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EC number: 201-877-4
CAS number: 89-04-3
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
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
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 a
structural analogue of the substance (tris-(2
-ethylhexyl)trimellitate), in which the ester chains are C-8 branched
rather than C-8 linear, has been investigated in the rat following
oral administration of a single dose. Findings indicate that the
substance 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
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