Human Exposure to Environmental Tobacco Smoke: Is What You See What You Get??

Roger A. Jenkins, Ph.D.

Presented to the Bloomberg School of Public Health Johns Hopkins University February 9, 2005

Sponsors of the ORNL Tobacco Smoke Characterization Program
National Cancer Institute Federal Trade Commission National Institute on Drug Abuse Council for Tobacco Research USA University of California-Davis Center for Indoor Air Research Brown & Williamson Tobacco Co. Philip Morris USA Hotel Association of Canada

ORNL ETS “Real World” Studies
Restaurant patron study part of airborne nicotine method development Area vs Personal Monitoring
32 venues, published in 1989 Variety of venues (ca. 25) included restaurants, laundromats, bowling alleys, etc. Reported in 1990 ca. 1600 subjects geographically dispersed Published in 1996 ca. 160 subjects, area & personal monitoring. Published in 2000 Personal exposure monitoring of ca. 240 subjects. Reported in 2000 Intense area monitoring of 6 restaurants and bars. Reported in 1999, some results published in 2004. 25 subjects in one facility: area vs personal monitoring. Published in 2001 Area samples demonstrated that one can achieve “regulated non-smoking levels” with ventilation: Published in 2002

16 Cities Personal Exposure Monitoring Waiters/waitresses/bartenders

Demographically representative study

Phoenix/Louisville area monitoring study: Unrestricted smoking workplace “Black Dog Pub Study

ETS Exposure Variability: on-going

Environmental Tobacco Smoke 101

The Two Phases of Tobacco Smoke
Particle Phase, made up of liquid droplets which are comprised of higher MW hydrocarbons.
This is the smoke that is visible, because the tiny droplets scatter light.

Vapor Phase, made up of volatile organic chemicals and permanent gases, such as carbon dioxide, carbon monoxide, methane, ammonia.
The vapor phase is not visible to the human eye.

Environmental Tobacco Smoke: What Is It?
Highly diluted mixture of sidestream (70 - 90%) and exhaled mainstream (10 - 30%) tobacco smoke

+

Sidestream Tobacco Smoke

Exhaled Mainstream Tobacco Smoke

Environmental Tobacco Smoke: What Is It? (continued)
Mainstream, sidestream, and ETS are not the same material. The term “second hand smoke” is probably misleading, since most ETS is derived from smoke which is emitted by the smoldering firecone of the cigarette. Differences between ETS and mainstream smoke are primarily due to differences in combustion mechanisms between sidestream and mainstream tobacco smoke. Differences between ETS and sidestream smoke are mostly due to the interactions of various components with the surrounding environment.

How Do We Determine Human Exposure to ETS?

Cooking Cleaning

Indoor Air Pollution Can Be Derived From a Variety of Non-Tobacco Sources

Consumer Products

Wood Burning

All Incomplete Combustion Processes Produce Smoke Comprised of Thousands of Constituents

Many components are toxic at some level, and all smokes are likely to contain a few “ signature” components

Desirable Characteristics of Marker Compounds
(Taken from the National Academy of Sciences Report on ETS)

Useful for describing the concentration of complex materials. Unique to the substance in question. Behaves like the material or phase of the substance that is being assessed. Present in measurable quantities even at low substance concentrations

Environmental Tobacco Smoke Markers
N CH3O N CH3 HO O O

Nicotine

Scopoletin

N

H CH2 CH3 CH3 CH3 8

CH2OH

3-ethenyl pyridine
N N

Solanesol

Myosmine

60,000 Foot View of the Analytical Chemistry
Analysis of sub-ppb concentrations of airborne pollutants still ain’t all that easy. Nicotine and 3-EP: collection on XAD-4 resin, extraction with ethyl acetate spiked with an adsorption blocker, and analyzed via GCNPD. Solanesol: extraction with methanol, reverse phase HPLC with UV absorption detection at 205 nm. UV-PM/FPM: Column-less HPLC with UV and fluorescence detection.

