Manganese di(acetate)

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Performed similar to OECD 429 guideline, Read-across from Manganese chloride resp. Lead acetate. However, the study performance is well-documented and meets scientific principles which indicates that the study is well-performed and suitable to cover this endpoint.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

Dose concentrations: 25, 10, 5 % (w/v) (MnCl2) resp. 10, 5, 2.5 % (w/v) (Lead acetate)

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

other: CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac, Bicester, United Kingdom
- Age at study initiation: young adult, 7 - 12 weeks
- Weight at study initiation: no data
- Housing: four mice per group are caged separately
- Acclimation period: at least 2 days

Vehicle:

other: petrolatum (manganese chloride), DMSO (lead acetate)

Concentration:

25, 10, 5 % (w/v) (manganese chloride)
10, 5, 2.5 % (w/v) (lead acetate)

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
The dose selection is made to provide the highest possible test concentration, while avoiding unacceptable dermal trauma or systemic toxicity

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: ³H-Thymidine incorporation
- Criteria used to consider a positive response: For each concentration of test material a stimulation index is derived, using values from vehicle control nodes as the comparator. On the basis of local lymph node assay responses, chemicals are classified as either "sensitizers" or "not strong sensitizers". There are two criteria for a positive response. First, at least one concentration of the test chemical must induce a three-fold or greater increase in 3H-thymidine incorporation compared with vehicle control values. Secondly, the data must not be incompatible with a conventional biological dose response. Chemicals that fail to induce a three-fold or greater response at any test concentration are classified as being not strong sensitizers. In practice, equivocal results will suggest that a repeat test, if possible using higher application concentrations, is appropriate.

TREATMENT PREPARATION AND ADMINISTRATION:
25 µl of each treatment concentration or an equal volume of the vehicle alone are applied to the dorsum of both ears ensuring even distribution. Treatment is performed daily for 3 consecutive days.

Statistics:

no data

Parameter:

SI

Remarks on result:

other: Stimulation index (SI) dependent on the test concentration Manganese chloride: SI = 1.1 (5 %) SI = 0.6 (10 %) SI = 1.0 (25 %) Lead acetate: SI = 0.7 (2.5 %) SI = 0.8 (5 %) SI = 1.0 (10 %)

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: no data

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study was performed similar to OECD 429 guideline on the Read-across substance Manganese chloride for the cation resp. Lead acetate for the anion of Manganese (II) acetate. The study performance is well-documented and meets scientific principles which indicates that the study is well-performed and suitable to cover this endpoint. Therefore, the results can considered to be reliable and sufficient for the assessment of the sensitizing properties of manganese (II) acetate.
Both substances exhibited at all tested concentrations (which are also considered to be of a sufficient magnitude) a stimulation index not greater than 1.1, so it can be concluded, that neither the cation Mn2+ nor the anion CH3COO- have sensitizing properties and consequently also Manganese (II) chloride is not sensitizing. So, Manganese (II) acetate does not need to be classified as skin sensitizing according regulation 1272/2008/EC nor according directive 67/548/EEC.

Executive summary:

In a dermal sensitization study similar to OECD 429 (murine local lymph node assay) with manganese chloride (25, 10, 5 % (w/v)) and lead acetate (10, 5, 2.5 % (w/v)) in petrolatum resp. DMSO, 7-12 week old CBA/Ca mice (4 animals / dose group) were tested using the ³H-thymidine incorporation method. The test substance was applied on three consecutive days on the dorsum of each ear, local lymph nodes were isolated on the fifth day, 5 h after ³H-thymidin was injected in the tail vein, and beta-scintillation was measured. No clinical signs and mortality was recorded. The stimulation index (SI) was determined to be 0.6 – 1.1 for both substances, so manganese (II) acetate is not a dermal sensitizer. This study is considered to be reliable and to fulfill the requirements for a study similar to OECD 429.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Both studies performed on manganese chloride (Ikarashi 1992) and manganese chloride and lead acetate (Basketter 1999)are performed similar to EU method B.42 resp. OECD guideline 429 with only minor deviations. The studies’ performances are well-documented and meet the guideline requirements for a murine local lymph node assay and general scientific principles. So the results can considered to be reliable and useful for the assessment of the sensitizing potential of Manganese (II) acetate. MnCl2 serves a read-across substance for Mn(acO)2, and taking into account the results from MnCl2 and lead acetate, manganese (II) acetate as a whole can be assessed by regarding both the cation Mn2+ and the anion CH3COO-. In both studies, the stimulation index SI was mostly below 1, only once 1.1, at all tested substances and concentrations. Therefore, all tested substances and concentration can considered to be not sensitizing to the skin, and neither is Manganese (II) acetate.

Hence, it can be concluded that the provided data is sufficient for classification as "not sensitizing" according to regulation 1272/2008/EC and directive 67/548/EEC and further testing would not reveal any other contradicting data, so it can be omitted.

Migrated from Short description of key information:
Manganese (II) acetate is not a skin sensitizer.

Justification for selection of skin sensitisation endpoint:
This study is one of two studies within a weight-of-evidence approach with similar, i.e. negative results. Here, not only manganese chloride was teested, but also lead acetate, which allows to draw conclusions to Manganese (II) acetate itself by regarding both the anion and cation. Additionally, the deviations from the respective guideline are minor.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to regulation 1272/2008/EC, a substance must be classified as skin sensitizer Category 1 if the following criteria are met:

(i) if there is evidence in humans that the substance can lead to sensitisation by skin contact in a substantial number of persons, or

(ii) if there are positive results from an appropriate animal test.

According to directive 67/548/EEC, a substance may cause sensitisation by skin contact

if practical experience shows the substance or preparation to be capable of inducing a sensitisation by skin contact in a substantial number of persons, or

where there are positive results from an appropriate animal test.

So far, human data is not available for manganese (II) acetate, but both animal studies gave clear evidence that manganese (II) acetate is not a skin sensitizer. Consequently, it does not need to be classified, neither according 1272/2008/EC nor directive 67/548/EEC.