HDI oligomers, allophanate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

As the test item was found to be poorly soluble in water it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004). As agreed with the sponsor a further hydrolysis test with acetonitrile as organic solvent additive was performed. The following investigations were performed:
• Preparation of an aqueous solution of the test item using acetonitrile as organic solvent additive and storage under stirring
• Recording of IR spectra of the precipitated solid particles after drying and comparison with the IR-spectrum of the original test item

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Transformation products:

not measured

Temp.:

20 °C

DT50:

ca. 24 h

Type:

not specified

Remarks on result:

other: half-life in water-ACN mixture

Other kinetic parameters:

The pH of the water used for the test was about 7. Howver pH was not measure in the mixture contained a high portion of Acetnonitrile (70 %).

Details on results:

A comparison of the IR spectra of the original test item and the dried sediment after 5 min stirring time shows only marginal differences. However, with increasing stirring time the intensity of the absorption band corresponding to the NCO-function of the test item decreases significantly whereas the allophanate functional group remains unchanged.
Relevant structure elements of the test item:
NCO: 2253 cm-1 representing the isocyanate functional group
C(=O)-N-H 1527 cm-1 representing the allophanate functional group
Therefore it can be assumed that the decreasing isocyanate function as relevant structure element for hydrolytic behavior indicates the hydrolysis of the test item.
Comparing the signal intensities, a hydrolysis of approx. 50 % within 24 hours can be visually estimated.
No significant additional absorption bands were detected. It could not be distinguished between degradation products and potentially precipitated test item, which is known to be poorly soluble.

Identification of hydrolysis products was technically not feasible

Conclusions:

The test item undergoes a hydrolysis reaction with demineralized water using 70 volume % acetonitrile as organic solvent additive. Relating to this test mixture a degradation of approx. 50 % within 24 hours can be estimated.

Executive summary:

For the test item the hydrolysis behaviour should be investigated. As the test item was found to be poorly soluble in water it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004). A further hydrolysis test with acetonitrile as organic solvent additive was performed.

The following investigations were performed:

a) Preparation of an aqueous solution of the test item using acetonitrile as organic solvent additive and storage under stirring

b) Recording of IR spectra of the precipitated solid particles after drying and comparison with the IR-spectrum of the original test item. Identification of hydrolysis products was technically not feasible.

The test item undergoes a hydrolysis reaction with demineralized water using 70 volume % acetonitrile as organic solvent additive. Relating to this test mixture a degradation of approx. 50 % within 24 hours can be estimated.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

Preparation of aqueous suspensions in 2 different concentrations at 20°C for 24 h. - Determination of TOC in the aqueous phases after filtration.- Recording of IR spectra of the undissolved sediments and comparison with IR-spectrum of the orig. substance.

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Duration:

24 h

pH:

5.5

Temp.:

20 °C

Preliminary study:

For the substance the hydrolysis behaviour should be investigated. As the test item was found to be poorly soluble in water (water solubility study no. 2011/0034/14) it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004).

Transformation products:

no

Key result

pH:

5.5

Remarks on result:

hydrolytically stable based on preliminary test

Details on results:

In the filtrate of the test solutions different contents of total organic carbon at different concentrations (100 mg/l and 1000 mg/l) were determined, even though the TOC values are negligible in relation to the test item concentrations.
In a mixture, multi-constituent substance, or UVCB (Unknown or Variable composition, Complex reaction products or Biological materials) substance, each constituent has its own solubility which may differ from the solubility of the others. Due to increased TOC values at higher test item concentration the existence of constituents with higher solubility can be supposed, indicated by TOC in the aqueous phase of the hydrolysis test solution. This soluble part of the test item was consid-ered to be marginal and was therefore not investigated with regard to hydrolysis behaviour.
On the other hand the IR spectra of the undissolved particles and the original test item show no difference. Therefore it can be assumed that the liquid particles are identical with the test item. The most predominant part of the test item undergoes no hydrolysis reaction in demineralized water within 24 hours and remains as an undissolved liquid residue.
No further investigations were performed.

