the hazards of secondhand smoke

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NHANES III Distribution of Cotinine in U.S. Population >4 yrs of Age .... estimated serum cotinine level of a ...... plasma cotinine clearance rate (64 ml/minute).
CYPRUS INTERNATIONAL INSTITUTE FOR THE ENVIRONMENT AND PUBLIC HEALTH IN ASSOCIATION WITH HARVARD SCHOOL OF PUBLIC HEALTH

THE HAZARDS OF SECONDHAND SMOKE J.L. Repace, MSc., Biophysicist Adjunct Professor, Tufts University School of Medicine

Repace Associates, Inc. Secondhand Smoke Consultants www.repace.com © Repace Associates, Inc. 2007

Secondhand Smoke: 90% Sidestream + 10% Exhaled Mainstream Sidestream Smoke SS ~90% All smoke fractions formed in combustion zone

Mainstream Smoke

Exhaled Mainstream Smoke ExMS ~10%

Mainstream smoke goes into the smoker; sidestream and exhaled mainstream smoke go into the air.

Secondhand Smoke: Science Policy Issues •  •  •  •  •  •  • 

Evidence for Hazard? Magnitude and Extent of Exposure? Biomarkers for SHS Dose? Evidence for Dose-Response? How Big is the Risk? Risk Management: Ventilation or Bans? Forensics: Estimating Individual Risk

Tobacco Smoke Diseases (2004 Surgeon General’s Report)

•  •  •  •  •  •  •  •  •  •  •  • 

Bladder cancer Cervical cancer Esophageal cancer Kidney cancer Laryngeal cancer Leukemia Lung cancer Oral cancer Pancreatic cancer Stomach cancer Abdominal aneurism Atherosclerosis

•  Cataract •  Cerebrovascular disease •  Chronic Obstructive Pulmonary diseases •  Chronic Morbidity •  Coronary heart disease •  Lung function decline •  Osteoporosis •  Pneumonia •  Peptic Ulcers •  Reproductive effects •  Respiratory Symptoms

and more...

UK male doctors study: 40 yrs, 1951 - 1991 Effects of cigarette smoking on survival 100

Source: Doll, Peto et al., 1994

90

80%

80

HAZARD

% Alive

70

Includes Passive Smokers

60

50%

50

Never Smoked Regularly 40

33%

Current Smokers (1-14 cig/day)

30

Current Smokers(15-24 cig/day)

20

Current Smokers (25+ cig/day)

10

8% No Evidence of a Threshold Exposure Causes Loss of Life Expectancy

0 35

40

45

50

55

60

65

Age

70

75

80

85

90

95

100

Lung Cancer Risks in Non-Inhaling Cigarette Smokers Exposed to SHS are Major Fractions of Those in Inhalers Odds Ratio for Lung Cancer

14 12

IN

10 8

NI

6 4

NS

2 0

Non Smokers Non Inhalers Inhalers

ACS 25 States

Swedish Men

PASSIVE SMOKING BY SMOKERS CAUSES SIGNIFICANT RISKS

Cigar Smokers Who Dont Inhale (NCI Monograph 9, Ch. 4)

PASSIVE SMOKING BY CIGAR SMOKERS HAS SIGNIFICANT CANCER RISKS

10

5

Cancer Type

Pancreas

Bladder & Urinary

Esophagus

Pharyngeal Cancer

Larynx

NONSMOKERS’ LEVEL

0

Lung Cancer

Cancer Odds Relative to Nonsmokers

15

SMOKERS WHO LIVE WITH SMOKERS HAVE HIGHER CANCER RISK

RELATIVE RISK OF CANCER

SMOKERS' PASSIVE SMOKING CANCER RISK Sandler et al. Lancet Feb. 9, 1985 312-315. 2.5

2.0

1.5

1.0

0.5

0.0

0

1

2

3

#of Additional Household Smokers

Toxic Substances in Secondhand Smoke Include:

•  •  •  •  • 

67 Human or Animal Carcinogens 47 Hazardous Wastes 33 Hazardous Air Pollutants 3 OSHA-Regulated Carcinogens 3 EPA Criteria Pollutants (CP)

Secondhand Smoke Contains Numerous Workplace Carcinogens 4-aminobiphenyl: bladder cancer arsenic: lung & lymphatic cancer benz(a)pyrene: lung cancer 1,3 butadiene: cancer of blood-forming organs cadmium: prostate,blood & lung cancer chromium VI: lung cancer

formaldehyde: nasal sinus cancer b-napthylamine: bladder cancer 210Polonium:

lung cancer vinyl chloride: liver cancer vinyl cyanide: brain tumors, lung & bowel cancer

Epidemiological Studies Use Spousal Smoking Status as a Measure of Passive Smoking Exposure

Odds Ratio for Lung Cancer Relative Risk for LCD Death

Hackshaw et al., BMJ 315:981-988 (1997)

Mean Risk of Lung Cancer Death (LCD) Appears to be 30% Using Spousal Smoking Status as index of exposure

3.00

M:1.34 (0.97-1.84)

2.50

2.00

LCD RR (F)

1.50 LCD RR (M)

1.00

0.50

F:1.24 (1.13-1.36) 0.00 0

10

20

30

40

37 Studies of Passive Smoking and LCD

META-ANALYSIS OF BEST STUDIES OF ETS & LUNG CANCER

Relative Risk for CHD Odds Ratio for Coronary Heart Disease Death

He, et al., NEJM 340:921-926 (1999)* *(Garland study corrected from 14.9 to 2.7) 3.00

OR = 1.24 (1.17-1.32)

Mean Risk of Coronary Heart Disease Death (CHD)Appears to be 24% using spousal smoking status as exposure index

2.50

2.00

1.50

1.00

0.50

0.00 0

5

10

15

20

18 Studies of CHD & Passive Smoking

Is Spousal Smoking Status an Adequate Exposure Measure for Passive Smoking?

88% of U.S. Population is Exposed to ETS; but only ~ 40% Report Exposure No reported home or work ETS exposure

% of Population

4

Overlap

3

Cotinine Dosimetry

Reported home or work ETS exposure

Passive Smoking Risk Is Underestimated Because Unexposed Persons Are Rare

2 1

0.1

1.0

10

Serum Cotinine, ng/mL NHANES III Distribution of Cotinine in U.S. Population >4 yrs of Age

Pirkle et al., JAMA 275: 12-33-1240 (1996)

100

EXPOSURE-RESPONSE IN PASSIVE SMOKING: LUNG CANCER (Hirayama T., Proc. 5th World Conf. Smoking & Health (1983) >20 cpd

75

15-19 cpd 50

1-14 cpd exsmoker

25

nonsmoker

Spouse's Smoking Category (cigarettes per day)

5

4

3

2

0 1

Excess Lung Cancer Risk (%)

100

NONSMOKERS’ CANCER RISK INCREASES WITH NUMBER OF HOME SMOKERS NONSMOKERS' PASSIVE SMOKING CANCER RISK Sandler et al. Lancet Feb. 9, 1985 312-315.

