Date: Sat, 22 Feb 97 13:09:07 -0800
From: Stan Glantz glantz@cardio.ucsf.EDU
Subject: CalEPA report on Secondhand Smoke

The California Environmental Protection Agency has just released the first
comprenensive review of secondhand smoke since the 1986 Surgeon General's
Report for public comment.  I encourage you to comment on the document;
comments are due by May 5, as explained in the document itself.  The entire
document is available on the World Wide Web at the following locations:

To view executive summary:

http://www.calepa.cahwnet.gov/oehha/docs/ets/execsum.htm

To download document, go to:

http://www.calepa.cahwnet.gov/oehha/docs/ets/ets-main.htm

For those of you with Web pages, I suggest that you link to this document.

To obtain a paper copy of the document, you may also contact Ms. Joyce Smylie at (510) 540-2084. 

Here is the Executive Summary without the nice formatting.

Executive Summary

Exposure to environmental tobacco smoke (ETS) has been linked to a variety
of adverse health outcomes.  Many Californians are exposed at home, at work
and in public places.  In the comprehensive reviews published as Reports of
the Surgeon General and by the U.S. Environmental Protection Agency (U.S.
EPA) and the National Research Council (NRC), ETS exposure has been found to
be causally associated with respiratory illnesses, including lung cancer,
childhood asthma and lower respiratory tract infections.  Scientific
knowledge about ETS-related effects has expanded considerably since the
release of these reviews.  The State of California has therefore undertaken
a broad review of ETS, covering the major health endpoints potentially
associated with ETS exposure: perinatal and postnatal manifestations of
developmental toxicity, adverse impacts on male and female reproduction,
respiratory disease, cancer, and cardiovascular disease.  A "weight of
evidence" approach has been used to describe the body of evidence for an
effect and to support a conclusion as to whether ETS exposure is causally
associated with a particular effect. Because the epidemiological data are
extensive, they serve as the primary basis for assessment of ETS-related
effects in humans.  The report also presents an overview on measurements of
ETS exposure, particularly as they relate to characterizations of exposure
in epidemiological investigations, and on the prevalence of ETS exposure in
California and nationally.

ETS, or "secondhand smoke", is the complex mixture formed from the escaping
smoke of a tobacco product, and smoke exhaled by the smoker. The
characteristics of ETS change as it ages and combines with other
constituents in the ambient air. Exposure to ETS is also frequently referred
to as "passive smoking", or "involuntary tobacco smoke" exposure.  Although
all exposures of the fetus are "passive" and "involuntary", for the purposes
of this review in utero exposure resulting from maternal smoking during
pregnancy is not considered to be ETS exposure.

General Findings

ETS is an important source of exposure to toxic air contaminants indoors.
Despite an increasing number of restrictions on smoking and increased
awareness of health impacts, exposures in the home, especially of infants
and children, continue to be a public health concern. ETS exposure is
causally associated with a number of health effects.  Listed in Table ES.1
are the developmental, respiratory, carcinogenic and cardiovascular effects
for which there is sufficient evidence of a causal relationship, including
fatal outcomes such as sudden infant death syndrome and heart disease
mortality, as well as serious chronic diseases such as childhood asthma.
There are in addition effects for which evidence is suggestive of an
association but further research is needed for confirmation.  These include
spontaneous abortion, cervical cancer, and exacerbation of asthma in adults
(Table ES.1).  Finally, it is not possible to judge on the basis of the
current evidence the impact of ETS on a number of endpoints, including
congenital malformations, changes in female fertility and fecundability,
male reproductive effects, rare childhood cancers and cancers of the
bladder, breast, stomach, brain, hematopoietic system, and lymphatic system.  


