Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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:
key study
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.

Data source

Reference
Reference Type:
publication
Title:
Effects of ethylbenzene, toluene, and xylene on the induction of micronuclei in bone marrow polychromatic erythrocytes of mice
Author:
Mohtashamipur E, Norpoth K, Woelke U and Huber P
Year:
1985
Bibliographic source:
Arch Toxicol 58: 106-109

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
only one sex tested
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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%

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals 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)
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2 x 0.12, 0.25, 0.37, 0.50 mL/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
106, 220, 320, 440 mg/kg
Basis:

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):
yes, concurrent vehicle

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.
Statistics:
Students t-test



Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid

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.