Tris(N-hydroxy-N-nitrosophenylaminato-O,O')aluminium

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September-November 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tris(N-hydroxy-N-nitrosophenylaminato-O,O')aluminium

EC Number:

239-341-7

EC Name:

Tris(N-hydroxy-N-nitrosophenylaminato-O,O')aluminium

Cas Number:

15305-07-4

Molecular formula:

C18H15AlN6O6

IUPAC Name:

aluminum tris(2-oxo-1-phenylhydrazinolate)

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Name: Addtive 02-967 (GENORAD* 19)
CAS No.: 15305-07-4
Batch No.: SAN 149
Purity: > 98%
Chemical Name: Aluminium-N-nitrosophenylhydroxylamine (NPAL)
Aggregate State at RT: solid needles
Colour: whitish
Storage Conditions: room temperature, protected from light
Stability: Instable after repeated contact to air and/or light, undergoes hydrolysis
Expiry Date: 30 June 2003
Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9 fraction (Aroclor 1254 induced)

Test concentrations with justification for top dose:

For S. typhimurium strains: 31.3, 62.5, 125.0, 250,0, 500.0 and 1000.0 µg/plate, based on the results of a range-finding toxicity test up to 5000 µg/plate in TA 100. These concentrations were also used in the first and in the second mutagenicity test.
In a supplement test to the first mutagenicity tes with E. coli WP2 uvrA: 500, 1000 and 2000 µg/plate. In the second test with E. coli WP2 uvrA, the following concentrations were used: 62.5, 125.0, 250,0, 500.0,1000.0 and 2000.0 µg/plate.

Vehicle / solvent:

dimethyl sulphoxide (DMSO)

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

E. coli WP2 uvrA, without metabolic activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535 and TA 100, without metabolic activation

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537, without metabolic activation

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

TA 98, without metabolic activation

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

TA 1535, with metabolic activation

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

E. coli, TA 100, TA 98, TA 1537, with metabolic activation

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test substance is considered to be non-mutagenic in the S. typhimurium and E. coli reverse mutation assay.

Executive summary:

Under the experimental conditions reported, the test substance did not induce gen mutations by base-pair changes or frameshifts in the genome of any of the strains used. Therefore, the test substance is considered to be non-mutagenic in the S. typhimurium and E. coli reverse mutation assay.