Acute animal and human poisonings from cyanotoxin exposure — A review of the literature

Cyanobacterial blooms are a potential health hazard due to the ability of some species to produce toxins that are harmful to other living organisms. This review provides a comprehensive summary of anecdotal and case reports on acute poisonings in animals and humans attributable to cyanotoxin exposure in fresh- and brackish-waters. Approximately two-thirds of reported poisonings have occurred in Europe and the United States. Dogs and livestock account for the majority of reported cases involving animal exposure to cyanotoxins, while recreational activities are responsible for approximately half of reported incidents involving human exposure. Due to data limitations it is difficult to estimate the total number of animals and humans affected by cyanotoxins, however, some general observations regarding frequency and numbers affected are made. The review demonstrates that cyanotoxins have, and will likely to continue to have, potentially serious consequences for public health and animal welfare worldwide.     

Balancing the health benefits and environmental risks of pharmaceuticals: Diclofenac as an example

Pharmaceuticals are designed to improve human and animal health, but even the most beneficial pharmaceuticals might raise some questions concerning the consequences of exposure to non-target organisms. To illustrate this situation and using diclofenac as a case-study, we analyze global consumption and occurrence data to identify hot spots of consumption without occurrence data, review the scientific literature on the harmful environmental effects to determine whether the observed concentrations in freshwater are of environmental concern, summarize the current pharmaceutical and environmental policies to highlight policy gaps, and suggest a series of research and policy recommendations, which can be summarized as follows: we need to improve the current knowledge on occurrence in freshwaters to properly implement environmental policies (i), diclofenac might pose a risk to non-target organisms in freshwater (ii); the harmful effects that some pharmaceuticals may have on the environment are not always addressed by environmental policies (iii).     

State of knowledge and concerns on cyanobacterial blooms and cyanotoxins

Cyanobacteria are ubiquitous microorganisms considered as important contributors to the formation of Earth's atmosphere and nitrogen fixation. However, they are also frequently associated with toxic blooms. Indeed, the wide range of hepatotoxins, neurotoxins and dermatotoxins synthesized by these bacteria is a growing environmental and public health concern. This paper provides a state of the art on the occurrence and management of harmful cyanobacterial blooms in surface and drinking water, including economic impacts and research needs. Cyanobacterial blooms usually occur according to a combination of environmental factors e.g., nutrient concentration, water temperature, light intensity, salinity, water movement, stagnation and residence time, as well as several other variables. These environmental variables, in turn, have promoted the evolution and biosynthesis of strain-specific, gene-controlled metabolites (cyanotoxins) that are often harmful to aquatic and terrestrial life, including humans. Cyanotoxins are primarily produced intracellularly during the exponential growth phase. Release of toxins into water can occur during cell death or senescence but can also be due to evolutionary-derived or environmentally-mediated circumstances such as allelopathy or relatively sudden nutrient limitation. Consequently, when cyanobacterial blooms occur in drinking water resources, treatment has to remove both cyanobacteria (avoiding cell lysis and subsequent toxin release) and aqueous cyanotoxins previously released. Cells are usually removed with limited lysis by physical processes such as clarification or membrane filtration. However, aqueous toxins are usually removed by both physical retention, through adsorption on activated carbon or reverse osmosis, and chemical oxidation, through ozonation or chlorination. While the efficient oxidation of the more common cyanotoxins (microcystin, cylindrospermopsin, anatoxin and saxitoxin) has been extensively reported, the chemical and toxicological characterization of their by-products requires further investigation. In addition, future research should also investigate the removal of poorly considered cyanotoxins (β-methylamino-alanine, lyngbyatoxin or aplysiatoxin) as well as the economic impact of blooms.     