Area vs Personal Monitoring
Personal

Area

Sample Collection in the Workplace

Sampling Head

Sampling Pump

Technology is Always Improving: Opaque Filter Holders May Mitigate PostCollection Degradation of Solanesol
Filter Holder

Cyclone Separator XAD-4 Vapor Collection Cartridge
Clear plastic filter holder used in 16 Cities Study (1993-94) Opaque plastic filter holder used from 1997 on

16 Cities Study: Urban Areas Distributed Geographically
Seattle Buffalo Boise Grand Rapids Indianapolis Columbus St. Louis Phoenix Knoxville San Antonio Daytona Beach New Orleans Portland Philadelphia Baltimore

Fresno

Distribution of 24-hour TWA RSP Levels
Subject Segregation by Self-Reported Home and Workplace Smoking

Status Confirmed by Diary Observations (All Subjects with Avg. Cotinine <15 ng/mL)

120
Subject Distribution, %

100 80 60 40 20 0 0.1 1 10 100
3

Cell 1 Cell 2 Cell 3 Cell 4

1000

Respirable Suspended Particulate Matter, (RSP), ug/m

Distribution of 24-hour TWA Nicotine Levels
Subject Segregation by Self-Reported Home and Workplace Smoking

Status Confirmed by Diary Observations (All Subjects with Avg. Cotinine <15 ng/mL)
1.2 S u b je c t D is trib u tio n , F ra c tio n 1 0.8 0.6 0.4 0.2 0 0.001

Cell 1 Cell 2 Cell 3 Cell 4

0.01

0.1

1

10
3

100

24-hr TWA Nicotine Concentration, ug/m

Concentrations of Selected ETS Markers: Confirmed Smoking/Non-Smoking Locations Median 24-hr TWA Levels, ug/m3
10 9 8 7 6 5 4 3 2 1 0
Smkg Home/NS NS Home/Smkg NS Home/NS Smkg Work Work Work Home/Smkg Work

2 4 h r T W A L e v e l, u g /m 3

3-EP Nicotine RSP/10 FPM Sol-PM

Median ETS Exposures* in Environments Where Smoking is Unrestricted
Exposure = Concentration x Time

25
Exposure, ug-hr/m 3

20 15 10 5 0
3-EP Nicotine FPM/10 Home (n = 113) Workplace (n = 139)

* Smoking confirmed by diary reports

Distributions of Bartender TWA Nicotine Levels:
Multi-Room Bar/Restaurants vs. Single Room Bars
100 Percent Subject Distribution 90 80 70 60 50 40 30 20 10 0

Multi-room Bars/Restaurants Single Room Bars

0.01

0.1

1

10

100

3 TWA Nicotine, ug/m

Exposures of Wait Staff and Bartenders vs. Subjects in Unrestricted Smoking Workplaces and Homes (16 Cities Study)
Exposures in µg-hr/m3
25 Exposures, ug-hr/m3 20 15 10 5 0 Nicotine 3-EP Sol-PM/10
Bartenders Waiters Urstr Smkg Wrkpl Unrstr Smkg Home

Typically Encountered Concentrations of ETS Are Pretty Low
Highest encountered level of respirable suspended particulates (RSP) in our wait staff/bartenders study was about 1/7th of OSHA Permissible Exposure Limit (PEL). Median area concentration of nicotine was 0.9 parts per billion.

Are People Good Observers of their Own Exposures?
Workplace Nicotine Exposure Concentrations of Subjects Reporting “A Little” Exposure to ETS
10

Workplace Nicotine Level, ug/m^3

1 0 2000 4000 6000 8000 10000 12000 14000 16000

0.1

0.01

0.001

Subject Number

How Does Living with a Smoker Compare to Being a Smoker?

