<<

Toxic Element Clearance Profile Ratio to Creatinine

JANE Order Number: DOE

Toxic Elements Sulfur esults in g g reatinine esults in g g reatinine le ent e eren e ange TMP e eren e le ent e eren e ange e eren e ange ange

Creatinine Concentration

Collection Information

TMPL Tentative Ma i u Per issi le i it

Tin To i ology Tungsten T e Basi S ien e o Poisons

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient: JANE DOE Page 2

Commentary

Commentary is provided to the practitioner for educational purposes, and should not be interpreted as diagnostic or treatment recommendations. Diagnosis and treatment decisions are the responsibility of the practitioner.

Reference Range Information: Elemental reference ranges were developed from a healthy population under non-provoked/non-challenged conditions. Provocation with challenge substances is expected to raise the urine level of some elements to varying degrees, often into the cautionary or TMPL range. The degree of elevation is dependent upon the element level present in the individual and the binding affinities of the challenge substance.

Urine creatinine concentration is below the reference range. This may be due to increased fluid intake, a low protein diet, low body weight, or low levels of physical activity. Conditions such as diuretic use, dietary deficiencies of precursor amino acids (arginine, glycine, or methionine), malnutrition, or hypothyroidism may also lower creatinine levels. Measurement of serum creatinine or a creatinine clearance test can help determine if there are changes in renal function.

Lead is above the reference range. 75% to 80% of absorbed lead is typically excreted via urine, 15 to 20% via bile, and the remainder via sweat, hair and nails. In non-provoked urine, lead levels can fluctuate according to variable dietary and physiological factors, and the level does not necessarily reflect body burden. Provoked levels, however, can be indicative of excess lead in body tissues. It is notable that for children (compared with adults), lead can be more toxic, with detrimental effects occurring at much lower levels. Furthermore, toxicity of lead can be significantly increased synergistically by the presence of either or cadmium.

Most lead uptake occurs via ingestion of contaminated food or water. Inhalation of lead dusts and transdermal absorption of organic lead salts are other modes of uptake. While temporarily carried in the bloodstream, lead is at least 90% bound to erythrocytes, however, with chronic low-level or long-ago exposure, only 2% or less of total body lead remains in the blood. Lead primarily deposits and accumulates in the aorta, liver, kidneys, adrenal and thyroid glands, bones and teeth. This element interferes with membrane functions, bonds to sulfhydryl (-SH), , hydroxyl and amino sites on proteins and enzyme cofactors, and interferes with heme synthesis, transport, erythrocyte life span, and hepatic cytochrome P-450 functions. Other deleterious effects include: reduced vitamin D synthesis, slowed nerve conduction, peripheral neuropathy, hypertension (adults) and loss of IQ and developmental disorders (children). Anemia, neuropathies and encephalopathy are end-stage conditions of severe lead excess.

Although historic uses of lead (housepaint, anti-knock gasoline additives, and soldered joints in water systems) have been discontinued, old building materials, paint chips, plumbing and the environment may contain residual amounts from these sources. Other sources include batteries in cars, trucks, boats, and power backup systems, art supplies, colored glass kits, bullets, fishing sinkers, balance weights, radiation shields, bearing alloys, babbitt , some ceramic glazes or pigments, and sewage sludge. Some cities that have not replaced old water mains may have variable amounts of lead in the drinking water.

Mercury is measured to be elevated. In body tissues, mercury behaves differently in different tissues, depending on its chemical form, and interchange between forms can occur in vivo. For elemental and inorganic mercury, biliary excretion predominates with low-level toxicity, but urinary excretion increases and is favored as the degree of exposure and burden increases. For organic mercury (methyl, ethyl, alkyl), bile accounts for about 90% of excretion and urine accounts for about 10%. Significant day-to-day and diurnal variations are typically observed. Urinary excretion of mercury is notably increased following administration of chelating or detoxifying agents (DMSA, DMPS);

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient:JANE DOE Page 3

Commentary

intravenous administration of EDTA results in relatively minor urinary increases. The Genova Diagnostic Inc. laboratory procedure measures total urine mercury, regardless of chemical form, and the procedure is not hindered by tightly-bound sulfhydryl-mercury that might be unavailable (and unmeasured) by the old standard procedure ("-vapor atomic absorption").