Occurrence,fate and ecological risk of five typical azole fungicides as therapeutic and personal care products in the environment: A review

Azole fungicides are widely used to treat fungal infection in human. After application, these chemicals may reach to the receiving environment via direct or indirect discharge of wastewaters, thus posing potential risks to non-target organisms. We aimed to review the occurrence, fate and toxicological effects of some representative household azole fungicides in the environment. Azole fungicides were widely detected in surface water and sediment of the aquatic environment due to their incomplete removal in wastewater treatment plants. These chemicals are found resistant to microbial degradation, but can undergo photolysis under UV irradiation. Due to different physiochemical properties, azole fungicides showed different environmental behaviors. The residues of azole fungicides could cause toxic effects on aquatic organisms such as algae and fish. The reported effects include regulation changes in expression of cytochrome P450-related genes and alteration in CYP450-regulated steroidogenesis causing endocrine disruption in fish. Further studies are essential to investigate the removal of azole fungicides by advanced treatment technologies, environmental fate such as natural photolysis, and toxic pathways in aquatic organisms.     

Occurrence,fate and effects of azoxystrobin in aquatic ecosystems: A review

The use of pesticides for crop protection may result in the presence of toxic residues in environmental matrices. In the aquatic environment, pesticides might freely dissolve in the water or bind to suspended matter and to the sediments, and might be transferred to the organisms' tissues during bioaccumulation processes, resulting in adverse consequences to non-target species. One such group of synthetic organic pesticides widely used worldwide to combat pathogenic fungi affecting plants is the strobilurin chemical group. Whereas they are designed to control fungal pathogens, their general modes of action are not specific to fungi. Consequently, they can be potentially toxic to a wide range of non-target organisms. The present work had the intent to conduct an extensive literature review to find relevant research on the occurrence, fate and effects of azoxystrobin, the first patent of the strobilurin compounds, in aquatic ecosystems in order to identify strengths and gaps in the scientific database. Analytical procedures and existing legislation and regulations were also assessed. Data gathered in the present review revealed that analytical reference standards for the most relevant environmental metabolites of azoxystrobin are needed. Validated confirmatory methods for complex matrices, like sediment and aquatic organisms' tissues, are very limited. Important knowledge of base-line values of azoxystrobin and its metabolites in natural tropical and estuarine/marine ecosystems is lacking. Moreover, some environmental concentrations of azoxystrobin found in the present review are above the Regulatory Acceptable Concentration (RAC) in what concerns risk to aquatic invertebrates and the No Observed Ecologically Adverse Effect Concentration (NOEAEC) reported for freshwater communities. The present review also showed that there are very few data on azoxystrobin toxicity to different aquatic organisms, especially in what concerns estuarine/marine organisms. Besides, toxicity studies mostly address azoxystrobin and usually neglect the more relevant environmental metabolites. Further work is also required in what concerns effects of exposure to multi-stressors, e.g. pesticide mixtures. Even though Log K_ow for azoxystrobin and R234886, the main metabolite of azoxystrobin in water, are below 3, the bio-concentration factor and the bioaccumulation potential for azoxystrobin are absent in the literature. Moreover, no single study on bioaccumulation and biomagnification processes was found in the present review.     

Uncertainties in human health risk assessment of environmental contaminants: A review and perspective

Addressing uncertainties in human health risk assessment is a critical issue when evaluating the effects of contaminants on public health. A range of uncertainties exist through the source-to-outcome continuum, including exposure assessment, hazard and risk characterisation. While various strategies have been applied to characterising uncertainty, classical approaches largely rely on how to maximise the available resources. Expert judgement, defaults and tools for characterising quantitative uncertainty attempt to fill the gap between data and regulation requirements. The experiences of researching 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) illustrated uncertainty sources and how to maximise available information to determine uncertainties, and thereby provide an ‘adequate’ protection to contaminant exposure. As regulatory requirements and recurring issues increase, the assessment of complex scenarios involving a large number of chemicals requires more sophisticated tools. Recent advances in exposure and toxicology science provide a large data set for environmental contaminants and public health. In particular, biomonitoring information, in vitro data streams and computational toxicology are the crucial factors in the NexGen risk assessment, as well as uncertainties minimisation. Although in this review we cannot yet predict how the exposure science and modern toxicology will develop in the long-term, current techniques from emerging science can be integrated to improve decision-making.     