Validity criteria fulfilled:

yes

Conclusions:

For the substance the hydrolysis behaviour should be investigated. As the test item was found to be poorly soluble in water (water solubility study no. 2011/0034/14), it was therefore not possible to prepare an aqueous solution of the test item and not necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004).

Executive summary:

For the substance the hydrolysis behaviour should be investigated. As the test item was found to be poorly soluble in water (water solubility study no. 2011/0034/14) it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004).

In deviation to OECD 111 the following investigations were decided to be suitable to evaluate the hydrolysis behaviour of the test item and were therefore performed in agreement with the sponsor.

• Preparation of aqueous suspensions in two different concentrations and incubation at 20 °C for 24 hours under stirring

• Determination of the contents of total organic carbon (TOC) in the aqueous phases after filtration

• Recording of IR spectra of the undissolved sediments and comparison with the IR-spectrum of the original test item

Result and conclusion:

In the filtrate of the test solutions different contents of total organic carbon at different concentrations (100 mg/l and 1000 mg/l) were determined, even though the TOC values are negligible in relation to the test item concentrations.

In a mixture, multi-constituent substance, or UVCB (Unknown or Variable composition, Complex reaction products or Biological materials) substance, each constituent has its own solubility which may differ from the solubility of the others. Due to increased TOC values at higher test item concentration the existence of constituents with higher solubility can be supposed, indicated by TOC in the aqueous phase of the hydrolysis test solution. This soluble part of the test item was considered to be marginal and was therefore not investigated with regard to hydrolysis behaviour.

On the other hand the IR spectra of the undissolved sediment and the original test item show no difference. Therefore it can be assumed that the liquid sediment is identical with the test item. The most predominant part of the test item undergoes no hydrolysis reaction in demineralized water within 24 hours and remains as an undissolved liquid residue.

Reference 3

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

No final test report was prepared but a summary of all relevant results.

Principles of method if other than guideline:

The data contain information on a number of pre-tests which were performed in order to perform a full hydrolysis study according to OECD 111 with a maximum of 1 % modifier as accepted by the guideline OECD 111. This pre-test also contains information on trials using higher concentration of modifier up to 10 %. The study report is not presented in a typical report format but is a summary of the experiments performed

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

0, 0.25, 1, 2, 4, 6, 8, 10, and 24 hours

Buffers:

- pH 4: ammonium formate/ fomic acid
- pH 7: water (pH was checked at each sampling time point)
- pH 9: ammonia/ ammonium formate

Estimation method (if used):

no extraction, direct injection after derivatisation with dibutlylamine

Duration:

24 h

pH:

4

Temp.:

23 °C

Initial conc. measured:

2 mg/L

Remarks:

starting concentration 2 mg/L

Duration:

24 h

pH:

7

Temp.:

23 °C

Initial conc. measured:

2 mg/L

Remarks:

starting concentration 2 mg/L

Duration:

24 h

pH:

9

Temp.:

23 °C

Initial conc. measured:

2 mg/L

Remarks:

starting concentration 2 mg/L

Number of replicates:

three

Positive controls:

no

Negative controls:

no

Test performance:

A stock solution of IPDI allophanat was prepared using acetonitrile. Subsequently, this solution was diluted by adding the stock solution with stirring to a specified amount of water resulting in a target concentration of 2 mg/L including 1 % modifier (acetonitrile). In consequence of the moderate repeatability the samples were prepared in triplicate. According to a sampling protocol aliquots of the sample were taken and added to a solution of derivatisation agent (Dibutylamine) within a time period of 24 hours (0, 0.25, 1, 2, 4, 6, 8, 10, and 24 hours). Temperature was room temperature (23 °C ± 1 °C)
Semi-quantification was performed by means of an external calibration curve. Due to the lack of reference substances the sample IPDI allophanat was diluted to different concentration levels between 0 and 5 mg/L. The obtained samples were derivatised with dibutylamine, too.

Transformation products:

no

Remarks:

Transformation products were screened but could not be identified.

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

In tests with 1 % modifyer (ACN) and a starting concentration of 2 mg/L no signals at all could be detected. This was found although the starting concentration of 2 mg/L was not that low and the analytical instrumentation used (UPLC with high resolution mass spectroscopy)

pH:

4

Temp.:

23 °C

DT50:

ca. 4 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: The degradation of three main components was monitored: C28H46N4O3, C29H48N4O5 and C36H54N6O6

pH:

7

Temp.:

23 °C

DT50:

ca. 2 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: The degradation of three main components was monitored: C28H46N4O3, C29H48N4O5 and C36H54N6O6

pH:

9

Temp.:

23 °C

DT50:

ca. 2 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: The degradation of three main components was monitored: C28H46N4O3, C29H48N4O5 and C36H54N6O6

Other kinetic parameters:

No kinetic parameters were calculated. The half life was estimated using the degradation curves yielding a half-life of about 2 hours.

Validity criteria fulfilled:

no

Remarks:

Due to the rapid hydrolysis and the difficult behavour of the substance in water the reproducibility between replicates is higher than foreseen in the guideline. Nevertheless, a trend can clearly be seen and an estimation of the half-life can be given

Conclusions:

Three main components of the substance yielded in half-lives of about two hours at 23 °C. No degradation products could be found although a sensitive UPLC-HRMS method has been used. It is therefore assumed that oligomeric and polymeric ureas are the hydrolysis products.

Executive summary:

Several attempts have been made to find a guideline compliant and technically feasible way in order to describe the hydrolysis behaviour. The challenge was to reduce the start concentration of the substance which - on the one hand - is suspected to have an extremely poor water solubility (QSAR estimation: about 1 ng/L) and - on the other hand - shall be kept soluble in water containing not more than 1 % modifier. For this goal high-end technology (UPLC-high-resolution-mass spectrometry) was used. Finally, conditions were found which in fact led to increased variations between replicates but showed a tendency in the hydrolysis behaviour. For the main components, a half-life of about 4 hours at room temperature in pure water is estimated. However, it was found that already at time zero a relevant portion of the substance (>50 %) had been disappeared. After having performed all these experiments we believe that an OECD 111 hydrolysis test at 3 pH-values could be performed but it is doubtful whether the guideline´s criteria, especially those for repeatability (recovery >70 %) can be fulfilled. Nevertheless, in view of the complex nature of the substance, a hydrolysis study even not fulfilling all quality criteria would give useful data on half-lifes and hydrolysis products. In one pre-test using low concentrations, structure elucidation of hydrolysis products was performed, but no relevant structures were found. It is well known that isocyanates rapidly react with water under formation of an amino group. The amino group is rather nucleophilic and reacts further with remaining isocyanate groups yielding urea substances. The three main products which also have the lowest molecular weight of the constituents are C28H46N4O5 (518 D), C29H48N4O5 (532 D) and C36H54N6O6 (666 D). They consist of two or three isocyanate groups. This means that ureas formed by two isocynate groups have molecular weights of at least 1000 D, and ureas formed by reaction of three isocyanate groups have molecular weights >1500 D. The detection range of the HRMS instrument used is up to 1800 D. As none of these lower ureas have been formed it can be assumed that higher oligo and polyureas are formed which cannot be detected with the instrument used.

In a pre-test using higher concentrations of test item and modifyer, some structural information was received but the results are doubtful as precipitation occurred during the test.

Reference 4

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The test was not performed in solution as required by the guideline but with particles in aqueous medium.

