Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

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. 

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
90
Absorption rate - dermal (%):
0.065

Additional information

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.