Pectenotoxins--an issue for public health: a review of their comparative toxicology and metabolism.

Pectenotoxins (PTXs) are a group of toxins associated with diarrhetic shellfish poisoning (DSP) and isolated from DSP toxin-producing dinoflagellate algae. Consumption of shellfish contaminated with PTXs has been associated with incidences of severe diarrhetic illness resulting in hospitalisation. Concern has been raised for public health following the discovery that these toxins are not only hepatotoxic and can cause diarrhetic effects in mammals, but that they are potently cytotoxic to human cancer cell lines and have been found to be tumour promoters in animals. With advances in knowledge and technology, more PTXs are being identified, but little is known of their toxicology and the potential impact these toxins may have on public health in the long term. Without such information, adequate health-risk assessments for the consumption of shellfish contaminated with PTXs cannot be performed. This review gives a brief introduction to diarrhetic shellfish toxins, details the known toxicology and metabolism of PTXs in animals, and discusses known incidences of PTX poisoning in humans.     

Guidance on assessing the methodological and reporting quality of toxicologically relevant studies: A scoping review

Assessments of methodological and reporting quality are critical to adequately judging the credibility of a study's conclusions and to gauging its potential reproducibility. To aid those seeking to assess the methodological or reporting quality of studies relevant to toxicology, we conducted a scoping review of the available guidance with respect to four types of studies: in vivo and in vitro, (quantitative) structure-activity relationships ([Q]SARs), physico-chemical, and human observational studies. Our aims were to identify the available guidance in this diverse literature, briefly summarize each document, and distill the common elements of these documents for each study type. In general, we found considerable guidance for in vivo and human studies, but only one paper addressed in vitro studies exclusively. The guidance for (Q)SAR studies and physico-chemical studies was scant but authoritative. There was substantial overlap across guidance documents in the proposed criteria for both methodological and reporting quality. Some guidance documents address toxicology research directly, whereas others address preclinical research generally or clinical research and therefore may not be fully applicable to the toxicology context without some translation. Another challenge is the degree to which assessments of methodological quality in toxicology should focus on risk of bias – as in clinical medicine and healthcare – or be broadened to include other quality measures, such as confirming the identity of test substances prior to exposure. Our review is intended primarily for those in toxicology and risk assessment seeking an entry point into the extensive and diverse literature on methodological and reporting quality applicable to their work.     

Diclofenac and its transformation products: Environmental occurrence and toxicity - A review

Diclofenac (DCF) is a prevalent anti-inflammatory drug used throughout the world. Intensive researches carried out in the past few decades have confirmed the global ubiquity of DCF in various environmental compartments. Its frequent occurrence in freshwater environments and its potential toxicity towards several organisms such as fish and mussels makes DCF an emerging environmental contaminant. At typical detected environmental concentrations, the drug does not exhibit toxic effects towards living organisms, albeit chronic exposure may lead to severe effects. For DCF, about 30–70% removal has been obtained through the conventional treatment system in wastewater treatment plant being the major primary sink. Thus, the untreated DCF will pass to surface water. DCF can interact with other inorganic contaminants in the environment particularly in wastewater treatment plant, such as metals, organic contaminants and even with DCF metabolites. This process may lead to the creation of another possible emerging contaminant. In the present context, environmental fate of DCF in different compartments such as soil and water has been addressed with an overview of current treatment methods. In addition, the toxicity concerns regarding DCF in aquatic as well as terrestrial environment along with an introduction to the metabolites of DCF through consumption as well as abiotic degradation routes are also discussed. Further studies are required to better assess the fate and toxicological effects of DCF and its metabolites and must consider the possible interaction of DCF with other contaminants to develop an effective treatment method for DCF and its traces.     

