Molecular docking: A potential tool to aid ecotoxicity testing in environmental risk assessment of pharmaceuticals

A cocktail of human pharmaceuticals pollute aquatic environments and there is considerable scientific uncertainty about the effects that this may have on aquatic organisms. Human drug target proteins can be highly conserved in non target species suggesting that similar modes of action (MoA) may occur. The aim of this work was to explore whether molecular docking offers a potential tool to predict the effects of pharmaceutical compounds on non target organisms. Three highly prescribed drugs, diclofenac, ibuprofen and levonorgestrel which regularly pollute freshwater environments were used as examples. Their primary drug targets are cyclooxygenase 2 (COX2) and progesterone receptor (PR). Molecular docking experiments were performed using these drugs and their primary drug target homologues for Danio rerio, Salmo salar, Oncorhynchus mykiss, Xenopus tropicalis, Xenopus laevis and Daphnia pulex. The results show that fish and frog COX2 enzymes are likely to bind diclofenac and ibuprofen in the same way as humans but that D. pulex would not. Binding will probably lead to inhibition of COX function and reduced prostaglandin production. Levonorgestrel was found to bind in the same binding pocket of the progesterone receptor in frogs and fish as the human form. This suggests implications for the fecundity of fish and frogs which are exposed to levonorgestrel. Chronic ecotoxicological effects of these drugs reported in the literature support these findings. Molecular docking may provide a valuable tool for ecotoxicity tests by guiding selection of test species and incorporating the MoA of drugs for relevant chronic test end points in environmental risk assessments.     

New measurements of cyanobacterial toxins in natural waters using high performance liquid chromatography coupled to tandem mass spectrometry

The presence and levels of the cyanobacterial toxins microcystin-LR, anatoxin-a, and cylindrospermopsin were measured in various Wisconsin waters where algal nuisance or bloom conditions were noted. Out of 74 samples analyzed, 36 had detectable levels of microcystin-LR (49%), and four had detectable levels of anatoxin-a (5%). Cylindrospermopsin, the toxin produced by Cylindrospermopsis (a warm water species that has been moving its range northward, including to Wisconsin), was not detected in the field samples tested. Concentrations of microcystin-LR ranged from 1.2 to 7600 microg L(-1). Anatoxin-a ranged from 0.68 to 1750 microg L(-1), which is the highest concentration reported from around the world. Cyanobacterial toxins, because of their high potency, deserve continued scrutiny by resource managers and public health officials responsible for recreational waters.     

The Predatory Bird Monitoring Scheme: identifying chemical risks to top predators in Britain

The Predatory Bird Monitoring Scheme (PBMS) is a long term (>40 y), UK-wide, exposure monitoring scheme that determines the concentration of selected pesticides and pollutants in the livers and eggs of predatory birds. This paper describes how the PBMS works, and in particular highlights some of the key scientific and policy drivers for monitoring contaminants in predatory birds and describes the specific aims, scope, and methods of the PBMS. We also present previously unpublished data that illustrates how the PBMS has been used to demonstrate the success of mitigation measures in reversing chemical-mediated impacts; identify and evaluate chemical threats to species of high conservation value; and finally to inform and refine monitoring methodologies. In addition, we discuss how such schemes can also address wider conservation needs.     

Manipulation of food and photoperiod promotes out-of-season gametogenesis in the green sea urchin, Strongylocentrotus droebachiensis: implications for aquaculture

Green sea urchins, Strongylocentrotus droebachiensis OF Müller, collected off the coast of New Hampshire, USA, in late February 1995, were brought into the laboratory and fed an artificial diet ad libitum, and subjected to a photoperiod advanced by 4 months. During this study, temperatures and salinities for experimental urchins mirrored those recorded at the collection site. We examined the effects of changes in feeding regime and photoperiod on gametogenesis and compared the experimental urchins with those from the source population. During the 7-month period, experimental urchins showed no detectable changes in mean test height or diameter. Experimental urchins had a significantly higher gonad index (GI) in March, April and May (18 ± 6%) compared with field urchins in March (11 ± 3%). Subsequently, experimental urchins had a mean monthly GI of 25 to 30%, while the mean GI for field urchins was 11 to 13%. Gonial cell mitosis and gametogenesis occurred earlier in experimental male and female urchins compared with field urchins. Stereological and histological observations and stage–frequency data showed that the ovaries of experimental urchins were large because of the accelerated development of nutritive phagocytes, the volume fraction (V _v) of which was 89 to 90% of the gonad, while new vitellogenic primary oocytes occupied <1% V _v. In males, stereological and histological observations and stage–frequency data suggested a mobilization of materials from the nutritive phagocytes beginning between June and August, i.e. earlier than in females, and, by September, new gametes occupied a V _v of 49 ± 3% of the testes. Oocyte size–frequency distributions demonstrated that most primary oocytes were <80 μm in diameter between March and September, suggesting that cold temperatures may be needed for completion of vitellogenesis. We describe changes in the two principal cell types in the germinal epithelium of urchin gonads and indicate how knowledge of their population dynamics may be useful in aquaculture applications. Received: 21 February 1997 / Accepted: 3 June 1998     

