PROVIDER DATA SHEET

Heavy Metals & Essential Elements Testing in Dried Urine & Dried Blood Spot

We are all exposed to different amounts of essential and toxic elements depending on where we live, our diet and supplementation routine, or our lifestyle choices. Available Tests Levels of both essential and toxic elements that we consume or are exposed Toxic & Essential Elements – Urine to from the environment are determined by where we live, the water we drink, Tests included: Iodine, Selenium, Bromine, Lithium, Arsenic, Cadmium, Mercury, Creatinine the supplements we take, and the levels in soil/irrigation water used to grow the Assesses whether an individual has adequate, foods we eat. We are also exposed to toxic elements through environmental deficient, or excessive levels of the essential pollution of the air we breathe, as well as exposure through our skin. nutrients, or if they have been exposed to How do different levels of essential and toxic excessive levels of toxic heavy metals. elements affect health? Toxic & Essential Elements – Blood Essential elements are only conducive to optimal health when they are within Tests included: Cadmium, Mercury, Selenium, optimal ranges. Levels that are too low or too high can have detrimental effects Zinc, Magnesium, Copper, *Lead on health. Therefore, it is important to know if essential or toxic elements are *Research only outside their optimal ranges. Assesses whether an individual has adequate, deficient, or excessive levels of the essential Both iodine and selenium are good examples of essential elements that can be nutrients, or if they have been exposed to both beneficial and toxic, depending on their levels. Severe iodine deficiency excessive levels of toxic heavy metals. and extreme excesses cause thyroid deficiency and goiter. The same is true for selenium. A severe deficiency impairs the enzymes necessary for anti-oxidant Comprehensive Toxic & Essential Elements actions and thyroid deiodinases that convert inert T4 to bioactive T3. In contrast, Tests included: Cadmium, Mercury, Selenium, Zinc, an excess of selenium can cause death. Magnesium, Copper, and *Lead in Dried Blood Spot; Iodine, Selenium, Bromine, Lithium, Arsenic, Bromine is in the same chemical family as iodine and excessive amounts Cadmium, Mercury, Creatinine in Dried Urine will compete with iodine in the thyroid. This becomes particularly problematic *Research only when iodine levels are borderline low, or lower, and bromine is high. Lithium is Combines both Dried Urine and Dried Blood Spot Elements. important for brain health in trace amounts but is toxic when used in excessive amounts pharmacologically. Iodine Panel Copper and zinc are essential micronutrients that are needed in very small Tests included: Iodine in Dried Urine quantities in the diet, but are toxic at concentrations greater than is necessary Assesses sufficiency of iodine, for their biological functions. Magnesium is an essential element with a an element essential to thyroid health. significant role in cellular metabolism and protein synthesis, and its deficiency causes problems from muscle weakness to cardiac arrhythmias.

866.600.1636 | [email protected] | zrtlab.com PAGE 1 Revised 6.17.2021 Arsenic, mercury, cadmium, and lead are toxic heavy metals Very little lead is excreted in urine, but it is readily taken up by with no known nutritional benefits in the human body. High red blood cells where it forms a tight complex with hemoglobin. levels of them lead to an increase in Reactive Oxygen Species For this reason whole blood, and not serum or urine, is used (ROS) that damage proteins, lipids, and DNA. They also form to monitor exposure to lead. Arsenic is only measured in tight bonds with essential elements such as selenium, reducing urine and is not included in the blood spot profile because it its bioavailability for enzymes such as glutathione peroxidase is rapidly cleared from the bloodstream after exposure, and and thyroid deiodinase, both essential for thyroid hormone would therefore only be detected in blood if testing was done synthesis and activation. Arsenic, mercury, lead, and cadmium immediately after exposure. are extremely hazardous to human health. They represent the In summary, testing for these elements provides an excellent top four most toxic heavy metals according to the CDC’s priority assessment of overall body burden of toxic elements, and is list of hazardous substances1. Lead, mercury, and cadmium an indicator of excessive or inadequate supplementation with accumulate and are retained in the body, and so their toxic nutritionally essential elements. effects are cumulative and more pronounced with aging.

