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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: equivalent to current guidelines, according to GLP
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: equivalent to current guidelines, according to GLP
Justification for type of information:
See read-across justification attached in section 13.2
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
alternative parameters used
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)
Test material information:
Composition 1
Species:
mouse
Strain:
other: CBA/JICO
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 9 weeks
- Weight at study initiation: 19.5 g - 25.0 g
- Housing: single housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
propylene glycol
Concentration:
10, 30, and 60 %
No. of animals per dose:
6
Details on study design:
- Criteria used to consider a positive response:

lf a test substance does not show a statistically significant increase in ceII count and/or lymph node weight as compared to the vehicle control in the presence of statistically significantly increased ear weights as indication of skin irritation, it is considered not to be a sensitizer.

lf at least one concentration tested causes a concentration dependent statistically significant increase in cell count and/or lymph node weight without being accompanied by a statistically significant increase in ear weight, the test substance is considered to be a sensitizer.

lf statistically significant increases in ear weights are running in parallel to the increase in ceII count and/or lymph node weight, it cannot be ruled out, that the lymph node response was caused by irritation and not by skin sensitization. Then, for identification of the relevance of the statistical evaluation, a comparison of the results of the present test to appropriate historical control values is performed. lt one or a combination of the measured parameters change statistical significance, evaluation on basis of the criteria described above may be possible. lf the statistical comparison with
the historical control does not yield results useful tor evaluation, further investigations may be necessary to differentiate between irritation and sensitization response.

lf a test substance does not elicit a statistical significant increase in lymph node weight and/or cell count but shows a clear concentration related increase in response, further investigating of the sensitization potential at higher concentrations would be considered.
Positive control substance(s):
other: Historical control: Alpha-Hexylcinnamaldehyde
Statistics:
WILCOXON-test
Parameter:
SI
Test group / Remarks:
untreated
Remarks on result:
other: see Remark
Remarks:
Lymphnode weight Index: untreated: 0.89 Cell count index: untreated: 0.89 Ear weight index: untreated: 0.97
Parameter:
SI
Test group / Remarks:
vehicle
Remarks on result:
other: Lymphnode weight Index: vehicle: 1 Cell count index: vehicle: 1 Ear weight index: vehicle: 1
Parameter:
SI
Test group / Remarks:
10 %
Remarks on result:
other: Lymphnode weight Index: 10% TS: 0.95 Cell count index: 10% TS: 1.05 Ear weight index: 10% TS: 1.06
Parameter:
SI
Test group / Remarks:
30 %
Remarks on result:
other: Lymphnode weight Index: 30% TS: 0.87 Cell count index: 30% TS: 0.92 Ear weight index: 30% TS: 1.08* *for p<=0.05
Parameter:
SI
Test group / Remarks:
60 %
Remarks on result:
other: Lymphnode weight Index: 60% TS: 0.76 Cell count index: 60% TS: 0.88 Ear weight index: 60% TS: 1.04

No signs of systemic toxicity were noticed.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
alternative parameters used
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,9-Nonandiol
- Physical state: Crystalline / white at room temperature; Liquid / white after heating at about 80 - 100°C
- Analytical purity: 98.8 cor. area%
- Lot/batch No.: 42638
- Stability under test conditions: The stability under storage conditions was confirmed by reanalysis.
- Storage condition of test material: Room temperature, exclusion of oxygen (storage under nitrogen)

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/JICO
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: 9 weeks
- Weight at study initiation: 19.5 g - 25.0 g
- Housing: single housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
propylene glycol
Concentration:
10, 30, and 60 %
No. of animals per dose:
6
Details on study design:
- Criteria used to consider a positive response:

lf a test substance does not show a statistically significant increase in ceII count and/or lymph node weight as compared to the vehicle control in the presence of statistically significantly increased ear weights as indication of skin irritation, it is considered not to be a sensitizer.

lf at least one concentration tested causes a concentration dependent statistically significant increase in cell count and/or lymph node weight without being accompanied by a statistically significant increase in ear weight, the test substance is considered to be a sensitizer.

lf statistically significant increases in ear weights are running in parallel to the increase in ceII count and/or lymph node weight, it cannot be ruled out, that the lymph node response was caused by irritation and not by skin sensitization. Then, for identification of the relevance of the statistical evaluation, a comparison of the results of the present test to appropriate historical control values is performed. lt one or a combination of the measured parameters change statistical significance, evaluation on basis of the criteria described above may be possible. lf the statistical comparison with
the historical control does not yield results useful tor evaluation, further investigations may be necessary to differentiate between irritation and sensitization response.

lf a test substance does not elicit a statistical significant increase in lymph node weight and/or cell count but shows a clear concentration related increase in response, further investigating of the sensitization potential at higher concentrations would be considered.
Positive control substance(s):
other: Historical control: Alpha-Hexylcinnamaldehyde
Statistics:
WILCOXON-test

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Test group / Remarks:
untreated
Remarks on result:
other: see Remark
Remarks:
Lymphnode weight Index: untreated: 0.89 Cell count index: untreated: 0.89 Ear weight index: untreated: 0.97 Lymphnode weight Index: untreated: 0.89 Cell count index: untreated: 0.89 Ear weight index: untreated: 0.97
Parameter:
SI
Test group / Remarks:
vehicle
Remarks on result:
other: Lymphnode weight Index: vehicle: 1 Cell count index: vehicle: 1 Ear weight index: vehicle: 1
Parameter:
SI
Test group / Remarks:
10 %
Remarks on result:
other: Lymphnode weight Index: 10% TS: 0.95 Cell count index: 10% TS: 1.05 Ear weight index: 10% TS: 1.06
Parameter:
SI
Test group / Remarks:
30 %
Remarks on result:
other: Lymphnode weight Index: 30% TS: 0.87 Cell count index: 30% TS: 0.92 Ear weight index: 30% TS: 1.08* *for p<=0.05
Parameter:
SI
Test group / Remarks:
60 %
Remarks on result:
other: Lymphnode weight Index: 60% TS: 0.76 Cell count index: 60% TS: 0.88 Ear weight index: 60% TS: 1.04

Any other information on results incl. tables

No signs of systemic toxicity were noticed.

Applicant's summary and conclusion