Reaction product of ammonium molybdate and C12-C24-diethoxylated alkylamine (1:5-1:3)

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Remarks:

Non-GLP study following test guideline EU C.7/OECD 111, "Hydrolysis as a function of pH". Follow up and final study following a previous feasibility study aimed at determining optimal conditions to test substance material.

Type of information:

experimental study

Remarks:

Non-GLP feasibility study

Adequacy of study:

key study

Study period:

December 2016 - June 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Remarks:

Feasability study

Justification for type of information:

The European Chemicals Agency, ECHA requested in the decision letter SEV-412-780-3-1, dated 9 September 2016, for reaction product of ammonium molybdate and C12-C24 diethoxylated alkylamine (1:5-1:3) EC 412-780-3, (referred to as Additiv 104 hereinafter) the following new data: Hydrolysis as a function of pH of Additiv 104 (test method EU C.7/OECD 111. BP commissioned the study to the only institution that expressed interest in the test, Fraunhofer's Institute for Toxicology and Experimental Medicine - ITEM- in Hannover, Germany. However, the deadline of September 18 2017 will not be enough to carry the experiment to full completion. In the meantime, a feasibility study conducted by ITEM (ITEM Study No 15N17556) has provided NEW and SUBSTANTIAL information, which will be detailed wherever appropriate in the sections below. On the basis of this information, which is critical for the continuation of the study and was not known before, BP respectfully requests consideration for an extension of the deadline for an additional 8 months, until May 2018.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Version / remarks:

Feasibility study, based on OECD guideline 111

Deviations:

no

GLP compliance:

no

Remarks:

Feasibility study, GLP compliance was not applicable although study is well documented

Test material

Test material information

Constituent 1

Reference substance name:

Reaction product of ammonium molybdate and C12-C24-diethoxylated alkylamine (1:5-1:3)

EC Number:

412-780-3

EC Name:

Reaction product of ammonium molybdate and C12-C24-diethoxylated alkylamine (1:5-1:3)

Cas Number:

1380226-46-9

Molecular formula:

A complex mixture of species so no unique molecular formula can be given

IUPAC Name:

dimolybdenum(6+) diammonium 2-{2-[(octadec-9-en-1-yl)amino]ethoxy}ethan-1-ol heptaoxidandiide

Test material form:

liquid: viscous

Details on test material:

Name of test material (as cited in study report): Additiv 104
- Description: Dark red liquid
- Physical state: Liquid
- Analytical purity: 75% Active ingredient (with 25% carrier oil).
- Lot/batch No.: 0000683159
- Fraunhofer ITEM Ref No A005/17
- Storage condition of test material: Room temperature in the dark

NOTE on 'purity': The reaction to make Additiv 104 is done in naphthenic base oil (EC# 265-155-0) which cannot be removed from the resulting mixture, and which therefore forms part of (ca. 25% w/w) of the resulting mixture.

Specific details on test material used for the study:

Test items and Reference items
1. Test Items
BP Optimol® Additiv 104, Dialysate (DS) (0.3% Mo), identified by Fraunhofer-ITEM under Ref. No. A003/17
BP Optimol® Additiv 104, Dialysis Residue DR (26% Mo), identified by Fraunhofer-ITEM under Ref. No. A004/17
BP Optimol® Additiv 104, Lot: 0000683159, identified by Fraunhofer-ITEM under Ref. No. A005/17

Active Ingredient: Ethomeen-molybdates, ethomeen: molybdate (1:3.86) molar fraction, mixture of monomers and polymers; EC No. 412-780-3; Content: 13% molybdate and 61% ethomeen condensates; Stability = Stable under normal storage conditions (-5 to 40°C)

2. Reference Items

BP-Technology Ref: Fraunhofer-ITEM Ref:
Ammonium dimolybdate, Lot: 0000723434 A006/17
Nynas NS 100, Lot: 0000714432 A007/17
Ethomeen O/12LC, Lot: 0000719160 A008/17
Ethomeen OV/17, Lot: 0000634622 A009/17
Silfoam SC 155, Lot: ECHANTILLO A010/17

3. Analytical Standards and Solvents

Product Name: DMSO-D6, 99.8% atom % D CAS-No.: 2206-27-1
Expiration Date: August 16, 2018 Supplier / Order No.: Deutero / 00905

