1-[([[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl)oxy]pyrrolidine-2,5-dione

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:

14 to 15 March 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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))

Version / remarks:

January 2001

Deviations:

no

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))

Version / remarks:

2001

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

Version / remarks:

2003

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC estimation method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: JNJ-26144612-AAA (T002632), batch I18IB2522
- Expiration date of the lot/batch: 19 March 2020 (retest date)
- Purity test date: 17-10-2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2-8°C)
- Stability under test conditions: In course of Test Facility Study No. 520034 it was observed that the test item degraded quickly in water. The disappearance time 50% of the test item in aqueous surroundings was less than 1 hour. The HPLC method using soil-adsorption-reference data was, therefore, applied for the determination of the adsorption coefficient (Koc) of the test item and of its aqueous degradation product(s).

Radiolabelling:

no

Test temperature:

35°C +- 1°C

Details on study design: HPLC method:

EQUIPMENT
- Apparatus: Acquity UPLC system (Waters, Milford, MA, USA)
- Type, material and dimension of analytical (guard) column: Acquity UPLC HSS Cyano, 100 mm ´ 2.1 mm i.d., dp = 1.8 µm (Waters)
- Detection system: Acquity UPLC TUV detector (Waters)
- UV detection: 210 nm

MOBILE PHASES
- Type: 55/45 (v/v) methanol/water
- Flow: 0.4 mL/min
- pH: neutral.
According to the guidelines, the determination of the Koc for test items that are ionized for at least 10% within pH 5.5 to 7.5 should be performed with both the ionized and non-ionized form. Therefore, the pKa values of the test item were calculated using the Perrin calculation method (pKalc 5.0, module in Pallas 3.0, CompuDrug International San Francisco, CA, USA). Based on the calculations, the UPLC analysis was performed at neutral pH.

- Solutes for dissolving test and reference substances:
* Water: Tap water purified by a Milli-Q water purification system (Millipore, Bedford, MA, USA)
* Methanol: Biosolve, Valkenswaard, The Netherlands
* Acetonitrile: Biosolve.

PREPARATION OF TEST SOLUTIONS
Three studies were performed: one study to determine the adsorption coefficient of the test item (i.e. Test solution 2, stock and end solution in acetonitrile), one for the degradation product(s) (i.e. Test solution 3, stock solution in water) and one study to show that using acetonitrile as end solution did not affect the retention time. The study with Test solution 2 was repeated, as observed test-item related responses were too weak in the first experiments.

- Solution of the unretained compound:
A 5.0 g/L stock solution of formamide (99.2%, [75-12-7], Alfa Aesar, Karlsruhe, Germany) 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 blank solution for the mixture of reference substances was 55/45 (v/v) methanol/water.

- Test solution 1:
A 1000 mg/L stock solution of the test item was prepared in acetonitrile. 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 10.0 mg/L.
The test item blank solution was 55/45 (v/v) methanol/water.

- Test solution 2:
A 1000 mg/L stock solution of the test item was prepared in acetonitrile. The stock solution was diluted with acetonitrile. The final concentration of the test item solution was 50.0 mg/L.
The test item blank solution was acetonitrile.

- Test solution 3:
A 1000 mg/L stock solution of the test item was prepared in water. In order to dissolve the test item the stock solution was ultrasonicated for 10 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 10.0 mg/L.
The test item blank solution was 55/45 (v/v) methanol/water.

REFERENCE SUBSTANCES
- Identity:
Reference substance Purity CAS number Supplier log Koc#
Acetanilide > 99.9% 103-84-4 Sigma-Aldrich 1.26
Monuron 99.9% 150-68-5 Sigma-Aldrich 1.99
2,5-Dichloroaniline 99.9% 95-82-9 Merck 2.55
Naphthalene 100% 91-20-3 Acros Organics 2.75
Benzoic acid phenylester > 99.9% 93-99-2 Sigma-Aldrich 2.87
Fenthion 98.6% 55-38-9 Sigma-Aldrich 3.31
Phenanthrene 98.5% 85-01-8 Acros Organics 4.09
4,4’-DDT 98.7% 50-29-3 Sigma-Aldrich 5.63


DETERMINATION OF RETENTION TIMES
- Quantity of test substance introduced in the column: 1 µL (test solution 2), 5 µL (test solution 1 and 3)
- Quantity of reference substances:
- Intervals of calibration:

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

EVALUATION
- Calculation of capacity factors k':
k' = (tr - t0) / t0
where tr = retention time of test item or reference substance
t0 = UPLC dead time

- Determination of the log Koc value:
log k' = a log Koc + b
where a = slope
b = intercept

Key result

Type:

log Koc

Value:

< 1.26 dimensionless

pH:

7

Remarks on result:

other: test item

Key result

Type:

log Koc

Value:

< 1.26 dimensionless

pH:

7

Remarks on result:

other: aqueous degradation product

Key result

Type:

Koc

Value:

< 18

pH:

7

Remarks on result:

other: test item

Key result

Type:

Koc

Value:

< 18

pH:

7

Remarks on result:

other: aqueous degradation product

Details on results (HPLC method):

- Retention times of reference substances used for calibration:
Substance tr,1 [min] tr,2 [min] log Koc
Acetanilide 0.934 0.934 1.26
Monuron 1.125 1.124 1.99
2,5-Dichloroaniline 1.255 1.258 2.55
Naphthalene 1.440 1.444 2.75
Benzoic acid phenylester 1.677 1.671 2.87
Fenthion 2.173 2.172 3.31
Phenanthrene 2.384 2.378 4.09
4,4’-DDT 5.362 5.399 5.63

- Details of fitted regression line (log k' vs. log Koc):
* Test solution 1 and 3:
In the chromatogram of Test solution 1, one major peak and one small test item peak were observed. In the chromatogram of Test solution 3, one test item peak was observed. As the retention times of Test solution 1– peak 1 and the signal in Test solution 3 agreed, the first peak in Test solution 1 was considered the degradation product of the test item.
The equation of the regression line was: log k’ = 0.307 ´ log Koc – 0.862 (r = 0.98, n = 16).

* Test solution 2:
In the chromatogram of the test solution, one test item peak was observed. As the retention times of Test solution 1– peak 2 and the signal in Test solution 2 agreed, the second peak in Test solution 1 was considered the test item.
The equation of the regression line was: log k’ = 0.305 ´ log Koc – 0.857 (r = 0.98, n = 16).

- Average retention data for test substance:
Substances tr,1 [min] tr,2 [min] mean tr (n=2) log Koc Koc Area %
Test solution 1– peak 1 0.723 0.729 0.726 < 1.26 < 1.8E1 97
Test solution 1– peak 2 0.861 0.862 0.862 < 1.26 < 1.8 E1 3.1
Test solution 3 0.737 0.740 0.739 < 1.26 < 1.8E1 100
Test solution 2– peak 1 0.852 0.855 0.854 < 1.26 < 1.8E1

Validity criteria fulfilled:

yes

Conclusions:

The HPLC method using soil-adsorption-reference data was applied for the determination of the adsorption coefficient (Koc) of JNJ 26144612-AAA (T002632) and of its aqueous degradation product. No pKa values for acidic and basic groups in the molecular structure of the test item in the logarithm range of 1 - 14 were calculated. The log Koc and Koc values of both the test item and its aqueous degradation product at neutral pH were < 1.26 (Koc < 1.8 E1).