GHS Classification Guidance for the Japanese Government

7) Data from various kinds of tests using drosophila(sex-linked or recessive lethal test, wing
spot test, etc.) are, generally, not used in this classification since biological dynamics and
reproduction development process are not the same between insects and mammals.
However when other suitable mammalian in vivo mutagenicity/genotoxicity test data are
not available, and especially when positive results from drosophila sex-linked or recessive
lethal test are available, judgement by experts in this fields shall be sought for using the
data and GHS classification category.
8) There exist many kinds of in vitro genotoxicity tests (Comet testin mammalian culture
cells, UDS test in mammalian culture cells, DNA (Rec-assay) in Bacillus subtilis, umu test
in Salmonella typhimurium, SOS test in Escherichia coli, chromatid aberration with
aneuploid test in yeast, etc.) and Host-mediated assay, but results of theses tests are, in
principle, not used in this classification.
9) In in vivo mutagenicity/genotoxicity tests, various administration routes are used.
Although the common human exposure routes take precedence, test data with any
administration route may be utilized unless the inappropriateness of the route is rationally
explained.
10) Substances that have been concluded by epidemiological studies to induce heritable
mutation in human population shall be classified in Category 1A. Since, however, positive
results have so far been obtained with many test methods such as in vivo mutagenicity
tests using germ cells without above substances, substances shall be classified in Category
1B which should be regarded as if they induce gene mutation or chromosomal abnormality
to human germ cells. Category 1B includes substances showing positive result(s) in in vivo
heritable mutagenicity tests in mammalian germ cells (rodent dominant lethal mutation
test, mouse heritable translocation assay, mouse specific locus test, etc.), positive result(s)
in in vivo mutagenicity tests in mammalian somatic cells (mammalian bone marrow
chromosome aberration test, mammalian erythrocyte micronucleus test, mouse spot test,
etc.) coupled with some evidence that the substnces have potential to induce mutation in
germ cells (for example, positive results in such as mammlian spermatogonial
chromosome aberration test, spermatid micronucleus assay, sister chromatid exchange
analysis in spermatogonia, unscheduled DNA synthesis (UDS) test in testicular cells, or
evidence of exposure of germ cells to the active substnces or its metabolite(s)), or positive
results showing mutagenicity in human germ cells without evidence of transmission to
progeny (for example, an increase in the frequency of aneuploidy in sperm cells of
exposed human subjects).
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