Principles of method if other than guideline:

Preparation of aqueous suspensions in two different concentrations and incubation at 20 °C for 24 hours under stirring, Determination of the contents of total organic carbon (TOC) in the aqueous phases after filtration, Recording of IR spectra of the undissolved sediments and comparison with the IR-spectrum of the original test item

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on test conditions:

Based on the results of a pretest and an additionally conducted water solubility study, the test item was found to be poorly soluble in demineralized water with a solubility of <2 mg/L Total Organic Carbon (TOC) corresponding to <3.1 mg/L test item (CURRENTA study no. 2010/0045/05).
The test item was applied in demineralized water receiving suspensions in concentrations of 100 mg/L and 1000 mg/L.
Approximately 20 mg and approximately 200 mg of the test item were weighed into Erlenmeyer flasks. 200 mL of demineralized water were added to receive concentrations of 100 mg/L and 1000 mg/L. The test item appeared as colourless crystalline sediment on the bottom of the flask. The mixtures were agitated with a magnetic stirrer for 24 hours at 20 °C under nitrogen atmosphere in a temperature-controlled water bath.
After 24 hours saturated mixtures with undissolved sediment were received. The test item appeared unchanged as colourless crystalline sediment. The received suspensions were filtered through 0.45 μm Chromafil Xtra PET 45/25 filter. Clear aqueous phases were obtained after filtration.
After phase separation the concentrations of the total organic carbon (TOC) in the aqueous phases were determined.
The sediments of a test concentration of 1000 mg/L test item were carefully dried at 50 °C for 24 hours. IR spectra of the dried sediments were recorded and compared with an IR spectrum of the original test item.

Duration:

24 h

pH:

5.5

Temp.:

20 °C

Initial conc. measured:

100 mg/L

Number of replicates:

2

Preliminary study:

The study is to be undersood as a preliminary study: Only one pH value was tested and no hydrolysis products were monitored. Further, the substance was not fully dissolved in water but hydrolysis was investigated with solid particles in water.

Transformation products:

no

pH:

5.5

Temp.:

20 °C

Remarks on result:

not determinable because of methodological limitations

The IR spectra of the sediments and of the original test item show no difference. No additional absorption bands were detected . Therefore it can be assumed, that the following structure elements as functional groups relevant for the hydrolysis behavior remained unchanged.

Relevant structure elements:

NCO: 2252 cm^-1 representing the isocyanate functional group

C(=O)-N-H 1528 cm^-1 representing the allophanate functional group

The content of total organic carbon in the filtrate of the test solutions is determined to be <2 mg/L TOC (limit of quantification of the analytical method). Therefore it can be assumed that no organic constituents were present in the aqueous phase of the hydrolysis test solution (below the limit of quantification).

Validity criteria fulfilled:

yes

Conclusions:

The test item undergoes no hydrolysis reaction in demineralized water within 24 hours and remains as an undissolved solid residue.

Executive summary:

The test item was found to be poorly soluble in water therefore the following deviations of OECD TG 111 were made: Preparation of aqueous suspensions in two different concentrations and incubation at 20 °C for 24 hours under stirring. Determination of the contents of total organic carbon (TOC) in the aqueous phases after filtration, Recording of IR spectra of the undissolved sediments and comparison with the IR-spectrum of the original test item.

The content of total organic carbon in the filtrate of the test solutions is determined to be <2 mg/L TOC (limit of quantification of the analytical method). Therefore it can be assumed that no organic constituents were present in the aqueous phase of the hydrolysis test solution (below the limit of quantification).

The IR spectra of the undissolved sediment and the original test item show no difference. Therefore it can be assumed that the solid sediment is identical with the test item.

The test item undergoes no hydrolysis reaction in demineralized water within 24 hours and remains as an undissolved solid residue.

