Differential sensitivity in embryonic stages of the zebrafish (Danio rerio): The role of toxicokinetics for stage-specific susceptibility for azinphos-methyl lethal effects

The occasionally observed differential chemical sensitivity in embryonic life stages of fish is still poorly understood and could represent an important issue for understanding the time course of toxicity and the toxic modes of action of chemicals. In this study we analyzed the toxicity of the acetylcholinesterase inhibitor azinphos-methyl (APM) in different life-stages of zebrafish embryos. To this end, the LC50 of three 48 h-exposure windows were determined (12 mu M for 0-48, no mortality observed for 24-72 and 72-120 hpf up to a concentration of 79 mu M). We hypothesized that the differential sensitivity of the stage-specific embryos may be related to differences in uptake of the compound and/or internal concentrations. Therefore, internal concentrations were determined using HPLC. Similar levels and time courses of internal concentrations for all three exposure windows were observed. Bioconcentration amounted to a factor of about 30. Short-term exposure windows for a concentration 4-fold above the calculated LC50 (47 mu M) identified the period of 0-4 hpf as the most sensitive time window for APM toxicity. Our results indicate that the differential sensitivity of APM in the embryos is not related to differences in internal concentrations but related to a stage specific mechanisms of toxicity. (C) 2015 Elsevier B.V. All rights reserved.