Tissue-specific accumulation, elimination, and toxicokinetics of illicit drugs in adult zebrafish (Danio rerio)

Abstract

The abuse of illicit drugs has led to their extensive detection worldwide and subsequently exerted adverse effects upon aquatic organisms and ecosystem. However, less attention has been paid to the uptake, biotransformation, internal distribution, and toxicokinetic processes in the exposed organisms. In this study, zebrafish (Danio rerio) was exposed to methamphetamine (METH) and ketamine (KET) at three different concentrations in a semi-static exposure system. METH and KET, together with their metabolites, amphetamine (AMP) and norketamine (NK), were consistently detected in zebrafish. Over 14-day exposure, the relative magnitude of mean concentrations of illicit drugs in zebrafish generally followed the order of brain > liver > intestine > ovary > muscle. The uptake rate constants (Ku) of METH and KET were in the range of 0.590–1.38 × 103 L/(kg·d), the elimination rate constants (Ke) were in the range of 0.18–6.98 1/d, and the half-lives were in the range of 0.18–6.98 d, respectively. METH and KET demonstrated relatively rapid uptake and elimination kinetics and short half-lives, and concentrations in organs were driven by external concentrations. Illicit drugs were not persistent within zebrafish organs when there were no substantial external contaminant sources. The observed values of bioconcentration factor (BCFo, L/kg) and kinetically-derived bioconcentration factor (BCFk, L/kg) were at the similar level. The ability of different zebrafish organs accumulating target chemicals from the aquatic environment was different, and brain was the target organ of the test illicit drugs.