RELATIVE CANCER RISK

3.0

2.5

2.0

1.5

1.0

0.5

0.0

0

1

2

#Household Smokers

3

Airways Obstructive Disease, Outdoor Air Pollution, and Passive Smoking Abbey, et al. Int. J. Epidemiol 22:809-817 (1993)

Child,Adult Home, Work ETS Adult Work & Childhood ETS

125

100

75

50

P 30 years of exposure = 100% increase

Years of Exposure to Secondhand Smoke Pangiotakos D, et al. Presented at the European Society of Cardiology Congress, Vienna, Austria, 30 August-3 September 2003

HEART ATTACK RISK REDUCED BY SMOKE-FREE LAWS

EXPOSURE-RESPONSE IN PASSIVE SMOKING: STROKE Passive Smoking as well as Active Smoking increases the risk of acute stroke

7.0

PS Unexposed

6.0

PS Exposed

5.0

ExS 2-10 Yrs

4.0

ExS 20 CPD

1

0

Increasing Exposure -------> 1

Odds Ratio for Breast Cancer

5

Tobacco Smoke Exposure Status

Morabia et al. American J Epidemiol 143:918-928 (1996)

©Repace Associates, Inc. 2003*

CARBON MONOXIDE (CO) IN A GALWAY PUB Mean Secondhand Smoke CO Level is 8 ppm Galway Pub Venue #4 15 14 13 12

Total CO, ppm

Measurements Continuous monitor CO trace for Galway, Ireland, Pub #4, a large bar and music venue of 276 m3 volume. Ave. # occupants: 128 (SD 7.0); ave. # active smokers: 7.3 (SD 1.5). Estimated Mean SHS-CO is 8 pm (SD 2.5). ETS-CO Data for all pubs is shown in figure 2. Analysis The air exchange rate is 0.87 h-1; Calculated smoke particle concentration (SHS-RSP is 1,976 g/m3. For an 8-hr workday, at a respiration rate of 1 m3/h, the estimated serum cotinine level of a pubworker is 9.9 ng/ml.

11 10 9

Mean

8 7 6 5 4 3 2 1 0

Background Level 0

(Mulcahey M, Repace J, Indoor Air 2002)

20

40

60

80

100

Time, min

120

140

160

Exposure to SHS Impairs Healthy Adult Nonsmokers’ Coronary Circulation to Smokers’ Levels at SHS-CO Concentrations 25%Lower than found in Irish Pubs Otsuka et al. JAMA 2001;286436-441

Coronary Flow Velocity Reserve

4.5

Nonsmokers 4.0

3.5

Smokers

3.0

Before PS

After PS

Exposure Level: 6 ppm SHS-Carbon Monoxide for 30 minutes

Even occasional secondhand smoke increases the risk of developing acute coronary syndromes, especially when other risk factors are present.

Panagiotakos DB, et al. The association between secondhand smoke and the risk of developing acute coronary syndromes, among non-smokers, Under the presence of several cardiovascular risk factors: The CARDIO2000 case-control study. BMC Public Health 2002, 2

THE HELENA SMOKING BAN: ASSOCIATED WITH A 40% DROP IN HOSPITAL ADMISSIONS FOR ACUTE MYOCARDIAL INFARCTION (Sargent et al., BMJ 2004:328:977-983)

Helena

BAN

Outside Helena

Admissions for acute myocardial infarction during six month periods June-November before, during (2002) and after the smoke-free ordinance (ordinance did not apply outside Helena). The law was implemented on 5 June 2002, and repealed on 3 December 2002

TOBACCO SMOKE EFFECTS AT LOW DOSES

ESTIMATED U.S. & CALIF. MORBIDITY AND MORTALITY FROM ETS EXPOSURE (California Air Resources Board, 2005)

(range: 3423-8866)

Estimated Passive Smoking Deaths (U.S. Values from AJ Wells, Env. Internat. 25:515-519, 1999)

Cause Lung Cancer Heart Disease Breast Cancer Cervical Ca. Nasal Sinus Ca.

Brain Cancer, Leukemia, & Lymphoma

Total Total 2001 Population

U.S.A. 3060 47000 8700 500 200 1000

Nebraska U.K. Cyprus

60 460

12357 300 141

290 million

18 8 623 277 128 9562 5124 1770 31.4 102 10.5 41 6 3 203

59 million 0.79 1.71

Per Year Year Per

[Nebr. deaths scaled from U.S. deaths by relative population J.L. Repace] Cyprus

U.S. Authorities Condemn Secondhand Smoke •  •  •  •  •  •  •  •  •  •  • 

• 

U.S. Surgeon General 1986: SHS causes lung cancer National Academy of Sciences 1986: SHS causes lung cancer U.S. NIOSH 1991: SHS an occupational carcinogen, may cause heart disease U.S. EPA 1992: SHS causes lung cancer, respiratory disease U.S. National Cancer Institute 1993: SHS causes lung cancer U.S. OSHA 1994: SHS causes cancer and heart disease California EPA 1997: causes lung cancer, nasal sinus cancer, heart disease, and respiratory disease U.S. National Toxicology Program 2000: listed as “known human carcinogen” U.S. Surgeon General 2001: causes fatal heart disease U.S. Centers for Disease Control 2004: persons at risk of cardio-vascular disease should avoid all indoor environments that permit smoking California EPA 2006 report: Adults: causes lung, nasal sinus, & breast cancer; acute & chronic heart disease morbidity & mortality, altered vascular properties, asthma induction; eye & nasal irritation. Suggestive evidence of stroke, allergic sensitizization & chronic respiratory symptoms. SIDS ... U.S. Surgeon General 2006: No safe level of SHS Exposure; Spatial Separation, Ventilation, or Air Cleaning Won’t Control SHS

CYPRUS INTERNATIONAL INSTITUTE FOR THE ENVIRONMENT AND PUBLIC HEALTH IN ASSOCIATION WITH HARVARD SCHOOL OF PUBLIC HEALTH

EXPOSURE TO SECONDHAND SMOKE J.L. Repace, MSc., Biophysicist Adjunct Professor, Tufts University School of Medicine

Repace Associates, Inc. Secondhand Smoke Consultants © Repace Associates, Inc. 2007 www.repace.com

Integrated Exposure Equation {A person i is present at location j and is exposed to concentration C for a time t}

m

Qi = ∑ C( j)t j j =1

(

g-hr/m3)

Total RSP Exposure 1428 Percent of Total RSP Exposure

82% 10% 8%

g-h/m3

Secondhand Smoke: 90% Sidestream + 10% Exhaled Mainstream Sidestream Smoke SS ~90%

Mainstream Smoke

Exhaled Mainstream Smoke ExMS ~10%

Mainstream smoke goes into the smoker; sidestream and exhaled mainstream smoke go into the air.

