4-chloro-3-nitrobenzoic acid

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)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

4-chloro-3-nitrobenzoic acid

EC Number:

202-550-9

EC Name:

4-chloro-3-nitrobenzoic acid

Cas Number:

96-99-1

Molecular formula:

C7H4ClNO4

IUPAC Name:

4-chloro-3-nitrobenzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Frequency of treatment:

single

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, it can be stated that during the study described and under the experimental conditions reported, the test item
Acido 4-cloro-3-nitro benzoico did not induce structural and/or numerical chromosomal damage in the immature erythrocytes of the mouse.
Therefore, the test item Acido 4-cloro-3-nitro benzoico is considered to be non-mutagenic with respect to clastogenicity and/or aneugenicity
in the Mammalian Erythrocyte Micronucleus Test.

Executive summary:

This study was perfonned to investigate the potential of Acido 4-c1oro-3- nitro benzoico to induce micronuc1ei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse, which is the endpoint of this test to assess genotoxicity. The test item was prepared with Cottonseed oil. The volume administered ip was 10 mL/kg bw. Peripheral blood sampies were collected for micronuc1ei analysis 44 h and 68 h after a single application of the test item. Apre-experiment was perfonned as range finding study based on the OECD guideline 474 and other relevant documents. A dose of 300 mglkg bw was selected as maximum tolerable dose (MTD). Signs of toxicity were noted. In the main experiment three dose levels were used covering a range from the maximum tolerable dose to slightlor no toxicity. The following dose groups were selected based on the toxicity observed in the pre-experiment:

Doses	Concentration [mg/kg bw]
1 MTD	300 mg/kg bw
0.5 MTD	150 mg/kg bw
0.2 MTD	67 mglkgbw

The animals treated with a dose of 0.2 MTD and 0.5 MTD showed slight signs of systernic toxicity. The animals treated with a dose of 1 MTD showed signs of systemic toxicity. The signs of toxicity noted were reduction of spontaneous activity, rough fur, prone position and cramps. For all dose groups, inc1uding positive and negative controls, 10000 polychromatic erythrocytes per animal were scored for incidence of micronuc1eated immature erythrocytes. The negative controls (44 h, 68 h) were within the range ofthe historicallabour control data. The mean values noted for the dose groups which were treated with the test item (44 h, 68 h) were within or decreased compared to the negative control data range. No biologically relevant increase of micronuc1ei was found after treatment with the test item in any of the dose groups evaluated. The nonpararnetric Mann-Whitney test was perfonned to verify the results. No statistically significant enhancement (p<0.05) of cells with micronuc1ei was noted in any dose group ofthe test item evaluated (Table 12).

Cyc1ophospharnide (40 mglkg bw) administered ip was used as positive control which induced a significant increase in micronuc1eus frequency. This demonstrates the validity of the assay.