Reference 5

Endpoint:

hydrolysis

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Isocyanates have their high reactivity in common. This and a unique combination of physico-chemical properties which dictate a high degree of uniformity in their environmental fate and ecotoxicological effects. The most important process affecting the fate and hazard potential of these isocyanate substances in the environment is hydrolysis. In the environment, when isocyanates come into contact with water, they do not disperse readily, but form globules or solid masses, which react at their surface (also called heterogeneous reaction). The particles or droplets of isocyanate substances will be readily transformed (hydrolyzed) to particles of inert, insoluble, and non-toxic polyurea polymers (cf. Figure 1). This is regardless of the environmental compartment (i.e., water, sediment, or soil) where their emission may occur. These polyureas are the predominant reaction product formed when these isocyanate substances contact water.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target substances are UVCB substances belonging to the larger group of oligomerized diisocyanates, resulting in complex mixtures of higher molecular allophanates. The source substance, Oligomerisation products of 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate and butan-1-ol and pentan-1-ol and 2-ethylhexan-1-ol, allophanate type (EC No. 933-047-9), is for better readability referred to as IPDI allophanate in this document. For the same reason, the target substance, Hexamethylene diisocyanate, oligomerisation product (allophanate type) (EC No. 939-657-1), is referred to as HDI allophanate.

The reactive group present in source and target substance is the terminal isocyanate function, which appears in both. Yet, through the difference in starting materials the structural complexity of both substances differs. The positions in which the terminal isocyanate groups appear are different, but as it is always linked to either linear or cyclic aliphatic carbon chains, reactivity is considered equivalent.
The substances are similar with respect to their behavior in the environment, as both exhibit a very limited water solubility and similar partition coefficient over the threshold value, logKow > 3. Therefore, presence in the aquatic compartment is limited. With densities around 1.1 g/cm3, their negligible vapour pressure (< 0.01 Pa) and low volatility dispersion into the air compartment can be excluded. Both form high molecular polyureas, when released into aquatic or soil compartment, which are not subject to biodegradation nor bioaccumulation due to their high molecular weight (> 1800 Da).

3. ANALOGUE APPROACH JUSTIFICATION
Both substances are UVCB substances and no transformation into each other can be assumed. The common compound is described by the individual substance. Similarities in effects due to structural similarities are however suggested.

4. DATA MATRIX
Pease refer to the justification document procided in chpt. 13.

Reason / purpose for cross-reference:

assessment report

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

The test was not performed in solution as required by the guideline but with particles in aqueous medium.

Principles of method if other than guideline:

Preparation of aqueous suspensions in two different concentrations and incubation at 20 °C for 24 hours under stirring, Determination of the contents of total organic carbon (TOC) in the aqueous phases after filtration, Recording of IR spectra of the undissolved sediments and comparison with the IR-spectrum of the original test item

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on test conditions:

Based on the results of a pretest and an additionally conducted water solubility study, the test item was found to be poorly soluble in demineralized water with a solubility of <2 mg/L Total Organic Carbon (TOC) corresponding to <3.1 mg/L test item (CURRENTA study no. 2010/0045/05).
The test item was applied in demineralized water receiving suspensions in concentrations of 100 mg/L and 1000 mg/L.
Approximately 20 mg and approximately 200 mg of the test item were weighed into Erlenmeyer flasks. 200 mL of demineralized water were added to receive concentrations of 100 mg/L and 1000 mg/L. The test item appeared as colourless crystalline sediment on the bottom of the flask. The mixtures were agitated with a magnetic stirrer for 24 hours at 20 °C under nitrogen atmosphere in a temperature-controlled water bath.
After 24 hours saturated mixtures with undissolved sediment were received. The test item appeared unchanged as colourless crystalline sediment. The received suspensions were filtered through 0.45 μm Chromafil Xtra PET 45/25 filter. Clear aqueous phases were obtained after filtration.
After phase separation the concentrations of the total organic carbon (TOC) in the aqueous phases were determined.
The sediments of a test concentration of 1000 mg/L test item were carefully dried at 50 °C for 24 hours. IR spectra of the dried sediments were recorded and compared with an IR spectrum of the original test item.