??
Typical smoker will inhale 480 mg/day of smoke particles, and 32 mg per day of nicotine. In a home where smoking is unrestricted, the typical non-smoker will inhale the equivalent of 0.45 mg of smoke particles and 0.028 mg of nicotine. Do the Math: The difference is about a factor of 1100

Breathing ETS Will Expose You to Toxins, but Not Like Breathing Urban Air
Volatile Compound Mean Daily Exposure Estimate Based on Living with a Smoker, µg/day* Confirmed Exposures of Teenagers in Urban Environments from NonSmoking Homes, µg/day**

Benzene

14 126 66

94 260 230

Acetaldehyde

Formaldehyde

* Estimate based on 16 Cities exposures to nicotine and Baek/Jenkins chamber study,
Atm. Env, 38, 6583 (2004) ** Estimate based on Kinney et al, Env. Hlth. Persp. 110/S4, 539 (2002)

Variation of 16 hr TWA Nicotine Concentrations, Subjects Residing in Smoking Homes 2004 Exposure Study
5.0 4.5

4.0

3.5

Nicotin e, u g /m^3

3.0

2.5

2.0

1.5

1.0

0.5

0.0

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47

Subject

Range of Max/Min Ratios: 1 - 80

Biomarkers for ETS Exposure It’s Not So Simple

Avg. Salivary Cotinine Level as a Function of Nicotine Exposure
All Subjects with Both Markers >95% CL above LOD
Nicotine: 0.063 ug/m3; Cotinine: 1.01 ng/mL

Avg. Salivary Cotinine Level, ng/mL

14 12 10 8 6 4 2 0 0 5 10 15 20 25
24-hr TWA Nicotine Concentration, ug/m3

R2 = 0.105

Key Findings from Some Exposure Studies
For non-smokers in these environments, exposure at home is greater than exposure at work. BUT …. “Living with a smoker” can mean different things for different people. Salivary cotinine not a good quantitative indicator of ETS nicotine exposure. Humans, as a class, are not good at estimating their exposure to ETS. For non-smoking bartenders (if you can find one) who live with smokers, their exposure to ETS at home is at least as important as their exposure in the workplace. Demographics is EVERYTHING!

How do ORNL Results Fit into THE BIG PICTURE?

Ratios of 24-hr Exposures of Never Smoking Women:
Married to Smokers vs. Married to Non-Smokers Comparison of EPA Estimate with 16 Cities Data
45 40 35 Z-Factors 30 25 20 15 10 5 0
Calc'd from Medians Calc'd from Means

EPA Estimated Ratio: 1.75

3-EP Nicotine Myosmine UVPM FPM Solanesol Avg. Cotinine RSP

Impact of Differences in Z-Factor: EPA Estimate vs. ORNL 16 Cities Data
Z = Exposure ratio of women exposed from smoking spouse compared with women not exposed from spouse
1.7
Relative Risk Factor

1.6 1.5 1.4 1.3 1.2 1.1 1 0

EPA Estimate: Z = 1.75 16 Cities FPM Solanesol: 33 Nicotine: 36 3-EP: 24

5

10

15

20

25

"Z Factor"

Implications for Risk Assessment: Never Smoking Female “Misclassification” Rates
3 M isclassificatio n Rate, % EPA Estimated 2.5 2 1.5 1 0.5 0 Estimate from 16 Cities Data

How “Never-Smoker” Misclassification Rates Impact EPA’s Relative Risk Estimation
1.4
E s tim a te d R e la tiv e R is k

16 Cities Females Cutoff: 100 ng/mL

1.3 1.2 1.1 1 0.9 0.8 0.7 0.00% 2.00% 4.00% 6.00%
EPA’s Point Estimate 16 cities Females Cutoff: 30 ng/mL

Point Estimate Lower 90% CI Upper 90% CI

8.00%

10.00%

At the ORNL determined mis-classification rate, there is virtually no statistically significance for increased lung cancer risk to never-smokers

External “Validation” of ORNL Exposure Studies by OSHA and Upheld by US Circuit Court of Appeals for the District of Columbia
“ ….For most of those subjects who worked or lived in smoking environments, the home appears to be a more important source of ETS exposure. This appears to be due to the larger amounts of time spent away from work, as well as somewhat greater ETS constituent levels encountered outside the workplace……..”
ORNL 16 Cities Study (Jenkins et al, 1996)

The Waters at the Confluence of Science and Public Policy Get Pretty Choppy Sometimes

Oak Ridge Lab to Do Smoke Study
Front Page, Knoxville News Sentinel, Thursday, February 13th, 2003

