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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Administrative data

Description of key information

The test item revealed no sensitising properties in a guinea pig maximisation test of Magnusson and Kligman according to EU method B.6 and OECD Guideline 406.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-01-11 until 1999-02-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992-07-17
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Directive 96/54 EEC
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A skin sensitisation test in guinea pigs following OECD 406 (Magnusson-Kligman) had already been performed.
Species:
guinea pig
Strain:
other: Hsd POC: DH
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen, Germany
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 300-314 g
- Housing: Terluran-cages on Altromin saw fibre bedding
- Diet: ad libitum, Altromin 3122 maintenance diet for guinea pigs, rich in crude fibre, totally pathogen free-TPF
- Water: drinking water, municipal residue control, microbiol. controlled periodically

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3C°
- Humidity: 55 +/- 10%
- Air changes: >= 10 x / hour
- Photoperiod: 12:12 (hrs dark / hrs light), light 6:30 - 18:30
Route:
intradermal and epicutaneous
Vehicle:
CMC (carboxymethyl cellulose)
Concentration / amount:
Intradermal induction exposure: Injection 1: 2000 mg test item in 0.9 % NaCl solution; Injection 3: Test item as a 12.5% (w/v) formulation in FCA/diluted with isotonic saline (50% v/v)
Topical application induction exposure: 2 g of the test item, moistened with CMC 1%
Topical application challenge exposure: 2 g of the test item, moistened with CMC 1%
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Concentration / amount:
Intradermal induction exposure: Injection 1: 2000 mg test item in 0.9 % NaCl solution; Injection 3: Test item as a 12.5% (w/v) formulation in FCA/diluted with isotonic saline (50% v/v)
Topical application induction exposure: 2 g of the test item, moistened with CMC 1%
Topical application challenge exposure: 2 g of the test item, moistened with CMC 1%
No. of animals per dose:
10 test female animals, 5 control female animals
Details on study design:
RANGE FINDING TESTS:

For the justification of dose levels a preliminary test was performed. This test had the purpose of evaluating the irritation potential of test material at the levels to be used in the injection induction, topical induction, and challenge phase.
Two animals were topically treated with the test item. No signs of irritation were recorded after a contact period of 24 h. Thus, an undiluted concentration of the test item, suspended in the vehicle, was used for the induction second stage and the challenge. For the first stage of the induction the highest concentration applicable as intradermal injection (25 % w/v) was chosen.

MAIN STUDY:

A. Induction Exposure
- No. of exposures: 2 exposures, i.e. a single intradermal exposure in week 1 (6 injections/animal) and an epicutaneous exposure in week 2 (closed patch)
- Exposure period: single application (intradermal exposure), 48 hours (topical exposure)
- Test groups: 1 group of 10 animals (female)
- Control group: 1 group of 5 animals (female)
- Site: shoulder region
- Frequency of applications: 1 intradermal application (week 1) and 1 topical application (week 2)
- Site: nape and upper back area

A1. Intradermal Injection
- No. of exposures: 3 intradermal injections of 0.1 mL volume in groups of two per animal
-Test group: 10 animals (female)
Injection 1: 50% (v/v) FCA/diluted with isotonic saline
Injection 2: Test item as a 25% (w/v) formulation in NaCl
Injection 3: Test item as a concentration of 12.5% (w/v) formulation in FCA/diluted with isotonic saline (50% v/v)

Control group 5 animals:
Injection 1: 50% (v/v) FCA/diluted with isotonic saline
Injection 2: NaCl 0.9%
Injection 3: NaCl 0.9% as a 50% (v/v) formulation FCA/diluted isotonic saline
-Site: shoulder region (injections 1 and 2 were placed close to each other and nearest to the head, while 3 were placed towards the caudal part of the test area)
- Frequency of applications: 1

A2.Topical Application
-Test and control Group: Day 6
Approx. 24 h before the topical application, the test area of each animal was clipped and 0.5 mL of 10% sodium lauryl sulfate in vaseline was applied in order to create a local irritation.
-Test Group Day 7:
A patch loaded with 2 g of the test item, moistened with CMC 1% , was applied to the test area and held in contact by an occlusive dressing for 48 hours.
-Control Group: Day 7
A patch loaded with 2 g of isotonic saline was applied to the test area and held in contact by an occlusive dressing for 48 hours.

