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.

The test chemical 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:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
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.Study 2,3,4 are referred as study 1,2,3
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on various test chemicals
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: petroleum jelly
Concentration / amount:
500mg (0.5 g) of the test chemical at a concentration of 30% (w/w) (diluted in petroleum jelly
Day(s)/duration:
6 hours for 3 weeks
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % concentration
Day(s)/duration:
3 6 hour patches
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:
intradermal -24 h; epicutaneous- 48 h
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: petroleum jelly
Concentration / amount:
.1 g each of 30%, 10%, 3%, or the petroleum jelly
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
0.1-0.2 ml 25 and 10% w/w test chemical in arachis oil.
Adequacy of challenge:
not specified
No. of animals per dose:
1. Ten animals were used in the treatment group and 10 in the control group
2. twenty guinea pigs (ten males and ten females)
3. 20 Dunkin Hartley guinea pigs in test group and 10 Dunkin Hartley guinea pigs in negative controls
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
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. The test chemical 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 skin sensitization potential of the test chemical was assessed based on the available results from the various test chemicals.

A delayed contact hypersensitivity test was conducted on Guinea pigs to evaluate the skin sensitization potential of test chemical under occlusive condition.

Ten animals were used in the treatment group and 10 in the control group.during induction, the test site on the flank was clipped and shaved and 500mg (0.5 g) of the test chemical at a concentration of 30% (w/w) (diluted in petroleum jelly) was applied for 6 h under a closed patch, once a week, for 3 weeks. A control site received only the petroleum jelly.  

Two weeks after the last application, 0.1 g each of 30%, 10%, 3%, or the petroleum jelly were applied to the shaved skin and left for 24 h under a closed patch. Skin reactions were scored on a −, ±, +, ++, +++ scale at 24 and 48 h.

None of the treated animal showed any signs of delayed contact hypersensitivity within 48 hours. Thus, the test chemical was considered to be not sensitizing in Guinea pigs.

This is supported by the results of thestudy 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 pigs.

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

These studies are also supported by a study performed according to OECD 406 Guidelines to observe the sensitizing efficacy of the test chemical in Dunkin Hartley guinea pigs. 

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.

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. The test chemical 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:

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

A delayed contact hypersensitivity test was conducted on Guinea pigs to evaluate the skin sensitization potential of test chemical under occlusive condition.

Ten animals were used in the treatment group and 10 in the control group.during induction, the test site on the flank was clipped and shaved and 500mg (0.5 g) of the test chemical at a concentration of 30% (w/w) (diluted in petroleum jelly) was applied for 6 h under a closed patch, once a week, for 3 weeks. A control site received only the petroleum jelly.  

Two weeks after the last application, 0.1 g each of 30%, 10%, 3%, or the petroleum jelly were applied to the shaved skin and left for 24 h under a closed patch. Skin reactions were scored on a −, ±, +, ++, +++ scale at 24 and 48 h.

None of the treated animal showed any signs of delayed contact hypersensitivity within 48 hours. Thus, the test chemical was considered to be not sensitizing in Guinea pigs.

This is supported by the results of the 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 pigs.

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

These studies are also supported by a study performed according to OECD 406 Guidelines to observe the sensitizing efficacy of the test chemical in Dunkin Hartley guinea pigs. 

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.

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. The test chemical 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 study available

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.

The test chemical was estimated to be not sensitizing to skin. Thus it can be further classified under the category “Not Classified” as per CLP regulation.