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

Table 2 Comparison of parameters between in vivo positive and in vivo negative compounds - in vivo positive 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
A	2.65	59.9	69	1020	–	7.0	98.9	short (+/− S9) continuous^c	RCC: 87 (RICC: 83)^d	16.8
B	121	96.5	726	1719	MFD	24.0	86.2	short (− S9)	RCC: 84 (RICC: 79)^d	3.89
C	0.250	1.53	6	14.6	–	3.0	98.6	continuous	RCC: 92 (RICC: 89)^d	8.0

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); t_max, time to maximum plasma concentration; PPB, the ratio of plasma protein binding; short (+/-S9), short-term with/without S9 mix; continuous, continuous without S9 mix
^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
^cThe data of marked treatment condition showing positive responses with the lowest exposure levels were adopted for the comparison
^dEstimated RICC from RCC data

ISSN: 1880-7062