Product Name: CDCl3, 99.95% atom % D CAS-No.: 67-66-3
Expiration Date: July 23, 2019 Supplier / Order No.: Deutero / 00407

Product Name: CD3CN, 99% atom % D CAS-No.: 2206-26-0
Expiration Date: July 26, 2019 Supplier / Order No.: Deutero / 00202

Product Name: Ammonium molybdate CAS-No.: 13106-75-8
Expiration Date: March 3, 2022 Supplier / Order No.: Aldrich / 277908

Product Name: Dichloromethane, SupraSolv CAS-No.: 75-09-2
Expiration Date: December 12, 2018 Supplier / Order No.: Merck / 1.06054.2500

Product Name: Acetonitrile, Chemsolute CAS-No.: 75-05-8
Expiration Date: July, 2020 Supplier / Order No.: TH. Geyer / 2653.2500

Product Name: Dimethylsulfoxide >99.9% CAS-No.: 67-68-5
Expiration Date: September, 2018 Supplier / Order No.: Aldrich / 276855

Product Name: Sodium hydroxide >98% CAS-No.: 1310-73-2
Expiration Date: December, 2020 Supplier / Order No.: Aldrich / S5881

Product Name: Hydrochloric acid 35% CAS-No.: 7647-01-0
Expiration Date: January, 2018 Supplier / Order No.: Roth / HN53

Product Name: Cyclohexane, SupraSolv CAS-No.: 56-23-5
Expiration Date: January, 2018 Supplier / Order No.: Merck / 1.02817.2500

Product Name: Tetrachloromethane CAS-No.: 110-82-7
Expiration Date: March, 2021 Supplier / Order No.: Aldrich / 289116

Product Name: Ammonium bicarbonate >99.5% CAS-No.: 1066-33-7
Expiration Date: October, 2020 Supplier / Order No.: Aldrich / 09830

Product Name: Ammonia solution, p.a. 25% CAS-No.: 1066-33-7
Expiration Date: September, 2019 Supplier / Order No.: Merck / 1.05432

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

SAMPLE PREPARATION FOR NMR (NUCLEAR MAGNETIC RESONANCE) AND MASS SPECTROMETRY MEASUREMENTS

NMR measurements were carried out by weighing 2 – 40 mg of sample and dissolving it in 600 µL of solvent mainly 50/50 v/v CDCl3/DMSO-D6. The samples were homogenised in an ultra-sonic bath, centrifuged at 1000 G, transferred to 5-mm NMR tubes and capped. 760 µL water samples from the Tier 1 hydrolysis tests were prepared by adding 40 µL DMSO/D2O-standard (0.1484% DMSO in D2O) and mixed.
ESI-MS / MSn (electrospray ionization and multidimensional mass spectrometry) measurements were carried out with 20 – 60 µg/mL solutions of the sample diluted in mainly 50/50 v/v CH2Cl2/acetonitrile. 100 µL water samples from the Tier 1 hydrolysis tests were prepared by adding 900 µL 50/50 acetonitrile/water and mixed.
All pulse sequences used were Bruker stand pulse sequences. 1H / 13C NMR chemical shifts were referenced to the residual solvent signal of DMSO-D6 (δ = 2.50 / 39.50 ppm).

Buffers:

Used to facilitate the preliminary determination of hydrolysis. CH2Cl2/CH3CN/NH3-NH4-buffer at pH 9 and 50°C, was used on a precipitate DR fraction to optimize detection of negative ions.

Estimation method (if used):

NMR and MS techniques were used to better estimate crude composition of the DS and DR fractions of Additiv 104.

NMR-Spectrometer: AVANCE III 600 MHz (Bruker)
Probe Head: 5mm TCl cryo-probe head with Z-gradient, Software: TopSpin 2.1, NMR Tubes: 5-mm tubes (Wilmad)

MS-Spectrometer: HCT (Bruker)
ESI, positive / negative Mode, Flow Injection 400µL/h, Nebulizer 3 psi, Dry temp: 200°C, Dry Gas N2, scan 50 – 3000 AMU, target mass: 1000 -2000 AMU wide range, ICC 100000, 16 scans average

Details on test conditions:

For NMR, MS, UV-Vis, IC, GC and Cryoscopy

NMR-Spectrometer: AVANCE III 600 MHz (Bruker)
Probe Head: 5mm TCl cryo-probe head with Z-gradient, Software: TopSpin 2.1, NMR Tubes: 5-mm tubes (Wilmad)

MS-Spectrometer: HCT (Bruker)
ESI, positive / negative Mode, Flow Injection 400µL/h, Nebulizer 3 psi, Dry temp: 200°C, Dry Gas N2, scan 50 – 3000 AMU, target mass: 1000 -2000 AMU wide range, ICC 100000, 16 scans average

UV/Vis-Spectrometer: Cary 300 (Varian), Double-monochromator, 190 – 800 nm
Ion Chromatograph: Dionex LC20 with suppressor system, GP40 gradient pump, CD20 conductivity detector, column: Dionex IonPack AS 4A, eluent 1.0 mM NaHCO3 with 1.5 mM Na2CO3, flow: 1.6 mL/min, isocratic

Gas Chromatograph: HP5890 with autosampler, split-injector and FID-detector, Injector: split 1:1, 250°C, Detector: 320°C, Temp-program: 40°C 3 min isocratic, 9°C/min to 120°C, 0.5 min isocratic, 11°C/min 320°C, 9.5 min isocratic. Column: BD-5MS 30 m x 0.32 mm, fth: 0.25 µm, Carrier gas: Helium: 3 mL/min const. flow

Cryoscopy: Using a semi-micro-scale double-wall freezing-glass, first inner diameter: 8 mm, first glass outer diameter: 10 mm, second inner diameter: 13 mm, stainless-steel mixing ring, solvent volume 1.5 to 2.5 mL, EBRO digital-thermometer TFX 430 with 3 mm PT100 probe resolution 0.01°C between -100 to +200C°, Dewar ID: 40 mm for freezing mixture.

NMR measurements were carried out by weighing 2 – 40 mg of sample and dissolving it in 600 µL of solvent mainly 50/50 v/v CDCl3/DMSO-D6. The samples were homogenised in an ultra-sonic bath, centrifuged at 1000 G, transferred to 5-mm NMR tubes and capped. 760 µL water samples from the Tier 1 hydrolysis tests were prepared by adding 40 µL DMSO/D2O-standard (0.1484% DMSO in D2O) and mixed.

ESI-MS / MSn measurements were carried out with 20 – 60 µg/mL solutions of the sample diluted in mainly 50/50 v/v CH2Cl2/acetonitrile. 100 µL water samples from the Tier 1 hydrolysis tests were prepared by adding 900 µL 50/50 acetonitrile/water and mixed.

All pulse sequences used were Bruker stand pulse sequences. 1H / 13C NMR chemical shifts were referenced to the residual solvent signal of DMSO-D6 (δ = 2.50 / 39.50 ppm).

Additiv 104 is practically insoluble in water. To conduct the screening test (Tier 1) for hydrolysis small amounts of sample were added to water to form an emulsion and pH and temperature adjusted. Thus, the mixtures were left stirring for 5-6 days at 50°C and sampled daily to determine rate and extent of hydrolysis at pH 4, 7 and 9. A deuterated solvent mixture with selectively higher polarity proved critical in the analytical verification step.

Duration of test

Duration of test 1

Duration:

5 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

ca. 0.003 - < 0.01 mol/L

Remarks:

Range within OECD 111 guideline

Duration of test 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

ca. 0.003 - < 0.01 mol/L

Duration of test 3

Duration:

5 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

ca. 0.003 - < 0.01 mol/L

Number of replicates:

Not specified

Positive controls:

no

Negative controls:

no

Statistical methods:

None specified in the preliminary study

Results and discussion

Preliminary study:

Additiv 104, dialysis fractions and Additiv 104 starting materials have been further characterised, however there remains some materials at greater than 0.1% that have not been formally characterised.

