Pharmaceuticals in the aquatic environment : β-blockers as a case study

The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern and yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. This study used mammalian pharmacodynamics to predict the mode of action of the 13-blocker, propranolol, on fish, in order to identify chronic effects in fathead minnows. β-blockers target β1- and β2-adrenergic receptors in humans and hence these receptors were characterised in the fathead minnow. It was found that fish possess β1- and β2-ARs that are structurally very similar to their mammalian counterparts. Further, the distributions of these two β-ARs in various organs of the fathead minnow were similar to those in mammals. Pair-breeding assays were conducted, in which fathead minnows were exposed to various concentrations of propranolol. To discover whether β-ARs had been up or down regulated by propranolol, molecular analysis was conducted on different tissues of the exposed fish using real-time polymerase-chain reactions (RT-PCR). Exposure of fathead minnows to propranolol caused acute toxicity at 10 mg/L. Propranolol caused a statistically significant decrease in reproduction at 1.0 mg/L, dose-related decreases in male weight, condition index and fatpad weight, and a dose-related increase in female GSI. Molecular analysis of βl- and β2-AR expression levels revealed a dose-related decrease in β2-AR expression in fathead liver and heart. LOEC and NOEC values were 0.1 mg/L and 0.01 mg/L, respectively. Propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0 mg/L were greater than the human therapeutic concentration and hence these data very strongly support the fish plasma model proposed by Huggett et al. (2001).EThOS - Electronic Theses Online ServiceEuropean Union (as part of the ERAPharm consortium)GBUnited Kingdo

The read-across hypothesis and environmental risk assessment of pharmaceuticals

This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 American Chemical Society.Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.BBSRC Industrial Partnership Award BB/ I00646X/1 and BBSRC Industrial CASE Partnership Studentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme

Anomalous mode, elastic constants and phonon images in CaWO4

Stimulated by the “anomalous mode” observed in the time-of-flight measurement of phonon signals [J.K. Wigmore, A.G. Kozorezov, H. bin Rani, M. Giltrow, H. Kraus, B.M. Taele, Physica B 316–317 (2002) 589], we have theoretically studied the group velocities and the phonon images in CaWO4. Comparing the phonon caustics of transverse modes in the low-frequency nondispersive and slightly dispersive 1 THz regions, we propose that the anomalous phonon mode is originated from the phonons near the cuspidal edge of the group velocity curve of the fast transverse branch. Also the low-frequency phonon images (two-dimensional maps of phonon group velocities) calculated from the two sets of published elastic-constant data of CaWO4 [J.M. Farley, G.A. Saunders, J. Phys. C: Solid State Phys. 5 (1972) 3021] and [M. Gluyas, F.D. Hughes, B.M. James, J. Phys. D: Appl. Phys. 6 (1973) 2025] are compared. A significant difference is found in the images in the X–Y plane owing to the variance of the reported values of C13 of about 40%

Targeting the environmental risk assessment of pharmaceuticals Facts and fantasies

In contrast to industrial chemicals, pharmaceuticals and pesticides are designed to show specific pharmacological actions or biocidal activities. Despite this difference, the same principles for environmental risk assessment, e.g.;risk characterization by comparing compartment-specific exposure and effect, are applied to both nonspecifically and specifically acting substances. In addition, many pharmaceuticals are relatively hydrophilic, polar, or charged compounds. However, standardized guidelines for generating fate and effects data have been developed predominantly for neutral substances. For these reasons, the risk characterization of biologically active pharmaceuticals might contain a considerable degree of uncertainty. In this paper, we propose a conceptual approach for a targeted environmental risk assessment to reduce the uncertainties of risk characterization for pharmaceuticals by using the information provided in the nonenvironmental part of the regulatory dossier. Three steps have been defined for this purpose 1) The first is collation of specific information contained in regulatory dossiers for pharmaceuticals, e.g.;data produced to understand the interaction of the active substance with biological structures, 2) Based on this information, conclusions might be drawn with regard to environmental compartments likely to be exposed and organisms likely to be affected, and 3) Selection can be made of single-species or multispecies tests to generate additional information for the ecotoxicological risk characterization of pharmaceuticals. Furthermore, some thoughts will be presented on the integration of targeted testing strategies into conceptual regulatory guidance. Integr Environ Assess Manag 2010;6603 613. © 2009 SETAC

Interference-free optical power delivery for electronics modules.

The elimination of electromagnetic pickup and interference for microcircuits is demonstrated by replacing the wired power connection with a plastic optical fibre and a photo-voltaic converter. The coupling of light from an inexpensive source to the fibre is facilitated easily with a plastic bulb-lens antenna