Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 February 1995 - 5 April 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
A reliable study (GLP and following an OECD Guideline methodology) was available that did not use the LLNA method. Given that it was reliable (Klimisch 1) the results of this study was considered to be satisfactory in assessing the sensitisation potential of the substance.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH
- Age at study initiation: young adult females
- Weight at study initiation: less than 500 g
- Housing: Makrolon cages Type IV (max. 5 animals per cage)
- Diet: Ssniff G 4- complete diet food for guinnea pigs, ad libitum
- Water: tap water, ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- Pre-test: From: 06.02.1995 To: 09.02.1995
- Main test: From: 06.03.1995 To: 05.04.1995
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
demineralised
Concentration / amount:
Induction exposure: 59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (pure product MARLOPON AT 50)
Challenge exposure: 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (dilution of MARLOPON AT 50 in demineralised water)
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
demineralised
Concentration / amount:
Induction exposure: 59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (pure product MARLOPON AT 50)
Challenge exposure: 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (dilution of MARLOPON AT 50 in demineralised water)
No. of animals per dose:
Rangfinding tests: 3 animals for establishing the induction concentration, 3 animals for establishing the challenge concentration
Main test: 20 animals in the test group (one dose) and 10 animals in the control group
Details on study design:
RANGE FINDING TESTS:
Pilot study for establishing the concentration used for each induction exposure:
- Test concentrations: 5.0, 20.0, 40.0 and 59.2% (w/w) Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) in demineralised water
- Exposure period: 6 hours
- No. of exposures: 1
- Replica's: 3 (the posterior, anterior, left and right flank of each of three animals were used for the four different test concentrations)
- Evaluation (hr after start application): 30 and 54 h

Pilot study for establishing the concentration used for the challenge exposure (performed in the fourth week of the main test):
- Test concentrations: 5, 20, 40 and 50% (w/w) Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) in demineralised water
- Exposure period: 6 hours
- No. of exposures: 1
- Replica's: 3 (the posterior, anterior, left and right flank of each of three animals were used for the four different test concentrations)
- Evaluation (hr after start application): 30 and 54 h

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: three
- Exposure period: 6 h
- Test groups: one test group (20 animals) induction with 59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (pure product MARLOPON AT 50)
- Control group: 10 animals, induction with vehicle (demineralised water)
- Site: left flank previously shaved
- Frequency of applications: Induction phase I: Day 0, induction phase II: Day 7, induction phase III: Day 14
The dermal reaction was assessed 30 h after the application,
- Concentrations: vehicle only or 59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) (pure product MARLOPON AT 50)


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: Day 28
- Exposure period: 6 h
- Test groups: one test group (20 animals)
- Control group: 10 animals
- Site: right flank previous shaved
- Concentrations: 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) or vehicle only
- Evaluation (hr after challenge): 30 and 54 h

OTHER:
Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole(2-MCBT), in a seperate test
Positive control results:
A positive skin response (irritation scored as erythema, scaling and oedema) was observed in 90% of the test animals challenged with 50% 2-MCBT, and in 5-10% of the test animals challenged with vehicle, compared to 0% response in the control group (both for the challenge with 50% 2-MCBT and vehicle). Therefore, it can be concluded that the sensitivity of the guinea pigs is sufficient.
Reading:
1st reading
Hours after challenge:
30
Group:
test group
Dose level:
20%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
very slight erythema and oedema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: test group. Dose level: 20%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: very slight erythema and oedema.
Reading:
2nd reading
Hours after challenge:
54
Group:
test group
Dose level:
20%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
very slight erythema and slight oedema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: test group. Dose level: 20%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: very slight erythema and slight oedema.
Reading:
1st reading
Hours after challenge:
30
Group:
test group
Dose level:
vehicle
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
very slight erythema and oedema in animal 11
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: test group. Dose level: vehicle. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: very slight erythema and oedema in animal 11.
Reading:
2nd reading
Hours after challenge:
54
Group:
test group
Dose level:
vehicle
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
very slight erythema and oedema in animal 1 (none in animal 11)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: test group. Dose level: vehicle. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: very slight erythema and oedema in animal 1 (none in animal 11).
Reading:
1st reading
Hours after challenge:
30
Group:
negative control
Dose level:
20%
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
very slight erythema and oedema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: negative control. Dose level: 20%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: very slight erythema and oedema.
Reading:
2nd reading
Hours after challenge:
54
Group:
negative control
Dose level:
20%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: negative control. Dose level: 20%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
30
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 30.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
54
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Range finding tests:

