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International Journal of Nanomedicine 2008The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery... (Review)
Review
The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.
Topics: Drug Compounding; Drug Delivery Systems; Nanomedicine; Nanoparticles
PubMed: 18686775
DOI: 10.2147/ijn.s596 -
Dermatologic Clinics Apr 2017Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household... (Review)
Review
Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. Because chemical-induced depigmentation is clinically and histologically indistinguishable from nonchemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as "chemical-induced vitiligo," rather than less accurate terms that have been previously used.
Topics: Autoimmunity; Catechols; Hair Dyes; Humans; Hydroquinones; Hypopigmentation; Phenols; Phenylenediamines; Skin Lightening Preparations; Vitiligo
PubMed: 28317525
DOI: 10.1016/j.det.2016.11.006 -
Molecular and Cellular Endocrinology Sep 2020Obesity has become a very large concern worldwide, reaching pandemic proportions over the past several decades. Lifestyle factors, such as excess caloric intake and... (Review)
Review
Obesity has become a very large concern worldwide, reaching pandemic proportions over the past several decades. Lifestyle factors, such as excess caloric intake and decreased physical activity, together with genetic predispositions, are well-known factors related to obesity. There is accumulating evidence suggesting that exposure to some environmental chemicals during critical windows of development may contribute to the rapid increase in the incidence of obesity. Agrochemicals are a class of chemicals extensively used in agriculture, which have been widely detected in human. There is now considerable evidence linking human exposure to agrochemicals with obesity. This review summarizes human epidemiological evidence and experimental animal studies supporting the association between agrochemical exposure and obesity and outlines possible mechanistic underpinnings for this link.
Topics: Agrochemicals; Animals; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Genetic Predisposition to Disease; Humans; Obesity
PubMed: 32619583
DOI: 10.1016/j.mce.2020.110926 -
Annual Review of Public Health Apr 2018In the United States, breast cancer is the most common invasive malignancy and the second most common cause of death from cancer in women. Reproductive factors,... (Review)
Review
In the United States, breast cancer is the most common invasive malignancy and the second most common cause of death from cancer in women. Reproductive factors, estrogen, and progesterone have major causal roles, but concerns about other potential causes in the external environment continue to drive research inquiries and stimulate calls for action at the policy level. The environment is defined as anything that is not genetic and includes social, built, and chemical toxicant aspects. This review covers the scope of known and suspected environmental factors that have been associated with breast cancer and illustrates how epidemiology, toxicology, and mechanistic studies work together to create the full picture of environmental effects on this malignancy. Newer approaches to risk-related evaluations may allow this field to move forward and more clearly delineate actionable environmental causes of this most common of cancers in women.
Topics: Breast Neoplasms; Environmental Exposure; Female; Humans; Research; United States
PubMed: 29328875
DOI: 10.1146/annurev-publhealth-040617-014101 -
Neurobiology of Disease Jan 2020This special issue will describe cutting-edge translational research on the development of safe and effective therapeutics for treating exposure to toxic chemical threat...
This special issue will describe cutting-edge translational research on the development of safe and effective therapeutics for treating exposure to toxic chemical threat agents that target the nervous system. These studies are supported by the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program. Chemical threats include chemical warfare agents, pesticides and other toxic chemicals whose primary mode of action is targeted within the nervous system. Depending on the dose, the effects of these toxic chemicals can be lethal or cause serious morbidity including neuropathology and neurological deficits. Current topics in research on organophosphorus pesticides and chemical warfare agents include developing alternatives to currently approve acetylcholinesterase reactivators, control of seizures that are refractory to benzodiazepine drugs, and treatments for serious morbidity caused by non-lethal exposures. There is also an effort to understand the mechanisms of toxicity and treatments for other neuro-active agents such as tetramine and hydrogen sulfide. A robust translational research effort on nerve agents is essential for being better prepared with an effective medical response capability during chemical emergencies.
