Registration Dossier

Administrative data

Description of key information

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not sensitizing to skin.

Thus it can be further classified under the category “Not Classified” as per CLP regulation.

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
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. The study 2,3,4 are represented as 1,2,3
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on various test chemicals
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
25% of the test chemical
Day(s)/duration:
twice weekly for 2 weeks using 24 hours
Adequacy of induction:
not specified
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
intradermal -0.1ml Freund’s complete adjuvant in water,1% w/v test chemical in arachis oil, and Freund’s + 1% w/v test chemical in arachis oil (1:1)
epicutaneous- 2 – 0.3 ml 50% w/w test chemical in arachis oil
Day(s)/duration:
24 hours
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
three six-hour
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
0.2 – 0.3 ml 25 and 10% w/w test chemical in arachis oil
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: NaCl/PEG400 (50/50, v/v)
Concentration / amount:
25% in 0.9% NaCl/PEG400 (50/50, v/v)
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Adequacy of challenge:
not specified
No. of animals per dose:
1. 10 in the test group and 4 in the control group
2. 20 Dunkin Hartley guinea pigs in test group and 10 Dunkin Hartley guinea pigs in negative controls
3. twenty guinea pigs (ten males and ten females
Details on study design:
The data is based on weight of evidence approach based on various test chemicals
Challenge controls:
The data is based on weight of evidence approach based on various test chemicals
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test chemical
No. with + reactions:
0
Clinical observations:
no dermal reactions observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Executive summary:

The dermal sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

Cumulative contact enhancement test (CCET) was performed on guinea pigs to assess the dermal sensitization potential of the test chemical. Preliminary irritation tests were carried out to determine concentrations of the test chemical suitable for induction of sensitization and for sensitization challenge. Dunkin-Hartley Guinea pigs weighing approximately 350 grams, 10 in the test group and 4 in the control group were used for the assay. 25% of the test chemical was applied twice weekly for 2 weeks using 24 hours occlusive patches to the shoulder area of test animals to induce dermal reactions. Immediately before the third application,

the test and 4 control guinea pigs were injected with Freund's complete adjuvant in the shoulder region at the site to be patched.Test and control animals were challenged after a 12 days rest period by open application at the maximum non-irritant concentration (25%). 25% in 0.9% NaCl/PEG400 (50/50, v/v) was applied to the shoulder region of the test animals and observed for erythema. Challenge sites were scored for erythema (scale 0-3) at 24 and 48 hours.

0% guinea pigs were sensitized when evaluated after the challenge exposure. the test chemical failed to induce any evidence of sensitization at higher concentrations in the cumulative contact enhancement test (CCET). Therefore, the test chemical was considered to be not sensitizing.

This is supported by the results of the OECD 406 Guideline study perfomed on Dunkin Hartley guinea pigs to observe the sensitizing efficacy of the test chemical

20 Dunkin Hartley guinea pigs in test group and 10 Dunkin Hartley guinea pigs in negative controls were used. Guinea pigs were induced with intradermal injections of 0.1ml Freund’s complete adjuvant in water,1% w/v test chemical in arachis oil, and Freund’s + 1% w/v test chemical in arachis oil (1:1) into three separate sites.After 1 week, a single topical application of 0.2 – 0.3 ml 50% w/w test chemical in arachis oil under occlusion for 48 hours was applied. On day 21 animals were challenged with 0.1-0.2 ml 25 and 10% w/w test chemical in arachis oil.

Since there was no evidence of any skin reaction, the test chemical can be concluded as not sensitizing to guinea pigs.

These results are further supported by a study performed to determine if the test chemical causes delayed hypersensitivity in guinea pigs

In a preliminary dose-range finding study, four animals (two males and two females) were exposed to one concentration (as received) of the test chemical at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %.

The test chemical was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration. An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4 -dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4 -dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge.

No positive responses were observed in guinea pig receiving the test chemical at 100 % concentration at 24 or 48 hours after the challenge exposure. The test chemical did not cause hypersensitivity in quinea piqs.

Hence, the test chemical was considered to be not sensitizing to the skin of Guinea pig.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

 

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

Skin Sensitization:

The dermal sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

Cumulative contact enhancement test (CCET) was performed on guinea pigs to assess the dermal sensitization potential of the test chemical. Preliminary irritation tests were carried out to determine concentrations of the test chemical suitable for induction of sensitization and for sensitization challenge. Dunkin-Hartley Guinea pigs weighing approximately 350 grams, 10 in the test group and 4 in the control group were used for the assay. 25% of the test chemical was applied twice weekly for 2 weeks using 24 hours occlusive patches to the shoulder area of test animals to induce dermal reactions. Immediately before the third application,

the test and 4 control guinea pigs were injected with Freund's complete adjuvant in the shoulder region at the site to be patched.Test and control animals were challenged after a 12 days rest period by open application at the maximum non-irritant concentration (25%). 25% in 0.9% NaCl/PEG400 (50/50, v/v) was applied to the shoulder region of the test animals and observed for erythema. Challenge sites were scored for erythema (scale 0-3) at 24 and 48 hours.

0% guinea pigs were sensitized when evaluated after the challenge exposure. the test chemical failed to induce any evidence of sensitization at higher concentrations in the cumulative contact enhancement test (CCET). Therefore, the test chemical was considered to be not sensitizing.

This is supported by the results of the OECD 406 Guideline study perfomed on Dunkin Hartley guinea pigs to observe the sensitizing efficacy of the test chemical

20 Dunkin Hartley guinea pigs in test group and 10 Dunkin Hartley guinea pigs in negative controls were used. Guinea pigs were induced with intradermal injections of 0.1ml Freund’s complete adjuvant in water,1% w/v test chemical in arachis oil, and Freund’s + 1% w/v test chemical in arachis oil (1:1) into three separate sites.After 1 week, a single topical application of 0.2 – 0.3 ml 50% w/w test chemical in arachis oil under occlusion for 48 hours was applied. On day 21 animals were challenged with 0.1-0.2 ml 25 and 10% w/w test chemical in arachis oil.

Since there was no evidence of any skin reaction, the test chemical can be concluded as not sensitizing to guinea pigs.

These results are further supported by a study performed to determine if the test chemical causes delayed hypersensitivity in guinea pigs

In a preliminary dose-range finding study, four animals (two males and two females) were exposed to one concentration (as received) of Dapsone at four skin sites. Based upon the results of the dose-range finding study, the dose chosen for induction was 100 %.

The test chemical was dermally applied to twenty guinea pigs (ten males and ten females for a total of three six-hour insult periods at a 100 % concentration. An additional group of ten guinea pigs (five males and five females) was treated with 1-chloro-2,4-dinitrobenzene at 0.3% concentration for a total of three six-hour insult periods. Fourteen days after the last induction period, all animals were challenged at a naive site. A positive response was elicited in the animals receiving the positive control article, 1-chloro-2,4 -dinitrobenzene (DNCB). Redness and edema scores in all animals at 24 and 48 h recorded after each treatment and at 24 and 48 h after the challenge.

No positive responses were observed in guinea pig receiving the test chemical at 100 % concentration at 24 or 48 hours after the challenge exposure. The test chemical did not cause hypersensitivity in quinea piqs.

Hence, the test chemical was considered to be not sensitizing to the skin of Guinea pig.

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Respiratory sensitisation

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

Justification for classification or non-classification

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.