Effects of soil properties on the uptake of pharmaceuticals into earthworms

AbstractPharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered

Development of a conceptual model to account for pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus

Our previous studies as well as analysis of literature data revealed that pharmaceuticals with aliphatic amine function exert an extraordinary high toxicity in algae, which is similar to that exhibited by specifically acting herbicides. However, the clear identification of the underlying mode of action is still pending because the time and endpoint pattern pointed to baseline toxicity despite the high toxic ratio (ratio between predicted baseline toxicity EC50 and experimental EC50), which serves as a measure for specificity of effect. On this basis we hypothesize that the high toxicity of amines in algae is not due to a highly specific mode of toxic action but due to speciation effects of the amine function. The pH-dependent toxicity of 5 basic pharmaceuticals can be explained by an ion-trapping mechanism. We hypothesize that only the neutral species can permeate the membrane. Since algae are capable of biological homeostasis, the fraction of charged species can be different in the cytoplasm and in the external medium depending on the pH in the cytoplasm and the acidity of the base. If the high toxicity of basic pharmaceuticals in algae is a speciation effect, then the internal effect concentrations in the cytoplasm and at the target membranes should be similar with varying external pH values. The developed model shows that the specific toxicity of basic pharmaceuticals with amine function in algae is a toxicokinetic effect, not a toxicodynamic effect related to a specific mode of toxic action. This toxicokinetic effect is presumably more pronounced for algae than for other aquatic organisms (for which these aliphatic amines are generally baseline toxicants) because green algae have a relatively high internal pH

Mixture toxicity of the antiviral drug Tamiflu® (Oseltamivir Ethylester) and its active metabolite oseltamivir acid

Tamiflu® (oseltamivir ethylester) is an antiviral agent for the treatment of influenza A and B. The prodrug Tamiflu® is converted in the human body to the pharmacologically active metabolite, oseltamivir acid, with a yield of 75%. Oseltamivir acid is indirectly photodegradable and slowly biodegradable in sewage works and sediment/water systems. A previous environmental risk assessment has concluded that there is no bioaccumulation potential of either of the compounds. However, little was known about the ecotoxicity of the metabolite. Ester hydrolysis typically reduces the hydrophobicity and thus the toxicity of a compound. In this case, a zwitterionic, but overall neutral species is formed from the charged parent compound. If the speciation and predicted partitioning into biological membranes is considered, the metabolite may have a relevant contribution to the overall toxicity. These theoretical considerations triggered a study to investigate the toxicity of oseltamivir acid (OA), alone and in binary mixtures with its parent compound oseltamivir ethylester (OE). OE and OA were found to be baseline toxicants in the bioluminescence inhibition test with Vibrio fischeri. Their mixture effect lay between predictions for concentration addition and independent action for the mixture ratio excreted in urine and nine additional mixture ratios of OE and OA. In contrast, OE was an order of magnitude more toxic than OA towards algae, with a more pronounced effect when the direct inhibition of photosystem II was used as toxicity endpoint opposed to the 24 h growth rate endpoint. The binary mixtures in this assay yielded experimental mixture effects that agreed with predictions for independent action. This is consistent with the finding that OE exhibits slightly enhanced toxicity, while OA acts as baseline toxicant. Therefore, with respect to mixture classification, the two compounds can be considered as acting according to different modes of toxic action, although there are indications that the difference is a toxicokinetic effect, not a true difference of mechanism of toxicity. The general mixture results illustrate the need to consider the role of metabolites in the risk assessment of pharmaceuticals. However, in the concentration ratio of parent to metabolite excreted by humans, the experimental results confirm that the active metabolite does not significantly contribute to the risk quotient of the mixture. Copyright © 2009 Elsevier B.V. All rights reserved