Per- and polyfluoroalkyl substances (PFAS) are a group of over 4700 heterogeneous compounds with amphipathic properties and exceptional stability to chemical and thermal degradation. The unique properties of PFAS compounds has been exploited for almost 60 years and has largely contributed to their wide applicability over a vast range of industrial, professional and non-professional uses. However, increasing evidence indicate that these compounds represent also a serious concern for both wildlife and human health as a result of their ubiquitous distribution, their extreme persistence and their bioaccumulative potential. In light of the adverse effects that have been already documented in biota and human populations or that might occur in absence of prompt interventions, the competent authorities in matter of health and environment protection, the industries as well as scientists are cooperating to identify the most appropriate regulatory measures, substitution plans and remediation technologies to mitigate PFAS impacts. In this review, starting from PFAS chemistry, uses and environmental fate, we summarize the current knowledge on PFAS occurrence in different environmental media and their effects on living organisms, with a particular emphasis on humans. Also, we describe present and provisional legislative measures in the European Union framework strategy to regulate PFAS manufacture, import and use as well as some of the most promising treatment technologies designed to remediate PFAS contamination in different environmental compartments.

Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As²⁺ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As²⁺-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.

Humans are exposed to a significant number of chemicals that are suspected to produce disturbances in hormone homeostasis. Hence, in recent decades, there has been a growing interest in endocrine disruptive chemicals. One of the alleged thyroid disrupting substances is cadmium (Cd), a ubiquitous toxic metal shown to act as a thyroid disruptor and carcinogen in both animals and humans. Multiple PubMed searches with core keywords were performed to identify and evaluate appropriate studies which revealed literature suggesting evidence for the link between exposure to Cd and histological and metabolic changes in the thyroid gland. Furthermore, Cd influence on thyroid homeostasis at the peripheral level has also been hypothesized. Both in vivo and in vitro studies revealed that a Cd exposure at environmentally relevant concentrations results in biphasic Cd dose-thyroid response relationships. Development of thyroid tumors following exposure to Cd has been studied mainly using in vitro methodologies. In the thyroid, Cd has been shown to activate or stimulate the activity of various factors, leading to increased cell proliferation and a reduction in normal apoptotic activity. Evidence establishing the association between Cd and thyroid disruption remains ambiguous, with further studies needed to elucidate the issue and improve our understanding of Cd-mediated effects on the thyroid gland.