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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (OECD 406, GPMT): not sensitising

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:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Principles of method if other than guideline:
Chemical substances may sensitise after single or repeated dermal application. Further application after the elapse of a certain period may cause allergic reactions. If this sensitisation occurs not after application of the test substance alone, but only in the presence of sufficient luminous energy, this is a so-called "photoallergic reaction". "Photoallergy" is defined as an increased reactivity of the skin to ultraviolett and/or visible radiation caused by an immunologic reaction to a chemical agent.
GLP compliance:
yes
Type of study:
other: photosensitisation test
Justification for non-LLNA method:
The test was performed in 1995 before the alternative OECD guidelines (LLNA and in vitro test methods) were set into force.
Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 307 g mean
- Housing: in fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate, in groups of 5 animals
- Diet (e.g. ad libitum): Altromin 3112 for guinea pigs and rabbits ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, open
Vehicle:
other: DAE (dimethylacetamid : acetone : ethanol, 40 : 30 : 30)
Concentration / amount:
induction: 0.1%
Route:
epicutaneous, open
Vehicle:
other: DAE (dimethylacetamid : acetone : ethanol, 40 : 30 : 30)
Concentration / amount:
challenge: 0.1%
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 12
- Test groups: Test substance in solvent + 7min h*v (week 1 UVA/vis >315 nm; week 2/3 UVA/B/vis >300 nm), single application of FCA at beginning of week 2
- Control group: solvent + 7min h*v (week 1 UVA/vis >315 nm; week 2/3 UVA/B/vis >300 nm), single application of FCA at beginning of week 2
- Site: front part of shaven dorsal skin
- Frequency of applications: 4/week
- Duration: day 1 - 18
- Concentrations: 0.1 %


B. CHALLENGE EXPOSURE
- No. of exposures: 3
- Day(s) of challenge: 35, 36, 37
- Test groups: Test substance + 2 min h*ν (UVA/B/vis >300 nm)
- Control group: Test substance + 2 min h*ν (UVA/B/vis >300 nm)
- Site: rear part of the dorsal skin
- Concentrations: 0.1 %
- Evaluation (hr after challenge): Macroscopic examination of the skin 24 h after each challenge application


OTHER:
The formation of dermal reactions, such as erythema, oedema and scab formation are major clinical indications of photoallergy or contact allergy. The decisive criterion for evaluation of the photoallergic properties of a test substance is the number of sensitised test animals. The substance is considered to be photosensitising if 30 % or more of the animals treated with the the test substance show a positive reaction and at the same time no irritant effects have emerged in the negative control group.

At the end of the study the animals were weighed and sacrificed by carbon dioxide asphyxiation.
Positive control substance(s):
yes
Remarks:
chlorpromazine
Positive control results:
During the induction phase the animals in the positive control group showed slight to well defined erythema and a number of local dermal findings.
The challenge treatment caused slight to well defined erythema in all animals and slight to moderate oedema in 90 % of the animals in the positive control group.
In the positive control all animals showed erythema and 90 % showed oedema
Reading:
other: 1st challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 1st challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 1st challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 1st challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 2nd challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd challenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.1 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 3rd challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 1st challenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 % chlorpromazine
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
very slight to well-defined erythema and very slight oedema
Remarks on result:
other: see Remark
Remarks:
Reading: other: 1st challenge. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1 % chlorpromazine. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: very slight to well-defined erythema and very slight oedema.
Reading:
other: 2nd challenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 % chlorpromazine
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
very slight to moderate/severe erythema and very slight oedema
Remarks on result:
other: see Remark
Remarks:
Reading: other: 2nd challenge. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1 % chlorpromazine. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: very slight to moderate/severe erythema and very slight oedema.
Reading:
other: 3rd challenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 % chlorpromazine
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
very slight to moderate/severe erythema and very slight to well-defined oedema; dry rough skin, fine scales, indurations, scabbed skin
Remarks on result:
other: see Remark
Remarks:
Reading: other: 3rd challenge. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1 % chlorpromazine. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: very slight to moderate/severe erythema and very slight to well-defined oedema; dry rough skin, fine scales, indurations, scabbed skin.

No clinical signs of intoxication were observed at any time during the study. There were no impairements of body weight gains.

During the induction phase from weeks 1 to 3 in both the control and treatment groups slight to moderate erythema were recorded. The challenge treatment caused no dermal irritation in both the control and treatment groups.

Based on the results of this study the test substance has no photosensitising potential.

