There are possibly millions of mold species on earth. The vast majority of these mold spores live in harmony with humans, rarely causing disease. The rare species that does cause disease does so by triggering allergies or asthma, or may be involved in hypersensitivity diseases such as allergic bronchopulmonary aspergillosis or allergic fungal sinusitis. Other hypersensitivity diseases include those related to occupational or domiciliary exposures to certain mold species, as in the case of Pigeon Breeder’s disease, Farmer’s lung, or humidifier fever. The final proven category of fungal diseases is through infection, as in the case of onchomycosis or coccidiomycosis. These diseases can be treated using anti-fungal agents. Molds and fungi can also be particularly important in infections that occur in immunocompromised patients. Systemic candidiasis does not occur unless the individual is immunodeficient. Previous reports of “toxic mold syndrome” or “toxic black mold” have been shown to be no more than media hype and mass hysteria, partly stemming from the misinterpreted concept of the “sick building syndrome.” There is no scientific evidence that exposure to visible black mold in apartments and buildings can lead to the vague and subjective symptoms of memory loss, inability to focus, fatigue, and headaches that were reported by people who erroneously believed that they were suffering from “mycotoxicosis.” Similarly, a causal relationship between cases of infant pulmonary hemorrhage and exposure to “black mold” has never been proven. Finally, there is no evidence of a link between autoimmune disease and mold exposure.

The management of patients with chronic pain is a nearly daily challenge to rheumatologists, neurologists, orthopedic surgeons, pain specialists and indeed a issue in nearly every clinical practice. Among the myriad of causes of pain are often included a unique syndrome, generally referred to as complex regional pain syndrome type I (CRPS). Unfortunately CRPS I has become a catch all phase and there are serious questions on whether it exists at all; this has led to an extraordinary number of poorly defined diagnostic criteria. It has also led to an etiologic quagmire that includes features as diverse as autoimmunity to simple trauma. These, in turn, have led to overdiagnosis and often overzealous use of pain medications, including narcotics. In a previous paper, we raised the issue of whether CRPS type I reflected a valid diagnosis. Indeed, the diagnostic criteria for CRPS I, and therefore the diagnosis itself, is unreliable for a number of reasons: 1) the underlying pathophysiology of the signs and symptoms of CPRS I are not biologically plausible; 2) there are no consistent laboratory or imaging testing available; 3) the signs and symptoms fluctuate over time without a medical explanation; 4) the definitions of most studies are derived from statistical analysis with little consideration to required sample size, i.e. power calculations; 5) interobserver reliability in the assessment of the signs and symptoms are often only fair to moderate, and agreement on the diagnosis of "CRPS I" is poor. Even physicians who still believe in the concept of "CRPS I" admit that it is vastly overdiagnosed and has become a diagnosis of last resort, often without a complete differential diagnosis and an alternative explanation. Finally, one of the most convincing arguments that there is no clinical entity as "CRPS I" comes from the enormous heterogeneity in sign and symptom profiles and the heterogeneity of pathophysiological mechanisms postulated. This observation is underscored by the diversity of responses among "CRPS I" patients to essentially all treatment modalities. It has even led to the concept that the signs and symptoms of CRPS can spread throughout the body, as if it is an infectious disease, without any medical plausible explanation. If true progress is to be made in helping patients with pain, it will require entirely new and different concepts and abandoning CRPS I as a legitimate diagnosis.

In the United States, as in most of the world, there are large numbers of nutraceuticals that are sold and which people take to boost their immune response. There are, in addition, almost an equal number of products sold to reduce allergies. However, very few consumers, and indeed physicians, are aware of what a structure/function claim is. Structure/function claims are labeling claims that can be used to describe the potential effects of a dietary ingredient or similar substance on the structure or function of the human body. This category of claims was created by legislation contained in the Dietary Supplement Health and Education Act. The intent was to supply consumers with reasonably substantiated information that would allow them to make educated choices about their diet and health. They were not intended to have the same weight and substantiation as the claims made for conventional prescription pharmaceuticals. Rather, they were proposed to fill the gap between consumer desire for over-the-counter supplements and foods, and rigorous and generally more potent and potentially "toxic" prescription medications. The legally mandated disclaimer, stating that the U.S. Food and Drug Administration has not evaluated the structure/function claim, often leads to misinterpretation. While there should be a biologic premise underlying the claim, there is not an absolute requirement for a conventional rigorous placebo-controlled dose response trial. While this may not be the clinical standard that a typical scientific oriented society might desire, it reflects the attempts of the FDA to find common grounds and to allow consumers to use products that are generally considered as safe based on historical use and biologic comparisons. The logic of, indeed need for, structure/function claims is straightforward; however, of equal importance is that nutraceuticals should be properly labeled, have accuracy in their ingredients, be free of contamination, be safe, and have a reasonable body of data that supports their efficacy.

