Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with 2-propanamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Unavailable - date of publication 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1978

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

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

Test material

Test material information

Constituent 1

Reference substance name:

LAS, sodium salt

IUPAC Name:

LAS, sodium salt

Details on test material:

Alkyl benzene sulfonate, sodium salt; mean molecular weight 349 (supplied by the Japan Soap and Detergent Association)

Radiolabelling:

yes

Remarks:

[14C]LAS

Test animals

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)

Administration / exposure

Route of administration:

other: single or repeated oral or subcutaneous

Vehicle:

not specified

Doses / concentrations

Doses / concentrations 1

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

Doses / concentrations 2

Dose / conc.:

30 other: mg/kg

Remarks:

single or repeated oral tests

Doses / concentrations 3

Dose / conc.:

150 other: mg/kg

Remarks:

single or repeated oral tests

Doses / concentrations 4

Dose / conc.:

300 other: mg/kg

Remarks:

single or repeated oral tests

Doses / concentrations 5

Dose / conc.:

0.1 other: mg/kg

Remarks:

subcutaneous test

Doses / concentrations 6

Dose / conc.:

0.5 other: mg/kg

Remarks:

subcutaneous test

Doses / concentrations 7

Dose / conc.:

1 other: mg/kg

Remarks:

subcutaneous test

No. of animals per sex per dose / concentration:

2 males and 2 females

Control animals:

not specified

Details on study design:

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 at 25 uCi) 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 at 26 uCi and 300 mg/kg at 28 uCi) 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 uCi/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 at 16 -40 uCi), 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 (8 -22 and 2 -5 uCi, 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/day (about 24 uCi/day) in water. Blood samples were taken in both cases.

Details on dosing and sampling:

Blood samples were collected for the excretion and plasma studies.

Results and discussion

Toxicokinetic / pharmacokinetic 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).

Metabolite characterisation studies

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.

Applicant's summary and conclusion

Conclusions:

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.