Perfluorinated compounds: occurrence and risk profile

Perfluorinated compounds (PFCs) such as perfluoro-octane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) are emerging environmental pollutants, arising mainly from their use as surface treatment chemicals, polymerization aids and surfactants. They are ubiquitous, persistent and bioaccumulative in the environment. Perfluorinated compounds are being proposed as a new class of POPs. Although tests in rodents have demonstrated numerous negative effects of PFCs, it is unclear if exposure to perfluorinated compounds may affect human health. This review provides an overview of the recent toxicology and toxicokinetics, monitoring data now available for the environment, wildlife, and humans and attempts to explain the mechanisms of action of PFCs.     

A veterinary perspective on One Health in the Arctic

Exposure to long-range transported industrial chemicals, climate change and diseases is posing a risk to the overall health and populations of Arctic wildlife. Since local communities are relying on the same marine food web as marine mammals in the Arctic, it requires a One Health approach to understand the holistic ecosystem health including that of humans. Here we collect and identify gaps in the current knowledge of health in the Arctic and present the veterinary perspective of One Health and ecosystem dynamics. The review shows that exposure to persistent organic pollutants (POPs) is having multiple organ-system effects across taxa, including impacts on neuroendocrine disruption, immune suppression and decreased bone density among others. Furthermore, the warming Arctic climate is suspected to influence abiotic and biotic long-range transport and exposure pathways of contaminants to the Arctic resulting in increases in POP exposure of both wildlife and human populations. Exposure to vector-borne diseases and zoonoses may increase as well through range expansion and introduction of invasive species. It will be important in the future to investigate the effects of these multiple stressors on wildlife and local people to better predict the individual-level health risks. It is within this framework that One Health approaches offer promising opportunities to survey and pinpoint environmental changes that have effects on wildlife and human health.     

Australian ecosystems, capricious food chains and parasitic consequences for people

Characteristic Australian ecosystems or environments contain numerous food chains some of which may become capriciously side-tracked or appropriated by humans, with parasitic consequences for people in Australia and overseas. Twelve of 13 arboviruses affecting humans are of wildlife origin and all are transmitted by mosquitoes. In this case, transmission is thus associated with aquatic environments, many artificial. Zoonotic trematode (brachylaimiasis) and cestode (rodentoleposis) infections have been reported from semi-arid environments. Scabies and angiostrongylosis are associated with work, recreational and home environments. Four species of Rickettsia endemic in wildlife are acquired by humans from fleas, mites and ticks in bush and semi-urban environments. The enigmatic and life-threatening muspiceoid nematode, Haycocknema perplexum, is known from people associated with the natural environment in Tasmania; whether it comes from vertebrates, invertebrates, plants, soil or water is unknown. Food chains occurring in a range of Australian ecosystems and environments, some associated with feeding arthropods, others with accidental ingestion of invertebrates, may result in human exposure and infection. A range of organisms normally occurring in wildlife, domestic animals or the environment may be involved in causing human disease.     

Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems

The use of human and veterinary pharmaceuticals is increasing. Over the past decade, there has been a proliferation of research into potential environmental impacts of pharmaceuticals in the environment. A Royal Society-supported seminar brought together experts from diverse scientific fields to discuss the risks posed by pharmaceuticals to wildlife. Recent analytical advances have revealed that pharmaceuticals are entering habitats via water, sewage, manure and animal carcases, and dispersing through food chains. Pharmaceuticals are designed to alter physiology at low doses and so can be particularly potent contaminants. The near extinction of Asian vultures following exposure to diclofenac is the key example where exposure to a pharmaceutical caused a population-level impact on non-target wildlife. However, more subtle changes to behaviour and physiology are rarely studied and poorly understood. Grand challenges for the future include developing more realistic exposure assessments for wildlife, assessing the impacts of mixtures of pharmaceuticals in combination with other environmental stressors and estimating the risks from pharmaceutical manufacturing and usage in developing countries. We concluded that an integration of diverse approaches is required to predict ‘unexpected’ risks; specifically, ecologically relevant, often long-term and non-lethal, consequences of pharmaceuticals in the environment for wildlife and ecosystems.     