Pre-test for establishing the induction concentration:

The 5 and 20% test concentrations did not result in skin irritation in any of the animals. One animal did not repsond to any of the test concentrations. One animal responded to the 40 and 59.2% test concentration after 30 hours with hardly visible erythema which had disappeared at the 54 hour observation. One animal responded to the 59.2% test concentration at both 30 and 54 hour interval with a very slight red discoloration of the skin. See also Table 1 in attached background information.

The 59.2% test concentration was chosen for the induction phase as the highest test concentation causing slight to mild irritation.

Pre-test for establishing the induction concentration:

No skin irritation was observed in any of the three test animals tested at 5, 20, 40 and 50% test concentration. See also Table 2 in attache background information. Because of the increasing skin irritation over the course of the trhee induction phases from slight to severe skin irritation, combined with the observation of slight skin irritation in one animal exposed to 40% test concentration in the first pre-test, it was decided to use the 20% test concentration as challenge treatment in the main test.

Main test:

The results of the main test are given in Tables 3 (induction phase), 4 (test group) and 5 (control group) in the attached background material.

During the study no systemic effects or effects on body weight were observed in animals from both the test and control group.

The dermal application during induction phase I resulted after 30 hours in skin irritation in 11 out of 20 test animals consisting of very sligth erythema, in 5 animals this additionally hardly noticable oedema was observed. Further, occasionally dry skin, scaling and scratches at the application site were observed. Nine test animals and all control animals showed no skin irritation.

Thirty hours after application in induction phase II all test animals showed well-defined erythema and oedema, and in 14 animals also dry skin was observed at the application site. The control animals showed no skin irritation.

At the shaving before the third induction apllication scaling of the skin at the application sites was observed in all test animals. Thirty hours after the third application all test animals showed wel-defined to severe erythema and oedema, in three animals associated with scaling, in eight animals with necrotic patches and three animals showed clear necroses at the application site. The control animals showed no skin irritation.

The challenge with 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) resulted at 30 and 54 hours after application in a skin respons in 2 out of 20 animals. The response consisted of very slight erythema and oedema, and in one animal the oedema was slightly increased after 54 hours. One control animal showed after 30 hours also a hardly visible red discoloration of the skin at the application site of the 20% test solution. The remaining animals (18 test anmals and 9 control animals) showed no signs of irritation (erythema or oedema) at the application site treated with 20% test solution.

The challenge with vehicle (water) did not result in a skin reaction at 18 test animals and all 10 control animals. One test animals showed hardly visible irritation of the skin after 30 hours, whereas another test animals showed this respons after 54 hours.

Summary table:

 

Number of animals with skin response at x hours after application

Total number of animals with skin response

30 hours

54 hours

30 and 54 hours

20% TS

Vehicle

20% TS

Vehicle

20% TS

Vehicle

E / O

E / O

E / O

E / O

E / O

E / O

Control group

(n = 10)

1 / 0

0 / 0

0 / 0

0 / 0

1 / 0

0 / 0

Test group

(n = 20)

2 / 2

1 / 1

2 / 2

1 / 1

2 / 2

2 / 2

TS = Test substance (Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4))

E = Erythema and Eschar formation

O = Oedema formation

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Classification Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4): not sensitising
Executive summary:
In a dermal senisitization study with MARLOPON AT 50 (59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) = test substance) in water, young adult guinea pigs (20 females in test group, 10 in control group) were tested using the method of Buehler according to OECD 406 (59.2% and 20% substance concentration in induction and challenge phase, respectively). As control vehicle (water) was used. As positive control material 2-Mercaptobenzothiazol was used which gave an adequate response.

