3,4-xylenol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

2,4-xylenol

EC Number:

203-321-6

EC Name:

2,4-xylenol

Cas Number:

105-67-9

Molecular formula:

C8H10O

IUPAC Name:

2,4-dimethylphenol

Constituent 2

Reference substance name:

3,5-xylenol

EC Number:

203-606-5

EC Name:

3,5-xylenol

Cas Number:

108-68-9

Molecular formula:

C8H10O

IUPAC Name:

3,5-dimethylphenol

Constituent 3

Reference substance name:

2,6-xylenol

EC Number:

209-400-1

EC Name:

2,6-xylenol

Cas Number:

576-26-1

Molecular formula:

C8H10O

IUPAC Name:

2,6-dimethylphenol

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Vehicle:

- Vehicle(s)/solvent(s) used: olive oil

Results and discussion

Test results

Remarks on result:

other: Detail see Any other information field

Any other information on results incl. tables

The three isomeric Xylenols were tested for clastogenicity and for the ability to have spindle poison effects in NMRI mice using the micronucleus test method. For this purpose, the test substance, dissolved in olive oil was administered once orally to male and female animals at dose levels of 250 mg/kg, 500 mg/kg and 1,000 mg/kg body weight in a volume of 10 ml/kg body weight in each case.

As a negative control, male and female mice were administered merely the vehicle, olive oil, by the same route, which gave frequecies of micronucleated polychromatic erythrocytes within the historical control range.

Both of the positive control chemicals, i.e. cyclophosphamide for clastogenicity and vincristine for spindle poison effects, led to the expected increase in the rate of polychromatic erythrocytes containing small or large micronuclei.

Animals which were administered the vehicle or the positive control substances cyclophosphamide or vincristine did not show any clinical signs of toxicity.

The administration of the test substances in a dose 1,000 mg/kg body weight led to evident signs of toxicity.

The animals were sacrificed and the bone marrow of the two femora was prepared 24 and 48 hours after administration in the highest dose group of 1,000 mg/kg body weight and in the vehicle controls. In the test groups of 250 mg/kg and 500 mg/kg body weight and in the positive control groups, the 24-hour sacrifice interval was investigated only, After staining of the preparations, 2,000 polychromatic erythrocytes were evaluated per animal and investigated for micronuclei. The normocytes with and without micronuclei occurring per 2000 polychromatic erythrocytes were also registered.

According to the results of the present study, the single oral administration of the Xylenols did not lead to any increase in the number of polychromatic erythrocytes containing either small or large micronuclei. The rate of micronuclei was always in the same range as that of the negative control in all dose groups and at all sacrifice intervals.

No inhibition of erythropoiesis determined from the ratio of polychromatic to normochromatic erythrocytes was detected.

Thus, under the experimental conditions chosen here, the test substances do not have any chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative