Benzenesulfonic acid, C10-13-alkyl derivs., calcium salt

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study in peer-reviewed publication conducted by experienced testing laboratory.

Objective of study:

metabolism

Principles of method if other than guideline:

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.

GLP compliance:

not specified

Radiolabelling:

yes

Remarks:

(radioactively labeled with 35S)

Species:

rat

Strain:

other: Charles River albino

Sex:

male

Details on test animals or test system and environmental conditions:

The animals were housed in individual cages which permitted the separate collection of urine and feces. Food and water were provided ad libitum after dosing.

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Male rats (150-200 g) were fasted for 16 hours and given orally an aqueous solution containing LA35S. The dose was given in 1.0 mL volume. The urine was collected under toluene, removed daily, and refrigerated until it could be examined. The feces were removed each day and allowed to dry at room temperature. At the termination of the study, the animals were killed and selected organs and tissues were taken for radioassay.

Also, 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 sufactant was quantifed 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. A cannula was inserted into the proximal end of the bil deuct of Rat A and into the distal end of the bile duct in Rat B such that the bile from Rat A could flow through the cannula into the bile duct, and finally into the intestin of Rat B. A second cannula was inserted into the proximal end of the bile duct of Rat B so that is bile could be collected. LA35S was fed orally to Rat A. Urine and feces of Rats A and B and bile of Rat B were collected for 90 hours after dosing.

Duration and frequency of treatment / exposure:

See details of exposure section

Remarks:

Doses / Concentrations:
0.6, 1.2, 8.0 and 40.0 mg (averages of three animals for the two lower doses and five animals for the two higher doses) for the excretion test, 1.2 mg/rat for the absorption and enterohepatic circulation tests.

No. of animals per sex per dose / concentration:

Three or five males per dose for the excretion test, six males for the absorption and enterohepatic tests.

Control animals:

not specified

Details on absorption:

The compound was readily absorbed from the gastrointestinal tract (80-90% of the dose).

Details on distribution in tissues:

Primarily excreted in the urine.

Details on excretion:

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.

Metabolites identified:

yes

Details on metabolites:

Urine - sulfophenyl butanoic and sulfophenyl pentatonic acid. These metabolites were sufficiently polar to avoid being reabsorbed from the kidney tubules. Although the metabolites in the bile were not identified, it was shown that no unchanged LAS was eliminated via this pathway.

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
LAS is readily absorbed by the gastrointestinal track and rapidly excreted with its metabolites, primarily in the urine.

Executive summary:

The absorption, distribution, metabolism and elimination of LAS (radioactively labeled 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.

Reference 2

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented peer-reviewed publication of contract laboratory study.

Objective of study:

metabolism

Principles of method if other than guideline:

The disposition of radioactivity was studied in single and repeated oral doses of [14C]LAS to rhesus monkeys.

GLP compliance:

not specified

Radiolabelling:

yes

Species:

monkey

Strain:

other: Macaca mulatta

Sex:

male/female

Details on test animals or test system and environmental conditions:

Four (2 male, 2 female; 5 kg average body weight) adult rhesus monkeys (Macaca mulatta)

Route of administration:

other: single or repeated oral or subcutaneous

Remarks:

Doses / Concentrations:
single or repeated oral (30, 150 or 300 mg/kg) or subcutaneous (0.1, 0.5 or 1 mg/kg) doses of 14C-LAS

No. of animals per sex per dose / concentration:

2 males and 2 females

Control animals:

not specified

Details on dosing and sampling:

Blood samples were collected for the excretion and plasma studies.

Details on distribution in tissues:

When 14C-LAS was injected into the skin, most of the radioactivity remained at the site of injection. No localization of radioactivity in any tissue occurred

Details on excretion:

After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 hours. Means of 71.2% and 23.1% of the dose were excreted in the urine and feces, respectively, during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and feces, respectively, during 5 days, mostly during the first 24 hours. During the 120 hours after single oral (30 mg/kg) or subcutaneous doses (1 mg/kg) the average rate of excretion was between 63 and 74% in the urine and between 9 and 26% in the feces. No unchanged LAS was detected in urine samples after oral or subcutaneous doses (either single or repeated).

Metabolites identified:

no

Details on metabolites:

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 corresponding conjugates.

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results

Executive summary:

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.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The absorption, distribution, metabolism and elimination of LAS (CAS68411-30-3 and Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts) (radioactively labeled with 35S) has been studied in male Charles River rats and rhesus monkeys. In rats, LAS was readily absorbed by the gastrointestinal tract and rapidly metabolized and excreted in the urine. The disposition of radioactivity given as single and repeated oral or subcutaneous doses of [14C]LAS to rhesus monkeys demonstrated 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 in either species. Results demonstrate that LAS does not bioaccumulate in the tissues.