Manufactured nanoparticles: their uptake and effects on fish—a mechanistic analysis

Richard D. Handy, Theodore B. Henry, Tessa M. Scown, Blair D. Johnston, Charles R. Tyler

There is an emerging literature reporting toxic effects of manufactured nanomaterials (NMs) and nanoparticles (NPs) in fish, but the mechanistic basis of both exposure and effect are poorly understood. This paper critically evaluates some of the founding assumptions in fish toxicology, and likely mechanisms of absorption, distribution, metabolism and excretion (ADME) of NPs in fish compared to other chemicals. Then, using a case study approach, the paper compares these assumptions for two different NPs; TiO2 and C60 fullerenes. Adsorption of NPs onto the gill surface will involve similar processes in the gill microenvironment and mucus layer to other substances, but the uptake mechanisms for NPs by epithelial cells are more likely to occur via vesicular processes (e.g., endocytosis) than uptake on membrane transporters or by diffusion through the cell membranes. Target organs may include the gills, gut, liver and sometimes the brain. Information on metabolism and excretion of NPs in fish is limited; but hepatic excretion into the bile seems a more likely mechanism, rather than mainly by renal or branchial excretion. TiO2 and C60 share some common chemical properties that appear to be associated with some similar toxic effects, but there are also differences, that highlight the notion that chemical reactivity can inform toxic effect of NPs in a fundamentally similar way to other chemicals. In this paper we identify many knowledge gaps including the lack of field observations on fish and other wildlife species for exposure and effects of manufactured NMs. Systematic studies of the abiotic factors that influence bioavailability, and investigation of the cell biology that informs on the mechanisms of metabolism and excretion of NMs, will greatly advance our understanding of the potential for adverse effects. There are also opportunities to apply existing tools and techniques to fundamental studies of fish toxicology with NPs, such as perfused organs and fish cell culture systems.