Additiv 104 composition: Oligomers of Ethomeen (42%), Ethomeen- molybdates (28%), Nynas NS 100 (26%), Ethomeen Anhydride (2%) and Ethomeen- polyglycol-ethers (PEG 1 – 13) (1%). The overall composition is in good agreement with the previous report from BP (IAR0109, Feb 2013). The Fraunhofer ITEM study No 15N17556 herein provides a more detailed breakdown of the un-complexed Ethomeen components, and proposes additional (although still tentative) structures for the Ethomeen molybdate complexes, which are likely to be a mixture of different structures both straight chain and cyclic with molecular weights between 500 - 4000 g/mol. There is significant challenge in formally identifying the complexes and thus the structures described in the preliminary report are working proposals. Preliminary results acquired by cryoscopy propose a tentative structure of the main compound of Ethomeen molybdates, with a molecular weight of 3460 ± 300 g/mol, which differed from what has been previously proposed by BP (IAR0109, 2013).

Preliminary hydrolysis:
• pH 4 – milky white suspension with a ring of dark red greasy agglomerate; 8% Mo hydrolysis
• pH 7 – milky white suspension with dark red greasy agglomerate; 16% Mo hydrolysis
• pH 9 – Clear solution with colourless greasy agglomerate; 99% Mo hydrolysis

Test performance:

The preliminary results indicate that the test performed within expectations and that based on the pH and the critical polarity of the solvents used a step-wise hydrolysis was observed.

Transformation products:

not specified

Remarks:

Pending further work under final study

Details on hydrolysis and appearance of transformation product(s):

Additiv 104 is practically insoluble in water. To conduct the screening test (Tier 1) for hydrolysis small amounts of sample were added to water to form an emulsion and pH and temperature adjusted. Thus, the mixtures were left stirring for 5-6 days at 50°C and sampled daily to determine rate and extent of hydrolysis at pH 4, 7 and 9. A deuterated solvent mixture with selectively higher polarity proved critical in the analytical verification step:
• pH 4 – milky white suspension with a ring of dark red greasy agglomerate. 8% Mo hydrolysis
• pH 7 – milky white suspension with dark red greasy agglomerate. 16% Mo hydrolysis
• pH 9 – Clear solution with colourless greasy agglomerate. 99% Mo hydrolysis

Hydrolysis rates appear to increase with time, which is explained by the proposal that molybdenum exists in different Mo-Mo and Mo-ethomeen structures in terminal and internal positions, in cyclic and linear structures. The concentration of ethomeen in solution should be proportional to molybdenum; however, this is not observed. It is proposed that ethomeen partitions into the oil phase in experiments.

Likewise, in a Tier 1 preliminary hydrolysis test at pH 9 (50°C/5 days) on the red-ochre precipitate isolated from the DR fraction (representing Additiv 104 with as much oil removed as possible) the precipitate was not fully soluble. After 6 days the red colour of the Mo complex had been removed to form a colourless, but slightly milky white emulsion with 94% Mo hydrolysis – very similar to the experiments on the whole Additiv 104. After 6 days only 2% of the Ethomeen was observed in solution. The remaining Ethomeen was found after concentrating down the mixture. It was proposed that the ethomeen materials were therefore dissolved in an oily phase of Di-ethomeen-ether, since an emulsion was again formed with greasy material on the sides of the vessel. The results of the hydrolysis of this DR fraction suggest that it would be more advantageous for the final OECD TG 111 test to use the whole Additiv 104 as opposed to the purified Ethomeen-molybdates.

With regard to the observed hydrolysis, the following reaction sequences can be assumed. The non-mono-exponential hydrolysis could occur from the slower release of di-ethomeen-ether whose position should be at the end of a chain since it is generated at the end of synthesis. As a consequence the ethomeen-molybdates have three different kinds of molecule connections that can be hydrolyzed: firstly molybdate-molybdate, secondly molybdate-ethomeen and thirdly ethomeen-ethomeen. In Addition it is assumed that their hydrolysis rate slows down according to this order. At the beginning only 9% of the open-chain molecules with di-molybdate quickly hydrolyse, then the di-molybdates are hydrolyzed into cyclic or chain molecules without the release of molybdate, and finally molybdate is released by hydrolysis of molybdate-ethomeen.

Dissipation DT50 of parent compound

DT50:

ca. 2 yr

Type:

other: The hydrolysis proceeded stepwise at different rates due to different activities at possible cleavage sites. The molybdate release revealed multistep kinetics. It is assumed that phase separation may interfere with the course of reaction.

