Chlorimuron ethyl

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Similar to OECD Guideline 475 with significant methodological deficiencies. The power of the assay is too low and there is no evidence of target cell (bone marrow) exposure.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study was designed to evaluate the clastogenic potential of the test substance as measured by increases in numerical and structural chromosomal aberrations in rat bone marrow cells. A single dose of the test material was administered by oral gavage to three groups of 20 male and 20 female rats at levels of 500, 1500, and 5000 mg/kg of body weight. At approximately 4, 10, 22, and 46 hours after administration of the test and control substances the appropriate groups of animals received a single intraperitoneal injection of colchicine to inhibit mitosis and arrest cells in metaphase and the animals were sacrificed after 2 hours of injection and bone marrow cells collected to prepare slides for measuring the numerical and structural chromosomal aberrations.

GLP compliance:

no

Type of assay:

other: Chromosomal aberration assay

Test material

Test material information

1

Reference substance name:

ethyl 2-({[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)benzoate

EC Number:

618-690-2

Cas Number:

90982-32-4

Molecular formula:

C15H15ClN4O6S

IUPAC Name:

ethyl 2-({[(4-chloro-6-methoxypyrimidin-2-yl)carbamoyl]amino}sulfonyl)benzoate

Test material form:

solid: particulate/powder

Details on test material:

Purity: 96%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

CD (albino)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Frequency of treatment:

Once

Post exposure period:

6, 12, 24, and 48 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

500 mg/kg bw (total dose)

Doses / concentrations 2

Dose / conc.:

1 500 mg/kg bw (total dose)

Doses / concentrations 3

Dose / conc.:

5 000 mg/kg bw (total dose)

No. of animals per sex per dose:

20
Positive control: 5

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide

Examinations

Tissues and cell types examined:

Bone marrow

Statistics:

The mean mitotic indices, mean modal numbers, percent aberrant cells and the mean number of aberrations per cell for each group were statistically compared using the Kruskal-Wallis nonparametric analysis of variance and nonparametric pairwise group comparisons (KW-ANOVA). Body weight data was analyzed by analysis of covariance (ANCOVA). All analyses were one-tailed at the 95% confidence level (p <0.05).

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test substance is considered not to be clastogenic at any of the levels tested.

Executive summary:

This study was designed to evaluate the clastogenic potential of the test substance as measured by increases in numerical and structural chromosomal aberrations in rat bone marrow cells from Charles River Sprague-Dawley, CD rats. A single dose of the test material was administered by oral gavage to three groups of 20 male and 20 female rats at levels of 500, 1500, and 5000 mg/kg of body weight.

5 males and 5 females from each group were sacrificed at 6, 12, 24, and 48 hours after the single administration of the test material. Results show that no statistically significant increases in the frequency of chromosomal aberrations compared to control values were seen for any of the dose levels that were tested. No statistically significant differences were seen between the mean modal numbers and the mean mitotic indices of the test groups and the vehicle controls.