Fibromyalgia is a disorder that is part of a spectrum of syndromes that lack precise classification. It is often considered as part of the global overview of functional somatic syndromes that are otherwise medically unexplained or part of a somatization disorder. Patients with fibromyalgia share symptoms with other functional somatic problems, including issues of myalgias, arthralgias, fatigue and sleep disturbances. Indeed, there is often diagnostic and classification overlap for the case definitions of a variety of somatization disorders. Fibromyalgia, however, is a critically important syndrome for physicians and scientists to be aware of. Patients should be taken very seriously and provided optimal care. Although inflammatory, infectious, and autoimmune disorders have all been ascribed to be etiological events in the development of fibromyalgia, there is very little data to support such a thesis. Many of these disorders are associated with depression and anxiety and may even be part of what has been sometimes called affected spectrum disorders. There is no evidence that physical trauma, i.e., automobile accidents, is associated with the development or exacerbation of fibromyalgia. Treatment should be placed on education, patient support, physical therapy, nutrition, and exercise, including the use of drugs that are approved for the treatment of fibromyalgia. Treatment should not include opiates and patients should not become poly pharmacies in which the treatment itself can lead to significant morbidities. Patients with fibromyalgia are living and not dying of this disorder and positive outlooks and family support are key elements in the management of patients.

Lyme disease was originally identified in Lyme, Connecticut, based upon an unusual cluster of what appeared to be patients with juvenile rheumatoid arthritis. It was subsequently identified as a new clinical entity originally called Lyme arthritis based on the observation that arthritis was a major clinical feature. However, Lyme arthritis is now called Lyme disease based upon the understanding that the clinical features include not only arthritis, but also potential cardiac, dermatologic and neurologic findings. Lyme disease typically begins with an erythematous rash called erythema migrans (EM). Approximately 4–8% of patients develop cardiac, 11% develop neurologic and 45–60% of patients manifest arthritis. The disease is transmitted following exposure to a tick bite containing a spirochete in a genetically susceptible host. There is considerable data on spirochetes, including Borrelia burgdorferi (Bb), the original bacteria identified in this disease. Lyme disease, if an organism had not been identified, would be considered as a classic autoimmune disease and indeed the effector mechanisms are similar to many human diseases manifest as loss of tolerance. The clinical diagnosis is highly likely based upon appropriate serology and clinical manifestations. However, the serologic features are often misinterpreted and may have false positives if confirmatory laboratory testing is not performed. Antibiotics are routinely and typically used to treat patients with Lyme disease, but there is no evidence that prolonged or recurrent treatment with antibiotics change the natural history of Lyme disease. Although there are animal models of Lyme disease, there is no system that faithfully recapitulates the human disease. Further research on the effector mechanisms that lead to pathology in some individuals should be further explored to develop more specific therapy.

Complex regional pain syndrome (CRPS) is a term used to describe a variety of disorders characterized by spontaneous or stimulus-induced pain that is disproportional to the inciting event and accompanied by a myriad of autonomic and motor disturbances in highly variable combinations. There are no standards which can be applied to the diagnosis and would fulfill definitions of evidence-based medicine. Indeed, there are almost as many diagnostic criteria as there are names to this disorder. The umbrella term CRPS has been subdivided into type I and type II. CRPS I is intended to encompass reflex sympathetic dystrophy and similar disorders without a nerve injury; while CRPS II occurs after damage to a peripheral nerve. There are numerous etiological pathophysiological events that have been incriminated in development of CRPS, including inflammation, autoimmune responses, abnormal cytokine production, sympathetic-sensory disorders, altered blood flow and central cortical reorganization. However, the number of studies that have included appropriate controls and have sufficient numbers of patients to allow statistical analysis with appropriate power calculations is vanishingly small. This has led to over-diagnosis and often excessive pharmacotherapy and even unnecessary surgical interventions. In this review we provide a detailed critical overview of not only the history of CRPS, but also the epidemiology, the clinical features, the pathophysiological studies, the proposed criteria, the therapy and, in particular, an emphasis that future research should apply more rigorous standards to allow a better understanding of CRPS, i.e. what it is, if it is, and when it is.