Factors affecting metal toxicity to (and accumulation by) aquatic organisms — Overview

This literature review encompasses aquatic environmental toxicities of metals and metalloids. The emphasis is on the influencing factors on metal toxicity to aquatic organisms. The effects of environmental factors on metal uptake are also discussed. The factors can be divided into biotic and abiotic. The biotic factors include tolerance, size and life stages, species, and nutrition related to the test organisms. The abiotic factors include organic substances, pH, temperature, alkalinity and hardness, inorganic ligands, interactions, sediments, and others. These factors can alter metal toxicity in the aquatic environment substantially, mostly causing attenuating effect. The literature shows divergent results. For example, the interactions between Cd and Zn were reported to be synergistic by some researchers and antagonistic by others. It is recommended that environmental hazard assessment takes into consideration the results of standard toxicity tests and site-specific conditions which can moderate metal toxicity considerably.     

Assessing the human health impacts of exposure to disinfection by-products — A critical review of concepts and methods

Understanding the public health implications of chemical contamination of drinking water is important for societies and their decision-makers. The possible population health impacts associated with exposure to disinfection by-products (DBPs) are of particular interest due to their potential carcinogenicity and their widespread occurrence as a result of treatments employed to control waterborne infectious disease.We searched the literature for studies that have attempted quantitatively to assess population health impacts and health risks associated with exposure to DBPs in drinking water. We summarised and evaluated these assessments in terms of their objectives, methods, treatment of uncertainties, and interpretation and communication of results.In total we identified 40 studies matching our search criteria. The vast majority of studies presented estimates of generic cancer and non-cancer risks based on toxicological data and methods that were designed with regulatory, health-protective purposes in mind, and therefore presented imprecise and biased estimates of health impacts. Many studies insufficiently addressed the numerous challenges to DBP risk assessment, failing to evaluate the evidence for a causal relationship, not appropriately addressing the complex nature of DBP occurrence as a mixture of chemicals, not adequately characterising exposure in space and time, not defining specific health outcomes, not accounting for characteristics of target populations, and not balancing potential risks of DBPs against the health benefits related with drinking water disinfection. Uncertainties were often poorly explained or insufficiently accounted for, and important limitations of data and methods frequently not discussed. Grave conceptual and methodological limitations in study design, as well as erroneous use of available dose–response data, seriously impede the extent to which many of these assessments contribute to understanding the public health implications of exposure to DBPs. In some cases, assessment results may cause unwarranted alarm among the public and potentially lead to poor decisions being made in sourcing, treatment, and provision of drinking water. We recommend that the assessment of public health impacts of DBPs should be viewed as a means of answering real world policy questions relating to drinking water quality, including microbial contaminants; that they should be conducted using the most appropriate and up-to-date data and methods, and that associated uncertainties and limitations should be accounted for using quantitative methods where appropriate.     

Sources and environmental behaviors of Dechlorane Plus and related compounds — A review

Although Dechlorane Plus (DP) has been used as a polychlorinated flame retardant for almost half a century, its detection in the environment was not reported until 2006. The subsequent intensive research has confirmed its global ubiquity. A few reviews have presented the properties, analytical methods and environmental occurrence of DP and related compounds in the past several years. The present review emphasizes on the environmental behavior of DP isomers which is assessed by the variation of the isomer ratio of DP in various matrices. Other aspects including the analytical methods, emission sources, general environmental occurrence and bioaccumulation of DP are also summarized.In this review, three typical emission sources in the environment are categorized after introducing the measurement method of DP. The temporal-spatial distribution is then evaluated at the global scale, which provides an integrated representation of the environmental occurrence of DP and potential impact on the human health and ecosystems. The variations of DP isomer ratio in various matrices reinforce its source related distribution and their stereoselective bioaccumulation. Thereafter, DP related compounds and dechlorinated analogs are briefly summarized in regards to their occurrence in various matrices, suggesting their ubiquity in the environment and bioavailability. Further studies are required to better assess the exposures and toxicological effects of DP and its analogs. A special concern is the serious contamination in e-waste recycling areas in developing countries, where long-term monitoring data on the association of DP exposure and adverse effects to human health and ecosystems is urgently needed.     

