2,5-bis-isocyanatomethyl-bicyclo[2.2.1]heptane

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

N/A

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Remarks:

The Hydrolysis was calculated with Hydrowin Program (v.2.00), part of Episuite. This model is considered reliable by ECHA.

Justification for type of information:

1. SOFTWARE: EPI Suite (v.4.11). The EPI (Estimation Programs Interface) Suite™ is a Windows®-based suite of physical/chemical property and environmental fate estimation programs developed by EPA’s and Syracuse Research Corp. (SRC).

2. MODEL (incl. version number) HYDROWIN (v2.00)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: O=C=NCC2C1CC(CN=C(=O))C(C2)C1

This endpoint study record is part of a Weight of Evidence approach comprising a QSAR (this study) and a hydrolysis study . Both data sources agree that the half -life of NDBI is less than 12 hours and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Reason / purpose for cross-reference:

data waiving: supporting information

Principles of method if other than guideline:

HYDROWIN (the hydrolysis program) was developed at Syracuse Research Corporation for the US Environmental Protection Agency. HYDROWIN requires only a chemical structure to estimate the hydrolysis. Structures are entered into HYDROWIN by SMILES (simplified molecular Input Line Entry System) notifications.

HYDROWIN™: Estimates aqueous hydrolysis rate constants and half-lives for the following chemical classes: esters, carbamates, epoxides, halomethanes, selected alkyl halides, and phosphorus esters. Estimates rate constants for acid- and base-catalyzed hydrolysis, but with the exception of phosphorus esters, not neutral hydrolysis. In addition, HYDROWIN™ identifies a variety of chemical structure classes for which hydrolysis may be significant (e.g. carbamates) and gives relevant experimental data.

This endpoint study record is part of a Weight of Evidence approach comprising a QSAR (this study) and a hydrolysis study . Both data sources agree that the half -life of NDBI is less than 12 hours and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

GLP compliance:

no

Transformation products:

not specified

Key result

DT50:

< 12 h

Remarks on result:

other: QSAR Calculation Using HYDROWIN (v2.00)

HYDROWIN Program (v2.00) Results:

================================

SMILES : O=C=NCC2C1CC(CN=C(=O))C(C2)C1

CHEM   :

MOL FOR: C11 H14 N2 O2

MOL WT : 206.25

--------------------------- HYDROWIN v2.00 Results ---------------------------

 Hydrolyzable Function detected:  Isocyanates      

 

  -N=C=O

 

    Isocyanates hydrolyze readily in water to yield a carbamic acid, which

    decarboxylates to produce CO2 and an amine; the latter immediately

    reacts with more isocyanate to yield a disubstituted urea. The hydrolysis

    rate increases with electron-withdrawing substituents. Steric hindrance

    also influences hydrolysis rate; aliphatic isocyanate rates are:

    primary > secondary > tertiary  (Ullmann's Encycl, A14:611-613).

 

    Even at low pHs, hydrolysis Half-Life < 10 minutes (25 deg C)

          Experimental Hydrolysis Half-Lifes (HSDB, 2007):

            Methyl isocyanate:   9 minutes (25 deg C)

            Phenyl isocyanate:   55 seconds (water/dioxane solution)

Validity criteria fulfilled:

not applicable

Conclusions:

The Hydrolysis of the substance has been calculated with the HYDROWIN program (v.2.00). The Even at low pH's, hydrolysis Half-Life < 10 minutes (25 deg C)

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 1991 - November 1991

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Not conducted according to Guideline, still providing useful supporting information.

Justification for type of information:

This endpoint study record is part of a Weight of Evidence approach comprising a non GLP hydrolysis study (this study) and a QSAR calculation. Both data sources agree that the half -life of NDBI is less than 12 hours and are sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Preliminary study: The substance was added to water in 3 different initial concentrations (10; 30 and 70 mg/L). These 3 concentrations were stirred for 3 up to 48 hours. The conversion rate of the substance was determined.
Main study: The substance was added to water (100 mg in 1000 ml). After stirring for 24 hours, NBDI was analysed by GC. The hydrolysis product NBDA was analysed by HPLC. The oligomers were analyzed by FD-MS and IR.

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

yes

Duration:

24 h

Initial conc. measured:

100 mg/L

Preliminary study:

Average conversion rate of the substance to NBDA
(averaged over the 4 stirring times of 3, 6, 24 and 48 hours):
10 mg/L: 85.9 %
30 mg/L: 74.7%
70 mg/L: 62.6%
The highest conversion rate is found after 24 hours of stirring in all 3 concentrations. Therefore 24 hours was choosen for the main study.

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#2

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

The substance (NBDI) reacts immediately with water to form the diamine NBDA (Mixture of 5-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine and 6-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine). NBDA reacts with NBDI to form oligomers. No other hydrolysis products are assumed to be formed under the conditions of this test.

Key result

Remarks on result:

other: No DT50 was calculated. The conversion rate of NBDI to NBDA in water is fast; after 3 hours a conversion rate of 60-85% was shown

Validity criteria fulfilled:

not applicable

Conclusions:

The substance reacts with water to form the diamine NBDA (Reaction mass of 5-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine and 6-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine). This hydrolysis product can react further in water with the substance NBDI, to form oligomers. The conversion rate of NBDI to NBDA in water is fast; after 3 hours a conversion rate of 60-85% was shown (depending on the initial concentration).

Description of key information

In accordance with REACH Annex XI section 1.2 a weight of evidence approach was used to fulfil the data requirements for section 5.1.2 (hydrolysis).

A hydrolysis study was performed with the substance NBDI. The substance reacts with water to form the diamine NBDA (Reaction mass of 5-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine and 6-(aminomethyl)-bicyclo[2.2.1]heptan-2-yl)methanamine). The conversion rate of NBDI to NBDA in water is fast; after 3 hours a conversion rate of 60-85% was shown (depending on the initial concentration).

The results of the QSAR calculation (HYDROWIN program v2.00) showed an half-life of <10 minutes at 25 deg. Celsius.

Based on the results of the hydrolysis study and the QSAR calculation, it can be concluded that the half-life of NDBI is considerably less than 12 hours and is sufficient to fulfil the information requirements.

It has been shown, in the environmental studies, that NBDA is hydrolytically stable and that the parent compound (NBDI) is not. Based on this information (e.g. half-life NBDI less than 12 hours), it is considered justified to conclude that the CSA for the environment needs to based on NBDA.

Additional information

The half-life of NBDI is considered to significant less than 12 hours.