Arsenic is considered radioactive

Murderous and healing at the same time

arsenicby Harald Mückter, Munich

The classic poison murder is committed in the detective novel with arsenic. Despite its toxicity, the trace element is part of the metabolism of plants and animals. Various arsenic compounds have been used as drugs against sleeping sickness since the 19th century.

According to current knowledge, arsenic is not one of the essential trace elements for humans. Nevertheless, no one can avoid taking small doses, because it occurs everywhere in the environment - in organic compounds, in the air and in water. In rural areas, the arsenic concentration in the air is between 0.02 and 4 ng / m3 and in cities between 3 and 200 ng / m3. The daily intake of arsenic through food is between 12 and 60 µg worldwide. Fish and grain products in which the semimetal is organically bound or pentavalent have particularly high concentrations.

Groundwater contains around 1 to 2 µg / l arsenic, with regions with volcanic activity and ore mining in their history, such as the Black Forest, the Ore Mountains or the Eifel, regionally showing higher values ​​for groundwater and seepage water. Sometimes they are above 3 mg / l. The limit value recommended by the World Health Organization (WHO) for arsenic in drinking water of 10 µg / l has been complied with in Germany since 1997 and has been a legal requirement in the EU since 1998. For mineral water there are currently higher limit values ​​for arsenic (50 µg / l). Significant health effects from the daily intake of arsenic through food and drinking water alone are not to be expected in Germany.

In other regions of the world, however, the arsenic levels in drinking water are much higher, so that chronic exposure here can lead to diseases of the population. In India (West Bengal), Taiwan, Argentina, Nepal and Inner Mongolia in particular, arsenic concentrations of more than 3 mg / l were found in the water. More than 80 million people in these regions live from drinking water that sometimes significantly exceeds the limit of 50 µg of the element per liter.

A metabolic poison

Since arsenic is not an essential trace element, deficiency symptoms in humans are not yet known. Rather, its toxic properties are in the foreground: Most arsenic compounds are potent metabolic toxins. They intervene in numerous biochemical processes by blocking sulfhydryl groups (SH groups) of enzymes and other protein structures. As a result, they interfere with cellular energy metabolism, receptor-mediated transport processes, signal transduction and DNA repair processes, among other things.

The toxicity depends on the chemical substitution of the arsenic: For humans, halogeno- and oxo-compounds of the trivalent arsenic are more toxic than those of the highest oxidation level (pentavalent). Arsenic trioxide (arsenic) is particularly toxic, while organic compounds such as arsenic sugar, arsenobetaine and arsenocholine, which are mainly found in marine animals, but also in some plants, are less toxic. They are excreted unchanged from the human body via the kidneys within a few days. Many organisms produce methylated forms from the arsenic oxides arsenate and arsenite. These, too, are largely eliminated renally from the human body within a few days.

Symptoms of intoxication

Arsenic poisoning can be divided into acute and chronic. Even a dose of 60 to 170 mg of arsenic is fatal, depending on the age and constitution of the person. In acute poisoning, cerebral cramps and gastrointestinal complaints such as nausea, vomiting, diarrhea, colic and bleeding occur. The poisoning can lead to kidney or circulatory failure. While the symptoms of acute poisoning appear just a few hours after an overdose, the latency period until the manifestation of chronic symptoms can be up to 30 years, depending on the daily intake.

In the case of chronic poisoning, certain skin changes such as efflorescence, pigmentation disorders and hyperkeratoses, i.e. increased keratinization of the skin, occur. In regions with geogenic arsenic contamination of the drinking water, such hyperkeratoses and hyperpigmentation of the skin lead to severe disfigurement even in adolescents. A chronic intake of drinking water heavily contaminated with arsenic can also damage the capillaries, which in severe cases leads to the death of the affected extremities ("black foot disease"). Then there is often only the amputation of the diseased body parts. Furthermore, chronic exposure to arsenic can induce malignant tumors of the skin, lungs, liver and urinary bladder.

