ARSENIC, As

The order of decreasing toxicity (most to least) for arsenic is: arsines, inorganic arsenites, organic arsenoxides, inorganic arsenates, arsenorganics with As valence of +5, and metallic As.

Arsines can penetrate rubber and are well absorbed through the skin which will become vesicated and blistered during the exposure. Arsines combine with hemoglobin in RBCs, cause hemolysis and cell destruction. Chronic exposures to arsines can result in anemia. Myocardial failure due to oxygen deprivation can occur in severe cases.

Sources of arsenic include: contaminated foods (especially seafoods), water or medications.  Industrial sources are: ore smelting/refining/processing plants, galvanizing, etching and plating processes. Tailings from or river bottoms near gold mining areas (past or present) may contain arsenic. Insecticides, rodenticides and fungicides (Na-, K- arsenites, arsenates, also oxides are commercially available). Commercial arsenic products include: sodium arsenite, calcium arsenate, lead arsenate and "Paris green" (cupric acetoarsenite) a wood preservative.

70% of commercial chickens raised for meat in the U.S. are fed Roxarsone, a benzene arsenic compound, according to Science News.  There is concern that this deposits in the meat that humans consume and has become a source of arsenic.

Arsenic effects are multiple and complex in terms of biochemistry. The mitochondria of cells accumulate the element. The pyruvate dehydrogenase complex (catalyzes formation of acetyl coenzyme A from mitochondrial pyruvic acid) is inhibited by As⁺⁺⁺. Pyruvic acidosis may result; citric acid cycle function and formation of ATP are slowed.  The citric acid cycle itself is impaired at the alpha-ketoglutaric acid dehydrogenase step; formation of succinyl coenzyme A is impaired.  Both of these enzymatic steps require the active thiol, lipoic acid.  Arsenic readily combines with sulfhydryl (-SH) groups. Lipoic acid is

 

CH2(SH)-CH2,-CH(SH)-(CH2)4-COOH

 

Depending upon transport in various tissues, arsenic may react with any of the enzymes in the body that have sulfhydryl groups. Monoamine oxidase, which has eight cysteinyl residues with –SH groups is an example.  Monoamine Oxidase inhibitors are used for severe depression.  Other effects of arsenic include irritation of the skin and mucous membranes, chromosomal damage in lymphocytes and erythroblasts in bone marrow with leukopenia, and myocardial capillary damage.

 

Symptoms of arsenic exposure include:

1.                 Slight exposure may clear skin lesions such as acne.

2.                 Garlic-like breath occurs with fatigue, malaise, and nausea.  Skin and mucus membrane lesions may develop with eczema or allergic-type dermatitis, raindrop areas of lost skin color (hypopigmentation), hair loss, white marks on fingernails, thickening of the skin of the palms and soles (hyperkeratosis), “melanosis” of the eyelids, areolae of nipples, and neck), conjunctivitis, bronchitis, and gingivitis.

3.                 Excessive salivation, stomatitis, abdominal pain.

4.                 Jaundice, peripheral neuropathy, polyneuritis, hemolysis, anemia, leukopenia, cyanosis of the fingers, Raynoud’s Syndrome.  Chronic arsenic exposure has been associated with basal cel1 carcinomas (Harrison's Principles, ll^th ed, p. 850.)

5.                 Long term arsenic exposure may lead to the progression or acceleration of carotid artery atherosclerotic disease.

DIAGNOSTIC TESTING TO ASSESS ARSENIC STATUS

1. Blood chemistry analysis, CBC with cell differential.  Red cell arsenic levels are part of the several red cell mineral panels. Blood plasma or serum levels of arsenic do not correlate well with exposure or with cellular levels capable of causing disturbed physiology or pathologies.

2. Hair element analysis. Arsenic exceeding 7 ppm in hair is cause for concern.

3. Urinary arsenic in unchelated, non-glutathione-dosed individuals is expected to be below the levels tabulated below for optimal physiological functioning of -SH bearing enzymes and coenzymes.

 

Age Group (yrs)	<ppm	<mg/24 hr	<ug/hr
3-5	0.27	0.20	9
6-13	0.27	0.27	12
14-99	0.29	0.46	20
CONCERN	0.40	0.60	30

 

If high urinary As is found it is recommended that the test be repeated for confirmation with a new urine collection 4 to 5 days later. This is because urine As levels can and commonly do vary by a factor of 5 from day to day depending on diet.  Seafoods and some canned foods may contain variable and high As levels.

4. A reduced L-glutathione (GSH) provocation can be done using 300 mg of GSH orally, fid. A 24-hour urine collection skipping the first am urination and collecting for the next 24 hours including the first urination of the next am provides the urine specimen.  Levels of concern are the same as in the above table.

Symptoms consistent with arsenic excess include (garlic breath, dermatitis) together with elevated hair As provide strong evidence of toxicity. With symptoms and two urine analyses showing high arsenic, the evidence is irrefutable. Other confirming laboratory results would be:  elevated pyruvic acid in serum or plasma, elevated alpha-ketoglutaric acid in a plasma organic acid analysis, and hematuria.

ARSENIC DETOXIFICATION THERAPY DETOXICATION OF ARSENIC

Arsenic must be methylated using methyl donors such as SAMe, trimethylglycine, dimethylglycine, methionine, etc.  Some arsenic is bound to sulfur groups such as glutathione and excreted in the urine or bile.

1. Remove the individual from sources of arsenic. Treat for anemia if indicated.
2. Give sulfurated methyl groups and foods rich in sulfurated amino acids (garlic, eggs, beans)
3. Nutrients protective against the effects of arsenic include selenium, iodine, calcium, zinc, and vitamin C.  Supportive therapy with magnesium, B-vitamins, vitamin C, vitamin E, selenomethionine, lipoic acid is recommended. 
4. Drink adequate water (an adult's urine volume should be > 2 liters/day).
5. Do not give cysteine. Although it will readily combine with As, it will also move it around in body tissues and will not necessarily clear it from the body. 
6. Aggressive therapy for excess arsenic can employ sulfhydryl-group type conjugating agents.

 

Therapy should be continued until urinary arsenic levels are consistently below those stated above

REFERENCES ON ARSENIC:

 

Bibliography of texts dealing with arsenic exposure, toxokinetics, laboratory findings and treatments:

 

1. Carson B.L., H.V. Ellis and J.L. McCann Toxicology and Biological Monitoring of Metals in Humans, Lewis Publishers, Chelsea, MI, 1987, p. 27-33.
2. Tsalev D.L. and Z.K. Zaprianov Atomic Absorption Spectrometry in Occupational and Environmental Health Practice, Vol. I, CRC Press, Boca Raton, FL 1983, p. 87-93.
3. Clarkson T.W., et al., Eds. Biological Monitoring of Toxic Metals. Plenum Press, New York NY 1988, p. 309-315.
4. Harrison's Principles of Internal Medicine, various editions, McGraw Hill, New York, NY.
5. Science News, April 6, 2002; p 214