Reaction mass of methyl 2-[[(E)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and methyl 2-[[(Z)-(2,4-dimethylcyclohex-3-en-1-ylidene)methyl]amino]benzoate and oxydipropanol

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met with acceptable deviations.

Reason / purpose for cross-reference:

other:

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

yes

Remarks:

15% variability between 24 to 72 hour measurement was ignored, not considered a significant deviation due to clear test item degradation during the study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

yes

Remarks:

see above

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

Deviations:

yes

Remarks:

see above

Principles of method if other than guideline:

Determination of the water solubility of the test item employing the flask method with slow stirring approach. The decision of the slow stirring method was made due to the test item properties. The test guideline was consistent with OECD Guideline 105 (water solubility) modified according to Letinski et al ., “Slow-stir water solubility measurements of selected alcohols and diesters”, Chemosphere, 48, 257 – 265); 2002. To avoid intensive mixing of the test substance with the water phase and slow-stirring at a stirring speed of ≤100 rpm was employed. Two different test item loadings were utilised.

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: September 2015; signature: November 2015

Type of method:

flask method

Water solubility:

16.4 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

30 mg/L

Temp.:

20 °C

pH:

8.2

Remarks on result:

other: stirred at ≤100 rpm ; 24 hours

Water solubility:

16.7 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

30 mg/L

Temp.:

20 °C

pH:

8.4

Remarks on result:

other: stirred at ≤100 rpm ; 48 hours

Water solubility:

15.8 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

30 mg/L

Temp.:

20 °C

pH:

8.8

Remarks on result:

other: stirred at ≤100 rpm ; 72 hours

Water solubility:

79 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

300 mg/L

Temp.:

20 °C

pH:

7.8

Remarks on result:

other: stirred at ≤100 rpm ; 24 hours

Water solubility:

63 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

300 mg/L

Temp.:

20 °C

pH:

7.9

Remarks on result:

other: stirred at ≤100 rpm ; 48 hours

Water solubility:

46.2 mg/L

Conc. based on:

test mat.

Loading of aqueous phase:

300 mg/L

Temp.:

20 °C

pH:

7.9

Remarks on result:

other: stirred at ≤100 rpm ; 72 hours

Preliminary test:

Not applicable.

 

Definitive test:

1. Complete disappearance of chromatograph peak 2 occurred at both loading rates within the period of the test (24 to 72 hours) under the conditions of the study. Therefore the water solubility of the test item at 20°C is estimated on the basis of chromatograph peak 1. It was estimated to be 16.4 mg/L at and initial loading rate 30 mg/L and 63 mg/L at an initial loading rate of 300 mg/L.

2. The maximum difference (MD) of the concentrations determined in the 24, 48 and 72 hour test samples for the initial loading rate 30 mg/L was ≤ 15%. Based on this, the water solubility of the test item is given as the mean value of the analysed concentrations.

3. The maximum difference (MD) of the concentrations determined in the 24, 48 and 72 hour test samples for the initial loading rate 300 mg/L was much higher than 15%. However due to the decrease in concentration and the complex nature of the test item the deviation is accepted and the water solubility of the test item is given as the mean value of the analysed concentrations.

Conclusions:

Interpretation of results: slightly soluble (0.1-100 mg/L)
The test item water solubility was determined to be between:
16.4 mg/L at a loading rate of 30 mg/L of solution at 20.0 °C and pH 8.8
63.0 mg/L at a loading rate of 300 mg/L of solution at 20.0 °C and pH 7.8.
There was clear evidence of hydrolytic instability of the test item over a period of 72 hours.

Executive summary:

Flask Method, OECD TG 105, 2016: The water solubility of the substance was determined using the slow stirring flask method according to OECD TG 105 and EU Method A.6 under GLP. The test item water solubility was determined to be between two loading rates. Complete disappearance of chromatograph peak 2 occurred at both loading rates within the period of the test (24 to 72 hours) under the conditions of the study. Therefore the water solubility of the test item at 20°C is estimated on the basis of chromatograph peak 1. It was estimated to be 16.4 mg/L at and initial loading rate 30 mg/L and 63 mg/L at an initial loading rate of 300 mg/L. The pH of the aqueous samples was 7.8 - 8.8. Applicant assessment indicates there was clear hydrolytic degradation at (pH 7 to pH 8) during the conduct of the study. With potentially faster degradation at lower concentration of test item. The degradation rate occurred within a period of 24 to 72 hours. Within the lower loading rate all water solubility concentrations were based upon chromatograph peak 1. Which was observed to remain during the study. Within the higher loading rate the water solubility was based upon chromatograph peak 1 and 2. The latter chromatograph peak 2 completely disappeared during the period of the test (< 72 hours).

