Perhydroimidazo[4,5-d]imidazole-2,5-dione

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11.
Contact EPISuite:
U.S. Environmental Protection Agency
1200 Pennsylvania Ave.
N.W. (Mail Code 7406M)
Washington, DC 20460

2. MODEL (incl. version number)
HYDROWIN v2.00.
September 2010 (model development); November 2012 (model publication).

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See QPRF attached: ‘QPRF Title: Substance: Perhydroimidazo[4,5-d]imidazole-2,5-dione using the model HYDROWIN v2.00: for the endpoint: Hydrolysis’ version 1.0; 10 April 2018.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: HYDROWIN v2.00 for the endpoint: Hydrolysis’ version 1.0; Date: 01 April 2018; updated 24 April 2018.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See attached QPRF attached: ‘QPRF Title: Substance: Perhydroimidazo[4,5-d]imidazole-2,5-dione using the model HYDROWIN v2.00: for the endpoint: Hydrolysis’ version 1.0; 10 April 2018.

6. ADEQUACY OF THE RESULT
1) QSAR model is scientifically valid. 2) The substance falls within the general properties and mechanistic applicability domains, with limited applicability of the structural domain of the QSAR model (although all constituents > 80% correctly predicted ACF). Expert judgement considers the results reliable and relevant and the results are consistent with established literature. 3) The results are adequate when taken under consideration of REACH Regulation (EC) 1907/2006 in a weight of evidence as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Specifically, when combined with further information, details of which are available.

Reason / purpose for cross-reference:

assessment report

Guideline:

other: REACH Guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

Full details of the method are provided in the attached QMRF named ‘QMRF Title: HYRDOWIN v2.00 for the endpoint: Hydrolysis’ version 1.0; Date: 01 April 2018; updated 24 April 2018.

Specific details on test material used for the study:

Detailed information on the 'test material identity' is provided in the attached QSAR Prediction Reporting Format (QPRF) document including information on individual constituents.

Transformation products:

no

Remarks:

Based on the (Q)SAR output no transformation output are expected to generate until after >1 year of introduction of the test substance in water.

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

Not applicable, no transformation products were identified.

Key result

Type:

other: (Q)SAR predition value.

Remarks on result:

other: >1 year

Remarks:

The substance has been shown to be hydrolytically stable with a half-life of >1 year.

Details on results:

See QPRF attached: ‘QPRF Title: Substance: Perhydroimidazo[4,5-d]imidazole-2,5-dione using the model HYDROWIN v2.00: for the endpoint: Hydrolysis’ version 1.0; 10 April 2018.

1. Defined Endpoint:

QMRF 2. Hydrolysis

QMRF 2.1.a Persistence: Abiotic degradation in water: Hydrolysis

Reference to type of model used and description of results:

HYDROWIN v2.00; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11; September 2010 (model development); November 2012 (model publication).

2. Description of results and assessment of reliability of the prediction:

The predicted values are provided within the QPRF attached: ‘QPRF Title: Substance: Perhydroimidazo[4,5-d]imidazole-2,5-dione using the model HYDROWIN v2.00: for the endpoint: Hydrolysis’ version 1.0; 10 April 2018. The results of the hydrolysis predictions is not applicable since the test item is not expected to be readily hydrolytic in water.

Assessment of the substance within the applicability domains recommended by the developers is documented within the corresponding QMRF named ‘QMRF Title: HYRDOWIN v2.00 for the endpoint: Hydrolysis’ version 1.0; Date: 01 April 2018; updated 24 April 2018 – section 5; indicates the substance (constituents):

(i) All constituents fall within the Descriptors Domain (general properties, Molecular Weight range, Log Pow, Water Solubility).

(ii) All constituents fall within the mechanistic domain of the model.

3. Uncertainty of the prediction and mechanistic domain:

External validation has not been performed on the model (see QMRF: section 7).

Internal validation has been perfomed:

To be effective an estimation model must be capable of making accurate predictions for chemicals not included in the training set. Currently, HYDROWIN warns the operator when it encounters structures not found in its training set. Minimal testing and reviewing indicates that the method accuracy drops in these situations, but may still be acceptable or qualitatively correct (Millet et al., 1987).

The HYDROWIN model is based on the thermodynamic relationship between surrogate chemical structure (atom or group contribution) fragments and their chemical activity. The model includes data for several hundred structures, including substitution reaction constants and reaction-type constants. These, along within substructure steric and polar correction factors, are used to predict hydrolytic activity. In order to improve the model additional substances could be added to the model; new fragments and substructure corrections introduced.

Validity criteria fulfilled:

yes

Conclusions:

The results are adequate for the regulatory purpose.

Executive summary:

HYDROWIN v2.00 (model publication: November 2012)

Transformation products: Not expected; >1 year.

Adequacy of the QSAR:

1) QSAR model is scientifically valid. 2) The substance falls within the general properties and mechanistic applicability domains, with limited applicability of the structural domain of the QSAR model (although all constituents > 80% correctly predicted ACF). Expert judgement considers the results reliable and relevant and the results are consistent with established literature. 3) The results are adequate when taken under consideration of REACH Regulation (EC) 1907/2006 in a weight of evidence as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Specifically, when combined with further information, details of which are available.

Description of key information

The substance is stable in aqueous solution; hydrolysis is not seen and is not predicted based on a theoretical assessment of the structure of the molecule. HYDROWIN within EpiSuite (v4.11) has provided a prediction of >1 year and as such the substance is not considered to be readily hydrolytic in water.