SHS Exposure Assessment

J.L. Repace Repace Associates, Inc. Secondhand Smoke Consultants

THE TIME-AVERAGED MASS-BALANCE MODEL Theoretical

g(T ) x(T ) ≅ φv

(1)

Time-Averaged Pollutant Concentration x(t1-to) [ Pollutant Generation Rate g(t1-to) [

g/m3] =

g/h] / Supply Rate of Clean Air

[m3/h]

Pollutant Generation Rate (mg/h) = (mg/min)(min/cigarette)(cigarettes/h) Supply Rate of Clean Air = (m3 of space volume)(air changes per hour)

Practical

Ds x=Κ φ

Ds = space cigarette density; rate;

(2) = effective air exchange

K = mass of pollutant emitted per cigarette/h

RJ Reynolds OSHA Submission, 1995 ETS-RSP Emissions, Top 50 Brands 1 8 1 6 1 4

Frequency

1 2 1 0 8 6 4 2 0 6

8

1 0

____ G( T)/ T:

1 2

1 4

1 6

1 8

ETS-RSP

2 0

2 2

(mg/cig)

2 4

ETS-RSP & Nicotine, Top 50 US Cigarette Brands [RJ Reynolds OSHA Testimony, 1994] 25

ETS-RSP (mg/cig)

20

15

means: 14 mg RSP, 1.8 mg Nicotine 10

5

0 0

5

10

15

20

ETS-Nicotine (mg/cig)

25

DYNAMIC GROWTH AND DECAY OF TOBACCO SMOKE Growth Curve: (G/ φ)[1-exp(-φT)] ; Decay Curve: (G/φ)[exp(-φT)] 12 SMOKING STOPS GROWTH CURVE

Smoke Concentration

10

ACH: φ = 0.1 ACH : φ = 0.3

LOW EFFECTIVE AIR EXCHANGE RATE 8 DECAY CURVE

6

4

HIGH EFFECTIVE AIR EXCHANGE RATE 2 SMOKING STARTS 0 0

20

40

60

Elapsed Time

80

100

120

Exponential Growth & Decay of A Cigarette for 2 Air Exchange Rates 1

1cig φ = 0.1 ACH

NORMALIZED CONCENTRATION

1 cig φ = 0.3 ACH

Y(t) = Y(0)e-

t

y = 1.81 * e^(-0.1 T) R2= 0.999 DECAY CURVE 0.1

Calculate from slope of decay curve

y = 20 * e^(-0.3 T) R2= 0.999 DECAY CURVE

0.01 0

10

20

30

ELAPSED TIME

40

50

60

Dynamic RSP & PAH Levels Controlled Experiment: 7 Marlboro Cigarettes burned at rate of 1 per hour (14 mg/cig)

Smokers, Millions

Cigarettes, Billions

Cigarettes/Smoker-Day

U.S. Cigarette Consumption 1965 - 2000 [US CDC, FTC 650

600 BILLIONS OF CIGARETTES SOLD PER YEAR

550

500

NUMBER

450

400 60 50

MILLIONS OF SMOKERS

40 30

CIGARETTES PER SMOKER PER DAY

20 10 0

1965

1970

1975

1980

1985 Year

1990

1995

2000

WHAT PERCENT OF A MIXED GROUP OF SMOKERS & NONSMOKERS WOULD BE EXPECTED TO BE FOUND SMOKING AT ANY RANDOM INSTANT?

U.S. If 1/5 of adults smoke*, and the average smoker smokes 1/3 of the time, then 1/15 or 6.7% of a mixed group of smokers & nonsmokers might be found smoking at any instant in a U.S. setting.

In 70 hospitality venues** studied 2004-2006 in Delaware, Virginia, Pennsylvania, Massachusetts, and Texas, an average of 6.6% (range 0% to 26%) of persons were smoking at any instant

*2004 PREV.

**Hospitality studies: DE, JOEM Repace, 2004; MA, Repace et al, BMC Public Health, 2006; TX Waring & Siegel, JESEE, 2007; VA & PA, Repace unpublished.

ASHRAE STANDARD 62 SPECIFIES DEFAULT OCCUPANCY & VENTILATION RATE PER OCCUPANT FOR COMMERCIAL FACILITIES

Basic Assumptions of the Habitual Smoker Model •  At 30 cigarettes per smoker per day, assuming a 15 hour smoking day, yields an average of 2 cigarettes smoked per smoker per hour. Thus the average “habitual smoker” spends ~1/3 of the time smoking. •  One third of any group of smokers encountered in public will be found to be smoking at any instant. •  All smokers may be represented by a typical “habitual smoker” who smokes a standard cigarette emitting 14 mg of SHS-RSP when smoked to completion, or 1.4 mg of SHS-RSP per minute for 10 minutes.

Habitual Smoker Model Derivation (i) •  If it takes 10 minutes to smoke a cigarette, a single smoker will smoke 2 cigarettes per hour, or 1/3 of the time. •  At a rate of 2 cigarettes per smoker-hour, 3 “habitual smokers” will smoke 6 cigarettes per hour. •  If each smoker smoked consecutively, 1 cigarette would be burning constantly for every 3 smokers. •  At a generation rate of 14 mg of secondhand smoke (SHS) respirable particles (RSP) per 10 minute cigarette, each cigarette generates SHS-RSP at g = 1.4 mg/min. •  Let the space volume = , and the SHS-RSP removal rate = . •  The time-averaged SHS-RSP concentration from the massbalance model is: X(T) = g(T)/ = X(1 h) = g(1 h)/ . •  X(1 h)=[(6 cig/h)(1.4 mg/min-cig)(10 min/cig)/ = 84 mg/cig-h/ .

Habitual Smoker Model Derivation (ii) •  Since 1 mg = 1000 g, X(1 h)=84000 g/cig-h/ •  Dividing numerator and denominator by 100: •  X(1 h)= 840 g/cig-h/ per 1 constantly burning cigarette •  = 840n g/cig-h/ per n constantly burning cigarettes •  = removal rate in air changes per hour (h-1) and •  = space volume in cubic meters. •  Define: = space volume in hundred cubic meter units •  = 840n/ 840 (n/ )/ g/cig-h/ 100 m3] •  Define 1 constantly burning cigarette = 1 active smoker •  Define: Ds = (n/ ) in units of active smokers per 100 m3. •  Then: = 840 Ds/ g/m3], •  Where Ds is the Active Smoker Density (# burning cig/100 m3) •  a + k, the effective air exchange rate for ventilation + deposition

Habitual Smoker Model Derivation (iii) •  •  •  •  •  • 

• 

= 840 Ds /

g/m3]; Active Smoker Model for Field

Surveys Ds = Active Smoker Density (Burning Cigarettes/100 m3) Effective Air Exchange Rate (Air Changes per Hour) Define Dhs = Habitual Smoker Density (units: HS/100 m3) Recall: It takes 3 habitual smokers to equal 1 active smoker. Thus: DS = DHS / 3;

= 280 DHS /

g/m3]; Habitual Smoker Model for

Modeling

•  a (ventilatory air exchange rate) + k (surface sorption rate) •  Use k value if known. Useful Default Assumption: k = 0.29 a. •  a+k = 1.29 a.

