RE TECH are exported all over the world and different industries with quality first. Our belief is to provide our customers with more and better high value-added products. Let's create a better future together.
Abstract
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
Keywords:
arsenic, cancer, exposure
The word &#;arsenic&#; elicits a fearful response in most people. This is because arsenic has a long history of being a poison, both intentional and unintentional, to humans. However, most laymen do not know or understand that we are constantly exposed to arsenic because it is naturally present in the environment, is used in commercial products, and has medical applications. Although most typical environmental exposures to arsenic do not pose a health risk, several areas of the world contain arsenic from natural or anthropogenic sources at levels that create a toxicological concern. Many of these areas have been identified, and efforts are being made to either remediate these areas or limit access to them.
Arsenic is the number one substance in the most recent (ATSDR, a) Comprehensive, Environmental, Response, Compensation and Liability Act (CERCLA) Priority List of Hazardous Substances published by the Agency for Toxic Substances and Disease Registry (ATSDR). This list is comprised of substances found at hazardous waste sites on the National Priorities List. The substances are ranked on frequency or occurrence, toxicity, and potential for human exposure.
An understanding of the chemistry of arsenic is needed to appreciate the toxicology of this metalloid, which shares properties of metals and nonmetals. (A metal has luster, conducts heat and electricity, and is malleable and ductile. Elemental arsenic tends to be nonductile.) In the environment, arsenic is found in inorganic and organic forms and in different valence or oxidation states. The valence states of arsenic of environmental interest are the trivalent (III) and pentavalent (V) states. Elemental arsenic has a valence state of (0). Arsine and arsenides have a valence of (&#;III). In this review, we will be focused on the arsenicals in the trivalent and pentavalent states that are found in the environment and to which humans are exposed. A list of relevant environmental arsenicals is shown in . The structure of some of these arsenicals is shown in .
TABLE 1
Trivalent oxidation statePentavalent oxidation stateArseniteArsenateArsenic trioxideArsenic pentoxideMonomethylarsonous acidMonomethylarsonic acidDimethylarsinous acidDimethylarsinic acidTrimethylarsine oxideArsanilic acidArsenobetaineOpen in a separate window
Open in a separate window
The most toxicologically potent arsenic compounds are in the trivalent oxidation state. This has to do with their reactivity with sulfur containing compounds and generation of reactive oxygen species (ROS). However, humans are exposed to both trivalent and pentavalent arsenicals. In this review, we will discuss in a historical context the exposure of these compounds, how we have learned that the metabolism of arsenic is a critical determinant of its toxic effects, and potential modes of action (MOA), animal carcinogenicity, and the epidemiology of this metalloid. highlights some of the historical aspects of arsenic over the past 250 years.
TABLE 2
Fowler&#;s solution (1% potassium arsenite)Marsh Test for detection of arsenic developedDimethylarsinic acid detected in the environmentParis green (copper acetoarsenite) used as insecticide in United StatesHutchison proposes arsenic is a human skin carcinogenSalvarsan used as a chemotherapeutic agentsBritish antilewisite is developedU.S. arsenic drinking water interim standard set at 50 μg/lTseng et al. publish findings on prevalence of skin cancer in an arsenic-exposed Taiwanese populationEPA adopts drinking water interim standard at 50 μg/lWHO recommends drinking water standard of 10 μg/lDimethylarsinic acid a tumor promoter in four rat organsDimethylarsinic acid a complete carcinogen in rat urinary bladderFDA approves arsenic trioxide for leukemia chemotherapyEPA lowers U.S. arsenic drinking water standard to 10 μg/l (ruling delayed to )Inorganic arsenic a complete carcinogen in adult mice after transplacental exposureArsenic (+3 oxidation state) methyltransferase isolated in rat liver cytosolInorganic arsenic a complete carcinogen in adult mice after whole life exposureOpen in a separate window
Arsenic as an Intentional Homicidal and Suicidal Poison
Arsenic is a naturally occurring element that an individual typically encounters every day in food, water, soil, and air. While understanding how environmental exposures may affect human health, especially at low levels, is currently an active area of research, humans have known on some level about the toxicity of arsenic for centuries.
