Why is childhood exposure to certain trace elements relevant to health?
Some elements—such as mercury, lead, arsenic, and cadmium—are biologically active even though they may be present in the body at very low (trace or ultratrace) levels. All elements can be toxic if exposure is excessive; some are nutritionally essential in smaller amounts. Disruption of trace element metabolism and overexposure to certain trace elements can impact child growth, health, and development.
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.
Some elements are also of interest because a number of diseases (e.g., Wilson’s disease, hemochromatosis, and thalassemia) are related to their metabolism.
How can exposure to trace metals and metalloids be measured?
Historically, children’s exposure has been assessed indirectly by analyzing environmental samples (air, water, soil, dust, etc.) for metals and metalloids, a practice still used today. However, biomonitoring can be used to measure a child’s internal exposure to metals and metalloids by analyzing blood, urine, or other tissues for trace elements or their metabolites.
The primary types of biospecimens collected for trace element biomonitoring are whole blood, serum/plasma, and urine. Other types of samples such as deciduous teeth, hair, nails, and placenta may be used for certain analyses. Which specimen 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 methylmercury (MeHg) exposure are quite different from those related to exposure to inorganic mercury (iHg).
Because variation of the concentration of trace elements may result from either variation of exposure or variation of the concentration/dilution of urine, urine analyses are typically normalized to urine dilution.
How does CHEAR ensure the quality of its analyses?
CHEAR analytical methods for metals and metalloids are validated against international reference standards. CHEAR laboratory performance is also assessed three times per year via participation in an external proficiency testing (PT) program designed specifically for the purpose of biomonitoring trace elements. This PT program not only monitors performance between the six CHEAR Lab Hubs but also provides a measure of comparability to other international laboratories conducting trace element biomonitoring.
Each CHEAR 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.
CHEAR investigators work with the CHEAR Lab Hub to review specimen integrity for the desired analysis, as well as storage recommendations and protocols for specimen transfer for trace element analysis.
What sample quality and quantity are necessary?
The requirements for quantity and quality vary by assay and by laboratory method. Analyses that use inorganic mass spectrometry could require as little as ~200-500 µL, but repeat analysis will require additional volume. Typically, at least 1 mL is desirable. Other analytical techniques (e.g., direct mercury analyzer) may require an additional volume of sample. The use of alternative technologies may provide lower detection limits, and specificity in identifying trace elements will require larger volumes of sample. If a large number of analytes is to be determined, a larger sample volume may be needed.
Clinical and Laboratory Standards Institute. Control of Preanalytical Variation in Trace Element Determinations; Approved Guideline. CLSI document C38-A. Wayne, PA: Clinical and Laboratory Standards Institute; 1997. (This document contains guidelines for patient preparation, specimen collection, transport, and processing for the measurement of trace elements in a variety of biological matrices.)
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.
Templeton DM, Ariese F, Cornelis R, et al. Guidelines for terms related to chemical speciation and fractionation of elements. Definitions, structural aspects, and methodological approaches (IUPAC Recommendations 2000). Pure and Applied Chemistry. 2000;72(8):1453-1470.