Table ES.1 
Health Effects Associated with Exposure to Environmental Tobacco Smoke
	
Effects Causally Associated with ETS Exposure

Developmental Effects	
Fetal Growth:  Low birthweight or small for gestational age	
Sudden Infant Death Syndrome (SIDS)	
	
Respiratory Effects
Acute lower respiratory tract infections in children 
(e.g., bronchitis and pneumonia)	
Asthma induction and exacerbation in children 	
Chronic respiratory symptoms in children	
Eye and nasal irritation in adults	
Middle ear infections in children	
	
Carcinogenic Effects
Lung Cancer	
Nasal Sinus Cancer	
	
Cardiovascular Effects
Heart disease mortality	
Acute and chronic coronary heart disease morbidity	
	
Effects with Suggestive Evidence of a Causal Association with ETS Exposure

Developmental Effects
Spontaneous abortion	
Adverse impact on cognition and behavior	
	
Respiratory Effects
Asthma exacerbation in adults	
Exacerbation of cystic fibrosis	
Decreased pulmonary function	
	
Carcinogenic Effects
Cervical cancer	
	
Many Californians are exposed to ETS,  and the number of  people adversely
affected may be correspondingly large.  Table ES.2 presents morbidity and
mortality estimates for health effects causally associated with ETS
exposure.  For cancer, cardiovascular and some respiratory endpoints,
estimates are derived from figures published for the U.S. population,
assuming that the number affected in California would be 12% of the total.
The estimates for middle ear infection, sudden infant death syndrome and low
birthweight were derived using information on prevalence of ETS exposure in
California and the U.S.

Table ES.2
Estimated Annual Morbidity and Mortality
IN NONSMOKERS
Associated with ETS Exposure 

Condition	Number of People or Cases	
                in the U.S. 	in California (a)

Developmental Effects			
Low birthweight
	÷ 9,700 - 18,600 cases	÷ 1,200 - 2,200 cases	
Sudden Infant Death Syndrome (SIDS)
	÷ 1,900 - 2,700 deaths 	÷ 120 deaths
	
Respiratory Effects in Children			
Middle ear infection	0.7 to 1.6 million 
physician office visits	78,600 to 188,700 
physician office visits	
Asthma induction
	8,000 to 26,000 new cases	960 to 3120 new cases	
Asthma exacerbation
	400,000 to 1,000,000 children	48,000 to 120,000 children	
Bronchitis or pneumonia in infants and toddlers 
(18 months and under)
	150,000 to 300,000 cases

7,500 to 15,000 
hospitalizations
136 - 212 deaths	18,000 to 36,000 cases

900 to 1800 hospitalizations
16 - 25 deaths	
Cancer			
Lung    
	3000 deaths	360 deaths	
Nasal sinus
	 N/Ab	 N/Ab	
Cardiovascular Effects			
Ischemic heart disease
	35,000 - 62,000 deaths	4,200 - 7,440 deaths	
(a)  California predictions are made by multiplying the U.S. estimate by 12%,
the fraction of the U.S. population residing in the State.  The exceptions
are California estimates for low birthweight, SIDS, and otitis media which
are provided in Chapters 3, 4, and 6 respectively.  For these cases the
sources cited provided the odds or risk ratios serving as the basis for the
analyses. b Estimates of the impact of ETS exposure on the occurrence of
nasal sinus cancers are not available at this time. 
Relative risk estimates associated with some of these endpoints are small,
but because the diseases are common the overall impact can be quite large.
A relative risk estimate of 1.3 for heart disease mortality in nonsmokers is
supported by the collective evidence; this corresponds to a lifetime risk of
death of roughly 1 to 3% for exposed nonsmokers and perhaps 4,000 deaths
annually in California.  The relative risk estimate of 1.2 to 1.4 associated
with low birthweight implies that ETS may impact fetal growth of 1,200 to
2,200 newborns in California, roughly 1 to 2% of newborns of nonsmokers
exposed at home or work. ETS may exacerbate asthma  (RR » 1.6 to 2) in
48,000 to 120,000 children in California.  Large impacts are associated with
relative risks for respiratory effects in children such as middle ear
infection (RR » 1.62), and lower respiratory disease in young children (RR »
1.5 to 2).  Asthma induction (RR » 1.75 to 2.25) may occur in as many as 0.5
to 2% of ETS-exposed children.  ETS exposure may be implicated in 120 SIDS
deaths per year in California (RR » 3.5), with a risk of death to 0.1% of
infants exposed to ETS in their homes.  Lifetime risk of lung cancer death
related to ETS-exposed nonsmokers may be about 0.7% (RR » 1.2).  For nasal
sinus cancers, observed relative risks have ranged from 1.7 to 3.0, but
future studies are needed to confirm the magnitude of ETS-related risks.

