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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:
experimental study
Adequacy of study:
key study
Study period:
1991-06-03 to 1992-05-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Principles of method if other than guideline:
Mouse lymphoma assay, suspension plate, no further details
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1,2,3,4-tetrahydronaphthalene
EC Number:
204-340-2
EC Name:
1,2,3,4-tetrahydronaphthalene
Cas Number:
119-64-2
Molecular formula:
C10H12
IUPAC Name:
1,2,3,4-tetrahydronaphthalene
Details on test material:
1,2,3,4-tetrahydronaphthalene from Chem Service Inc. (West Chester, Pennsylvania, USA), purity 98.2 %

Method

Target gene:
tymidin kinase gene
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
 Aroclor 1254-induced rat liver S9 mix
Test concentrations with justification for top dose:
-S9: 30-50 and 35-47.5 µg/ml;
+S9: 1-15 and 10-20 µg/ml
Vehicle / solvent:
 DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
 3-methylcholanthrene with S9-mix   Migrated to IUCLID6: without S9-mix
Details on test system and experimental conditions:
Mouse lymphoma assay
Metabolic activation system: Aroclor 1254-induced rat liver S9 mix
ADMINISTRATION: 
- Dosing:   
-S9: 30, 35, 40, 45, 50 µg/ml  
 +S9:  1, 2.5, 5, 10, 15 µg/ml  
follow-up -S9: 35, 40, 42.5, 45, 47.5 µg/ml   
follow-up +S9: 10, 12.5, 15, 17.5, 20 µg/ml  
solvent: DMSO
- Number of replicates: 2
- Positive and negative control groups and treatment:    
positive: ethylmethanesulfonate (-S9); 3-methylcholanthrene (+S9)   
negative: solvent and untreated
- Pre-incubation time: two-day expression period
Evaluation criteria:
CRITERIA FOR EVALUATING RESULTS: dose-dependent increase in mutant  frequency

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
other: see Results
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
GENOTOXIC EFFECTS:  Initial study: 
- positive with and without metabolic activation
- validity questionable due to findings in controls
Follow-up study:
- negative without metabolic activation
- equivocal with metabolic activation (the only cultures exhibiting a  significant increase in mutant frequency had less than 10% total growth)
Controls:    Positive controls were as expected in both studies.   
Negative controls showed unacceptably high mutant frequencies in the  initial study and were as expected in the follow-up study.
CYTOTOXIC CONCENTRATION:
- Toxicity screening study:   Complete toxicity >= 100 µg/ml, almost complete at 50 µg/ml (-S9);   complete toxicity >= 50 µg/ml (+S9)
- Initial study:   "too toxic to clone" at 52 µg/ml (-S9) and 20 µg/ml (+S9)
- Follow-up study:    "too toxic to clone" at 50 µg/ml (-S9) and 22.5 µg/ml (+S9)
Remarks on result:
other: other: L5178Y TK+/-
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In a mouse lymphoma test tetrahydronaphthalene showed no relevant genotoxic effects.
Executive summary:

In a mouse lymphoma test, a negative result was obtained in the absence of a metabolic activation system (dose range 35-47.5 μg/ml), while with the addition of S-9 mix the test was equivocal (dose range 10-20 μg/ml): The only cultures exhibiting a significant increase in mutant frequency had less than 10 % total growth.