Arsenic (As)

As – Arsenic is found in igneous rock at 1.0 to 8.0 ppm; shale at 13.0 ppm; sandstone and limestone at 1.0 ppm; fresh water at 0.0004 ppm; sea water at 0.003ppm; soils at 6.0 *ppm (Argentina and New Zealand have toxic high arsenic soils in some regions); marine plants 30.O ppm; land plants 0.2 ppm; marine animals 0.005 to 0.3ppm (accumulated by coelenterates, mollusca and crustaceans; land animals < 0.2 ppm (concentrates in hair and nails). essential for survivability of newborn and neonatal growth.

Arsenic metabolism is affected by tissue and blood levels of zinc, selenium, arginine, choline, methionine, taurine and guaniacetic acid, all of which affect methyl-group metabolism and polyamine synthesis which is the site of arsenic function in human physiology.

Arsenic promotes the growth rate of chicks at 90 to 120 ppms. The rate of growth and metamorphosis of tadpoles is enhanced by the presence of arsenic.

The French Academy first identified arsenic in dead human bodies in 1834. Arsenic normally appears in female human blood at 0.64 ppm, it rises to 0.93 PPM during menstruation and 2.20 ppm during months five and six of pregnancy.

All marine life is richer in tissue arsenic levels than in terrestrial animals:

Sea Fish (vertebrates)
0. 1 to 3.0 ug/Kg
Prawns and clams
3.0 to 174 ug/Kg

Shrimp (October)

152 to 172 ug/Kg
Shrimp (May/June)
21 to 5 1 ug/Kg

Eighteen percent of dietary As2O3 was stored in rat liver whereas only 0.7 percent of shrimp tissue arsenic was stored in rat livers (65 times greater toxicity potential from metallic arsenic than from organically bound or water-soluble arsenic).

Arsenic in combination with choline prevents 100 percent of perosis (“slipped tendon) in chickens and poultry. Perosis in birds results in a “carpal tunnel,” “TMJ” and repetitive motion” type degenerations.

Arsenic occurs in the trivalent and pentavalent forms in foods, water and the environment, and is widely distributed geologically as a component of about 245 different minerals. Unweathered soils may contain 0.1-40 mg of arsenic/kg; the amount of arsenic in the biomass of the earth has been estimated at 30 million tons. Industrial production is approximately 50 000 tons/ year; the main uses are in agricultural chemicals, such as pesticides, herbicides, cotton desiccants and wood preservatives, and as additives to animal feeds, as well as in pharmaceutical products, all of which have a direct impact on the environment.

Although arsenic compounds are best known historically for their toxicity, their pharmacological action is also well documented. Less well documented is the increasing evidence of the essential function fulfilled by very low dietary arsenic intakes in four species of experimental animals. The biological effects of arsenic depend markedly on the chemical form in which the element is presented, inorganic compounds being more toxic than most organic ones. Most living organisms convert the former by methylation into a large variety of less toxic organoarsenic compounds, which are then excreted. Cacodylic acid and methanearsonic acid are typical urinary excretion products in humans, whereas organic compounds containing arsenobetaine, dimethylarsenoribosides or arsenolipids are metabolites of aquatic organism. These compounds contribute substantial amounts of arsenic to human diets containing fish and other seafood.

Arsenic Toxicity

The major cause of concern in connection with arsenic is the potential toxicity of its compounds to humans. Acute poisoning, characterized by nausea, vomiting, diarrhea and severe abdominal pain, is relatively rare. Chronic toxicity, on the other hand, is known to occur as a result of exposure to natural sources in some countries, or from accidental contamination of foods. Consumption of water containing 0.8 mg of arsenic/liter over extended periods of time and a dietary intake of approximately 3 mg or arsenic/day for 2-3 weeks have been identified as causes of arsenic intoxication. However, the toxicity of arsenic compounds depends so greatly on their chemical nature that general estimates of safe intakes cannot be made with confidence.

A substantial number of organic arsenicals, most of them derivatives of phenylarsonic acid, are used as feed additives in poultry and swine production. At dietary concentrations in the range of a few g/kg they increase weight gain, possibly by protecting against enteric diseases and by increasing the efficiency of feed utilization for reasons as yet unknown. Whether treatment with arsenicals such as Fowler’s solution (potassium arsenite solution) or the consumption of arsenic produces any beneficial effects is difficult to prove. On the other hand, the antisyphilitic activity of arsphenamine, much used before the advent of modern antibiotics, is well documented.