Respiratory syncytial virus (RSV) is amongst the most important pathogenic infections of childhood and is associated with significant morbidity and mortality. Although there have been extensive studies of epidemiology, clinical manifestations, diagnostic techniques, animal models and the immunobiology of infection, there is not yet a convincing and safe vaccine available. The major histopathologic characteristics of RSV infection are acute bronchiolitis, mucosal and submucosal edema, and luminal occlusion by cellular debris of sloughed epithelial cells mixed with macrophages, strands of fibrin, and some mucin. There is a single RSV serotype with two major antigenic subgroups, A and B. Strains of both subtypes often co-circulate, but usually one subtype predominates. In temperate climates, RSV infections reflect a distinct seasonality with onset in late fall or early winter. It is believed that most children will experience at least one RSV infection by the age of 2 years. There are several key animal models of RSV. These include a model in mice and, more importantly, a bovine model; the latter reflects distinct similarity to the human disease. Importantly, the prevalence of asthma is significantly higher amongst children who are hospitalized with RSV in infancy or early childhood. However, there have been only limited investigations of candidate genes that have the potential to explain this increase in susceptibility. An atopic predisposition appears to predispose to subsequent development of asthma and it is likely that subsequent development of asthma is secondary to the pathogenic inflammatory response involving cytokines, chemokines and their cognate receptors. Numerous approaches to the development of RSV vaccines are being evaluated, as are the use of newer antiviral agents to mitigate disease. There is also significant attention being placed on the potential impact of co-infection and defining the natural history of RSV. Clearly, more research is required to define the relationships between RSV bronchiolitis, other viral induced inflammatory responses, and asthma.

Objective: To review the epidemiology, presentation, diagnosis, treatment, pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of this entity.Methods: We conducted a Medline search using SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and extracted further relevant articles from the retrieved references.Results: The SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular disorders that are frequently accompanied by dermatoses characterized by neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is rare, although probably underrecognized because its diagnosis may be challenging because of the wide variability in its musculoskeletal and cutaneous manifestations. This is especially true when atypical sites are involved and when specific skin lesions are absent. There are no standardized treatment protocols available. Current treatments are empirical and have the objective of providing relief from the at times debilitating pain associated with SAPHO syndrome. They include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents. Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have all been beneficial in some patients, but ineffective in others. This suggests that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect remains poorly explored, although bacteria and immunological dysfunction are hypothesized to play a role.Conclusions: The early recognition, diagnosis, and prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term antibiotics or invasive procedures, while rapidly alleviating pain in a majority of affected patients. (C) 2012 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:254-265

Lupus nephritis remains one of the most severe manifestations of systemic lupus erythematosus associated with considerable morbidity and mortality. A better understanding of the pathogenesis of lupus nephritis is an important step in identifying more targeted and less toxic therapeutic approaches. Substantial research has helped define the pathogenetic mechanisms of renal manifestations and, in particular, the complex role of type I interferons is increasingly recognized; new insights have been gained into the contribution of immune complexes containing endogenous RNA and DNA in triggering the production of type I interferons by dendritic cells via activation of endosomal toll-like receptors. At the same time, there have been considerable advances in the treatment of lupus nephritis. Corticosteroids have long been the cornerstone of therapy, and the addition of cyclophosphamide has contributed to renal function preservation in patients with severe proliferative glomerulonephritis, though at the cost of serious adverse events. More recently, in an effort to minimize drug toxicity and achieve equal effectiveness, other immunosuppressive agents, including mycophenolate mofetil, have been introduced. Herein, we provide a detailed review of the trials that established the equivalency of these agents in the induction and/or maintenance therapy of lupus nephritis, culminating in the recent publication of new treatment guidelines by the American College of Rheumatology. Although newer biologics have been approved and continue to be a focus of research, they have, for the most part, been relatively disappointing compared to the effectiveness of biologics in other autoimmune diseases. Early diagnosis and treatment are essential for renal preservation.

