Inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons and induces motor neuron development via Sonic hedgehog pathway in zebrafish.

The mechanism of inorganic arsenic-induced neurotoxicity at the cellular level is not known. In zebrafish, teratological effects of inorganic arsenic have been shown at various concentrations. Here, we used similar concentrations of inorganic arsenic to evaluate the effects on specific neuron types. Exposure of zebrafish embryos at 5 h post fertilization (hpf) to sodium arsenite induced developmental toxicity (reduced body length) in 72 hpf larvae, beginning at a concentration of 300 mg/L concentration. Mortality or overt morphological deformity was detected at 500 mg/L sodium arsenite. While 200 mg/L sodium arsenite induced development of tyrosine hydroxylase-positive (dopaminergic) neurons, there was no significant effect on the development of 5-hydroxytryptamine (serotonergic) neurons. Sodium arsenite reduced acetylcholinesterase activity. In the hb9-GFP transgenic larvae, both 200 and 400 mg/L sodium arsenite produced supernumerary motor neurons in the spinal cord. Inhibition of the Sonic hedgehog (Shh) pathway that is essential for motor neuron development, by Gant61, prevented sodium arsenite-induced supernumerary motor neuron development. Inductively coupled plasma mass spectrometry (ICP-MS) revealed that with 200 mg/L and 400 mg/L sodium arsenite treatment, each larva had an average of 387.8 pg and 847.5 pg arsenic, respectively. The data show for the first time that inorganic arsenic alters the development of dopaminergic and motor neurons in the zebrafish larvae and the latter occurs through the Shh pathway. These results may help understand why arsenic-exposed populations suffer from psychiatric disorders and motor neuron disease and Shh may, potentially, serve as a plasma biomarker of arsenic toxicity.

Lionfish (Pterois volitans) as biomonitoring species for oil pollution effects in coral reef ecosystems.

With oil spills, and other sources of aromatic hydrocarbons, being a continuous threat to coral reef systems, and most reef fish species being protected or difficult to collect, the use of the invasive lionfish (Pterois volitans) might be a good model species to monitor biomarkers in potentially exposed fish in the Caribbean and western Atlantic. The rapid expansion of lionfish in the Caribbean and western Atlantic, and the unregulated fishing for this species, would make the lionfish a suitable candidate as biomonitoring species for oil pollution effects. However, to date little has been published about the responses of lionfish to environmental pollutants. For this study lionfish were collected in the Florida Keys a few weeks after Hurricane Irma, which sank numerous boats resulting in leaks of oil and fuel, and during the winter and early spring after that. Several biomarkers indicative of exposure to PAHs (bile fluorescence, cytochrome P450-1A induction, glutathione S-transferase activity) were measured. To establish if these biomarkers are inducible in PAH exposed lionfish, dosing experiments with different concentrations of High Energy Water Accommodated Fraction of crude oil were performed. The results revealed no significant effects in the biomarkers in the field collected fish, while the exposure experiments demonstrated that lionfish did show strong effects in the measured biomarkers, even at the lowest concentration tested (0.3% HEWAF, or 25 µg/l Æ©PAH50). Based on its widespread distribution, relative ease of collection, and significant biomarker responses in the controlled dosing experiment, it is concluded that lionfish has good potential to be used as a standardized biomonitoring species for oil pollution in its neotropical realm.

A Petri Net Approach to Physiologically Based Toxicokinetic Modeling.

Physiologically based toxicokinetic (PBTK) modeling enables researchers to predict internal tissue concentrations for various species exposed to exogenous compounds through different routes at varying concentrations without having to run in vivo experiments for each scenario. Parameters for the models may be gathered from in vivo or in vitro measurements, cross-species or cross-chemical extrapolations, literature reviews, or other models. The PBTK models, described using ordinary differential equations (ODEs), are then simulated using these parameters for a given compound/exposure/species scenario. Although they are potentially useful for regulatory toxicology, the complexity of ODE programming and simulation remains a barrier for many would-be researchers. Petri nets, a graphical modeling framework, offers a more intuitive approach to PBTK modeling. To demonstrate their utility and ease of use, we present a model of waterborne fluoranthene exposure to rainbow trout (Oncorhynchus mykiss) written and simulated in Snoopy, a graphical Petri net development and simulation software package. We converted an existing ODE PBTK model and evaluated the Petri net model against the ODE model results. The simulated tissue concentrations of the Petri net model closely mirrored the simulated concentrations of the ODE model. To convert the ODE model to a Petri net model, we introduced a new parameter, blood volume (V BLOOD ). Sensitivity analysis found V BLOOD to be very robust when varied over an order of magnitude. The resulting Petri net PBTK model has a number of advantages over ODE models, while maintaining equivalent predictive functionality. Environ Toxicol Chem 2019;00:1-10. © 2019 SETAC.