Duration:

24 h

pH:

5.5

Temp.:

20 °C

Initial conc. measured:

100 mg/L

Number of replicates:

2

Transformation products:

no

pH:

5.5

Temp.:

20 °C

Remarks on result:

not determinable because of methodological limitations

The IR spectra of the sediments and of the original test item show no difference. No additional absorption bands were detected . Therefore it can be assumed, that the following structure elements as functional groups relevant for the hydrolysis behavior remained unchanged.

Relevant structure elements:

NCO: 2252 cm^-1 representing the isocyanate functional group

C(=O)-N-H 1528 cm^-1 representing the allophanate functional group

The content of total organic carbon in the filtrate of the test solutions is determined to be <2 mg/L TOC (limit of quantification of the analytical method). Therefore it can be assumed that no organic constituents were present in the aqueous phase of the hydrolysis test solution (below the limit of quantification).

Validity criteria fulfilled:

yes

Conclusions:

Based on data available on the test item as well as gathered through the read-across approach on a structural analogue the substance undergoes complete hydrolysis after 2 h at room temperature. As a result high molecular polyureas are formed, which are insoluble in water.

Executive summary:

The test item was found to be poorly soluble in water. The beahavior of the structural analogue towards hydrolysis has been thoroughly investigated. Therefore, the read-across approach has been chosen to provide a comprehensive database for this endpoint.
In two studies (Neuland 2012, Neuland 2013), the structural analogue was found to be poorly soluble in water, it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004). A further hydrolysis test with acetonitrile as organic solvent additive was performed and relating to this test mixture a degradation of approx. 50 % within 24 hours can be estimated. These investigations had also been performend on the source substance itself, yielding the same results.

In a third attempt (Allmendinger and Tretzel, 2018), a lot of tests were made to find a guideline compliant and technically feasible way in order to describe the hydrolysis behaviour. The challenge was to reduce the start concentration of the substance which - on the one hand - is suspected to have an extremely poor water solubility (QSAR estimation: about 1 ng/L) and - on the other hand - shall be kept soluble in water containing not more than 1 % modifier. For this goal high-end technology (UPLC-high-resolution-mass spectrometry) was used. Finally, conditions were found which in fact led to increased variations between replicates but showed a clear tendency in the hydrolysis behaviour. For the main components, a half-life of about 2 hours at room temperature in pure water was estimated. However, it was found that already at time zero a relevant portion of the substance (>50 %) had been disappeared. After having performed all these experiments it can be concluded that

1. performance of an OECD 111 hydrolysis test at 3 pH-values cannot be performed meeting the relevant quality criteria: Especially the criteria for repeatability (recovery >70 %) cannot be fulfilled. Further, potential hydrolysis products such as oligomeric and polymeric ureas are essentially insoluble in water as well as in organic solvents. Therefore these compounds cannot be analysed even by high-end analytical instrumentation. Finally this will lead to an analytical gap as that full quantitative recovery or mass balance of parent substance and all hydrolysis products is technically not possible.

2. nevertheless, in view of the complex nature of the substance, the hydrolysis experiments even not fulfilling all quality criteria will give useful data on half-lifes and hydrolysis products. In one pre-test using low concentrations, structure elucidation of hydrolysis products was performed, but no relevant structures were found although highly sensitive and analytical high end technique was used (UPLC-HRMS). It is well known that isocyanates rapidly react with water under formation of an amino group. The amino group is rather nucleophilic and reacts further with remaining isocyanate groups yielding urea substances. The three main products which also have the lowest molecular weight of the constituents are C28H46N4O5 (518 D), C29H48N4O5 (532 D) and C36H54N6O6 (666 D). They consist of two or three isocyanate groups. This means that ureas formed by two isocyanate groups have molecular weights of at least 1000 D, and ureas formed by reaction of three isocyanate groups have molecular weights >1500 D. The detection range of the HRMS instrument used is up to 1800 D. As none of these lower ureas have been formed it can be assumed that higher oligo and polyureas are formed which cannot be detected with the instrument used.