The dermal application during induction phase I resulted after 30 hours in skin irritation in 11 out of 20 test animals consisting of very sligth erythema, in 5 animals this additionally hardly noticable oedema was observed. Further, occasionally dry skin, scaling and scratches at the application site were observed. Nine test animals and all control animals showed no skin irritation.

Thirty hours after application in induction phase II all test animals showed well-defined erythema and oedema, and in 14 animals also dry skin was observed at the application site. The control animals showed no skin irritation.

At the shaving before the third induction apllication scaling of the skin at the application sites was observed in all test animals. Thirty hours after the third application all test animals showed wel-defined to severe erythema and oedema, in three animals associated with scaling, in eight animals with necrotic patches and three animals showed clear necroses at the application site. The control animals showed no skin irritation.

The challenge with 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) resulted at 30 and 54 hours after application in a skin respons in 2 out of 20 animals. The response consisted of very slight erythema and oedema, and in one animal the oedema was slightly increased after 54 hours. One control animal showed after 30 hours also a hardly visible red discoloration of the skin at the application site of the 20% test solution. The remaining animals (18 test anmals and 9 control animals) showed no signs of irritation (erythema or oedema) at the application site treated with 20% test solution.

The challenge with vehicle (water) did not result in a skin reaction at 18 test animals and all 10 control animals. One test animal showed hardly visible irritation of the skin after 30 hours, whereas another test animals showed this respons after 54 hours.

For both the challenge with vehicle (water) as well as with 20% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4), 10% of the animals responded with light skin irritation. Therefore Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) is considered to have no skin sensitisation potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

LAS TEA:

In a dermal senisitization study with MARLOPON AT 50 (59.2% Benzenesulfonic acid, C10-13-alkyl derivs., compds. with triethanolamine (CAS no. 68411-31-4) = test substance) in water, guinea pigs were tested in a Buehler test. The results revealed that CAS 68411-31-4 is not a dermal sensitizer.

Supporting information

LAS Na:

One test available examined the senistisation potential of LAS Na to the skin. 10 male and 10 female guinea pigs were given intradermal injections of 25% test solution. Control animals (5 male and 5 female) were given injections of vehicle only. One week later, a second induction was done by dermal exposure to 25% test solution for 24 hrs. Control animals were again exposed to vehicle only. On day 21, the challenge exposure was performed. All animals were exposed to 12.5% test solution dermally. Exposure was for 24 hrs, with observations made at 48 and 72 hrs after the start of exposure. No positive reactions were noted. The test substance is not sensitizing.

 

TEA:

The sensitising potential of TEA was investigated in a Guinea Pig Maximisation Test according to OECD TG 406 under GLP conditions (Hoechst, 1988). Based on the results of a pre-test, animals were dermally injected twice with 0.1 mL 2% TEA on day 1, followed by an epicutaneous induction (occlusive) with 0.5 mL undiluted TEA for 48 hours starting on day 9, and a dermal challenge (occlusive) with 0.5 mL 10% TEA for 24 hours on day 22. Dermal reactions were evaluated according to Draize 48 and 72 hours after the start of the dermal challenge. No clinical signs were noticed and all readings were negative.

Regarding the available human data, the positive reactions interpreted as allergic seem to be caused by exposure to TEA in cosmetics and/or topical therapeutic preparations possibly on damaged skin. The diagnosis of TEA contact sensitisation should therefore not be based on a positive patch test reaction alone but on a combination of history and preferably validation tests.

The negative experimental findings in animals and the level of exposure to TEA in the population, together with the low frequency of positive reactions to low TEA concentrations in patch-tested patients indicate a very low sensitisation potential in humans, and the risk of sensitisation to TEA on uncompromised skin seems to be very low (Lessmann, 2009).


Migrated from Short description of key information:
No positive reactions were observed in the Buehler test with LAS TEA.

Justification for selection of skin sensitisation endpoint:
Only one study available performed with LAS TEA; GLP, Klimisch 1 study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The substance shall not be classified as a sensitizer according to the criteria laid down in the CLP Regulation 1272/2008.