Bis(5-oxo-L-prolinato-N1,O2)zinc

Endpoint summary

Description of key information

The repeat dose oral toxicity of the test material was evaluated using a read-across approach. Suitable analogues were found in the OECD QSAR Toolbox using the Organic Functional Group category, and the results were refined using relevant subcategories.

Based on the modelled conditions, the subacute NOEL of the test material in the rat was determined to be ca. 7.8 mg/kg bw/day.

The target chemical falls within the applicability domain of the prediction.

However, according to an EFSA opinion (please refer to Section 13 for more information), ZN-100, also known as zinc L-pidolate, is used as a food supplement. Once in the body ZN-100 will dissociate into its components i.e. L-pidolic acid and zinc.

According to EFSA a daily intake of L-pidolic acid of 3 g/day in humans is of no safety concern. This value corresponds to 50 mg/kg bw/day of L-pidolic acid or 62 mg/kg bw/day of zinc L-pidolate (ZN-100). 

Nevertheless, based on the Scientific Committee on Food (please refer to Section 13 for more information), a clear NOAEL for zinc is established at 50 mg/day for humans, which corresponds to a human NOAEL of 4 mg/kg bw/day for ZN-100.

Therefore, the human NOAEL of 4 mg/kg bw/day was considered to be the most appropriate and conservative value to be used for the DNEL derivation.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Both subchronic and subacute data were used in the prediction. As a worst case, the prediction is submitted as subacute toxicity data.

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The following prediction was performed using the OECD QSAR Toolbox using an appropriate category based on the current endpoint. The prediction was further refined using subcategories.

Justification for type of information:

A read-across justification report (RAAF) will be added to Section 13 as soon as possible.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

The repeat dose oral toxicity of the test material was evaluated using a read-across approach. Suitable analogues were found in the OECD QSAR Toolbox using the Organic Functional Groups category, and the results were refined using relevant subcategories.

GLP compliance:

no

Remarks:

As no laboratory work took place, compliance with GLP is not required.

Limit test:

no

Specific details on test material used for the study:

SMILES: [Zn+2].[O-]C(=O)C1CCC(=O)N1.[O-]C(=O)C1CCC(=O)N1

Species:

rat

Route of administration:

oral: unspecified

Dose descriptor:

NOEL

Effect level:

7.77 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Based on the modelled conditions

Remarks on result:

other: The prediction was based on the average value from the 5 nearest neighbours compared by prediction descriptors.

Critical effects observed:

not specified

The prediction was based on dataset comprised from the following descriptors: NOEL

Estimation method: Takes average value from the 5 nearest neighbours

Domain logical expression:Result: In Domain

Substances used for the prediction should:

Contain Carboxylic acid<OR>Saturated heterocyclic fragment<OR>Lactams<OR>Pyrrolidine<OR>Pyrrolidone/Pyrrolidinedione<OR>Zinc, organo (Organic functional groups)

<AND> be Bioavailable (Lipinski Rule Oasis)

Conclusions:

Based on the modelled conditions, the subacute NOEL of the test material in the rat was determined to be ca. 7.8 mg/kg bw/day.

Executive summary:

The repeat dose oral toxicity of the test material was evaluated using a read-across approach. Suitable analogues were found in the OECD QSAR Toolbox using the Organic Functional Group category, and the results were refined using relevant subcategories.

Based on the modelled conditions, the subacute NOEL of the test material in the rat was determined to be ca. 7.8 mg/kg bw/day.

The target chemical falls within the applicability domain of the prediction.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008 (CLP), the substance does not require classification with respect to Specific Target Organ Toxicity repeated dose (STOT RE) via the oral route.