Giant cell arteritis is a chronic vasculitis affecting large and medium-sized arteries, most commonly the temporal and other cranial arteries. Temporal artery biopsy has long been the gold standard for establishing the diagnosis of giant cell arteritis. There is growing evidence that simultaneous color Doppler and duplex ultrasonography of temporal arteries of GCA patients represents a valid alternative for this somewhat invasive procedure. Ultrasonography and other imaging modalities such as magnetic resonance imaging and positron emission tomography have also provided evidence that involvement of the aorta and its proximal branches is much more common in giant cell arteritis than previously appreciated; it will be important to clarify whether these patients need to be treated more aggressively. It has long been known that patients with giant cell arteritis face a markedly increased risk of developing aortic aneurysms and of dying from aortic dissection. This raises important questions as to whether patients should be screened regularly for extra-cranial large-vessel involvement and whether and how treatment of patients with positive screening results should be adjusted. In this review we discuss the pathophysiology of this disease and also the issues of epidemiology and sex differences.

OBJECTIVE:To review the epidemiology, presentation, diagnosis, treatment, pathogenesis, and genetics of the syndrome known under the acronym of SAPHO for Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis to heighten awareness of this entity.METHODS:We conducted a Medline search using SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms as keywords and extracted further relevant articles from the retrieved references.RESULTS:The SAHPO acronym identifies a syndrome encompassing a variety of osteoarticular disorders that are frequently accompanied by dermatoses characterized by neutrophilic pseudoabscesses, but can also occur in isolation. SAPHO syndrome is rare, although probably underrecognized because its diagnosis may be challenging because of the wide variability in its musculoskeletal and cutaneous manifestations. This is especially true when atypical sites are involved and when specific skin lesions are absent. There are no standardized treatment protocols available. Current treatments are empirical and have the objective of providing relief from the at times debilitating pain associated with SAPHO syndrome. They include nonsteroidal anti-inflammatory drugs and analgesics as first-line agents. Systemic corticosteroids, disease-modifying anti-rheumatic drugs, biologicals targeting tumor necrosis factor alpha and interleukin-1, and bisphosphonates have all been beneficial in some patients, but ineffective in others. This suggests that the pathogenesis of SAPHO syndrome is multifactorial, but this aspect remains poorly explored, although bacteria and immunological dysfunction are hypothesized to play a role.CONCLUSIONS:The early recognition, diagnosis, and prompt treatment of SAPHO syndrome can prevent the unnecessary use of long-term antibiotics or invasive procedures, while rapidly alleviating pain in a majority of affected patients.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) affecting the pulmonary interstitium. Other forms of interstitial lung disease exist, and in some cases, an environmental etiology can be delineated. The diagnosis of IPF is typically established by high-resolution CT scan. IPF tends to have a worse prognosis than other forms of ILD. Familial cases of IPF also exist, suggesting a genetic predisposition; telomerase mutations have been observed to occur in familial IPF, which may also explain the increase in IPF with advancing age. Alveolar epithelial cells are believed to be the primary target of environmental agents that have been putatively associated with IPF. These agents may include toxins, viruses, or the autoantibodies found in collagen vascular diseases. The mechanism of disease is still unclear in IPF, but aberrations in fibroblast differentiation, activation, and proliferation may play a role. Epithelial-mesenchymal transition may also be an important factor in the pathogenesis, as it may lead to accumulation of fibroblasts in the lung and a disruption of normal tissue structure. Abnormalities in other components of the immune system, including T cells, B cells, and dendritic cells, as well as the development of ectopic lymphoid tissue, have also been observed to occur in IPF and may play a role in the stimulation of fibrosis that is a hallmark of the disease. It is becoming increasingly clear that the pathogenesis of IPF is indeed a complex and convoluted process that involves numerous cell types and humoral factors.

There are an enormous number of incorrect stereotypes that characterize the differences between women and men. Indeed, nearly all of these stereotypes are based on cultural inaccuracies and faulty data without consideration of biology and the distinct sociological differences between genders. Sociological differences are those that relate to the development, structure, interaction and behavior of organized groups of human beings, or societies, and their values and beliefs. Gender is a social construct referring “to the culturally and historically based differences in the roles, attitudes and behaviors of men and women” ([1], p.1) as shaped by norms and stereotypes. Sex, on the other hand, serves to classify living things according to their reproductive organs and functions assigned by chromosomal complement (according to the US Institute of Medicine) and the physical and biological characteristics arising from these organs and functions. The two terms are generally viewed as dichotomous; however, they are closely intertwined in as yet hardly understood ways, and it is frequently difficult to distinguish between them since gendered life experiences can have profound effects on body structure and function [2]. In this review, we will examine to what extent gender roles and stereotypes shape the daily lives of women in their roles as students, employees, wives, and mothers and their health. These data have implications for the etiology of autoimmunity and also for differences in the natural history of disease.

Biological agents represent a major advance in the treatment of rheumatic diseases, most particularly in the prevention of irreversible structural damage. While generally well tolerated, their increasing use continues to reveal a variety of immune-mediated adverse effects. The most frequent adverse events are infusion reactions and injection site reactions, but despite their fairly common occurrence the precise mechanisms are not fully understood. Another adverse event that became appreciated early in the era of biologicals is the increased risk of Mycobacterium tuberculosis and other granulomatous infections in patients treated with tumor necrosis factor (TNFα) antagonists. Although it is evident that this enhanced susceptibility to intracellular infections must be due to immunosuppression arising from the blockade of TNFα, the mechanisms have not been fully elucidated; such an understanding is likely to provide important insights into the role of TNFα in granulomatous and other infectious diseases. In addition, the biologicals may paradoxically induce autoimmunity. The development of autoantibodies is seen in a considerable proportion of patients, but clinical autoimmune disease develops much less commonly, including systemic lupus erythematosus, multiple sclerosis and other demyelinating diseases, psoriasis, sarcoidosis, and interstitial lung disease. The mechanisms leading to their induction are very poorly understood, but an intriguing hypothesis is that interferon α provides a common link, at least for lupus, psoriasis and possibly sarcoidosis. Finally, the potential risk of infection with use of the biologicals is an issue that clinicians should always be aware of. These comments aside, the biologics are the most important advance in the treatment of rheumatic disease in the history of rheumatology and their usage has not only greatly helped patient care, but also provided key data on the immunobiology of the disease processes.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absolute insulin deficiency resulting from the progressive immune-mediated destruction of pancreatic islet β cells. It is thought to be triggered by as yet unidentified environmental factors in genetically susceptible individuals, the major genetic contribution coming from loci within the HLA complex, in particular HLA class II. The worldwide incidence of T1D varies by at least 100-fold, being highest in Finland and Sardinia (Italy) and lowest in Venezuela and China. The incidence has been increasing worldwide at an annual rate of approximately 3%. While genetic factors are thought to explain some of the geographic variability in T1D occurrence, they cannot account for its rapidly increasing frequency. Instead, the declining proportion of newly diagnosed children with high-risk genotypes suggests that environmental pressures are now able to trigger T1D in genotypes that previously would not have developed the disease during childhood. Although comparisons between countries and regions with low and high-incidence rates have suggested that higher socioeconomic status and degree of urbanization are among the environmental factors that play a role in the rising incidence of T1D, the findings are too inconsistent to allow firm conclusions. Morbidity and mortality as well as causes of death also show considerable geographic variation. While glycemic control has been identified as a major predictor of the micro- and macrovascular complications of T1D and shows considerable geographical variability, it does not appear to be the only factor involved in the regional differences in complication rates. The role of genetics in susceptibility to nephropathy, retinopathy and other diabetic complications largely remains to be explored.

