Manganate(1-), glycinato-N,O)[sulfato(2-)-O]-, hydrogen

Endpoint summary

Description of key information

There are no data regarding the skin sensitzing potential of manganese monoglycinate sulfate. Based on its ionic structure, manganese monoglycinate sulfate

is considered to dissociate into its ions namely, glycine and manganese sulfate and the cells are predominantly exposed to the single constituents of the salt.

There are information about the skin sensitizing potential of manganese sulfate and glycine.

- publication, 1999, test similar to LLNA conducted in CBA/CA mice, the animals were exposed for 3 consecutive days with 0, 5.0, 10.0, 25.0% MnCl2 in Petrolatum. Five days after initiation of the exposure the animals received 250 µL  of  phosphate buffered  saline  (PBS)  containing  20  µCi  of  tritiated  thymidine  (2 Ci  mmol/L;  Amersham  International,  Amersham,  UK) via the tail vein and were sacrificed after 5h.

Subsequently the draining lymphnodes were collected and evaluated, based on an overall SI < 3, MnCl2 is not considered to be a dermal sensitizer. Read-across

- QSAR estimation using VEGA-QSAR platform, the prediction clearly showed no sensitizing potential for glycine. The substance lies within the applicability domain of the model thus the result is regarded reliable. Read-across

- QSAR Toolbox request, a request of the QSAR Toolbox database revealed reliable data (LLNA, according to OECD guideline 429, 2012, in mice) proving that glycine is not a dermal sensitizer. Read-across

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

adopted 22 July, 2010

Principles of method if other than guideline:

- Principle of test: Test conducted similar to OeCD guideline 429
- Short description of test conditions: Groups of 4 CBAKa mice were treated with 25 µL of test material, or with an equal volume of the vehicle alone, on the dorsum of both ears. Treatment was performed once daily for 3 consecutive days. Five days after the initiation of exposure, all mice were injected by the tail vein with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine. Mice were killed 5 hours later and the draining lymph nodes excised and pooled for each experimental group. A single-cell suspension of lymph node cells was prepared by mechanical disaggregation. The lymph node cell suspension was washed twice in an excess of PBS and then precipitated with 5% trichloroacetic acid (TCA) at 4°C for 18 hours. Pellets were resuspended in TCA and the incorporation of tritiated thymidine measured by β-scintillation counting.
- Parameters analysed / observed: cell proliferation measured by incorporation of tritiated thymidine

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA/Ca

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac, Bicester, United Kingdom)
- Age at study initiation: 7- 12 weeks
- Housing: in groups of four animals

Vehicle:

other: Petrolatum

Concentration:

5, 10, 25%

No. of animals per dose:

4

Details on study design:

MAIN STUDY
Groups of 4 CBA/Ca mice were treated with 25 µL of test material, or with an equal volume of the vehicle alone, on the dorsum of both ears. Treatment was performed once daily for 3 consecutive days. Five days after the initiation of exposure, all mice were injected by the tail vein with 250 µL of phosphate buffered saline (PBS) containing 20 µCi of tritiated thymidine (2 Ci mmol/L; Amersham International, Amersham, UK). Mice were killed 5 hours later and the draining lymph nodes excised and pooled for each experimental group. A single-cell suspension of lymph node cells was prepared by mechanical disaggregation. The lymph node cell suspension was washed twice in an excess of PBS and then precipitated with 5% trichloroacetic acid (TCA) at 4°C for 18 hours. Pellets were resus- pended in TCA and the incorporation of tritiated thymidine measured by B-scintillation counting. A substance was regarded as a skin sensitizer if, at any test concentration, the proliferation in treated lymph nodes was threefold or greater than that in the concurrent vehicle treated controls.

- Criteria used to consider a positive response: A substance was regarded as a skin sensitizer if, at any test concentration, the proliferation in treated lymph nodes was threefold or greater than that in the concurrent vehicle treated controls.

Positive control substance(s):

other: see 'Remarks'

Statistics:

Not reported

Positive control results:

From the PC substances mercury and cobalt resulted in a SI value of over 3 at least in two of three concentration and were thus be considered as dermal sensitizer.

Key result

Parameter:

SI

Value:

1.1

Test group / Remarks:

at 5 % manganese chloride

Key result

Parameter:

SI

Value:

0.6

Test group / Remarks:

at 10% manganese chloride

Key result

Parameter:

SI

Value:

1

Test group / Remarks:

at 25 % manganese chloride

Cellular proliferation data / Observations:

CLINICAL OBSERVATIONS: For Manganese chloride no adverse effects were reported

Interpretation of results:

GHS criteria not met

Conclusions:

In the present publication the sensitizing potential of Manganese chloride was investigated using a test method similar to OECD guideline 429 (LLNA). Treatement of mice with 5.0, 10.0, and 25.0% Manganese chloride does not result in a SI value of over 3. Based on these results Manganese chloride is not considered to be a dermal sensitizer.

Executive summary:

In a dermal sensitization study similar to OECD guideline 429 (22 July, 2010) with Manganese chloride in Petrolatum, young adult CBA/CA mice (4/group) were tested in a LLNA. Additionally, beside Manganese chloride other metal salts were investigated in the LLNA which are known dermal sensitizers, these metal salts are considered to be the positive controls. No adverse clinical signs or mortality was observed during the study.  In this study Stimulation Indices (S.I.) of 1.1, 0.6 and 1 were determined with the test item at concentrations of 5, 10 and 25% in petrolatum, respectively. These results indicate that the test substance could not elicit an SI ≥ 3 and manganese chloride is therefore not regarded as skin sensitizer under the conditions of this study.

