Diethylbenzene

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:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This is a GLP study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Diethylbenzene

EC Number:

246-874-9

EC Name:

Diethylbenzene

Cas Number:

25340-17-4

Molecular formula:

C10H14

IUPAC Name:

diethylbenzene

Details on test material:

IUCLID4 Test substance: as prescribed by 1.1 - 1.4

Mixed Diethylbenzenes (CAS No. 25340-17-4)
Purity:Not specified

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Details on exposure:

Type:  Micronuclei formation in bone marrow erythrocytes

Vehicle and positive controls were dosed intraperitoneally with  peanut oil and cyclophosphamide, respectively. 
Number of animals:  18/sex/group, except for the positive control group (5/sex).  Bone marrow  smears, 5 animals/sex/dose, were made at approximately 24, 48, and 72  hours post-dosing, according to the method of Schmid (1976).  The slides  were fixed in methanol and stained with 5% Giemsa for approximately 20  minutes.  The percentage of PCE was calculated by counting a total of  >200 erythrocytes.  On each slide, a total of 1000 PCEs were evaluated  for the presence of micronuclei.

Schmid, W (1976).  The micronucleus test for cytogenetic analysis.  In:  A. Hollaender (Ed), Chemical Mutagens.

Duration of treatment / exposure:

Single dose

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 000 other: mg/kg

Doses / concentrations 2

Dose / conc.:

2 000 other: mg/kg

Doses / concentrations 3

Dose / conc.:

4 000 other: mg/kg

No. of animals per sex per dose:

18/sex/group, except for the positive control group (5/sex). 

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide

Examinations

Tissues and cell types examined:

Bone marrow  smears

Details of tissue and slide preparation:

Bone marrow  smears, 5 animals/sex/dose, were made at approximately 24, 48, and 72  hours post-dosing, according to the method of Schmid (1976).  The slides  were fixed in methanol and stained with 5% Giemsa for approximately 20  minutes.  

Evaluation criteria:

The percentage of PCE was calculated by counting a total of  >200 erythrocytes.  On each slide, a total of 1000 PCEs were evaluated  for the presence of micronuclei.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

Cytotoxicity was noted in females dosed with 4000 mg/kg  and sampled at 48 hours.

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Cytotoxicity:  Cytotoxicity was noted in females dosed with 4000 mg/kg  and sampled at 48 hours.

Genotoxic effects:  No treatment-related effect on micronucleated  polychromatic erythroctyes in either sex.

Toxicity NOEL:  1000 mg/kg

Genotoxicity NOEL > 4000 mg/kg 

Statistical results:  No statistically significant differences between  mixed diethylbenzene-exposed animals and controls. 

Remarks:  Evidence of toxicity was found at > 2000 mg/kg in both sexes.   Clinical signs of toxicity observed were decreased motor activity,  collapse, labored breathing, convulsions, and weakness.  In addition,  on  Day 1, one male at 2000 mg/kg and three males and one female at 4000  mg/kg died before the scheduled sampling time; two moribund females at  4000 mg/kg were euthanized.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the conditions of this study, mixed diethylbenzenes was considered non-genotoxic, since micronuclei were not induced in the bone marrow erythrocytes of mice, even at doses that exceeded the MTD.