NOTE: Readers may want to visit the site linked below to gain some information on the Bengal arsenic crisis (where an estimated 24 million in Bangladesh and several million more in West Bengal were provided with tubewell water where it was later discovered to have Arsenic concentrations in excess of 50 ug/l, in some cases into the 1000’s ug/l.

Please visit the West Bengal & Bangladesh Arsenic Crisis Info Centre for more information.

Benefits of Organic Arsenic

The beneficial effects of substantially lower intakes of arsenic have been demonstrated in three independent studies involving four animal species where basic diets provided less than lug of arsenic/gm. Rats, chickens, minipigs and goats raised on low-arsenic diets (< 35 ng of arsenic/g) exhibited reduced growth rates during early life. In goats, the most closely investigated species, reproductive performance is also impaired, as a result of decreased conception rates, increased abortion frequency, greatly increased maternal mortality (especially during lactation) and reduced viability of newborn kids. Cardiomyopathy, associated with a derangement of cardiac mitochondrial structure, may be the cause. Several biochemical changes accompanying the signs of arsenic deficiency have been described, but the fundamental mode and site of action of the element are not yet known.

Sources and Intake

Most foods and feeds of terrestrial origin contain less than 1 ug of arsenic/gm dry weight; the levels present in those of marine origin are substantially higher, ranging up to 80 mcg/g. Dietary intake is therefore greatly influenced by the amount of seafood in the diet. Based on recent surveys in several countries, the daily arsenic intake of adults is estimated to be < 200 mcg, and often below 100 mcg/day. It is unlikely that the arsenic intake from uncontaminated diets poses a risk of toxicity. Extrapolation from animal experiments suggests that human adult intakes in the range 12-25 mcg/day are probably adequate to meet any possible requirement.

In contrast to dietary intake, contaminated drinking water can be a significant source of arsenic at near toxic and toxic levels. The arsenic concentration in the oceans and in uncontaminated rivers, lakes and groundwaters varies from non-detectable levels to a few mcg/l. Much higher concentrations, at the mg/l level, are present in hot springs and waters in contact with natural arsenic deposits or exposed to industrial contamination. The consumption of such waters is associated with subacute toxicity and an increased risk of cancer of the skin and possibly of other sites.

Because inorganic arsenic is known to be carcinogenic in humans, there is understandable concern to limit human exposure to excessive environmental concentrations of the element. However, the metabolism and effects of arsenic can differ markedly, depending on the chemical nature of the arsenic source; these differences partly account for the provisional nature of the recommended safe exposure limit for adults of 15 mcg/kg of body weight per week. Since experimental arsenic deficiency has been produced in four species, the element may have an essential function. If a human requirement for arsenic does exist, it is probably close to 20 mcg/day for adults and is easily met by most diets.

Arsenic: A Sulfur amino acid metabolism effector?

Other reviews have described in detail the signs of arsenic deprivation in four animal species: chick, goat, rat, and miniature pig. In the goat, rat, and miniature pig the most consistent signs of arsenic deprivation have been depressed growth and abnormal reproduction characterized by impaired fertility and elevated perinatal mortality. Other signs of deprivation described for goats include depressed serum triglycerides and death during lactation. Myocardial damage, which in advanced stages included ruptured mitochondria, has also been found in arsenic-deficient lactating goats. Other responses to arsenic deprivation have been described. However, these responses have varied in nature and severity with variation in the dietary concentrations of a variety of substances including zinc, arginine, choline, methionine, and guanidoacetic acid. These substances are interrelated because they are effectors of methionine metabolism.

Additional findings have appeared recently which suggest that arsenic has a biological role that affects formation of various metabolites from methionine, including taurine and polyamines. For example, arsenic deprivation depressed the taurine concentration in plasma of hamsters. It also has been reported that arsenic deprivation depressed the concentrations of putrescine, spermidine, and spermine, and the activity of S-adenosylmethionine decarboxylase in liver of rats fed diets containing marginal amounts of methionine. The transfer of an aminopropyl group from decarboxylated S-adenosylmethionine to putrescine and spermidine forms spermidine and spermine, respectively.

