The sensitivity of metabolomics versus classical regulatory toxicology from a NOAEL perspective.

The identification of the no observed adverse effect level (NOAEL) is the key regulatory outcome of toxicity studies. With the introduction of "omics" technologies into toxicological research, the question arises as to how sensitive these technologies are relative to classical regulatory toxicity parameters. BASF SE and metanomics developed the in vivo metabolome database MetaMap®Tox containing metabolome data for more than 500 reference compounds. For several years metabolome analysis has been routinely performed in regulatory toxicity studies (REACH mandated testing or new compound development), mostly in the context of 28 day studies in rats (OECD 407 guideline). For those chemicals for which a toxicological NOAEL level was obtained at either high or mid-dose level, we evaluated the associated metabolome to investigate the sensitivity of metabolomics versus classical toxicology with respect to the NOAEL. For the definition of a metabolomics NOAEL the ECETOC criteria (ECETOC, 2007) were used. In this context we evaluated 104 cases. Comparable sensitivity was noted in 75% of the cases, increased sensitivity of metabolomics in 8%, and decreased sensitivity in 18% of the cases. In conclusion, these data suggest that metabolomics profiling has a similar sensitivity to the classical toxicological study (e.g. OECD 407) design.

Caged Gammarus fossarum (Crustacea) as a robust tool for the characterization of bioavailable contamination levels in continental waters: towards the determination of threshold values.

We investigated the suitability of an active biomonitoring approach, using the ecologically relevant species Gammarus fossarum, to assess trends of bioavailable contamination in continental waters. Gammarids were translocated into cages at 27 sites, in the Rhône-Alpes region (France) during early autumn 2009. Study sites were chosen to represent different physico-chemical characteristics and various anthropic pressures. Biotic factors such as sex, weight and food availability were controlled in order to provide robust and comparable results. After one week of exposure, concentrations of 11 metals/metalloids (Cd, Pb, Hg, Ni, Zn, Cr, Co, Cu, As, Se and Ag) and 38 hydrophobic organic substances including polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyles (PCBs), pentabromodiphenylethers (PBDEs) and organochlorine pesticides, were measured in gammarids. All metals except Ag, and 33 organic substances among 38 were quantified in G. fossarum, showing that this species is relevant for chemical biomonitoring. The control of biotic factors allowed a robust and direct inter-site comparison of the bioavailable contamination levels. Overall, our results show the interest and robustness of the proposed methodological approach for assessing trends of bioavailable contamination, notably for metals and hydrophobic organic contaminants, in continental waters. Furthermore, we built threshold values of bioavailable contamination in gammarids, above which measured concentrations are expected to reveal a bioavailable contamination at the sampling site. Two ways to define such values were investigated, a statistical approach and a model fit. Threshold values were determined for almost all the substances investigated in this study and similar values were generally derived from the two approaches. Then, levels of contaminants measured in G. fossarum at the 27 study sites were compared to the threshold values obtained using the model fit. These threshold values could serve as a basis for further implementation of quality grids to rank sites according to the extent of the bioavailable contamination, with regard to the applied methodology.

Selenium bioaccumulation by the water boatman Trichocorixa reticulata (Guerin-Meneville).

The input of selenium from subsurface agricultural drainage into surface water systems can result in the accumulation of toxic concentrations of selenium in aquatic food chains. Elevated selenium concentrations in aquatic systems is a significant environmental problem in many areas of the United States. A laboratory investigation was conducted to determine the dominant route of selenium bioaccumulation by the corixid Trichocorixa reticulata, an important food chain organism. The roles of waterborne and foodborne exposure in selenium bioaccumulation were examined using 48-h bioassays. Waterborne selenium concentrations ranged from 0 to 1,000 microgram Se/L as selenate. A mixture of two species of blue-green algae cultured in media with selenium concentrations ranging from 0 to 1,000 microgram Se/L as selenate was used as a corixid diet in the foodborne treatments. Corixids exposed to waterborne selenate did not accumulate selenium above control concentrations. Corixids fed algae exposed to >/=100 microgram Se/L as selenate had significantly higher selenium concentrations than control organisms. These data suggest that corixids may be effectively isolated from the water and selenium accumulation is solely through dietary exposure.