Dipotassium 3,4,5,6-tetrabromophthalate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data taken from peer-reviewed primary research paper
Methods and results described in good detail
Not following standard guidelines

Data source

Reference

Reference Type:

publication

Title:

In Vitro Metabolism of the Brominated Flame Retardants 2-Ethylhexyl-2,3,4,5-Tetrabromobenzoate (TBB) and Bis(2-Ethylhexyl) 2,3,4,5-Tetrabromophthalate (TBPH) in Human and Rat Tissues

Author:

S C Roberts, et al

Year:

2012

Bibliographic source:

Chem Res Toxicol. 2012 Jul 16; 25(7): 1435–1441.

Materials and methods

Objective of study:

metabolism

other: Biotic and abiotic transformation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The objective was to investigate the potential metabolism of brominated flame retardants in human and rat tissues through in-vitro experiments with liver and intestinal subcellular fractions
Incubations were performed in 100 mM potassium phosphate buffer at pH 7.4 at 37°C.
The enzyme kinetics were evaluated using a microsomal protein for 10 minute incubations.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) tetrabromophthalate

EC Number:

247-426-5

EC Name:

Bis(2-ethylhexyl) tetrabromophthalate

Cas Number:

26040-51-7

Molecular formula:

C24H32Br4O4

IUPAC Name:

Bis(2-Ethylhexyl) 2,3,4,5-Tetrabromophthalate

Specific details on test material used for the study:

Commercially sourced material
A second ester was also examined, but Bis(2-Ethylhexyl) 2,3,4,5-Tetrabromophthalate is used in this endpoint as being closer to the target substance for read-across

Radiolabelling:

no

Test animals

Species:

other: Human

Details on species / strain selection:

Human liver microsomes (HLM) from 50 doners

Sex:

not specified

Details on test animals or test system and environmental conditions:

Rat microsomes and cytosol were also prepared from the liver and small intestinal tissues from adult, female Wistar rats

Administration / exposure

Route of administration:

other: In vitro

Results and discussion

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Potential metabolites were analysed using GC/MS,
The ester was quickly removed leading to formation of the acid.

Applicant's summary and conclusion

Conclusions:

Although the primary metabolic step to the mono-ester was quickly identifed under the condition of the test, in the presence of certain enzyme co-factors consistent if absorbed after ingestion, the onward formation of the acid was difficult to detect.
The theory is that the mono-ester would quickly metabolise further to the acid, but the methods used were unable to detect the acid formation
A similar mono-ester evaluated in the same research was shown to quickly cleave to form the acid.
The authors indicate that further analytlical techniques are needed to confirm final metabolic rates.