Some of the signs of arsenic deprivation described are harmonious with the suggestion that arsenic influences taurine function or effects. The myocardium has a very high taurine content, which changes in several pathophysiological conditions affecting the heart. The administration of taurine to patients suffering from congestive heart failure alleviated their physical signs and symptoms of this disorder. Cardiomyopathy associated with low plasma taurine has been reported to occur in cats fed a taurine-deficient diet. Taurine also apparently plays an important role in stabilization of cell membranes. Perhaps the ruptured mitochondrial membranes and damage found in arsenic-deprived goat hearts involved changes in myocardial taurine. A major source of taurine for growing animals is milk; taurine deficiency results in reduced growth and survival in kittens. An important physiologic function of taurine is bile acid conjugation necessary for lipid solubilization and absorption. These taurine findings could be related to the arsenic deprivation signs of perinatal mortality, depressed perinatal growth, and depressed serum triglycerides.

Perhaps some biochemical and physiologic changes considered to be toxicologic manifestations of arsenic have nutritional significance. If so, additional support for the suggestion that arsenic affects polyamine function and effects can be found. Polyamines have an integral role in controlling cell proliferation and growth. Chronic high intakes of arsenic have been associated with hyperkeratosis, hyperpigmentation, and the skin cancers, squamous cell carcinoma and basal cell carcinoma. Often the skin affected does not contain elevated amounts of arsenic. In experimental animals exposed to physical or chemical stimuli (e.g., phorbal esters) that result in benign hyperproliferation or transformation of epidermal cells to produce skin cancer, the changes are almost universally accompanied by an early stimulation of polyamine synthesis. Inhibition of polyamine synthesis has been helpful in controlling cellular hyperproliferation in human skin disorders.

Although arsenic might affect gene expression through the polyamines, another possibility exists, that is, through histone methylation. It is believed the reaction by which inorganic arsenic is methylated by S-adenosylmethlonine exists mainly to facilitate the movement of arsenic through and out of the body in a nontoxic form, to detoxify inorganic arsenic. However, because nutrients that affect methyl group metabolism (e.g., guanidoacetic acid) affect the response to arsenic deprivation, arsenic may have an essential role in the labile methyl metabolism involving methionine. Further support for this suggestion can be gained from the finding that arsenite can induce the isolated cell production of certain proteins known as heat shock or stress proteins. The control of production of these proteins in response to arsenite apparently is at the gene level. Some studies have related the control to changes in the methylation of core histones. Also, arsenite induces small stress proteins that can be detected by methionine incorporation; these proteins are not induced by heat shock.

Any possible nutritional requirement by humans can only be estimated by using data from animal studies. The arsenic requirement for growing chicks and rats has been suggested to be near 25 ng/g diet. A possible human arsenic requirement is 12 mcg/day. The reported arsenic content of diets from various parts of the world indicates that the average daily intake of arsenic is in the range of 12-40 mcg. Fish, grain and cereal products contribute the most arsenic to the diet.

Arsenic Abstracts

Uthus EO. Arsenic essentiality and factors affecting its importance. In: Arsenic Exposure and Health, Chappell WR, Abernathy CO, and Cothern CR, eds. Northwood: Science and Technology Letters, 199-208, 1994.

For the most part, the body can adapt to a variety of dietary insults making the occurrence of simple, or uncomplicated, deficiencies of trace or ultratrace elements in humans relatively uncommon. Certain situations (for example, pregnancy, lactation, certain diseases) can confound the deficiency, making it of practical concern. Initial studies on arsenic deprivation in animals used pregnancy and lactation to exacerbate the deficiency. These studies showed that arsenic, in very small quantities, may be of nutritional importance. Further studies, that used various dietary stresses have indicated that arsenic may have a physiologic role in the metabolism of the sulfur-containing amino acids, methionine and cysteine. Amino acids are the building blocks of proteins. Also, a recent study with patients on hemodialysis indicates that maintaining a certain, but very small, amount of arsenic in blood may be important. The studies of arsenic essentiality have used patients on hemodialysis treatment, or animal studies using pregnancy, lactation or specific nutritional stressors, to identify biochemical signs of arsenic deficiency. The need for metabolic or dietary stressors to produce or see deficiencies with other trace or ultratrace elements is not uncommon. The studies indicate that arsenic may be of nutritional importance to humans and animals.

Selected reported deficiency signs

Depressed growth and abnormal reproduction characterized by impaired fertility and elevated perinatal mortality in goats and rats; depressed triglycerides, myocardial damage and death during lactation in goats; depressed taurine (an amino acid) concentration in plasma of hamsters; depressed concentrations of putrescine, spermidine and spermine in livers of rats.

Possible function

Arsenic plays a role that affects the conversion of methionine (an amino acid) to its metabolites taurine (another amino acid), labile methyl and the polyamines; involved in the methylation of various biomolecules (e.g., histones).