Diagnosis

Arsenic contamination is detected today by measuring the blood level and the daily excretion with the urine by means of atomic absorption or emission spectroscopy. In unexposed persons, the arsenic levels in the blood are between 5 and 15 µg / l. If marine animals and plant products contaminated with arsenic are consumed in abundance, the concentrations are higher and can be mistaken for an undesirable chronic exposure to arsenic. Only the exact specification of the arsenic helps here. The concentration in the urine of persons not occupationally exposed fluctuates between 5 and 20 µg / l, but can also exceed 1000 µg / l if food containing arsenic is consumed. Chronic exposure to arsenic is best diagnosed by analyzing parts of the body that contain keratin, such as hair or nails. As a rule of thumb, a tenfold increase in the arsenic concentration in drinking water doubles the arsenic content of the toenails in the long term. Due to the growth in length of hair and nails, a "time-resolved" analysis is even possible in favorable cases.

Until 1940, treatment of arsenic poisoning was only possible symptomatically. The development of the first antidote dimercaprol (BAL) by Sir Rudolph Peters ushered in a turning point after 1945. In the meantime, dimercaprol, which is rich in side effects, has been supplemented by the better tolerated derivatives DMPS (Unithiol, 1956) and DMSA (Succimer, 1959), so that at least three effective antidotes are available. Their role in chronic arsenic poisoning is, however, still controversial.

Arsenic as a remedy

Despite the known toxicity of arsenic compounds, arsenicals have a long history as medicinal products. According to travel reports by the Scottish missionary David Livingstone, a 1 percent solution of potassium arsenite was used as an antipyretic and as a remedy for sleeping sickness in Africa in 1887. It was also used in Germany as Fowler's solution until the 1960s, where it was indicated as a tonic for psoriasis treatment.

In 1905, Harold Wolferstan Thomas and Anton Breinl demonstrated that the arsenic preparation Atoxyl kills the pathogen sleeping sickness, the trypanosomes. Initially, the preparation was used in febrile conditions, although the recurring damage to the optic nerve and frequent relapses were a serious problem. Inspired by these observations, Paul Ehrlich tested over 600 substances containing arsenic until he introduced salvarsan in syphilis treatment in 1910. In 1918/19 Michael Heidelberger and Walter Jacobs developed tryparsamide, which was used in 1920 in what was then the Belgian Congo for the treatment of sleeping sickness. In a mass poisoning in 1930, 800 treated soldiers went blind because a lieutenant had doubled the dose on his own initiative. As a result, the use of tryparsamide in humans has been abandoned more and more.

In the 1940s and 1950s, Ernst Friedheim and his colleagues examined better-tolerated alternatives to trypanosomes and developed a new substance that he called melarsoprol. This combined the poor accessibility of basic melamine to the central nervous system with the trypanocidal effect of arsenic, which as an adduct with the then newly described arsenic antidote dimercaprol should be even better tolerated. In fact, melarsoprol has been able to assert itself in the treatment of sleeping sickness to this day, where it is now only used in advanced stages of the disease thanks to better alternatives, and even more rarely in the past few years due to the emergence of resistances.

For the treatment of humans, arsenic trioxide (arsenic) has also been approved in the USA for the antineoplastic chemotherapy of rare forms of acute promyelocytic leukemia since the end of 2000. It should induce the apoptosis of degenerate cells and thus lead to the elimination of malignant clones.

 

History of the white poison The name "arsenic" is derived from the Greek word "arsenikon", which means something like "male", but is also the Greek name for auripigment, a gold-shining arsenic sulfur mineral (As2S3) that aroused the curiosity of naturalists in ancient times . Arsenic is a semimetal that, with an abundance of 2.1 mg / kg, is one of the less common elements in the earth's crust. The toxicity of mixtures of substances containing arsenic was already known 2500 years ago. Dioskourides, personal physician at the court of Nero, described the effects of arsenic in the 1st century AD. Albertus Magnus is said to have produced the element arsenic around 1250 by reducing arsenic with coal. In 1638 Agricola recognized the arsenic-containing character of the "white poison", as arsenic trioxide was called, which was created during the thermal decomposition of arsenic-containing minerals and ores. But it was not until the last century that the mechanistic elucidation of the biological effects of arsenic began. During this time, arsenic compounds were used as pesticides, plant and wood preservatives. Arsenicals also gained a certain importance as a remedy, especially in the first half of the last century. Some of them are still approved today.

 

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