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EC number: 287-494-3
CAS number: 85536-14-7
The absorption, distribution, metabolism and elimination of LAS
(radioactively labelled with 35S) were studied in male Charles River
rats. LAS was readily absorbed by the gastrointestinal tract and rapidly
metabolized and excreted in the urine.
The disposition of radioactivity was studied in single and repeated oral
or subcutaneous doses of [14C]LAS to rhesus monkeys. Results show that
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
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 cadavars. 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.
A series of toxicokinetic studies in rats and monkeys indicates that LAS
(read across) is rapidly absorbed when the exposures are intravenous or
oral, then rapidly eliminated from the body, mostly via the urine and to
a lesser extent in the bile and faeces. LAS provides suitable read
across for LAB Sulfonic Acids as both form the identical chemical
species in aqueous solutions at physiological pH’s, namely, the LAS ion
(C10-13 linear alkyl benzene-SO3-).
In the first key study (Michael 1968), the absorption, distribution,
metabolism and elimination of LAS (radioactively labeled 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 radioassay. 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-hour fraction. The enterohepatic ciruclation of the
surfactant was quantified by oral feeding of 1.2 mg of LAS to bile
duct-cannulated rats and to rats prepared in a manner similar to the
dual rat study described by Boquet and Fromageot. 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 hours 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 has very low bioaccumulation potential.
In the second key study (Cresswell et al. 1978), the disposition of
radioactivity was studied in 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 of 30 mg/kg
14C-LAS (at 28 µCi) were administered by oral intubation as aqueous
solutions. For the plasma level studies the same animals were
administered single oral doses (14C-LAS of 150 mg/kg at 26 µCi and 300
mg/kg 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
14C-LAS (30 mg/kg/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 LAS is 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. LAS does not bioaccumulate in the tissues.
In the third key study (Howes 1975), the dermal absorption of a C12 LAS
homologue, sodium p-1 [1-14C]dodecolybenzenesulfonate (read across), 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 material (250 μg) applied
to a 7.5 cm2 clipped area of the back. The contact time was 15 minutes,
after which the test material was rinsed off. The 14C levels in the skin
and protective patch were determined 24 hours after application and the
penetration results based on levels of 14C excreted in urine, faeces and
expired CO2 during the 24 hours after application plus levels of 14C in
the carcass of the animals at 24 hours. No LAS was detected in skin
(<0.1 μg/cm2), indicating that less than 0.04% of applied dose was
disposed in the skin. In the second part of the study, 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. Penetration of 14C was measured at 2, 6,
24 and 48 hours. No LAS was detected (<0.1 μg/cm2), indicating that less
than 0.065% of the applied dose penetrated the skin in 48 hours.
LAB sulfonic Acid would be expected to show a comparable toxicokinetic
profile to LAS.
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