Why is exposure to certain trace elements relevant to health?
Trace elements (which includes metals as well as metalloids) – such as mercury, lead, arsenic, and cadmium—can exhibit toxic effects even though they may be present in the body at very low (trace or ultratrace) levels. Some elements such as copper, zinc, selenium, and manganese are considered essential at trace levels. “Trace” is defined as concentrations from 10 to 104 µg/L in blood or serum, or 0.01 to 100 µg/g in tissues. Other elements such as cobalt and chromium (i.e., as Cr3+) are also essential but at “ultratrace” levels, defined as <0.01 µg/g or <10 µg/L. Regardless whether they are trace or ultratrace, all elements can be toxic if exposure is excessive. Disruption of essential trace element metabolism and overexposure to non-essential trace elements can impact growth, health, and development. Some elements are also of interest because a number of specific diseases (e.g., Wilson’s disease, hemochromatosis, and thalassemia) are related to their metabolism.
Children are particularly vulnerable to the harmful effects of some elements such as lead. For example, a child’s gastrointestinal tract absorbs five times more lead compared to adults, and given a child’s smaller blood volume, this leads to much higher blood lead levels. Furthermore, a young child’s organs are still developing and are particularly vulnerable to the toxic effects of lead. Yet lead’s toxic effect have also been demonstrated at low levels in adults too.
Interest in a sub-group of trace elements known as the Rare-Earth Elements (REE), which includes scandium, yttrium and lanthanum, plus 13 elements of the lanthanide series, has expanded over the years. REE are used in catalysts, alloys, magnets, electronics, ceramics, glass and medicine. They have also been used in agriculture to increase plant growth, productivity, and stress resistance. While no adverse health effects have been observed at existing low REE concentrations, long term effects and accumulation in the environment are unknown prompting calls for more research. Exposure to high levels of REE can lead to a wide range of adverse health outcomes such as cancer, respiratory issues, and dental loss. Gadolinium, administered as metal-chelates, are used as contrast agents in magnetic resonance imaging (MRI) studies. However, the “free” dissociated gadolinium ion is now known to accumulate in bone and has been associated with nephrogenic systemic fibrosis, a chronic painful condition that causes diffuse fibrosis in tissues.
How can exposure to trace elements be measured?
Historically, exposure has been assessed indirectly by analyzing environmental samples (air, water, soil, house dust) for trace elements, a practice still used today. However, biomonitoring can provide information on internal exposure by analyzing blood, urine, or other tissues for trace elements or their metabolites.
- Analytes: A wide variety of trace elements including metals, metalloids and rare earth elements can be analyzed in both environmental samples and biospecimens.
- Methods: Most trace elements are quantified using methods based on atomic spectrometry, which includes inductively coupled plasma mass spectrometry (ICP-MS). Limits of detection for ICP-MS range from ng/L (ppt) to µg/L (ppb). When liquid (or gas) chromatography is coupled to ICP-MS, the ability to quantify different chemical species of the same element, i.e., speciation analysis becomes possible.
- Types of biospecimens: The primary types of biospecimens collected for trace element analysis are whole blood, serum/plasma, and urine. Other types of samples such as deciduous teeth, hair, nails, and placenta may be analyzed for trace element content. Which biospecimen is the best indicator of internal exposure will depend on the specific absorption, distribution, metabolism, and elimination (ADME) kinetics of each element/species, its toxicological properties, and the route of exposure to the element. Ideally, investigators should consult both a medical toxicologist and the analyzing laboratory before specimens are collected and stored for trace element analysis.
Another key issue to be resolved before specimens are collected is the type of measurements to be performed. Often, measuring the total elemental content is sufficient. However, for some elements, knowledge of specific chemical species is important. For example, potential health outcomes related to inorganic arsenic exposure are quite different from those related to exposure to dietary sources of arsenic.
Because variation of the concentration of trace elements may result from either variation of exposure or variation of the urine dilution, urine measurements based on volume (m/v) are typically normalized to creatinine excretion, or even specific gravity.
- Types of environmental samples: Trace elements are measured in a variety of environmental matrices, including air, water, dust, and soil.
How does HHEAR ensure the quality of its analyses?
HHEAR analytical methods for trace elements are validated against appropriate certified reference materials, where available. Since ICP-MS instruments are calibrated with NIST-traceable primary standards, the resulting measurements are deemed traceable to the International System of Units, i.e., Système international (d'unités), or SI units. HHEAR biospecimen laboratory performance is also assessed via participation in the New York State Department of Health’s (NYS DOH) Proficiency Testing (PT) program for trace element biomonitoring studies. This PT program not only monitors performance between the HHEAR Lab Hubs but also provides a measure of comparability to other laboratories conducting trace element biomonitoring both within the US and internationally. Urine and blood-based reference materials have been developed and well characterized specifically for use in the HHEAR Lab Hubs and have been validated in the NYS DOH PT program.
In addition to external PT, each HHEAR Lab Hub implements its own internal quality assurance protocols, which include analysis of multi-level internal quality control materials for each assay offered, where appropriate.
HHEAR investigators work directly with the HEAR Lab Hub to review sample integrity for the desired analysis, as well as storage recommendations and protocols for sample transfer for trace element analysis.
What sample quality and quantity are necessary?
The requirements for sample quantity and quality vary by assay and by laboratory method. Analyses based on inorganic mass spectrometry could require as little as ~200-500 µL of biological material or 1 gram of house dust, 5 grams soil, or 100 mL drinking water; repeat analysis will require additional material. Other analytical techniques (e.g., direct mercury analyzer) may require an additional quantity of sample. The use of alternative technologies may provide lower detection limits, and specificity in identifying trace elements but may require larger quantities of sample. If a large number of elements is to be determined on the same sample, a larger quantity may be needed. For quality control purposes, it is highly desirable to include several empty tubes and/or collection containers to check as a blank for background contamination.
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Clinical and Laboratory Standards Institute. Measurement Procedures for the Determination of Lead Concentrations in Blood and Urine. Approved Guideline Second Edition. CLSI document C40-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2013.
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