Pesticide Registration Toolkit

#616 In-vivo cytogenetics

Objective of the study

 
The aim of genotoxicity testing is to: 
  • predict genotoxic potential
  • identify genotoxic carcinogens at an early stage
  • elucidate the mechanism of action of some carcinogens.
 
The mammalian in vivo micronucleus test is used for the detection of damage induced by the test substance to the chromosomes or the mitotic apparatus of erythroblasts, by analysis of erythrocytes as sampled in bone marrow and/or peripheral blood cells of animals, usually rodents (mice or rats).
 
The mammalian in vivo chromosome aberration test is used for the detection of structural chromosome aberrations induced by test compounds in bone marrow cells of animals, usually rodents (rats, mice and Chinese hamsters).
 

Circumstances under which the study is recommended to be required

If all the results of the in vitro studies are negative, at least one in vivo study should be conducted.
 
A negative result in the first in vivo test in somatic cells shall provide sufficient reassurance for active substances that are negative in the three in vitro tests.
 
For pesticides for which an equivocal or a positive test result is obtained in any in vitro test, the nature of additional testing needed should be evaluated on a case-by-case basis taking into account all relevant information.
 

Test organism

The following in-vivo studies in mammalian somatic cells are generally recommended: 
  • The mammalian erythrocyte micronucleus test is preferred. Mice or rats are recommended if bone marrow is used, although any appropriate mammalian species may be used.
  • The rodent bone marrow chromosome aberration tests is acceptable as an alternative. Rats, mice, and Chinese hamsters are commonly used for this test, although any appropriate mammalian species may be used.
 
If other in vivo studies in mammalian somatic cells are conducted, the applicant should provide a justification.
For most of the active substances recognised as in vivo somatic cell mutagens no further genotoxicity testing will normally be necessary since they will be considered to be potential genotoxic carcinogens and potential germ cell mutagens. However, in some specific cases germ cells studies may be undertaken to demonstrate whether a somatic cell mutagen is or is not a germ cell mutagen.
 

Test substance

  • Technical grade active ingredient
 

Typical endpoints of the study

Specific endpoints of the various assays can be found in the testing guidelines cited below
 

Test guidelines

The following test guidelines may be used for the mammalian cell assays: