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EC number: 287-335-8
CAS number: 85480-55-3
1: Distribution of LA35S in urine and feces after administration of
single dose of various quantities by stomach tube (Michael, 1968)
Average of 3 animals
Average of 5 animals
2: Disposition of 3% in bile duct ligated rats 90 hours after a single
dose of LAS (Michael, 1968).
The purpose of the study was to determine
the absorption, distribution and metabolic fate of test substance,
C10-13 LAS in rats.
Charles river male rats (150-200 g) were
used in this study. The rats were housed in individual
cages which permitted the separate collection of urine and feces. For
the determination of disposition profile of chemical, rats were fasted
for 16 hours and given orally an aqueous solution containing LA35S. The
dose was given in 1.0 mL volume. The urine and feces were collected
daily for examination. At the termination of the study, the animals were
killed, and selected organs and tissues were taken for radioassay.
The absorption, route of absorption and
enterohepatic circulation of test substance were also quantified in the
study. The route of absorption was determined by oral
feeding of 40 mg of LAS to thoracic duct-cannulated rats. The lymph was
collected from each animal in a single 42-hour fraction. For absorption
study, each rat received orally 1.2 mg of test substance. The urine and
feces of each animal were collected for 90 hours after dosing for
The enterohepatic circulation of the
surfactant was quantified by using a dual rat study. In this, Rat A of
one pair received 1.2 mg of LAS by stomach tube, while Rat A of second
pair received another chemical. The 35S containing compounds from LA35S
that were excreted in bile of Rat A and transferred by cannula to Rat B
were completely absorbed from the gastrointestinal tract of Rat B, and
nearly two-thirds of this activity was excreted in the bile of Rat B.
For the excretion study, the cumulative
excretion of LA35S, at dose levels 0.6, 1.2, 8.0 and 40.0 mg over a 3-
day period following a single administration is determined.
Urine and feces samples were also analyzed
for the identification of metabolites. Various analytical techniques
like column chromatography, infrared, nuclear magnetic resonance (NMR),
and mass spectra were used for the determination of metabolites.
The results revealed 80-90% of the
administered dose was readily absorbed from the gastrointestinal tract
and excreted primarily through urine. Of the absorbed LA35S, 60-65 % was
excreted in the urine as a mixture of sulfo - phenyl butanoic and
sulfophenyl pentanoic acids. 35% of the absorbed 35S was excreted in the
bile and was reabsorbed completely from the gastrointestinal tract. Very
little was found in the lymph, so transport of LAS is probably by way of
portal venous blood.
Based on the above, LAS was readily absorbed
by the gastrointestinal tract, rapidly metabolized and excreted in the
1: Mean rates of excretion of radioactivity in urine and faeces of
rhesus monkeys after single oral dose of [14C] LAS at a nominal dose
level of 30 mg/kg bw (Cresswell et al., 1978)
are expressed as percent dose
Mean of 2 animals
Includes radioactivity in cage washes and cage debris.
2: Mean rates of excretion of radioactivity in urine and faeces of
rhesus monkeys after single subcutaneous doses of [14C] LAS at a nominal
dose level of 1 mg/kg bw(Cresswell
et al., 1978)
axe expressed as percent dose
Concentrations of radioactivity in organs and tissues after 7
consecutive daily oral doses of [14C] LAS at a nominal dose level of 30
et al., 1978)
are expressed asµg
4: Concentrations of radioactivity in organs and tissues after 7
consecutive daily subcutaneous doses of [14C] LAS at a nominal dose
level of 1.0 mg/kg bw(Cresswell
et al., 1978)
are expressed as µg
The purpose of the study was to determine
the disposition of radioactivity after single and repeated oral or
subcutaneous doses of [14C] LAS to rhesus monkeys.
Four adult rhesus monkeys (2 male and 2
female) of body weight approximately 5 kg each were used for all
experiments. For excretion studies, single oral doses (14C-LAS of 30
mg/kg bw at 25 µCi) were administered by oral intubation as a solution
in water. For the plasma level studies, the same animals were
administered single oral doses (14C-LAS of 150 mg/kg bw at 26 µCi and
300 mg/kg bw at 28 µCi) at intervals of 2 -3 weeks. About 2 -3 weeks
after the last saingle dose each animal received 7 consecutive daily
oral doses of 14C-LAS (30 mg/kg bw/day at 28 µCi/day) in water (6 mL).
Blood samples were taken, and animals were sacrificed at a different
time after the last dose.
For subcutaneous dosing, single doses
(14C-LAS of 1 mg/kg bw at 16-40 µCi), as a solution in water, were
administered by injection into the subcutaneous tissue between the
shoulder blades. Similarly, for the plasma level tests, the same animals
received subcutaneous doses of 0.5 and 0.1 mg/kg bw (8 -22 and 2-5 µCi,
respectively) at intervals of 2 -3 weeks. About 2 -3 weeks after the
last single dose the animals received 7 consecutive daily subcutaneous
doses of 1 mg/kg bw/day (about 24 µCi/day) in water. Blood samples were
taken in both cases.
After single oral doses of 30, 150 and 300
mg/kg bw, peak plasma concentrations (at 4 hours in all cases) were very
similar, with levels of 34, 41 and 36 µg/mL, respectively.
Concentrations declined during the period of 6-24 hours, with a
biological half-life of about 5-6 hours. After single
subcutaneous doses of 0.1, 0.5 and 1 mg/kg bw, peak plasma
concentrations increased almost proportionately, with levels of 0.16,
0.72 and 1.13 µg/mL, respectively. During seven consecutive daily oral
(30 mg/kg bw/day) or subcutaneous (1 mg/kg bw/day) doses, there was no
accumulation of radioactivity in plasma. Mean peak concentrations and
biological half-lives were similar after the first and seventh doses. Two
hours after the last dose, the highest radioactivity was observed in the
stomach. Radioactivity was also observed in the intestinal tract,
kidneys, liver, lung, pancreas, adrenals and pituitary. At
24 hours, concentrations were highest in the intestinal tract, probably
indicating biliary excretion. Since the concentrations
in the tissues in general were lower than in plasma, no specific
accumulation of LAS occurred.
No unchanged LAS was detected in urine
samples after oral or subcutaneous doses (either single or repeated).
Five metabolites were excreted but they were not identified. Incubations
with beta glucuronidase/sulfatase did not affect the metabolites,
indicating that the metabolites were probably not present as the
Based on the above, in single and repeated
oral or subcutaneous disposition study of [14C] LAS with rhesus monkeys,
LAS is rapidly absorbed, then rapidly metabolized and excreted,
primarily in the urine but also in the bile and feces. No accumulation
or localization of radioactivity or change in elimination was observed.
LAS does not bioaccumulate in the tissues.
The amount of test substance that penetrated
the skin was below the detection limit of 0.1 micrograms/cm2
or less than 0.3% of the initial dose.
Radiolabelled test substance (3 mM solution)
was applied to the shaved skin of female rats. The exposure lasted 15
min, after which is was rinsed off. After a 24 hr observation period
during feces, urine, and expired air was collected, the animals were
sacrificed and the excised skin was examined by autoradiography. Results
show that the test substance, which is of low solubility, did not
penetrate through the skin to any significant degree. The amount of test
substance penetrating the skin was below the detection limit. The
penetration through rat skin was < 0.3%.
Radiolabelled test substance was applied
(0.1 ml of a 3 mM solution) to samples of human abdominal skin from four
female cadavers. Exposure time was 48 hrs. Analysis by liquid
scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48
hrs. Penetration through human skin was negligible, with <0.07% absorbed
in 48 hrs.
series of toxicokinetics studies in rats and monkeys using C10-13 LAS
and C12 LAS sodium salts suggest that MEA-LAS would be rapidly absorbed
and distributed following intravenous or oral exposure, then rapidly
eliminated from the body, mostly via the urine and to a lesser extent in
the bile and faeces.
