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Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
excretion
Qualifier:
no guideline followed
Principles of method if other than guideline:
8 male Wistar rats (160-200g) were given a single i.p. dose of 384.7 μg sodium alkylbenzene-[14C]sulfonate (DBS) (2.26±0.15 mg/kg bw) in a 0.6% physiological NaCl solution. Excretion of14C in feces and urine was monitored for 10 days.
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
14C-labelled Sodium alkylbenzene sulfonate
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
male Wistar rats(160-200g)
Route of administration:
intraperitoneal
Vehicle:
other: 0.6% physiological NaCl solution
Details on exposure:
14C-labelled Sodium alkylbenzene sulfonate was mixed homogeneously into a powdered rat chow. The [14C]DBS-treated diet and the drinking water were given daily ad lib.
Duration and frequency of treatment / exposure:
10days
Remarks:
Doses / Concentrations:
single i.p. dose of 0.385mg [14C]DBS per rat(2.26 +/- 0.1 5 mg/kg bw).
No. of animals per sex per dose / concentration:
8 male rats
Control animals:
yes
Details on study design:
8 male Wistar rats (160-200 g) were kept in individual metabolism cages that allowed separate collection of urine and feces. Each rat was given a single i.p. dose of 0.3847 mg [14C]DBS in a 0.6% physiological NaCl solution. Excretion of 14C in feces and urine was monitored for 10 days.
Details on dosing and sampling:
8 male rats each received a single i.p. dose of 0.3847 mg [14C]DBS per animal resulting in a dose of 2.26 +/- 0.15 mg/kg bw.
Details on excretion:
Within 10 days after dosing, the animals excreted 94.5% of the dose applied, 84.7% in the first 24h.
Metabolites identified:
yes
Details on metabolites:
Analysis of feces and urine for the acid and its metabolites :Approx. 90% of the 14C in feces and 65% in urine samples, collected from the long–term and the i.p. study, respectively, could be extracted. By means of column chromatography, a polar metabolic fraction was purified and isolated by t.l.c. techniques. Unchanged DBS could not be detected either in feces or in urine extracts. No further attempts were made to identify the polar metabolites. The metabolic studies with rhesus monkeys by Crosswell were confirmed with respect to the fact that no unchanged acid was excreted in the urine. Michael showed that 19% of LAS excreted in the feces of rats was not metabolized following a single oral dose. From the present long-term feeding and the single i.p. experiments with rats, however, it is obvious that the 14C activity in feces too, consisted only of a polar fraction.
Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Single i.p. application of 0.385 mg [14C]acid/rat (2.26 +/- 0.15 mg/kg bw) resulted in a total elimanation of 94.5% within 10 days. 84.7% of the dose was elimenated in the first 24 h. All fecal and renal [14C]acid-derived activity consisted of highly polar metabolities.
Executive summary:

8 male Wistar rats (160-200g) were given a single i.p. dose of 384.7 μg sodium acid-[14C]sulfonate (DBS) (2.26±0.15 mg/kg bw) in a 0.6% physiological NaCl solution. Excretion of14C in feces and urine was monitored for 10 days.Within 10 days after dosing, the animals excreted 94.5% of the dose applied, 84.7% in the first 24h. i.p. treatment resulted in a minor14C elimination in the feces(35.0±4.6%) on the first day of the experiment, whereas renally excreted radioactivity amounted to 49.7±5.7%. From days 2-10 of the excretion study, however, the percentage of radioactive products in the feces wassignificantly higher than in the urine.The results of this experiment showed that, independent of the route of administration, the daily excretion of radioactive products occurs mainly in the feces with the exception of the first day of the i.p. experiment, when the peak of14C elimination was in the urine.

