m-cresol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: deficiencies in experimental procedure

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Principles of method if other than guideline:

In accordance with OECD Guideline 475, 5 mice/sex/dose, bone marrow cells, sacrifice 6,24,48 hrs post treatment, negative and positive controls, stat. method: Kruskal-Wallis test.

GLP compliance:

yes

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

m-cresol

EC Number:

203-577-9

EC Name:

m-cresol

Cas Number:

108-39-4

Molecular formula:

C7H8O

IUPAC Name:

m-cresol

Details on test material:

Test substance: m-cresol, purity: 99.8 %

Test animals

Species:

other: mouse bone marrow cells

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

adult mice (age: 9 weeks at the time of dosing), 5 days for acclimatisation, 5 mice/cage.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

single application, application volume: 5 ml/application.

Duration of treatment / exposure:

once

Frequency of treatment:

once

Post exposure period:

no

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 96, 320, 960 mg/kg bw in corn oil
Basis:
actual ingested

No. of animals per sex per dose:

5 mice/sex/dose/ for the 6 hr-, for the 24 hr- and for the 48 hr- period, respectively, post dosing.

Control animals:

other: vehicle controls and positive controls (CP)

Positive control(s):

yes : CP

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

according to guideline

Evaluation criteria:

The criteria for a positive response are a statistically significant dose-related increase in the number of structural aberrations at 3 dose levels.

Statistics:

Kruskal-Wallis test

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

mortality 3/40 in the highest dose group
clinical signs not attributable to systemic availability
mitotic index in bone marrow cells of treated animals similar to those of controls

Any other information on results incl. tables

The treatment did not increase the frequency of chromosomal aberrations, indicating that m-cresol was not clastogenic under the conditions of this assay. The positive control was functional.
Mortality: 3/5 male mice in the 960 mg-group
Signs of toxicity:
960 mg-group: within 10 min after dosing: squinty eyes, scruffy coats, mild tonic convulsions and rapid breathing which ceased after 30 min., breathing difficulties.
320 mg/kg bw: slightly scruffy coats within 22 hours after dosing.
96 mg/kg bw: no signs of toxicity.

Applicant's summary and conclusion

Executive summary:

m-cresol did not increase chromosomal aberrations in bone marrow cells, however mitotic index in bone marrow cells of treated animals is similar to those of controls.