Selecting appropriate animal models and experimental designs for endocrine disruptor research and testing studies

Evidence that chemicals in the environment may cause developmental and reproductive abnormalities in fish and wildlife by disrupting normal endocrine functions has increased concern about potential adverse human health effects from such chemicals. US laws have now been enacted that require the US Environmental Protection Agency (EPA) to develop and validate a screening program to identify chemicals in food and water with potential endocrine-disrupting activity. EPA subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro and in vivo test systems to identify chemicals that may adversely affect humans and ecologically important animal species. However, the endocrine system can be readily modulated by many experimental factors, including diet and the genetic background of the selected animal strain or stock. It is therefore desirable to minimize or avoid factors that cause or contribute to experimental variation in endocrine disruptor research and testing studies. Standard laboratory animal diets contain high and variable levels of phytoestrogens, which can modulate physiologic and behavioral responses similar to both endogenous estrogen as well as exogenous estrogenic chemicals. Other studies have determined that some commonly used outbred mice and rats are less responsive to estrogenic substances than certain inbred mouse and rat strains for various estrogen-sensitive endpoints. It is therefore critical to select appropriate biological models and diets for endocrine disruptor studies that provide optimal sensitivity and specificity to accomplish the research or testing objectives. An introduction is provided to 11 other papers in this issue that review these and other important laboratory animal experimental design considerations in greater detail, and that review laboratory animal and in vitro models currently being used or evaluated for endocrine disruptor research and testing. Selection of appropriate animal models and experimental design parameters for endocrine disruptor research and testing will minimize confounding experimental variables, increase the likelihood of replicable experimental results, and contribute to more reliable and relevant test systems.     

Pesticide-Induced Immunotoxicity: Are Humans at Risk?

One of the first immunotoxicology studies determined that exposure of ducks to DDT reduced their resistance to a virus infection. The immunotoxic potential of insecticides and herbicides has subsequently been studied extensively in laboratory animals, driven by the global distribution and use of these chemicals. (Ten of the twelve persistent organic pollutants, identified by the United Nations Environmental Program as posing the greatest threat to humans and wildlife, are pesticides; all have been reported to alter immune function under laboratory conditions.) Nevertheless, our knowledge of the human health risks associated with pesticide use and exposure is far from complete. This paper provides a brief overview of the potential effects of chemicals on the immune system, and host factors that mitigate or exacerbate immunotoxic effects. Examples of rodent studies that exemplify categories of pesticide-induced immune system effects are then provided as an introduction to a discussion of pesticide immunotoxicity in humans.     

Chlorinated Hydrocarbon Insecticides: Recent Animal Data of Potential Significance for Man

The environmental persistence of chlorinated hydrocarbon insecticides is posing a serious threat to the survival of several wildlife species. Sublethal effects, completely unrelated to the insecticidal properties of these chemicals, have contributed markedly to impaired reproduction in many species and to toxicity in neonatal animals. Considering the insecticide levels found in man, are these chemicals potentially dangerous to human infants and adults? Of special concern are the potential long-term, subtle effects of low concentrations of insecticides to which many persons are ordinarily exposed. These agents affect both the peripheral and central nervous systems. They markedly elevate hepatic enzyme levels, enhancing the biotransformation of many pharmacological agents as well as interfering with endogenous steroid biosynthesis and degradation. The DDT-like insecticides are potent estrogenic agents and some have shown teratogenic and carcinogenic activity. These aspects are discussed in relation to present levels found in humans and to possible adverse effects on perinatal and adult individuals.     

A review on emerging persistent organic pollutants: Current scenario in Pakistan

During the last few years, a new drift on screening of persistent organic pollutants (POPs) present in the environment of Pakistan has been observed. However, across the globe a number of reports have been devoted to the screening levels, distribution, and risk assessment and on the emission of POPs. In the case of Pakistan, the knowledge achieved and understanding of POPs contamination in the environmental compartments are still limited. Recently published literature has been a key to explore the mystery of new emerging POPs from the environment of the country. In this review, an effort was made to summarize the results of recently published reports on POPs (PCNs, PBDEs, DPs, and PCBs) from biotic and abiotic environments of Pakistan. This review also presents the available data published to date for organochlorines. The results of previously reported studies reflected that newly emerging POPs were influenced by the industrial and urban fractions and were in line with the distribution pattern of other regions of the world. These results revealed that urgent attention must be paid to these new emerging POPs, as they are reported to be present in considerable concentrations. Such detected concentrations of these banned pollutants should be checked/screened by scientific authorities to avoid adverse health risks to humans and animals.     

Biodegradation of endocrine‐disrupting compounds by ligninolytic fungi: mechanisms involved in the degradation

Without any doubt, endocrine‐disrupting compounds (EDCs) represent an environmental risk for wildlife and human beings. Endocrine‐disrupting effects were found for many chemicals in products for personal use, industrial compounds and even in classical persistent organic pollutants (POPs). In order to understand the fate of EDCs in the environment, it is highly important to identify and to clarify the biodegradation mechanisms that can lead to their decomposition. Ligninolytic fungi (LF) are interesting microorganisms that are capable of participating in a variety of versatile decomposition mechanisms. The microorganisms represent a useful model group and, moreover, LF or their enzymes can be actively used for decontamination. Potential optimization of the decontamination process provides another important reason why it is necessary for understanding the mechanisms of EDC transformation. This minireview summarizes current knowledge about the LF biodegradation mechanisms of the most important micropollutants (xenoestrogens), including nonylphenols, bisphenol A and 17α‐ethinylestradiol and polychlorinated biphenyls as POPs with endocrine‐disrupting potency. Generally, LF exhibit the ability to either polymerize the target pollutants or to substantially decompose the original structure using ligninolytic enzymes and cytochrome P‐450. Moreover, most of the transformation processes are accompanied by reduction of the endocrine‐disrupting activity or ecotoxicity.     

