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Biomarkers that are typically used to assess heavy metal exposure are concentrations of heavy metals in blood, urine, bone, nail, hair, and other tissues and fall into both monitoring and safety biomarker subtypes. These traditional biomarkers are practical and reliable measures of exposure, can be vital when signs and symptoms of metal exposure are lacking, and can be useful for assessing the risk for disease development (Gil and Pla 2001). Typically, blood and urine are used to assess recent exposure, whereas bone, nail, and hair can be used to indicate chronic or past exposure. However, the type of biological tissue examined is highly dependent on the biological half-life of the metal, or the time it takes to excrete the metal from the body. For instance, lead can be retained in bone decades after exposure, whereas the half-life of lead in blood is only a few weeks. However, these traditional biomarkers of exposure are useful only in defining the severity and the duration of exposure (which can be either acute or chronic, depending on the biological sample and metal tested for) and do not have the capacity to determine disease susceptibility or whether adverse health effects can be mitigated. Additionally, metal toxicity can present non-descript and non-specific symptoms, which do not pinpoint a specific metal exposure if the type of exposure is unknown (Hackenmueller et al. 2019). Therefore an immediate need exists to find additional, specific, and reliable biomarkers that play dual roles in identifying exposures to types of heavy metals (i.e., in monitoring and safety) and may be used as early indicators of disease as a result of heavy metal exposure (i.e., for diagnostic purposes). In the last decade or so, ribonucleic acid (RNA) has emerged as a major target for diagnostics and therapeutics (Zampetaki et al. 2018), including in heavy metal exposure. This chapter focuses on microRNAs (miRNAs) as potential biomarkers in heavy metal toxicity and disease.

Table 4.4 Description of biomarker subtypes.

Biomarker Subtypes	Description
Diagnostic	Confirms the presence of a disease or condition with precision and reliability
Monitoring	Measured over a span of time and monitors the status of a disease or medical condition due to exposure of an individual to medicinal or environmental agents
Pharmacodynamic/Response	Changes in response to exposure to a medicinal or environmental agent
Predictive	Predicts whether favourable or unfavourable outcomes are more likely to be experienced by an individual or group of individuals
Prognostic	Identifies the likelihood of a clinical event, disease recurrence, or disease progression
Safety	Measures before or after exposure to a medicinal or environmental agent to indicate likelihood, presence or extent of toxicity as an adverse event

This table has been created on the basis of information from Califf (2018).