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Toxicological information

Genetic toxicity: in vitro

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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to OECD guideline 476. Aluminium chloride used as read across partner.

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity of Metal Salts in the L5178Y Mouse Lymphoma Assay
Author:
Oberly, T. J.
Year:
1982
Bibliographic source:
Journal of Toxicology and Environmental Health, 9:367-376

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): AlCl3
- Analytical purity: ACS grade, purchased from Fisher Scienctific Co. (Pittsburgh)

Method

Target gene:
Thymidine kinase (TK)
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Test concentrations with justification for top dose:
570, 580, 590, 600, 625 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
620 µg/mL
Details on test system and experimental conditions:
METHOD OF APPLICATION: in suspension

DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): 12 days

SELECTION AGENT (mutation assays): trifluorothymidine (TFT)

DETERMINATION OF CYTOTOXICITY
- Method: percent total survival
Evaluation criteria:
A test agent will be considered positive if a dose-realated response is obtained in which two or more concentrations elicit a greater than 2-fold increase in mutation frequency over the solvent control with a minimum of 10% survival.
Statistics:
N.A.

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: after adding the chemical to the medium, a dramatic change in pH occured over the 4h expression period

Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table1: Mutagenic response after treatment with AlCl3

Chemical Dose [µg/mL] Percent total survival Mutation frequency Increase over solvent (-fold)
 
Solvent 0 100 2.5 -
EMS 620 31 85.0 34.0
AlCl3 625 63 5.6 2.2
  600 38 5.0 2.0
590 42 4.9 2.0
580 88 4.3 1.7
570 69 5.0 2.0

Applicant's summary and conclusion

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

The test substance AlCl3 did not induce gene mutation in the TK locus in L5178Y mouse lymphoma cells under the tested experimental conditions.
Executive summary:
In a mammalian cell gene mutation assay conducted similar to OECD guideline 476, L5178Y mouse lymphoma cells cultured in vitro were exposed to AlCl3, solved in water, at concentrations of 570, 580, 590, 600, and 625 µg/mL in the absence of mammalian metabolic activation. The induced mutation frequencies without metabolic activation were not increased by more than 2 fold in comparison to the untreated control, except the 625 µg/mL dose group dose with a 2.2 fold increase. The results of the mutant frequencies did not fulfill the criteria for a positive study result outcome. The positive control did induce the appropriate response.

In summary, the test item AlCl3 did not induce gene mutation in L51178Y mouse lymphoma cells.

This study is classified as acceptable and satisfies the requirement for test guideline OECD 476 for in vitro mutagenicity (mammalian forward gene mutation) data.