 

Proliferation of the treated lymph nodes was in no concentration increased to over 3-fold of that of the vehicle control lymph nodes. Thus, in this study, Manganese chloride is not a dermal sensitizer and does not need to be classified as dermal sensitizer according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

other: Information from the QSAR Toolbox database

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

not specified

Vehicle:

not specified

Key result

Parameter:

EC3

Remarks on result:

other: Value not reported in QSAR Toolbox

Key result

Parameter:

SI

Value:

< 3

Test group / Remarks:

mean of all tested groups

Remarks on result:

other:

Remarks:

Result as reported by the OECD QSAR Toolbox

Interpretation of results:

GHS criteria not met

Conclusions:

The OECD QSAR Toolbox was used in order to gather all available information about the skin sensitizing potential of glycine. The QSAR Toolbox revealed two identical entries exhibiting the same result from a test conducted accoding to OECD guideline 429 (LLNA). Glycine does not meet the classification criteria of Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemcials (GHS) and is therefore no classified as dermal sensitizer.

Executive summary:

No data are available regarding the skin sensitizing potential of glycine. Beside the QSAR prediction of skin sensitization using the VEGA-Module data was also gathered from the OECD QSAR Toolbox. The QSAR Toolbox revealed two identical entries exhibiting the same result from a test conducted accoding to OECD guideline 429 (LLNA). In both cases glycine was niot classified as skin sensitizer because there was no SI value above 3 in the mentioned study reports, thus, glycine is not considered to be a skin sensitizer according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemcials (GHS).

Reference 3

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
VEGA-QSAR:AI inside a platform for predictive toxicology
2. MODEL (incl. version number)
1.1.5
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(O)CN
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
For more detailed information please refer to the 'attached justification' section

5. APPLICABILITY DOMAIN
For more detailed information please refer to the 'attached justification' section

6. ADEQUACY OF THE RESULT
For more detailed information please refer to the 'attached justification' section

Qualifier:

no guideline followed

Principles of method if other than guideline:

Result of a QSAR prediction using VEGA-QSAR platform Skin Sensitization model (CAESAR) 2.1.6.

GLP compliance:

no

Justification for non-LLNA method:

No data are available for the source substance glycine, thus, based on a weight of evidence approach i.a. the results of a QSAR prediction were used to determine the skin sensitizing potential of glycine.

Species:

other: not applicable for an in silico system

Strain:

other: not applicable for an in silico system

Details on test animals and environmental conditions:

not applicable for an in silico system

Vehicle:

other: not applicable for an in silico system

Concentration:

not applicable for an in silico system

No. of animals per dose:

not applicable for an in silico system

Details on study design:

not applicable for an in silico system

Key result

Parameter:

other: not applicable for an in silico system

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

Interpretation of results:

study cannot be used for classification

Conclusions:

In the present QSAR calculation using VEGA-QSAR platform and its Skin Sensitization model (CAESAR) 2.1.6. the skin sensitizing potential of Glycine was estimated. There are no indications for skin sensitisation by appliying this QSAR prediction method. The results are considered to be reliable because the substance falls in the applicability domain of the used model. Glycine is not a sensitizier according to this prediction.

Executive summary:

No data are available for the soure substance glycine with regard to its skin sensitizing potential. Thus, a QSAR prediction with the VEGA module was performed. It predicts the skin sensitizing potential based on atom-centered fragments of a set of structural similar molecules. Based on the evaluation summary contained in the prediction results the QSAR estimation can be regarded as reliable. The accuracy of the prediction for similar structures is considered to be good, the concordance for similar structures is good, the Atom Centered Fragments similarity is good. Thus, there are no inconclusive predictions to be discussed and Glycine is predicted as NOT SENSITIZING TO THE SKIN.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no data available reagarding the sensitization potential of the target substance manganese monoglycinate sulfate. However, based on the read-across hypothesis it is assumed that the target substance,once it is dissolved in aqueous solutions, dissociates at least in parts into its constituents, namely glycine, Mn2+ and SO42-. For a detailed description of the read-across hypothesis please refer to the attached justification for read-across in Chapter 13.

Based on the aforementioned hypothesis the cells are primarily exposed to the constituents of which glycine is not expected to be a sensitizer due to its ubiquitous occurrence and its well-known and fast metabolism as ernergy source. There are information about the skin sensitizing effects of Mn2+ ions. In the study of Basketter et al. (1999) Mn2+ (dissolved MnCl2) was used in a LLNA at concentrations of 5%, 10% and 25% manganese chloride solution. None of the concentrations used resulted in an SI above 3, thus MnCl2 is not considered a dermal sensitizer. There are only minor information about the sensitizing properties of glycine. Therefore, two QSAR prediction tools were used. The sensitizing properties of glycine were estimated with the QSAR tool VEGA and revealed no alert for dermal sensitisation. Second, the QSAR Toolbox was used to gather information about the senitizing properties of glycine. According to the QSAR Toolbox entry glycine does not need to be classified as dermal sensitizer according to Regulation (EU) No. 122/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemcials (GHS). Furthermore, the performance of new in vitro testing with glycine is probably technically not feasible based on the methods used to detect skin sensitisation.

In summary, manganese monoglycinate sulfate is not considered to be dermal sensitizer and is therefore not classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the information available the test item does not need to be classified as dermal sensitizer according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).