Four-day monitoring to cover all types of indoor pollution
By FRANK MUNGER, munger@knews.com February 13, 2003 OAK RIDGE - Oak Ridge National Laboratory researchers plan to do a first-of-its-kind study on indoor air pollution, including but not limited to exposure to secondhand tobacco smoke. About 65 to 70 nonsmokers of varied backgrounds in the Knoxville area will be recruited for the project. The Oak Ridge team will begin screening volunteers this spring, and the work itself will take place in the summer or fall, said Dr. Roger Jenkins, an analytical chemist who heads the research project. Individuals will be monitored over a four-day period so researchers can better understand how exposures vary from day to day and under different circumstances, Jenkins said. Most …………………..

Oak Ridge National Laboratories seems to be doing Big Tobacco's dirty work once again.
Globalink Listserve, Friday, February 14th, 2003

Please remind advocates in your areas to watch out for the Oak Ridge National Laboratories studies and to proactively inoculate coalition members, policymakers, and the media against this tobacco industry white-washed science. As a reminder, Roger Jenkins is funded by the tobacco industry. This work is bought and paid for by Philip Morris and is done on a private contracting basis by the Oak Ridge nuclear energy lab apart from its official Department of Energy work. It comes with a fine print disclaimer saying that it does not reflect government opinion.

The Tobacco Wars

March 5, 1998
Dunn/Wiley et al vs RJR Nabisco

Question: (Dr. Jenkins, you are aware aren’t you) …. that Oak Ridge is also the facility known for radiating children, is it not, with leukemia, conducting those experiments on children?

When I Start to Hear “Marketing Hype” in what Should be Scientific Discussions, my BS Antennae Go Up

“My doctor says that there is nothing better than Brand X for preventing symptom Y.” Translation Brand X is no better than any of the other brands at preventing these symptoms

“Marketing Hype” #1 Promulgated by SOME Anti- Smoking Activists
“There is NO level of ETS exposure.”

SAFE

Example Permissible Exposure Limits
Compound Acetaldehyde Acrolein 1,3-butadiene Nicotine Respirable suspended particulate matter Concentration, ppm 200 0.1 1 500 5000 Concentration, ug/m3 360,000 250

Translation: no governing body has established a “permissible exposure limit” for ETS. In fact, standards exist for many of the components of concern in ETS.

“Marketing Hype” #2 Promulgated by SOME Anti- Smoking Activists
“Ventilation can not remove all traces of ETS.” Well, duh! Ventilation can not remove all traces of anything, and nothing can.

Low Ventilation (CO2 > 1000 ppm) is Often the Culprit When High ETS Levels are Observed in Public Places
Phoenix Barbeque Restaurant, Feb 19,1999
CO2 above 1000 ppm usually indicates inadequate ventilation
1800 1600

CO 2 Concentration, ppm

1400 1200 1000 800 600 400 200 0

Inside CO2 Level Outside CO2 level

17:00

18:12

19:24

20:36

Time

Determining Meaningful ETS Levels in Hospitality Venues Can Pose Additional “Challenges”
“Recycled” air External Sources

Intelligently Designed Ventilation Systems Can Do Quite a Bit
Heat recovery ventilation system at 3100 cfm Directional air flow from nonsmoking to smoking section. 1600 cfm added on west side NS section 1500 cfm added at S/NS boundary through three ceiling diffusers. All air exhausted from smoking section.

Ventilation Works to Reduce Exposures
Laboratory scientists use key principles to minimize their exposures to hazardous volatile chemicals all the time.
Segregation of the source term (object that causes the pollution) Directional air flow Significant replacement with “clean” air.

