GHS Classification Guidance for the Japanese Government

principle, these test methods are not required to be used in classification. When using these
test methods, it is preferable to seek for an expert's judgement.
Sperm abnormality test using rodents (See A 6))
Several drosophila tests sex-linked recessive lethal test, wing spot test, etc. (See A 7) )
In vitro genotoxicity tests(See A 8))
-comet assay、
-UDS test using mammalian cultured cells
-DNA repair test (Rec-assay) in bacteria
-umu test or SOS test using bacteria
-aneuploidy test using yeast,etc.
host-mediated assay in bacterial gene mutation test(See A 8))
B) Order of Precedence when Conflicting Data Exist
By referring to “3-1-2 Order of precedence when Conflicting Data Exist” (p.97), basically
the following data are adopted with precedence. All of appropriate data, however, should be
utilized, and classification should be performed based on the overall weight of evidence.
1) Classification should be based on tests which were conducted appropriately and validated
sufficiently. For example, tests conducted according to internationally recognized test
methods such as OECD test guidelines and GLP satisfy this condition.
2) Data concerning mutagenicity tests are abundant, but such data are assigned greater
evidential weight which shows more appropriately that the tested substances are regarded
to induce heritable mutations in human germ cells (in vivo tests using germ cells rather
than somatic cells, in vivo tests rather than in vitro tests, in vitro tests using human cells
rather than mammalian cells).
3) As can be seen from the classification criteria described in the UN GHS second evised
edition, generally, classification in Category 2 is not based only on positive results from in
vitro mutagenicity tests. An attention needs to be paid also to results from in vivo
mutagenicity tests in drosophila. Some test reports may contain multiple negative or
positive results, and the classification based on a part of positive results alone is required
to be verified of its validity.
C) Comparison with conventional classification systems
The concept of GHS classification for Germ Cell Mutagenicity is fundamentally in accord
with that for Mutagen Categories 1, 2, and 3 in EU classification.
Mutagens classified as Category 1 (R46) in EU classification correspond to substances in
Category 1A.(To date, no such substance has been identified.)
Mutagens classified as Category 2 (R46) in EU classification correspond to substances in
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