GHS Classification Guidance for the Japanese Government

humans. In this guidance, to facilitate understanding, the term “heritable
mutagenicity” is used in addition to “germ cell mutagenicity.” The “germ cell
mutagenicity” means effects to induce mutagenicity/genotoxicity in germ cells, and
“heritable mutagenicity” means effects to induce gene mutation chromosamal
abnormality in future generation of the mutagenicity recognized in germ cells. In
the UN GHS second revised edition, the term “heritable mutagenicity” is not used,
but the corresponding phrase “to induce heritable mutations in germ cells of
humans” is used.
2) The UN GHS second revised edition 3.5.5.1 “Decision logic 3.5.1 for substances” starts
with the question, “Does the substance have data on mutagenicity ?”. The phrase “data on
mutagenicity” basically means data obtained from in vivo mutagenicity/genotoxicity tests
that are generally used and normally means a set of data including those obtained from in
vitro tests. Expert's support is required for making a decision on mutagenicity based on
multiple conflicting test results.
3) For many chemicals, results from many mutagenicity tests (or genotoxicity tests) are
reported including in vitro tests, but results from in vivo tests using mammalian germ cells
are rare. Expert's evaluation and decision are required for passing judgment on
mutagenicity to human germ cells based on a large amount of In vitro and in vivo test
reports.
4) Although human data are precious, usage of epidemiological data is extremely limited
since , in many cases, data obtained from human monitoring exposed with some chemicals
(for example, chromosome analysis on human peripheral lymphocytes) show unclear
effects by the chemicals, and since the number of subjects is not sufficient to give a
generalized conclusion. Epidemiological data may provide conflicting results, but they
may be easily used when the validity of the finding (negative or positive) is recognized by
assessment documents in List 1.
5) Chemicals having dataset from in vivo and in vitro tests are less in number than chemicals
having in vitro test data only. In general, it is difficult to determine the existence of
heritable mutagenicity based on results of in vitro tests only.
6) Results from rodent spermshape abnormality test shall not be used in this classification in
principle since they may be affected by effects to other than genetic materials
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