Toxicology
The study of adverse effects of drugs and substances on living organisms. Preclinical toxicology studies for peptide drugs include single-dose, repeated-dose, reproductive, genotoxicity, and carcinogenicity assessments. These studies are mandatory before a peptide can enter human clinical trials.
Technical Context
Preclinical toxicology programme for peptide drugs (ICH M3/S6 guidelines): single-dose toxicity (acute effects, determine maximum non-lethal dose), repeat-dose toxicity (2-4 weeks for Phase I, 13 weeks for Phase II, 26 weeks for Phase III/marketing — in two species, one non-rodent), genotoxicity battery (Ames bacterial mutation, in vitro chromosomal aberration or mouse lymphoma, in vivo micronucleus — note: for biotechnology-derived peptides/proteins, genotoxicity may be waived per ICH S6(R1) if no DNA-reactive components), reproductive toxicity (fertility and early embryonic development, embryo-foetal development, peri/postnatal development), and carcinogenicity (2-year rodent studies — required for chronically administered drugs; may use 6-month transgenic mouse + 2-year rat, or justified waiver). For peptides ≥40 amino acids produced by recombinant technology, ICH S6(R1) provides specific guidance acknowledging that standard small molecule toxicology approaches may not be appropriate.