Elements Testing Minimally-invasive home test kits

Dried Urine Testing Urine dried on filter paper strips is a convenient and practical way in red blood cells (*lead and zinc). Whole blood is also to test essential and toxic elements that are excreted into urine. advantageous for testing magnesium because it represents ZRT Laboratory is a pioneer in commercial testing for elements intracellular magnesium, whereas serum magnesium is not a using a simple, two-point (morning and night) urine collection, useful test because it is kept within a tight range by homeostatic into which filter paper strips are dipped and then allowed to mechanisms and the test is therefore normal in most people, dry. Filter strips containing the dried urine are then shipped to masking deficiency at the intracellular level. For the nutritional ZRT Laboratory where the elements are extracted from the filter elements copper and zinc, dried blood spot (DBS) testing strips and tested for elements by Inductively Coupled Plasma reflects intracellular as well as blood (serum) levels and can Mass Spectrometry (ICP-MS). Published research from ZRT reveal deficiencies earlier than a typical blood (serum/plasma) Laboratory2,3 has shown the dried urine test to be accurate and test. comparable to full 24-hour liquid samples. Arsenic is not tested in DBS because it is rapidly cleared from the bloodstream and therefore urine testing is the only clinically Dried Blood Spot Testing useful determinant of arsenic exposure. Whole blood dried on filter paper is a convenient alternative to liquid whole blood testing for elements, and is preferable to DBS reference ranges are used for elements since published serum testing for certain elements that are found predominantly serum reference ranges are not comparable to whole blood/ DBS reference ranges.

*Research only

866.600.1636 | [email protected] | zrtlab.com PAGE 2 Elements Tested in the Profiles Deficiency of magnesium results in muscle weakness or cramping, confusion, seizures, and even cardiac arrhythmias.

Essential Elements Magnesium levels are affected by problems with kidney function and alcoholism, and some drugs such as diuretics and proton Iodine pump inhibitors can cause deficiency. It is estimated that up to An essential component of the thyroid hormones T4 and 60% of people in the US do not get sufficient dietary magnesium T3, iodine is an essential nutrient, commonly found in dairy and could be deficient; magnesium-rich foods include kelp, products, seafood, iodized salt, and grains. Severe iodine nuts, green vegetables, and whole grains. A serum magnesium deficiency compromises thyroid hormone production and leads test is not useful because the body raises serum levels at the to serious diseases including irreversible cretinism, pregnancy expense of intracellular levels to keep serum levels within a 4 complications, goiter, and decreased cognitive function . Mild tight physiological range, and therefore most people have to moderate iodine insufficiency can lead to thyroid deficiency. normal serum magnesium even in a deficient state. DBS testing Excessive iodine intake, paradoxically, can also lead to thyroid includes intracellular magnesium and is a better indicator of deficiency. Iodine deficiency has also been associated with nutritional status. breast cancer. Since over 90% of dietary iodine is eliminated in urine, adequacy of recent iodine intake can be accurately Zinc assessed with dried urine testing5. For a fuller discussion of Zinc is an essential dietary nutrient with an important role in the iodine’s role in overall health and the value of testing, please immune system, partly because of its bactericidal properties. see the Provider Data Sheet, “Iodine Testing in Dried Urine.” Zinc is a cofactor in multiple enzyme systems and is present in the zinc fingers that are involved with stabilization of folds in protein Selenium structures, in particular those that interact with specific areas of Selenium is an essential dietary element that is incorporated DNA. Like copper, zinc is transported bound to ceruloplasmin, into the selenoproteins in the body, which include glutathione but it also binds to hemoglobin. Zinc deficiency compromises peroxidases, thioredoxin reductases, iodothyronine deiodina- the immune system, wound healing, and the senses of taste and 6 ses, and the extracellular glycoprotein, selenoprotein P . These smell10. Excessive zinc intake above the Recommended Daily selenoproteins play vital roles in thyroid hormone synthesis, free Alloswance (RDA) of 15 mg/day can cause copper deficiency, 7 radical scavenging, DNA synthesis, and cancer prevention . impaired immune function, and adverse effects on the LDL/HDL Foods such as brazil nuts, seafood, eggs, and grains are cholesterol ratio11. Disturbances in zinc and copper metabolism, significant selenium sources. The optimal therapeutic range including a low zinc/copper ratio, low zinc levels, or high copper for selenium is narrow. Excess selenium intake can result in levels, have been implicated in autism spectrum disorders12. toxicity, while inadequate selenium affects thyroid function Good sources of dietary zinc include red meat, poultry, beans, because of impaired synthesis and conversion of T4 into the nuts, seafood (especially oysters), whole grains, and dairy 8 active T3 . Urine is the major route of selenium elimination; products. therefore urinary selenium is an indicator of dietary selenium intake. For individuals using dried DBS for elements testing, the Copper selenium test assesses nutritional adequacy of selenium. This An essential element that is required as a cofactor in multiple is particularly helpful when determining if selenium is present enzyme systems, usually as a participant in redox reactions, in sufficient quantities to counteract heavy metal toxicity that copper is transported in the bloodstream bound to the protein impacts selenium’s essential functions in the body, since heavy ceruloplasmin. Since copper is toxic at concentrations higher metals form tight complexes with selenium and reduce its than required for its cellular functions, ceruloplasmin delivers bioavailability. DBS selenium levels reflect both free selenium copper safely to target tissues without causing damage. Copper in the blood and selenium as a component of selenoproteins. is necessary for normal development of connective tissue, nerve sheaths, and bone, and is also a participant in energy Magnesium metabolism. Deficiency can result in neurological dysfunction Magenesium is an essential element required for over 600 and connective tissue abnormalities, while excess copper can enzymatic reactions involved in cellular metabolism and cause liver dysfunction10. The inherited genetic disorder Wilson’s 9 protein synthesis . Magnesium is important for strong bones Disease is characterized by abnormal copper accumulation in and muscles, heart health, nerve function, and cellular energy the liver and other vital organs, resulting in copper toxicity. Too production. much dietary zinc can cause copper deficiency.