Endpoint:
basic toxicokinetics in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Objective of study:
distribution
excretion
Qualifier:
no guideline followed
Principles of method if other than guideline:
The [14C]acid part-treated diet and the drinking water were given daily ad lib. The chemical was mixed homogeneously into a powdered rat chow, resulting in an actual concentration of 1.40mg/kg diet. The measurement of food consumption and the collection of feces and urine were carried out in a 24h cycle
GLP compliance:
not specified
Radiolabelling:
yes
Remarks:
14C-labelled Sodium salt of the acid part
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
male Wistar rats (120-140 g)
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
14C-labelled Sodium dodecylbenzene sulfonatel was mixed homogeneously into a powdered rat chow. The [14C]DBS-treated diet and the drinking water were given daily ad lib.
Duration and frequency of treatment / exposure:
35 days
Remarks:
Doses / Concentrations:
1.40 mg/kg
No. of animals per sex per dose / concentration:
12
Control animals:
yes
Details on study design:
The [14C]DBS was administered daily in the diet at a concentration of 1.4 mg/kg to male rats for 5 weeks. 6 rats were killed for the determination of radioactive residues in different tissues, while the remaining 6 rats served for a 1 week clearance study.
Details on dosing and sampling:
The [14C]DBS-treated diet and the drinking water were given daily ad lib. The chemical was mixed homogeneously into a powdered rat chow, resulting in an actual concentration of 1.40mg/kg diet. The measurement of food consumption and the collection of feces and urine were carried out in a 24h cycle.
Details on distribution in tissues:
Low levels of [14C]DBS-derived residues were detected in all tissues
Details on excretion:
14C excretion in feces : 0.635 +/- 0.036mg14C excretion in urine : 0.357 +/- 0.041mg
Metabolites identified:
yes
Details on metabolites:
Analysis of feces and urine for DBS and its metabolites :Approx. 90% of the 14C in feces and 65% in urine samples, collected from the long–term and the i.p. study, respectively, could be extracted. By means of column chromatography, a polar metabolic fraction was purified and isolated by t.l.c. techniques. Unchanged DBS could not be detected either in feces or in urine extracts. No further attempts were made to identify the polar metabolites. The metabolic studies with rhesus monkeys by Crosswell were confirmed with respect to the fact that no unchanged DBS/LAS was excreted in the urine. Michael showed that 19% of LAS excreted in the feces of rats was not metabolized following a single oral dose. From the present long-term feeding and the single i.p. experiments with rats, however, it is obvious that the 14C activity in feces too, consisted only of a polar fraction.
Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
This chemical was administered daily in the diet at a concentration of 1.4 mg/kg to male rats for 5 weeks. From the total uptake (1.213 +/- 0.08mg/animal) of DBS, 81.8% was excreted during the dosing period; 52.4% in feces and 29.4% in urine. Low levels of [14C]DBS-derived residues were detected in all tissues analyzed on day 35 of the experiment. Following 1 week on normal diet only 7.8% of the nominally stored amount of 14C was found in the excreta
Executive summary:

Sodium acid-[14C]sulfonate was administered daily in the diet at a concentration of 1.4 mg/kg bw to male rats for 5 weeks. From the total uptake (1,213±0.08 mg/animal) of the acid, 81.8% was excreted during the dosing period: 52.4% in feces and 29.4% in urine. Low levels of Sodium acid sulfonate-derived residues were detected in all tissues in rat body analyzed on day 35 of the experiment. Colon is the tissue containing the highest amounts of radioactivity.

Endpoint:
dermal absorption in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study in peer-reviewed publication.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography
GLP compliance:
not specified
Radiolabelling:
yes
Species:
rat
Strain:
other: Colworth-Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 100-120 g
- Housing: sealed metabolism cages
- Individual metabolism cages: yes

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 1.5 L/min
Type of coverage:
open
Vehicle:
other: Two test solutions were made: water, and 25% polyethylene glycol 400 in water.
Duration of exposure:
15 min
Doses:
- Nominal doses: 3 mM solution
- Dose volume: 0.2 ml
No. of animals per group:
no data
Control animals:
no
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: The test substance was added to the vehicle and homogenized and equilibrated at 40 degrees C for 24 hrs. The pH was then adjusted to 9.5 by adding 0.01 n NaOH or HCl.

