Reaction mass of aluminium chloride, iron dichloride, magnesium chloride and manganese dichloride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Research publication. Well documented meets generally accepted scientific principles, acceptable for assessment. Read across to the registered substance is considered scientifically justified.

Data source

Reference

Reference Type:

publication

Title:

Genotoxicity of iron compounds in Salmonella typhimurium and L5178Y mouse lymphoma cells.

Author:

Dunkel V C, San R H C, Seifried H E, Whittaker P

Year:

1999

Bibliographic source:

Environ Mol Mutagenesis 33: 28-41

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

Method: other: Clive et al/1975 and 1979

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Iron trichloride

EC Number:

231-729-4

EC Name:

Iron trichloride

Cas Number:

7705-08-0

Molecular formula:

Cl3Fe

IUPAC Name:

Iron (III) trichloride

Details on test material:

The substance tested was the hexahydrate (CAS number 10025-77-1), but this does not affect the chemical species available to the test organisms.

Method

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Metabolic activation system:

Aroclor induced rat liver S9

Test concentrations with justification for top dose:

without S9 309-1030, with S9 0.206-1.236

Vehicle / solvent:

Vehicle used: distilled water

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

distilled water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: methylmethanesulphonate

Remarks:

without activation

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9,10-dimethylbenzanthracene

Remarks:

with activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk


DURATION
- Preincubation period: 4 hours
- Exposure duration: 4 hours
- Expression time (cells in growth medium): 48 hours
- Selection time (if incubation with a selection agent): 10-12 days
- Fixation time (start of exposure up to fixation or harvest of cells): 12-14 days

SELECTION AGENT (mutation assays): trifluorothymidine

NUMBER OF REPLICATIONS: duplicate cultures

NUMBER OF CELLS EVALUATED: 1E+06 for mutant selection, 200/plate for mutant count, colony size range 0.2-1.1 mm.

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

Doubling of mutant frequency over concurrent solvent treated control value together with dose relationship.

Statistics:

Colonies larger than 0.1 mm diameter were counted with an Artek automated colony counter. Colony size was also determined.

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

positive

Remarks:

without activation

Cytotoxicity / choice of top concentrations:

other: without S9 ca 1030 µg Fe/ml; with S9 >1.236 µg Fe/ml

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: other: L5178Y TK+/- 3.7.C mouse lymphoma cells

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Number of revertants per plate (mean of 2 plates) 

Concentration µg Fe/ml	Mutant frequency*	Growth**	Concentration µg Fe/ml	Mutant frequency*	Growth**
	-MA	- MA		+MA	+MA
0*	26	100	0	44	100
309.0	28	49.5	0.206	45	115..5
412	24	50.5	0.412	50	94.5
515	28	32.5	0.824	98	85.5
618	32	35	1.030	107	76.5
1030	49	12.5	1.236	121	66
Positive control	450	49	Positive control	447	16

* per 1E+06 survivors

** as % of control

PRECIPITATION CONCENTRATION: None reported

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation

In the mouse lymphoma TK+/- assay ferric chloride FeCl3.6H2O showed a negative response in the absence of metabolic activation and a positive dose related response in the presence of metabolic activation.