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Physical & Chemical properties

Melting point / freezing point

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Endpoint:
melting point/freezing point
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Remarks on result:
not determinable
Remarks:
no melting point could be determined. the observed broad endotherm in the range 192-205 °C, probably representing a thermal transition
Conclusions:
The melting point of insulin human methyl ester was estimated based on read across to MI3 (S2) and X14DesB30 (S3). Based on the structural similarities very similar physical chemical properties would be expected.
The determination of the melting point for S2 (MI3) and S3 (X14desB30) was performed using DSC in accordance to OECD guideline 102 (1995) and EC Directive 92/69/EEC Methods A1. The melting point was not determined. The observed broad endotherm in the range 192-205 °C for MI3 and >185 °C for X14DesB30, probably representing a thermal transition rather than a melting point.
Therefore, the melting point for Insulin human methyl ester is estimated to be >185 °C.
Executive summary:

The melting point of insulin human methyl ester was estimated based on read across to MI3 (S2) and X14DesB30 (S3). Based on the structural similarities very similar physical chemical properties would be expected.

The determination of the melting point for S2 (MI3) and S3 (X14desB30) was performed using DSC in accordance to OECD guideline 102 (1995) and EC Directive 92/69/EEC Methods A1. The melting point was not determined. The observed broad endotherm in the range 192-205 °C for MI3 and >185 °C for X14DesB30, probably representing a thermal transition rather than a melting point.

Therefore, the melting point for Insulin human methyl ester is estimated to be >185 °C.

For further details, please refer to read across justification document in section 13

Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003.06.30 - 2003.07.14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method A.1 (Melting / Freezing Temperature)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
differential scanning calorimetry
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL (MI3)
- Appearance: cream powder
- Source and lot/batch No.of test material: QC202426
- Expiration date of the lot/batch: June 2004
- Purity test date: 2003-06-18
- Purity: 84% w/w (stated ny Sponsor)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Frozen below - 10°C


Key result
Remarks on result:
not determinable
Remarks:
no melting point could be determined. the observed broad endotherm in the range 192-205 °C, probably representing a thermal transition

The table below lists the thermal data . A small broad endothermic peak between nominally 192 and 205°C , considered to be a thermal transition rather than a melting point.

Parameter

First Scan

Second Scan

Onset (°C)

191.8

194.4

Peak (°C)

199.3

200.8

Endset (°C)

205.3

205.1

Enthalpy (J/g)

-15.06

-7.15

 

Conclusions:
Determination of the melting temperature was performed in accordance to OECD 102. It was not possible to determine the melting temperaure, since a small broad endotherm, considered to be a thermal transistion rather than melting, was observed between approximately 192 and 205°C.
Executive summary:

Determination of the melting temperature was performed in accordance to OECD guideline 102 (1995) and EC Directive 92/69/EEC Methods A1 and A2. The thermal behavior of MI3 (dried) was assessed by Differential Scanning Calorimetry. It was not possible to determine the melting point. An endotherm onset nominally 193°C was generated, and because of its broad nature, was considered to be a thermal transition rather than a melting event.

Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003.05.12 -2003.10.24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method A.1 (Melting / Freezing Temperature)
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
yes (incl. QA statement)
Type of method:
differential scanning calorimetry
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL (X14desB30, dried)
- Appearance: cream powder
- Source and lot/batch No.of test material: QX14203119
- Expiration date of the lot/batch: June 2004
- Purity test date: 2003-06-18
- Purity: 75% w/w

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Frozen below - 10°C


Key result
Remarks on result:
not determinable
Remarks:
The melting point could not be determined.

 The table below lists the thermal data. A small broad endothermic peak between nominally 186 and 198°C , considered to be a thermal transition rather than a melting point.

Parameter

First Scan

Second Scan

Onset (°C)

185.8

185.3

Peak (°C)

193.1

192.8

Endset (°C)

198.2

197.7

Enthalpy (J/g)

-8.45

-8.40

 

Conclusions:
The melting point of X14desB30 (dried) was assessed by Differential Scanning Calorimetry. The procedure conformed to the OECD Guideline 102 (1995). No melting point was determined.
Executive summary:

The melting point of X14desB30 (dried) was assessed by Differential Scanning Calorimetry. The procedure conformed to the EC Directive 92/69/EEC Method A1 and OECD Guideline 102 (1995). An endotherm with an onset at nominally 185oC was generated, and because of its broad nature, was considered a thermal transition rather than a melting event.

No melting point was determined.

Description of key information

Data on target substance not available. Thus, read-across has been applied using data from source substances (S2, S3).

The molecular structure of the target substance is a small protein consisting of 51 amino acids have at least 48 amino acids in common with the source substances (consisting of 50-53 amino acids) and having very identical amino acid sequences.

Based on these structural similarities very similar physicochemical properties would be expected. This is further documented by the results from physicochemical guideline testing for S2 and S3, where the test results found for melting point, boiling point, flammability, self-ignition, and explosion were identical. The vapour pressure determined for S2 is extremely low but consistent to what would be expected, as a single amino acid on its own has a very low vapour pressure (below 0.4 Pa) and thus, a protein of more than 50 amino acids would have an even lower vapour pressure. Based on these data and the marginal differences in composition between the target and the source chemicals a read-across approach for physicochemical properties using data on S1, S2 and S3 is considered scientifically justified. 

For further details, please refer to read across justification document in section 13

Key value for chemical safety assessment

Melting / freezing point at 101 325 Pa:
185 °C

Additional information

The determination of the melting point for S2 (MI3) and S3 (X14desB30) was performed using DSC in accordance to OECD guideline 102 (1995) and EC Directive 92/69/EEC Methods A1. The melting point was not determinede. The observed broad endotherm in the range 192-205 °C for MI3 and > 185 °C for X14desB30

, probably representing a thermal transition rather than a melting point.

Therefore, the melting point for the target substance (Insulin human methyl ester) was estimated to be > 185 °C