Bis(4-(1,1,3,3-tetramethylbutyl)phenyl) ether

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov. 10, 2020 to Dec. 02, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: SANCO/3029/99 rev. 4 dated 11. Jul. 2000: “Residues: Guidance for generating and reporting methods of analysis in support of pre-registration data requirements for Annex II (part A, Section 4) and Annex III (part A, Section 5) of Directive 91/414”

Version / remarks:

4, dated 11. Jul. 2000

Qualifier:

according to guideline

Guideline:

other: Guideline on bioanalytical method validation (EMEA/CHMP/EWP/192217/2009 Rev.1 Corr. 2, Committee for Medicinal Products for Human Use (CHMP), adopted 21 July 2011)

Version / remarks:

Rev. 1, adopted 21 July 2011

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Key result

Water solubility:

< 1 µg/L

Conc. based on:

test mat. (dissolved fraction)

Temp.:

20 °C

pH:

ca. 6

Details on results:

Analytical Method:
The validation of a HPLC-Method for the determination of Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)ether was tested.
The test item was separated with an Agilent Poroshell EC-120 C18, 2.7 µm, 150*4.6 mm column and detected with HPLC-UV.

Validation Results:
Calibrated Range: 1 – 29 µg/L
Quadratic term c: 0.0000058430 mAU*min / (µg/L)2
Linear term / Slope b: 0.0014928 mAU*min / µg/L
Constant / Intercept a: 0.00124864
Method Variation Coefficient (Precision): 2.37 %
Specificity: was given
Solubility in demineralised water < 1 µg/L
Solubility in Algal test medium < 1 µg/L
Solubility in Daphnia test medium < 1 µg/L
Accuracy / Stability in demineralised water: Testing not possible
Accuracy / Stability in Algal test medium: Testing not possible
Accuracy / Stability in Daphnia test medium: Testing not possible

Solubility

Table: Solubility estimation results

Medium	Nominal concentration	Dilution factor	Peak Area	Concen- tration	Mean Concentration
	[g/L]		[mAU*min]	[µg/L]	[µg/L]
Demineralised water	1	2	n.d.	n.c.	n.c.
			n.d.	n.c.
			0.00057	< LOQ
			n.d.	n.c.

  n.d. = not detectable

No evaluable test item concentration was found.

All acceptance criteria defined in the validation plan are fulfilled for the calibration range of 1 - 29 µg/L using a quadratic calibration function.

After the injection of the highest calibration level, a solvent blank was injected. As no test item peak area was detectable in the blank, the condition “≤ 20 % of the measured value of the lowest calibration level” was fulfilled. The relative standard deviation of fivefold determination of 11 µg/L calibration level showed an RSD = 2.6 %.

In demineralised water, a peak area of 68 % of the smallest calibration standard was detectable. However, the two replicates after stirring of 2 g/L test item in demineralised water showed no or substantially smaller noise peaks, this was considered uncritical.

The pre-test for solubility of the test item in demineralised water (pH 6.3) indicated that the solubility at 16.6-22.2 °C is substantially lower than 1 µg/L.

Due to the low solubility, testing of accuracy and stability in matrices was not possible.

No observations arousing doubts concerning the accuracy of the results and the validity of the study were made. No deviations were ascertained.

Conclusions:

A limit test up to the detection limit was carried out during the validation of the analytical method.
No evaluable test item concentration was found. Therefore, the solubility in water is considered as < 1 µg/L at pH ca. 6 and Temp. 16.6-22.2 °C.
According to REACH Regulation (REGULATION (EC) No 1907/2006) Annex VII, COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1, 7.7 “If the substance appears ‘insoluble’ in water, a limit test up to the detection limit of the analytical method shall be performed.”

Description of key information

A limit test up to the detection limit was carried out during the validation of the analytical method.

No evaluable test item concentration was found. Therefore, the solubility in water is considered as < 1 µg/L at pH ca. 6 and Temp. ca. 20 °C.

Additional information

According to REACH Regulation (REGULATION (EC) No 1907/2006) Annex VII, COLUMN 2 SPECIFIC RULES FOR ADAPTATION FROM COLUMN 1, 7.7 “If the substance appears ‘insoluble’ in water, a limit test up to the detection limit of the analytical method shall be performed.”