Reaction mass of aluminium fluoride and chromium trifluoride and nickel difluoride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: other: gene mutation and DNA repair

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Before 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study comparable to guideline study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

E. coli WP2 uvrA, E. coli WP2 uvrA (pKM101), or S. typhimurium TA102 strain not tested - Only plate-incorporation method used

GLP compliance:

no

Type of assay:

other: bacterial reverse mutation assay (Ames test) and bacterial DNA-repair test

Test material

Test material information

Constituent 1

Reference substance name:

nickel acetate, nickel chloride and nickel nitrate

IUPAC Name:

nickel acetate, nickel chloride and nickel nitrate

Details on test material:

Commercially available as reagent grade pure compounds, from British Drug Houses (BDH)

Method

Target gene:

his gene (mutagenicity assay)

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Species / strain 3

Species / strain / cell type:

bacteria, other: E. coli WP2, WP67 and CM871 (DNA-repair test)

Details on mammalian cell type (if applicable):

WP2: wild-type, repair-proficient; WP67: uvrA- polA-; CM871: uvrA- recA- lexA-

Additional strain / cell type characteristics:

other: ochre nonsense mutation blocking an intermediate process in the synthesis of tryptophan

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9 mix

Test concentrations with justification for top dose:

Not specified - Various dilutions performed by a geometric ratio of 2, starting from the test compound solubility or toxicity limit, were tested

Vehicle / solvent:

Bidistilled water or dimethyl sulfoxide (DMSO)

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

NUMBER OF REPLICATIONS: duplicate or triplicate plates

OTHER:
- Ames reversion test:
The plate-incorporation test was performed according to the standard procedure described by Ames et al. (1975), with some revisions suggested by Bruce N. Ames (personal communication) and now published by Maron and Ames (1983).
- DNA-repair test in E. coli
Liquid micromethod procedure: This procedure is similar to those described by Kada et al. (1980) in the rec-assay System with B. subtilis and by McCarroll et al. (1981) with various strains of E. coli.

Evaluation criteria:

- Ames reversion test:
Criteria for positivity of results included rate of increase of induced versus spontaneous revenants, dose dependence and reproducibility in separate experiments.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Test results 2

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Test results 3

Species / strain:

other: E. coli WP2, WP67 and CM871 (DNA-repair test)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Detailed results of the Ames test

Test compound	S. typhimuriumstrain						Potency (revertants/nmole)
	TA1535	TA100	TA1538	TA98	TA1537	TA97
Nickel acetate	-	-	-	-	-	-	< 0.007
Nickel chloride	-	-	-	-	-	-	< 0.0007
Nickel nitrate	-	-	-	-	-	-	< 0.0007

-: No increase of revertants in at least 3 separate experiments

Table 2: Detailed results of the DNA-repair assay

Test compound	E. colistrain						Potency (delta MIC/nmole)
	MIC (µg) without S9 mix			MIC (µg) with S9 mix
	WP2	WP67	CM871	WP2	WP67	CM871
Nickel acetate	125	125	80	250	250	250	0
Nickel chloride	125	125	125	250	180	225	0
Nickel nitrate	125	125	125	375	250	250	0

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with or without metabolic activation

Nickel acetate, nickel chloride and nickel nitrate did not induce any genotoxic effects in bacteria when tested for point mutations (Ames test) or DNA-repair (liquid micromethod).

Executive summary:

Nickel acetate, nickel chloride and nickel nitrate were comparatively assayed in the bacterial Ames reversion test (plate incorporation method) with his- S. typhimurium strains TA1535. TA1537, TA1538, TA98, TA100 and TA97, as well as in a DNA-repair test (liquid micromethod) with trp- E. coli strains WP2 (repair-proficient), WP67 (uvrA- polA-) and CM871 (uvrA- recA- lexA-), up to concentrations based on solubility or toxicity limits, in the absence or presence of S9 metabolic activation system.

No significant changes were observed with any of the three test compounds in either test, illustrating their absence of genotoxic effects in such bacterial test systems.