Benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study is similar to OECD Test Guidelines with acceptable deviations.

Justification for type of information:

REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE CATEGORY APPROACH
The read across follows Scenario 5 - Qualitatively and quantitatively similar effects are caused by a common compound, which is formed from all category members (as described in the 2017 Read-Across Assessment Framework document).
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
TARGET: Benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts
SOURCE: Sodium 4-undecylbenzenesulfonate
3. CATEGORY APPROACH JUSTIFICATION

Linear and non-linear or branched alkylbenzene sulfonates are anionic surfactants with molecules characterized by a hydrophobic (apolar) and a hydrophilic (polar) group. As a group of chemicals, they are generally mixtures of closely related isomers and homologues. Each molecule contains an aromatic ring sulfonated at the para position and attached to either a linear or a branched alkyl chain at any position except the terminal carbons. The sulfonate group is a common functional group present in each of the category members, and is expected to exhibit similar biological activities with little influence from the length of carbon chain. The cation components of the chemicals (e.g. calcium, magnesium, sodium, or barium) are not expected to contribute significantly to the toxicity.
4. DATA MATRIX
See Read Across document attached to CSR

Data source

Reference

Reference 1

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 2

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 3

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

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

Test material information

Constituent 1

Reference substance name:

68411-30-0

IUPAC Name:

68411-30-0

Constituent 2

Reference substance name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

EC Number:

270-115-0

EC Name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

Cas Number:

68411-30-3

IUPAC Name:

sodium 4-undecylbenzenesulfonate

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 or test system 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 / concentration:

Two/sex/dose/timepoint

Control animals:

no

Positive control reference chemical:

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 results

Main ADME results 1

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.

Main ADME results 2

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 parameters

Toxicokinetic parameters 1

Key result

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

Toxicokinetic parameters 2

Key result

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.