Dietary need and sources

Human requirements most likely near 12mcg per day; rich food sources can be fish, grain and cereal products.

Magnes Trace Elem 1990;9(4):227-232

Effects of arsenic deprivation in hamsters.
Uthus, EO

United States Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks.

An experiment was conducted to ascertain the effects of arsenic deprivation in hamsters. Male weanling Golden Syrian hamsters were fed a casein-corn-based diet containing approximately 12 ng arsenic/g. Controls were fed 1 microgram arsenic/g of diet, as Na2HAsO4.7 H2O. After 6 weeks arsenic deprivation elevated heart weight/body weight ratio and the concentration of liver zinc and decreased the concentrations of the plasma amino acids alanine, glycine, phenylalanine and taurine. Although no biological role has been found for arsenic, the findings indicate that the hamster is a suitable animal for arsenic deprivation studies and support the hypothesis that arsenic may have a physiological role that influences methionine/methyl metabolism.

Lead, Cadmium, and Arsenic

In the mid-1970s, Schwarz and others directed their attention to the study of the nutritional roles of lead, cadmium, and arsenic, three elements that until then had always been regarded only as poisonous. Schwarz could still report initial evidence for the biological essentiality of all three of them (Schwarz, 1977), but his death prevented completion of these studies. Although not all criteria of essentiality of Cd and Pb have been met, his observations were independently confirmed and extended by Anke et al. (1977) and Kirchgessner and Reichlmayr-Lais (1981). With arsenic, positive growth responses in young rats were observed (Schwarz, 1977), but at that time convincing evidence for the essentiality of arsenic had already been produced by two other groups (Anke et al., 1976; Nielsen et al., 1975). Nielsen’s arsenic-deficient rats exhibited rough fur, increased osmotic fragility of the erythrocytes, and abnormally enlarged spleens containing excessive amounts of iron. Anke’s As-deficient goats and pigs showed decreased fertility, low birth rates, and retarded growth. Lactating arsenic-deficient goats were also observed to die suddenly with myocardial damage. The discovery of the essentiality of arsenic and of the possible essentialities of lead and cadmium should of course not detract from the established fact that higher concentrations of these elements pose definite health hazards.

Arsenic Summary

Knowledge of the biochemistry of arsenic is important not only because arsenicals can have toxic and pharmacologic actions, but also because arsenic has a physiologic role in vivo. Arsenic deprivation signs have been described for the chick, goat, minipig, and rat. For the mammals, these signs include depressed growth, impaired reproduction characterized by elevated perinatal mortality and depressed fertility, and sudden death (in goats) during lactation from myocardial damage. For the rat and chick, more than 25 ng of arsenic/g of diet apparently is required to prevent deficiency.

Arsenic is present in all living material. The form of arsenic most important in the biochemistry, nutrition, and physiology of living organisms is not known. However, organic arsenic compounds that contain methyl groups, and are closely related to some phospholipids, are most likely to be found of primary importance. Evidence to date indicates that the absorption, retention, and excretion of arsenic involve methylated compounds. In marine organisms, these compounds include trimethylarsoniumlactate, arsenobetaine and arsenocholine. In some bacteria, and in mammals studied to date, these compounds include dimethylarsinic acid and methylarsonic acid. Arsenic compounds other than those of the methylated form that are of interest in biochemistry are those formed when arsenate binds to biological molecules to form arsenate esters. Because arsenylated compounds may be the form of arsenic that performs an essential function they should not be ignored.

Arsenic may be essential for humans

To date no specific biological function of arsenic has been found. Recent findings suggest that arsenic has a function that influences arginine and zinc metabolism in mammals. Arsenic may do this through a function in some enzyme system(s) because arsenic can either activate or inhibit enzymes in vitro. Another possibility is that arsenic has a structural role as part of a membrane phospholipid.

Although arsenic has been synonymous with poison for centuries, and a number of reports have associated arsenic with some forms of cancer, it is actually much less toxic than selenium, a trace element with a well-established nutritional value. Toxic quantities of arsenic generally are measured in milligrams and the ratio of the toxic to nutritional dose for rats apparently is near 1250. Thus any beliefs that any form or amount of arsenic is unnecessary, toxic, or carcinogenic are unrealistic and of concern. The findings described in the preceding show that there are safe and, most likely, necessary levels of arsenic intakes that would permit optimal health for animals and humans throughout a lifetime.