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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Study period:
04 August 1992 to 11 February 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a reliable in vivo test conducted before the enforcement of Commission Regulation (EU) 640/2012 of 06 July 2012 amending, for the purpose of its adaptation to technical progress, Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) are available.

Test material

Constituent 1
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
code number: FAT 45155/B
purity: 60 - 70 %
physical appearance: powder, dark red
storage: room temperature, keep dark
expiration date: May. 15, 1997
Specific details on test material used for the study:
Test article: FAT 45155/B
Trade name: ERIONYL ROT HT 3728
Batch No.: HT 3728/TV 1
Purity: 60 - 70 %
Physical properties: powder; dark red
Storage conditions: room temperature; keep dark
Validity: May 15, 1997

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White Strain
Sex:
male/female
Details on test animals and environmental conditions:
The guinea pigs were recognized by the international guideline as the recommended test system.
The test was performed on 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group.
- Breeder: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Date of acclimatisation: August 12, 1992
- Weight at study initiation: 301-396 g
- Housing: individually in Macrolon cages
- Diet : Pelleted standard Kliba 342, Batch 24/85 guinea pig breeding/ maintenance diet ad libitum.
- Water: fresh water, ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%):30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): a 12 hours light cycle day

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
1 %
Day(s)/duration:
Week 1
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30 %; patch 2x4 cm; approx. 0.4 g paste per patch
Day(s)/duration:
Week 2
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30 %; 2x2 cm; approx. 0.2 g paste per patch
Day(s)/duration:
Week 5
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control group
Details on study design:
See materials and methods
Challenge controls:
Vehicle: Vaseline
Positive control substance(s):
yes
Remarks:
Potassium dichronate

Results and discussion

Positive control results:
90 % of the animals were positive after treatment with the reference substance at the concentration of 1 % in vaseline. Therefore reference article Potassium dichronate should be considered to be an extreme sensitizer under the test conditions.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
erythema and edema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
erythema and edema
Key result
Reading:
other:
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
See remarks on result
Remarks on result:
other: See remarks
Remarks:
Skin sensitizer based on histopathological examination: all treated animals at the application-site changes characteristic for contact dermatitis, including spongiosis, acanthosis, hyper- and parakeratosis, pustules, congestion and lymphohistiocytic infiltration
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and edema and histopathological examination
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema and edema and histopathological examination
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
1 % in Vaseline
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
erythema and edema
Remarks on result:
other: Potassium dichronate
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
1 % in Vaseline
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
erythema and edema
Remarks on result:
other: Potassium dichronate

Any other information on results incl. tables

The evaluation of a possible skin erythema was impeded by the red-coloured test article which could not be washed off entirely. Therefore, histopathological examination of the application and remote site from all animals was carried out at the end of this study. Only results from histopathological examination were used for classification of FAT 45155/B according to Magnusson and Kligman. Thus, under the experimental conditions employed, 100 % of the animals of the test group were sensitised by FAT 45155/B.


 


Pathology


Microscopical findings


When compared to the tissues from control animals and to the "remote site" in treated animals, the application site of skin from all animals treated with the test article showed prominent changes compatible with contact dermatitis. This finding was characterized by following features: a minimal to moderate spongiosis (without prominent presence of blisters-formation), a minimal to moderate congestion in the upper dermis, a minimal to marked acanthosis with minimal to moderate hyper- and parakeratosis and a minimal to marked lymphohistiocytic infiltration predominantly in the upper dermis, in some animals with invasion in to the epidermis. Two animals showed additionally pustules with cell debris in the epidermis. In some animals, there was a minimal lymphohistocytic infiltration also in the subcutaneous tissue, mostly located around blood vessels. One animal (No. 3, treated group) showed similar, minimal, focal changes at the remote site. Since this focus was localized at the margin of the sample, it could be assumed, that the test article spread beyond the testing site during the application. A minimal lymphocytic infiltration, in some cases associated with admixture of eosinophils or lymphohistiocytic infiltrations of the subcutaneous tissue, occurred at the remote site in nearly all control and treated animals. This is attributed to the application procedure (fur clipping) and not to an effect of the test article. Irritative changes occurred neither at the application- nor at the remote site.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
FAT 45155/B is considered as skin sensitiser.
Executive summary:

A skin sensitization study was performed to assess the allergenic potential of FAT 45155/B in albino guinea pigs. The study was carried out according to OECD guideline 406 under GLP-compliance.


The induction was a two-stage operation. First (at week 1 with 1 % test article concentration in physiological saline), intradermal injections (into the neck region); second (at week 2 with 30 % test article concentration in vaseline), closed patch exposure over the injection sites one week later. During weeks 3 and 4 no treatments were performed. The animals were challenged at week 5 with 30 % test article concentration in Vaseline (w/w). A control group of 10 animals (5 m/5 f) was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum sub irritant concentration of the test article in adjuvant treated animals. 24 and 48 hours after removing the dressings, the challenge reactions were graded according to the Draize scoring scale. The evaluation of a possible skin erythema was impeded by the red-coloured test article which could not be washed off entirely. At the end of the test period all controls and treated animals were bled under ether anesthesia and from each animal samples of skin (the application- and the remote site) were taken and preserved in neutral buffered 4 % formalin. Each sample was trimmed longitudinally to hair direction, embedded in paraplast, sectioned at 3-5 microns, stained with hematoxylin and eosin, and subjected to a microscopical examination. The evaluation of a possible skin erythema was impeded by the red-coloured test article which could not be washed off entirely. Therefore, histopathological examination of the application and remote site from all animals was carried out at the end of this study. Only results from histopathological examination were used for classification of FAT 45155/B according to Magnusson and Kligman. Macroscopical evaluation of a possible skin erythema was impeded by the red-coloured test article. Therefore histopathological examination of the skin (application and remote site) of all animals was carried out at the end of this study. Microscopical examination revealed in all treated animals at the application-site changes characteristic for contact dermatitis, including spongiosis, acanthosis, hyper- and parakeratosis, pustules, congestion and lymphohistiocytic infiltration. Under the experimental conditions employed, 100 % of the animals of the test group were sensitised by FAT 45155/B. Based on the study results, FAT 45155/B is, therefore, classified as an extreme sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.