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Dissociation constant

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Reference
Endpoint:
dissociation constant
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 112 (Dissociation Constants in Water)
Deviations:
no
GLP compliance:
not specified
Dissociating properties:
not determined
Remarks on result:
not determinable
Remarks:
Due to test material being insoluble in water and only sparingly soluble in one water-miscible solvent (THF), the determination of the dissociation constant by OECD 112 was not possible.

- All three methods listed in OECD 112 require the chemical substance to be dissolved in water. The expected water solubility of the test material is <1 mg/mL, therefore the test material is only sparingly soluble in water. In cases where the test material is only sparingly soluble in water, OECD 112 allows for the use of a small amount of water-miscible solvent to dissolve the test material prior to addition to water. The final concentration should not exceed the lesser of 0.01 M or half the saturation concentration.

- The only water-miscible solvent in which the test material was observed to be soluble was THF, and only to a maximum solubility of ~1 mg/mL. A test solution with a target test material concentration of 0.1 mg/mL was therefore prepared from a 1 mg/mL solution of the test material in THF by 10-fold dilution into water. The resulting solution was composed of 10% THF, beyond what may be considered a small amount (1%) of water-miscible solvent by OECD 112. Additionally, small amounts of solid precipitate could be observed, indicating that the target concentration of 0.1 mg/mL was well in excess of half the saturation concentration.

Conclusions:
Due to the test material being insoluble in water and only sparingly soluble in one water-miscible solvent (THF), the determination of the dissociation constant by OECD 112 was not possible. For this reason, a waiver from OECD 112 testing is requested.
Executive summary:

The test material, is a pale yellow solid. During preliminary evaluation of solvent solubility, the test material was found to be insoluble in water and most common organic solvents, with the exception of chloroform and tetrahydrofuran (THF).

OECD 112 lists three methods for determining the dissociation constant of a compound in water (titration, spectrophotometric, conductometric), all of which require the chemical substance to be dissolved in water. In cases where the test material is only sparingly soluble in water, the use of a small amount of water-miscible solvent is permitted to dissolve the test material prior to addition to water. The final concentration should not exceed the lesser of 0.01 M or half the saturation concentration.

The test material was not observed to be soluble in water at a target concentration of 1 mg/mL. The only water-miscible solvent in which the test material is soluble is THF, and only to ~1 mg/mL. A test solution with a target test material concentration of 0.1 mg/mL was prepared from a 1 mg/mL solution of the test material in THF by 10-fold dilution into water. The resulting solution was 10% THF, beyond what may be considered a small amount (1%) of water-miscible solvent by OECD 112. Additionally, small amounts of solid precipitate could be observed, indicating that the target concentration of 0.1 mg/mL was well in excess of half the saturation concentration.

Due to the lack of solubility of the test material in water, a waiver from OECD 112 testing is requested.

Description of key information

Due to the test material being insoluble in water and only sparingly soluble in one water-miscible solvent (THF), the determination of the dissociation constant by OECD 112 was not possible. For this reason, a waiver from OECD 112 testing is requested.

Key value for chemical safety assessment

Additional information

The test material, is a pale yellow solid. During preliminary evaluation of solvent solubility, the test material was found to be insoluble in water and most common organic solvents, with the exception of chloroform and tetrahydrofuran (THF).

OECD 112 lists three methods for determining the dissociation constant of a compound in water (titration, spectrophotometric, conductometric), all of which require the chemical substance to be dissolved in water. In cases where the test material is only sparingly soluble in water, the use of a small amount of water-miscible solvent is permitted to dissolve the test material prior to addition to water. The final concentration should not exceed the lesser of 0.01 M or half the saturation concentration.

The test material was not observed to be soluble in water at a target concentration of 1 mg/mL. The only water-miscible solvent in which the test material is soluble is THF, and only to ~1 mg/mL. A test solution with a target test material concentration of 0.1 mg/mL was prepared from a 1 mg/mL solution of the test material in THF by 10-fold dilution into water. The resulting solution was 10% THF, beyond what may be considered a small amount (1%) of water-miscible solvent by OECD 112. Additionally, small amounts of solid precipitate could be observed, indicating that the target concentration of 0.1 mg/mL was well in excess of half the saturation concentration.

Due to the lack of solubility of the test material in water, a waiver from OECD 112 testing is requested.