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.

Toxic Effect of Antibiotics on Freshwater Algal Systems and the Mechanisms of Toxicity: A Review

Antibiotics are used to treat bacterial infections in humans and animals and also act as a growth promoter for poultry. Due to incomplete metabolism, these antibiotics are excreted in the environment in their parental forms and accumulates in the aquatic ecosystem. Besides the evolution of antibiotic-resistant bacteria, these drugs can damage non-target organisms. Green algae are highly sensitive to different antibiotics. Damage in the algal population will cause imbalances in the ecosystems. Till now, the mechanisms of antibiotic toxicity towards algae have not been completely elucidated. It was observed that antibiotics mainly affected the photosynthetic machinery and decreased the carbon fixation process, finally resulting in algal growth inhibition. This present review deals with antibiotics classification, various routes of antibiotics exposure to the freshwater environment, sensitivity towards the different classes of antibiotics, possible Mode-of-Action (MOA) on algal systems, and gaps that need to be filled. Significant gaps include the unavailability of proper eco-toxicological data for antibiotics. Moreover, they exist in nature as complex mixtures, and their behavior in the ecosystem may vastly differ from the parent molecules. To improve our understanding of antibiotic responses mechanism in real-life scenarios, mixture toxicity studies may be the first step.

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.

A Fast and Automated Strategy for the Identification and Risk Assessment of Unknown Substances (IAS/NIAS) in Plastic Food Contact Materials by GC-Q-Orbitrap HRMS: Recycled LDPE as a Proof-of-Concept

A fast and automated approach has been developed for the tentative identification and risk assessment of unknown substances in plastic food contact materials (FCM) by GC-Q-Orbitrap HRMS. The proposed approach combines GC-HRMS full scan data acquisition coupled to Compound Discoverer™ 3.2 software for automated data processing and compound identification. To perform the tentative identification of the detected features, a restrictive set of identification criteria was used, including matching with the NIST Mass Spectral Library, exact mass of annotated fragments, and retention index calculation. After the tentative identification, a risk assessment of the identified substances was performed by using the threshold of toxicological concern (TTC) approach. This strategy has been applied to recycled low-density polyethylene (LDPE), which could be used as FCM, as a proof-of-concept demonstration. In the analyzed sample, 374 features were detected, of which 83 were tentatively identified after examination of the identification criteria. Most of these were additives, such as plasticizers, used in a wide variety of plastic applications, oligomers of LDPE, and substances with chemical, industrial, or cosmetic applications. The risk assessment was performed and, according to the TTC approach, the obtained results showed that there was no risk associated with the release of the identified substances. However, complementary studies related to the toxicity of the unidentified substances and the potential mixture toxicity (cocktail effects) should be conducted in parallel using bioassays.