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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
modification refer to measurement of cell proliferation by cell counting instead of radioactive labeling; in addition the acute inflammatory skin reaction is determined to discriminate specific from non-specific activation of immune competent cells in the
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
modification refer to measurement of cell proliferation by cell counting instead of radioactive labeling; in addition the acute inflammatory skin reaction is determined to discriminate specific from non-specific activation of immune competent in the drai
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
6,6’-di-tert-butyl-2,2’-methylendi-p-cresol (Vulkanox BKF), purity: 97 to 98%

In vivo test system

Test animals

Species:
mouse
Strain:
NMRI
Sex:
female

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 2%, 10% 50%
No. of animals per dose:
6 per dose group

Results and discussion

In vivo (LLNA)

Results
Parameter:
SI
Remarks on result:
other: neither a non-specific (irritant nor a specific immunostimulating (sensitzing) potential of the test item was revealed; cell count index: vehicle control: 1.00, 2%: 1.17, 10%: 1.16, 50%: 1.22

Any other information on results incl. tables

Groups of female NMRI mice were treated with vehicle, 2%, 10% or 50% test substance in AOO.

The NMRI mice treated with the test substance 6,6’-di-tert-butyl-2,2’-methylendi-p-cresol did not show an increase in the stimulation indices for cell counts or for weights of the draining lymph nodes. The "positive level" which is 1.4 for the cell count index was not reached or exceeded in any dose group (cell count index: 1.0, 1.17, 1.16, 1.22 at 0, 2%, 10% or 50% test substance solution, respectively). The “positive level” of ear swelling, which is 2x 10-2 mm increase, i.e. about 10% of the control values, was not reached or exceeded in any treatment group. In addition, no substance specific effects were determined for ear weights.

no treatment-related effcts on body weights were noted.

Based on the findings of this study, the author suggested that neither a non-specific (irritant) nor a specific immune stimulating (sensitizing) potential of the test substance was indicated.

Table: Direct LLNA (NMRI mice, 6 animals/group) lymph node weight index and cell count index (index mean ± SD in %)

 Dose (%)  Weight index (index mean ± SD in %)  Cell count index (index of mean ± in %)
 0  1.00 ± 13.89  1.00 ±16 .46
 2  1.11 ± 16.92  1.17 ± 17.57
 10  1.09 ± 11.56  1.16 ± 13.12
 50  1.08 ± 14.16  1.22 ± 8.07

Table: Ear swelling (NMRI mice, female, 6 animals/group, in 0.01 mm)

 Dose (%)  day 1 (mean ± SD in %)  day 4 (mean ± SD in %)  Index day 4
 17.42 ± 2.96  17.67 ± 2.79  1.00
 2  17.25 ± 2.62  18.42 ± 4.89  1.04
 10  17.58 ± 3.80  18.58 ± 8.10  1.05
 50  17.67 ± 2.79  18.33 ± 3.55  1.04
       

Table Ear weight (NMRI mice, female, 6 animals/group, in mg per 8 mm diameter punch)

 Dose (%)  day 4 (mean ± SD in %)  Index day 4
 0  12.20 ± 7.11  1.00
 2  12.83 ± 8.30  1.05
10 12.90 ± 7.62  1.06
 50  12.63 ± 9.88  1.04

Applicant's summary and conclusion