p-(trifluoromethoxy)phenyl 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

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

The micronucleus test was employed to investigate 4-trifluoromethoxyphenyl isocyanate in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, Trenimon, served as positive control. The treated animals received 2 oral application within 24 hoursof the test substance, the positive control was applied intraperitoneal. The femoral marrow of groups treated with 4-trifluoromethoxyphenyl isocyanate was prepared 6 hours after administration.

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

p-(trifluoromethoxy)phenyl isocyanate

EC Number:

252-328-0

EC Name:

p-(trifluoromethoxy)phenyl isocyanate

Cas Number:

35037-73-1

Molecular formula:

C8H4F3NO2

IUPAC Name:

1-isocyanato-4-(trifluoromethoxy)benzene

Details on test material:

content: 99.78%

Test animals

Species:

mouse

Strain:

other: Bor: NMRI (SPF Han)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Duration of treatment / exposure:

2 oral treatments within 24 hours

Frequency of treatment:

2 oral treatments within 24 hours

Post exposure period:

Animals were sacrificed 6 after the second application

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day (nominal)

Remarks:

2 x 100 mg/kg bw

Doses / concentrations 2

Dose / conc.:

50 mg/kg bw/day (nominal)

Remarks:

2 x 50 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female mice/group

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

Remarks:

in the 2 x 50 mg/kg bw no signs of toxicity; in the 2 x 100 mg/kg bw group 11 of 20 animals died

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect.

Applicant's summary and conclusion

Conclusions:

No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect. Under the conditions of the test 4-trifluoromethoxyphenyl isocyanate was negative in the in-vivo micronucleus test.

Executive summary:

The micronucleus test was employed to investigate 4-trifluoromethoxyphenyl isocyanate in male and female mice for a possible clastogenic effect on the chromosomes of bone-marrow erythroblasts. The known clastogen and cytostatic agent, Trenimon, served as positive control. The treated animals received 2 oral application of the test substance within 24 hours, the positive control was applied intraperitoneal. The femoral marrow of groups treated with 4-trifluoromethoxyphenyl isocyanate was prepared 6 hours after administration.

No signs for a mutagenic effect of 4-trifluoromethoxyphenyl isocyanate in doses up to 2 x 100 mg/kg bw was evident. No relevant, treatment related alteration of the ratio polychromatic to normochromatic erythrocytes was found. the positive control (Tremonin) had a clear mutagenic effect. Under the conditions of the test 4-trifluoromethoxyphenyl isocyanate was negative in the in-vivo micronucleus test.