Food can never be entirely safe. Food safety is threatened by numerous pathogens that cause a variety of foodborne diseases, algal toxins that cause mostly acute disease, and fungal toxins that may be acutely toxic but may also have chronic sequelae, such as teratogenic, immunotoxic, nephrotoxic, and estrogenic effects. Perhaps more worrisome, the industrial activities of the last century and more have resulted in massive increases in our exposure to toxic metals such as lead, cadmium, mercury, and arsenic, which now are present in the entire food chain and exhibit various toxicities. Industrial processes also released chemicals that, although banned a long time ago, persist in the environment and contaminate our food. These include organochlorine compounds, such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene) (DDT), other pesticides, dioxins, and dioxin-like compounds. DDT and its breakdown product dichlorophenyl dichloroethylene affect the developing male and female reproductive organs. In addition, there is increasing evidence that they exhibit neurodevelopmental toxicities in human infants and children. They share this characteristic with the dioxins and dioxin-like compounds. Other food contaminants can arise from the treatment of animals with veterinary drugs or the spraying of food crops, which may leave residues. Among the pesticides applied to food crops, the organophosphates have been the focus of much regulatory attention because there is growing evidence that they, too, affect the developing brain. Numerous chemical contaminants are formed during the processing and cooking of foods. Many of them are known or suspected carcinogens. Other food contaminants leach from the packaging or storage containers. Examples that have garnered increasing attention in recent years are phthalates, which have been shown to induce malformations in the male reproductive system in laboratory animals, and bisphenol A, which negatively affects the development of the central nervous system and the male reproductive organs. Genetically modified foods present new challenges to regulatory agencies around the world because consumer fears that the possible health risks of these foods have not been allayed. An emerging threat to food safety possibly comes from the increasing use of nanomaterials, which are already used in packaging materials, even though their toxicity remains largely unexplored. Numerous scientific groups have underscored the importance of addressing this issue and developing the necessary tools for doing so. Governmental agencies such as the US Food and Drug Administration and other agencies in the USA and their counterparts in other nations have the increasingly difficult task of monitoring the food supply for these chemicals and determining the human health risks associated with exposure to these substances. The approach taken until recently focused on one chemical at a time and one exposure route (oral, inhalational, dermal) at a time. It is increasingly recognized, however, that many of the numerous chemicals we are exposed to everyday are ubiquitous, resulting in exposure from food, water, air, dust, and soil. In addition, many of these chemicals act on the same target tissue by similar mechanisms. “Mixture toxicology” is a rapidly growing science that addresses the complex interactions between chemicals and investigates the effects of cumulative exposure to such “common mechanism groups” of chemicals. It is to be hoped that this results in a deeper understanding of the risks we face from multiple concurrent exposures and makes our food supply safer.

Food can never be entirely safe. Food safety is threatened by numerous pathogens that cause a variety of foodborne diseases, algal toxins that cause mostly acute disease, and fungal toxins that may be acutely toxic but may also have chronic sequelae, such as teratogenic, immunotoxic, nephrotoxic, and estrogenic effects. Perhaps more worrisome, the industrial activities of the last century and more have resulted in massive increases in our exposure to toxic metals such as lead, cadmium, mercury, and arsenic, which now are present in the entire food chain and exhibit various toxicities. Industrial processes also released chemicals that, although banned a long time ago, persist in the environment and contaminate our food. These include organochlorine compounds, such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene) (DDT), other pesticides, dioxins, and dioxin-like compounds. DDT and its breakdown product dichlorophenyl dichloroethylene affect the developing male and female reproductive organs. In addition, there is increasing evidence that they exhibit neurodevelopmental toxicities in human infants and children. They share this characteristic with the dioxins and dioxin-like compounds. Other food contaminants can arise from the treatment of animals with veterinary drugs or the spraying of food crops, which may leave residues. Among the pesticides applied to food crops, the organophosphates have been the focus of much regulatory attention because there is growing evidence that they, too, affect the developing brain. Numerous chemical contaminants are formed during the processing and cooking of foods. Many of them are known or suspected carcinogens. Other food contaminants leach from the packaging or storage containers. Examples that have garnered increasing attention in recent years are phthalates, which have been shown to induce malformations in the male reproductive system in laboratory animals, and bisphenol A, which negatively affects the development of the central nervous system and the male reproductive organs. Genetically modified foods present new challenges to regulatory agencies around the world because consumer fears that the possible health risks of these foods have not been allayed. An emerging threat to food safety possibly comes from the increasing use of nanomaterials, which are already used in packaging materials, even though their toxicity remains largely unexplored. Numerous scientific groups have underscored the importance of addressing this issue and developing the necessary tools for doing so. Governmental agencies such as the US Food and Drug Administration and other agencies in the USA and their counterparts in other nations have the increasingly difficult task of monitoring the food supply for these chemicals and determining the human health risks associated with exposure to these substances. The approach taken until recently focused on one chemical at a time and one exposure route (oral, inhalational, dermal) at a time. It is increasingly recognized, however, that many of the numerous chemicals we are exposed to everyday are ubiquitous, resulting in exposure from food, water, air, dust, and soil. In addition, many of these chemicals act on the same target tissue by similar mechanisms. "Mixture toxicology" is a rapidly growing science that addresses the complex interactions between chemicals and investigates the effects of cumulative exposure to such "common mechanism groups" of chemicals. It is to be hoped that this results in a deeper understanding of the risks we face from multiple concurrent exposures and makes our food supply safer.