Tmax M (h) F T1/2 M F Vd M F CLT M F F (%) M = male F = female T1/2 = half-life of elimination Vd = volume of distribution CLT = clearance F (%) = bioavailability Toxicology Single dose toxicity Table 3: Summary of single dose toxicity studies. Number/ Dose/Route of Approx. Lethal dose/ Species Sex Major findings Group administration MTD/LD50 Repeat-dose toxicity Table 4: Summary of repeated administration studies NOEL/ AUC Species/ Doses Route and NOAEL (ng.h/ml) Number of Major findings (mg/kg/day) duration (mg/kg/joday) For Antibodies = animals (µg.day/ml) Genotoxicity Table 5: Summary of genotoxicity studies Concentrations / Concentration Type of test/GLP Test System range / Results Metabolising system Gene mutations in bacteria Salmonella typhimurium / E.coli +/- S9 Gene mutations in mammalian cells CHO-cells, HGPRT-locus +/- S9 Mouse, micronuclei in bone Chromosomal aberrations in-vivo mg/kg marrow Others Carcinogenicity Table 6: Summary of carcinogenicity studies Species/Number Dose/route of Duration NOEL/ NOAEL AUC Major findings of animals administration (mg/kg/day) (ng.h/ml)
Tmax (h) M F T1/2 M F Vd M F CLT M F F (%) M = male F = female T1/2 = half-life of elimination Vd = volume of distribution CLT = clearance F (%) = bioavailability Toxicology Single dose toxicity Table 3: Summary of single dose toxicity studies. Species Sex Number/ Group Dose/Route of administration Approx. Lethal dose/ MTD/LD50 Major findings Repeat-dose toxicity Table 4: Summary of repeated administration studies Species/ Number of animals Doses (mg/kg/day) Route and duration NOEL/ NOAEL (mg/kg/joday) AUC (ng.h/ml) For Antibodies = (µg.day/ml) Major findings Genotoxicity Table 5: Summary of genotoxicity studies Type of test/GLP Test System Concentrations / Concentration range / Metabolising system Results Gene mutations in bacteria Salmonella typhimurium / E.coli +/- S9 Gene mutations in mammalian cells CHO-cells, HGPRT-locus +/- S9 Chromosomal aberrations in-vivo Mouse, micronuclei in bone marrow mg/kg Others Carcinogenicity Table 6: Summary of carcinogenicity studies Species/Number of animals Dose/route of administration Duration NOEL/ NOAEL (mg/kg/day) AUC (ng.h/ml) Major findings
AEC_FOR115A_V01_DOC_ADD_FT1.docx