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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: The method used was basically that described by Ames et al., Mutation Res. 31, 347-364 (1975)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether
EC Number:
926-564-6
Cas Number:
1179964-22-7
Molecular formula:
not applicable
IUPAC Name:
2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether
Specific details on test material used for the study:
- Stability under test conditions: it is very unlikely that the test substance would react with acetone at ambient temperature in the time scale of the storage of the solutions - less than 7.5 hours. On this basis it was considered that the formulations of the test substance were stable for the period of use.

Method

Target gene:
mutant histidine gene
Species / strain
Species / strain / cell type:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 1538 TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 microsomal fraction was obtained from a rat liver homogenate from male Fischer 344 rats pre-terated with Aroclor 1254. The S9 mix comprised 10% S9 fraction.
Test concentrations with justification for top dose:
plate incorporation assay (two replicate assay):
0, 31.25, 62.5, 125, 250, 500, 1000, 2000 and 5000 µg/plate with and without S9 mix
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: deionized water (positiv controls: sodium azide, neutral red, potassium dichromate); DMSO (positive controls: 2-nitrofluorene, 9-aminoacridinehydrochloride, 2-aminoanthracene; Benzo(a)pyrene); acetone (test item)
- Justification for choice of solvent/vehicle: no information available
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
benzo(a)pyrene
other: neutral red, potassium dichromate, 2-aminoanthracene
Details on test system and experimental conditions:
20 µl volumes of solutions of test item in acetone /1.56, 3.125, 6.25, 12.5, 25, 50, 100 or c250 mg/ml) were added to top agar mix. The cultures were incuabted at 37°C for 48-72 h before revertant colonies were counted. All tests were carried out in triplicate. two replicatee assays were carried out on different days to confirm the reproducibility of the results.
Evaluation criteria:
no information available
Statistics:
no statistics perfomed

Results and discussion

Test results
Species / strain:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 1538 TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Test item precipitation occurred at 1000 µg per plate and above. No bacteriotoxic effects were produced up to 5000 µg/plate.
No indication of mutagenic effects could be found for the test item at doses of up to 5000 µg per plate in any of the Salmonella typhimurium strains and E. coli strain used, without and with metabolic activation, under the experimental conditions applied. Preliminary pH checks of the media at the maximum amounts of test item to be tested showed no effects.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

The test item was evaluated in an Ames Test on S. 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.