Theophylline

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1998

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Theophylline

EC Number:

200-385-7

EC Name:

Theophylline

Cas Number:

58-55-9

Molecular formula:

C7H8N4O2

IUPAC Name:

1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Details on test material:

- Name of test material (as cited in study report): theophylline
- Physical state: white crystalline powder
- Analytical purity: >99%

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced male Sprague-Dawley rat liver S9 and cofactor mix

Test concentrations with justification for top dose:

510, 555, 600 ug/ml

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO;

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

mitomycin C

Remarks:

Doses: 0.025; 0.063 µg/mL

Migrated to IUCLID6: without S9 Mix.

Controls 2

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Positive control substance:

cyclophosphamide

Remarks:

Doses: 7.5; 37.5 µg/mL

Migrated to IUCLID6: with S9 Mix.

Details on test system and experimental conditions:

METHOD: according to Galloway, S.M. et al. 1987: Environ. Mol. Mutagen. 10 (suppl. 10), 1-175.

METHOD OF APPLICATION: in medium (McCoy's 5A medium);

DURATION
- Exposure duration: without S9 Mix: 20 hours; with S9 Mix: 2 hours
- Expression time (cells in growth medium): with S9-Mix: by the time the treatment medium was removed, the cells were incubated for 10 hours in fresh medium before addition of the spindle inhibitor.
- Fixation time (start of exposure up to fixation or harvest of cells): 22 h (without S9 Mix) and 12 h (with S9 Mix).

SPINDLE INHIBITOR (cytogenetic assays): Colcemid was added and incubation continued for 2 more hours
STAIN (for cytogenetic assays): Giemsa

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: 100 first-division metaphase cells were scored at each dose level.

OTHER:
Cultures were handled under gold lights to prevent photolysis of bromodeoxyuridine-substituted DNA.

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.