Insulin DesB30

Vapour pressure

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

vapour pressure

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000.03.16 – 2000.09.18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method A.4 (Vapour Pressure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

effusion method: Knudsen cell

Remarks:

The MI3(solution) was highly hydroscopic and had unknown thermal (melting) characteristics, why an initial thermal analysis was performed by differential scanning calorimetry.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL (MI3 solution)
- Appearance: brown paste
- 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

Temp.:

< 54 °C

Remarks on result:

not determinable because of methodological limitations

Remarks:

At 54oC the vapour pressure of MI3 was 10-fold lower than the lowest detection limit of the apparatus.

Key result

Temp.:

ca. 20 °C

Vapour pressure:

<= 0 Pa

Remarks on result:

other: calculated

Remarks:

In cases where the test substance stability places constrains on the maximum temperature a, a highest estimate of the vapour pressure is made.

Transition / decomposition:

no

Remarks:

Reversible chemical change

Transition temp.:

> 58 - ca. 61 °C

DSC analysis revealed no endotherm due to water melting (around 0^oC), nor any chemical change around 58^oC. However, the thermograms were broadly similar above that temperature, and therefore no significant changes had occurred to the samples during the vapour pressure testing.

The measured weight losses were to small for reliable vapour pressure calculations to be made and to be measured by the system. At 54^oC the vapour pressure of MI3 was 10-fold lower than the lowest detection limit of the apparatus (1x10^-5Pa).

At temperatures at above 58^oC there is a chemical change in MI3. Hence, extrapolation back to 20 or 25^oC using the Ln(vapour pressure) versus 1/K relationship cannot be made above this temperature since it only holds true over one chemical phase.

In cases where the test substance stability places constrains on the maximum temperature a, a highest estimate of the vapour pressure is made. This is performed by assuming a vapour pressure of 1x10^-5Pa at the highest temperature measured , and applying a slope of -2000 to the Ln (vapour pressure) versus 1/temperature (K) relationship. This figure is based on experimental evidence from many years of testing in different laboratories. A slope less negative than this has never been reported, typically the slopes are between – 18,000 and -8,000.

The calculated vapour pressure at 25^oC will be 2.2 x 10^-6Pa, and at 20^oC will be 4.9 x 10^-6Pa. from the measuremets it is evident that the vapour pressure will not exceed 4.9 x 10^-6Pa at 20^oC or 25^oC.

Conclusions:

The vapour pressure of MI3 (solution) was determined by DSC and Knudsen cell effusion method. The procedure conformed with EC Directive 92/69/EEC Method A4, and OECD Guideline 104 (1995). The vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20 oC or 25 oC.

Executive summary:

The vapour pressure of MI3 (solution) was determined by DSC and Knudsen cell effusion method. The procedure conformed with EC Directive 92/69/EEC Method A4, and OECD Guideline 104 (1995). The vapour pressure was below sensitivity of the apparatus and could not be determined experimentally. At temperatures at 58^oC there is a chemical change in the MI3. Hence, extrapolation back to 20 or 25^oC using the Ln(vapour pressure) versus 1/K relationship cannot be made above this temperature since it only holds true over one chemical phase. However, from calculations, it was estimated that MI3 will not exceed 4.9 x 10^-6Pa at 20^oC or 25^oC.

Reference 2

Endpoint:

vapour pressure

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Remarks on result:

not determinable because of methodological limitations

Remarks:

the vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20 oC or 25 oC

Conclusions:

Data on target substance not available. Thus, read-across has been applied using data from source substance (S2).
Based on the structural similarities very similar physical chemical properties would be expected. This is further documented by the results from physical chemical guideline testing for S2 and S3 where the test results found for melting point, boiling point, flammability, self-ignition, and explosion were identical.
The determination of the vapour pressure for S2 (MI3) was performed using DSC in accordance to OECD guideline 104 (1995) and EC Directive 92/69/EEC Methods A4. The vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20oC or 25oC. Therefore, the same conclusion for the target substance (Insulin DesB30) applies justified by the read-across hypothesis.

Executive summary:

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

Based on the structural similarities very similar physical chemical properties would be expected. This is further documented by the results from physical chemical guideline testing for S2 and S3 where the test results found for melting point, boiling point, flammability, self-ignition, and explosion were identical.

 

Specifically, for S2 the vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20 oC or 25 oC.

The determination of the vapour pressure for S2 (MI3) was performed using DSC in accordance to OECD guideline 104 (1995) and EC Directive 92/69/EEC Methods A4. The vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20^oC or 25^oC. Therefore, the same conclusion for the target substance (Insulin DesB30) applies justified by the read-across hypothesis.

Description of key information

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

 

As can be seen from the molecular structure (see attached document in section 13) the target substance is a small protein consisting of 50 amino acids have at least 49 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 physical chemical properties would be expected. This is further documented by the results from physical chemical guideline testing for S2 and S3 where the test results found for melting point, boiling point, flammability, self-ignition, and explosion were identical.

 

Specifically, for S2 the vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20 oC or 25 oC.

Key value for chemical safety assessment

Vapour pressure:

0 Pa

at the temperature of:

25 °C

Additional information

The determination of the vapour pressure for S2 (MI3) was performed using DSC in accordance to OECD guideline 104 (1995) and EC Directive 92/69/EEC Methods A4. The vapour pressure was below sensitivity of the apparatus, but calculated not to exceed 4.9 x 10-6 Pa at 20 ^oC or 25 ^oC. Therefore, the same conclusion for the target substance (Insulin DesB30) applies justified by the read-across hypothesis.