There is great variability in individual tolerances to mercury. In some individuals, relatively low levels can cause immune dysregulation. Lymphocyte inhibition and dysfunction is reported, immunosupression can occur, and autoimmune conditions are documented in animals. At the cellular level, mercury can induce cytotoxicity, oxidative stress (via loss of glutathione function), and increased secretion of beta-amyloid in neuronal cells, linking it to Alzheimer's disease. Outside cells, mercury can bind to and strongly inhibit a cell surface-bound protein called dipeptidylpeptidase IV, CD26, and adenosine deaminase binding protein. This one protein is responsible for digestion of proline-containing dietary peptides, T-cell activation, and the metabolism of adenosine. Inside cells, mercury binds to lipoic acid, glutathione, coenzyme A and cysteinyl sites, and it can impair pyruvate metabolism and citric acid (Kreb's) cycle function, leading to impaired energy production. Chronic mercury exposure may produce increased excitability and tremor, memory loss, insomnia, lassitude, anorexia and weight loss, gingivitis and stomatitis. Young children may exhibit "pink disease" (acrodynia), commonly featuring rash, photophobia, increased perspiration and salivation. Acute mercury vapor exposure may inflame the bronchial tubes and cause pneumonitis. Irreversible neurologic damage is reported in acute mercury toxicity. Inorganic mercury concentrates mostly in kidneys, while organic (methyl) mercury has high affinity for the posterior cortex of the brain.

Mercury sources have increased in the environment, resulting in increased amounts in soils, sediments and bodies of water. Coal-fired power plants emit over 30% of environmentally released mercury. Other industrial sources are chlorine or "chlor-alkali" plants, cement plants, pulp and paper mills, municipal waste incinerators (19% of total release), and hazardous/medical waste incinerators. As of 2001, over 100 tons of mercury are "missing" from the EPA-surveyed inventory of chlor-alkali plants which admit to releasing the element to air and landfills. These sources, along with increased farming, forest fires, mining and excavations, and volcanoes, have served to increase surface deposition (micrograms per square meter) of mercury in surveyed areas by over 300% since 1850. This mercury can be biologically changed into organic forms and made bioavailable. Fish, shellfish and edible seaweed then become dietary sources of this element. Other sources include: old latex paint (manufactured before 1990), antifungal and antifouling (marine) paints, some fluorescent tubes and vapor lamps, medicinal products such as those containing "Thimerosal" ( ethyl mercurithiosalicylate or mercurothiolate--often contained in routine vaccines), explosives and detonators, batteries and "calomel" electrodes, electrical switches, thermostats and relays, and scientific or laboratory equipment (thermometers, barometers). Dental amalgams are primarily a source of elemental or amalgamated mercury that is typically found in feces for several days following dental procedures; very little of this dental-procedure mercury appears in urine. However, mercury vapor from in-place fillings can be absorbed, biotransformed and excreted in urine, but its level is typically much less than that which is attributable to food sources, especially seafood.

Arsenic is above the reference range. Most forms of ingested arsenic are excreted in urine, and variations in dietary intake, such as a single meal of arsenic containing shellfish, can cause urine levels to temporarily increase by a factor of 50 to 100. Therefore, increased urine arsenic indicates exposure but does not necessarily imply tissue accumulation or toxicity. Besides ingestion, arsenic can be assimilated by inhalation and via contact with the skin. Detoxication occurs via methylation, requiring S-adenosylmethionine (SAMe). Arsenic can be increased in urine following administration of sulfhydryl (-SH) detoxifying agents such as DMSA, DMPS, or D-Penicillamine.

