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No experimental studies with the UVCB substance 400160 are available. Published data for the alcoholic component (2-EH) and fatty acids were used to derive an assessment on the toxicokinetic behaviour of 400160. Based on the molecular weight and physicochemical properties of all constituents of 400160 it can be expected that they can be absorbed or are able to penetrate human skin. An extensive metabolisation and excretion is expected for the components of 400160.
on the molecular weight and physicochemical properties all constituents
of 400160 are expected absorbable after oral or dermal exposure.
Subsequent to absorption, the esters may become hydrolysed to the
corresponding dicarboxylic acid and 2-ethylhexanol (2 -EH).
the alcoholic component (2-EH) in vivo data on toxicokinetics after oral
or dermal administration is available. 2-EH is rapidly absorbed
following oral administration, but is only slowly absorbed following
dermal application (Deisinger et al. 1994). Systemic 2-EH is subjected
to extensive oxidative metabolism and glucuronidation followed by rapid
excretion, primarily in the urine. Only at very high dosages some
evidence of metabolic saturation was observed, but repeated dosing with
2-EH at 50 mg/kg produced no evidence of metabolic induction (Deisinger
et al. 1994).
rats 2-EH was efficiently absorbed following oral administration and
rapidly excreted mainly in the urine (80 -82%); minor fractions were
excreted via the lungs (6 -7%) and feces (8 -9%). Elimination was
essentially complete by 28 h. The major urinary metabolite of 2-EH in
the rat was shown to be 2-ethylhexanoic acid through acid extraction of
urine. This metabolite can undergo partial β-oxidation and
decarboxylation to produce 14CO2 in the lung and
2- and 4-heptanone in the kidneys. Other urinary metabolites of 2-EH
were identified as 2-ethyl-5-hydroxyhexanoic acid,
2-ethyl-5-ketohexanoic acid, and 2-ethyl-1,6-hexanedioic acid.
Approximately 3% of the parent compound was excreted unchanged (WHO;
Environ Health Criteria Number 32: Toxicological Evaluation of Certain
Food Additives and Contaminants. p. 35 (1993)).
in vitro dermal absorption study of 2-EH was conducted with full
thickness rat skin and human stratum corneum. The ratio of the rate of
absorption of 2-EH through rat and human skin (rat/human) was reported
to be 5.8, indicating that rat skin is more permeable to 2-EH than human
skin (WHO; Environ Health Criteria Number 32: Toxicological Evaluation
of Certain Food Additives and Contaminants. p. 36 (1993)).
commonly known for long-chain fatty acids also the dicarboxylic acid is
subjected to β-oxidation, leading finally to C2-moieties that enter the
citric acid cycle for endoxidation.
acids are usually ingested as triglycerides, which cannot be absorbed by
the intestine. Therefore, fatty acids are emulsified by bile salts from
the gall bladder and form micelles. In the small intestine the enzyme
pancreatic lipase degrades the triglycerides into fatty acids and
with apoproteins and cholesterol the triacylglycerols form blood-soluble
complexes (chylomicrons) which are able to move across the blood vessel
membrane. Chylomicrons are transported via the bloodstream to fat cells
(adipocytes) or muscle fibers, where they are either stored or oxidized
for energy supply. For storage of fat in adipocytes, the triacylglycerol
is cleaved by lipoprotein lipase into fatty acids and glycerol and are
able to pass the membrane of adipocytes. Then they can be released and
transported to myocytes by serum albumin. For energy utilization in
muscle cells (myocytes) fatty acids undergo β-oxidation. This process
finally releases carbon dioxide and ATP via the citric acid cycle.
has been generally well established that the length of carbon chain
determines the intestinal absorption pathway of fatty acids (Bernard and
Carlier, 1991). The shorter the chain length the better is the
absorption into blood, and unsaturated fatty acids can be better
resorbed than saturated fatty acids. The differences might partial be
related to the differences in the fatty acid hydrosolubility (Bernard
and Carlier, 1991).
general the components of 400160 are expected to be absorbed and undergo
extensive oxidative metabolisation.
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