3-ethoxy-4-hydroxybenzaldehyde

Dissociation constant

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 22 DEC 2016 to 16 FEB 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2015-07-28

Dissociating properties:

yes

pKa:

7.51

Remarks on result:

other: Temperature is between 19.8°C and 21°C

Minimal temperature during the test phase: 19.8 °C

Maximal temperature during the test phase: 21.0 °C

The values of the pH during the three titrations were between 6.17 and 10.53.

The pH curves show the equivalence point found during the titrations.

The tables summarise the results on the 10 most representative incremental additions before the equivalence point.

First determination

CNaOH(mol/L)	0.00508
w NaOH(g)	1.02402
Purity of NaOH(%)	99.3
Molar mass(g/mol)	40.0
Volume(mL)	250
Dilution factor	20
w test item(g)	0.08309

VNaOH (mL)	pH	pKa	Mean pKa	SD	RSD (%)
5	7.08	7.55	7.51	0.022	0.30
6	7.18	7.54
7	7.27	7.53
8	7.35	7.51
9	7.44	7.51
10	7.52	7.50
11	7.60	7.50
12	7.69	7.49
13	7.78	7.49
14	7.87	7.48

Second determination

CNaOH(mol/L)	0.00508
w NaOH(g)	1.02402
Purity of NaOH(%)	99.3
Molar mass(g/mol)	40.0
Volume(mL)	250
Dilution factor	20
w test item(g)	0.08112

VNaOH (mL)	pH	pKa	Mean pKa	SD	RSD
5	7.10	7.55	7.50	0.033	0.45
6	7.19	7.53
7	7.28	7.52
8	7.36	7.51
9	7.44	7.49
10	7.53	7.49
11	7.61	7.48
12	7.69	7.47
13	7.78	7.46
14	7.88	7.45

 

The mean average of the pKa for the three determinations was equal to 7.51.

The mean Relative Standard Deviation for the tree determinations was equal to 0.35%.

The results obtained during the three determinations were less than ± 0.1 log units.

Conclusions:

Under the conditions of the study, the pKa of the test material is equal to 7.51 between 19.8 °C and 21 °C.

Executive summary:

The determination of the dissociation constant (pKa) of the test material was studied in compliance with OECD TG No. 112 using the titration method.

During this study, it was shown that the value of the water dissociation constant of 3-ethoxy-4-hydroxybenzaldehyde (ethylvanillin) [121-32-4] is equal to 7.51 between 19.8 °C and 21 °C.

Reference 2

Endpoint:

dissociation constant

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Result from ECHA recommended QSAR model.

Justification for type of information:

QSAR prediction

Qualifier:

no guideline required

Principles of method if other than guideline:

QSAR

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

-5.01

Remarks on result:

other: corresponds to ionisation of the aldehyde (calculated) / no data on T°C

No.:

#2

pKa:

7.84

Remarks on result:

other: corresponds to ionisation of the OH (calculated) / no data on T°C

No more data on results.

Reference 3

Endpoint:

dissociation constant

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The value is not an experimental result, however the available elements justify the validity of the estimated value. The QSAR model SPARC was validated for compounds having one until 8 ionization sites and for all organic compounds except : covalent hydrates, tautomers, carbon acid reaction center where the perturbations for this group are very large and quaternary amines. Ethylvanillin is not part of this kind of compounds and has one possible ionization site implying that SPARC model is validated for this test item.

Justification for type of information:

QSAR prediction

Principles of method if other than guideline:

QSAR estimation

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

7.84

Temp.:

25 °C

Predicted value (model result): see the attach illustration

Predicted value (comments): No comments

Input for prediction: SMILES

Table of results: pKa is function of pH:

pH	Species 1	Species 2
0	1	0
1	1	0
2	1	0
3	1	0
4	1	0
4.8	0.999	0.001
5	0.999	0.001
5.2	0.999	0.001
5.4	0.998	0.002
5.6	0.996	0.004
5.8	0.994	0.006
6	0.991	0.009
6.2	0.986	0.014
6.4	0.977	0.023
6.6	0.965	0.035
6.8	0.945	0.055
7	0.916	0.084
7.2	0.873	0.127
7.4	0.812	0.188
7.6	0.732	0.268
7.8	0.632	0.368
8	0.52	0.48
8.2	0.406	0.594
8.4	0.302	0.698
8.6	0.214	0.786
8.8	0.147	0.853
9	0.098	0.902
9.2	0.064	0.936
9.4	0.041	0.959
9.6	0.027	0.973
9.8	0.017	0.983
10	0.011	0.989
10.2	0.007	0.993
10.4	0.004	0.996
10.6	0.003	0.997
10.8	0.002	0.998
11	0.001	0.999
12	0	1
13	0	1
14	0	1

Conclusions:

The model has been run in November 2015 for this substance.
Ethylvanilline has a pka value of 7.84.

Executive summary:

The dissociation constant was predicted using a reliable QSAR model: SPARC (SPARC Automated Reasoning Calculator v5.1, March 2013). After confirmation that ethylvanillinfalls into the model applicability domain, it was shown that the test item has a pka value of 7.84.

Description of key information

Dissociation constant = 7.51 between 19.8°C and 21°C.

Key value for chemical safety assessment

pKa at 20°C:

7.51

Additional information

One experimental GLP study (Défitraces, 2017), OECD 112 compliant, was available and was selected as key study. The dissociation constant value in this study is 7.51 between 19.8°C and 21°C. The study was with reliability 1 according to Klimisch scale.

Two other data issue from QSAR model were selected as supporting studies and were with reliability 2.