Arsenic has multiple toxic effects including inhibition of mitochondrial function, including metabolism of pyruvate,

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient: JANE DOE Page 4

Commentary

succinate and alpha-ketoglutarate (Kreb's Cycle metabolites), inactivation of lipoic acid, impairment of lymphocyte stimulation and proliferation, and interference with DNA repair processes. Symptoms consistent with excessive arsenic ingestion include garlic breath and increased salivation, fatigue, chest pain, diarrhea and hypotension. Long term or chronic signs may include hair loss, skin hypopigmentation, white-streaked fingernails, anorexia, peripheral neuropathy, leukopenia, and erythrocyte fragility.

Commonly encountered sources of arsenic include contaminated shellfish or other seafoods, edible seaweeds, production of semiconductor or photoelectric components (particularly, arsenide), electroplating, galvanizing and etching processes, certain fungicides and pesticides, chemical process industry (reagents, catalysts), (intense white and blue colors), leather tanning and taxidermy, textile printing, lead and alloys (cable sheaths, solders, shot), and specialty glass manufacture (opal glass, IR transmitting, decolorizing).

Barium is above the reference range. Under normal conditions, most absorbed barium is excreted via the bile and feces (about 90%), with urine and sweat accounting for the remainder. Excessive body burden, especially from ingestion of soluble barium salts, can increase urine levels, and chelating agents used for detoxification (such as EDTA) can increase urinary barium levels. Insoluble (unabsorbable) barium, such as barium sulfate, is routinely used in medical diagnostic scanning and x-ray procedures because barium is radio-opaque. These forms are considered to be nontoxic. Soluble forms of barium (chloride, sulfide, nitrate and carbonate) may be encountered occupationally or in contaminated water or food. These forms are bioavailable and can be quite toxic.

Once absorbed, barium has a digitalis-like activity. Tingling in the extremities and muscle stimulation followed by paralysis can occur, as can ventricular fibrillation and respiratory distress. If the exposure is oral, nausea, vomiting and colic can precede muscle and myocardial effects. Toxic effects of barium include displacement of (extracellular potassium is decreased, intracellular potassium may be increased) and hypersecretion of adrenal catecholamines. Symptoms of low-level or chronic barium vapor exposure include bronchoconstriction and increased blood pressure.

Toxic barium sources include arc-welding and metal fabrication work, contact with welding flux materials, some rat poisons and insecticides, manufacture and use of flares and fireworks (barium nitrate and chlorate which produce green fumes), manufacture of paints, pigments and glazes, manufacturing of "phosphors" for cathode ray tubes and photo cells.

Cesium is above the reference range. This element is known for its radioactive , which are uranium fission products and arise from nuclear power plant fuel and from atomic bomb testing. It is also known for its medical and research uses (Cs-137, "Radiogardase-Cs"). Measured and reported here is the stable (nonradioactive), natural of cesium, Cs-133; natural cesium is 100% Cs-133. 210 Elevation of Cs-133 does not imply, and has no relationship to, the presence (or absence) of radioactive isotopes of cesium. When ingested or otherwise assimilated, cesium behaves like, and transports like, potassium in body tissues; in blood it binds inside erythrocytes. Much of the body s long-term burden is in muscle tissue where there is higher affinity for cesium than for potassium. Tests with injected Cs-137 show that 70% is excreted within seven days, mostly via urine. Dietary cesium forms may have a longer biologic half-time in humans; 50 to 60 days is reported. Increased dietary intake of potassium can increase urinary excretion of cesium. Cesium (like ) can be chelated and removed with "Prussian Blue" (potassium ferrihexacyanoferrate II).

Cesium has multiple toxic effects. In erythrocytes, cesium obstructs the release of from hemoglobin, thereby decreasing the RBC's ability to oxygenate body tissues. Additionally, exposure during pregnancy can result in organ

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient: JANE DOE Page 5

Commentary

abnormalities, impaired liver function (weak aldehyde and alcohol dehydrogenase), and reduction of CNS tissue mass in offspring.

