Liraglutide precursor

Flash point

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

flash point of flammable liquids

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because decomposition occurred during the melting point study

Justification for type of information:

Hypothesis and justification for read-across of physical chemical data:

Data on target substance not available. Data is waived based on data from source substance (S3).

The target substance liraglutide precursor is a single-chain polypeptide consisting of 31 amino acids having an almost identical amino acid sequence as the human glucagon-like peptide 1 (GLP-1) that has 30 amino acids of which 29 amino acids in common with the target substance.
The target substance is a part of the active pharmaceutical ingredient: liraglutide (S1) as the liraglutide molecule has been obtained from the liraglutide precusor be the addition of a plamitoyl-ϒ-glutamate unit attached to the amino acid lysine in position 26 of the precusor.

S3 and S4 substances are somewhat larger polypeptides as consisting of 53 and 50 amino acids in the polypeptide chain.
 
Each of the amino acids in the above mentioned substances are and very polar molecules and when linked together in polypeptides the very polar nature of the polypeptides are considered as having very similar physicochemical properties irrespective whether they contain 31 (T) or 50 amino acids (S3,S4) for which physicochemical properties have been obtained. Thus, the results from physicochemical guideline testing for S3 and S4 for melting point, boiling point, flammability, self-ignition, and explosionwere identical and can be considered as representative for the target substance as well. With respect to vapour pressure the vapour pressure for single amino acids is extremely low (below 0.4 Pa) and thus, the vapour pressure for polypeptides would be expected to be even lower.
Data matrix for S1, S2, S3 and T is provided in section 13.

Key result

Remarks on result:

not determinable, other reason:

Remarks:

The flash point of MI3 was not tested experimentally. MI3 is a proteinaceous material, which is solid at room temperature. It has negligible vapour pressure and consequently will not emit flammable vapours. This is further confirmed by the fact that no melting or boiling points could be determined.

Conclusions:

Flash point not a relevant parameter as the substance does not emit vapours.

Executive summary:

Data on the flash point of Liraglutide precursor (T) waived based on informatiom on MI3 (S3). MI3 is -as Liraglutide precusor -a proteinaceous material, which is solid at room temperature. It has negligible vapour pressure and consequently will not emit flammable vapours. This is further confirmed by the fact that no melting or boiling points could be determined.

Reference 2

Endpoint:

flash point of flammable liquids

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because decomposition occurred during the melting point study

Description of key information

Data on target substance not available. Thus, read-across has been applied using registration data from source substance (S3).

The flash point of MI3 was not tested experimentally because of decomposition during determination of the melting point. MI3 (S3) is a proteinaceous material, which is solid at room temperature. It has negligible vapour pressure and consequently will not emit flammable vapours. This is further confirmed by the fact that no melting or boiling points could be determined.Therefore, the same conclusion for the target substance (Liraglutide precursor) applies, justified by the read-across hypothesis.

Thus a flash point cannot be determined for liraglutide precursor.

Support for read-across from S3 is provided in section 13.