•  SHS-RSP

Active Smoker Model with default k

•  SHS-RSP

Habitual Smoker Model with default k

DS / a DHS /a

g/m3]; g/m3];

Predicting ETS in Restaurants •  Assumed Design Occupancy as per: ASHRAE Standard 62: 70 persons/100 m2 •  Typical Ceiling Height (12 ft x .3048 ft/m): 3.7 m •  ASHRAE Standard 62-1999 Design Air Flow: 10 L/s per person •  Volume : (100 m2)(3.7m) = 370 m3 •  Air Exhange Rate: [(10L/s-P)/(1000 L/m3)] (70 P/370 m3) (3600 s/hr) = 7 hr-1

Predicting SHS in Restaurants •  Occupancy: 70 persons/100 m2 •  Smoking Prevalence 29%

nhs = (0.29)(70) persons) = 20 habitual smokers

•  Dhs = 100 nhs/V •  V = 370 m3 •  Dhs = 20 hs/370 m3 •  (Ds=Dhs/3 = 1.8 brng cigs)

•  Dhs = 5.4 hs/100 m3 •  a = 7 hr-1 •  N = 22 Dhs/Cv ( g/m3) N = (22)(5.4)/(7) = 17 g/m3; •  R=10 N = 170 g/m3 •  COmean = 0.88 Dhs/ a = 0.7 ppm @ 100% occupancy, during smoking

ETS in 9 Mass. Offices, 1991-1992 [Hammond, et al., JAMA 274:956-960(1995)]

•  Weekly Average Nicotine Sampled in 200-2500 Employee Worksites in Massachusetts •  9 Open-plan Offices, Unrestricted Smoking •  Passive Monitors, 0.1 g/m3 detection limit •  Results: Workday (9-hr) average nicotine concentration: Nmedian = 8.6 g/m3 (range 0 to 130 g/m3 ), lognormally distributed; •  Nmean = 14 g/m3; adj. to 8-hr day: 16 g/ m3

Predicting SHS in 9 Mass. Offices, 1991-1992 •  Assumed Design Occupancy as per: ASHRAE Standard 62: 7 persons/100 m2 •  Typical Ceiling Height (10 ft x .3048 ft/m): 3.0 m •  ASHRAE Standard 62 Design Air Flow: 10 L/s per person •  Volume : (100 m2)(3.0m) = 300 m3 •  Air Exhange Rate: [(10L/s-P)/(1000 L/m3)] (7 P/300 m3) (3600 s/hr) = 0.84 hr-1

Predicting ETS in 9 Massachusetts Offices, 1991-1992 •  Smoking Prevalence 29%

•  nhs = (0.29)(7 persons) = 2 habitual smokers •  •  •  •  • 

Dhs = 100 nhs/V V = 300 m3 Dhs = 2 hs/300 m3 Dhs = 0.67 hs/100 m3 Cv = 0.84 hr-1

•  N = 22 Dhs/Cv ( g/m3) N = (22)(0.67)/(0.84) •  Nmean = 17.5 g/m3 (steady-state value) Observations: •  N8-hr mean = 16

g/m3

Estimated Range in Ave. Habitual Smoker Density, Dhs, for 1-Smoker U.S. Residences

•  A Habitual Smoker smokes 2 cigarettes/hr. •  Dhs = 100 nhs/V, where V is the space

volume, and nhs is the number of smokers. •  For 1975-built Single-Family homes with a single smoker, Ave. Dhs = 0.27 hs/100m3. •  For 1975-built Multi-Family homes with a single smoker, Ave. Dhs = 0.44 hs/100m3.

U.S. PM2.5 National Ambient Air Quality Standards (NAAQS) The PM2.5 NAAQS protects against premature death, increased hospital admissions and emergency room visits (primarily the elderly and individuals with cardiopulmonary disease); increased respiratory symptoms and disease (children and individuals with cardiopulmonary disease such as asthma); decreased lung function (particularly in children and individuals with asthma); alterations in lung structure, and in respiratory tract defense mechanisms. Annual PM 2.5 Standard 15 g/m3;24-hr Standard: 35 g/m3 .

Modeled ETS for N.Y. State homes Repace/Lowrey# Habitual Smoker* Model vs. Observations

7-Day Meas. Averages •  ETS-RSP = 29 g/m3 •  ETS-Nico = 2.2 g/ m3 Modeling Equations •  •  •  •  • 

Dhs = 100 nhs/V R = 217 Dhs/Cv Rdaily Ave. = (7.1/24) R N = R/10

Modeled Values •  Rdaily Ave. = 33 g/m3 •  Ndaily ave= 3.3 g/m3 •  R = 114 g/m3 (during •  N = 11.4 g/m3 smoking)

•  (14.2 cig/day)/(2cig/hr) =

7.1 hr of smoking/day •  nhs = 1 habitual smoker •  Dhs = 0.28 hs/100 m3

#RISK * 2 cig/habitual ANALYSIS, 13:463-475 (1993) smoker-hr

Predicted Nhs = 3*2.21 = 6.63 smokers Observed Nhs = 6+1/2+1/2 = 7 smokers

10 min aves. Time Smokers

8:40 8:50 9:00 9:10 9:20 9:30

3 4 2 2 2 2

Mean

2.5

(SD)

(0.83)

Predicted min/cig = 10 Observed min/cig = 8.2 (SD 2.5)

Ns = 1-min Average Number of Active Smokers = 2.21

THE BLACK DOG PUB Toronto, Canada SMOKING SECTION

Black Dog Pub, Scarborough, Ontario, Friday Dec. 13, 2002 7:00 1200

8:00

10 77

7

7

9:00

9 526 60 # burning cigarettes

10

1000

7

6

9

7

5 41

5 37

534

10 47

5

# of persons in smoking area

V = 195 m3

1100

458 744

4

11:00

10:00

7

5

7 49

13

5

1200

516

a = Cv = 8.5 h-1 5

# of burning cigarettes

5

10

5

7

5

13

1100 6

1000

Smoking prevalence 42%

900

900

800

Outdoor RSP Ave. = 20

g/m3; SHS-RSP ≈ 180

g/m3

Smoking Section

700

Pub Ave. PPAH = 134 ng/m3 Outdoor PPAH Ave. = 27 ng/m3; SHS-PPAH ≈ 107 ng/m3

600

PPAH ng/m3

RSP µg/m3

Mean # Persons 50; Active Smokers Ns = 6.94; Pub Ave. RSP = 200

g/m3 800

700

600

500

500

400

400

300

300

200

200

100

100

0

0 0

10

7:00 PM

20

30

40

50

60

70

80

90

RSP µg/m3 PPAH ng/m3

100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290

9:00 PM

Time, minutes

11:00 PM

Black Dog Pub Air Exchange Rate Calculation using the Habitual Smoker Model

•  SHS-RSP

a •  •  •  • 

R g/m3]

Indoor - Outdoor RSP difference: R = 180 g/m3 Black Dog Pub Volume V = 295 m3 Ave. # Active Smokers Ns = 6.94 Active Smoker Density Ds = (6.94)/2.95 = 2.35 AS/100m3

•  a

DS /R h-1 (Calculated)

• 

DS /

Predicted from ASHRAE or CO2:

Black Dog Pub Air Exchange Rate Calculation using ASHRAE Design Ventilation Standard 62-1999 •  •  •  •  •  •  •  •  •  •  •  • 

Maximum Occupancy (Restaurant & Bar): 150 persons Total Volume: Bar: 295 m3 [(45 P)(15 lps/occ)(3600 s/h)/295 m3][1m/1000 l) = 8.2 h-1 Design Air Exchange Rate: 8.2 ACH (air changes per hour) Air Exchange Rate Calculated from Hab. Sm. Model: 8.5 ACH Measured Carbon Dioxide Concentration: 760 ppm Ventilation Rate/person Calculated from ASHRAE Standard 62 CO2 Model: Vo (lps/P) = 5000 (lps/P-ppm)/(CO2 indoors - CO2 outdoors) Vo (lps/P) = 5000 (lps/P-ppm)/(760 - 532)ppm = 22 lps/P, with 32 persons; scaled to 45 persons: (32/45)(22) = 15.6 lps/P CO2 Measured Air Exchange Rate: 15.6 lps/occ 8.5 ach Predicted ACH = Observed ACH ≈ Design ACH Conclusion: Habitual Smoker Model Useful for Air Exchange Rate Calculation in Mechanically Ventilated Premises

