Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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
Study period:
17 Dec 1984 - 22 Jul 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to acceptable standards including GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
GLP compliance:
yes
Type of assay:
other: In Vitro Mammalian Cell Gene Mutation Test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ODA-FG-11-27-94

Method

Target gene:
hypoxanthine-guanine phosphoribosyl-transferase locus
Species / strain
Species / strain / cell type:
other: Chinese hamster Ovary (CHO-K2-BH4 cells)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 homogenate: from adult male Sprague-Dawley rats that had been injected with Aroclor 1254 at 500 mg/kg bw ; 2 days after injection, the livers were excised and prepared
Test concentrations with justification for top dose:
first assay:
without metabolic activation: 0.1, 0.5, 1.0, 1.5, 2.0 nL/mL
with metabolic activation: 9.0, 8.0, 7.0, 6.0, 5.0 nL/mL

second assay:
without metabolic activation: 2.0, 1.5, 1.0 nL/mL
with metabolic activation: 10.0, 9.5, 9.0, 8.0, 7.0 nL/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: acetone
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: ethylmethanesulphonate and benzo(a)pyrene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 5 h
- Expression time (cells in growth medium): 7-9 days
- Selection time (if incubation with a selection agent): 7 days

SELECTION AGENT (mutation assays): 6-thioguanine
STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS:
preliminary toxicity test: single culture per treatment
mutation assay: duplicate cultures per treatment

NUMBER OF CELLS EVALUATED: cloning efficiency: 100 cells; mutation assay: 2000 cells or 10000 cells

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
The assay is considered positive in the event a dose-dependent increase in mutation frequency is observed with one or more of th four concentrations tested inducing a mutation frequency which is at least twice that of the solvent control. The assay is considered suspect if there is no dose response but one or more doses induce a mutation frequency which is at least twice that of the solvent control.
The positive control must induce a mutation frequency at least three time that of the solvent control.

Results and discussion

Test results
Species / strain:
other: Chinese hamster Ovary (CHO-K2-BH4 cells)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
≥2.25 nL/mL (without S9); ≥10 nL/mL (with S9)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The test material is considered to be negative in the hgpr test either with or without exogenous metabolic activation.
Executive summary:

Mutagenicity of octadecenylamine (ODA-FG-11 -27 -84) at the hprt locus was investigated in Chinese hamster ovary cells at concentrations of 0.1 to 2.0 nl/ml without S-9 mix and of 5.0 to 10 nl/ml with S-9 mix. No relevant cytotoxicity (decrease in cloning efficiency) was found for the analysed concentrations; without S-9 mix concentrations higher than 2.0 nl/ml led to strong cytotoxicity so that cloning was not successful. In general, there was no increase in mutation frequencies after treatment, with the exception of the highest concentrations of 2.0 nl/ml (without S-9 mix) and 9.0 nl/ml (with S-9 mix) in the first experiment. Since no genetic effects were seen at lower concentrations and the second experiments were clearly negative with and without S-9 mix, these increased mutation frequencies can be interpreted as outliers (due to the low statistical power of this test system). Altogether, the test result is negative.