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Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on guinea pigs. Based on the available data for the target and supporting studies, it can be concluded that the test chemical is able to cause skin sensitization and thus can be considered as sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
Data is from experimental study report
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Principles of method if other than guideline:
A maximization test was carried out in female Dunkin-Hartley guinea pigs to assess the skin sensitization potential of test chemical according to EU Method B.6 (Skin Sensitisation).
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not specified
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Body weight at the beginning of the study : 275 - 310 g
Acclimatization period: At least 7 days before the beginning of the study in the laboratory for dermal toxicity.
The animals were housed in fully air-conditioned rooms in which a central air-conditioning system ensured a temperature in the range of 20 - 24°C and a relative humidity in the range of 30 - 70%.
The illumination period was 12 h dark and 12 h light.
Type of cage: Makrolon, type IV
No . of animals per cage: 5
Identification of the animals: Ear tag numbering
Type of diet: Kliba 341.4 mm
Water was available ad libitum (tap water; about 2 g of ascorbic acid per 10 l water was added to the drinking water twice a week)
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
1st application: Induction 5 % intracutaneous;
2nd application: Induction 50 % occlusive epicutaneous
Day(s)/duration:
96 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
25% in aqua bidest.
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
25% in aqua bidest.
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
control: 5
test group: 10

Details on study design:
For detecting a possible influence on irritating effects of previous intradermal treatment with Freund's adjuvant, animals pretreated with Freund's adjuvant / 0.9% aqueous NaCl-solution (1 : 1) each, in the same manner as intradermal induction about 3 weeks prior to the application of the test substance were used.
In the preliminary test after two 24-hour percutaneous occlusive applications within 96 hours the minimum irritant concentration was found to be a 50% test substance preparation in aqua bidest. and the maximum non-irritant concentration a 25% test substance preparation in aqua bidest. (48 hours after the beginning of application).
Applicability: It was possible to inject a 5% test substance preparation in 0.9% aqueous NaCl-solution resp. in Freund's adjuvant / 0.9% aqueous NaCl-solution (1 : 1) with a syringe.
Positive control substance(s):
yes
Remarks:
(1-chlor-2.4-dinitro-benzol)
Reading:
other: 1st percutaneous challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
moderate to severe erythema and very slight edema; well-defined erythema could be observed in 2 out of 10 animals.
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 2nd challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
moderate to severe erythema and very slight edema; well-defined erythema (1 animal with very slight erythema.
Remarks on result:
positive indication of skin sensitisation
Cellular proliferation data / Observations:
moderate to severe erythema and very slight edema; well-defined erythema could be observed in 2 out of 10 animals.
Interpretation of results:
other: sensitising
Conclusions:

The number of animals sensitized is primarily taken into account in the evaluation. The control animals are used to rule out any substance-induced primary skin irritation.
The findings obtained 24 hours after the removal of the patch are taken into account for the determination of the sensitization rate.
The evaluation "sensitizing" results if at least 30 per cent of the animals exhibit skin reactions in this adjuvant test.
Under the test conditions chosen and following the described results, the test chemical has a sensitizing effect on the skin of the guinea pig.
Executive summary:

A maximization test was carried out in female Dunkin-Hartley guinea pigs to assess the skin sensitization potential of test chemical according to EU Method B.6 (Skin Sensitization). In the preliminary test after 24-hour percutaneous occlusive applications within 96 hours, the minimum irritant concentration was observed to be a 50% of test substance preparation in water and the maximum non-irritant concentration was 25% test substance preparation in water (48 hours after the beginning of application).The test was conducted on 10 guinea pigs in test group and 5 guinea pigs in control group. During the induction, the animals were treated intracutaneously at concentration of 5 % and dermally at concentration 50 % under occlusive condition. Later, challenge and rechallenge was performed at a dose of 25% of test chemical in water under occlusive condition and skin reactions were observed. Also 1-chlor-2.4-dinitro-benzol was used as positive control. The findings revealed, moderate to severe erythema, very slight edema and well-defined erythema in 2 out of 10 animals. Thus under the test conditions chosen and the described results, the test chemical was considered as sensitizing to the skin of the guinea pig.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Various studies has been investigated for the test chemical to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs for test chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below;

 

A maximization test was carried out in female Dunkin-Hartley guinea pigs to assess the skin sensitization potential of test chemical according to EU Method B.6 (Skin Sensitization). In the preliminary test after 24-hour percutaneous occlusive applications within 96 hours, the minimum irritant concentration was observed to be a 50% of test substance preparation in water and the maximum non-irritant concentration was 25% test substance preparation in water (48 hours after the beginning of application).The test was conducted on 10 guinea pigs in test group and 5 guinea pigs in control group. During the induction, the animals were treated intracutaneously at concentration of 5 % and dermally at concentration 50 % under occlusive condition. Later, challenge and rechallenge was performed at a dose of 25% of test chemical in water under occlusive condition and skin reactions were observed. Also 1-chlor-2.4-dinitro-benzol was used as positive control. The findings revealed, moderate to severe erythema, very slight edema and well-defined erythema in 2 out of 10 animals. Thus under the test conditions chosen and the described results, the test chemical was considered as sensitizing to the skin of the guinea pig.

 

Another Skin sensitization study of chemical was reported by in guinea pigs by using maximization test according to Directive 84/449/EEC, B.6 "Acute toxicity (skin sensitization)". Since the chemical caused skin sensitizing effects in treated guinea pigs, the test chemical was considered to be sensitizing to the skin of guinea pigs.

 

The overall results were further supported by the predicted data estimated by Danish QSAR database. According to Danish QSAR database, the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, skin sensitization reactions were observed in guinea Pig and Human. Therefore, the test chemical was considered to be sensitizing.

 

Thus based on the above key and supporting studies for test chemical, it can be concluded that the test chemical is able to cause skin sensitization. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitization potential of test substance were observed in various studies. From the results obtained from these studies it is concluded that the test chemical is likely to cause skin sensitization and hence can be classified as “Skin Sensitizer”.