In a pre-test using higher concentrations of test item and modifier, some structural information was received but the results are doubtful as precipitation occurred during the test.

 

According to ECHA guidance document R11 (July 2017) "careful consideration of the hydrolysis test is required" and the removal of parent substance shall be evaluated by several means:

1. "Hidden loss" by evaporation: The smallest main constituent has a molecular weight of 518 and a vapour pressure of 1.7E-04 Pa at 20 °C. This makes substance loss by evaporation very unlikely.

2. "Hidden loss" by adsorption: Hydrolysis tests (Allmendinger and Tretzel 2018) were performed with a modifier (1 % ACN). Earlier tests used higher concentrations of a modifier in order to avoid potential losses yielded similar results. Visual examinations of the flasks did not indicate any particles or adsorption to the glass wall although they were carefully examined using scattering light. It was found that already at time 0 (i.e.1 min after addition of sample to water) only 50 % of the theoretical amount was found indicating a rather rapid hydrolysis. It must be discussed and finally cannot be excluded that the loss might be due to limited solubility and precipitation. However, the use of derivatisation agents DBA would made precipitation visible as derivatives.

3. Preliminary experiments at pH 4 and 9 show rapid hydrolysis as well.

4. Abiotic degradation: The key reaction of an isocyanate in water is hydrolysis. Amines as the primary degradation products were not found in the tests. They are known to react must faster with isocyanates than with water. Thus, ureas are formed. Ureas could not be detected with the UPLC-HRMS instrument which is able to detect masses up to 1800 D. Consequently, there is evidence that higher oligomeric and polymeric ureas have been formed which cannot be analysed although high-end instrumentation was used.

5. The requirement for a full mass balance in a hydrolysis test cannot be fulfilled for a UVCB substance. About 30 components have been identified. However each of the components consists of a variety of structural isomers and stereoisomers.

Description of key information

As the test item was found to be poorly soluble in water, it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004). A further hydrolysis test with acetonitrile as organic solvent additive was performed and relating to this test mixture a degradation of approx. 50 % within 24 hours could be estimated.

Additional testing has been performed on a structural analogue, Oligomerisation products of 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate and butan-1-ol and pentan-1-ol and 2-ethylhexan-1-ol, allophanate type (EC No. 933-047-9) and a read-across-approach has been used to better assess the hydrolysis behavior of Hexamethylene diisocyanate, oligomerisation product (allophanate type) (EC 939-657-1).

Three main components of the structural analogue yielded in half-lives of about 2 hours at 23 °C. No degradation products could be found although a sensitive UPLC-HRMS method had been used with a mass range up to 1800 D. It is therefore assumed that oligomeric and polymeric ureas are the hydrolysis products which are not detectable due to their high molecular weights.

Key value for chemical safety assessment

Half-life for hydrolysis:

2 h

at the temperature of:

23 °C

Additional information

The beahavior of the structural analogue towards hydrolysis has been thoroughly investigated. Therefore, the read-across approach has been chosen to provide a comprehensive database for this endpoint.
In two studies (Neuland 2012, Neuland 2013), the structural analogue was found to be poorly soluble in water, it was therefore not possible to prepare an aqueous solution of the test item necessary to perform a hydrolysis test according to the requirements of OECD TG 111 (2004). A further hydrolysis test with acetonitrile as organic solvent additive was performed and relating to this test mixture a degradation of approx. 50 % within 24 hours can be estimated. These investigations had also been performend on the source substance itself, yielding the same results.