Remarks on result:

other:

Remarks:

Preliminary study, at present no conclusions can be made about dissipation half-life of the tentatively identified main components

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

Preliminary results, subject to further confirmation

Conclusions:

Based on the feasibility study, evidence to date suggests that hydrolysis occurs as follows: first, the open-chain molecules with di-molybdate hydrolyse without the release of molybdate; secondly, the di-molybdates in the more stable cyclic conformation hydrolyse without the release of molybdate, and; finally, molybdate is released by hydrolysis of molybdate-ethomeen. Ethomeen-Ethomeen molecules are the last to hydrolyse.

Executive summary:

The Registrant, BP France SA, of Additiv 104, commissioned the analytical department of Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), in Hannover Germany to carry out the required study. This institution was chosen due to its broad experience in hydrolysis studies, including for UVCB substances. Other laboratories were approached but they declined the work indicating that in their opinion this study was not scientifically and technically feasible.

 

The study design for these preliminary investigations consisted of:

·        Determination of the composition of the starting materials in Additiv 104

·        Determination of the composition of the DS and DR fractions of Additiv 104

·        Estimation of the composition of Additiv 104

·        Preliminary Tier 1 hydrolysis tests according to OECD TG 111;

o  Hydrolysis of Additiv 104 at pH 4, 7 and 9 (50°C/5 days)

o  Hydrolysis of DR red-ochre isolated precipitate at pH9 (50°C/5 days)

 

Determination of the composition of the starting materials in Additiv 104

The decision letter (SEV-412-780-3-1) mentioned above is based on knowledge derived from the BP analyses (Additiv 104 analysis for REACH registration, IAR 0109, 2013). The BP study suggested that Additiv 104 consists of two fractions that were separated by dialysis into a liquid (dialysate, DS 66.5%) and solid (dialysis residue, DR 33.2%) fraction. This result has been confirmed in this preliminary study. The elaborate characterization of the individual fractions (DR and DS) proved to be an appropriate approach, showing an agreement in the overall composition, but impurities of the starting materials and individual compounds, which are considered elementary for the envisaged hydrolysis test, were only partially elucidated. Hence there are reasons to further characterize the starting materials and impurities.

Determination of the composition of the Dialysate (DS) and Dialysis Residue (DR) fractions of Additiv 104

In this preliminary study the two fractions (DS and DR) were further characterized by NMR and MS to better estimate a crude composition, and to better specify the main components of Additiv 104. The DS fraction mainly consists of 59% diethylamino-derivates and 40% Nynas NS 100. About 1% corresponds to ethomeen-molybdates (30% Mo), from the DR fraction. Recrystallization of DR revealed that an additional 15% DS remains in the DR, and a red-ochre compound, the ethomeen-molybdates, could be isolated. This resulting red-ochre compound can thus be considered as more purified ethomeen-molybdates (purified DR fraction). However, at this stage of the study it still remains unclear which exact molecular structure(s) the ethomeen-molybdates actually have a Mo-content of 30% and likely account for the reddish colour of the product. This reddish mass melts with simultaneous pyrolysis at 218°C and a molar weight of 3460(±300) g/M as roughly determined by cryoscopy. The molecular weight has yet to be confirmed by mass spectrometry.

Estimation of the composition of Additiv 104

The detailed analysis of the starting compounds and the DS and DR fractions gave a much more detailed picture of the total composition of Additiv 104. The main compounds detected were approx. 21% ethomeen-dimer (di-oleic), with 28% different ethomeen-molybdates (in contrast to the MSDS >50%), and with about 26% paraffinic, naphthenic and aromatic from Nynas NS 100.This newly determined composition is roughly consistent with the data of the BP study.

Table showing estimated crude composition of Optimol Additiv 104 provided by Fraunhofer study No 15N17556, 2017 (left),and by BP Study IAR 0109, 2013.

%	Proposed identity by ITEM	Proposed identity by BP	%
21.4	Dimer-bis-nC18(9)en	Ethomeen monomers, dimers and trimers formed by condensation reactions	36.07 - 37.84
5.1	Monomer-nC18(9)en
3.9	Trimer-tris-nC18(9)en
4.3	Dime-nC18diene / -nC18(9)en
3.4	Dimer-nC16 / -nC18(9)en
3.4	Dimer-nC16 -en / -nC18(9)en
1.7	Monomer-nC18(9)en anhydrid
1.1	Ethomeen polyglycol ether (PEG 1 -13)
28.1	Ethomeen-molybdates cont. species (30% Mo), with considerable higher MW	Ethomeen-molybdates cont. species (25% Mo), five proposed structures	33.15
		Mo-cont. species, low mass, fairly nonpolar	2.34 - 4.11
26.4	Nynas NS 100: paraffinic 53%, naphthenic 40%, aromatic 7%	Nynas NS 100	26.45
1.2	Unknowns	Unknowns	?

Preliminary Tier 1 hydrolysis tests according to OECD TG 111;

o   Hydrolysis of Additiv 104 at pH 4, 7 and 9 (50°C/5 days)

Preliminary tests have shown that, in contrast to the recommendations from decision letter (SEV-412-780-3-1), hydrolysis of the whole Additiv 104 is possible. Furthermore, these recommendations are based on a more up-to-date composition of Additiv 104. This fact alone justifies to test for preliminary hydrolysis on the full product. These preliminary tests were conducted at 50°C and the main solvent used for NMR was CDCl₃/DMSO-D₆instead of pure CDCl₃due to the higher polarity. The higher polarity was considered key to the additional envisaged NMR monitoring of the hydrolysis. Primarily the hydrolysis was quantified by molybdate ion determination using ion chromatography (IC). Accordingly after 5 days at 50°C, hydrolysis progression was calculated to be at pH 9, 96%, at pH 7, 16%, and at pH 4, 8%.

The hydrolysis proceeded stepwise at different rates due to different activities at possible cleavage sites.Less polar compounds, including the ethomeen-molybdates were confined in the oily phase whereas the molybdate ions were fully released into the aqueous phase. The molybdate release revealed, however, not the expected pseudo first order reaction course, but rather a multistep kinetics phenomenon. It is assumed that phase separation (oily and aqueous) may interfere with the course of reaction.

o   Hydrolysis of DR red-ochre isolated precipitate at pH 9 (50°C/5 days)

Simplified hydrolysis conditions with respect to the phase formation should be possible by the use of the DR fraction, as per recommendations of thedecision letter (SEV-412-780-3-1). Unfortunately, this was not the case and the hydrolysis proceeded in an unpredictably complex manner.The hydrolytic test of the purified DR fraction (red-ochre precipitate) in ammonia/ammonium buffer at pH 9 and 50°C of the purified ethomeen-molybdates (red-ochre compound) in 15/85 CD₃CN/H₂O showed a 1 : 6 ratio in di-ethomeen-ether/ethomeen release, in addition to 1.5% molybdate.The discovery of thedi-ethomeen-etherprovides a deeper insight into the synthesis ofAdditiv 104.Furthermore, the release of molybdate occurred at different reaction rates when compared with the previous experiments. In comparison with Additiv 104 the hydrolysis proceeded initially 10 times slower but ended up with nearly the same reaction velocity. It seems as if constituents in Additiv104 support the hydrolysis of the ethomeen-molybdates, which contradicts the assumed reaction course. Thus, it could be advantageous for the OECD tests to use Additiv 104 instead of purified ethomeen-molybdates.These and still other remarkable deviations show that the processes during the hydrolysis of theethomeen-molybdates containing speciesare not yet fully understood.

·        Planned next tasks to accomplish the requirements under OECD TG 111

• Hydrolysis of Additiv 104 DS fraction at pH 4 and 9 to test the hydrolysis stability of the identified di-ethomeen-ether
• Improved characterization of the higher molecular (3460±300 g/mol) main ethomeen-molybdate compounds
• Improved use of organic modifier (solvent combinations) to enable the use of NMR monitoring for the detection of hydrolysis compounds
• Establishment of feasible hydrolysis tests with Additiv 104 or red-ochre precipitate (reference ethomeen-molybdate compounds) at pH 4, 7 and 9, using IC for Mo release detection (final decision for suitable test compound required)
• Preparation of Study Plan for the hydrolysis test of according to OECD111 guideline and under GLP conditions
• Identification of the hitherto unknown di-ethylamine compounds