Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow 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: 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:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Principles of method if other than guideline:
Method: other: 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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: other TS: m-cresol, purity: 99.8 %

Test animals

Species:
other: mouse bone marrow cells
Strain:
ICR
Sex:
male/female
Details on test animals 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

RS-Freetext:
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.