Mixture toxicity of six pharmaceuticals towards Aliivibrio fischeri, Daphnia magna, and Lemna minor

As the knowledge on the joint effects of pharmaceuticals towards different non-target organisms is still limited, the aim of our study was to evaluate the toxicity of mixtures of pharmaceuticals, as well as their baseline toxicity towards three selected organisms, namely the bioluminescent bacteria Aliivibrio fischeri, the crustacean Daphnia magna, and the duckweed Lemna minor. Different mixtures composed of three up to five pharmaceuticals having the same or different mechanisms of action in terms of their therapeutic activity (non-steroidal anti-inflammatory drugs, opioid analgesic, antibacterial and anti-epileptic drugs) were investigated. The observed EC50s were compared with those predicted using the concentration addition (CA) and independent action (IA) models. In general, the EC50 values for mixtures predicted with the CA model were lower than those obtained with the IA model, although, in some cases, test predictions of these two models were almost identical. Most of the experimentally determined EC50 values for the specific mixtures were slightly higher than those predicted with the CA model; hence, a less than additive effect was noted. Based on the obtained results, it might be concluded that the CA model assumes the worst-case scenario and gives overall closer predictions; therefore, it should be recommended also for modeling the mixture toxicity of pharmaceuticals with different modes of action.

The Acute Single and Mixture Toxicity of Paraquat Dichloride and Deltamethrin to Guppy (Poecilia reticulata)

Although herbicide and insecticide contamination of surface waters normally occurs in the form of mixtures, the toxicity interactions displayed by such mixtures have only rarely been characterized. This study evaluated the acute effects of single pesticides (paraquat dichloride and deltamethrin, tested in their commercial formulations Gramoxone 276 SL and Decis 25EC) and their equitoxic mixtures on the survival of adult male guppy fish (Poecilia reticulata). Mixture toxicity was evaluated against the reference models of Concentration Addition (CA) and Independent Action (IA). In the single treatments, the 72h LC10 and LC50 values were 1.5 and 6.0 mg a.s. L-1 and 0.53 and 3.6 µg a.s. L-1 for paraquat dichloride and deltamethrin, respectively. The equitoxic mixtures showed significant paraquat dichloride-deltamethrin antagonism, both based on the CA and the IA model, without significant dose-level dependent deviations.

Inhibitory Effects of Ternary Mixtures of Sodium Dodecyl Sulfate and Heavy Metals to Acinetobacter seifertii from Otamiri River Sediment in Southeastern Nigeria

Toxicities of sodium dodecyl sulfate (SDS) and heavy metals, Pb(II), Cd(II), Ni(II), Zn(II) and Co(II), as individuals and ternary mixtures of two heavy metals and SDS to Acinetobacter seifertii isolated as preponderant bacterium from Otamiri river sediment, were assessed, using inhibition of dehydrogenase activity as end point. Among the individual toxicants, the EC50S observed ranged from 0.011 ± 0.000 mM for Cd(II) to 2.810 ± 0.140 mM for SDS. The EC50S of the toxicants were statistically different from one another and the order of increasing toxicities were SDS > Ni(II) > Pb(II) > Zn(II) > Co(II) >Cd(II). The responses of the bacterium were concentration -dependent. Arbitrary (ABCR) and EC50 equieffect (EECR) fixed ratio mixtures were used to evaluate the combined toxicities of the toxicants. The concentration-response relationships of all mixtures and individual toxicants were sigmoidal and fitted with logistic function. The observed toxicities (EC50S) were compared with toxicities predicted from concentration addition (CA) and independent action (IA) models. In ABCR1 and ABCR3 mixture ratios of SDS+Ni(II)+Cd(II) and SDS+Co(II)+Cd(II) ternary mixtures, both CA- and IA-predicted EC50S were not statistically different from each other. Furthermore, in all ternary mixtures, both models underestimated the mixture toxicities to A. seifertii, except in ABCR1 of SDS+Ni(II)+Cd(II) mixture, where both models almost correctly predicted the toxicities. Basically, synergistic interaction of the mixture components observed against A. seifertii, indicates their possible toxicological effects on the bacterial population of the aquatic ecosystems.

