances with log Pow values above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. However, for substances with a water solubility between 1-100 mg/l and vapor pressure below 100 Pa, absorption via skin is possible (ECHA GD 7c, 2008). In addition to the mentioned physical properties, the structural analogue to the registered substance was identified as a skin sensitizer in a conducted Local Lymph Node Assay (RCC, 2003. CAS 376588-17-9). The only difference between the structural analogue and the registered substance mainly refers to the main components of the multi-constituent. The structural analogue is esterified with stearic acid (C17), whereas the registered substance is a mixture of stearate (C17) and palmitate (C15). For more details to the analogue approach please refer to chapter 13. Overall, as the test substance was identified as a skin sensitizer, some uptake must have occurred although it may only have been a small fraction of the applied dose.

No data from acute or repeated dose toxicity studies by the inhalation route are available, which could provide information about the systemic distribution of the test substance after inhalation. Inhalative exposure is not of relevance as the substance has a very low vapor pressure.

 

Metabolism

Once systemically available, the main components of the multi-constituent are prone to ester hydrolysis. Ester hydrolysis will transform both main components to an alcohol residue and a carboxylic acid. The only difference is limited to the identity of the carboxylic acid. Hydrolysis of component (1) will release stearic acid, while from compound (2) palmitic acid will be released. Referring to component (1), the carboxylic acid is proposed to be further metabolized via beta-oxidation to palmitic acid and acetic acid. Referring to component (2), the carboxylic acid is proposed to be further metabolized via beta-oxidation to myristic acid and acetic acid. The alcohol residue (for component 1 and 2) is proposed to be further metabolized to an aldehyde residue and afterwards an acid residue via aliphatic c-oxidation (proposed pathway assessed using kinetic modeling via OASIS TIMES v.2.31.2.82) 

 

Excretion

The excretion pathway is largely dependent on molecular size, polarity and water solubility. Since the test substance has a molecular weight larger than 500 g/mol and only a slight solubility in water, it is expected to be excreted predominantly via feces (ECHA GD Chapter R.7c, 2017). Potential metabolites are either excreted via feces or urine, depending on their molecular size and water solubility.