Pharmaceuticals and personal care products (PPCPs): A review on environmental contamination in China

Pharmaceuticals and personal care products (PPCPs) which contain diverse organic groups, such as antibiotics, hormones, antimicrobial agents, synthetic musks, etc., have raised significant concerns in recently years for their persistent input and potential threat to ecological environment and human health. China is a large country with high production and consumption of PPCPs for its economic development and population growth in recent years. This may result in PPCP contamination in different environmental media of China. This review summarizes the current contamination status of different environment media, including sewage, surface water, sludge, sediments, soil, and wild animals, in China by PPCPs. The human body burden and adverse effects derived from PPCPs are also evaluated. Based on this review, it has been concluded that more contamination information of aquatic environment and wildlife as well as human body burden of PPCPs in different areas of China is urgent. Studies about their environmental behavior and control technologies need to be conducted, and acute and chronic toxicities of different PPCP groups should be investigated for assessing their potential ecological and health risks.     

Study sensitivity: Evaluating the ability to detect effects in systematic reviews of chemical exposures

A critical step in systematic reviews of potential health hazards is the structured evaluation of the strengths and weaknesses of the included studies; risk of bias is a term often used to represent this process, specifically with respect to the evaluation of systematic errors that can lead to inaccurate (biased) results (i.e. focusing on internal validity). Systematic review methods developed in the clinical medicine arena have been adapted for use in evaluating environmental health hazards; this expansion raises questions about the scope of risk of bias tools and the extent to which they capture the elements that can affect the interpretation of results from environmental and occupational epidemiology studies and in vivo animal toxicology studies, (the studies typically available for assessment of risk of chemicals). One such element, described here as “sensitivity”, is a measure of the ability of a study to detect a true effect or hazard. This concept is similar to the concept of the sensitivity of an assay; an insensitive study may fail to show a difference that truly exists, leading to a false conclusion of no effect. Factors relating to study sensitivity should be evaluated in a systematic manner with the same rigor as the evaluation of other elements within a risk of bias framework. We discuss the importance of this component for the interpretation of individual studies, examine approaches proposed or in use to address it, and describe how it relates to other evaluation components. The evaluation domains contained within a risk of bias tool can include, or can be modified to include, some features relating to study sensitivity; the explicit inclusion of these sensitivity criteria with the same rigor and at the same stage of study evaluation as other bias-related criteria can improve the evaluation process. In some cases, these and other features may be better addressed through a separate sensitivity domain. The combined evaluation of risk of bias and sensitivity can be used to identify the most informative studies, to evaluate the confidence of the findings from individual studies and to identify those study elements that may help to explain heterogeneity across the body of literature.     

Transfer of radionuclides in aquatic ecosystems--default concentration ratios for aquatic biota in the Erica Tool

The process of assessing risk to the environment following a given release of radioactivity requires the quantification of activity concentrations in environmental media and reference organisms. The methodology adopted by the ERICA Integrated Approach involves the application of concentration ratios (CR values) and distribution coefficients (K(d) values) for aquatic systems. Within this paper the methodologies applied to derive default transfer parameters, collated within the ERICA Tool databases, are described to provide transparency and traceability in the documentation process. Detailed information is provided for the CR values used for marine and freshwater systems. Of the total 372 CR values derived for the marine ecosystem, 195 were identified by literature review. For the freshwater system, the number of values based on review was less, but still constituted 129 from a total of 372 values. In both types of aquatic systems, 70-80% of the data gaps have been filled by employing "preferable" approaches such as those based on substituting values from taxonomically similar organisms or biogeochemically similar elements.     