Jones et al. KMA Journal 104:281-288 (2006) Paducah KY RSP smoking areas 1000

RSP (PM2.5), micrograms per cubic meter

y = -6.6668 + 225.67x R2= 0.89107

Total RSP & Active Smoker Density In 5 Kentucky Bar/Restaurants

800

600

400

200

0 0

0.5

1

1.5

2

2.5

3

3.5

Smoker Density, D (active smokers per hundred cubic meters) s

Repace JL, J Occup Environ Med. 2004;46:887–905 RSP (PM3.5) in 6 Wilmington, Delaware bars, 2002 350

350

RSP (micrograms per cubic meter)

y = 67.823 + 195.08x R2= 0.97394 300

300

Total RSP & Active Smoker Density In 6 Delaware Bar/ Restaurants

250

200

250

200

150

150

Statistic 100

50

Boston RSP Boston Ds

Minimum

43

0.03

Maximum

338

1.31

Points

6

6

Mean

179

0.60

Median

157

0.525

Std Deviation

129

0.480

100

50

0

0 0

0.5

1

1.5

Active Smoker Density, D (active smokers per hundred cubic meters) s

PM

2.5

in 14 Western New York State Bars & Restaurant/Bars Travers, et al. MMWR, Nov. 12, 2004 1038-1041

RSP Pre-Post Ban, micrograms per cubic meter

1400

1200

RSP = 252 + 97.8x R2= 0.071 Regression Line, RSP Pre-Post Ban 1000

Scatter Due to heterogenity in ACH 800

600

400

CH

HIGH A

200

0 0

0.5

1

1.5

2

2.5

3

3.5

D Pre-Ban Active Smoking Density (ave. number of burning cigarettes per 100 cubic meters) s

PM

2.5

in 14 Western New York State Bars & Restaurant/Bars

RSP Pre-ban - Post-ban, micrograms per cubic meter

Travers, et al. MMWR, Nov. 12, 2004 1038-1041 1400

curve-fit: RSP

pre-post

= 643/a

-0.9

R 2= 0.66

1200

RSP Pre-ban - Post-ban 1000

800

600

400

200

0 0

2

4

a = 650D /RSP s

pre-post

6

8

(air changes per hour)

10

PM

2.5

in 14 Western New York State Bars & Restaurant/Bars Travers, et al. MMWR, Nov. 12, 2004 1038-1041

RSP (micrograms per cubic meter)

500

400

Pre-Ban RSP Post-Ban RSP 300

93% drop

200

100

0

Pre-Ban RSP

Post-Ban RSP Smoking Status

PM

2.5

in 14 Western New York State Bars & Restaurant/Bars Travers, et al. MMWR, Nov. 12, 2004 1038-1041 SHS-RSP = RSPpre-ban - RSPpost-ban

RSP Pre-Post, micrograms per cubic meter

10

4

RSP = 266* e^(0.955norm(%))

R2= 0.97

SHS-RSP is log-normally distributed 1000

3

Median of data = 349 µ g/m

3

Geometric Mean = Median for Curve Fit: 266 µ g/m

100

log-normal curve-fit, RSP

Pre-Post

LOG-PROBABILITY PLOT 10 .01

.1

1

5

10

20

30

50

70

80

90

95

CUMULATIVE FREQUENCY, Percent

99

99.9

99.99

FIELD SURVEYS OF SECONDHAND SMOKE

Ecochem PAS 2000 CE PPAH Monitors

MIE pDR 1200 RSP Monitors

Monitors for SHS

ToC, RH%, CO, CO2 Monitors

MEASURING SHS EXPOSURE TAKES CALIBRATED EQUIPMENT

SCEM+BKGND Model PZBR1 RSP (PZB) MIEA RSP

(MIE)

7 Marlboros Smoldered At a rate of 1 per hour in a 41 m3 California Bedroom (Ott & Repace, 2003) Silicon Valley Calibration Experiments, March per 11, 2003 Air Exchange Rate: 0.8 air changes hourExpt.

PPAH

RSP

800

800

TimeAveraged Value 600

600

400

400

Cyclones

3

PPAH Concentration, ng/m

Model, PZB, MIE Concentration,µg/m

3

Fine Particle & Carcinogen Air Pollution Levels

200

200

PZB Cleaned 0

0 0

100

200

300

400

Elapsed Time, minutes ELAPSED TIME, MINUTES

500

The 2002-2003 Delaware Air Quality Study: Air Pollution Before & After a Smoking Ban

Repace (2003), www.repace.com

AIR POLLUTION IN 7 HOSPITALITY VENUES BEFORE A SMOKING BAN Delaware Hospitality Industry Secondhand Smoke Survey: Real-time RSP & PPAH, Friday Nov. 15, 2002 1200

1200

1100

1000

PPAH ng/m3 particle-bound carcinogens

900

900

800

800

700

700

600

SMOKING

BAR B

600

500

500 BAR G

400

400

CASINO A

300

300 BAR F BAR E

200

200

BAR D

100

100

BAR C

0

0 0

6:15 pm

30

60

90

120

150

180

9:15 pm

Elapsed Time (minutes)

210

240

270

300

330

11:45 pm

PPAH, nanograms per cubic meter (ng/m3)

POOL HALL H

RSP µ g / m3

1000

RSP, micrograms per cubic meter (µg/m3)

1100

fine-particle air pollution

AIR POLLUTION IN 7 HOSPITALITY VENUES AFTER A SMOKING BAN Delaware Hospitality Industry Secondhand Smoke Survey: Real-time RSP & PPAH After The Smoking Ban 1200

1200

1100

1100

fine-particle air pollution

1000

1000

RSP µg/m3 PPAH ng/m3

900

900

particle-bound carcinogens 800

PPAH ng/m3

RSP µg/m3

800

700

600

SMOKE-FREE

500

700

600

500

400

400

300

300 BAR B

CASINO A

200

BAR C

BAR D

BAR F

BAR E

BAR G

POOL HALL H

200

100

100

0

0 0

6:15 PM

30

60

90

120

150

180

210

9:15 PM

Elapsed Time (minutes)

240

270

300

330

11:45 PM

360

SMOKE-FREE LAW CLEARS THE AIR CARCINOGEN (PPAH) LEVELS DROP BY 95% 150

100

50

0

BEFORE Nov 15, 2002

AFTER Jan 24, 2003

FINE PARTICLE AIR POLLUTION (RSP) LEVELS DROP BY 90% RSP, micrograms per cubic meter

PPAH, nanograms per cubic meter

Repace JL, JOEM 46:887-905 (2004)

250

200

150

100

50

0

BEFORE

AFTER

Nov 15, 2002

Jan 24, 2003

8 Delaware Hospitality Venues: Casino, 6 Bars, & Pool Hall

Effect of Increasing Proximity to a Smoker Outdoors

(smoked cigarette)

(smoldered cigarette)

CYPRUS INTERNATIONAL INSTITUTE FOR THE ENVIRONMENT AND PUBLIC HEALTH IN ASSOCIATION WITH HARVARD SCHOOL OF PUBLIC HEALTH

DOSIMETRY OF SECONDHAND SMOKE J.L. Repace, MSc., Biophysicist Adjunct Professor, Tufts University School of Medicine

