Table 1.
Biomarkers of exposure with abbreviations, half-lives, and analytical methods.
| Biomarker of Exposure (Abbreviation) | Half-Life | Analytical Assay Method |
|---|---|---|
| Urinary Nicotine Metabolites ^ | ||
| Cotinine (COTT) | 16–18 h | All nicotine metabolites were assessed using two separate isotope dilution high performance liquid chromatography/tandem mass spectrometric (HPLC-MS/MS) methods [20,21] |
| Nicotine (NICT) | 1–2 h | |
| Cotinine N-oxide (COXT) | N/A | |
| Nicotine 1′-oxide (NOXT) | N/A | |
| Norcotinine (NCCT) | N/A | |
| Nornicotine (NNCT) | N/A | |
| trans-3′-Hydroxycotinine (HCTT) | 6.4 h | |
| Minor Tobacco Alkaloids | ||
| Anabasine (ANBT) | 16 h | Same as above |
| Anatabine (ANTT) | 10 h | |
| Arsenic and Arsenic Compounds | ||
| Arsenous Acid | 10 h | All arsenic compounds were assessed using high performance liquid chromatography/inductively coupled plasma dynamic reaction cell mass spectrometry (HPLC-ICP-DRC-MS) |
| Arsenic Acid | 10 h | |
| Dimethylarsinic acid | 10 h | |
| Monomethylarsonic acid | 10 h | |
| Tobacco Specific Nitrosamines (TSNAs) | ||
| 4-methylnitrosamino)-4-(3-pyridyl)-1-butanol (NNAL) | 10.3 days [31] | All TSNAs were assessed using isotope dilution high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC-MS/MS) [22] |
| N’-nitrosonornicotine (NNN) | N/A | |
| N’-nitrosoanatabine (NAT) | N/A | |
| N’-nitrosoanabasine (NAB) | N/A | |
| Metals | ||
| Beryllium (UBE) | Several years | All metals were assessed using inductively coupled plasma mass spectrometry (ICP-MS) [23,24] |
| Cadmium (UCD) | 13.6 years | |
| Cobalt (UCO) | Several days | |
| Manganese (UMN) | 39 days | |
| Lead (UPB) | 1–2 months in blood & soft tissues, years to decades in bone | |
| Strontium (USR) | 47.3 h | |
| Thallium (UTL) | 1–3 days | |
| Uranium (UUR) | 24 h | |
| Polycyclic Aromatic Hydrocarbons (PAHs) | ||
| 1-Naphthol or 1-hydroxynaphthalene (1-NAP) | 4.3 h | All PAHs were assessed using enzymatic hydrolysis, on-line solid phase extraction, and isotope dilution liquid chromatography tandem mass spectrometry [27] |
| 2-Naphthol or 2-hydroxynaphthalene (2-NAP) | 9.4 h | |
| 3-Hydroxyfluorene (3-FLU) | 8.2 h | |
| 2-Hydroxyfluorene (2-FLU) | 2.1 h | |
| 1-Hydroxyphenanthrene (1-PHE) | 5.1 h | |
| 1-Hydroxypyrene (1-PYR) | 6.0 h | |
| 2-Hydroxyphenanthrene and 3-Hydroxyphenanthrene (2-3PHE) | 4.1 h | |
| Volatile Organic Compounds (VOCs) | ||
| 2-Methylhippuric acid (2MHA) (Xylene) | 34 h | All VOCs were assessed using isotope dilution UPLC-MS/MS [28,29] |
| 3,4-Methylhippuric acid (34MH) (Xylene) | 34 h | |
| N-Acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (Acrylamide) | 11 or 17.4 h | |
| N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCA) (N,N-Dimethylformamide/isocyanates) | 23 h | |
| N-Acetyl-S-(benzyl)-L-cysteine (BMA) (Toluene) | <10 h | |
| N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) (Acrolein) | N/A | |
| N-Acetyl-S-(1-cyano-2-hydroxyethyl)-L-cysteine (CYHA) (Acrylonitrile) | N/A | |
| N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA) (Acrylonitrile) | 8 h | |
| N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBM) (1,3 Butadiene) | N/A | |
| N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) (Acrylamide) | 19 or 25.1 h | |
| N-Acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA) (Acrylonitrile, vinyl chloride, ethylene oxide) | >5 h | |
| N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (HPM2) (Propylene Oxide) | N/A | |
| N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (HPMA) (Acrolein) | N/A | |
| N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMM) (Crotonaldehyde) | N/A | |
| N-Acetyl-S-(4-hydroxy-2-methyl-2-buten-1-yl)-L-cysteine (IPM3) (Isoprene) | N/A | |
| Mandelic acid (MADA) | 2.1, 3.6, or 3.9 h | |
| N-Acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine (MHB3) (1,3 Butadiene) | >9 or <6 h * | |
| Phenylglyoxylic acid (PGHA) (Ethylbenzene, styrene) | 8.1, 8.8 or 10.5 h | |
| N-Acetyl-S-(phenyl)-L-cysteine (PMA) (Benzene) | 9.1 h | |
| 2-Thioxothiazolidine-4-carboxylic acid (TTCA) (Carbon Disulfide) | 8 h | |
* Estimated from animal study. Multiple values indicate areas in which the literature lists multiple half-life values. N/A = “Not Available”. ^ Assays were conducted for each of the seven major nicotine metabolites listed. In addition to the nicotine metabolites listed above, “Total Nicotine Equivalents” (TNE-2) was computed and included in statistical analyses. TNE-2 was calculated as the molar sum of cotinine and trans-3′-Hydroxycotinine. For arsenic and arsenic compounds, individual assays were conducted for each of the four listed compounds. The analysis used a summary variable, “Total Inorganic Arsenic”, representing the sum of the arsenous acid, arsenic acid, dimethylarsinic acid, and monomethylarsonic acid levels in each urine sample. As these are summary variables, TNE-2 and Total Inorganic Arsenic do not have listings for limits of detection.