Large-Scale Assessment of the Zebrafish Embryo as a Possible Predictive Model in Toxicity Testing

Background: In the drug discovery pipeline, safety pharmacology is a major issue. The zebrafish has been proposed as a model that can bridge the gap in this field between cell assays (which are cost-effective, but low in data content) and rodent assays (which are high in data content, but less cost-efficient). However, zebrafish assays are only likely to be useful if they can be shown to have high predictive power. We examined this issue by assaying 60 water-soluble compounds representing a range of chemical classes and toxicological mechanisms. Methodology/Principal Findings: Over 20,000 wild-type zebrafish embryos (including controls) were cultured individually in defined buffer in 96-well plates. Embryos were exposed for a 96 hour period starting at 24 hours post fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for LC 50 determination. Zebrafish embryo LC50 (log mmol/L), and published data on rodent LD50 (log mmol/kg), were found to be strongly correlated (using Kendall’s rank correlation tau and Pearson’s product-moment correlation). The slope of the regression line for the full set of compounds was 0.73403. However, we found that the slope was strongly influenced by compound class. Thus, while most compounds had a similar toxicity level in both species, some compounds were markedly more toxic in zebrafish than in rodents, or vice versa. Conclusions: For the substances examined here, in aggregate, the zebrafish embryo model has good predictivity for toxicit

Enrichment pattern of leachable trace metals in roadside soils of Miri City, Eastern Malaysia

This article presents the results on distribution and enrichment pattern of acid-leachable trace metals (ALTMs) from roadside soil of Miri city, Sarawak, East Malaysia. The city is one of the fastest developing in the Malaysian region with huge petroleum resources. ALTMs Fe, Mn, Cr, Cu, Ni, Co, Pb, Zn and Cd along with organic carbon and carbonates (CaCO3) were analyzed in 37 soil sediments collected from roadside. The enrichment of ALTMs [especially Cu (0.4-13.1 µg g-1), Zn (9.3-70.7 µg g-1), Pb (13.8-99.1 µg g-1)] in the roadside soils indicate that these metals are mainly derived from sources related to traffic exhausts, forest fires and oil refineries. The comparative study and enrichment pattern of elements indicates that Mn, Cu, Zn and Pb are enriched multi-fold than the unpolluted soil and Ni, Pb, Cd in some samples compared to Sediment Quality Guidelines like Lowest Effect Level (LEL) and Effects Range Low (ERL) in the region which is mainly due to the recent industrial developments in the region. © 2014 Springer-Verlag Berlin Heidelberg