866.600.1636 | [email protected] | zrtlab.com PAGE 3 Good sources of dietary copper include liver, oysters, nuts, Urinary arsenic is a good indicator of recent arsenic exposure, seeds, dark chocolate, and whole grains. since around 80% of dietary arsenic is excreted into urine within three days21. Bromine Bromine is a common component of flame-proofing agents, Cadmium fumigants, medications, food products, and pool/spa sanitizers. A toxic metal that is extremely hazardous to human health, Although bromine was once thought to have no essential cadmium is classified by the World Health Organization’s function in the body, recent studies suggest that it may also be International Agency for Research on Cancer as a group an essential element at low levels and play a role in connective I carcinogen22,23. Occupational exposure arises mainly tissue formation13. High environmental exposure can lead to from smelting, battery manufacturing, and colored glass excess accumulation14. If iodine status is low, bromine competes manufacturing24. Cadmium gets into the atmosphere as a with iodine uptake in the thyrocyte and for tyrosine binding sites result of industrial activity, as well as via fossil fuel combustion within thyroglobulin, and thereby impedes thyroid hormone and waste incineration. It is deposited in the soil where it is synthesis. Bromine is mostly excreted in urine, so urine analysis taken up by food plants and enters the human food supply25. can indicate excessive bromine exposure. Tobacco leaves are particularly efficient at accumulating high levels of cadmium from soil, so smoking is a major source of Lithium human cadmium exposure. Smokers have about twice the Historically used as a mood-stabilizing agent, lithium is now body burden of cadmium compared to non-smokers. In non- known to play a positive role in overall health. By influencing the smokers, the primary source of exposure is through the food expression of more than 50 genes, this powerful mineral restores supply. Particularly high cadmium levels are seen in green, neural function and improves brain health15. One way in which leafy vegetables, potatoes and grains, peanuts, soybeans, and lithium can help is by augmenting the activity of the enzyme sunflower seeds that have been grown in soils containing high responsible for metabolizing serotonin: aggression can result levels of cadmium. It also accumulates in shellfish. Apart from when serotonin levels build up with respect to its metabolite, occupational exposure in cadmium-emitting manufacturing 5-hydroxyindoleacetic acid. Small amounts of ingested lithium plants or waste incinerators, cadmium inhalation from the air appear to have other effects on well-being, including reduced is not a major source for most people. Once inside the body, susceptibility to cardiovascular and neurological disorders16. cadmium binds to albumin and metallothionein in the circulation, Multiple independent studies based on populations from and is filtered by the kidneys where it accumulates inthe different parts of the world report that when lithium exposure kidney cortex. In the kidneys, the half-life of cadmium is more is too low, mood is affected and people are more easily than 10 years. Urinary cadmium correlates with tissue levels in agitated and reactive – manifested in increased rates of suicide, the kidneys and is thus accepted as an accurate measure of homicide, and violent crimes in areas with low lithium in the long-term total body burden of cadmium25. Cadmium can also water supply17. Sources of lithium include well water, meat, accumulate in the thyroid gland, resulting in damage to thyroid dairy, grains, and vegetables. There is no RDA, but exposure tissues with chronic exposure26. An overall positive association to high levels of lithium is associated with renal damage, skin has been observed between urinary cadmium and levels of total lesions, and thyroid disorders18. The majority of ingested lithium T4, total T3, free T3, and thyroglobulin in the National Health is excreted in urine within 24 hours, so urine testing is a good and Nutrition Examination Survey27. Cadmium contributes to indicator of recent dietary exposure. unexplained infertility in both men and women, having detrimental effects on both male and female reproductive organs through Heavy Metals a variety of mechanisms, including endocrine signal disruption Arsenic and testicular accumulation affecting spermatogenesis28,29. Arsenic is an environmental toxin found in well water as well Cadmium also acts as an estrogen mimic or metalloestrogen by as some foods such as fish, shellfish, seaweed, rice, and fruit. stimulating cell proliferation in estrogen-responsive tissues and Arsenic is a heavy metal with multiple toxic effects in the body therefore increasing risk of uterine fibroids and other reproductive including carcinogenesis, goiter, diabetes, skin diseases, and tract diseases30. Cadmium was originally thought to act by binding damage to the liver, kidney, and the cardiovascular, nervous, directly to the estrogen receptor, but recent research suggests that and endocrine systems19. It also competes with selenium, it circumvents the estrogen receptor and activates the zinc-finger preventing its incorporation into the selenoproteins. This gene region that is ordinarily activated by estrogen receptor bound reduces the levels of selenium-containing antioxidants and to estrogen31. Short-term cadmium exposure, reflected in elevated also the selenoenzymes that are essential for thyroid hormone DBS but not urine levels, has been associated with modest blood production, thereby compromising thyroid function20. pressure elevations32,33.

