Butyl hydrogen maleate

Dissociation constant

Administrative data

Endpoint:

dissociation constant

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
ACD/I-Lab Web Service

2. MODEL (incl. version number)
(I-Lab 2.0).

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCCOC(=O)\C=C/C(=O)O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
No data

5. APPLICABILITY DOMAIN
No data

6. ADEQUACY OF THE RESULT
The predicted dissociation constant was 3.34 ± 0.10 using ACD/I-Lab Web Service (I-Lab 2.0). In the partition coefficient study, the mobile phase was adjusted to pH 2.2 so the test item was tested in a predominantly non-ionized form.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 May 2012 and 13 August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

1.39

Temp.:

30 °C

pH:

2.2

Details on results:

Preliminary estimate
The log10 Pow was calculated to be: 2.40
The full KOWWIN calculation is presented in Appendix 1 (Attachment 2 - KOWWIN calculation).
Definitive test
Typical Chromatography can be found in Attachment 3 - Typical Chromatography.

Calibration

The retention times of the dead time and the retention times, capacity factors (k'-) and log₁₀ P_ow values for the reference standards are shown in the following tables:

Table 1.

Dead Time	Retention Time (mins)		Mean Retention Time (mins)
	Injection 1	Injection 2
Thiourea	1.613	1.618	1.616

Table 2.

Standard	Retention Time (mins)		Mean Retention Time (mins)	Capacity Factor (k’)	Log10 k’	Log10Pow
	Injection 1	Injection 2
2-Butanone	2.240	2.240	2.240	0.386	-0.413	0.3
Benzyl alcohol	2.877	2.877	2.877	0.78	-0.108	1.1
Benzonitrile	3.411	3.411	3.411	1.111	4.58 x 10^-2	1.6
Benzene	7.293	7.293	7.293	3.514	0.546	2.1
Toluene	12.770	12.765	12.767	6.902	0.839	2.7
Naphthalene	19.835	19.835	19.835	11.277	1.05	3.6
Phenanthrene	58.669	58.669	58.669	35.313	1.55	4.5

Partition coefficient of sample

The retention times, capacity factor and log₁₀ P_ow value determined for the sample are shown in the following table:

Table 3.

Injection	Retention Time (mins)	Capacity Factor (k)	Log10K’	Log10Pow
1	3.562	1.21	8.08 x 10^-2	1.39
2	3.562	1.21	8.08 x 10^-2	1.39

Mean log₁₀ P_ow: 1.39

Partition coefficient: 24.4

Conclusions:

The partition coefficient of the test item has been determined to be 24.4, log10 Pow 1.39.

Executive summary:

An investigation was carried out to assess the partition coefficient of the test material, using the HPLC method, designed to be compatible with Method A8 Partition Coefficient of Commission Regulation (EC) No 440/2008 of 30 May 2008 and Method 117 of the OECD Guidelines for Testing of Chemicals, 13 April 2004.

The partition coefficient of the test item has been determined to be 24.4, log₁₀ Pow 1.39.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

the dissociation constant was predicted using ACD/I-Lab Web Service (I-Lab 2.0).

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Butyl hydrogen maleate

EC Number:

213-116-3

EC Name:

Butyl hydrogen maleate

Cas Number:

925-21-3

Molecular formula:

C8H12O4

IUPAC Name:

(2Z)-4-butoxy-4-oxobut-2-enoic acid

Test material form:

other: liquid

Details on test material:

Description, Identification and Storage Conditions
Sponsor's identification : Butyl Hydrogen Maleate
Description : pale yellow liquid
Lot number : 120224
Purity : ≥95%
Date received : 20 March 2012
Expiry date : 30 March 2013
Storage conditions : room temperature in the dark

Results and discussion

Dissociating properties:

yes

Dissociation constant

No.:

#1

pKa:

3.34

Remarks on result:

other: The predicted dissociation constant was 3.34 ± 0.10 using ACD/I-Lab Web Service (I-Lab 2.0).

Applicant's summary and conclusion

Conclusions:

The predicted dissociation constant was 3.34 ± 0.10 using ACD/I-Lab Web Service (I-Lab 2.0).