Dipotassium 3,4,5,6-tetrabromophthalate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Although testing was performed on the chloro derivative and not bromo, the use of this for read-across has been justified in other REACH dossiers on the basis that the chloro derivative will be more biologically active. The justification is driven by the need to avoid unecessary animal testing.
The anhydride will quickly hydrolyse to the acid form once ingested and will behave in the same way as salts that will dissociate under biological conditions.
The source data is from peer-reviewed US National Toxicity Program research.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosomal Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Tetrachlorophthalic anhydride

EC Number:

204-171-4

EC Name:

Tetrachlorophthalic anhydride

Cas Number:

117-08-8

Molecular formula:

C8Cl4O3

IUPAC Name:

Tetrachlorothphalic anhydride

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9

Test concentrations with justification for top dose:

0, 75, 250, 750 ug/ml

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Although the work was performed on the tetrachloro derivative instead of tetrabromo, the effects observed would not have been due to the presence of chlorine ions and can be attributed to the phthalic acid. The anhydride use in the test would quickly form as the acid on ingestion.
The substance is considered a valid read-across surrogate as the potassium salt will dissociate and behave in the same was as the acid form when exposed to biological media.