Benzene-1,3,5-tricarbonyl trichloride

Water solubility

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

water solubility

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is hydrolytically unstable at pH 4, 7 and 9 (half-life less than 12 hours)

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 7.7, and in accordance with section 2 of REACH Regulation (EC) No. 1907/2006 Annex XI the study of water solubility does not need to be completed as testing is not technically possible. The available guidelines (OECD TG 105 and EU Method A.6) are only applicable to ‘the solubility in water of essentially pure substances which are stable in water’. The substance is hydrolytically unstable and therefore testing of the substance by the flask method is precluded by respecting the technical limitations of the specific method referred to. The applicant adapts the information requirement by providing (1) a reliable QSAR prediction for hydrolysis and/or (2) a reliable QSAR prediction for water solubility (which indicates the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis) for comparative purposes) and/or (3) weight of evidence calculation of n-octanol/water Log P, for both parent and transformation product. For the parent substance, it is noted that the predicted hydrolysis half-life is < 10 minutes at pH 4, 7 and 9. Expert judgement indicates that the rate of hydrolysis is accelerated by acid/base catalytic hydrolysis with a correspondingly lower predicted half-life at pH 4 and pH 9, than the pH 7.0 half life is << 10 minutes (ref: Benzoyl Chloride : t1/2 = 16 seconds). According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.7.4, v6.0, July 2017) the study does not need to be conducted. Furthermore, the hydrolysis transformation product that is rapidly formed is noted to be itself (biotically) ‘rapidly degraded’ within a period of 28 days. This was demonstrated within an available ‘readily biodegradable’ screening test conducted on the transformation product.

Reference 2

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

08-04-2022

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 adequate and reliable documentation / justification

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)
WSKOWWIN v1.42
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: benzene-1,3,5-tricarbonyl trichloride using the model WSKOWWIN v1.42 for the endpoint: Water Solubility’ version 1.0; 08 April 2022.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: WSKOWWIN v1.42 and parallel model WATERNT v1.01: Water Solubility’ version 1.1 ; date: 04 April 2022.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See attached QPRF attached: ‘QPRF Title: Substance: benzene-1,3,5-tricarbonyl trichloride using the model WSKOWWIN v1.42 for the endpoint: Water Solubility’ version 1.0; 08 April 2022.

6. ADEQUACY OF THE RESULT
1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The results are adequate when taken under consideration of REACH Regulation (EC) 1907/2006 in a weight of evidence. Provision of measured experimental water solubility and/or Partition Coefficient (n-octanol/water) has been determined as not technically possible under guidelines due to the substance being hydrolytically unstable (all pH) with half-life of much less than 12 hours and/or since the substance would decompose/reacts violently during the performance of the test. Therefore, in accordance with the tonnage driven information requirements: the weight of evidence approach to water solubility, partition coefficient and abiotic degradation: hydrolysis has been adopted by the provision of screening and modelled data. This is in conjunction to provision of measured biotic degradation and (eco)toxicological data on the degradant. It is noted that for highly hydrolytically unstable substances that the endpoint Water Solubility has limited applicability in the first instance. For the purpose of interpretation, the prediction should be considered as equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis). The prediction is provided for comparative purposes to support environmental hazard/risk assessment.

Guideline:

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

Principles of method if other than guideline:

- Model(s) used: WSKOWWIN v1.42
- Model description: Full details of the method are provided in the QMRF named ‘QMRF Title: WSKOWWIN v1.42 and parallel model WATERNT v1.01: Water Solubility’ version 1.1 ; date: 04 April 2022.
- The model applies the following methodology to generate predictions:
WSKOWWIN: physical-property correlation QSAR; based on multiple linear-regression modelling
- The model and the training and validation sets are published by US Environmental Protection Agency (USA).
The experimental Water Solubility values in the training set and validation set were measured using one or more methods equivalent or similar to the following guidelines:
- Flask or column elution methods (OECD TG 105)
- Slow Stirring methods (modified OECD TG 105) according to methods similar to those described by Letinksi and coworkers: Slow-stir water solubility measurements of selected alcohols and diesters”, Chemosphere, 48, 257 – 265 (2000).
Plus relevant EU and US EPA OPPTS methods may be also used where appropriate.
A full list of experimental Log Kow reference citations is provided in the WSKOWWIN help menu with additional reference citations.
- Justification of QSAR prediction: The result should be considered in relation to corresponding information presented and in accordance with the tonnage driven information requirements of REACH Regulation (EC) 1907/2006 in a weight of evidence.
Provision of measured experimental water solubility and/or Partition Coefficient (n-octanol/water) has been determined as not technically possible under guidelines due to the substance being hydrolytically unstable (all pH) with half-life of much less than 12 hours and/or since the substance would decompose/reacts violently during the performance of the test. Therefore, in accordance with the tonnage driven information requirements: the weight of evidence approach to water solubility, partition coefficient and abiotic degradation: hydrolysis has been adopted by the provision of screening and modelled data. This is in conjunction to provision of measured biotic degradation and (eco)toxicological data on the degradant. It is noted that for highly hydrolytically unstable substances that the endpoint Water Solubility has limited applicability in the first instance. For the purpose of interpretation, the prediction should be considered as equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis). The prediction is provided for comparative purposes to support environmental hazard/risk assessment.

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.

Key result

Water solubility:

71.36 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

pH:

7

Remarks on result:

other: Parent substance (benzene-1,3,5-tricarbonyl trichloride)

Remarks:

equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis)

Water solubility:

ca. 2 400 mg/L

Conc. based on:

test mat.

Temp.:

25 °C

pH:

7

Remarks on result:

other: Transformation product (benzene-1,3,5-tricarboxylic acid)

Remarks:

See attached QPRF for further details

Conclusions:

The results are adequate for the for the regulatory purpose.

Executive summary:

WSKOWWIN v1.42 (model publication: November 2012)

Parent substance (benzene-1,3,5-tricarbonyl trichloride) : WSOL = 71.36 mg/Lshould be considered as equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis).

Transformation product (benzene-1,3,5-tricarboxylic acid) : WSOL = ca. 2400 mg/L

The substance is in the slightly soluble (1 – 100 mg/L) range.

The hydrolysis products have increasing solubility in the soluble (1000 - 10000 mg/L) range.

 

Adequacy of the QSAR:

1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.

The prediction is adequate for the Classification and Labelling and/or risk assessment of the substance 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

Water Solubility : 71.36 mg/L should be considered as equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis) at 25 °C and ca. pH 7, QSAR Prediction – WSKOWWIN v1.42; EpiSuite 4.11 - US EPA, 2022

The substance consists of constituents in the slightly soluble (1 – 100 mg/L) range.

Note: The substance rapidly hydrolyses at all relevant pH 4, 7 and 9. Refer to ‘Hydrolysis’ and/or ‘Biodegradation’ sections for further information.

Key value for chemical safety assessment

Water solubility:

71.36 mg/L

at the temperature of:

25 °C

Additional information

In accordance with REACH Regulation (EC) No. 1907/2006 Annex VII, column 2 section 7.7, and in accordance with section 2 of REACH Regulation (EC) No. 1907/2006 Annex XI the study of water solubility does not need to be completed as testing is not technically possible. The available guidelines (OECD TG 105 and EU Method A.6) are only applicable to ‘the solubility in water of essentially pure substances which are stable in water’. The substance is hydrolytically unstable and therefore testing of the substance by the flask method is precluded by respecting the technical limitations of the specific method referred to. The applicant adapts the information requirement by providing (1) a reliable QSAR prediction for hydrolysis and/or (2) a reliable QSAR prediction for water solubility (which indicates the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis) for comparative purposes) and/or (3) weight of evidence calculation of n-octanol/water Log P, for both parent and transformation product. For the parent substance, it is noted that the predicted hydrolysis half-life is < 10 minutes at pH 4, 7 and 9. Expert judgement indicates that the rate of hydrolysis is accelerated by acid/base catalytic hydrolysis with a correspondingly lower predicted half-life at pH 4 and pH 9, than the pH 7.0 half life is << 10 minutes (ref: Benzoyl Chloride : t1/2 = 16 seconds). According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.7.4, v6.0, July 2017) the study does not need to be conducted. Furthermore, the hydrolysis transformation product that is rapidly formed is noted to be itself (biotically) ‘rapidly degraded’ within a period of 28 days. This was demonstrated within an available ‘readily biodegradable’ screening test conducted on the transformation product. 

 

Key data : QSAR - water solubility : 71.36 mg/L should be considered as equivalent to the ‘maximum achievable water solubility’ (i.e. in the absence of hydrolysis) at 25 °C and ca. pH 7, QSAR Prediction – WSKOWWIN v1.42; EpiSuite 4.11 - US EPA, 2022

The substance consists of constituents in the slightly soluble (1 – 100 mg/L) range.

Note: The substance rapidly hydrolyses at all relevant pH 4, 7 and 9. Refer to ‘Hydrolysis’ and/or ‘Biodegradation’ sections for further information.

 

Under REACH Regulation No. (EC) 1907/2006: Annex XI: section 1.2 - weight of evidence, adequate information is available for environmental hazard and risk assessment and therefore further testing is omitted. Specifically, the parent substance and/or its transformation product have log Pow < 4.0 and/or the transformation product is (biotically) rapidly degradable. Furthermore, there are no identified (eco)toxicities triggering classification and labelling.