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Administrative data

Description of key information

The read across source substance methyl pyruvate was determined to have a skin sensitising potential in a local lymph node assay (reference 7.4.1 -1). An in silico assessment of the test item did not indicate a skin sensitisation potential (reference 7.4.1 -2). As a worst case, the test item is considered to be a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance sodium pyruvate is the sodium salt of pyruvic acid. It is similar to the source substance 3-methyl pyruvate, which is a methyl ester of pyruvic acid. 3-methyl pyruvate (source substance) only differentiates from sodium pyruvate (target substance) by one methyl group instead of a sodium cation. Studies on skin sensitisation were not performed for the target substance sodium pyruvate due to availability of reliable experimental data for 3-methyl pyruvate. Sodium pyruvate is considered to be a suitable read across substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance 3-methyl pyruvate, which was used in a skin sensitisation study, had a purity of 99%. No information on impurities is available. The purity of the target substance sodium pyruvate is similar (99 - 100 %).

3. ANALOGUE APPROACH JUSTIFICATION
Experimental data i.e. a skin senstisation study in mice is available for 3-methyl pyruvate. 3-methyl pyruvate was tested in a local lymph node assay according to OECD 429. The study revealed a skin sensitising potential (GHS Category 1B). The information given on 3-methyl pyruvate is considered to be sufficient to cover the required endpoint information for the target substance sodium pyruvate.
Reason / purpose:
read-across source
Key result
Parameter:
EC3
Value:
2.4
Parameter:
SI
Value:
1.2
Test group / Remarks:
concentration: 1 %
Parameter:
SI
Value:
2.3
Test group / Remarks:
concentration: 2.5 %
Parameter:
SI
Value:
4.7
Test group / Remarks:
concentration: 5 %
Parameter:
SI
Value:
8
Test group / Remarks:
concentration: 10 %
Endpoint:
skin sensitisation, other
Remarks:
in silico
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:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Qualifier:
no guideline available
Principles of method if other than guideline:
Estimates the skin sensitising properties of chemicals using structural alert relationships.
GLP compliance:
no
Specific details on test material used for the study:
SMILES: [Na+].CC(=O)C(=O)[O-]
Key result
Parameter:
other: alerts
Value:
0
Remarks on result:
no indication of skin sensitisation
Remarks:
QSAR predicted value. The substance is within the applicability domain of the model.
Interpretation of results:
other: Derek result: No alerts matched.
Conclusions:
Using Derek Nexus v5.0, no skin sensitising properties of the test item were estimated. The substance is within the applicability domain of the model. Thus the estimation can be regarded as accurate.
Executive summary:

The skin sensitising properties were estimated using Derek Nexus v5.0. No skin sensitising properties were estimated based on the described QSAR method (Derek, 2017).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model is applicable to the query chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model is relevant for the regulatory purpose.

For assessment and justification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

For the evaluation of the skin sensitisation potential of the test substance a Weight of Evidence approach was used. The skin sensitising potential of the read across source substance methyl pyruvate was determined in a local lymph node assay. Furthermore, an in silico assessment of the test substance was carried out using Derek Nexus v5.0.

LLNA (reference 7.4.1 -1)

A local lymph node assay was performed according to OECD guideline 429 to assess the skin sensitising potential of the source substance methyl pyruvate. The test was performed with four CBA mice per dose group. As vehicle acetone/olive oil (4:1) was used. The mice were treated topically in the dorsum with 25 µL of the test item (1, 2.5, 5 or 10 %.) or the vehicle alone. Treatment was performed daily for 3 consecutive days. 5 days following the initiation of exposure, all mice were injected via the tail vein with 250 µL of phosphate-buffered saline (PBS) containing 20 µCi of tritiated thymidine. Mice were sacrificed 5h later, and the draining lymph nodes excised and pooled for each experimental group. The determined stimulation indices were 1.2 (1 %), 2.3 (2.5 %), 4.7 (5 %) and 8.0 (10 %) and the determined EC3 value was 2.4. Therefore, the test item was determined to have a skin sensitising potential (GHS Category 1B).

In silico assessment (reference 7.4.1 -2)

For in silico assessment, Derek Nexus v5.0 was used. No skin sensitising properties of the test item were estimated. The substance is within the applicability domain of the model. Thus the estimation can be regarded as accurate.

Conclusion

The read across source substance methyl pyruvate was determined to have a skin sensitising potential in a local lymph node assay. An in silico assessment of the test item did not indicate a skin sensitisation potential. As a worst case, the test item is considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on this data, the substance is considered to be classified for skin sensitisation (Cat 1B, H317) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EC) No 2017/776.