Significant exposures are industrial or occupational. The element is used in the petrochemical industry as a catalyst for hydrogenation and polymerization, and it is used to manufacture some types of photoelectric cells. Halogenated cesium (chloride, bromide or iodide) is used in x-ray fluorescent screens. It may also be used in the manufacture of glass, lenses and prisms.

Nickel is above the reference range. Up to 90% of absorbed nickel is excreted via urine; sweat and bile/feces account for the remainder. Administration of sulfhydryl agents (D-Penicillamine, DMPS) can mobilize sequestered nickel and increase its concentration in urine. Besides food, cigarettes are a common source of bioavailable nickel. Usually, excretion of nickel is rapid being nearly completely released in five days.

Inhaled nickel, especially nickel carbonyl, is a respiratory tract carcinogen, producing squamous cell carcinomas. Nickel typically distributes to bone, lung, liver, kidney, intestinal mucosa, and skin. At low concentrations, nickel induces heme-oxygenase activity; at high concentrations it inhibits it, thus disordering heme metabolism. Both nickel sulfide and sulfate can disrupt immune function by depressing natural killer cell and CD4 lymphocyte populations in blood. Nickel salts at low concentrations can also suppress the natural oxidant cascade following the respiratory burst in phagocytes.

Typically, most absorbed nickel is of dietary origin; hydrogenated oils, cocoa and chocolate are notable sources. Cigarette smoke, plumes from fossil-fuel fired power plants, exhaust from diesel engines and some catalytic converters on engine exhaust systems provide airborne nickel. Batteries (nickel-cadmium), nonprecious dental materials, costume jewelry, and nickel-plated hardware are other sources that may be of concern in nickel dermatitis. Smelting and refining of metal ores and electroplating also add nickel to the environment.

Rubidium is above the reference range. Natural rubidium is present in virtually all soils, plants and vegetables, and animal products. Foods with highest rubidium content are soybeans, tomatoes and beef. Rubidium has very low toxicity, and health problems arise primarily from industrial or occupational exposures. Ingested rubidium is almost completely absorbed into portal blood, carried temporarily by erythrocytes, and deposited in muscle, liver, spleen, kidney, heart, lung and brain. The biologic half time in humans is 50 to 60 days with about 85% excreted via urine and about 15% excreted via bile/feces. Increased potassium intake can cause increased excretion of accumulated rubidium.

Rubidium can dysregulate potassium-dependent transport processes and metabolism and is believed to increase the release of norepinephrine. When tissue levels are excessive, excitability and aggressive behaviors occur. Human occupational exposures to high levels of rubidium have produced headaches, lassitude, irritability, disturbed sleep, cardiac arrhythmia, peripheral neuropathy, inflammation of the respiratory tract, and kidney damage with proteinuria.

Some photoelectric cells, specialized glasses, lenses and prisms, and vacuum tubes contain this element. Rubidium is encountered wherever alkali elements are processed, often by electrolysis. Potassium deposits and natural brines usually have high rubidium content.

Sulfur is above the reference range. Sulfur is an essential macroelement that is required by body tissues for structure and function. Urine sulfur is composed of inorganic sulfates, sulfated organic metabolites, including

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient: JANE DOE Page 6

Commentary

substances that are detoxified by sulfation, and metabolites that contain sulfur as an integral part of their structure, such as taurine and cystine. Sulfur-containing medications are expected to increase urinary sulfur. When sulfur-containing detoxification agents are administered, a significant amount of these agents is excreted via urine (some also is excreted via bile). About 21% of orally-administered DMSA, for example, is excreted in urine mostly in disulfide form bound to two molecules of cysteine. D-Penicillamine (Cuprimine) can also complex with cysteine. Such agents may or may not also complex and remove sulfur-seeking elements such as lead, mercury, arsenic, copper, etc.

Administration of these detoxifying agents in recommended amounts is expected to raise urine sulfur levels by about 20 to 30% or more.

