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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study (this record) and two QSAR predictions. All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Cross-referenceopen allclose all
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Reference
Endpoint:
skin sensitisation: in vitro
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study and two QSAR predictions (one of which is this record). All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reference:
Composition 0
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
Times v.2.28.1.6
Toolbox prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
Smiles: O=[N+]1C(C2CCC(N1[O-])(CC2)C)(C)C
Parameter:
other: QSAR skin sensitization model
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
The test substance is predicted to be a non-sensitiser.
Executive summary:

The Times model for skin sensitisation was used. The test substance is predicted to be a non-sensitiser. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Reference
Endpoint:
skin sensitisation: in vitro
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study and two QSAR predictions (one of which is this record). All data sources agree in the estimated skin sensitization potential (i.e., non-sensitizing according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reference:
Composition 0
Guideline:
other: QSAR prediction
Principles of method if other than guideline:
BIOVIA Discovery Studio v4.5
Prediction report is attached in IUCLID
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: O=[N+]1C(C2CCC(N1[O-])(CC2)C)(C)C
Parameter:
other: QSAR skin sensitisation
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
The test substance is predicted to be a non-sensitiser.
Executive summary:

The BIOVIA model for skin sensitisation was used. The test substance is predicted to be a non-sensitiser. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reason / purpose:
reference to same study
Remarks:
skin irritation results
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Justification for type of information:
This endpoint record is part of a Weight of Evidence approach comprising an in vivo study (this record) and three QSAR predictions. All data sources agree in the estimated skin irritation potential (i.e., non-irritating according to EC 1272/2008 as amended) as further explained in the provided endpoint summary.
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to other study
Remarks:
part of a Weight of Evidence approach
Related information:
Composition 1
Reason / purpose:
reference to same study
Remarks:
skin sensitization results
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
Haskell No. 9864
Species:
guinea pig
Strain:
not specified
Details on test animals and environmental conditions:
Albino males
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
other: propylene glycol
Controls:
no
Amount / concentration applied:
1 drop (apprx. 0.05 mL) each of a 50% and a 5% suspension (wt/vol) of the test material in propylene glycol were applied.
Duration of treatment / exposure:
Not specified
Observation period:
48 hrs
Number of animals:
10
Details on study design:
1 drop of each suspension (50% or 5%) was applied and lightly rubbed in on the shaved intact shoulder skin.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
10 animals
Time point:
24/48 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
mild irritation in three animals as a 50% suspension
Irritation parameter:
erythema score
Basis:
mean
Remarks:
10 animals
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
results only reported for 14 & 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
10 animals
Time point:
24/48 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
mild irritation in three animals as a 50% suspension
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
only 24 & 48 hours reported

This study has limitations: duration of the exposure and coverage/dressing information were not provided and the test substance was only tested up to 50%, which did not induce irritation. 

Interpretation of results:
study cannot be used for classification
Conclusions:
This study has limitations: duration of the exposure and coverage/dressing information were not provided, and the test substance was only tested up to 50%, which did not induce irritation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
intracutaneous test
Justification for non-LLNA method:
The guinea pig skin sensitization test results were existing data and were not commissioned for the purposes of REACH.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Specific details on test material used for the study:
Haskell No. 9864

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
Albino males

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: saline
Concentration / amount:
0.1 mL of a 1% solution (wt/vol) of test material in 0.9% saline
Day(s)/duration:
3 wks
Adequacy of induction:
not specified
Challenge
Route:
intradermal
Vehicle:
propylene glycol
Concentration / amount:
0.05 mL each of a 50% and a 5% suspension (wt/vol) of test material in propylene glycol
Day(s)/duration:
48 hours
Adequacy of challenge:
not specified
No. of animals per dose:
9
Details on study design:
To test for the sensitization potential, a series of four sacral intradermal injections was given, one each week over a three-week period, which consisted of 0.1 ml of a 1% solution (wt/vol) of test material in 0.9% saline. Following a two-week rest period, the test animals were challenged for sensitization by applying, and lightly rubbing in 1 drop (approx. 0.05 mL) each of a 50% and a 5% suspension (wt/vol) of test material in propylene glycol on the shaved intact shoulder skin. A group of 10 previously unexposed guinea pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions on skin of similar age.
Challenge controls:
A group of 10 previously unexposed guinea pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions on skin of similar age.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
50% suspension (wt/vol)
No. with + reactions:
3
Total no. in group:
6
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
9
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
5% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
9
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
9
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
0
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
0
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
0
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50% suspension (wt/vol)
No. with + reactions:
0
Total no. in group:
0

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
part of a Weight of Evidence approach as further explained in the provided endpoint summary
Conclusions:
The test material produced mild irritation in three test guinea pigs and one control guinea pig when applied at challenge to the shaved intact skin of male albino guinea pigs as a 50% suspension in propylene glycol. No irritation was produced by a 5% suspension. No sensitization was observed at challenge; however, the material is a mild skin irritant. However, this study has limitations: induction did not have 3 pairs of intradermal injections and did not have topical application. Also, it is unclear whether the highest induction dose was the highest to cause mild to moderate skin irritation. Coverage information was not provided, and skin reaction observed during the induction period was not reported.