 

Reference 2

Endpoint:

water solubility

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with section 2 of REACH Regulation (EC) No. 1907/2006 Annex XI: further study of water solubility does not need to be completed as testing is not technically possible or scientifically needed. The available guidelines (OECD TG 105 and EU Method A.6) are typically applicable to ‘the solubility in water of essentially pure substances which are stable in water’. The substance is hydrolytically unstable and therefore further testing of the substance by the flask method is precluded. The applicant adapts the information requirement by providing an endpoint study record for (1) Water Solubility (up to 72hours) and (2) Hydrolysis as a function of pH. Furthermore no effects were observed in ecotoxicological testing up to WAF loading rate of 100 mg/L. There is adequate information available for classification and risk assessment. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.7.4, December 2016) further testing does not need to be conducted.

Description of key information

Water Solubility: The test item water solubility was determined to be between: 16.4 mg/L (at a loading rate of 30 mg/L of solution at 20.0 °C and pH 8.8 to 63.0 mg/L (at a loading rate of 300 mg/L of solution at 20.0 °C and pH 7.8. There was clear evidence of hydrolytic instability of the test item over a period of 72 hours. Concentrations based on: oxydipropanol constituent which was stable, slow stir flask method - OECD TG 105, 2016

Additional information

Flask Method, OECD TG 105, 2016: The water solubility of the substance was determined using the slow stirring flask method according to OECD TG 105 and EU Method A.6 under GLP. The test item water solubility was determined to be between two loading rates. Complete disappearance of chromatograph peak 2 occurred at both loading rates within the period of the test (24 to 72 hours) under the conditions of the study. Therefore the water solubility of the test item at 20°C is estimated on the basis of chromatograph peak 1. It was estimated to be 16.4 mg/L at and initial loading rate 30 mg/L and 63 mg/L at an initial loading rate of 300 mg/L. The pH of the aqueous samples was 7.8 - 8.8. Applicant assessment indicates there was clear hydrolytic degradation at (pH 7 to pH 8) during the conduct of the study. With potentially faster degradation at lower concentration of test item. The degradation rate occurred within a period of 24 to 72 hours. Within the lower loading rate all water solubility concentrations were based upon chromatograph peak 1. Which was observed to remain during the study. Within the higher loading rate the water solubility was based upon chromatograph peak 1 and 2. The latter chromatograph peak 2 completely disappeared during the period of the test (< 72 hours).

 

Conclusion: There is clear evidence of test item hydrolytic instability of specific constituents of the test item within the pH range 5 to 8.5 within the two separate studies and separate conditions. This was also evidenced in available ecotoxiciology studies in Daphnia sp. and Algae inhibition tests that utilised WAF loading rates of up to 100 mg/L. For example, detected actual concentrations of 6.1 mg/L (WAF: 10 mg/L) and 59 mg/L (WAF: 100 mg/L) in Daphnia medium (analytically maintained within 80 to 110% nominal) under static conditions. This corresponded to one specific test item component (oxydipropanol). No ecotoxicological effects were observed within the WAF loading ranges of concentration and between 48 and 72 hours, respectively.

 

In accordance with section 2 of REACH Regulation (EC) No. 1907/2006 Annex XI: further study of water solubility does not need to be completed as testing is not technically possible or scientifically needed. The available guidelines (OECD TG 105 and EU Method A.6) are typically applicable to ‘the solubility in water of essentially pure substances which are stable in water’. The substance is hydrolytically unstable and therefore further testing of the substance by the flask method is precluded. The applicant adapts the information requirement by providing an endpoint study record for (1) Water Solubility (up to 72hours) and (2) Hydrolysis as a function of pH. Furthermore no effects were observed in ecotoxicological testing up to WAF loading rate of 100 mg/L. There is adequate information available for classification and risk assessment. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.7.4, December 2016) further testing does not need to be conducted.