Reaction products of tetrabromophthalic anhydride with 2,2'-oxydiethanol and methyloxirane

Dissociation constant

Administrative data

Endpoint:

dissociation constant

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 (half-life less than 12 hours)

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

hydrolysis

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

key study

Study period:

February 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE : Episuit Hydrowin

2. MODEL (incl. version number) 2.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CAS: 77098-07-8
Model used:
SMILES : O=C(c1c(c(c(c(c1C(=O)OCCOCCO)Br)Br)Br)Br)OCC(C)O
CHEM : 1,2-Benzenedicarboxylic acid, 3,4,5,6-tetrabromo-, mixed esters with
diethylene glycol and propylene glycol
MOL FOR: C15 H16 Br4 O7
MOL WT : 627.91

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: ester hydrolysis is well validated in Hyrowin
- Unambiguous algorithm: yes
- Defined domain of applicability:
The following accuracy statistics are available for the Training Set QSARs from Mill et al. (1987):
The ester equation regression has the following statistics:
  number = 124
  correlation coef (r) = 0.982
correlation coef (r2) = 0.965
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The ester equation regression has the following statistics:
  number = 124
  correlation coef (r) = 0.982
correlation coef (r2) = 0.965
- Mechanistic interpretation:
the main functional groups of the substance subject to hydrolysis are the ester groups. This is correcly identified by the moidel.
5. APPLICABILITY DOMAIN
- Structural and mechanistic domains:
Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that aqueous hydrolysis estimates are less accurate for compounds that have a functional group(s) or other structural features not represented in the training set (see also Section 8.4. below).
Esters are designated by the formula:
R1 - C(=O) - O - R2
In the training set, the R2 substituent is an alkyl carbon or an aromatic carbon.  T
- Similarity with analogues in the training set: The substance falls within the applicability domain of the training set.

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]: All main components contain similar ester groups and therefore this result is relevant for the assessment.

Qualifier:

no guideline followed

Principles of method if other than guideline:

EPI Suite v4.11

GLP compliance:

no

Radiolabelling:

no

Analytical monitoring:

no

Estimation method (if used):

EPI Suite v4.1 HYDROWIN v2.2

Transformation products:

yes

No.:

#1

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

- Pathways for transformation: Hydrolyis of the este bond and formation of 1,2-Benzenedicarboxylic acid, 3,4,5,6-
tetrabromo-, diethyleneglycol and propyleneglycol is the most plausible hydrolysis pathway. Ester hydrolyis is typically fastest in alkaline media,
- Other:

Key result

pH:

8

Temp.:

25 °C

Hydrolysis rate constant:

ca. 5.89 s-1

DT50:

ca. 1.363 d

Type:

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

Key result

pH:

7

Temp.:

25 °C

DT50:

ca. 13.69 d

Type:

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

Other kinetic parameters:

pH > 8 and 25 deg. C
Kb 1 for the first ester group : 4.32 Lmol-1s-1 (ethyelenglycol ester)
Kb 2 for the second ester group: 1.57 Lmol-1s-1 (propylene glycol ester)
Kb total: 5.89 Lmol-1s-1
Half lives relate to complete hydrolysis of both ester groups.

Pathways for transformation: Hydrolyis of the este bond and formation of 1,2-Benzenedicarboxylic acid, 3,4,5,6-

tetrabromo-, diethyleneglycol and propyleneglycol is the most plausible hydrolysis pathway. Ester hydrolyis is typically fastest in alkaline media,

Validity criteria fulfilled:

yes

Conclusions:

Based on QSAR results on ester hydrolysis of the one ring component, a hydrolysis is likely to occur on all ester groups contained in the various components in a similar manner, provided the solubility is sufficient. Hydrolysis constants for the ethyleneglycol ester bond were predicted to be 4.32 Lmol-1s-1 and for the propyleneglycol ester bond 1.57 Lmol-1s-1 at pH > 8 and 25 deg. C.
The hysrolysis constant for the complete hydrolysis was predicted to be 5.89 Lmol-1s-1 at pH> 8 and 25 deg. C.
The half-live for complete hydrolysis of both ester bonds were 1.363 d a.t pH > 8 and 13.69 d at pH 7, both at 25 deg. C

Executive summary:

Based on QSAR results on ester hydrolysis of the one ring component, a hydrolysis is likely to occur on all ester groups contained in the various components in a similar manner, provided the solubility is sufficient. Hydrolysis constants for the ethyleneglycol ester bond were predicted to be  4.32 Lmol-1s-1 and for the propyleneglycol ester bond 1.57 Lmol-1s-1 at   pH > 8 and 25 deg. C.

The hydrolysis constant for the complete hydrolysis was predicted to  be 5.89  Lmol-1s-1 at pH> 8 and 25 deg. C.

The half-live for complete hydrolysis of both ester bonds were 1.363 d a.t pH > 8 and 13.69 d at pH 7, both at 25 deg. C