Tar acids, xylenol fraction

Genetic toxicity: in vivo

Administrative data

Endpoint:

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

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

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

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

first sample time should be 12-18 hours after treatment

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:

other: mammalian bone marrow chromosome aberration

Species:

mouse

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

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:

6, 24 and 48 hours

Dose / conc.:

96 mg/kg bw/day (actual dose received)

Dose / conc.:

320 mg/kg bw/day (actual dose received)

Dose / conc.:

960 mg/kg bw/day (actual dose received)

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

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

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY: m-cresol was solubilized in corn oil and dosed once by oral gavage to 3 ICR mice/sex/group at 400, 800, 1200, 1600 and 2000 mg/kg b. The survivors were killed 2 days later. Toxicity and mortality was assessed in mice. Based on the result of this assay the dose levels were selected.

RESULTS OF DEFINITIVE STUDY
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
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

Conclusions:

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.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Tar acids, xylenol fraction

EC Number:

284-895-5

EC Name:

Tar acids, xylenol fraction

Cas Number:

84989-06-0

Molecular formula:

not applicable

IUPAC Name:

2,3-dimethylphenol; 2,4-dimethylphenol; 2,5-dimethylphenol; 2,6-dimethylphenol; 3,4-dimethylphenol; 3,5-dimethylphenol

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Source: CAS 108-39-4, m-cresol, CMA, 1988

Applicant's summary and conclusion

Conclusions:

Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data on in vivo cytogenicity of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is not considered to have cytogenic potential.

Executive summary:

Available data on the source substance m-creosol show negative results in mammalian bone marrow chromosome aberration test according to OECD 475. The study result was negative. However, as there are no data available on in vivo chromosome aberration for Tar acids, Xylenol fraction (CAS 84989-06-0) a weight-of-evidence approach was conducted taken into account all available data on the source substances and Tar acids, Xylenol fraction (CAS 84989-06-0) was therefore not considered to induce chromosome aberrations in vivo.