1 (C10-13 LAS):
absorption, distribution, metabolism and elimination of C10 -13 LAS,
sodium salt (radiolabelled with 35S) were studied in male Charles River
rats. LAS was administered as an aqueous solution. The urine and faeces
were collected and removed daily for analysis. At the termination of the
study, the animals were killed and selected organs and tissues were
taken for radio assay. In addition, the route of absorption was
determined by oral feeding of 40 mg of LAS to thoracic duct-cannulated
rats. The lymph was collected from each animal in a single 42-h
fraction. The enterohepatic circulation of the surfactant was quantified
by oral feeding of 1.2 mg of LAS to bile duct-cannulated rats and to
rats. Three or five males per dose were used for the excretion test and
six males for the absorption and enterohepatic tests. The compound was
readily absorbed from the gastrointestinal tract (80-90% of the dose),
and rapidly excreted with its metabolites, primarily in the urine.
Specifically, most of the absorbed 35S was eliminated within 72 h and
60-65% of the absorbed dose was eliminated in the urine, 35% of the
absorbed 35S was excreted in the bile and was reabsorbed completely from
the gastrointestinal tract. Very little was found in the lymph, so
transport of LAS is probably by way of portal venous blood. The authors
suggested that metabolism proceeded via omega oxidation with subsequent
catabolism through a beta-oxidation mechanism to form the metabolites
that were excreted in the urine. Retention of radioactivity was not
observed in any organ, so LAS had very low bioaccumulation potential
under the conditions of the study (Michael, 1968).
2 (C10-13 LAS):
a toxicokinetics study, disposition of radiolabelled [14C] C10-13 LAS,
sodium salt was studied via single and repeated oral or subcutaneous
doses in Rhesus monkeys. Four adult monkeys (2 male and 2 female) of
body weight approximately 5 kg each were used for all experiments. For
excretion studies, single oral doses of 30 mg/kg bw (at 28 µCi) were
administered by oral intubation as aqueous solutions. For the plasma
level studies the same animals were administered single oral doses (150
mg/kg bw at 26 µCi and 300 mg/kg bw at 28 µCi) at intervals of 2 -3
weeks. About 2 -3 weeks after the last single dose each animal received
7 consecutive daily oral doses of the test substance (30 mg/kg bw/day at
28 µCi/day) in water. Blood samples were taken and animals were
sacrificed at a different time after the last dose. Results show that
the substance was rapidly absorbed, then rapidly metabolized and
excreted, primarily in the urine but also in the bile and faeces. No
accumulation or localization of radioactivity or change in elimination
was observed, therefore, the test substance was not found to
bioaccumulate in the tissues (Creswell, 1978).
1 (C12 LAS):
dermal absorption of [14C] radiolabelled C12 LAS, sodium salt was
studied in rats and in isolated human epidermis. In the first part of
the study, female Colworth-Wistar rats (n = 6) received a single dose
(0.2 ml) of an aqueous suspension of the test substance (250 μg) applied
to a 7.5 cm2 clipped area of the back. The contact time was 15 minutes,
after which the test substance was rinsed off. The 14C levels in the
skin and protective patch were determined 24 h after application and the
penetration results based on levels of 14C excreted in urine, faeces and
expired CO2 during the 24 h after application plus levels of 14C in the
carcass of the animals at 24 h. No LAS was detected in skin (< 0.1
μg/cm2), indicating that less than 0.04% of applied dose was disposed in
the skin (Howes, 1975).
2 (C12 LAS):
the second part of the above study (Howes, 1975), isolated human
epidermis (0.78 cm2, n = 4) was exposed to 0.1 ml of a 1.2 mg/ml
solution of the test substance C12 LAS, sodium salt. Penetration of 14C
was measured at 2, 6, 24 and 48 h. No LAS was detected (<0.1 μg/cm2),
indicating that less than 0.065% of the applied dose penetrated the skin
in 48 h.
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