Repace Associates, Inc. Secondhand Smoke Consultants www.repace.com

©Repace Associates, Inc. 2007

DISTRIBUTION OF SERUM COTININE IN U.S. POPULATION Pirkle et al. JAMA 275: 1233-1240 (1996)

1. Questionnaire Report: “Unexposed at Home or at Work”

2. Questionnaire Report: “Exposed at Home or at Work”

3. Questionnaire Report: “Smoker”

Pirkle et al. JAMA 275: 1233-1240 (1996)

Are Models Useful For Predicting Population Exposure to SHS? Typical non-tobacco-using persons

Most-exposed persons SERUM COTININE, ng/ml

Rosetta Stone Modeling of Nonsmoking U.S. Population to SHS Typical Adult non-tobacco-using persons (0.86 ng/ml)

Most-exposed persons (8.6 ng/ml) SERUM COTININE, ng/ml

Calculating Inhaled Dose of SHS-RSP to U.S. Population, early-mid 1980’s

•  Inhaled Dose = Concentration x duration x respiration rate x probability of exposure •  Concentration is estimated for the two most-frequented microenvironments: at home and at work •  Duration of Exposure is estimated from time-activity pattern studies. •  Respiration rate taken from physiological tables for different levels of activity. •  Probability of workplace exposure taken from national survey of smoking policies of 1000 large, medium, and small businesses. •  Probability of domestic exposure taken from national survey of the percent of children living in homes with 1 or more smokers.

MODELING DURATION:

Human Time Activity Patterns (Indoor Pollutants: National Research Council,1981)

Microenvironment Inside one’s home Just outside one’s home At one’s workplace In transit In other people’s homes In places of business In restaurants and bars In all other locations Total

Employed Men, All Days

13.4 0.2 6.7 1.6 0.5 0.7 0.4 0.5 24.0

Employed Women, All Days

15.4 0.0 5.2 1.3 0.7 0.9 0.2 0.3 24.0

Married Housewives, All Days

20.5 0.1 1.0 0.8 1.2 0.1 0.3 24.0

MODELING CONCENTRATION:

Prediction of Secondhand Smoke Air Pollution Levels from Ratio of Smoker Density to Air Exchange Rate nhs, number of habitual smokers

SHS-RSP = 217

(

V, volume of room, 100 m3 a, air exchange rate,

h-1

)

Units: micrograms per cubic meter (mg/m3) Repace & Lowrey, Environment International 11: (1985)

The time-averaged secondhand smoke respirable particulate pollution (SHS-RSP) level is directly proportional to the density of habitual smokers (nhs/V), and inversely proportional to the air exchange rate, a. Assumes each cigarette emits ~14 mg SHS RSP; 2 cigarettes per smoker-hour.

MODELING RESPIRATION

CHAPTER 5 INHALATION

MODELING DAILY SECONDHAND SMOKE EXPOSURE OF THE U.S. POPULATION: EXPOSURE = S(CONCENTRATION)(PROBABILITY)(RESPIRATION) MODEL SHS CONCENTRATION, C, IN MOST-FREQUENTED ENVIRONMENTS: HOME AND WORK (90% OF THE DAY) default 1-smoker U.S. Single-family home; ASHRAEdefault occupied and ventilated office. 2.  MULTIPLY SHS CONCENTRATION BY EXPOSURE PROBABILITY, P, (SURVEYS) TO YIELD WEIGHTED SHS CONCENTRATION, PC. 3.  MULTIPLY WEIGHTED CONCENTRATION BY RESPIRATION RATE (TABLES), TO YIELD INHALED LUNG EXPOSURE, E = CP. 4.  SUM INHALED EXPOSURE OVER 4 CATEGORIES: (i) AT WORK + AT HOME: 2.27 mg/day; P = 39% (ii) NEITHER AT WORK NOR AT HOME: 0 mg/day; P = 14% (iii) AT HOME BUT NOT AT WORK: 0.45 mg/day; P = 23% (iv) At WORK BUT NOT AT HOME: 1.82 mg/day; P = 24% 5. Exposure Probabilities estimated from surveys of workplace smoking policies and from percent of children raised in smoking homes. 1. 

Repace & Lowrey, Environment International 11:3-22 (1985)

ESTIMATED DAILY SHS-RSP EXPOSURE OF U.S. POPULATION IN 1980’s: R = 1.43 mg/day (Default respiration rates assumed; Repace & Lowrey, Env. Int. 11:1985)

P, Exposure Exposure % Environment Probability (smoking surveys) (time-activity studies)

C, Daily R = CP, Average Inhaled ProbabilityExposure, mg/day Weighted Daily (Habitual Smoker Model, Default respiration rates)

Exposure mg/ day

At Work and At Home

39

2.27

0.89

None

14

0.00

0.00

At Home Only

23

0.45

0.10

At Work Only

24

1.82

0.44

Total Exposure

100

-

1.43

Time-Averaged Plasma Cotinine Model [Repace and Lowrey, Risk Analysis 13: 463-475 (1993); *Risk Analysis 18: 71-83 (1998)]

P=(

E

T)

(ng/ml) E = HN = H(R/10) = Dose of nicotine (143 g/day) f  = fraction of nicotine absorbed by lung (0.71) f  = fraction of nicotine converted to cotinine (0.78)* = plasma cotinine clearance rate (64 ml/minute) T = # minutes/day (1440 minutes) x 1000 ng/ g} = P={ E T [(0.78)(0.71)(143)/(1440)(64)](1000) 0.86 ng/ml PHARMACOKINETIC MODEL RELATING SHS NICOTINE = EXPOSURE TO DOSE Most-exposed persons have 10 X exposure of Average persons: 8.6 ng/ml

Physical-Pharmacokinetic Models Plus Time-Activity Patterns Are Useful For Predicting Population Exposure to SHS *(Repace & Lowrey, Risk Analysis 13:463-475, 1993, adjusted to f = 0.78)

Repace & Lowrey (1985) SHS estimates validated using PPK modeling Modeled serum cotinine dose equivalent for 1.43 mg SHS-RSP probability-weighted exposure of typical U.S. person: 0.86 ng/ml*

Modeled dose, most-exposed U.S. person: 8.6 ng/ml*

...