Antibiotics in the aquatic environments: A review of the European scenario

The discovery of antibiotics is considered one of the most significant scientific achievements of the 20th century, revolutionizing both human and veterinary medicine. However, antibiotics have been recently recognized as an emerging class of environmental contaminants since they have been massively administrated in humans and animals and persist in the environment through a complex vicious cycle of transformation and bioaccumulation. The diffusion of antibiotics in the environment, particularly in natural water systems, contributes to the development and global dissemination of antibiotic resistance. This phenomenon is one of the most important challenges to the health care sector in the 21st century. As a result, studies on the occurrence, fate, and effects of antibiotics in European aqueous environments have increased in the last years. Nevertheless, their potential aquatic ecotoxicity and human toxicity via environmental exposure routes remain unknown. Consequently, antibiotics are not regulated through the current European environmental water quality standards, which requires evidence concerning their widespread environmental contamination and intrinsic hazard. In this context, this literature review summarizes the state of knowledge on the occurrence of antibiotics in the different aqueous environmental systems across the Europe, as reported since 2000. Relating this subject to antibiotic consumption and their dynamic behavior in the environment, the acquired insights provide an improved understanding on aquatic pollution by antibiotics to outline the European scenario. Moreover, it addresses challenges, prospects for future research, and typical topics to stimulate discussion.     

Immunotoxicity of carbon black nanoparticles to blue mussel hemocytes

The potential for human and ecological toxicity associated with nanomaterials is a growing area of investigation. In mammalian cells, nanoparticles have been shown to induce inflammation and oxidative stress, and changes in cell signalling and gene expression. As the nanotechnology industries increase production, nanoscale products and by products will enter the aquatic environment, posing a possible threat to aquatic organisms. In particular, filter-feeding organisms may represent a unique target group for nanoparticle toxicology. In this work, the effects of commercial nanosized carbon black (NCB) on the immune cells, the hemocytes, of the bivalve mollusc Mytilus, and the possible mechanisms involved were investigated. The results demonstrate that NCB (1, 5, and 10 microg/ml), did not induce significant lysosomal membrane destabilization, as evaluated by the NR retention time assay. A concentration-dependent uptake of NCB by hemocytes was observed and it was associated by a rapid increase in extracellular lysozyme release, extracellular oxyradical production, and nitric oxide (NO) release. Moreover, at the highest concentration tested, NCB induced significant changes in mitochondrial parameters (decrease mitochondrial mass/number and membrane potential), as evaluated by flow cytometry. The effects of NCB were mediated by rapid activation of the stress-activated MAPKs (Mitogen Activated Protein Kinases) p38 and JNKs, that play a key role in immune and inflammatory responses. The results demonstrate that in mussel hemocytes like in mammalian cells NCB exposure can induce inflammatory processes, and indicate that bivalve immunocytes can represent a suitable model for investigating the effects and modes of action of nanoparticles in the cells of aquatic invertebrates.     

Novel brominated flame retardants: a review of their analysis, environmental fate and behaviour

This review summarises current knowledge about production volumes, physico-chemical properties, analysis, environmental occurrence, fate and behaviour and human exposure to the "novel" brominated flame retardants (NBFRs). We define the term NBFRs as relating to BFRs which are new to the market or newly/recently observed in the environment. Restrictions and bans on the use of some polybrominated diphenyl ether (PBDE) formulations, in many jurisdictions, have created a market for the use of NBFRs. To date, most data on NBFRs have arisen as additional information generated by research designed principally to study more "traditional" BFRs, such as PBDEs. This has led to a wide variety of analytical approaches for sample extraction, extract purification and instrumental analysis of NBFRs. An overview of environmental occurrence in abiotic matrices, aquatic biota, terrestrial biota and birds is presented. Evidence concerning the metabolism and absorption of different NBFRs is reviewed. Human exposure to NBFRs via different exposure pathways is discussed, and research gaps related to analysis, environmental sources, fate, and behaviour and human exposure are identified.