Acute aquatic toxicity of western juniper (Juniperus occidentalis) foliage and Port Orford cedar (Chamaecyparis lawsoniana) heartwood oils

Recently, interest has developed for using essential oils from Western juniper (Juniperus occidentalis) foliage and Port Orford cedar (Chamaecyparis lawsoniana) heartwood in commercial products such as pest repellents and cosmetics. In order to gauge the relative toxicological risk that these oils pose to freshwater and marine organisms, the acute aquatic toxicity of these oils was evaluated using OPPTS guidelines to the cladoceran Daphnia magna, the rainbow trout Oncorhynchus mykiss and the green alga Selenastrum capricornutum. For western juniper foliage oil, no toxicity was exhibited toward D. magna or O. mykiss, even at 5.0 mg/L (the highest concentration tested and limit of solubility). For toxicity to S. capricornutum using algal cell density, the 72 and 96 h EC₅₀ value was 1.7 mg/L and the no observable effect concentration (NOEC) was 0.63 mg/L. For Port Orford cedar heartwood oil, no toxicity was exhibited toward O. mykiss or S. capricornutum, even at 5.0 mg/L (the highest concentration tested and limit of solubility). The 48-h D. magna EC₅₀ value was 1.9 mg/L; the NOEC values for algal cell density were 1.25 mg/L (72 h) and 0.63 mg/L (96 h). In summary, this study shows that western juniper foliage and Port Orford cedar heartwood oils demonstrate little to no risk to aquatic organisms.     

Predicting Radon Testing Among University Employees

Abstract

To determine covariates of radon testing behavior, we surveyed by mail a random sample of all Boston University employees (N = 915) six to nine months after they had been informed of the availability of radon testing services through the University's medical center. The response rate was 58%. Analysis suggests blue collar workers were underrepresented within the response rate. Slightly more than half of the respondents (51%) were men. The majority (69%) were under the age of 45. Twenty-seven percent of the respondents (N = 143) had tested their homes for radon. Bivariate analysis revealed important differences between radon testers and nontesters. Testers were 12 times more likely to be home owners than renters (p = 0.00), and were more knowledgeable about radon's characteristics and testing procedures (p = 0.00). Testers were more likely to view radon as a serious problem (p = 0.00), to consider radon testing efficacious (p = 0.00), and to consider themselves susceptible to exposure (p = 0.00). Testers were also less likely to perceive barriers to radon testing. We used logistic regression to compare the usefulness of the Health Belief Model and the Diffusion of Innovations Model in predicting radon testing. We concluded that the knowledge deficits and barriers to radon testing identified in this study should be targeted in radon educational interventions.     

UK interpretation and implementation of the EEC Shellfish directive

The EEC Shellfish Directive is a policy designed to protect and, where necessary, improve the quality of designated shellfish waters. Its implementation within the UK, however, has had no effect upon water quality for two reasons. First, the policy has important defects, having ambiguities concerning public health provisions and lacking designation criteria. Second, UK government has sought to achieve formal compliance, while at the same time ensuring that its full financial impact on public expenditure has been contained. Consequently, only those fisheries which already comply with water quality standards have been designated. Within Wales, one fishery has been designated, while other, commercially more important, but grossly contaminated shellfisheries have not.     

DESIGN BASIS FOR EVERGLADES STORMWATER TREATMENT AREAS1

ABSTRACT: The State of Florida (1994) has adopted a plan for addressing Everglades eutrophication problems by reducing anthropogenic phosphorus loads. The plan involves implementation of Best Management Practices in agricultural watersheds and construction of regional treatment marshes (Stormwater Treatment Areas or STA's). This paper describes the development, testing, and application of a mass-balance model for sizing STA's to achieve treatment objectives. The model is calibrated and tested against peat and water-column data collected in Water Conservation Area-2A (WCA-2A), where phosphorus dynamics and eutrophication impacts have been intensively studied. The 26-year-average rate of phosphorus accretion in peat is shown to be proportional to average water-column phosphorus concentration, with a proportionality constant of 10.2 m/yr (90 percent Confidence Interval = 8.9 to 11.6 m/yr). Spatial and temporal variations in marsh water-column data suggest that drought-induced recycling of phosphorus was important during periods of low stage in WCA-2A. Maintaining wet conditions will be important to promote phosphorus removal in STA's. Sensitivity analysis of STA performance is conducted over the range of uncertainty in model parameter estimates to assess the adequacy of the model as a basis for STA design.