Bridging epidemiology and model organisms to increase understanding of endocrine disrupting chemicals and human health effects

Concerning temporal trends in human reproductive health has prompted concern about the role of environmentally mediated risk factors. The population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products, subsequently multiple chemicals are found human populations around the globe. Recent reviews find that endocrine disrupting chemicals (EDCs) can adversely affect reproductive and developmental health. However, there are still many knowledge gaps. This paper reviews some of the key scientific concepts relevant to integrating information from human epidemiologic and model organisms to understand the relationship between EDC exposure and adverse human health effects. Additionally, areas of new insights which influence the interpretation of the science are briefly reviewed, including: enhanced understanding of toxicity pathways; importance of timing of exposure; contribution of multiple chemical exposures; and low dose effects. Two cases are presented, thyroid disrupting chemicals and anti-androgens chemicals, which illustrate how our knowledge of the relationship between EDCs and adverse human health effects is strengthened and data gaps reduced when we integrate findings from animal and human studies.     

A Review of Zoonotic Infection Risks Associated with the Wild Meat Trade in Malaysia

The overhunting of wildlife for food and commercial gain presents a major threat to biodiversity in tropical forests and poses health risks to humans from contact with wild animals. Using a recent survey of wildlife offered at wild meat markets in Malaysia as a basis, we review the literature to determine the potential zoonotic infection risks from hunting, butchering and consuming the species offered. We also determine which taxa potentially host the highest number of pathogens and discuss the significant disease risks from traded wildlife, considering how cultural practices influence zoonotic transmission. We identify 51 zoonotic pathogens (16 viruses, 19 bacteria and 16 parasites) potentially hosted by wildlife and describe the human health risks. The Suidae and the Cervidae families potentially host the highest number of pathogens. We conclude that there are substantial gaps in our knowledge of zoonotic pathogens and recommend performing microbial food safety risk assessments to assess the hazards of wild meat consumption. Overall, there may be considerable zoonotic risks to people involved in the hunting, butchering or consumption of wild meat in Southeast Asia, and these should be considered in public health strategies.     

A review of chemically-induced alterations in thyroid and vitamin A status from field studies of wildlife and fish

This paper reviews 22 published field studies that have found an association between exposure to environmental contaminants and alterations in thyroid gland structure, circulating thyroid hormones and vitamin A (retinoid) status in free-ranging populations of wildlife and fish. Vitamin A and thyroid hormones play critical roles during development, growth and function 'throughout life. Studies of captive wildlife and laboratory studies support a relationship between alterations in thyroid hormones and vitamin A status and exposure to dioxins, furans, and planar polychlorinated biphenyls, which bind to the aryl hydrocarbon receptor. Some studies have found adverse health effects in wildlife associated with exposure to polyhalogenated aromatic hydrocarbons and altered thyroid and retinoid status including: decreased reproductive success, immune system changes, dermatologic abnormalities and developmental deformities. A direct causal relationship between these effects and thyroid and retinoid changes has not been demonstrated. Field researchers studying the responses to these synthetic chemicals in wildlife and fish should include measurement of thyroid hormones and retinoids and histological examination of the thyroid gland in their study design as biomarkers of exposure to these chemicals in the environment.     

The rise and fall of photomutagenesis

UV is the most abundant human carcinogen, and protection from extensive exposure to it is a widespread human health issue. The use of chemicals (sunscreens) for protection is intuitive and efficacious. However, these chemicals may become activated to reactive intermediates when absorbing energy from UV, thus producing damage themselves, which may manifest itself in phototoxic, photoallergenic or photocarcinogenic reactions in humans. The development of safe sunscreens for humans is of high interest. Similar issues have been observed for some therapeutically used principles such as PUVA therapy for psoriasis or porphyrins for phototherapy of human cancers. Photoactivation has also been reported as a side effect of various pharmaceuticals such as the antibacterial fluoroquinolones. In this context, the authors have been involved over more than 20 years in the development and refinement of assays to test for photomutagenicity as an unwanted side effect of UV-mediated activation of such chemicals for cosmetic or pharmaceutical use. The initial years of great hopes for simple mammalian cell-based assays for photomutagenicity to screen out substances of concern for human use were followed by many years of collaborative trials to achieve standardization. However, it is now realized that this topic, albeit of human safety relevance, is highly complex and subject to many artificial modifiers, especially in vitro in mammalian cell culture. Thus, it is not really suitable for being engineered into a general testing framework within cosmetic or pharmaceutical testing guidelines. Much knowledge has been generated over the years to arrive at the conclusion that yes, photomutagenicity does exist with the use of chemicals, but how to best test for it will require a sophisticated case-by-case approach. Moreover, in comparison to the properties and risks of exposure to UV itself, it remains a comparatively minor human safety risk to address. In considering risks and benefits, we should also acknowledge beneficial effects of UV on human health, including an essential role in the production of Vitamin D. Thus, the interrelationships between UV, chemicals and human health remain a fascinating topic of research.     

Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21(st) Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.     

Pesticide-Induced Illness—Public Health Aspects of Diagnosis and Treatment

Over the past 25 years there has been a remarkable proliferation of new chemicals into our environment, among them the 57,000 different trade-named pesticide formulations now for sale in the United States. With them have come many new problems to physicians needing up-to-the minute toxocologic information, and also sizable problems in public health. Technology must be harnessed to bring to physicians, when they need it, help in the diagnosis and treatment of poisoning and other adverse effects from modern chemicals, for at present it is impossible for the practicing physician to keep up with what is known and unknown about the toxicology of all of these chemicals.     

Understanding risk perceptions to enhance communication about human-wildlife interactions and the impacts of zoonotic disease

Inclusion of wildlife in the concept of One Health is important for two primary reasons: (1) the physical health of humans, domesticated animals, and wildlife is linked inextricably through shared diseases, and (2) humans' emotional well-being can be affected by their perceptions of animal health. Although an explicit premise of the One Health Initiative is that healthy wildlife contribute to human health, and vice versa, the initiative also suggests implicitly that wildlife may pose threats to human health through zoonotic disease transmission. As people learn more about One Health, an important question surfaces: How will they react to communications carrying the message that human health and wildlife health are linked? In the absence of adequate relevant research data, we recommend caution in the production and dissemination of One Health messages because of possible unintended or collateral effects. Understanding how and why individuals perceive risks related to wildlife diseases is essential for determining message content that promotes public support for healthy wildlife populations, on the one hand, and, on the other, for identifying messages that might inadvertently increase concern about human health effects of diseased wildlife. To that end, we review risk perception research and summarize the few empirical studies that exist on perceived risk associated with zoonoses. We conclude with some research questions that need answering to help One Health practitioners better understand how the public will interpret their messages and thus how to communicate positively and without negative collateral consequences for wildlife conservation.     

Bisphenol A and Risk Management Ethics

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low‐dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low‐dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values.     

镉在土壤-植物-人体系统中迁移积累及其影响因子

环境镉(Cd)污染对微生物、植物、动物和人体均可产生较大的危害。食物链是镉对普通人群造成健康危害的主要途径之一。污染土壤中的镉通过植物根系吸收与体内转运最终在植物可食部分中积累。Cd通过食物链进人人体并在体内蓄积受许多因素的影响,这些影响因素主要有3个方面：土壤性质(土壤含镉量、pH、有机质、粘土矿物和土壤养分状况),植物特性(包括基因型差异、根际过程和植物生理机制)和人体微量元素营养状况等因素。本文就镉在食物链中迁移积累及其调控机理的研究进展进行简要的综述。     

Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21^st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) “toxicity pathways” (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.     

Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems

Global pharmaceutical consumption is rising with the growing and ageing human population and more intensive food production. Recent studies have revealed pharmaceutical residues in a wide range of ecosystems and organisms. Environmental concentrations are often low, but pharmaceuticals typically are designed to have biological effects at low doses, acting on physiological systems that can be evolutionarily conserved across taxa. This Theme Issue introduces the latest research investigating the risks of environmentally relevant concentrations of pharmaceuticals to vertebrate wildlife. We take a holistic, global view of environmental exposure to pharmaceuticals encompassing terrestrial, freshwater and marine ecosystems in high- and low-income countries. Based on both field and laboratory data, the evidence for and relevance of changes to physiology and behaviour, in addition to mortality and reproductive effects, are examined in terms of the population- and community-level consequences of pharmaceutical exposure on wildlife. Studies on uptake, trophic transfer and indirect effects of pharmaceuticals acting via food webs are presented. Given the logistical and ethical complexities of research in this area, several papers focus on techniques for prioritizing which compounds are most likely to harm wildlife and how modelling approaches can make predictions about the bioavailability, metabolism and toxicity of pharmaceuticals in non-target species. This Theme Issue aims to help clarify the uncertainties, highlight opportunities and inform ongoing scientific and policy debates on the impacts of pharmaceuticals in the environment.