Registration Dossier

Administrative data

Description of key information

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Weight of evidence approach based on various test chemicals
Justification for type of information:
Weight of evidence approach based on various test chemicals
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on various test chemicals
Principles of method if other than guideline:
Weight of evidence approach based on various test chemicals
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment
Species:
guinea pig
Strain:
other: 2. albino; 3.not specified
Sex:
female
Route:
epicutaneous, open
Vehicle:
propylene glycol
Remarks:
study 2
Concentration / amount:
10%
Day(s)/duration:
three times weekly (Monday, Wednesday, Friday) for three consecutive weeks.
Adequacy of induction:
not specified
Route:
epicutaneous, open
Vehicle:
other: gum arabic
Remarks:
Study 3
Concentration / amount:
5% in 25% Aqueous solution of gum Arabic
Day(s)/duration:
5 days
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
propylene glycol
Concentration / amount:
10.0%, 5.0%, and 2 .5% in propylene glycol
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#1
Route:
intradermal
Vehicle:
not specified
Concentration / amount:
0.1ml of 0.01, 0.001, and 0.001% in saline
Adequacy of challenge:
not specified
No. of animals per dose:
2. 10
3. not specified
Details on study design:
2. Details on study design
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period:48 hour
- Test groups: 10
- Control group: no data
- Site: the left flanks of ten albino guinea pigs were shavedand the test material applied three times weekly( Monday,Wednesday,Friday)for three consecutiv weeeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area.
- Frequency of applications: three times weekly (Monday, Wednesday Friday) for three consecutive weeks.
- Duration: 3 weeks
- Concentrations:10%

B. CHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: Two week rest period
- Exposure period: 24 hour
- Test groups: 10
- Control group: No data available.
- Site: right flank of each guinea pig was shaved and test material applied on it.
- Concentrations: 10.0%, 5.0%, and 2.5%
- Evaluation (hr after challenge): 24 hour and 48 hours post-application

Other – The test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale (0 = no reaction, 1 -- slight reaction, 2 = moderate reaction, 3 = severe reaction. A positive reaction was defined as an erythema/edema value during the challenge phase of at least one skin grade higher than during the last induction phase.

3. RANGE FINDING TESTS: No data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: no data
- Exposure period: no data
- Test groups: No data
- Control group: No data
- Site: No data
- Frequency of applications: daily for 5 days
- Duration: 5 days
- Concentrations: 5% in 25% Aqueous solution of gum arabic

B. CHALLENGE EXPOSURE
- No. of exposures: no data
- Day(s) of challenge: no data
- Exposure period: no data
- Test groups: no data
- Control group: no data
- Site: no data
- Concentrations: 0.1ml of 0.01, 0.001, and 0.001% in saline
- Evaluation (hr after challenge): no data
Positive control substance(s):
yes
Remarks:
DNCB
Positive control results:
2. The positive control DNCB (2,4-dinitrochlorobenze) control at the 0.5% induction /challenge concentration elicited positive response in all animals tested.
Reading:
other: Challenge (WoE 2)
Hours after challenge:
24
Group:
test chemical
Dose level:
10.0%, 5.0%, and 2.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No sensitization reaction observed.
Remarks on result:
no indication of skin sensitisation
Reading:
other: Challenge (WoE 2)
Hours after challenge:
48
Group:
test chemical
Dose level:
10.0%, 5.0%, and 2.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin sensitization reaction observed.
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
test chemical
Dose level:
0.1ml of  0.01, 0.001, and 0.001% in saline
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No dermal reaction were observed
Remarks on result:
no indication of skin sensitisation
Remarks:
WoE 3
Interpretation of results:
other: not sensitizing
Conclusions:
Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.
Executive summary:

Various studies have been reviewed to evaluate the skin sensitization potential of the test chemical in living organisms. These include in vivo experimental studies performed on guinea pigs for the test chemical.

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of the test chemical. The test chemical was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5% in propylene glycol. During the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations in propylene glycol(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale. A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases. No erythema/edema was observed after application of test material. The test result was observed to be negative for the test substance. Therefore, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

This is supported by a Guinea pig maximization test performed to evaluate the dermal sensitization potential of the test chemical. The test material was applied topically 5% in 25%Aqueous solution of gum Arabic to the skin of guinea pigs for 5 days. After 2 weeks of rest period the challenge treatment was provided by epicuteneous injection of concentration 0.1ml of 0.01, 0.001, and 0.001% in saline. The guinea pigs were observed for signs of dermal sensitization after the challenge exposure. No signs of any skin allergic reaction were observed. Hence, the test chemical can be considered to be not sensitizing to guinea pig skin.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Various studies have been reviewed to evaluate the skin sensitization potential of the test chemical in living organisms. These include in vivo experimental studies performed on guinea pigs for the test chemical.

A modified Buehler and Klecak method for open epicutaneous testing[OET] was performed to assess the sensitization potential of the test chemical. The test chemical was tested at an induction concentration of 10% and challenge concentrations of 10.0%, 5.0%, and 2 .5% in propylene glycol. During the induction phase, the left flanks of ten albino guinea pigs were shaved and the dye test material applied three times weekly (Monday, Wednesday, Friday) for three consecutive weeks. Each animal received 0.1 ml of the dye test material over a 1.8-cm circular area. Following the induction period, the guinea pigs entered the challenge phase. The challenge phase began after a two-week rest period when the right flank of each guinea pig was shaved and exposed to three different dye test material concentrations in propylene glycol(10.0%, 5.0%, and 2 .5%). Twenty-four hours after the last induction and challenge application, the animals were depilated to clearly observe dermal reactions. All test sites were graded for erythema and edema 24 and 48 hours post-application using a four-point ordinal scale. A positive control of 0.5% 2,4-dinitrochlorobenzene(DNCB) in ethanol was included for both the induction and challenge phases. No erythema/edema was observed after application of test material. The test result was observed to be negative for the test substance. Therefore, the test chemical was considered to be not sensitizing to the skin of guinea pigs.

This is supported by a Guinea pig maximization test performed to evaluate the dermal sensitization potential of the test chemical. The test material was applied topically 5% in 25%Aqueous solution of gum Arabic to the skin of guinea pigs for 5 days. After 2 weeks of rest period the challenge treatment was provided by epicuteneous injection of concentration 0.1ml of 0.01, 0.001, and 0.001% in saline. The guinea pigs were observed for signs of dermal sensitization after the challenge exposure. No signs of any skin allergic reaction were observed. Hence, the test chemical can be considered to be not sensitizing to guinea pig skin.

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available results and applying the weight of evidence approach, the test chemical can be considered to be not sensitizing to skin. Comparing the above annotations with the criteria of CLP Regulations, the test chemical can be classified under the category “Not Classified”.