866.600.1636 | [email protected] | zrtlab.com PAGE 4 Urinary cadmium has been linked with peripheral arterial disease34, Lead indicating some cardiovascular toxicity with cadmium exposure. A toxic heavy metal implicated in severe neurological defects in developing children. The presence of lead in the environment Mercury has been causing problems to human health since Roman Mercury is a highly toxic heavy metal that can accumulate times, but widespread occupational exposure to lead became in body tissues including the brain. Besides occupational a significant issue during the industrial revolution40. Exposure exposure, most human exposure to mercury is through dental of the general population to high levels of environmental lead amalgams, seafoods, and vaccinations35. Mercury toxicity can occurred largely as a result of its use as an additive in gasoline cause nervous system damage, leading to symptoms such and paint. Since these products have been discontinued, as paresthesia, mood changes, and sensory disturbances, overall lead exposure and levels have declined significantly. while very excessive exposure can also lead to renal toxicity, However, lead is still found in older plumbing systems and paint respiratory failure, and death36. Mercury and selenium have a and soil contaminated with this industrial chemical before its very high affinity for each other and form a tight complex37. As use was banned. For this reason lead remains ubiquitous in a result, mercury reduces the biological availability of selenium the environment. Lead exposure is particularly dangerous in and may inhibit the formation of selenium-dependent enzymes, children, in whom it can negatively affect brain development and affecting thyroid function in the same way as selenium intelligence. Since children tend to crawl on the floor or put toys deficiency or arsenic exposure. This is particularly problematic and other objects in their mouths, they are also more susceptible in people with inadequate selenium intake and consequent low than adults to lead exposure by oral ingestion of lead dust or selenium levels. Selenium can protect against mercury toxicity lead-based paint. Current guidelines recommend that there is by sequestering mercury, reducing its bioavailability38. The no safe level of lead exposure in children41. Gastrointestinal lead low toxicity of mercury in fish is related to its interaction with absorption is also considerably more efficient in children than selenium. in adults. In addition to causing neurological defects, high lead There are three forms of mercury in the environment: elemental, exposure can reduce vitamin D and hemoglobin synthesis. Lead inorganic, and organic. Elemental mercury comes from batteries, absorbed by the body is taken up by red blood cells and binds to thermometers, and dental amalgams. Elemental mercury is hemoglobin. Therefore, measurement in whole blood provides a most commonly breathed in as a vapor (e.g., from amalgams) more accurate assessment of lead exposure than urinary lead and absorbed through the lungs. It is volatile and nonpolar, and measurements, which are not clinically useful. Measurement of quickly penetrates the blood brain barrier where it is oxidized to lead* in DBS by ICP-MS is a reliable and convenient method to 42 inorganic mercury and retained in the brain. Inorganic mercury is assess lead exposure . found primarily in mercuric chloride and skin-lightening creams. *Research only Organic mercury, mostly in the form of methylmercury, is found in seafood. Inorganic and organic mercury compounds are Advantages of Dried Urine and DBS for ingested and absorbed through the intestine. The predominant form of mercury in urine is inorganic mercury, while in blood the Testing Toxic & Essential Elements organic species, mainly methylmercury, predominate. Urinary  Urine and DBS collections are simple and can mercury level is an excellent biomarker for whole body exposure be done conveniently at home and shipped to both elemental and inorganic mercury39. Assessment directly to the testing laboratory, saving time for of mercury in DBS is a good indicator of recent exposure to patients and their health care practitioner. organic mercury, mostly methylmercury, particularly from dietary sources such as fish.  Simple collections of urine directly on a filter strip in the morning and before bed at night are much easier than a Creatinine 24-hour urine collection, and provide equal accuracy. Creatinine is a metabolic by-product that is excreted at a relatively constant rate as long as kidney function is not impaired.  Essential and toxic elements in dried urine and DBS It is used to normalize the amount of elements extracted from are exceptionally stable for weeks at room temperature, the filter paper and to correct for hydration status; the greater allowing more flexibility in collection, storage, and the fluid intake, the lower the creatinine level. Iodine, bromine, shipment in an envelope from anywhere in the world. selenium, arsenic, mercury, and cadmium results in urine are  Urine element results expressed in µg/g creatinine therefore expressed in µg/g creatinine to allow for urine dilution. autocorrects for differences in urine concentration on the filter strip and for urine dilution, resulting from excessive liquid consumption. 866.600.1636 | [email protected] | zrtlab.com PAGE 5 References

