Xylene

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Near guideline study, GLP status unknown, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Justification for type of information:

N/A

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

only one sex tested

Principles of method if other than guideline:

not specified

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

o-xylene

EC Number:

202-422-2

EC Name:

o-xylene

Cas Number:

95-47-6

Molecular formula:

C8H10

IUPAC Name:

o-xylene

Details on test material:

- Name of test material (as cited in study report): o-dimethylbenzene (o-xylene)
- Supplier: Merck Co., D-8011 Hohenbrunn, Germany
- Purity: 98.0%

Specific details on test material used for the study:

not specified

Test animals

Species:

mouse

Strain:

NMRI

Details on species / strain selection:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: NMRI mice obtained from Zentralinstitut fur Versuchtstiere, D-3000 Hannover, Germany.
- Weight at study initiation: 25-30 g
- Housing: 5/cage
- Diet: Laboratory Purina chow ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS: no details reported

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil (when doses were too small to be injected)

Details on exposure:

not specified

Duration of treatment / exposure:

2 injections, 24 h apart

Frequency of treatment:

2 ip injections 24 hours apart

Post exposure period:

6 hours after 2nd injection

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.12 other: mL/kg (nominal)

Remarks:

106 mg/kg, 2 injections

Doses / concentrations 2

Dose / conc.:

0.25 other: mL/kg (nominal)

Remarks:

220 mg/kg, 2 injections

Doses / concentrations 3

Dose / conc.:

0.37 other: mL/kg (nominal)

Remarks:

320 mg/kg, 2 injections

Doses / concentrations 4

Dose / conc.:

0.5 other: mL/kg (nominal)

Remarks:

440 mg/kg, 2 injections

No. of animals per sex per dose:

5 (test groups), 5 (positive control groups), 10 (negative/vehicle control group)

Control animals:

yes, concurrent vehicle

Positive control(s):

benzene, cyclophosphamide; 4-nitroquinoline 1-oxide
- Route of administration: ip injection
- Doses / concentrations: benzene 2 x 0.15, 0.30 and 0.60 mL/kg; cyclophosphamide 2 x 0.05 and 0.25 mL/kg; 4-nitroquinoline 1-oxide 2 x 0.12, 0.25 and 0.50 mL/kg

Examinations

Tissues and cell types examined:

polychromatic erythrocytes

Details of tissue and slide preparation:

6 hr after 2nd injection, animals were killed and bone marrow aspirated from both femurs and suspended in serum. After centrifugation, the cells in the sediment were used to prepare smears (2/femur) which were fixed and stained. All smears were coded, and examined under high magnification without knowledge of treatment and doses. 1000 PCEs/smear were screened for the presence of micronuclei.

Evaluation criteria:

not specified

Statistics:

Students t-test

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

N/A

Any other information on results incl. tables

Effects of o-xylene on frequency of micronucleated polychromatic erythrocytes of femoral bone marrow of male NMRI mice

(based on Mohtashamipur E et al 1985, Arch Toxicol 58: 106-109, Table 2)

Substance Dose (mL/kg body weight) Micronuclei/1000 PCEs corn oil (vehicle control) 2 x 0.50 1.91± 1.037 o-xylene 2 x 0.12 1.80 ± 0.748   2 x 0.25 1.60 ± 0.663   2 x 0.37 1.70 ± 0.781   2 x 0.50 1.80 ± 0.748 4-nitroquinolin-1-oxide (positive control) 2 x 0.12 6.25 ± 0.829*   2 x 0.25 15.66 ± 4.784*   2 x 0.50 18.00 ± 2.160* cyclophosphamide (positive control) 2 x 0.05 7.20 ± 1.077*   2 x 0.25 21.10 ± 4.346* benzene (positive control) 2 x 0.15 4.40 ± 0.916*   2 x 0.30 8.40 ± 3.903*   2 x 0.60 12.90 ± 5.521*

* Significant (P<0.01)

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
o-xylene does not induce micronuclei in bone marrow polychromatic erythrocytes of mice and is not therefore genotoxic.

Executive summary:

o-xylene does not induce micronuclei in bone marrow polychromatic erythrocytes of mice and is not therefore genotoxic.