4-acetyl-2-methylbenzoic acid

Dissociation constant

Administrative data

Endpoint:

dissociation constant

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 112 (Dissociation Constants in Water)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-acetyl-2-methylbenzoic acid

EC Number:

856-079-4

Cas Number:

55860-35-0

Molecular formula:

C10H10O3

IUPAC Name:

4-acetyl-2-methylbenzoic acid

Test material form:

solid: particulate/powder

Results and discussion

Dissociating properties:

yes

Dissociation constant

No.:

#1

pKa:

3.03

Temp.:

20 °C

Any other information on results incl. tables

On analysis of the sample solutions, two sample solutions, nominal pH 2.8 replicate A and nominal pH 3.0 replicate B, demonstrated an erroneous rising baseline on spectrophotometric analysis. Therefore, although their spectral profile were consistent with the relevant remaining duplicate samples under those pH conditions, as the absorbance did not start from a zero value baseline, the resulting absorbance values were not considered valid or appropriate for use in further calculations. In addition to this, on calculation of the dissociation constant values from the remaining 19 intermediate pH value sample solutions, with the exception of a single sample solution, all values of pKa were within the range 3.00 to 3.06. On applying statistical analysis to the dissociation constant results, nominal pH 3.6 replicate A was identified as a statistically significant outlier using Grubbs’ test, P = 0.05 and consequently excluded from the overall mean value calculated. The exclusion of these three data points was concluded not to impact on the integrity or validity of the test, as the overall result was still calculated from 18 individual, intermediate sample solutions, presenting highly consistent results, such that a standard deviation value 0.02 was obtained.

Applicant's summary and conclusion

Conclusions:

The dissociation constant of the test item in water has been determined to be 3.03 at a temperature of 20 ± 1 °C.

Executive summary:

The dissociation of the test substance in water was studied under GLP to OECD TG 112 using a spectrophotometric method. The molecular form spectrum was determined in a matrix of 1.0 M hydrochloric acid (pH 1.0). Intermediate pH sample solutions were prepared from citrate buffer solutions that was adjusted to a series of nominal pH values between 2.4 and 3.6, using hydrochloric acid and sodium hydroxide solutions. The ionised form spetrum was determined using a pH 9 borate buffer solution. Sample solutions were prepared by dissolving an aliquot of about 0.1 g in 50 mL acetonitrile. An aliquot of 1 mL of this stock solution was diluted to a total of 100 mL using the previously described media. The actual concentration of each sample solution was 20.2 mg/L. The pH of each sample solution was recorded. Each sample solution was then analysed with a spectrophotometer, with quantification at 283 nm. The intermediate pH range of the solutions used for quantification of the dissociation constant (pH 2.43 to 3.56) represented a range from 35.4 to 62.9% ionisation of the test substance in solution, based on the finally determined pKa value of 3.03 at 20 °C.