Increasing the quality of anchovy (Stelophorus sp.) with additional concentration of chitosan

Anchovy is a main capture fishery commodity in North Maluku. Currently, the processing activity of anchovy is relatively simple and traditional, consequently, causing anchovy quality to be easily degraded. One solution to overcome the problem is through the addition of chitosan concentration. This study aimed to determine effect of concentration addition of chitosan on quality of water content, protein, fat, carbohydrates, organoleptic and Total Plate Count (TPC) test. Method used in this research was the analysis of water quality test, protein content, fat content, carbohydrate content, calorie content, organoleptic test and TPC test. The study results showed that the highest water content value was 13.65% at 0.1% concentration, the highest protein value was 61.16% at 0.5% concentration, the highest ash content value was 16.5% at 1% concentration, the highest fat value was 3.99% at 1% concentration, and the highest fat value was 3.99% at 1% concentration. The highest carbohydrate content found was 11.94% at 0.1% concentration, and the highest calorific value was 2.51% at 1% concentration. Meanwhile, average organoleptic value of the highest appearance was 6.87% at a 0.3% concentration, the highest odor was 7.55% at a 0.3% concentration, the highest texture was 7.45% at a 0.1% concentration and color was 6.25% at a 0.3% concentration. Results of the TPC tests showed that anchovy with chitosan treatment and without chitosan during storage changed for all treatments. The average TPC value at all concentrations (0.1%, 0.3% and 0.5%) had the lowest TPC value compared to the control.

Environmental concerns about the effects of effluents from wastewater treatment plants in tourist areas of the Alps: toxicity in aquatic microorganisms

Are the effluents of wastewater treatment plants in high mountains of concern for aquatic biodiversity? To answer this question, we carried out an experimental study testing the short-term toxicity of some Pharmaceutical Active Compounds (PhACs) in the effluents of a plant in a mountain valley of the Italian Alps sampled during the high tourist season (i.e., the ski season) when PhACs contamination is higher. We used different tools, taking as a model the bacterium Aliivibrio fischeri: the “whole-mixture approach” (Microtox test), “component-based approach”, predictive models “Concentration Addition (CA)”, “Independent Action (IA)”, and Combination Index (CI)”. We investigated the nature of interactions potentially occurring among seven selected PhACs (clarithromycin, naproxen, acetaminophen (paracetamol), ibuprofen, diclofenac, carbamazepine, and amoxicillin). This study showed that anti-inflammatory ibuprofen and diclofenac have higher short-term toxicity (IC50 <100 mg L-1) for A. fischeri compared with antibiotics, whose toxic effects are expected to become visible in the long term. Furthermore, based on the CI method, the seven PhACs seem not to interact in a synergistic or antagonistic way, but the final effect of their mixture seems to be equal to the sum of their individual effects. Notwithstanding the high tourist pressure, the Microtox test reported an overall toxicity of only 21%, which drops to 7% in the receiving water body, the Vermigliana stream. These values, besides the predictions by CA and IA, are not alarming per se, i.e., the treated effluent of the plant in the period of maximum tourist pressure can be considered no harmful to aquatic microorganisms. However, based on other studies highlighting negative effects of the diluted treated effluent of the same plant on macroinvertebrate community structure, we suggest that other model organisms be considered, including algae, insects, and fish, to assess the real ecological risk to wildlife of an effluent. The experimental tests on A. fischeri are useful for fast, preliminary information on the level of risk for freshwater ecosystems, but they should be combined with field studies and experiments on the wild populations to increase the ecological realism.

Prediction of herb-drug interactions involving consumption of furanocoumarin-mixtures and cytochrome P450 1A2-mediated caffeine metabolism inhibition in humans

Herb-drug interaction (HDI) has become important due to the increasing popularity of natural product consumption worldwide. HDI is difficult to predict as botanical drugs usually contain complex phytochemical-mixtures which interact with drug metabolism. Currently, there is no pharmacological tool to predict HDI since almost all in vitro-in vivo-extrapolation (IVIVE) Drug-Drug Interaction (DDI) models deal with one inhibitor-drug and one victim-drug. The objectives were to modify IVIVE models of Mayhew et al. (2000) and Wang et al. (2004) for prediction of in vivo interaction between caffeine and furanocoumarin-containing herbs, and to confirm model prediction by comparing the predictive results with experimental data. The models were modified to predict in vivo herb-caffeine interaction using the same set of inhibition constants but different integrated dose/concentration of furanocoumarin mixtures in the liver. Different hepatic inlet inhibitor concentration ([I]H) surrogates were used for each furanocoumarin. In the Mayhew et al., the [I]H was predicted using the concentration-addition model for chemical-mixtures. In the Wang et al., the [I]H was calculated by adding individual furanocoumarins together. Once [I]H was determined, the models predicted an area-under-curve-ratio (AUCR) of each interaction. The results indicate that both models were able to predict the experimental AUCR of herbal products reasonably well.