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

Long-term toxicity to fish

Administrative data

Endpoint:

adult fish: sub(lethal) effects

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

October 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Estimation performed by method recommended by REACH Guidance - Guidance on information requirements and chemical safety assessment, Chapter R7b: Endpoint specific guidance (May 2008, v1.1).

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: QSAR

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The structure-activity relationships (SARs) presented in ECOSAR are used to predict the aquatic toxicity of chemicals based on their similarity of structure to chemicals for which the aquatic toxicity has been previously measured.  Most SAR calculations in the ECOSAR Class Program are based upon the octanol/water partition coefficient (Kow). Further details on the methodology, accuracy and applicability domain are avilable in the QSAR Model Reporting Format available in the section entiled : "overall attachment and remarks".

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

EC Number:

243-885-0

EC Name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

Cas Number:

20566-35-2

Molecular formula:

C15H15Br4O7 (one ring component) C8 H2 Br4 O4 . C4 H10 O3 . C3 H8 O2 Unspecified reaction product of the three components

IUPAC Name:

2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl 3,4,5,6-tetrabromophthalate

Test material form:

other: SMILE notation

Details on test material:

- SMILE notation: CC(O)COC(=O)c1c(Br)c(Br)c(Br)c(Br)c1C(=O)OCCOCCO

Sampling and analysis

Analytical monitoring:

no

Test solutions

Vehicle:

no

Test organisms

Test organisms (species):

other: Refer to the attached document

Study design

Test type:

other: QSAR estimate

Water media type:

freshwater

Limit test:

no

Test conditions

Reference substance (positive control):

not specified

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

14 d

Dose descriptor:

LC50

Effect conc.:

71.959 mg/L

Nominal / measured:

estimated

Conc. based on:

other: ESTER (ECOSAR class)

Basis for effect:

mortality

Effect concentrations 2

Duration:

32 d

Dose descriptor:

other: chronic value

Effect conc.:

0.447 mg/L

Nominal / measured:

estimated

Conc. based on:

other: ESTER (ECOSAR class)

Basis for effect:

mortality

Effect concentrations 3

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

1.258 mg/L

Nominal / measured:

estimated

Conc. based on:

other: Neutral Organic SAR

Basis for effect:

mortality

Remarks on result:

ChV (chronic value, QSAR)

Remarks:

assumed to be based on 21 d

Details on results:

According to the estimated toxicity value for long-term toxicity on fish, the chemical may not be soluble enough to measure this predicted effect.
Note: ChV is defined as the geometric mean of the no observed effect concentration and the lowest observed effect concentration.

Reported statistics and error estimates:

Applicability domain:
In the development of the ECOSAR equations for neutral organics and classes with excess toxicity, the training sets generally include chemicals with log Kow values in the range of -3 to 8 and molecular weights less than 1000. The structure tested falls into these recommandations.

Any other information on results incl. tables

The registered substance (CAS # 20566-35-2) involves the heating and subsequent reaction of Tetrabromophthalic Anhydride (TBPA) with Di-Ethylene Glycol (DEG) and Propylene Oxide (PO). The nature of the reagents involves the formation of a complex mixture of products with different combinations of these 3 reagents. Current, QSAR models cannot test UVCB substances. Therefore, the QSAR has been performed on the major product which is also the structure with the lowest molecular weight (1 unit of region of TBPA, 1 DEG and 1 PO). In terms of predicted toxicology, it can reasonably be assumed that the structure having the lowest molecular weight should be the most bioavailable. Based on this toxicity principle, QSAR analyses were performed using the SMILE structure of the smallest molecular weight structure which is also the major product of the mixture (identified at 26% area by HPLC).

In addition, same model has been ran with SMILE notation of 1 unit of TBPA, 1 DEG and with 2 or 3 PO (See below SMILE notation and parameters) and same order of magnitude was found for these 2 moldecules presenting 1 unit of TBPA. In contrast, when looking at the results for 2 units of TBPA, values are dramatically decreasing but parameters are outside of the model boundaries limits.

*Smile notation for 1 unit of TBPA, 1 DEG and 2 PO:

C(=O)(c1c(C(=O)OCC(C)OCC(C)O)c(Br)c(Br)c(Br)c1Br)OCCOCCO

Parameters:

Mol For: C18 H22 Br4 O8

Mol Wt: 685.99

Log Kow (KOWWIN v1.68): 3.97

*Smile notation for 1 unit of TBPA, 1 DEG and 3 PO:

C(=O)(c1c(C(=O)OCC(C)OCC(C)OCC(C)O)c(Br)c(Br)c(Br)c1Br)OCCOCCO

  Parameters:

Mol For: C21 H28 Br4 O9

Mol Wt: 744.07

Log Kow (KOWWIN v1.68): 4.11

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Long-term toxicity to fish using the ECOSAR predicted a LC50 (14 days) 71.959 mg/L and a chronic value of 1.258 mg/L based on the structure with the lowest molecular weight in the UVCB substance. In addition, and based on the predicted water solubility, the estimated toxicity values are above the solubility limit.