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Physical & Chemical properties

Water solubility

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Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The data are considered to be reliable but with restrictions due to the non-standard methodology, and some lacking in the reported experimental detail. The smooth solubility-temperature curve indicates that the data are internally consistent and any uncertainty is likely to be systematic in nature. Uncertainty at each temperature quantified (average 2.5%) and lower than the guideline requirement for replicates (15%). Somewhat limited experimental detail and no explicit information on replicates, or equilibration time and demonstration that saturation was acheived (although stated). The analytical method for concentration determination was not substance specific. pH of the solutions not reported.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
Flask method
Deviations:
yes
Remarks:
Non-specific analytical method.
Principles of method if other than guideline:
The concentration was determined from saturated solutions of methanol, acetonitrile, acetic acid, acetone, water and ethyl acetate by a gravimetric method (evaporation of the solvent to constant weight). Saturation was achieved by two methods: dissolution and by cooling a saturated solution.
GLP compliance:
no
Type of method:
flask method
Water solubility:
1 220 mg/L
Temp.:
10 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±20
Water solubility:
1 560 mg/L
Temp.:
15 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±40
Water solubility:
1 980 mg/L
Temp.:
20 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±15
Water solubility:
2 410 mg/L
Temp.:
25 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±50
Water solubility:
2 960 mg/L
Temp.:
30 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±80
Water solubility:
3 700 mg/L
Temp.:
35 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±300
Water solubility:
4 490 mg/L
Temp.:
40 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±20
Water solubility:
5 700 mg/L
Temp.:
45 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±200
Water solubility:
7 320 mg/L
Temp.:
50 °C
pH:
> 4.5 - < 5.5
Remarks on result:
other: ±60
Details on results:
Solubility was reported in mole fraction and converted to mg/L by the registrant. Density of water at the relevant temperature was taken from the CRC Handbook of Chemistry and Physics, 69th Edition, 1989, Ed. Weast., CRC Press. pH added by Registrant based on data by Brodie, D.C. et al, J. Am. Pharm. Assoc., 1951, 40(8), 414-415, and Edwards, L.J., Trans. Faraday Soc., 1953, 49, 234-236 for saturated solutions of salicylamide.

Crystal morphology obtained from water was as needles.

Solubility data were fitted to the equation ln x = A(K/T)^2 + B(K/T) + C where A=12.693x10 -5, B=-12.437x10 -3, C=19.3719, x is the mole fraction, and for the fit R2>0.998.

Conclusions:
Interpretation of results (migrated information): soluble (1000-10000 mg/L)
The data are considered to be reliable but with restrictions due to the non-standard methodology, and some lacking in the reported experimental detail. However, the smooth solubility-temperature curve indicates that the data are internally consistent and any uncertainty is likely to be systematic in nature. The uncertainty in the solubility at each temperature was indicated, with an average of 2.5% (based on 95% C.I.) between replicates. This is significantly lower than the 15% required by the OECD Guideline 105.
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-guideline method. Purity of the sample not addressed. No information on the method used, or equilibration time. Overall, very limited experimental details.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
No information on the method used to determine the solubility was reported. The concentrations were determined at each temperature using UV spectroscopy and the experimentally derived pH-dependant extinction coefficients.
GLP compliance:
no
Type of method:
other: no data
Water solubility:
2 000 mg/L
Temp.:
20 °C
pH:
>= 4.5 - <= 5
Water solubility:
2 440 mg/L
Temp.:
25 °C
pH:
>= 4.5 - <= 5
Water solubility:
2 960 mg/L
Temp.:
30 °C
pH:
>= 4.5 - <= 5
Water solubility:
3 800 mg/L
Temp.:
35 °C
pH:
>= 4.5 - <= 5
Water solubility:
4 680 mg/L
Temp.:
40 °C
pH:
>= 4.5 - <= 5
Water solubility:
7 320 mg/L
Temp.:
50 °C
pH:
>= 4.5 - <= 5
Details on results:
Solubility data were derived from graphical results (Figure 2) by the Registrant. Temperature dependant data were fit to the curve: LogC=6.386-1788/T, where C is saturated concentration and T is temperature in Kelvin.
Conclusions:
Interpretation of results (migrated information): soluble (1000-10000 mg/L)
The data are not considered to be reliable due to the lack of reported experimental methodology and detail. However, the smooth solubility-temperature curve indicates that the data are internally consistent and any uncertainty is likely to be systematic in nature.

Description of key information

2000 mg/L, 20 °C, Edwards 1953
1980 ±15 mg/L, 20 °C, OECD 105, modified flask method, Nordström 2006

Key value for chemical safety assessment

Water solubility:
1 990 mg/L
at the temperature of:
20 °C

Additional information

The data from Gloria (1963) is discarded, as the solubility-temperature curve clearly shows problems with the experimental method.

The data from Edwards (1953), Nordström (2006) and Shah (1990) are in excellent agreement, although the latter only gives solubility at one temperature. The average uncertainty in the solubility reported by Nordstöm was 2.5% (95% C.I.), with a maximum of 8% (at 35 °C). Plots of both solubility-temperature curves show the expected smooth increase in solubility with increasing temperature, and are coincident to within ca. 2% at common temperatures. The data sets, which are produced by different methods and from independent samples, are thus consistent and considered to be reliable and adequate. The average was taken at 20 °C, 1990mg/L (±20 mg/L, 95% C.I.), and is taken forward for risk assessment, classification and labelling, based on the weight-of-evidence in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.2.