Formamide, N-[(2-bromo-5-hydroxy-4-methoxyphenyl)methyl]-N-[2-(4-hydroxyphenyl)ethyl]-

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-03-15 to 2017-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.19 (Estimation of the Adsorption Coefficient (KOC) on Soil and Sewage Sludge Using High Performance Liquid Chromatography (HPLC))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: European Commission (EC), Technical Guidance Document on Risk Assessment Part III, Chapter 4.3: “Use of (Quantitative) Structure Activity Relationships ((Q)SARs) - Soil and Sediment Sorption”, 2003.

Deviations:

no

GLP compliance:

yes

Type of method:

HPLC estimation method

Media:

other: HPLC column

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: I15EB1917
- Expiration date of the lot/batch: 2017-06-13 (retest date)
- Purity test date: 2017-03-17 (certificate of analysis release date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: not indicated
- Solubility and stability of the test substance in the solvent/vehicle: 0.01 g/L in water

Radiolabelling:

no

Test temperature:

Column temperature: 60°C ± 1°C

Details on study design: HPLC method:

EQUIPMENT
- Apparatus: Waters, Milford, MA, USA
- Type: Alliance Separation Module 2695
- Type, material and dimension of analytical (guard) column: Hypersil BDS-CN, 150 mm x 4.6 mm i.d., dp = 5 µm (Thermo Fisher Scientific, Waltham, MA, USA)
- Detection system: Dual λ Absorbance Detector 2487 (Waters)
- UV detection: 210 nm

MOBILE PHASES
- Type: 55/45 (v/v) methanol/water
- Solutes for dissolving test and reference substances:
* Solution of the unretained compound: Main component. A 5.0 g/L stock solution of formamide (99.2%, Alfa Aesar) in methanol was used. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/water. The formamide blank solution was 55/45 (v/v) methanol/water.
* Reference substance solutions: Stock solutions of the reference substances at concentrations of approximately 1 g/L in methanol were used. The stock solutions were diluted to obtain an end solution of 55/45 (v/v) methanol/water. The reference substances blank solution was 55/45 (v/v) methanol/water.
* Test solution: A 1000 mg/L stock solution of the test item was prepared in methanol. In order to dissolve the test item the stock solution was ultrasonicated for 5 minutes. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/water. The final concentration of the test item solution was 10 mg/L. The test item blank solution was 55/45 (v/v) methanol/water.

DETERMINATION OF DEAD TIME
- Method: by means of homologous series / by inert substances which are not retained by the column

REFERENCE SUBSTANCES
- Identity: combined reference solution containing Acetanilide, Monuron, 2,5-Dichloroaniline, Napthalene, Benzoic acid phenylester, Fenthion, Phenanthrene and 4,4’-DDT

DETERMINATION OF RETENTION TIMES
- Quantity of test substance introduced in the column: 10 µL (Injection volume)
- Quantity of reference substances: 10 µL (Injection volume)
- Intervals of calibration: no data


REPETITIONS
- Number of determinations: Duplicate reference substance solutions were analysed by single injection. The test item solutions were injected in duplicate. Blank solutions were analysed by single injection.

EVALUATION
- Calculation of capacity factors k': from retention time of reference items, the test item, and then on-sorbed chemical item
- Determination of the log Koc value: a correlation of log k' versus log Koc of the reference items is plotted using linear regression - the log k' value of the test item is then used to calculate its log Koc value

Analytical monitoring:

no

Key result

Type:

Koc

Value:

13 dimensionless

pH:

7

Remarks on result:

other:

Remarks:

mean of 2 analyses

Key result

Type:

log Koc

Value:

1.1 dimensionless

pH:

7

Remarks on result:

other:

Remarks:

Mean of 2 analyses

Details on results (HPLC method):

- Retention times of reference substances used for calibration: see part "Any other information on results incl.tables"
- Details of fitted regression line (log k' vs. log Koc): log k’ = 0.178 ´ log Koc – 1.50 (r = 0.96, n = 16).
- Average retention data for test substance: 2.101 minutes

Transformation products:

not measured

- The following pKa values in the logarithm range of 1 - 14 for acidic and basic groups in the molecular structure of the test item were calculated using the Perrin calculation method:

Acidic groups and pKa values		Basic groups and pKa values
Phenol	9.3	none
Phenol	9.5

-Retention time in minutes of the reference substances and test item and the Koc of the test item:

Substances	tr,1 (min)	tr,2 (min)	mean tr (n=2)	log Koc	Koc
Formamide (t0)	2.003	2.001	2.002
Acetanilide	2.091	2.083		1.26
Monuron	2.159	2.148		1.99
2,5-Dichloroaniline	2.164	2.151		2.55
Naphthalene	2.234	2.212		2.75
Benzoic acid phenylester	2.252	2.231		2.87
Fenthion	2.295	2.267		3.31
Phenanthrene	2.377	2.343		4.09
4,4’-DDT	2.560	2.517		5.63
Test item	2.102	2.100	2.101	1.10	1.3E+1

Validity criteria fulfilled:

yes

Conclusions:

The HPLC method using soil-adsorption-reference data (according to OECD guideline 121) was applied for the determination of the adsorption coefficient (Koc) of JNJ-28645409-AAA (T002078). The Koc and log Koc values of the test item at neutral pH were determined to be 1.3E+1 and 1.10 respectively. The results of the test can be considered reliable without restriction.

Description of key information

This endpoint is covered with a GLP-study (Brekelmans, 2017) performed according to standard test guideline OECD 121. The mean log Koc of T002078 was determined to be 1.10 using the HPLC estimation method.

Key value for chemical safety assessment

Koc at 20 °C:

13

Additional information

There is one GLP study available (Brekelmans, 2017) performed according to standard test guideline OECD 121. Based on pKa calculations, the UPLC analysis was performed at neutral pH.

The mean log Koc of T002078 was determined to be 1.10 using the HPLC estimation method according to OECD guideline 121. The results of the test can be considered reliable without restriction.