Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is similar to OECD Test Guidelines with acceptable deviations. However as this study is used in the context of a read across, Klimisch 2 is assigned.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicology studies of linear alkylbenzene sulphonate (LAS) in Rhesus monkeys. II. The disposition of [14C]LAS after oral or subcutaneous administration
Author:
Cresswell, D.G., Baldock, G.A., Chasseaud, L.F., and Hawkins, D.R.
Year:
1978
Bibliographic source:
Toxicology, 11:5-17
Reference Type:
secondary source
Title:
Linear alkylbenzene sulfonates and related compounds
Author:
World Health Organization
Year:
1996
Bibliographic source:
International Program on Chemical Safety, Environmental Health Criteria 169
Reference Type:
secondary source
Title:
LAS - Linear AlkylBenzene Sulphonate (CAS No. 68411-30-3).
Author:
HERA
Year:
2013
Bibliographic source:
Human and Environmental Risk Assessment on Household Cleaning Products (HERA). Revised Report
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
(1) Only focused on plasma and tissue distribution; (2) Non-standard route of exposure.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Sodium alkyl [14C] benzenesulphonate ([14C]LAS), stated specific activity of 2 mCi/mmol as a 2.178% (w/v) aqueous solution
- Non-radioactive sodium LAS as a 20.5% (w/v) aqueous solution
- Supplied by the Japan Soap and Detergent Association, Tokyo
- Radiochemical purity > 99%, checked by TLC
Radiolabelling:
yes
Remarks:
[14C]

Test animals

Species:
monkey
Strain:
other: Macacca mulatta
Sex:
male/female
Details on test animals and environmental conditions:
- Body weight: approx. 5 kg

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The solution of [14C] LAS was diluted to a specific activity of 26.6 uCi/mL (4.6 mg/mL) and individual doses were weighed out and diluted with appropriate amounts of the non-radioactive LAS solution.
- Each animal received seven consecutive daily subcutaneous doses of [14C] LAS (1 mg/kg/day, about 24 uCi/day) in water (3 mL).
Duration and frequency of treatment / exposure:
Single daily doses for 7 consecutive days
Doses / concentrations
Remarks:
Doses / Concentrations:
1 mg/kg
No. of animals per sex per dose:
Two/sex/dose/timepoint
Control animals:
no
Positive control:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: plasma, liver, kidneys, brain, spinal cord, pituitary, thyroid, eyes, lungs, gonads, heart, adrenals, pancreas, spleen, stomach, small and large intestine, omentum, mesentery, and samples of adipose tissue and muscle
- Time and frequency of sampling: Blood samples were withdrawn at predose and at 0.5, 1, 2, 4, 6 and 7.5 h after the first dose and immediately before administration of the following 6 doses. After the 7th and last dose, blood samples were taken at different times until sacrifice for the measurement of plasma concentrations. Single animals were sacrificed at 2, 4, 24 and 48 hr and tissues were taken.
Statistics:
N/A

Results and discussion

Preliminary studies:
N/A
Main ADME resultsopen allclose all
Type:
absorption
Results:
After the first seven consecutive daily 1 mg/kg subcutaneous doses, dose concentrations of radioactivity reached a maximum mean concentration of 1.13 ug/mL at 2 hrs.
Type:
distribution
Results:
Concentrations were generally highest at 2 h when they were greatest in the intestinal tract, kidneys, lungs, spleen, thyroid ,and pituitary.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
After the first seven consecutive daily 1 mg/kg subcutaneous doses, dose concentrations of radioactivity reached a maximum mean concentration of 1.13 ug/mL at 2 hrs. These levels declined to 0.28 ug/mL with a mean half-life of about 10 hrs. The mean predose levels on the succeeding 6 days increased gradually to 0.71 ug/mL before the final dose. After the seventh and final dose, mean plasma concentrations reached a peak of 1.1 ug/mL at 4 hrs and declined until 24 hrs with a mean half-life of about 13 h. Concentrations in the male and female sacrificed at 24 and 48 hrs, respectively, after the last dose were 0.49 and 0.47 ug/mL.
Details on distribution in tissues:
- Concentrations were generally highest at 2 h when they were greatest in the intestinal tract (2.41 ug/g), kidneys (1.83 ug/g), lungs (2.45 ug/g), spleen (2.43 ug/g), thyroid (1.24 ug/g) and pituitary (1.00 ug/g).
- Concentrations in most tissues were generally lower at 4 h except in the liver (1.74 ug/g) and kidneys (1.92 ug/g), organs associated with biotransformation and excretion.
- The relatively high concentrations of radioactivity in the gastrointestinal tract probably indicates the presence of material eliminated in the bile.
- At 24 h, concentrations had declined in most tissues, but were highest in the liver (0.39 ug/g), kidneys (0.29 ug/g), lungs (0.27 ug/g) and adrenals (0.41 ug/g), although lower than those in plasma (0.49 ug/g).
- In the animal sacrificed at 48 h, the plasma concentration (0.47 ug/g) was similar to that in the animal sacrificed at 24 h and correspondingly the tissue concentrations were also similar, being highest in the liver (0.41 ug/g), kidneys (0.22 ug/g), lungs (0.23 ug/g) and adrenals (0.53 ug/g).
- Apart from the gastrointestinal tract, tissue concentrations of radioactivity were similar to or lower than the corresponding plasma concentrations at all times indicating that there was no specific accumulation or localization of LAS and/or its metabolites in these tissues.
Details on excretion:
N/A
Toxicokinetic parametersopen allclose all
Test no.:
#1
Toxicokinetic parameters:
half-life 1st: Mean half-life of about 10 hrs after the first seven consecutive daily 1 mg/kg subcutaneous doses
Test no.:
#1
Toxicokinetic parameters:
Cmax: After the first seven consecutive daily 1 mg/kg subcutaneous doses, dose concentrations of radioactivity reached a maximum mean concentration of 1.13 ug/mL at 2 hrs

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
During seven consecutive daily subcutaneous doses, there was no accumulation of radioactivity from [14C]LAS in plasma. Mean peak concentrations and biological half-lives were similar after the first and seventh doses. After 7 doses, there was no localization of radioactivity in any tissue.
Executive summary:

During seven consecutive daily subcutaneous doses, there was no accumulation of radioactivity from [14C]LAS in plasma. Mean peak concentrations and biological half-lives were similar after the first and seventh doses. After 7 doses, there was no localization of radioactivity in any tissue.