Structure—activity relationships for chloro‐ and nitrophenol toxicity in the pollen tube growth test

—Acute toxicity of 10 chlorophenols and 10 nitrophenols with identical substitution patterns is analyzed with the pollen tubegrowth (PTG) test. Concentration values of 50% growth inhibition (IC50) between 0.1 and 300 mg/L indicate that the absolutesensitivity of this alternative biotest is comparable to conventional aquatic test systems. Analysis of quantitative structure–activityrelationships using lipophilicity (log Kow), acidity (pKa), and quantum chemical parameters to model intrinsic acidity, solvation interactions,and nucleophilicity reveals substantial differences between the intraseries trends of log IC50. With chlorophenols, a narcotictyperelationship is derived, which, however, shows marked differences in slope and intercept when compared to reference regressionequations for polar narcosis. Regression analysis of nitrophenol toxicity suggests interpretation in terms of two modes of action:oxidative uncoupling activity is associated with a pKa window from 3.8 to 8.5, and more acidic congeners with diortho- substitutionshow a transition from uncoupling to a narcotic mode of action with decreasing pKa and log Kow. Model calculations for phenolnucleophilicity suggest that differences in the phenol readiness for glucuronic acid conjugation as a major phase-II detoxication pathway have no direct influence on acute PTG toxicity of the compounds

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

Strategies in a metallophyte species to cope with manganese excess

The effect of exposure to high Mn concentration was studied in a metallophyte species, Erica andevalensis, using hydroponic cultures with a range of Mn concentrations (0.06, 100, 300, 500, and 700 mg L-1). At harvest, biomass production, element uptake, and biochemical indicators of metal stress (leaf pigments, organic acids, amino acids, phenols, and activities of catalase, peroxidase, superoxide dismutase) were determined in leaves and roots. Increasing Mn concentrations led to a decrease in biomass accumulation, and tip leaves chlorosis was the only toxicity symptom detected. In a similar way, photosynthetic pigments (chlorophylls a and b, and carotenoids) were affected by high Mn levels. Among organic acids, malate and oxalate contents in roots showed a significant increase at the highest Mn concentration, while in leaves, Mn led to an increasing trend in citrate and malate contents. An increase of Mn also induced an increase in superoxide dismutase activity in roots and catalase activity in leaves. As well, significant changes in free amino acids were induced by Mn concentrations higher than 300 mg L-1, especially in roots. No significant changes in phenolic compounds were observed in the leaves, but root phenolics were significantly increased by increasing Mn concentrations in treatments. When Fe supply was increased 10 and 20 times (7–14 mg Fe L-1 as Fe-EDDHA) in the nutrient solutions at the highest Mn concentration (700 mg Mn L-1), it led to significant increases in photosynthetic pigments and biomass accumulation. Manganese was mostly accumulated in the roots, and the species was essentially a Mn excluder. However, considering the high leaf Mn concentration recorded without toxicity symptoms, E. andevalensis might be rated as a Mn-tolerant speciesinfo:eu-repo/semantics/publishedVersio