Toluene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

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: Near guideline study. GLP status unknown, Limitations in design and reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Principles of method if other than guideline:

Rats were dosed with test compound on both an acute and a subchronic schedule. Acute study rats were killed at 6, 24 and 48 hours after treatment, subchronic study rats were killed 6 hours after last dose. Bone marrow spreads were prepared. The spreads were assessed for mitotically active cells that had been arrested at metaphase using colchicine, for structural changes and rearrangements of their chromosomes.

GLP compliance:

not specified

Type of assay:

other: rat bone marrow cytogenetic analysis

Test material

Test material information

Constituent 1

Reference substance name:

Toluene

EC Number:

203-625-9

EC Name:

Toluene

Cas Number:

108-88-3

Molecular formula:

C7H8

IUPAC Name:

toluene

Details on test material:

- Name of test material (as cited in study report): toluene
- Physical state: colourless liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

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

Duration of treatment / exposure:

single dose (acute study); 5 days (subchronic study)

Frequency of treatment:

single dose (acute study), once per day, 24 hours apart (subchronic study)

Post exposure period:

6, 24 and 48 hours after dose (acute study), 6 hours after final dose (subchronic study)

Doses / concentrations

Remarks:

Doses / Concentrations:
0.025, 0.082, 0.247 mL/kg
Basis:
other: nominal in DMSO

No. of animals per sex per dose:

5 per dose level (no information on sex of animals)

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: ip (assumed)
- Doses / concentrations: 0.3 mg/kg

Examinations

Tissues and cell types examined:

rat bone marrow

Evaluation criteria:

Evaluated for presence of chromosome aberrations. Breaks, gaps, fragments and chromosome rearrangement recorded. Wherever possible, 50 cells were located and scored per slide.

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
No evidence of genotoxicity

Executive summary:

An evaluation of the in vivo clastogenicity of toluene was investigated in rat bone marrow. Toluene was administrated i.p. to the animals at 0.025 mL/kg, 0.082 mL/kg and 0.247 mL/kg corresponding to 22, 71, and 215 mg/kg body weight. The study was negative, as all chromosomal aberrations observed were in the range of the spontaneous background. No depression of the mitotic index was observed at any of the dose levels tested.

Toluene is not genotoxic in mammalian cells in vivo.