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In tobacco studies, biomarkers to assess exposure to tobacco products and biomarkers of potential harm are both of interest. These biomarkers are used to characterize exposure to constituents present in tobacco products (such as HPHCs) and to determine the potential health impact from use of these products.

Biomarkers of exposure may be the constituents or their metabolites.

• Biomarkers of Exposure
• Biomarkers of Potential Harm
• Functional Endpoint biomarkers (cardiac function)

24 hour urine collected by sponsor (volume represented here)→ Urine aliquots sent to lab→ testing done→ results sent to sponsor (units of conc)→ sponsor converts to units/24hr  

or potential harm are both of interest. Biomarkers of exposure are tobacco constituents or their metabolites in a biological fluid, tissue, hair, nails, or exhaled breath.

The FDA has established a list of HPHCs in tobacco products and tobacco smoke (see https://www.fda.gov/tobacco-products/). Additionally, there is a  list of 20 HPHCs, selected from the full list of HPHCs, for which testing methods are well established and widely available. The HPHC list focuses on chemicals that are linked to the 5 most serious health effects of tobacco use (i.e., cancer, cardiovascular disease, respiratory effects, reproductive problems, addiction) 

The use of tobacco products result in the uptake of nicotine and a wide range of other chemicals. Biomarkers of exposure to tobacco and nicotine delivery products are limited to the chemicals taken up during product use or during exposure to product emissions. Total nicotine equivalents (TNE), defined as the molar sum of the urinary concentrations of nicotine and all of its known metabolites (e.g., nicotine, total cotinine, total 3-hydroxycotinine, nicotine N-oxide), is a biomarker of nicotine consumption. Cotinine is a metabolite of nicotine and is a widely used biomarker of nicotine exposure. Nicotine replacement therapy and tobacco use can be distinguished by the detection of a tobacco-specific alkaloid such as anabasine. Cotinine has 6 notable metabolites (i.e., 3-hydroxycotinine, cotinine glucuronide, 5-hydroxycotinine, cotinine N-oxide, cotinine methonium ion, norcotinine).

Biomarkers of exposure may be used to evaluated the pharmacokinetics of tobacco products. After the specific tobacco product is used, these biomarkers are measured serially to determine well-defined pharmacokinetic parameters ( e.g., AUC, TMX, T 1/2 ); the concentration levels at prespecified timepoints would be represented in the PC/PK SDTM domains (Section 3.3.3.2, Pharmacokinetics Concentration and Parameters (PC, PP)). Otherwise, these biomarkers would be represented in the Laboratory Testing Results (LB) domain.