Dichloromethylbenzene

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Dichloromethylbenzene

EC Number:

249-854-8

EC Name:

Dichloromethylbenzene

Cas Number:

29797-40-8

Molecular formula:

C7H6Cl2

IUPAC Name:

(dichloromethyl)benzene

Details on test material:

content: 99.02% (analytical result)
composition: 44.8 % 2.5-Dichlorotoluene
25.9 % 2.4-Dichlorotoluene
12.6 % 3.4-Dichlorotoluene
9.2 % 2.3-Dichlorotoluene
6.6 % 2.6-Dichlorotoluene

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

single treatment

Frequency of treatment:

single treatment

Post exposure period:

Time of sacrifice:
negative control: 24 hrs,
test substance: 16, 24, 48 hrs,
positive control cyclophosphamide: 24 hrs

Doses / concentrations

Remarks:

Doses / Concentrations:
1500 mg/kg bw
Basis:

No. of animals per sex per dose:

5

Control animals:

yes

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

not specified

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Summary of results of Micronucleus test with Dichlorotoluene (mixture of isomers) (after acute intraperitoneal treatment with 1500 mg/kg body weight:

			micronucleated cells per 1000
experimental groups	number of evaluated polychromatic erythrocytes	number of normochromatic erythrocytes per 1000 polychromatic erythrocytes	normochromatic erythrocytes	polychromatic erythrocytes
negative control	10.000	1138 + 460	2.0 + 2.5	2.0 + 2.2
test substance 16 hrs	10.000	977 + 232	1.9 + 1.3	1.7 + 1.5
test substance 24 hrs	10.000	1149 + 243	1.9 + 1.2	2.0 + 1.8
test substance 48 hrs	10.000	870 + 242	2.2 + 2.0	2.3 + 1.8
positive control CP 20 mg/kg	10.000	728 + 227	1.6 + 1.4	19.1* + 10.4

*P< 0.01 in non-parametric Wilcoxon ranking test

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

This micronucleus test was conducted to investigate the test substance dichlorotoluene (mixture of isomers) in male and female mice for a possible clastogenic effect on the chromosomes of bone marrow erythroblasts. The known clastogen and cytostatic agent, cyclophosphamide, served as control.

The treated animals received a single intraperitoneal administration of either the test substance or cyclophosphamide. The femoral marrow of groups treated with the test substance was prepared 16, 24 and 48 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of the test substance and the positive control, cyclphosphamide, were 1500 and 20 mg/kg body weight, respectively.

The animals treated with the test substance showed symptoms of toxicity (apathy, stretching of body, roughed fur, staggering gait, spasm and difficulty in breathing) after administration. However, all animals survived untill the end of the test.

There was no altered ratio between polychromatic and normochromatic erythrocytes.

Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologically relevant increase in polychromatic erythrocytes with micronuclei. The ratio of polychromatic to normochromatic erythrocytes was not altered.

No indications of a clastogenic effect of the test substance dichlorotoluene (mixture of isomers) were found after a single intraperitoneal treatment with 1500 mg/kg.