Three types of biomarkers are considered by environmental health researchers: biomarkers that can be used to quantify exposure to contaminants, biomarkers that can be used to examine the effects of contaminants, and biomarkers that can be used to determine the susceptibility of individuals to contaminants (Figure 1).1
A biomarker of exposure (which is also called the internal dose) is the concentration of an exogenous chemical or its metabolite(s) in human tissue. A biomarker of exposure can be a toxic chemical or compound (e.g. lead, PCBs), a product of a toxic substance (e.g. cotinine, a metabolite of nicotine), or an early reaction to or effect of a toxic substance (e.g. an increase in liver enzymes after excessive exposure to alcohol).
A biomarker of effect is an alteration of an endogenous factor that is linked with a disease, such as a decrease in cholinesterase levels following exposure to organophosphate insecticides.
A biomarker of susceptibility is an indicator of an inherent or acquired trait that alters or modifies the body’s response to an exogenous agent. For example, individuals who lack a gene for one of the glutathione transferases—enzymes involved in the detoxification of tobacco—are more susceptible to lung cancer.1
Biomarkers serve numerous functions. Clinically, they can be used to determine whether a patient’s symptoms are due to ingesting a toxic substance such as methyl mercury or being exposed to second hand tobacco smoke.4
Biomarkers can also be used to identify communities contaminated by industrial pollutants,2to develop reference ranges for contaminants (i.e. variations commonly found during measurement) for research purposes, and to provide an integrated measure of dose.
Another important function of biomarkers is their use in surveillance and identifying trends in exposures. For example, biomonitoring has been able to show that exposure to brominated diphenyl ethers (PBDE), a flame retardant, has dramatically increased in human breast milk over the past three decades.5
Finally, biomarkers can be used to evaluate prevention efforts. For example, researchers have measured cotinine in urine, serum, or hair to determine if education, smoking cessation, or air cleaners have benefited children by reducing their exposure to environmental tobacco smoke.67
Biomarkers are routinely measured in blood, tissue, saliva, urine, hair, and breast milk. Choosing one of these or another appropriate biological matrix is based on several considerations, including how quickly a chemical is absorbed, metabolized, and excreted, as well as the magnitude, frequency, and duration of exposure.
Fat-loving or lipophilic substances, such as DDT, are readily found in breast milk and serum or plasma, whereas non-persistent chemicals, such as bisphenol A, are typically easier to detect in urine. Hair, which absorbs some toxic substances, grows about 1 cm per month and can potentially provide a measure of long-term exposure to toxic substances such as tobacco or mercury (Clarkson et al. 2003, Eliopoulos et al. 1996).89
Finally, when choosing a biological matrix, the burden to the patient or research subject is an important consideration. If an invasive procedure is required to obtain a specimen—such as collection of amniotic fluid to measure fetal exposure—routine testing and large population-based studies may not be practical or safe.
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- 5. Ryan JJ, Patry B. Determination of brominated diphenyl ethers (BDEs) and levels in Canadian human milks. Organohalogen Compounds. 2000;47:57–60.
- 6. Wakefield M, Banham D, McCaul K, et al. Effect of feedback regarding urinary cotinine and brief tailored advice on home smoking restrictions among low-income parents of children with asthma: a controlled trial. Prev Med. 2002;34:58-65.
- 7. Conway TL, Woodruff SI, Edwards CC, et al. Intervention to reduce environmental tobacco smoke exposure in Latino children: null effects on hair biomarkers and parent reports. Tob Control. 2004;13;90-92.
- 8. Clarkson TW, Magos L, Meyers GJ. The toxicology of mercury – current exposures and clinical manifestations. New Engl J Med 2003;349:1731-1737.
- 9. Eliopoulos C, Klein J, Koren G. Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Ther Drug Monit. 1996;18:532-536.