Thallium is above the reference range. This toxic element can enter the body via ingestion, inhalation or skin contact. Although it is not chemically similar to potassium, thallium follows the transport path of the potassium into cells where it may then bind to sulfhydryl (-SH) sites. Most thallium is excreted via urine, and this excretion continues for months after a point-in-time exposure. A lesser excretion via bile can occur but is hindered by an enterohepatic recycle of the element. The use of Prussian blue (potassium ferrihexacyanoferrate II) has been described for removal of the element. Thallium has affinity for sulfhydryl compounds; however, cyst(e)ine and/or glutathione may spread the contamination. Literature is lacking regarding effectiveness of chelating agents such as DMSA and DMPS.

Multiple toxic effects are documented for thallium including hepatic effects, including cellular necrosis, fatty accumulation, and serum liver enzyme elevations; renal damage with tubular necrosis; dermal and ocular effects with hair loss and damage to oculomotor nerves and ocular muscle dysregulation; neurological problems with peripheral neuropathy, ataxia, tremor, hearing loss, and sometimes a "burning feet" sensation, all possibly related to histological findings of axonal degeneration and myelin loss. Inside cells, thallium enters the mitochondria and inhibits respiration by blocking oxidative phosphorylation.

Thallium is used to manufacture electronic parts (switches and contact materials that function at low temperatures), photoelectric cells, semiconductors, radiation counters, pigments, luminous paints, colored glass and artificial gems.

Tin is above the reference range. Dietary intake of this element can be quite variable, leading to considerable day-to-day differences in urine levels. Elemental, inorganic (two oxidation states, +2 or stannous, and +4 or stannic) and organic forms exist. Organic tin can be dermally absorbed. Elemental tin is very poorly absorbed from the GI tract, and inorganic tin salts are only about 5% absorbed (stannous better than stannic). Short-chain alkyl tins and organo-inorganic salt forms (e.g. triethyltin chloride) are well absorbed. Excretion also depends upon form. Absorbed inorganic tins are at least 85% excreted via urine, with bile handling the remainder. Organic forms are split between urine and bile with relative amounts depending on the organic component. The biological half-time of inorganic tin in the body is about 100 days, while organic tins vary in their tissue residence times. Administration of sulfhydryl (-SH) bearing detoxification agents lessens the toxic effects of organic tin and increases both urine and bile excretion.

Oral ingestion of elemental tin or inorganic forms requires large doses, on the order of 500 mg/kg continuously, to produce toxicity. However, organic tins and organo-inorganic forms can be highly toxic in small doses. Trialkyl tins cause cerebral edema and encephalopathy. Headaches, visual defects and abnormal EEGs have been noted following industrial exposures. Depletion of adrenal catecholamines, hyperglycemia, and uncoupling of cellular oxidative phosphorylation are other effects. Organic tins can also cause immune dysregulation and suppression by

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475 Patient: JANE DOE Page 7

Commentary

affecting lymphatic tissue and T-lymphocytes. Chronic exposure to dialkyltin damages liver cells and the bile duct; and trialkyltin damages the kidneys.

Most encountered tin sources are elemental or inorganic salts for which toxicity is low: tin from tin cans with damaged polymer coatings, stannous fluoride in toothpaste, food, and drinking water exposed to bronze, brass or tin-containing solders. Anti-corrosion electroplating of , pewter (tin, antimony, and copper), printer's type, dental amalgams, glazes and pigments, and plastics are other potential sources of inorganic tin. Of more concern are the potential sources of organic or organo-inorganic tins. These include: rodent poisons, fungicides, marine antifouling additives to paints and coatings, wood preservative, herbicide manufacture ("Chloromben"), and acaricides (mite or tick sprays, such as cyhexatin and fenbutatin ) used agriculturally on almonds, hops, apples, citrus, peaches, pears, nectarines and plums.

© Genova Diagnostics · A. L. Peace-Brewer, PhD, D(ABMLI), Lab Director · CLIA Lic. #34D0655571 · Medicare Lic. #34-8475