Analysis of elimination half-lives in MamTKDB 1.0 related to bioaccumulation: Requirement of repeated administration and blood plasma values underrepresent tissues

Environ Int. 2021 Jun 10;155:106592. doi: 10.1016/j.envint.2021.106592. Online ahead of print.ABSTRACTWhen building the novel public mammalian toxicokinetic database (MamTKDB) we collected and included 3927 elimination half-lives (elimt1/2) for 1407 xenobiotics in various species (rat, human, mouse, dog, monkey, rabbit, cattle, pig, sheep, guinea pig, hamster, horse and goat) with specification of compartment (whole body, organ/tissue, cell type, medium) studied. Here we describe and analyse the collected data in MamTKDB 1.0. Most elimt1/2 are for humans and rats and their data differ in some ways: whereas the rat data are mainly for pesticides, the human data are mainly for pharmaceuticals and environmental contaminants. There are also differences in types of compartments studied and in metabolites followed: human elimt1/2 are mainly whole body based (i.e. based on blood plasma or excretion), animal data are additionally for various organs/tissues, cells or media. Contrary to human studies, animal studies regularly administrate radiolabeled (e.g. 14C) substances and distribution of both parent and eventual metabolites are followed, measuring the radioactivity. In rats, substances had been given through single, preconditioning or repeated administration. Single administration studies dominated, but repeated studies generally had longer elimt1/2 than single or preconditioning studies for which elimt1/2 were similar. Repeated administration studies should better ascertain stead...
Source: Environment International - Category: Environmental Health Authors: Source Type: research