Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An appropriate GPMT test is available which would not justify conducting an additional LLNA due to animal welfare.

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
432-520-2
EC Name:
-
Cas Number:
232938-43-1
Molecular formula:
C21 H20 N2 O6 S2
IUPAC Name:
3-{[(4-methylbenzenesulfonyl)carbamoyl]amino}phenyl 4-methylbenzene-1-sulfonate
Details on test material:
- Physical state: white powder
- Analytical purity: >99%
- Lot/batch No.: Batch 1 Dry
- Stability under test conditions: Stable under storage conditions.
- Storage condition of test material: room temperature (20±3°C), away from direct sunlight

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 304 - 371 g
- Housing: Individually in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet (e.g. ad libitum): Pelleted standard Nafag Ecosan 845 25W4
- Water (e.g. ad libitum): Community tap water
- Acclimation period: One week for the control and test group under test conditions after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3 °C
- Humidity (%): 40-70 % (values above 70 % during cleaning process possible).
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Induction: 5 % in corn oil (intradermal); 50 % in corn oil (epidermal);
Challenge: 0.5 % in corn oil
Challengeopen allclose all
Route:
epicutaneous, semiocclusive
Vehicle:
corn oil
Concentration / amount:
Induction: 5 % in corn oil (intradermal); 50 % in corn oil (epidermal);
Challenge: 0.5 % in corn oil
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
Intradermal injections: Four intradermal injections (0.1 ml/site) of a 1:1 (v/v) mixture of Freund's Complete Adjuvant/physiological saline were made into the shaved neck of one guinea pig. One week later intradermal injections (0.1 ml/site) were made into the clipped flank of the same guinea pig at concentrations of 5, 3 and 1 % of the test article in corn oil. Dermal reactions were assessed 24 hours later. Based on the results, a test article concentration of 5 % was selected for intradermal induction in the main study.
Epidermal applications: after 4 intradermal injections (as described above), 2 guinea pigs were exposed to the test article at 50, 25, 15 and 10 % in corn oil under occlusive conditions for 24 h. The reaction sites were assessed approximately 24 and 48 hours after removal of the bandage for erythema and oedema according to the method of Magnusson and Kligman. No highest non-irritating concentration could be determined after the epidermal pretest described above. Therefore, a second pretest was performed with two additional naive guinea pigs, treated in the same way as that described previously, with the concentrations of 5, 3, 1 and 0.5 % in corn oil. Based on the results obtained the concentration selected for induction and challenge in the main study was 50 % and 0.5 %, respectively.

MAIN STUDY
INDUCTION EXPOSURE (Intradermal injection, on day 1)
- Test groups:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiologicalsaline.
2) The test article, at 5 % in corn oil.
3) The test article at 5 % in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
- Control group:
1) 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
2) Corn oil
3) 1:1 (w/w) mixture of corn oil in a 1:1 (v/v) mixture of Freund's Complete Adjuvant and physiological saline.
- Site: scapular region

INDUCTION EXPOSURE (Epidermal application, on day 8)
- No. of exposures: 1
- Exposure period: 48 h
- Test groups: A 2 x 4 cm patch of filter paper was saturated with approximately 0.3 g test article (50 % in corn oil) and placed over the injection sites under occlusive condition.
- Control group: same as described above with corn oil only (0.3 ml).
- Site: scapular area

CHALLENGE EXPOSURE
- No. of exposures: once
- Day(s) of challenge: on test day 22, two weeks after the epidermal induction application
- Exposure period: 24 h
- Test groups: Two patches (3x3 cm) of filter paper were saturated with 0.2 ml of test article at the highest non-irritating concentration of 0.5 % (left flank) and the vehicle only (corn oil applied to the right flank) using the same method as for the epidermal application.
- Control group: same as test group
- Site: dorsal skin from the scapular region
- Concentrations: highest non-irritating concentration of 0.5 %
- Evaluation (hr after challenge): 24 and 48

Challenge controls:
yes, 5 control animals were used as challenge controls
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole

Results and discussion

Positive control results:
The positive control at a concentration of 10 % in mineral oil is considered to be an extreme sensitizer.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
none
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 %
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 % . No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 % . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge control
Dose level:
0.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenge control. Dose level: 0.5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control
Dose level:
0.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control. Dose level: 0.5 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Any other information on results incl. tables

- There were no deaths during the course of the study.

- No signs of systemic toxicity were observed in the animals.

- The body weight of the animals was within the range commonly recorded for animals of this strain and age.

- Control group: No skin reactions were observed in the animals when treated with either corn oil only or when treated with the test article at 0.5 % in corn oil.

- Test group: Discrete/patchy erythema was observed in one out of 10 animals at the 24-hour reading after treatment with the test article at 0.5 % in com oil. No skin reactions were observed in the animals treated with corn oil only.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of an in vivo skin sensitizing study performed according to OECD guideline 406 (1993), the test substance was considered to be not sensitizing.
Executive summary:

The skin sensitizing potential of the test article was assessed in a study conducted according to OECD guideline 406 (1993). Induction was performed intradermal (5% in corn oil) and one week later epicutaneous (50% in corn oil, 48 h, occlusive). Two weeks after epidermal induction animals were challenged epicutaneous for 24 h with 0.5% test substance in corn oil and corn oil alone under semi-occlusive conditions (RCC740068, 1999). Discrete/patchy erythema was observed in 1/10 animals after 24 h. No skin reactions were observed after 48 h in treated animals or in any animal treated with corn oil only. No signs of systemic toxicity were observed in the animals. Thus, the test substance was considered to be not sensitizing.