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EC number: 701-008-3
CAS number: -
No data are
available on the toxicokinetics of S278. The absorption, distribution,
metabolism and excretion (ADME) of the structurally related material,
di(isononyl) phthalate (DINP; CAS 68515-48-0), were evaluated in young
rats exposed orally or by dermal application.
acute oral studies, groups of 20 males and 4 females received
radiolabelled DINP (in corn oil) by stomach tube on a single occasion at
50 or 500 mg/kg bw. For the repeated dose oral studies, groups of 15
males received radiolabelled DINP (in corn oil) by stomach tube at 50,
150 or 500 mg/kg bw/day for five consecutive days. For the dermal
studies, radiolabelled DINP was applied (occluded) to the skin of male
rats at 1.2 ml/kg bw for the first two studies (involving six rats each)
and at 0.6 ml/kg bw for the third study (involving only 3 rats). In the
second dermal study, the skin had previously been conditioned by the
application of 1.2 ml/kg bw of unlabelled DINP and covered for 3
days. Body fluids and certain tissues (including the urine, faeces,
blood, liver, kidneys, lungs, brain, spleen, testes/ovaries, skin,
skeletal muscle, fat and gastrointestinal tract) were sampled and
collected at various time points after oral or dermal treatment to
assess the distribution of radiolabel (14C) and to identify the
acute and repeated oral studies, absorption from the gastrointestinal
tract was rapid. Radioactivity was detected in the blood (about 1.5% of
the administered dose) within 1 hour of dosing, peaked 2-4 hours after
dosing, declining thereafter. The highest levels of radioactivity (after
the gastrointestinal tract) were found in the liver (about 4% of the
administered dose) and to a lesser extent the kidneys (about 0.35%).
These levels were highest 1 hour after dosing, and (as with the blood)
radioactivity declined to 10-20% of the peak values within 24 hours.
Levels of radioactivity in other tissues were much lower and declined
rapidly over time. No evidence of persistence or accumulation in any
organ was reported. When animals were sacrificed 24 hours after dosing,
the majority of the recovered material (16-23% of the administered dose)
was found in the gastrointestinal tract. Excretion occurred primarily in
the urine and was essentially complete within the first 24 hours, the
remainder recovered in the faeces within about 48 hours following oral
dosing. DINP was rapidly metabolised in the gastrointestinal tract to
the corresponding monoester (MINP). Both DINP and MINP were absorbed
from the gastrointestinal tract, and excreted, primarily in the urine,
as phthalic acid and oxidation products.
from the three dermal studies showed that 2-4% of the applied DINP was
absorbed within 7 days, with the highest absorption seen in the rats
conditioned with DINP. Data from animals sacrificed at 1 and 3 days
after dermal DINP application evidently suggested that the absorption
rate was about 0.3-0.6% per day.Around
1-2% of the dermally applied dose was excreted in the urine, and 0.5-1%
in the faeces.
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