2-(1,1-dimethylethyl)-6-[[3-(1,1-dimethylethyl)-2-hydroxy-5-methylphenyl]methyl]-4-methylphenyl acrylate

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 March to 12 April 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The mean water solubility values obtained from the two tests with different flows differed by 56.8%. This difference in mean recoveries is outside of the acceptance criteria of 30% for column elution as defined by the OECD Guideline 105.

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7840 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Remarks:

United States Environmental Protection Agency, Washington, D.C. 20460

Type of method:

column elution method

Water solubility:

0.123 µg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

5

Remarks on result:

other: mean value of two flow rates

Details on results:

0.158 μg/L at flow rate of approximately 12.5
0.0883 μg/L at flow rate of approximately 6.25

RESULTS

Prior to the definitive test, two initial definitive tests were conducted at Smithers Viscient in February and March 2017. Both experiments were repeated due to variable analytical recoveries and failure of the analytical recoveries to meet acceptance criteria. The test was repeated and the results of the definitive column elution test are presented below. The temperature during testing ranged from 20.0 to 20.4 °C. At the termination of the column elution test, all samples were measured to have a pH value of 5 using pH indicator strips.

Twelve of the fractions were collected from the test system for each of the respective flow rates for the evaluation of the water solubility. The mean water solubility of the test item was determined to be 0.158 ± 0.0362 μg/L at a flow rate of 12.5 mL/hour and 0.0883 ± 0.0147 μg/L at a flow rate of 6.25 mL/hour using the column elution method. The mean water solubility values obtained from the two tests with different flows differed by 56.8%. This difference in mean recoveries is outside of the acceptance criteria of 30% for column elution as defined by the OECD Guideline 105. The high variability has been attributed to the water solubility results being at approximately the LOQ. The overall mean water solubility was determined to be 1.23 × 10-7 g/L (0.123 μg/L).

Analysis of the quality control (QC) samples resulted in measured concentrations that were consistent with the predetermined recovery range and ranged from 82.1 to 94.0 % of the nominal concentrations. Based on these results, it was determined that the appropriate quality control was maintained during the analyses of the exposure solutions.

Results for the determination of water solubility for the test item in purified reagent water.

Replicate	12.5 mL/hour	pH^a	6.25 mL/hour	pHa
A1	--b	5	0.0783	5
A2	0.109	5	0.0832	5
A3	0.131	5	0.1097	5
A4	0.190	5	0.0965	5
A5	0.184	5	0.0739	5
A6	0.178	5	--b	5
Mean:	0.158		0.0883
Standard Deviation:	0.0362		0.0147
% Relative Standard Deviation:	22.9%		16.6%
Overall Mean:	0.123
Overall Standard Deviation:	0.0452
Overall % Relative Standard Deviation:	36.6%
Overall % Difference Between Flow Rates:	56.8%c

a pH measurements were recorded with EMD pH strips.

b Data not reported.

c See Protocol Deviations.

Note: Calculations were performed using unrounded analytical data, and not the rounded values (three significant figures) presented in this table.

PROTOCOL DEVIATIONS

1. The protocol states that a minimum of five of the samples eluted between the two turbidity samples will be assayed using a validated analytical method. Each sample to be analyzed must be separated from the sample before it by the passage of ten bed volumes. The unused samples that fall between the samples to be analyzed may be discarded. Due to problems encountered during this testing, the decision was made to analyze the “unused samples” to obtain more data that could be useful to troubleshooting the analysis. Since the wording of the protocol states, “Each sample analyzed must be separated from the sample before it by the passage of ten bed volumes”, this is a deviation from the protocol. This deviation will have no impact on the study because the samples marked for analysis were the only samples reported and were separated by the passage of ten bed volumes accordingly. The decision to analyze all samples was made and recorded appropriately in the raw data, but the wording of the protocol was not amended contemporaneously. Going forward, this protocol wording will be modified to allow the analysis of extra samples for troubleshooting purposes.

2. The protocol states that five successive fractions from the second set must also show an agreement within 30% concentration to demonstrate equilibrium. It also states that two sets must agree with one another in order for the test to be considered satisfactory. The samples reported for the two intervals of this analysis agree within the 30% concentration range among each individual flow rate, but are not within a 30% agreement of one another. The two flow rates have a calculated percent difference of 56.8%. The deviation will have minimal impact on the study. This requirement of the protocol and guideline works well for most compounds, but the extraordinarily low water solubility determined for this compound makes this requirement much more difficult to fulfill. The reported water solubility for this compound was 0.123 μg/L and the limit of quantitation for this analysis was 0.05 μg/L. At the low concentrations encountered in testing, the concentration variability was very high as demonstrated throughout the individual results of each sampling even processed. This high relative variability can be expected at such low concentrations since extremely small changes in concentration have a large impact by percentage. Since the variability was so high and the sample concentrations so close to the LOQ of the validated analysis, it was mutually decided with the Study Sponsor that reporting the data with this percent difference between flow rates was justified.

Executive summary:

The mean water solubility of the test item was determined in purified reagent water by the column elution method. The overall mean water solubility was determined to be 0.123 μg/L. The two flow rates have a calculated percent difference of 56.8%. The deviation will have minimal impact on the study.

Description of key information

The water solubility of the test substance is 0.123 µg/L at 20 °C, pH = 5 (OECD 105, column elution method method)

Key value for chemical safety assessment

Water solubility:

0.123 µg/L

at the temperature of:

20 °C