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EC number: 258-847-9 | CAS number: 53894-23-8
Disposition of Radioactivity -The excretion of radioactivity following administration of a single oral dose occurred mainly in the faeces, this accounting for approximately 75% of the administered dose with 16.3% found in the urine and 1.9% in expired air. Residual radioactivity in the carcass 144 hours post dose was <0.6% of the administered dose. Tissues analysed for radioactivity revealed only liver (5x) and adipose tissue (3x) containing levels of radioactivity greater than the carcass average. Recovery was 94.1% of the administered dose.
Characterisation of Faecal and Urinary metabolites -The radioactive components of faecal extracts were characterised by HPLC. Using the prepared standards it was possible to identify three monoesters and two diesters while evidence for a third diester was obtained by UV spectral analysis. Radioactivity in the faecal extracts was identified as 86% TOTM, 7% di-(2-ethylhexyl)trimellitate and 1% mono-(2-ethylhexyl)trimellitate. Only one of the three possible mono-ester isomers was found.
Analysis of urine by GC/MS revealed the presence of 2-ethylhexanol, 2-ethylhexanoic acid, 2-heptanone and mono-(2-ethylhexyl)trimellitate. HPLC retention times indicated that the mono-ester was the same isomer found in faecal extracts. No isomers of di-(2-ethylhexyl)trimellitate were found.
Kinetics -Two peaks in the plot of the rate of excretion of14CO2in expired air were observed for each rat in the study. The first was observed 2-3 hours post dose and the second 8-12 hours post dose, the authors suggesting this to be a result of metabolism of 2-ethylhexanol occurring from its release by hydrolysis from the tri-ester followed by a further hydrolysis step releasing 2-ethyl hexanol from the di-ester. The half-life for initial absorption was estimated to be approximately 0.7 hours. The die-away of14CO2was bi-phasic with half-lives of 4.3 and 31 hours. Urinary excretion of radioactivity was also bi-phasic with half-lives of 3.1 and 42 hours.
The absorption, distribution, metabolism and elimination of TOTM have been investigated in the rat following oral administration of a single dose. Findings indicate that TOTM is only 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.
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