Low-Level Exposure to Multiple Chemicals: Reason for Human Health Concerns?

BACKGROUND: A key question in the risk assessment of exposures to multiple chemicals is whether mixture effects may occur when chemicals are combined at low doses which individually do not induce observable effects. However, a systematic evaluation of experimental studies addressing this issue is missing. OBJECTIVES: With this contribution, we wish to bridge this gap by providing a systematic assessment of published studies against well-defined quality criteria. RESULTS: On reviewing the low-dose mixture literature, we found good evidence demonstrating significant mixture effects with combinations of chemicals well below their individual no observable adverse effect levels (NOAELs), both with mixtures composed of similarly and dissimilarly acting agents. CONCLUSIONS: The widely held view that mixtures of dissimilarly acting chemicals are "safe" at levels below NOAELs is not supported by empirical evidence. We show that this view is also based on the erroneous assumption that NOAELs can be equated with zero-effect levels. Thus, on the basis of published evidence, it is difficult to rule out the possibility of mixture effects from lowdose multiple exposures

Magnetoresistance through a single molecule

The use of single molecules to design electronic devices is an extremely challenging and fundamentally different approach to further downsizing electronic circuits. Two-terminal molecular devices such as diodes were first predicted [1] and, more recently, measured experimentally [2]. The addition of a gate then enabled the study of molecular transistors [3-5]. In general terms, in order to increase data processing capabilities, one may not only consider the electron's charge but also its spin [6,7]. This concept has been pioneered in giant magnetoresistance (GMR) junctions that consist of thin metallic films [8,9]. Spin transport across molecules, i.e. Molecular Spintronics remains, however, a challenging endeavor. As an important first step in this field, we have performed an experimental and theoretical study on spin transport across a molecular GMR junction consisting of two ferromagnetic electrodes bridged by a single hydrogen phthalocyanine (H2Pc) molecule. We observe that even though H2Pc in itself is nonmagnetic, incorporating it into a molecular junction can enhance the magnetoresistance by one order of magnitude to 52%.Comment: To appear in Nature Nanotechnology. Present version is the first submission to Nature Nanotechnology, from May 18th, 201

Test System Stability and Natural Variability of a Lemna Gibba L. Bioassay

BACKGROUND: In ecotoxicological and environmental studies Lemna spp. are used as test organisms due to their small size, rapid predominantly vegetative reproduction, easy handling and high sensitivity to various chemicals. However, there is not much information available concerning spatial and temporal stability of experimental set-ups used for Lemna bioassays, though this is essential for interpretation and reliability of results. We therefore investigated stability and natural variability of a Lemna gibba bioassay assessing area-related and frond number-related growth rates under controlled laboratory conditions over about one year. METHODOLOGY/PRINCIPAL FINDINGS: Lemna gibba L. was grown in beakers with Steinberg medium for one week. Area-related and frond number-related growth rates (r(area) and r(num)) were determined with a non-destructive image processing system. To assess inter-experimental stability, 35 independent experiments were performed with 10 beakers each in the course of one year. We observed changes in growth rates by a factor of two over time. These did not correlate well with temperature or relative humidity in the growth chamber. In order to assess intra-experimental stability, we analysed six systematic negative control experiments (nontoxicant tests) with 96 replicate beakers each. Evaluation showed that the chosen experimental set-up was stable and did not produce false positive results. The coefficient of variation was lower for r(area) (2.99%) than for r(num) (4.27%). CONCLUSIONS/SIGNIFICANCE: It is hypothesised that the variations in growth rates over time under controlled conditions are partly due to endogenic periodicities in Lemna gibba. The relevance of these variations for toxicity investigations should be investigated more closely. Area-related growth rate seems to be more precise as non-destructive calculation parameter than number-related growth rate. Furthermore, we propose two new validity criteria for Lemna gibba bioassays: variability of average specific and section-by-section segmented growth rate, complementary to average specific growth rate as the only validity criterion existing in guidelines for duckweed bioassays

Joint algal toxicity of phenylurea herbicides is equally predictable by concentration addition and independent action

Abstract\u2014Photosynthesis-inhibiting phenylurea derivatives, such as diuron, are widely used as herbicides. Diuron concentrations clearly exceeding the predicted-no-effect concentration have been regularly measured in European freshwater systems. The frequently observed exposure to mixtures of phenylureas additionally increases the hazard to aquatic primary producers. Fluctuating numbers and concentrations of individual toxicants make experimental testing of every potential mixture unfeasible. Thus, predictive approaches to the mixture hazard assessment are needed. For this purpose, two concepts are at hand, both of which make use of known toxicities of the individual components but are based on opposite mechanistic suppositions: Concentration addition is based on the idea of similar mechanisms of action, whereas independent action assumes dissimilarly acting mixture components. On the basis of pharmacological reasoning, it was therefore anticipated that the joint algal toxicity of phenylurea mixtures would be predictable by concentration addition. Indeed, we could demonstrate a high predictive power of concentration addition for these combinations. Surprisingly, however, the opposite concept of independent action proved to be equally valid, because both concepts predicted virtually identical mixture toxicities. This exceptional case has previously been derived from theoretical considerations. Now, the tested phenylurea mixtures serve as an example for the practical relevance of this situation for multicomponent mixtures