1. Agency for Toxic Substances and Disease Registry Priority List of Hazardous 26. Jancic SA, Stosic BZ. Cadmium effects on the thyroid gland. Vitam Horm. Substances. 2013. 2014;94:391-425. 2. Zava TT, Kapur S, Zava DT. Iodine and creatinine testing in urine dried on filter 27. Chen A, Kim SS, Chung E, et al. Thyroid hormones in relation to lead, mercury, paper. Anal Chim Acta. 2013;764:64-69. and cadmium exposure in the National Health and Nutrition Examination Survey, 3. Zava TT, Zava DT. Determination of iodine, bromine, selenium and arsenic by 2007-2008. Environ Health Perspect. 2013;121(2):181-186. ICP-DRC-MS using urine dried on filter paper. osterP presented at: The 83rd 28. Thompson J, Bannigan J. Cadmium: toxic effects on the reproductive system Annual Meeting of the American Thyroid Association; October 16-20, 2013; San and the embryo. Reprod Toxicol. 2008;25(3):304-315. Juan, Puerto Rico. 29. Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead 4. Zimmermann MB. Iodine deficiency. Endocr Rev. 2009;30(4):376-408. and cadmium. Hum Reprod Update. 2000;6(2):107-121. 5. WHO, Unicef, ICCIDD. Assessment of iodine deficiency disorders and 30. Kortenkamp A. Are cadmium and other heavy metal compounds acting as monitoring their elimination: a guide for programme managers. Third edition. endocrine disrupters? Met Ions Life Sci. 2011;8:305-317. WHO publications. Geneva, Switzerland. 2007. 31. Gao X, Yu L, Moore AB, et al. Cadmium and proliferation in human uterine 6. Brown KM, Arthur JR. Selenium, selenoproteins and human health: a review. leiomyoma cells: evidence of a role for EGFR/MAPK pathways but not classical Public Health Nutr. 2001;4(2B):593-599. estrogen receptor pathways. Environ Health Perspect. 2015;123(4):331-336. 7. Mehdi Y, Hornick JL, Istasse L, et al. Selenium in the environment, metabolism 32. Tellez-Plaza M, Navas-Acien A, Crainiceanu CM, et al. Cadmium Exposure and involvement in body functions. Molecules. 2013;18(3):3292-3311. and Hypertension in the 1999–2004 National Health and Nutrition Examination 8. Bianco AC, Salvatore D, Gereben B, et al. Biochemistry, cellular and molecular Survey (NHANES). Environ Health Perspect. 2008;116(1):51-56. biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr 33. Lee BK, Kim Y. Association of blood cadmium with hypertension in the Korean Rev. 2002;23(1):38-89. general population: analysis of the 2008-2010 Korean National Health and 9. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for Nutrition Examination Survey data. Am J Ind Med. 2012;55(11):1060-1067. health and disease. Physiol Rev. 2015;95(1):1-46. 34. Navas-Acien A, Silbergeld EK, Sharrett R, et al. Metals in urine and peripheral 10. Fraga CG. Relevance, essentiality and toxicity of trace elements in human arterial disease. Environ Health Perspect. 2005;113(2):164-169. health. Mol Aspects Med. 2005;26(4-5):235-244. 35. Clifton JC. Mercury exposure and public health. Pediatr Clin North Am. 11. Fosmire GJ. Zinc toxicity. Am J Clin Nutr. 1990;51(2):225-227. 2007;54(2):237-269. 12. Bjorklund G. The role of zinc and copper in autism spectrum disorders. Acta 36. United States Environmental Protection Agency. Health effects of exposures Neurobiol Exp (Wars). 