Correlation between the results of in vitro and in vivo chromosomal damage tests in consideration of exposure levels of test chemicals

Table 3 Comparison of parameters between in vivo positive and in vivo negative compounds - in vivo negative case with C_max and AUC_vivo being equal to or higher than in vitro LEC and AUC_vitro -

Compound	LEC (μg/mL)	C_max (μg/mL)	AUC_vitro (μg·h/mL)	AUC_vivo (μg·h/mL)	the highest dose in vivo	t_max (h)	PPB (%)	in vitro positive condition	CS at LEC^a (%)	Fold Increase^b
D	75.0	96.8	1800	1360	MFD	5.0	93.2	continuous	RCC: 59 (RICC: 39)	33.0
E	120	298	720	5351	MTD	8.0	99.8	short (+ S9)	RCC: 74 (RICC: 61)	ND
F	7.34	19.0	191	323	MTD	24.0	98.6	continuous	RCC: 81 (RICC: 74)	6.12
G	24.9	23.6	598	508	MTD	4.0	98.5	continuous	RCC: 48 (RICC: 31)	3.0
H	15.9	20.5	413	346	MTD	7.0	91.5	continuous	RICC: 71	3.0

LEC, the lowest effective (positive) concentration in the in vitro test; C_max, maximum plasma concentration; AUC, area under the concentration time curve; MFD, the maximum feasible dose (2000 mg/mg); MTD, the maximum tolerated dose; t_max, time to maximum plasma concentration; PPB, the ratio of plasma protein binding; CS, the ratio of cell survival; short (+S9), short-term with S9 mix; continuous, continuous without S9 mix; ND, not determined due to the vehicle control value “0”
^aCell survival ratio at LEC compared to concurrent vehicle control. RCC, relative cell survival; RICC, relative increase in cell count
^bMaximum fold increases of the incidence of micronucleated cells or cells with chromosomal aberration compared to the concurrent vehicle control value
Estimated RICC from RCC data

ISSN: 1880-7062