In the Middle Ages, arsenic gained notoriety as an effective homicidal and suicidal agent, both because of the frequency of its use and because of its involvement in many high-profile murders. In fact, arsenic is often referred to as the &#;king of poisons&#; and the &#;poison of kings&#; because of its potency and the discreetness, by which it could be administered, particularly with the intent of removing members of the ruling class during the Middle Ages and Renaissance (Vahidnia et al., ). For example, it is well documented that arsenic was among the poisons used by the Medici and Borgia families to eradicate rivals (Cullen, ). Arsenic continued to enjoy its reputation as a high-profile poison and was implicated in several other prominent murder cases, most famously in the death of Napoleon Bonaparte in , which some conspiracy theorists claim was a political assassination (Cullen, ).
Are you interested in learning more about Industrial Arsenic Furnace Factory? Contact us today to secure an expert consultation!
Up until the mid-s, arsenic remained a popular poison for several reasons. Arsenic was readily available and because it is odorless and tasteless, it was undetectable in food or beverages (Bartrip, ). The most visible symptoms of acute arsenic poisoning&#;nausea, vomiting, diarrhea, and abdominal pain&#;could be easily confused with other common diseases at the time (e.g., cholera and pneumonia) (ATSDR, b). Also, importantly, for a long time, there was no reliable analytical method for detecting, much less measuring, arsenic in tissue or other media, although early tests for arsenic were introduced in the mid-s. Interestingly, in the first trial ever recorded to present forensic evidence, a woman was sentenced to death because a white power recovered by a servant was &#;proven&#; to be arsenic, based on appearance, texture, behavior in water, and garlic-like odor when burned (Caudill, ; Cullen, ). The detection of arsenic took a leap forward in when James Marsh decided to investigate analytical methods to provide juries with more reliable evidence of &#;visible arsenic&#; (Cullen, ). His test method was first used in the trial of Marie LaFarge in France in , in which Mme. LaFarge was charged with poisoning her husband with arsenic-laden cakes (Cullen, ). Generally, the tests involved mixing the sample of interest with zinc and acid and heating the vessel with a flame, which would cause a silvery substance to accumulate on the glass vessel; this was considered diagnostic for arsenic in amounts as low as 0.02 mg (Marsh, ; Newton, ). Although this method would be considered primitive by today's standards, the Marsh test represented a turning point in arsenic analytics and the beginning of the end of undetected arsenic poisonings.
Although stories of murder by arsenic appeal to the morbid interests of the public, these murders provided important insights that advanced the knowledge of arsenic toxicology. For example, information on the acute effects of arsenic and the target organs involved was obtained by studying poisonings. Importantly, these cases also precipitated the development of analytical methods for different media, including biological samples, which eventually led to an increased understanding of metabolism of arsenic. Due to improved understanding of arsenic measurement, one cannot readily &#;get away with murder&#; by using arsenic anymore. Nonetheless, incidents do still occur. As recently as , arsenic poisoning made headlines when arsenic was detected in coffee served at a church meeting in Maine (Maine Rural Health, ; Zernike, ).
Arsenic as a Pigment and Use in Other Products
Arsenic&#;s use as a pigment (e.g., Paris Green or copper acetoarsenite) in the s was suspected as a major source of unintentional arsenic poisonings. Although the arsenic-based pigment was used in many consumer products (e.g., toys, candles, and fabric), its use in wallpaper was particularly linked to widespread sickness and death during this period (Scheindlin, ; Wood, ). Concerns associated with the use of wallpaper containing arsenic-based pigment were reported as early as , and the theory was eventually proposed that illnesses from wallpaper were related to the biotransformation of the arsenic compounds by mold to a toxic arsenic gas (Gosio gas) (Cullen and Bentley, ). This theory gained momentum, and in , Bartolomeo Gosio, an Italian physician, demonstrated that arsenic could be volatilized from arsenic-containing compounds, including Paris Green (Buck and Stedman, ; Cullen and Bentley, ). Although it became widely accepted at the time that arsenic gas from the wallpaper was responsible for the deaths and illnesses, this notion has been challenged recently by scientists who believe that there were insufficient quantities of the gas generated (now known to be trimethylarsine) to cause the reported effects; and possibly the mold, itself, was the responsible agent (Cullen and Bentley, ). Regardless of the toxicity of the wallpaper, the work conducted by Gosio and later by Frederick Challenger (in the late s), laid the groundwork for today&#;s understanding of arsenic metabolism, namely that the metabolism of arsenic involves sequential reduction and oxidative methylation steps (Cullen and Bentley, ).
