Registration Dossier

Administrative data

Endpoint:
vapour pressure
Type of information:
(Q)SAR
Adequacy of study:
key study
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:
1. SOFTWARE
EPIWIN software by US-EPA

2. MODEL (incl. version number)
MPBPWIN v1.43

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(O)c(c(O)c(cc1)C)c1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- The complete test sets of experimental data for (melting point, boiling point and) vapour pressure can be downloaded via the Internet at: http://esc.syrres.com/interkow/EpiSuiteData.htm

5. APPLICABILITY DOMAIN
Estimation accuracy: The accuracy of MPBPWIN's "suggested" VP estimate was tested on a dataset of 3037 compounds with known, experimental VP values between 15 and 30 deg C (the vast majority at 25 or 20 deg C).  The experimental values were taken from the PHYSPROP Database that is part of the EPI Suite. For this test, the CAS numbers were run through MPBPWIN as a standard batch-mode run (using the default VP estimation temperature of 25 deg C) and the batch estimates were compared to PHYSPROP's experimental VP. The plot clearly indicates that the estimation error increases as the vapour pressure (both experimental and estimated) decreases, especially when the vapour pressure decreases below 1x10-6 mm Hg (0.0001333 Pa).
The estimation methodology uses the normal boil point to estimate the liquid-phase vapour pressure. For solids, the melting point is required to convert the liquid-phase vapour pressure to the solid-phase vapour pressure. VP estimation error can be introduced by:
(1) poor Boiling Point estimates or values
(2) poor Melting Point estimates or values (for solids)

The 3037 compound test set contains 1642 compounds with available experimental Boiling points and Melting points. For this subset of compounds, the estimation accuracy statistics are (based on log VP):

  number = 1642
  r2 = 0.949
  std deviation = 0.59
  avg deviation = 0.32

These statistics clearly indicate that VP estimates are more accurate with experimental BP and MP data. Further, the plot clearly indicates that the estimation error increases as the vapour pressure (both experimental and estimated) decreases, especially when the vapour pressure decreases below 1x10-6 mm Hg (0.0001333 Pascals).

Estimation domain: The intended application domain is organic chemicals. Inorganic and organometallic chemicals generally are outside the domain.
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that property estimates are less accurate for compounds outside the Molecular Weight range ca. (ca. 16-943) of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.
The complete training sets for MPBPWIN's estimation methodology are not available. Therefore, describing a precise estimation domain for this methodology is not possible. The current applicability of the MPBPWIN methodology is best described by its accuracy in predicting vapour pressure as described above in the accuracy section.

6. ADEQUACY OF THE RESULT
The result calculated for the organic substance hydroxytoluic acid is reasonable and can be used without any further testing:
- The experimentally determined melting point of 166°C and boiling point of 246 °C has been used for calculation, which reduces the VP estimation error.
- The result is in the magnitude with a relatively low estimation error (estimation error increases as the vapour pressure decreases, especially when the vapour pressure decreases below 0.0001333 Pa).
- With a molecular weight of 152.1 the substance lies within the weight range of the training set compounds, does not have more instances of a given fragment than the maximum for all training set compounds and the functional groups are represented in the training sets (fragment coefficients were developed).

Data source

Reference
Title:
EPI Suite Version 4.10
Year:
2012
Bibliographic source:
MPBPWIN - three separate methods for VP: Antoine method (1990), modified Grain method (1985) and Mackay method (1985)

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: REACH guidance on QSARs Chapter R.6
Version / remarks:
May 2008
Principles of method if other than guideline:
Vapour Pressure is estimated by three methods; all three methods use the boiling point. The first is the Antoine method (see Chapter 14 of W.J. Lyman's book "Handbook of Chemical Property Estimation Methods", Washington, DC: American Chemical Society, 1990). The second is the modified Grain method (see page 31 of Neely and Blau's Environmental Exposure from Chemicals, Volume I, CRC Press, 1985). The third is the Mackay method (see page 31-2 of Neely and Blau's Environmental Exposure from Chemicals, Volume I, CRC Press, 1985).
GLP compliance:
no
Type of method:
other: QSAR calculation

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SMILES: O=C(O)c(c(O)c(cc1)C)c1

Results and discussion

Vapour pressureopen allclose all
Key result
Temp.:
25 °C
Vapour pressure:
0.065 Pa
Remarks on result:
other: Modified Grain Method (MPBPWIN v1.43) - most relevant for solids
Temp.:
25 °C
Vapour pressure:
0.07 Pa
Remarks on result:
other: Antoine Method (MPBPWIN v1.43)
Temp.:
25 °C
Vapour pressure:
0.307 Pa
Remarks on result:
other: Mackay Method (MPBPWIN v1.43)

Applicant's summary and conclusion

Conclusions:
The study report describes a scientifically accepted calculation method for the vapour pressure using the US-EPA software MPBPWIN v1.43.No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable. The result is adequate for the regulatory purpose.
Executive summary:

The vapour pressure of the substance hydroxytoluic acid was determined by the computer program MPBPWIN v1.43 (EPIWIN software) by US-EPA (2012). The program calculates the vapour pressure according to three different methods: Antoine, Modified Grain and Mackay. For solids, the value of the Modified Grain method is the most relevant.

The experimentally determined melting point of 166°C and boiling point of 246 °C have been used for calculation of the vapour pressure at 25 °C.

The Antoine Method gives a result of 0.07 Pa, the Mackay Method results in a vapour pressure of 0.307 Pa and according to the Modified Grain Method the substance has a vapour pressure of 0.0654 Pa (selected VP for solids).

The substance lies in the domain of the estimation model and the estimation errors are decreased by different factors (experimental melting & boiling point, magnitude of result). The result is adequate for the regulatory purpose and no further testing is required.