NHANES III U.S. Population probability sample of non-tobacco users, 1989-1991 Pirkle et al. JAMA 275:1233-1240 (1996)

PROBALISTIC MODELING OF NICOTINE IN OFFICE AIR AND COTININE IN OFFICE WORKERS

THE MONTE CARLO METHOD

Point-Estimate of Secondhand Smoke Nicotine in a 1990’s Model U.S. Office Workplace Using the Habitual Smoker Model •  Occupancy: ASHRAE Ventilation Design Standard 62:

7 occupants/100 m2

•  Ventilation rate: Q = 10 lps/occ = 36 m3/h •  Default ceiling height: 3 m; default volume: 300 m3 •  Air exchange rate: a = (7 occ)(36 m3/h)/300 m3= 0.84 h-1 •  Smoking Prevalence: 29% (Early 1990’s U.S.A.) •  Smoker Density: Dhs= 2 smokers/300 m3 = 0.67 HS/100 m3 •  SHS-RSP = 217 Dhs/a = (217)(0.67)/(0.84) = 172 g/m3 • SHS-Nicotine = 21.7 Dhs/a = (21.7)(0.67)/(0.84) = 17.2 g/m3 •  Assume 8 h workday; 1 hour off for lunch, yielding 7 h of smoking •  8-h time-weighted ave. SHS-Nicotine for 7 h of smoking: 15.1 •  Observed 8-h TWA Nicotine for 12 New England Offices*: 15.8 m3 • *Occupational Exposure to Environmental Tobacco Smoke (Hammond et al. JAMA 274: 956-960 (1995)

g/m3 g/

SHS-RSP = 10 N: Ratio of SHS air concentrations

How Does Variation in Parameters Affect Models? [Adapted from: RJ Reynolds OSHA Testimony, 1995]

Frequency

30

Nicotine Emissions, Top 50 U.S. Brands of Cigarette

20

10

0 0.50

1.00

1.50

2.00

2.50

ETS-Nicotine (mg/cig)

3.00

Monte-Carlo Estimate of Secondhand Smoke Nicotine Distribution in a 1990’s Model U.S. Office Workplace [Repace, Jinot et al., Risk Analysis 18: 71-83 (1998)]

Essence of Monte Carlo method: each model parameter is replaced by a distribution.

[Repace, Jinot et al., Risk Analysis 18: 71-83 (1998)]

Note change of notation: a = Cv

ETS in 9 Mass. Offices, 1991-1992 [Hammond, et al., JAMA 274:956-960(1995)]

•  Weekly Average Nicotine Sampled in 200-2500 Employee Worksites in Massachusetts •  9 Open-plan Offices, Unrestricted Smoking •  Passive Monitors, 0.1 g/m3 detection limit •  Results: Workday (9-hr) average nicotine concentration: Nmedian = 8.6 g/m3 (range 0 to 130 g/m3 ), lognormally distributed; •  Nmean = 14 g/m3, 9 hour time-weighted ave. 3 •  Nmean adjusted to an 8-hrofday: 15.8 g/m This is the mean a distribution in N

Nicotine, Theory vs Observation for the Office Workplace (2 sm/1000 ft2; 0.75 ach)

Nicotine Concentration (

µg/m 3 )

[Repace, Jinot, Bayard, al. (Submitted)] Repace, Jinot, Bayard, et al., RisketAnalysis 18: 71-83 (1998)] 90 80

Experiment (Hammond et al, JAMA 274, 1995)

70

Theory

60 50

Monte Carlo analysis

40 30 20 10 0 0

10

20

30

40

50

Percentile

60

70

80

90

100

Salivary Cotinine: Theory vs Obs. for 93 Office Workers (2 sm/1000 ft2; 0.75 ach) [Repace, Jinot, Bayard, Emmons & Hammond, Submitted]

Repace, Jinot, Bayard, et al., Risk Analysis 18: 71-83 (1998)]

5.00

Salivary Cotinine (ng/m l)

Experiment (Emmons et al., Prev Med 23, 1994) 4.00

Stheory

3.00

2.00

1.00

0.00 0

10

20

30

40

50

60

Percentile

70

80

90

100

Predicting and Interconverting Secondhand Smoke Atmospheric and Biological Markers

J.L. Repace, MSc.,

Visiting Assistant Clinical Professor Tufts University School of Medicine and Repace Associates, Inc. Secondhand Smoke Consultants

www.repace.com

WORKSHOP ON BIOLOGICAL & ATMOSPHERIC MEASUREMENT OF TOBACCO USE AND EXPOSURE IN TRANSDISCIPLINARY RESEARCH, TORONTO, CANADA, MAY 19-20, 2005

This work is " supported by" the Flight " Attendant " Medical " Research " Institute

CDC SECONDHAND SMOKE EXPOSURE CHAMBER EXPERIMENTS DESIGNED TO TEST COTININE LEVELS IN BLOOD FOR A GIVEN SHS NICOTINE CONCENTRATION [JT BERNERT, US CENTERS FOR DISEASE CONTROL, ATLANTA, GA, personal communication]

SHS OUTPUT SHS INPUT

APPARATUS FOR SMOKE GENERATION

SECONDHAND SMOKE EXPOSURE CHAMBER

•  CDC CHAMBER EXPERIMENT DESCRIPTION •  N = 40 SEATED ADULTS EXPOSED TO SHS FROM MARLBORO OR NEWPORT CIGARETTES FOR 4 HOURS IN A 17.3 m3 CHAMBER AT AN AVERAGE OF SHS NICOTINE CONCENTRATION OF 147 g/m3. •  COTININE PEAKED AT 2 HOURS POST EXPOSURE •  COTININE MEASURED AT H = 6 HOURS •  RESPIRATION RATES NOT MEASURED

•  40 SUBJECTS: 21 FEMALE, 19 MALE, 18 BLACK, 22 WHITE •  ALL SUBJECTS HAD SIMILAR COTININE KINETICS

Peak-Value Plasma Cotinine Model [Repace and Lowrey, Risk Analysis 13: 463-475 (1993)]

P=(

)H

N (ng/ml) = fraction of nicotine converted to cotinine (0.78) = fraction of nicotine absorbed (0.71) = respiration rate ( 0.54 m3/hr) [SEDENTARY] = plasma clearance rate (64 ml/min) = mean cotinine residence time (1470 minutes) H = exposure duration (4 hours) *Experimental value at 4 h = 1.85 ng/ml: extrapolated from measurement 2 h post-exposure N = average nicotine concentration (147 g/m3) P={ x 1000 ng/ g} rHN = 1.86

PREDICTED VALUE at 6 h: P = 0.019 N; OBSERVED VALUE: P = 0.019 N

Data taken at 2 hours post-exposure reflect increase due to nicotine-cotinine-conversion with a 2 hr half-life

SHS Exposure & Dose Models •  Dynamic & Time-Averaged Concentration models are well-devloped but under-utilized by epidemiologists •  Individual & Population Exposure can be predicted using time-activity patterns plus concentration models •  Individual & Population Dose can be predicted using pharmacokinetic models applied to exposures

Rosetta Stone Equations for SHS Repace, Al-Delaimy & Bernert, JOEM 48:181-194 (2006)].

•  •  •  • 

SHS Marker, Units Time-Averaged Eqn. RSP(PM3.5), mg/m3 R = 217 Dhs/a Atmospheric 3 Nicotine, mg/m N = 21.7 Dhs/a markers Carbon Monoxide, ppm CO = 0.88 Dhs/a [Dhs = habitual smoker density, time-averaged burning cigarettes per 100 m3; a = ventilatory air exchange rate h-1]

•  Saliva Cotinine, ng/mL S = 0.006 rHN •  Serum Cotinine, ng/mL P = S/1.16 •  Urine Cotinine, ng/mL U = 6.5 P •  Hair Nicotine, ng/mg W = 0.44 N = 0.70 U ( •  [Respiration r m3/hr, H = # hours/day]

Biomarkers ts)

Repace JL. Effects of passive smoking on coronary circulation. JAMA. 2002; 287 #3, January 16; Repace JL, Jinot J, Bayard S, Emmons K, and Hammond SK. Air nicotine and saliva cotinine as indicators of passive smoking exposure and risk. Risk Analysis 18: 71-83 (1998); Repace JL, and Lowrey AH. An enforceable indoor air quality standard for environmental tobacco smoke in the workplace." Risk Analysis, 13:463-475 (1993).