Although arsenic use has been phased out of pigment products, it is still used in the production of glass and semiconductors (ATSDR, b).
Summary and Looking Forward
The knowledge base of the exposure and toxicological effects of arsenic has expanded greatly, particularly in the past 10&#;20 years. We know that exposure to arsenic for most people is an everyday occurrence because it is a natural component of the environment. The exposure pathways of arsenic to most people are dietary and drinking water and these exposures occur at relatively low levels. However, there are areas of the world, such as India, Bangladesh, and others, where the levels of arsenic in drinking water are naturally excessive, which has led to toxic manifestations in these populations. The effects of arsenic in drinking water on the U.S. population are less clear, which may be due to a lower arsenic exposure than in other areas of the world such as Bangladesh. Data from Karagas et al. (, ) has suggested, especially among smokers, an increased risk of bladder and skin cancer is associated with toenail arsenic.
Other types of exposure can come from soil contaminated with arsenic, from its occupational use as a pesticide or a by-product of metal ore smelting, from its use as a chemotherapeutic agent, and what interests many people, but occurs rarely, as a homicidal agent. With increases in analytical technology, what most likely will occur is the discovery of presently unknown forms of arsenic (e.g., arsenolipids) that we are exposed to, particularly in our diet.
The metabolic pathway of arsenic is now more clearly but not exactly defined. The discovery of arsenic (+3 oxidation state) methyltransferase has been a major breakthrough, particularly with the findings that there are polymorphisms in this enzyme. Several of these polymorphisms are associated with the toxic effects that develop from exposure to arsenic. Experimental use of the As3mt knockout mouse in the investigation of the metabolism and toxicity of arsenic may provide new knowledge. Finally, elucidation of the pathway of formation of the thiolated arsenic metabolites (e.g., dimethyldithioarsinic acid), some of which are toxicologically potent in vitro, will aid in the understanding of the toxicology of arsenic.
We know that arsenic causes acute and chronic dose-dependent effects, in many organ systems. A major unknown is the mode of action for the toxic effects of arsenic. Certainly, metabolism of arsenic has a role in this effect. However, if one or several metabolites are the putative toxic species is not known. Many MOA have been studied including oxidative stress, genotoxicity, altered DNA methylation, and others. Several of these MOA may be interrelated. With the advent of the &#;omics&#; age, toxic pathways of arsenic may soon be elucidated. Other recent advances are the development of an animal (mouse) model for arsenic carcinogenicity following transplacental and whole-life exposure to arsenic and findings in mice that arsenic may impact stem cell population dynamics, which ultimately lead to transformed cells (Tokar et al., b). Also, there is important work in animal models that support a role for cytotoxicity and regenerative hyperplasia in the carcinogenic MOA for DMAsV.
More research is still needed to understand arsenic exposure, metabolism, effects, and MOA for cancer. Nevertheless, with recent findings and advances in technology, many of the unanswered questions regarding the toxicology of arsenic may soon be answered. This knowledge will lead to better protection of populations at risk from arsenic-related illnesses.
FUNDING
National Institute of Environmental Health Sciences (RO1ES;, P30Es to Y.C.); Intramural resources at U.S. EPA (to M.F.H. and D.J.T.).
Acknowledgments
We would like to thank Anna Engel of Gradient with assistance in researching the historical uses of arsenic. We also thank Drs Kirk Kitchin, Jane Ellen Simmons, and Erik Tokar for their helpful comments on an earlier version of this manuscript. Gradient, where B.D.B. and A.S.L. work, has conducted risk analyses for arsenic for a number of private and public sector clients. B.D.B. has been an expert in litigation matters involving arsenic. However, Gradient received no funding for preparation of this manuscript and the opinions are solely those of the author's.
For more information, please visit refining furnace supplier.
Comments
Please Join Us to post.
0