Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study has been performed according to a standard methodology and under laboratory conditions. There is no indication of GLP compliance and such this study is considered to be justified for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH) Annex XI, Section 1.1. Further this study is considered to be adequate and reliable for the purpose of assessing sensitisation potential in accordance with Regulation (EC) No 1272/2008 (EU CLP). Read-across in accordance with Annex XI, Section 1.5 of Regulation (EC) No. 1907/2006 (REACH) is justified on the following basis: Manganese phosphates such as manganese hydrogen phosphate and manganese bis(dihydrogen phosphate) are soluble manganese-containing inorganic compounds. The toxicology of these materials is considered to be related to the presence of the Mn2+ ion (as phosphate itself is not considered to be toxic). As such it is scientifically justified to read-across to other soluble materials containing Mn2+. In this instance the manganese chloride is considered to be appropriate as the chloride ion itself shows no propensity for sensitisation.

Data source

Reference
Reference Type:
publication
Title:
Indentification of metal allergens in the local lymph node assay
Author:
Basketter DA, Lea LJ, Cooper KJ, Ryan CA, Gerberick GF, Dearman RJ and Kimber I
Year:
1999
Bibliographic source:
American Journal of Contact Dermatitis, 10(4): 207-212

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
No justification for choice of vehicle (not a standard vehicle for this study)
Principles of method if other than guideline:
The protocol used followed the standard methodology as described in Kimber I, Basketter DA (1992) The murine local lymph node assay;collaborative studies and new directions: A commentary. Food ChemToxicol. 30:165-169.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Reference substance name:
Manganese dichloride
EC Number:
231-869-6
EC Name:
Manganese dichloride
Cas Number:
7773-01-5
IUPAC Name:
manganese(2+) dichloride
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): manganese chloride
- Molecular formula (if other than submission substance): MnCl2
- Substance type: inorganic
- Physical state: solid
- Analytical purity: 97%
- Source: Sigma, Poole, UK

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac, Bicester, UK
- Age at study initiation: 7-12 weeks

Study design: in vivo (LLNA)

Vehicle:
other: petrolatum
Concentration:
5, 10, 25%
No. of animals per dose:
4 (3 dose groups: vehicle and test)
Details on study design:


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Murine Local Lymph Node Assay
- Criteria used to consider a positive response: A substance was regarded as a skin sensitizer if, at any concentration, the proliferation in treated lymph nodes was threefold or greater than that in the concurrent vehicle treated controls

Results and discussion

In vivo (LLNA)

Results
Parameter:
SI
Remarks on result:
other: Test Concentration Stimulation Index 5.0% 1.1 10.0% 0.6 25.0% 1.0

Any other information on results incl. tables

Authors state that the negative result obtained in the LLNA study corresponds to human observations in which manganese is not considered to be a sensitiser.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Manganese chloride and hence manganese itself is not considered to be a sensitiser under the conditions of this study.
Read-across in accordance with Annex XI, Section 1.5 of Regulation (EC) No. 1907/2006 (REACH) is justified on the following basis:
Manganese phosphates such as manganese hydrogen phosphate and manganese bis(dihydrogen phosphate) are soluble manganese-containing inorganic compounds. The toxicology of these materials is considered to be related to the presence of the Mn2+ ion (as phosphate itself is not considered to be toxic). As such it is scientifically justified to read-across to other soluble materials containing Mn2+. In this instance the manganese chloride is considered to be appropriate as the chloride ion itself shows no propensity for sensitisation.