4-acetyl-2-methylbenzoic acid

Water solubility

Administrative data

Endpoint:

water solubility

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:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

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

Water solubility

Water solubility 1

Key result

Water solubility:

0.96 g/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

25 °C

pH:

2.8

Water solubility 2

Key result

Water solubility:

23 g/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

25 °C

pH:

5.1

Water solubility 3

Key result

Water solubility:

190 g/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

25 °C

pH:

6.8

Water solubility 4

Key result

Water solubility:

270 g/L

Conc. based on:

test mat.

Incubation duration:

24 h

Temp.:

25 °C

pH:

9

Any other information on results incl. tables

Details on results of solubility test with pure water

Sample	W1	W3	W5	W2	W4	W6 (excluded from calculation of average)
Amount of substance (mg) dispersed in 15.0 mL of water	100.8	100.6	102.3	100.9	100.6	100.3
Number of days at 30 °C	3	2	1	3	2	1
Number of days at 20 °C	1	1	1	1	1	1
Centrifugation time (minutes)	30	30	30	30	30	30
Centrifugation speed (G value)	30000	30000	30000	48000	48000	48000
pH of clear solution	2.81	2.80	2.82	2.78	2.78	2.80
Average pH value	2.8
Water solubility (mg/L), 1st run	993.145	996.766	890.075	949.060	971.641	853.110
Water solubility (mg/L), 2nd run	997.217	997.522	896.056	952.272	969.658	848.618
Average water solubility (mg/L)	995.181	997.144	893.066	950.666	970.650	850.864
Average per G value (mg/L)	961.797			960.658
Relative standard deviation (%)	5.54			5.98
Total average (mg/L)	960
Total relative standard deviation (%)	5.9

Applicant's summary and conclusion

Conclusions:

The solubility of the substance in pure water was 0.96 g/L at 25 °C (pH 2.8). The water solubility at 25 °C increased with pH value and was 23 g/L at pH 5.1, 190 g/L at pH 6.8 and 270 g/L at pH 9.0.

Executive summary:

The water solubility of the test substance was studied under GLP to OECD TG 105, using the flask method.
For the main study, two dispersions, each containing about three times the amount of material necessary for saturation, were prepared in stainless steel centrifuge tubes in pure water (with a resistivity of >15 MΩ.cm and which had been filtered through a 0.45 μm filter). The contents were then equilibrated by continuous gentle shaking at 30.0 °C (± 0.5 °C). At the fourth day the temperature of the water bath was reduced to the test temperature of 20.0 °C (± 0.5 °C), at which temperature the test dispersions were then re-equilibrated by continuous gentle shaking for at least further twenty-four hours. Finally, the dispersions were centrifuged for forty minutes at 30000 G or 48000 G, as appropriate, in a centrifuge, thermostated at 20 °C. Afterwards, each centrifuge tube contained a clear, aqueous solution with undissolved, excess test item still present. Subsequently, an aliquot from each clear, centrifuged, saturated solution was removed and analyzed by high performance liquid chromatography (HPLC). The six samples thus prepared represent the six permutations of two different centrifugation accelerations with three different pre-equilibrium periods (1, 2 or 3 days) at 30.0 °C.
Centrifugation at different G values gave similar results, demonstrating that clear solutions had been obtained by centrifugation. Pre-equilibration for different lengths of time also gave similar results indicating that equilibrium had indeed been reached.
The pH of each saturated solution was determined following centrifugation.
A comparison of the retention times of the substance in the reference solutions with those in the sample solutions indicated that the identity of the test item had not altered during the experiment.
The main experiment in pure water indicated that the solubility of the substance would be so large that the buffer capacity of commercially available buffer solutions would not be sufficient to keep the pH value at the nominal value. Experiments were therefore undertaken in sodium hydroxide solution with the aim of preparing three saturated solutions of the substance with neutral, alkaline and acidic pH values.
For the experiment at neutral, basic and acidic pH values, several aliquots of test substance were added to a 15 mL centrifuge tube containing 5.0 mL of 1, 2 or 0.1 M sodium hydroxide until a suitable pH value was reached, which was then adjusted by addition of smaller volumes of 1, 2 or 0.1 M sodium hydroxide solution. The final dispersion was equilibrated by continuous gentle shaking at 20.0 ± 0.5 °C for at least twenty-four hours, then centrifuged for 15 minutes at 3000 G, thermostated at 20 °C. The centrifuge tube contained a clear, aqueous solution with undissolved, excess test item still present in the bottom. An aliquot from the clear, centrifuged, saturated solution was removed and analyzed by high performance liquid chromatography (HPLC). The pH of the clear centrifuged solution was measured for each condition tested.
The water solubility at 25 °C was determined to be 0.96 g/L in pure water (pH 2.8), 23 g/L in acidic conditions (pH 5.1), 190 g/L in neutral conditions (pH 6.8) and 270 g/L in basic conditions.