coconut oil, reaction products with glycerol esters of 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoic acid

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Experimental data is not available. Based on the chemical structures of the components and on the subacute and subchronic toxicity data, no hazard for bioaccumulation is identified.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The substance contains several components. All of them either have a log Pow of less than 3 or they have a log Pow of >> 3 and contain an ester function that may undergo enzymatic hydrolysis. The toxicity profile is consistent with an adaptive and reversible liver enlargement. Therefore, the substance is considered to be non bioaccumulating.

Discussion on bioaccumulation potential result:

The substance is a mixture of esters generated from reacting glycerol, a natural oil and a sterically hindered phenol-alkylene-carboxylic acid. Considering the reversible liver enlargement observed upon subacute oral exposure, systemic uptake and elimination of at least some components are assumed. Systemic availability of the individual components will be different depending on their molecular weight, the log Pow and the bulkiness of the molecule. For the most bulky structure, which is a trimester of glycerol and thesterically hindered phenol-alkylene-carboxylic acid,modelling of the size gave for the smallest and largest diameter a length of 13 and 16 Angstöm, respectively. It has a calculated log Pow of 15.2 and a molecular mass of 873 g/mol. In contrast, the UVCB substance also contains glycerol and the monoester of glycerol and thesterically hindered phenol-alkylene-carboxylic acidwhich should be are easily taken up.

In the determination of water solubility, only two components were detected. It is expected that one component is unreacted glycerol and the other is the monoester of glycerol and the thesterically hindered phenol-alkylene-carboxylic acid. All other components are of higher molecular weight and contain a more lipophilic functions (eg alkyl-chains.). In the initiatial experimental determination of the log Pow, all of the UVCB substance was found in the octanol phase and nothing was detected in the aqueous phase.

The log P_OWwas therefore calculated for the different components showing that components adding up to 50% of the substance have a log Pow of > 9.

Esters of the sterically hindered phenol-alkylene-carboxylic acidand glycerol are expected to undergo enzymatic ester hydrolysis. Toxicokinetic data on the methyl ester of the sterically hindered phenol-alkylene-carboxylic acid is available in the registrant's files showing efficient hydrolysis and elimination of the acid (or its metabolites) via kidney and bile. The bulky groups are not too close to the ester bond for steric hindrance of hydrolytic enzymes.

The sterically hindered phenol-alkylene-carboxylic acid may in theory undergo oxidative metabolism at the side chain substituent. This substance is related to the food additive BHT (butylated hydroxytoluene) for which such metabolic transformations have been described. Phase-II conjugation at the hydroxy-group may be hindered by the bulky groups. Both pathways involve xenobiotic metabolism enzymes that are highly inducible in rat liver. This is consistent with the reversible liver enlargement observed in the rat studies.

For the fraction containing esters of the oil and glycerol, normal metabolism in analgoy to dietary fat is expected. Glycerol and natural oel acids are not expected to contribute to the hazard profile (enzyme induction in liver and secondary thyroid effects.)

 

Systemic availability upon ingestion is expected to be most efficient because the UVCB substance is a viscous liquid that becomes emulgated by the bile. It is structurally related to fat and as such uptake and metabolism is facilitated.

In contrast, no such facilitation occurs for the dermal route of exposure. The UVCB substance is not surface active and therefore does not facilitate its own uptake. The molecular weights of the components that are a glyercol ester with at least twosterically hindered phenol-alkylene-carboxylic acids or one sterically hindered phenol-alkylene-carboxylic acid and one natural oil acid are all higher than 500 g/mol. For these components, the calculated log P_OWvalues are higher than 9. In accordance with ECHA guidance documents, skin permeability of these components is unlikely and a default uptake of 10% is given. The component that may be sufficiently small and soluble for uptake is present in the mixture at less than 20%. So overall, a permeability of 30% is assumed.

In addition, the sterically hindered phenol-alkylene-carboxylic acid is the moiety that causes the effects on liver. The poorly permeating components contain one, two ore three times the number of this moiety and therefore, the permeating component is the one contributing least to the liver effects. For DNEL-derivation, an additional factor of 0.5 is used to take this into account.

 

Regarding the inhalation route, exposure is expected to be very low as the substance is a viscous liquid and the components contributing to the effects on liver have a very low vapour pressure. Esterases are ubiquous enzymes, so in principle, no difference in hazard profile is expected for any route of exposure.

Overall, the substance is not considered to be bioaccumulating.