Interpretation of results:
other: not photosensitising
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1991 before the alternative OECD guidelines (LLNA and in vitro test methods) were set into force.
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: about 4 weeks
- Weight at study initiation: 262.4 g mean
- Housing: in fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate, in groups of 5 animals
- Diet (e.g. ad libitum): Altromin 3112 for guinea pigs and rabbits, ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Intradermal induction: 5 %
Epicutaneous induction: 25%
Day(s)/duration:
48 h (epicutaneous)
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
25%
Day(s)/duration:
24 h
No. of animals per dose:
20 (in test groups), 10 (controls)
Details on study design:
RANGE FINDING TESTS:
In a dermal-occlusive test for primary skin irritation, 25, 5 and 1% in paraffin were applied to the left flank of two guinea pigs. The hair on the right and left flanks of the animals was removed mechanically. 0.5 mL of the test substance preparation was applied to a 2 x 2 cm cellulose
patch, which was then fixed to the left flank and covered occlusively for 24 hours with a bandage and film. 24 hours after removal of the patches, the treated skin areas were examined for erythema and oedema.

No irritation occurred after application of any of the tested concentrations.
For this reason the 25% concentration was selected for the main study.

To determine the tolerance of intradermal injections, each of the following preparations was administered twice by intradermal injection to 3 guinea pigs. The injection sites (sites 1, 2 and 3) were all within a dorsal area measuring 2 x 4 cm in the vicinity of the shoulder.
Site 1: 2 x 0.1 ml 5.0% in paraffin
Site 2: 2 x 0.1 ml 1.0% in paraffin
Site 3: 2 x 0.1 ml 0.2% in paraffin

The injections with the 5% substance preparation in paraffin caused very slight to well-defined erythema and slight oedema. The injection sites for the 1% and 0.2% preparations showed very slight to well-defined erythema and (very) slight oedema.
Based on this preliminary test, the 5% preparation in paraffin was selected for the intradermal injections in the main test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal day 1 and epicutaneously day 8)
- Test groups: Intradermal: 50% Freund's adjuvant alone, test substance in paraffin, test substance in 50% Freund's adjuvant; epicutaneous: test substance in paraffin
- Control group: Intradermal: 50% Freund's adjuvant alone, paraffin only, 50% Freund's adjuvant alone; epicutaneous: paraffin only
- Site: dorsal area 4 x 6 cm in the vicinity of the shoulders.
- Frequency of applications: 7 days
- Duration: day 1 to day 8
- Concentrations: Intradermal 5% test substance, epicutaneous 25 % test substance


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Test groups: test substance epicutaneously
- Control group: test substance epicutaneously
- Site: shaved left flank, shaved right flank remained untreated
- Concentrations: 25% test substance
- Evaluation (hr after challenge): 48 and 72
Challenge controls:
The control group actually is a challenge control.
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 5% intradermal, 25% epicutaneous; challenge: 25% epicutaneous
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
very slight erythema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
induction: 5% intradermal, 25% epicutaneous; challenge: 25% epicutaneous
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
very slight erythema, dry rough skin, fine scales
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested

The treated animals showed no clinical signs of intoxication at any time during the study. The intradermal injections with Freund's adjuvant (with and without test substance) caused moderate oedema, well-defined to moderate erythema. The injection site revealed white discoloured areas, and the skin was encrusted and scabbed. After dermal induction treatment the tissue of these injection sites became necrotic or developed open wounds in the control as well as in the treatment group. The body weight gains of the treated animals were not impaired.

Challenge:

48 and 72 hours after removal of the occlusive bandage, 4 out of 20 animals in the treated group (20%) showed dermal reactions in the form of very slight erythema, whereas no signs of dermal irritation were noticed in the control group. Additionally the skin surface was dry, rough and covered with fine scales.

Conclusion:

Based on the results of this study, Hoe 107892 00 ZC97 0001 is non-sensitising, and thus not subject to labelling requirements according to the criteria for classification in Directive 83/467/EEC.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
CLP: Not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A GPMT assay analysing the skin sensitising properties of the test item was conducted according to OECD guideline 406 and compliant with GLP.

Twenty female Pirbright-Hartley guinea pigs were induced intradermally with 5% test substance formulated in paraffin on study Day 1 and epicutaneously with 25% test substance formulated in paraffin on study Day 8. After 48 h of exposure under occlusive conditions, the patch was removed.

Three weeks later, the challenge was performed. The animals were epicutaneously treated with 25% test substance and exposed for 24 h under occlusive conditions. A similar constituted group of control animals was induced but remained untreated during the challenge.

Skin reactions were evaluated 48 and 72 h after removal of the test substance. At the first reading 48 h after challenge 4/20 (i.e. 20 %) of the test animals showed very slight erythema. At the second reading 72 h after the challenge, 3/20 (i.e. 15%) animals showed very slight erythema, dry rough skin and fine scales. Based on the results of the study, the test item is not considered to be a skin sensitiser.

 

Additionally, a test for photosensitisation was reported, in which the ability to increase the reactivity of the skin to UV and/or visible radiation caused by sensitisation to the test substance was assessed. In this test none of the 10 test animals showed positive reactions at the readings 24 hours after first, second and third challenge.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.