Topics: Animals; Humans; Nerve Agents; Nervous System Diseases; Translational Research, Biomedical
PubMed: 30468862
DOI: 10.1016/j.nbd.2018.11.020 -
Reviews on Environmental Health Sep 2020Background Epidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and... (Review)
Review
Background Epidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and nutrients may result in additive, synergistic, antagonistic, or potentiating effects on neurological endpoints. Investigating the impact of environmentally-relevant chemical mixtures, including heavy metals and endocrine disrupting chemicals (EDCs), is more reflective of human exposures and may result in more refined environmental policies to protect the public. Objective In this review, we provide a summary of epidemiological studies that have analyzed chemical mixtures of heavy metals and EDCs and neurobehavior utilizing multi-chemical models, including frequentist and Bayesian methods. Content Studies investigating chemicals and neurobehavior have the opportunity to not only examine the impact of chemical mixtures, but they can also identify chemicals from a mixture that may play a key role in neurotoxicity, investigate interactive effects, estimate non-linear dose response, and identify potential windows of susceptibility. The examination of neurobehavioral domains is particularly challenging given that traits emerge and change over time and subclinical nuances of neurobehavior are often unrecognized. To date, only a handful of epidemiological studies examining neurodevelopment have utilized multi-pollutant models in the investigation of heavy metals and EDCs. However, these studies were successful in identifying contaminants of importance from the exposure mixtures. Summary and Outlook Investigators are encouraged to broaden their focus to include more environmentally relevant mixtures of chemicals using advanced statistical approaches, particularly to aid in identifying potential mechanisms underlying associations.
Topics: Animals; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Humans; Metals, Heavy; Mice; Nervous System Diseases; Rats
PubMed: 32598325
DOI: 10.1515/reveh-2020-0010 -
Current Opinion in Pediatrics Apr 2014Humans are routinely exposed to multiple chemicals simultaneously or sequentially. There is evidence that the toxicity of individual chemicals may depend on the presence... (Review)
Review
PURPOSE OF REVIEW
Humans are routinely exposed to multiple chemicals simultaneously or sequentially. There is evidence that the toxicity of individual chemicals may depend on the presence of other chemicals. Studies on chemical mixtures are limited, however, because of the lack of sufficient exposure data, limited statistical power, and difficulty in the interpretation of multidimensional interactions. This review summarizes the recent literature examining chemical mixtures and pediatric health outcomes, with an emphasis on metal mixtures.
RECENT FINDINGS
Several studies report significant interactions between metals in relation to pediatric health outcomes. Two prospective studies found interactive effects of early-life lead and manganese exposures on cognition. In two different cohorts, interactions between lead and cadmium exposures were reported on reproductive hormone levels and on neurodevelopment. Effects of lead exposure on impulsive behavior and cognition were modified by mercury exposure in studies from Canada and Denmark. However, there is little consistency related to exposure indicators and statistical approaches for evaluating interaction.
SUMMARY
Several studies suggest that metals interact to cause health effects that are different from exposure to each metal alone. Despite the nearly infinite number of possible chemical combinations, mixtures research represents real-life exposure scenarios and warrants more attention, particularly in the context of uniquely vulnerable children.
Topics: Arsenic; Cadmium; Child; Child Welfare; Child, Preschool; Congenital Abnormalities; Environmental Exposure; Environmental Pollutants; Female; Humans; Infant; Lead; Manganese; Metals; Population Surveillance; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Prospective Studies; Risk Factors
PubMed: 24535499
DOI: 10.1097/MOP.0000000000000067 -
Anais Da Academia Brasileira de Ciencias Dec 2007The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the... (Review)
Review
The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair--i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.
Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Humans; Neoplasms; Risk Factors
PubMed: 18066431
DOI: 10.1590/s0001-37652007000400004 -
ALTEX 2014Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not...
Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.
Topics: Animal Testing Alternatives; Animals; Chemical Safety; Computer Simulation; Green Chemistry Technology; Humans; Structure-Activity Relationship; Toxicity Tests; Toxicology
PubMed: 25061898
DOI: 10.14573/altex.1406181