5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1-nonanol

Endpoint summary

Description of key information

Toxicokinetic studies on a similar trimellitate ester (TOTM) indicate that the substance is expected to be poorly absorbed through the gastro-intestinal tract following oral administration. If absorbed it is expected to be eliminated relatively rapidly, mainly via the urine as polar metabolites. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

No data are available on the substance itself, a trimellitate ester derived from predominately linear alcohols of C9 chain length. The most comprehensive data are on tri(2 -ethylhexyl)trimellitate (TOTM), this being an ester from a branched alcohol of C8 chain length. Hydrolysis by esterases is regarded as an important first step in the oral absorption of ortho-phthalates. The potential for such hydrolysis to occur with trimellitates has been examined in an in-vitro study using a rat gut homogenate. There was no evidence of hydrolysis of TOTM occurring while the corresponding phthalate, di(2-ethylhexyl)phthalate (DEHP), was significantly hydrolysed.

The absorption, distribution, metabolism and elimination of TOTM have been investigated in the rat following oral administration of a single dose. 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 TOTM may be partially hydrolysed in the gastro-intestinal tract to 2-ethylhexanol and the 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 TOTM is poorly absorbed through the gastro-intestinal tract following oral administration. If absorbed it is eliminated relatively rapidly, mainly via the urine as polar metabolites.