Time-Averaged PK Model Agrees With Experimental Results •  Steady State Results of Benowitz and Jacob (1994), based upon nicotine titration in human smokers: Smokers Nicotine Dose D = 80 P mg/day, where P is smokers’ steady-state Cotinine Dose (ng/ml); Smokers’ PK Parameters: = 0.72 and t = 40.6 ml/min. •  Steady State PK Model of Repace & Lowrey (1993): D= HN/Td /day, a HN/ Td)(1000 ng/ g) ng/ml P= ( Yielding D = ( )P mg/day = {(40.6 ml/min)(1440 min/day)/(720)} P, or D = 81 P mg/day.

43 London Barworkers (1) 72 Boston Barworkers (2)

Various Studies: 1. Jarvis (2001); 2. Hyde et al. (2002); 3. Lavergne et al. (1998); 4. Mulcahey et al. (2001); 5. Hedley, et al., 2001); 6. Hyde et al. (2001); 7. Bates et al.; (2001),; 8. Jarvis (2001); 9. CDC (2003).

42 Montreal Restaurant/Bar Workers (3) 14 Galway, Ireland, Pubs (4) *

World Cotinine Data, Standardized to Urine

104 Hong Kong Restaurant Workers (5)

104

Rosetta Stone Application

100

1000

10

100

5

4

3

2

0 1

Excess Lung Cancer Risk (%)

100

©Repace Associates, Inc. 2003*

DOSE-RESPONSE IN PASSIVE SMOKING: HEART DISEASE INCREASES WITH COTININE, A BIOMARKER FOR EXPOSURE

Odds Ratio for Coronary Heart Disease

(Tunstall-Pedoe, et al., J Epidemiol and Comm Health 49: 139-143 , 1995) 3.00

4 to 17 ng/ml

4100 SCOTS

2.50

2.00

1 to 4 ng/ml 0 to 1 ng/ml

1.50

Not Detectable 1.00

0.50

0.00 1

2

3

4

Increasing Dose -----------> Serum Cotinine Category

©Repace Associates, Inc. 2003*

[Sandler et al. Lancet, Feb 9, 1985 312-315] (N= 1036)

3.00

p 30 years of exposure = 100% increase

Years of Exposure to Secondhand Smoke Pangiotakos D, et al. Presented at the European Society of Cardiology Congress, Vienna, Austria, 30 August-3 September 2003

Estimated Passive Smoking Deaths (U.S. Values from AJ Wells, Env. Internat. 25:515-519, 1999)

Cause Lung Cancer Heart Disease Breast Cancer Cervical Ca. Nasal Sinus Ca.

Brain Cancer, Leukemia, & Lymphoma

Total Total 2001 Population

U.S.A. 3060 47000 8700 500 200 1000 60 460

Nebraska U.K. Norway 1847 623 } 15:1 Heart/ 277 729 Lung Mortality 9562 51 135 1770 Ratio 3 8 102 1 3 41 616 203

12357 300 938

Per Year Year Per ©Repace Associates, Inc. 2003*

290 million

59 million 4.5 1.71

[Nebr. deaths scaled from U.S. deaths by relative population J.L. Repace] Norway

EXPOSURE-RESPONSE FOR SECONDHAND SMOKE HEART DISEASE DEATH ESTIMATED FROM RATIO OF HEART/LUNG CANCER DEATHS •  WELLS(1999)RATIO: 10-15 HEART DEATHS PER LUNG DEATH** **[Adjusted for positive & negative exposure misclassification bias; derived from Epi Studies]

•  REPACE et al. (1998) RATIO: 10 HEART DEATHS/LUNG DEATH* [Derived from Wells (1999) lower-bound estimate of 32,000 heart deaths/3000 lung deaths]

*[CONSISTENT WITH RATIO DERIVED BY TAKING THE MEAN OF AGE-SPECIFIC HEART/LUNG DEATH RATES (FROM ACS CPS II)WEIGHTED BY THE NUMBER OF PERSONS ALIVE IN EACH 5-YEAR AGE GROUP (FROM ACS CPS I). YIELDS AGESTANDARDIZION TO 1974 POPULATION, FOR WHICH REPACE & LOWREY(1985) MODELED EXPOSURE-RESPONSE FOR LUNG CANCER FROM PASSIVE SMOKING.]

Passive Smoking CHD Exposure-Response: ER = 50 heart disease deaths (100 000 PY-mg/day) [ACS CPS II: see NCI Smoking & Tobacco Control Monograph #8]

REPACE et al.(1998) MODEL ASSUMES HEART DISEASE EXPOSURERESPONSE IS 10 TIMES THE DERIVED LUNG CANCER EXPOSURE RESPONSE

Heart Disease-to-Lung Cancer Mortality ratio

Age-Specific HDD/LCD ratio, Males and Females Combined ACS-CPS II data from NCI Monograph 8, Appendices 19-22 (1997).

100

100

Repace Model Assumption

10

10

1

1 10

50

100

Midpoint Year of 5-Year Age-group

IF THIS AGE-DEPENDENT RATIO IS AGESTANDARDIZED TO THE 1974 U.S. POPULATION THE VALUE IS ~10:1 1974 populationweighted mean ratio

WELLS (1999) DERIVED A RATIO OF 15:1 FOR TOTAL HEART/LUNG DEATHS FROM EPI STUDIES

RESPONSE MODEL FOR PASSIVE SMOKING COMPARED TO CPS II RATES

Heart Disease or Lung Cancer Mortality Rate per 100,000 person-years (CPS II)

Age-Specific HDD/LCD rates, Males and Females from ACS-CPS II, NCI Monograph 8, Appendices 19-22 (1997).

10000

10000

1000

1000

7.4 LCD/105 PY 74 HDD/105 PY

Female NS LCD rate CPS II Female NS HDD rate CPS II Repace Model ETS-HDD rate

100

100

Male NS LCD rate CPS II Male NS HDD rate CPS II

10

10

1 10

50

1 100

5-year Age-group Midpoint

Repace Model ETS-LCD Rate

DISCUSSION OF UNCERTAINTY FOR SECONDHAND SMOKECORONARY HEART DISEASE EXPOSURE-RESPONSE RELATIONSHIP 1.  Coronary Heart Disease (CHD)Mortality and Lung Cancer Mortality (LCD) Both Increase by ~25% in Nonsmoking Women Whose Spouses Smoke: (World Epi Studies). 2.  Coronary Heart Disease Deaths Estimated to Occur 10 to 15 Times More Frequently Than Lung Cancer Deaths: Repace et al. (1998); Wells (1999). 3.  Ratio of CHD/LCD in 5-year age groups for ACSCPS II Study, when Age-Standardized to the 1974 U.S. White Population, yields a 9:1 Ratio: (Fact). 4.  The Ratio Procedure used because of evidence that the Exposure-Response Relationship appears supra-linear (Otsuka et al. (2002); Repace (2002); estimating risk for standing population finesses curve shape problem.

COMPARATIVE ESTIMATED ANNUAL MORTALITY: ALL REGULATED U.S. HAZARDOUS OUTDOOR AIR POLLUTANTS VS. DEATHS FROM PASSIVE SMOKING Repace & Lowrey, Risk Analysis, 10: 1990 Wells, Environment International 25:1999

10000

1000

ASBESTOS 8 ARSENIC