Phenyl isocyanate

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Principles of method if other than guideline:

The micronucleus test was employed to investigate phenyl isocyanate 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 positive control. The treated animals received a single intraperitoneal administration of either phenyl isocyanate or cyclophosphamide.
The femoral marrow of groups treated with phenyl isocyanate was prepared 24, 48 and 72 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of phenyl isocyanate and the positive control, cyclophosphamide, were 30 and 20 mg/kg body weight, respectively.

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Phenyl isocyanate

EC Number:

203-137-6

EC Name:

Phenyl isocyanate

Cas Number:

103-71-9

Molecular formula:

C7H5NO

IUPAC Name:

isocyanatobenzene

Details on test material:

content: 99.9%

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Duration of treatment / exposure:

The femoral marrow of groups treated with phenyl isocyanate was prepared 24, 48 and 72 hours after administration.

Frequency of treatment:

single intraperitoneal administration

Post exposure period:

Animals were sacrificed 24, 48 and 72 hours after the administration, and the femoral marrow was prepared

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

30 mg/kg bw/day

No. of animals per sex per dose:

5 male and 5 female mice/dose

Control animals:

yes, concurrent vehicle

Examinations

Tissues and cell types examined:

Femoral marrow

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

The animals treated with phenyl isocyanate showed lasting symptoms of toxicity after administration. One of forty animals died before the end of the test due to the acute intraperitoneal toxicity of 30 mg/kg phenyl isocyanate. There was an altered ratio between polychromatic and normochromatic erythrocytes.

No indications of a relevant clastogenic effect of phenyl isocyanate were found after a single intraperitoneal treatment with 30 mg/kg.

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.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

Executive summary:

The micronucleus test was employed to investigate phenyl isocyanate 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 positive control.

The treated animals received a single intraperitoneal administration of either phenyl isocyanate or cyclophosphamide. The femoral marrow of groups treated with phenyl isocyanate was prepared 24, 48 and 72 hours after administration. All negative and positive control animals were sacrificed after 24 hours. The doses of phenyl isocyanate and the positive control, cyclophosphamide, were 30 and 20 mg/kg body weight, respectively.

The animals treated with phenyl isocyanate showed lasting symptoms of toxicity after administration. One of forty animals died before the end of the test due to the acute intraperitoneal toxicity of 30 mg/kg phenyl isocyanate.

There was an altered ratio between polychromatic and normochromatic erythrocytes. No indications of a relevant clastogenic effect of phenyl isocyanate were found after a single intraperitoneal treatment with 30 mg/kg.