Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) obtained from a solvent-based manufacturing process is not isolated throughout the process. The solvent-free N 8424-2 is a solid which would significantly complicate the manufacturing process. Beyond that N 8424-2 is not marketed as such. At the end of the process a blend of 53 weight-% N 8424-2 and 47 weight-% of a corresponding PO adduct of the alkylene oxide reactive solvent are dissolved in Tris(chloroisopropyl) phosphate (TCPP) to facilitate handling of the substance by downstream users and to improve the flame-retardant action. 70% of the blend (N 8424-2 and corresponding PO adduct of the alkylene oxide reactive solvent) and 30% TCPP represent the commercial product for which a base set of toxicological information was already available. Further, analysis of the toxicity profile of the solvents in the commercial product demonstrates that the available studies with the commercial product, which contains 37% N 8424-2 (0.7 x 53%), is sufficient for an adequate hazard characterisation of N 8424-2.

As displayed in table 1 the comparison of the data available for the commerial product and for some constituents showed that the commercial product is suitable as surrogate for  2,2',6,6'-Tetrabromo-4,4'-iso-propylidene-diphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2)

Table 1 Base set of toxicological data with regard to the commercial product as surrogate for 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2)

Target Substance

Acute oral

[mg/kg]

Acute dermal

[mg/kg]

Local irritation

Skin sensitization

Ames-Test

 

 

 

 

 

 

Commercial Product

(mixture of A + B +C)

LD50: 1977

 

 

C & L: Cat 4

LD50: > 2000

 

 

C & L: no category

Skin: no irritation

Eye: slight irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

A: a corresponding PO adduct of the alkylene oxide reactive solvent

LD50: > 2000

 

 

C & L: no category

LD50: > 2000

 

 

C & L: no category

Skin: no irritation

Eye: no irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

B: Tris(chloroisopropyl) phosphate

500 > LD50< 2000

 

 

C & L: Cat 4

LD50: > 2000

 

 

C & L: no category

Skin: slight irritation

Eye: no irritation

 

C & L: no category

Negative

 

 

C & L: no category

Negative

C: 2,2',6,6'-Tetrabromo-

4,4'-iso-propylidene-diphenol, oligomeric reaction products with Propylene oxide and

n-butyl glycidyl ether (= N 8424-2)

No data

 

 

 

 

 

 

C & L: Cat 4

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

 

 

C & L: no category

No data

 

 

 

 

No evidence for induction of point mutation in bacteria

In particular the comparison of the acute oral toxicity study with the results of the dose range finding study which was conducted before starting the subacute oral study proves that the toxicity of the commercial product well reflects the toxicity of N 8424 -2 (for details see IUCLID Chapter 7.2 Endpoint Summary "Acute Toxicity") because 2,2’,6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) as constituent of the commercial product behaves like the dissolved parent compound.

In vitro gene mutation study in bacteria:

The commercial product was evaluated in an Ames Test onS. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 and E. coli WP2. Doses of up to and including 5000 µg per plate did not produce bacteriotoxic effects. Substance precipitation occurred at 1000 µg per plate and above showing that the test item was not miscible in the aqueous test system at these amounts. The test material was considered to be non-mutagenic without and with S9 mix in the plate incorporation assay. Positive controls increased the mutant counts to well over those of the negative controls, thus demonstrated the system´s sensitivity. Since up to concentrations were tested, that caused precipitation, 2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether (= N 8424-2) is considered to be non-mutagenic in the in vitro gene mutation assay.

In vitro micronucleus study:

The test item was examined for mutagenic activity (chromsome breakage and misdistribution of chromosomes) in the in vitro micronucleus test using Chinese Hamster V79 cells in accordance to OECD Guideline 487. The negative control and appropriate positive controls with known mutagens demonstrated the suitability and sensitivity of the test system. The test item showed no biologically relevant increase in the frequency of micronucleus containing V79 cells in the absence (both pulse and continuous treatment) or in the presence of S9 mix (pulse treatment) when tested up to cytotoxic concentrations.

In vitro gene mutation study in mammalian cells

The test item was tested in an in vitro gene mutation assay in V79 cells (HPRT) according to OECD TG 476. The vehicle control and appropriate positive controls with known mutagens demonstrated the sensitivity of the test system and the activity of the metabolic activation system. No substantial and reproducible dose dependent increase of the mutation frequency was observed for the test item in the cultures with and without S9 mix when tested up to cytotoxic concentrations. Based on these results the test substance is considered to be non-mutagenic in this V79/HPRT test under the conditions tested.


Justification for selection of genetic toxicity endpoint
No study was selected since all three in vitro mutagenicity studies were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available study results (negative in Ames test, HPRT test and micronucleus test, in vitro) a classification according to EU-Directive 67/548/EEC, Annex VI and according to Regulation (EC) No 1272/2008, Annex I is not warranted.