3-chlorophenyl isocyanate

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No OECD Guideline defined.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Principles of method if other than guideline:

Method: other

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

3-chlorophenyl isocyanate

EC Number:

220-822-5

EC Name:

3-chlorophenyl isocyanate

Cas Number:

2909-38-8

Molecular formula:

C7H4ClNO

IUPAC Name:

1-chloro-3-isocyanatobenzene

Details on test material:

Purity: 99.8%, clear liquid, molecular weight: 153.6.

Test animals

Species:

mouse

Strain:

other: Bor: NMRI

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

single administration

Frequency of treatment:

single administration

Post exposure period:

Animals were sacrificed 16, 24 and 48 hours after the administration and femoral bone marrow was prepared.

Doses / concentrations

Remarks:

Doses / Concentrations:
50 and 20 mg/kg
Basis:

No. of animals per sex per dose:

no data

Control animals:

not specified

Examinations

Tissues and cell types examined:

femoral bone marrow.

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

After single intraperitoneal administration of 50 mg/kg test substance, treated animals showed the following compound-related symptoms until sacrifice: apathy, streching of body, roughened fur, blue discoloration of end of tail, spasm, twitching, shivering, difficulty in breathing, eyelids stuck together and reduced excretion. Their feeding behavior was normal. Two of 40 treated animals died during the test period, due to the acute toxicity of 50 mg/kg test substance. The abdomen of these animals was filled with a clear liquid. White spots were found on the organs in the surrounding of the injection site.

Applicant's summary and conclusion

Executive summary:

The micronucleus test was employed to investigate the test substance 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, cyclophosphamide, were 50 and 20 mg/kg body weight, respectively.

The animals treated with the test substance showed symptoms of toxicity after administration. Two of fourty animals died before the end of the test due to the acute intraperitoneal toxicity of 50 mg/kg test substance.

There was an altered ratio between polychromatic and normochromatic erythrocytes.

Cyclophosphamide, the positive control, had a clear clastogenic effect, as is shown by the biologicaly relevant increase in polychromatic to normochromatic erythrocytes was not altered.

No indications of a clastogenic effect of the test substance were found after a single intraperitoneal treatment with 50 mg/kg body weight.