2-nitro-4-(trifluoromethyl)benzonitrile

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: HJ/T153-2004, 474

Version / remarks:

Second edition, 2013

GLP compliance:

yes

Remarks:

The test complied with the Principles of Good Laboratory Practices (GLP) of the Certification and Accreditation Administration of the People’s Republic of China (2013 revised edition).

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2-nitro-4-(trifluoromethyl)benzonitrile

EC Number:

212-298-1

EC Name:

2-nitro-4-(trifluoromethyl)benzonitrile

Cas Number:

778-94-9

Molecular formula:

C8H3F3N2O2

IUPAC Name:

2-nitro-4-(trifluoromethyl)benzonitrile

Test animals

Species:

mouse

Strain:

other: Kun Ming (KM)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

pressed corn oil

Duration of treatment / exposure:

two exposures at an interval of 24 h
post-exposure period: 19 - 21 h

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

400 mg/kg bw/day

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

yes (Cyclophosphamide monohydrate (CP) in purified water)

Examinations

Tissues and cell types examined:

Slides were prepared from the sternum bone marrow, stained, examined by microscope, and analysed. At least 200 erythrocytes were observed in the bone marrow of each animal, and the proportion of immature erythrocytes to total erythrocytes (immature erythrocytes + mature erythrocytes) was counted. 2000 immature erythrocytes (PCE) were observed in each animal, in order to count the micronucleated (MN) incidence rate.

Evaluation criteria:

A result was interpreted as positive, if:
- micronucleated cell count increased in a dose-dependent way; or
- micronucleated cell count in a particular dose group increased significantly.

Statistics:

two-tailed t-test method

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

at 400 mg/kg bw/day

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

In the test period, with the exception of colour in urine in one animal, no clinical symptoms were noted. Except for a declining trend in animal body weight in the high dose group, animal body weight was comparable to the control group.
The ratio of PCE to RBC (total erythrocytes) in the exposure group was larger than 20% of the control group, and the ratio decreased with increasing doses. 400 mg/kg bw/day was able to induce bone marrow toxicity. Micronucleated incidence rates for males and females in all exposure groups were not statistically significant (P > 0.05). The positive control group produced a statistically significant response (P < 0.001).

Applicant's summary and conclusion

Conclusions:

The test results indicated that, under the conditions in this laboratory, the test substance 2-nitro-4-(trifluoromethyl)benzonitrile did not induce elevated incidence of micronucleated polychromatic erythrocytes in bone marrow in mice. The results of the present test were therefore assessed as negative.