Table 3.

Safety margins (SMs) of the 23 test compounds calculated either as the ratio between the lowest in vitro concentration that yielded a DICI-positive result (< 0.78) and the total plasma concentration (C_max,total) of the compound (i.e., the LOAEL method), or as the ratio between the highest in vitro concentration that yielded a DICI-negative result (≥ 0.78) and the C_max,total of the compound (i.e., the NOAEL method). The SMs were calculated based on the new DICI cut-off value of 0.78. Values in bold differ between both methods. N.D.; not determined.

Class	Compound	Cmax,total (µM)	DICI-based SM obtained with the NOAEL method		DICI-based SM obtained with the ‘original’ LOAEL method		References
			24 h	48 h	24 h	48 h
A	Acetaminophen	139	7.19	7.19	7.19	7.19	[24]
	Amiodarone	0.81	30.86	30.86	30.86	30.86	[24,25]
	Diclofenac	7.99	62.58	62.58	62.58	62.58	[24,25]
	Tolcapone	47.6	1.05	1.05	1.05	1.05	[3]
	Ximelagatran	0.3	500	500	500	500	[26, 27]
	Perhexiline	2.16	30.09	30.09	30.09	30.09	[24]
	Fialuridine	0.64	468.75	468.75	468.75	46.88	[3]
	Warfarin	6.97	71.74	N.D.	71.74	N.D.	[28]
B	Troglitazone	6.39	7.82	11.74	15.65	15.65	[24,25]
	Nefazodone	4.26	2.35	2.35	30.52	7.04	[3]
	Bosentan	7.39	27.06	6.77	27.06	27.06	[3]
	Ritonavir	13.24	1.51	1.51	7.55	7.55	[29], [30], [31]
	Cyclosporin A	0.77	19.48	19.48	19.48	19.48	[3]
	Midecamycin	2	50	50	50	50	[32]
	Erythromycin	3.97	50.38	N.D.	50.38	N.D.	[33,34]
	Rosiglitazone	1.776	56.31	N.D.	56.31	N.D.	[35]
	Ticlopidine	2.898	34.51	N.D.	34.51	N.D.	[36,37]
	Chlorpromazine	0.0376	265.96	N.D.	265.96	N.D.	[38,39]
	Atazanavir	4.82	31.12	10.37	31.12	31.12	[40], [41], [42]
C	Entacapone	4.34	6.91	6.91	29.95	29.95	[43]
	Metformin	7.75	116.13	116.13	116.13	116.13	[44]
	Buspirone	0.01	50	1000	5000	15000	[3]
	Pioglitazone	2.95	101.69	101.69	101.69	101.69	[24,25]