In a third attempt (Allmendinger and Tretzel, 2018), a lot of tests were made to find a guideline compliant and technically feasible way in order to describe the hydrolysis behaviour. The challenge was to reduce the start concentration of the substance which - on the one hand - is suspected to have an extremely poor water solubility (QSAR estimation: about 1 ng/L) and - on the other hand - shall be kept soluble in water containing not more than 1 % modifier. For this goal high-end technology (UPLC-high-resolution-mass spectrometry) was used. Finally, conditions were found which in fact led to increased variations between replicates but showed a clear tendency in the hydrolysis behaviour. For the main components, a half-life of about 2 hours at room temperature in pure water was estimated. However, it was found that already at time zero a relevant portion of the substance (>50 %) had been disappeared. After having performed all these experiments it can be concluded that

1. performance of an OECD 111 hydrolysis test at 3 pH-values cannot be performed meeting the relevant quality criteria: Especially the criteria for repeatability (recovery >70 %) cannot be fulfilled. Further, potential hydrolysis products such as oligomeric and polymeric ureas are essentially insoluble in water as well as in organic solvents. Therefore these compounds cannot be analysed even by high-end analytical instrumentation. Finally this will lead to an analytical gap as that full quantitative recovery or mass balance of parent substance and all hydrolysis products is technically not possible.

2. nevertheless, in view of the complex nature of the substance, the hydrolysis experiments even not fulfilling all quality criteria will give useful data on half-lifes and hydrolysis products. In one pre-test using low concentrations, structure elucidation of hydrolysis products was performed, but no relevant structures were found although highly sensitive and analytical high end technique was used (UPLC-HRMS). It is well known that isocyanates rapidly react with water under formation of an amino group. The amino group is rather nucleophilic and reacts further with remaining isocyanate groups yielding urea substances. The three main products which also have the lowest molecular weight of the constituents are C28H46N4O5 (518 D), C29H48N4O5 (532 D) and C36H54N6O6 (666 D). They consist of two or three isocyanate groups. This means that ureas formed by two isocyanate groups have molecular weights of at least 1000 D, and ureas formed by reaction of three isocyanate groups have molecular weights >1500 D. The detection range of the HRMS instrument used is up to 1800 D. As none of these lower ureas have been formed it can be assumed that higher oligo and polyureas are formed which cannot be detected with the instrument used.

In a pre-test using higher concentrations of test item and modifier, some structural information was received but the results are doubtful as precipitation occurred during the test.

 

According to ECHA guidance document R11 (July 2017) "careful consideration of the hydrolysis test is required" and the removal of parent substance shall be evaluated by several means:

1. "Hidden loss" by evaporation: The smallest main constituent has a molecular weight of 518 and a vapour pressure of 1.7E-04 Pa at 20 °C. This makes substance loss by evaporation very unlikely.

2. "Hidden loss" by adsorption: Hydrolysis tests (Allmendinger and Tretzel 2018) were performed with a modifier (1 % ACN). Earlier tests used higher concentrations of a modifier in order to avoid potential losses yielded similar results. Visual examinations of the flasks did not indicate any particles or adsorption to the glass wall although they were carefully examined using scattering light. It was found that already at time 0 (i.e.1 min after addition of sample to water) only 50 % of the theoretical amount was found indicating a rather rapid hydrolysis. It must be discussed and finally cannot be excluded that the loss might be due to limited solubility and precipitation. However, the use of derivatisation agents DBA would made precipitation visible as derivatives.

3. Preliminary experiments at pH 4 and 9 show rapid hydrolysis as well.

4. Abiotic degradation: The key reaction of an isocyanate in water is hydrolysis. Amines as the primary degradation products were not found in the tests. They are known to react must faster with isocyanates than with water. Thus, ureas are formed. Ureas could not be detected with the UPLC-HRMS instrument which is able to detect masses up to 1800 D. Consequently, there is evidence that higher oligomeric and polymeric ureas have been formed which cannot be analysed although high-end instrumentation was used.

5. The requirement for a full mass balance in a hydrolysis test cannot be fulfilled for a UVCB substance. About 30 components have been identified. However each of the components consists of a variety of structural isomers and stereoisomers.