1,2,3,4-tetrahydronaphthalene

Genetic toxicity: in vitro

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

Test material information

Constituent 1

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.