Table 2.

An outline summary of the current ICH guidelines for the genotoxicity testing of pharmaceuticals compared with the proposed two-option revised guideline, ICH S2(R1)

ICH S2 guidelines (A&B)	ICH S2(R1) – proposed revisions to S2
Current	Option 1	Option 2
Bacterial mutation (Ames)	Bacterial mutation (Ames)	Bacterial mutation (Ames)
With repeat test	One full test	One full test
In vitro mammalian cell test (to 10 mM)	In vitro mammalian cell test (to 1 mM)
CA	CA	No requirement
or	or
Mutation (e.g. tk)	Mutation (e.g. tk)
	or
	MNT
In vivo cytogenetic assay	In vivo cytogenetic assay	In vivo assay
	Integrated into 28-day acute toxicity study where possible	Two endpoints, integrated into 28-day acute toxicity study where possible

CA, chromosome aberrations; ICH, International Committee on Harmonisation; MNT, micronucleus test.