TEST SITE
- Preparation of test site: 24 hrs before application, hair was removed with clippers. Only animals with intact skin were used.
- Area of exposure: 7.5 cm^2

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: Animals were anesthetized during exposure. During the 24 hr observation period the animals were fitted with restraining collars or non-occlusive patches. Non-occlusive patches were made of three layers of surgical gauze 1 cm larger in each dimension than the exposure area. Over this, a stainless steel 100 mesh gauze was placed and secured with surgical strapping with holes punctured in it.

SAMPLE COLLECTION
- Collection of urine and faeces: for 24 hrs after exposure
- Collection of expired air: for 24 hrs after exposure

SAMPLE PREPARATION
- Preparation details: feces were freezed dried, carcasses were homogenized in a blender and then freeze dried

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting, excised skin was examined by autoradiography
Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
- Non-occlusive cover: < 2 micrograms
- Skin wash: 135 +/- 27 micrograms
- Skin test site: Heavy deposition was seen on the skin surface, and in the upper hair follicles, 11+/-4 micrograms
- Urine: none
- Faeces: none
Dose:
250 micrograms
Parameter:
percentage
Absorption:
< 0.3 %
Remarks on result:
other: 24 hrs after exposure

The amount of test substance that penetrated the skin was below the detection limit of 0.1 micrograms/cm2 or less than 0.3% of the initial dose.

Conclusions:
The in vivo penetration through rat skin after a 15 min exposure was < 0.3%.


Executive summary:

Radiolabelled test substance (3 mM solution) was applied to the shaved skin of female rats. The exposure lasted 15 min, after which is was rinsed off. After a 24 hr observation period during feces, urine, and expired air was collected, the animals were sacrificed and the excised skin was examined by autoradiography. Results show that the test substance, which is of low solubility, did not penetrate through the skin to any significant degree. The amount of test substance penetrating the skin was below the detection limit. The penetration through rat skin was < 0.3%.

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study in peer-reviewed publication.
Qualifier:
no guideline followed
Principles of method if other than guideline:
-Radiolabelled test substance was applied (0.1 ml of a 3 mM solution) to samples of human abdominal skin from four female cadavars. Exposure time was 48 hrs. Analysis by liquid scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48 hrs. Penetration through human skin was negligible, with < 0.07% absorbed in 48 hrs.
- Method for preparation of dose suspensions: The test substance was added to the vehicle and homogenized and equilibrated at 40 degrees C for 24 hrs. The pH was then adjusted to 9.5 by adding 0.01 n NaOH or HCl.
GLP compliance:
not specified
Radiolabelling:
yes
Species:
human
Sex:
female
Duration of exposure:
48 hrs
Doses:
0.1 ml of 3 mM solution
No. of animals per group:
four skin samples
Details on study design:
- Method for preparation of dose suspensions: The test substance was added to the vehicle and homogenized and equilibrated at 40 degrees C for 24 hrs. The pH was then adjusted to 9.5 by adding 0.01 n NaOH or HCl.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human cadavars
- Ethical approval if human skin:
- Type of skin: abdominal
- Preparative technique: Epidermal samples were heated at 58 degrees C for 2 min. Samples were placed in 1 cm diamter penetration cells, and saline with 0.012% penicillin, 0.01% streptomycin was placed on both surfaces of the cells. The cells were equilibrated at 37 degrees C for 24 hrs.
- Membrane integrity check: Only cells with electrical resistance greater than 50,000 ohms were used.
- Storage conditions: -70 degree C
Signs and symptoms of toxicity:
not examined
Dermal irritation:
yes
Remarks:
some swelling was seen after 48 hrs of contact
Absorption in different matrices:
Only 30% of the test substance was removed by rinsing, with 70 % remaining associated with the skin.
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Remarks on result:
other: 2 hrs
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Remarks on result:
other: 6 hrs
Dose:
152.9 micrograms/cm^2
Parameter:
percentage
Absorption:
< 0.07 %
Remarks on result:
other: 48 hrs
Conclusions:
The in vitro penetration through human skin after a 48 hr exposure was < 0.07%.

Executive summary:

Radiolabelled test substance was applied (0.1 ml of a 3 mM solution) to samples of human abdominal skin from four female cadavars. Exposure time was 48 hrs. Analysis by liquid scintillation counting was done at 0.5, 1, 2, 3, 4, 6, 7, 8, 24, and 48 hrs. Penetration through human skin was negligible, with < 0.07% absorbed in 48 hrs.

Description of key information

Toxicokinetics 

No experimental data on absorption, distribution and excretion is available for the target substance.

a.   Amine component  

In a review by the Australian authorities the following was included:

Toxicokinetic data available indicate that 25 % of 14C labelled amine applied (19.5 mg/kg) to the skin of four female Fischer 344 (F344) rats was absorbed through the skin after 48 hours. Almost half (12.5 %) of the absorbed chemical was excreted in urine and the other half remained in the tissues of the animals, although, no accumulation was detected in fat. In a further study, intravenous administration of carbon-14 labelled amine (19 mg/kg) to four female F344 rats showed a fast elimination rate with 70 % of the radioactivity cleared from the blood within six hours. The majority (90 %) of the dose was excreted as the parent chemical and no metabolites were identified in the urine within 12 hours[1].

b.     Acid component

The sodium salt of the acid is readily absorbed by the gastro-intestinal tract after repeated exposure for 5 weeks (82% of the administered dose), but absorption via the skin is very low (0.07-0.3% of the administered dose). The acid is distributed to most organs, except the uterus, and the major part is metabolised in the liver to sulfophenyl carboxyl acids. The substance metabolites are eliminated primarily via the urine and faeces (ca 30 and 50% respectively). No accumulation of the acid or its main metabolites has been observed has been observed[2][3].

 

c.     Salt compound

Based on the physico-chemical characteristics of the acid and the amine, taking into account that the salt will readily dissolve into the gastrointestinal fluids and thus be present in its dissociated form, the absorption after oral administration of the substance can be attributed to the absorption of cationic and the anionic part. As was found for the source substances, it is expected that absorption will be significant although the ionic nature of the parts will hamper absorption to a certain extent with the amine as the smaller molecule being the main candidate. The low vapour pressure indicates that the salt is non-volatile at room temperature and thus the exposure of the substance via inhalation route is unlikely. Therefore, absorption via inhalation is not further discussed. At dermal exposure the salt is expected to be present in its undissociated form and the uptake is expected to be very low based on high water solubility and low log Kow. The salt may be too hydrophilic to cross the lipid rich environment of the stratum corneum.

Based on the low Log Kow and high water solubility, both the acid and amine are expected to remain in the body fluids and to be rapidly excreted either via urine (the amine) or urine and faeces (the acid and its metabolites). No bioaccumulation is expected.

Concluding the absorption of the compound via the oral route is set at the default of 100%, while dermal absorption is set at the default value of 10%. This conclusion has been drawn in absence of data on toxicokinetics for the target substance. The metabolism and excretion data are based on the limited information from the acid and amine. No other metabolic pathways are however expected for these kinds of substances.

 

[1]INVENTORY MULTI-TIERED ASSESSMENT AND PRIORITISATION (IMAP), HUMAN HEALTH TIER II ASSESSMENT FOR 2-Propanol, 1-amino- n CAS Number: 78-96-6

[2](Lay JP et al., Elimination and biodistribution studies of [14C]Alkylbenzene sulfonate in rats, following low dosing in the daily diet and single i.p. administration Toxicology letters, 17(1983), 187-192

[3]Howes D, The percutaneous absorption of some anionic surfactants J. Soc. Cosmet. Chem. 26 (1975): 47-63.

 

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10

Additional information

Theoretical assessment based on information on the cation and anion.