Carbendazim

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Carbendazim was tested with several studies in somatic cells of insects and rodents using different endpoints as somatic recombination, gene mutations, structural chromosome aberration and /or numerical aberrations (micronucleus test) and in one in vivo/in vitro test (host mediated assay). Also the covalent binding to rat liver DNA was investigated.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Carbendazim

EC Number:

234-232-0

EC Name:

Carbendazim

Cas Number:

10605-21-7

Molecular formula:

C9H9N3O2

IUPAC Name:

carbendazim

Test animals

Species:

mouse

Strain:

NMRI

Remarks:

ICR, BDF1

Administration / exposure

Details on exposure:

dose of up to 5000 mg/kg bw

Results and discussion

Test results

Sex:

not specified

Genotoxicity:

positive

Toxicity:

not specified

Any other information on results incl. tables

Carbendazim induce micronuclei in plychromatic erythrocytes of NMRI mice. The positive effect was obtained when doses higher than 50 mg/kg were administered orally. Evidence that the induction of micronuclei resulted rather from a spindle inhibitory effect as from clastogenic mechanisms is given by the remarkable large size of the micronuclei observed and by a DNA-binding asaay, which proved that carbendazim did not bind to rat liver DNA but showed only chemical affinity for proteins.

Additionally, evidence that carbendazim has no clastogenic but aneugenic properties was obtained from studies investigating the effects of carbendazim on the spindle apparatus. It was shown that carbendazim and Benomyl bind to tubulin and inhibits the assembly of microtubules and their polymerisation inducing micronuclei, aneuploidy and polyploidy.

Carbendazim and Benomyl induced micronuclei in bone marrow polychromatic erythrocytes (PECs) of BDF1 mice are due to aneuploidy rather than structural chromosome damage using an immunofluorescent antikinetochore antibody technique. These results are in line with in vitro investigations in human lymphocytes and human-chinese hamster hybrid cells where the induction of micronuclei, polyploidy and aneuploidy with carbendazim and benomyl were observed.