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

QSAR analysis and specific endpoints for classifying the physiological modes of action of biocides in synchronous green algae

We propose the use of additional physiological endpoints in the 24 h growth inhibition test with synchronous cultures of Scenedesmus vacuolatus for the classification of physiological modes of toxic action of chemicals in green algae. The classification scheme is illustrated on the example of one baseline toxicant (3-nitroaniline) and five biocides (irgarol, diuron, Sea-Nine, tributyltin (TBT) and norflurazon). The well-established endpoint of inhibition of reproduction is used for an analysis of the degree of specificity of toxicity by comparing the experimental data with predictions from a quantitative structure–activity relationship (QSAR) for baseline toxicity (narcosis). For those compounds with a toxic ratio greater than 10, i.e. a 10 times higher effect in reproduction than predicted by baseline toxicity, additionally the physiological endpoints inhibition of photosynthesis, cell division and cell volume growth were experimentally assessed. Depending on the relative sensitivity of the different endpoints the chemicals were classified into five different classes of modes of toxic action using a flow chart that was developed in the present study. The advantage of the novel classification scheme is the simplicity of the experimental approach. For the determination of the inhibition of reproduction, the cell size and numbers are quantified with a particle analyzer. This information can be used to derive also the physiological endpoints of cell volume growth and inhibition of cell division. The only additional measurement is the inhibition of the photosynthesis efficiency, which can be easily performed using the non-invasive saturation pulse method and pulse-modulated chlorophyll fluorometry with the Tox-Y-PAM instrument. This mechanistic approach offers a great future potential in ecotoxicology for the physiological mode of action classification of chemicals in algae, which should be a crucial step considered in the risk assessment of chemicals

QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degraduation on the toxicity and mode of action of diuron in algae and daphnids

Even though the environmental occurrence of pesticide transformation products is well established, ecotoxicological data for transformation products are often lacking. Therefore, it remains an open question for regulators how to handle transformation products in the process of authorization and risk assessment. Transformation products may (1) possess a similar mode of toxic action as the parent compound, (2) exhibit unexpected effects towards non-target organisms or (3) contribute to overall mixture toxicity through baseline toxicity even if the specific activity of the parent compound is lost. In the present study, a systematic and integrated approach is presented to differentiate between these three options with the goal of identifying transformation products that significantly add to the risk posed by the parent compound. Quantitative structure–activity relationships (QSAR) and a toxic ratio (TR) analysis were used to evaluate the toxicity and mode of toxic action of the transformation products relative to the parent compound. In addition, mixture toxicity experiments were used as diagnostic tools to underpin the mode of action analysis and to elucidate whether the transformation products possess a similar risk potential as the parent compound. As an illustrative example, the phenylurea herbicide diuron was chosen since a sound basis of ecotoxicological data was available not only for diuron itself but also for most of its transformation products. Effects were investigated using the most sensitive species, algae, and the non-target organism Daphnia magna, for which a previous QSAR-analysis of literature data suggested a specific hazard. In the present study the primary transformation products 1-(3,4-dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of the methylurea group during degradation, which formed 3,4-dichloroaniline, led to a clear detoxification in algae but to an increase in toxicity in daphnids. It could be shown that 3,4-dichloroaniline acted as baseline toxicant in algae, but showed a specific mode of toxic action in daphnids. Mixture toxicity experiments confirmed this mode of action analysis