B. Challenge Exposure
- No. of exposures: 1
- Exposure period: 24 hours
- Site: flanks (cleared of hair)
-Test and control group Day 20:
A patch loaded with 2 g of the test item, moistened with CMC 1%, was applied to the left flank of the animals and a patch loaded with isotonic saline solution was applied to the right flank (intraspecific control), respectively.
The patch was held in contact by an occlusive dressing for 24 hours, followed by a cleaning of the application site with moistened gauze patches.

-Evaluation: 24, 48, and 72 hours after removal of the dressing
Challenge controls:
Vehicle only, CMC (carboxymethyl cellulose)
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole
Positive control results:
Positive control substance: Mercaptobenzothiazole, Purity > 98 %, CAS No. 149-30-4, Lot 19F3482, Sigma Chemicals Co.
Concentrations:
2% induction I phase
25% induction II phase
15% challenge
Number of animals: 10
Results:
1st reading: (24 h): 6/10 animals, erythema;
2nd reading (48 h): 6/10 animals, erythema;
3rd reading (72 h): 2/10 animals, erythema;
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2 g (moistened with CMC 1%)
No. with + reactions:
0
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: 2 g (moistened with CMC 1%). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2 g (moistened with CMC 1%)
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: 2 g (moistened with CMC 1%). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
2 g (moistened with CMC 1%)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2 g (moistened with CMC 1%). 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:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. 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:
positive control
Dose level:
15%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 15%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
15%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 15%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: erythema.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
positive control
Dose level:
15%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
erythema
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 15%. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: erythema.
Interpretation of results:
not sensitising
Conclusions:
Under the study conditions the test item caused no reactions identified as sensitisation.
Executive summary:

The test item was assessed for its skin sensitising properties using the guinea pig maximisation test of Magnusson and Kligman according to EU method B.6 and OECD Guideline 406. During the induction phase the guinea pigs were intradermally injected with a suspension of the test item and topically treated with 2 g of the test item moistened with CMC 1%. Following a latency period of 14 days the animals were challenged with another topical application of the test item (2 g moistened with CMC 1% (100 % test substance)), exposed to the flank.

The grade of skin reactions of treated animals was compared to controls (control animals were treated with isotonic saline during the induction phase and during challenge phase) The sensitisation rate after application of the test item was 0%. Under the test conditions the test item showed no sensitising properties. Additionally, no other signs of toxicity were observed. All animals showed normal food intake and weight gain.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test item was assessed for its skin sensitising properties using the guinea pig maximisation test of Magnusson and Kligman according to EU method B.6 and OECD Guideline 406. During the induction phase the guinea pigs were intradermally injected with a suspension of the test item and topically treated with 2 g of the test item moistened with CMC 1%. Following a latency period of 14 days the animals were challenged with another topical application of the test item (2 g moistened with CMC 1% (100% test substance)), exposed to the flank.


The grade of skin reactions of treated animals was compared to controls (control animals were treated with isotonic saline during the induction phase and during challenge phase) The sensitisation rate after application of the test item was 0%. Under the test conditions the test item showed no sensitising properties. Additionally, no other signs of toxicity were observed. All animals showed normal food intake and weight gain.


The test item revealed no sensitising properties in a guinea pig maximisation test of Magnusson and Kligman according to EU method B.6 and OECD Guideline 406.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results obtained, the test substance was not classified and labelled for skin sensitisation according to Regulation No (EC) 1272/2008 (CLP).