Concentrations of ETS in Non-Smoking Areas Black Dog Pub vs Comparative Facilities
Concentrations, ug/m3 UVPM
Black Dog NonSmoking Areas N = 12 NonSmoking Tavern & Food Court Areas N = 13

FPM 5.4 5.8 2.5 9.6 8.6 7.2 4.0 12.1

Sol-PM 0.0 2.5 3.7 8.1 1.5 2.6 5.5 7.1

Nicotine 0.00 0.44 0.76 1.75 0.00 0.21 0.28 0.64

3-EP 0.18 0.23 0.28 0.70 0.00 0.07 0.10 0.23

Median Mean Std. Dev 95th %ile Median Mean Std. Dev 95th %ile

3.4 3.5 1.8 6.4 5.2 4.6 2.3 7.9

Impact of Source Segregation and Ventilation on ETS Levels
Source: US Dept of Transportation Study

16 14 12 10 8 6 4 2 0
Distant

Nicotine

Boundary

Smoking

Boeing 737-400

Distant

Boundary

Smoking

Clearly, Prohibition of Smoking in indoor facilities reduces exposure to a significant source of Indoor Air Pollution, but ……
Ventilation can remove other indoor contaminants, instead of just one.

The MAJOR Reasons Why People Accept/Tolerate/Advocate Smoking Bans
They hate the smell of cigarette smoke, and are willing to overlook scientific inconsistencies because the absence of ETS makes for a more pleasant indoor environment. They hold a personal grudge against the industry because their father/mother/uncle died of lung cancer and they want revenge. They believe that de-normalizing smoking as socially acceptable behavior will lead to reduced health care costs for everyone. They need to be part of a crusade. It is easier for them to focus on one source of indoor air pollution than to understand the complexity of the “soup” we live in, with or without smoking. They legitimately believe that banning public smoking will reduce their exposure to toxic substances.

Biggest Science-Related Hurdles to Overcome
Getting the public to understand the difference between personal opinion/beliefs and science.
In a society where there are still serious debates about evolution, this can be a real challenge.

Avoiding the “means justifying the end” syndrome.
Distortion/”selective reporting” of science in the name of preventing teenagers from taking up smoking.

Demanding that public health officials provide perspective for the information they provide.
Sure there are 43 carcinogens in ETS, but there are probably about 40 carcinogens in diesel exhaust, wood smoke, etc

A Chemist’s Interpretation of the Heath Effects Studies

Guiding Principle
“The poison is in the dose…”
Paracelsus, early 1500’s

If we did not believe that, we would not drink tap water, eat lettuce, etc.

ETS Exposure and Lung Cancer
Most of the studies to date have been on a very narrow slice of the population:
Women who are truly lifetime never-smokers (< 100 cigts smoked ever) who have lived with their continuously smoking husbands for their entire life. (Applies to 2 – 5% of the female population.)

If all the studies are taken together, there MAY be a 25% increased risk in these subjects relative to lifetime never smokers. (10.8 per 100,000 vs 8.67 per 100,000). Risk assessment generally irrelevant for former smokers. Health effects only apply to TRUE LIFETIME NEVER SMOKERS EPA estimated excess lung cancers due to ETS 1/4th that due to radon exposure. Results have NOT been consistent. For example, a broader, more recent PROSPECTIVE study in California showed NO increase in risk to lung cancer, heart disease, or COPD.

ETS Exposure and Heart Disease
At the current measured exposure levels, it is very difficult to conceive of a plausible biological mechanism based on what we understand today. CO from other sources much more important, and nicotine levels from ETS just too low. Note that “health effects” studies used questionnaires to assess lifetime exposure.

ETS Exposure and Lower Respiratory Disease
Definitely seems to be a factor of 2 – 3 increase among pre-school age children whose parents smoke at home. Note that this matches the criteria used by NCI as a measurable increased risk.

Why I Remain Very Skeptical
The observed risk factors, if significant at all, are barely above “statistical significance.” The science being done in some cases – not all – is shoddy at best. The smear tactics used by advocates suggest an unscientific mindset.

The Bottom Line
Assessing actual human exposure to ETS can be very complex. Studies to date show that overall ETS exposures are low, and in most cases, you get more from living with a smoking spouse than anywhere else. From a chemist’s perspective, some acute problems (asthma, bronchitis, lower respiratory disease) associated with ETS are probably real. The increased risk of chronic diseases (lung cancer, heart disease) is probably below epidemiology’s detection limit, given the confounders. If you like to get verbally abused, study ETS and publish politically incorrect scientific findings.