Trioctyl benzene-1,2,4-tricarboxylate

Endpoint summary

Description of key information

The substance is expected to be poorly absorbed through the gastro-intestinal tract following oral administration. If absorbed it is eliminated relatively rapidly, mainly via the urine as polar metabolites. In-silico evaluation suggests dermal absorption is not significant.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

The substance is a trimellitate ester with linear C8 alkyl chains. Experimental data are not available for the assessment of the toxicokinetic properties of the substance and read-across to available information on structurally similar substances is therefore a possible approach to characterise toxicokinetic endpoints for the substance. Based on structurally similarity to phthalate esters (esters of 1,2-dicarboxylic acid rather than 1,2,4-tricarboxylic acid) a similar toxicokinetic behaviour is expected.

The phthalate esters have been extensively studied and various reviews of different phthalate esters by the Australian National Industrial Chemicals Notification and Assessment Scheme (NICNAS) are available. The data on the toxicokinetics indicate that phthalates in general are likely to be absorbed as the mono-ester from the gastro-intestinal tract following hydrolysis of the di-ester and excreted via the urine.

The similarity in toxicokinetic behaviour with the phthalate esters is supported by data on the absorption, distribution, metabolism and elimination of a structural analogue of the substance (tris-(2 -ethylhexyl)trimellitate), in which the ester chains are C-8 branched rather than C-8 linear. Rats were administered a single oral dose of the radiolabelled substance. Recovery of the administered dose was 94% with approximately 75% eliminated unchanged in the faeces, 16.3% found in the urine and 1.9% in expired air. Residual radioactivity in the carcass after 6 days was <0.6% of the administered dose. Findings indicate that the substance may be partially hydrolysed in the gastro-intestinal tract to the alcohol and corresponding di-ester and, following further hydrolysis, the mono-ester. Only 2 -ethylhexanol and a single isomer of mono-(2 -ethylhexyl)trimellitate appear to be absorbed. Following absorption, 2-ethylhexanol was extensively metabolised with metabolites eliminated in the urine and as expired14CO2.There was no evident metabolism of mono-(2-ethylhexyl)trimellitate, this being eliminated unchanged. Urinary excretion of radioactivity was bi-phasic with half-lives of 3.1 and 42 hours.

 

In summary, available toxicokinetic studies show that the substance is expected to be poorly absorbed through the gastro-intestinal tract following oral administration. If absorbed it is eliminated relatively rapidly, mainly via the urine as polar metabolites.

 

In-silico evaluation of dermal absorption indicates that after 4 hours there is no amount of deposited trioctyl benzene-1,2,4-tricarboxylate that is absorbed within viable epidermis and therefore that could enter in systemic circulation.