2013;73(2):225-236. to mercury. https://www.epa.gov/mercury/health-effects-exposures-mercury. 13. McCall AS, Cummings CF, Bhave G, et al. Bromine is an essential trace element Accessed June 16, 2020. for assembly of collagen IV scaffolds in tissue development and architecture. 37. Khan MA, Wang F. Mercury-selenium compounds and their toxicological Cell. 2014;157(6):1380-1392. significance: toward a molecular understanding of the mercury-selenium 14. Parfitt K (ed). Bromism. In: Martindale: The Complete Drug Reference. 32nd antagonism. Environ Toxicol Chem. 2009;28(8):1567-1577. edition. Pharmaceutical Press. 1999:1620-1623. 38. Branco V, Canário J, Lu J, et al. Mercury and selenium interaction in vivo: effects 15. Farah R, Khamisy-Farah R, Amit T, et al. Lithium’s gene expression profile, on thioredoxin reductase and glutathione peroxidase. Free Radic Biol Med. relevance to neuroprotection A cDNA microarray study. Cell Mol Neurobiol. 2012;52(4):781-793. 2013;33(3):411-420. 39. Park JD, Zheng W. Human exposure and health effects of inorganic and 16. Prosser JM, Fieve RR. Patients receiving lithium therapy have a elemental mercury. J Prev Med Public Health. 2012;45(6):344-352. reduced prevalence of neurological and cardiovascular disorders. Prog 40. Tong S, von Schirnding YE, Prapamontol T. Environmental lead exposure: Neuropsychopharmacol Biol Psychiatry. 2016;71:39-44. a public health problem of global dimensions. Bull World Health Organ. 17. Vita A, De Peri L, Sacchetti E. Lithium in drinking water and suicide prevention: a 2000;78(9):1068-1077. review of the evidence. Int Clin Psychopharmacol. 2015;30(1):1-5. 41. Schnur J, John RM. Childhood lead poisoning and the new Centers for Disease 18. McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic Control and Prevention guidelines for lead exposure. J Am Assoc Nurse Pract. review and meta-analysis. Lancet. 2012;379(9817):721-728. 2014;26(5):238-247. 19. Kapaj S, Peterson H, Liber K, et al. Human health effects from chronic arsenic 42.. Timko DM, Stickle DF. Measurement of filter paper bloodspot lead by inductively poisoning--a review. J Environ Sci Health A Tox Hazard Subst Environ Eng. coupled plasma-mass spectrometry (ICP-MS). Methods Mol Biol. 2010;603:327- 2006;41(1):2399-2428. 338. 20. Ciarrocca M, Tomei F, Caciari T, et al. Exposure to arsenic in urban and rural areas and effects on thyroid hormones. Inhal Toxicol. 2012;24(9):589-598. 21. Van Hulle M, Zhang C, Schotte B, et al. Identification of some arsenic species in human urine and blood after ingestion of Chinese seaweed Laminaria. J Anal At Spectrom. 2004;19(1):58-64. 22. International Agency for Research on Cancer Monograph 100C (2012): Cadmium and cadmium compounds. 23. Adams SV, Passarelli MN, Newcomb PA. Cadmium exposure and cancer mortality in the Third National Health and Nutrition Examination Survey cohort. Occup Environ Med. 2012;69(2):153-156. 24. Donovan GH, Jovan SE, Gatziolis D, et al. Using an epiphytic moss to identify previously unknown sources of atmospheric cadmium pollution. Sci Total Environ. 2016;559:84-93. 25. Agency for Toxic Substances and Disease Registry Priority List of Hazardous Substances Public Health Statement for Cadmium. 2012.

866.600.1636 | [email protected] | zrtlab.com PAGE 6