Chapter 7 
Biomarkers of Cigarette Smoking 
Neal L. Benowitz 
INTRODUCTION This chapter addresses the following question: To what extent do 
smoking-machine-derived tar, nicotine, and carbon monoxide ratings of 
cigarettes predict how much of those substances smokers actually absorb 
into their bodies? 
Two issues need to be clarified. First is the difference between delivery 
and content: What a cigarette delivers to the smoker is not the same as what 
is present in the cigarette tobacco. Second is the issue of compensation vs. 
regulation or titration: Kozlowski and Pillitterri (this volume) focus on 
compensation — the individual's smoking behavioral response to a change 
in a cigarette brand; this chapter focuses on cigarettes that people have 
self-selected to smoke. Whether behavioral adjustment to nicotine yields 
indicates regulation or titration or compensation is not important. What is 
important is the relationship between what people choose to smoke and 
their intake of various tobacco-derived toxins. 
USE OF The biomarkers most widely used to quantitate exposure to tobacco 
VARIOUS smoke include nicotine, its metabolite cotinine, carbon monoxide, 
BIOMARKERS and with less success, thiocyanate. Recent investigation has focused 
on various hemoglobin and DNA (deoxyribonucleic acid) adducts and 
excretion of nitrosamines in the urine. These latter measures represent 
important future directions, but there are inadequate data in large enough 
populations to make conclusions about the relationship between these 
measures and U.S. Federal Trade Commission (FTC) yields. The use of 
mutagenic activity of the urine is discussed to address the utility of the 
tar-to-nicotine ratio that is computed from the "FTC method" in predicting 
relative human exposure to tar and nicotine. This is an important 
consideration in estimating human risks from different types of cigarettes. 
NICOTINE Nicotine is rapidly absorbed from cigarettes. It enters arterial 
ABSORPTION circulation first, then venous circulation; nicotine levels then fall 
FROM relatively quickly as it is redistributed from the bloodstream to various 
CIGARETTES body tissues. Subsequently, nicotine levels fall off with an elimination 
half-life of about 2 hours (Benowitz, 1988). 
The intake of nicotine from a single cigarette can be approximated by 
measuring the nicotine blood concentration profile after a person smokes 
a single cigarette. The area under the plasma concentration-time curve is 
a reflection of systemic dose. The 24-hour nicotine consumption also can 
be estimated. Volunteer smokers have been studied smoking cigarettes on a 
research ward, where blood levels could be sampled frequently. Blood levels 
rise with smoking in the morning, more or less plateau through the latter 
part of the day, and then fall overnight (Benowitz and Jacob, 1984a). 
Carbon monoxide levels also build up during the day, plateau, and then 
