Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study not carried out to standard test method, full details of test procedure not available, but sufficient information available to make an assessment. No positive control, but the study included and compared results with metals known to be sensitising (nickel). Study carried out using manganese chloride.
Justification for type of information:
Study not carried out to standard test method, full details of test procedure not available, but sufficient information available to make an assessment. No positive control, but the study included and compared results with metals known to be sensitising (nickel). Study carried out using manganese chloride.

Data source

Reference
Reference Type:
publication
Title:
Detection of contact sensitivity of metal salts using the murine local lymph node assay
Author:
Ikarashi, Y et al.
Year:
1992
Bibliographic source:
Toxicology letters, 62(10):53-61

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Principles of method if other than guideline:
The study was carried out to evaluate modifications to the LLNA method to improve its ability to detect contact sensitivity in metal salts. Th study examined the ability of seven metal salts to induce lymph node cell (LNC) proliferation in LLNA. The application of metal salts was modified by the use
of dimethylsulfoxide (DMSO) or aqueous ethanol as vehicle. In some experiments, the skin of the ear was abraded prior to application of metal salts.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
MnCl2.4H2O

In vivo test system

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
female

Study design: in vivo (LLNA)

Vehicle:
other: 20% aqueous ethanol
Concentration:
10% MnCl2 in vehicle
No. of animals per dose:
3
Details on study design:
Groups of mice (n=3) were treated with the indicated concentrations of metal salts or vehicle (20% ethanol solution) by applying 25 µl to the dorsum of both ears for three consecutive days. Prior to the test chemicals treatment, the ears of each mouse were gently abraded using a 19-g needle. Four days following the initial application, draining lymph nodes were excised. A single cell suspension of LNC was prepared and incorporation of [3H]TdR was measured.

Results and discussion

In vivo (LLNA)

Results
Key result
Parameter:
SI
Value:
< 1

Any other information on results incl. tables

Chemical       [3H]TdR incorporation (mean cpm +/- SD (x 10 -3))       SI

20% EtOH       1.52 +/- 0.67                                                               _

10% FeSO4       2.03 +/- 0.63                                                             1.32

10% MnCl2       1.26 +/- 0.08                                                              0.82

10% ZnSO4        2.14 +/- 0.77                                                            1.41

10% CuSO4       4.08 +/- 1.20                                                             2.67

10% NiSO4       3.56 +/- 0.25                                                              2.32

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: other:
Conclusions:
Manganese is not considered to be a sensitiser.
Executive summary:

The local lymph node assay (LLNA) is a predictive test for the detection of contact allergens. Nickel and chromium sensitization are common cases in man. However, in previous studies topical application of nickel sulfate and potassium dichromate in aqueous solution failed to induce activation in the draining lymph node. This study describes the application of LLNA to evaluate the contact sensitivity of metal salts. The metal salts were applied in dimethylsulfoxide or aqueous ethanol solution. In some experiments, the skin of the ears was gently abraded using a needle prior to application of metal salts. The ability of seven metal salts to induce lymph node cell (LNC) proliferation was compared. Nickel, cobalt, chromium and copper salts increased LNC proliferation, whereas zinc, manganese and iron salts failed to induce LNC proliferation in this assay