Specific Findings and Conclusions

Exposure Measurement and Prevalence

ETS is a complex mixture of chemicals generated during the burning and
smoking of tobacco products.  Chemicals present in ETS include irritants and
systemic toxicants such as hydrogen cyanide and sulfur dioxide, mutagens and
carcinogens such as benzo(a)pyrene, formaldehyde and 4-aminobiphenyl, and
the reproductive toxicants nicotine, cadmium and carbon monoxide.  Many ETS
constituents have been identified as hazardous by state, federal and
international agencies.  To date, over 50 compounds in tobacco smoke have
been identified as carcinogens and six as developmental or reproductive
toxicants under California's Proposition 65 (California Health and Safety
Code 25249.5 et seq.).

Exposure assessment is critical in epidemiological investigations of the
health impacts of ETS, and in evaluating the effectiveness of  strategies to
reduce exposure.  Exposure can be assessed through the measurement of indoor
air concentrations of ETS constituents, through surveys and questionnaires,
or more directly through the use of personal monitors and the measurement of
biomarkers in saliva, urine and blood.  There are advantages and
disadvantages associated with the various techniques, which must be weighed
in interpreting study results.  One important consideration in epidemiologic
studies is misclassification of exposure.  Studies on the reliability of
questionnaire responses indicate qualitative information obtained is
generally reliable, but that quantitative information may not be.  Also,
individuals are often unaware of their ETS exposure, particularly outside
the home.  In studies using both self-reporting and biological markers, the
exposure prevalence was higher when determined using biological markers.

Available data suggest that the prevalence of ETS exposure in California is
lower than elsewhere in the U.S.  Among adults in California, the workplace,
home and other indoor locations all contribute significantly to ETS
exposure.  For children the most important single location is the home.
Over the past decade ETS exposures in California have decreased
significantly in the home, workplace and in public places.  Over the same
period, restrictions on smoking in enclosed worksites and public places have
increased (e.g., Gov. Code, Section 19994.30 and California Labor Code,
Section 6404.5) and the percentage of the adults who smoke has declined.
Decreases in tobacco smoke exposure may not be experienced for some
population subgroups, as patterns of smoking shift with age, race, sex and
socioeconomic status.  For example, from 1975 to 1988, the overall smoking
prevalence among 16 to 18 year olds declined, but after 1988 the trend
reversed. 

Perinatal Manifestations of Developmental Toxicity

ETS exposure adversely affects fetal growth, with elevated risks of low
birth weight or "small for gestational age" observed in numerous
epidemiological studies.  The primary effect observed, reduction in mean
birthweight, is small in magnitude.  But if the distribution of birthweight
is shifted lower with ETS exposure, as it appears to be with active smoking,
infants who are already compromised may be pushed into even higher risk
categories.  Low birthweight is associated with many well-recognized
problems for infants, and is strongly associated with perinatal mortality.

The impact of ETS on perinatal manifestations of development other than
fetal growth is less clear.  The few studies examining the association
between ETS and perinatal death are relatively non-informative, with only
two early studies showing increased risk associated with parental smoking,
and with the sparse data on stillbirth not indicative of an effect.  Studies
on spontaneous abortion are suggestive of a role for ETS, but further work
is needed, particularly as a recent report did not confirm the findings of
four earlier studies.  Although epidemiological studies suggest a moderate
association of severe congenital malformations with paternal smoking, the
findings are complicated by the use of paternal smoking status as a
surrogate for ETS exposure, since a direct effect of active smoking on sperm
cannot be ruled out.  In general, the defects implicated differed across the
studies, with the most consistent association seen for neural tube defects.
At this time, it is not possible to determine whether there is a causal
association between ETS exposure and this or other birth defects.

Postnatal Manifestations of Developmental Toxicity

Numerous studies have demonstrated an increased risk of sudden infant death
syndrome, or "SIDS," in infants of mothers who smoke. Until recently it has
not been possible to separate the effects of postnatal ETS exposure from
those of prenatal exposure to maternal active smoking.  Recent
epidemiological studies now have demonstrated that postnatal ETS exposure is
an independent risk factor for SIDS. 

Although definitive conclusions regarding causality cannot yet be made on
the basis of available epidemiological studies of cognition and behavior,
there is suggestive evidence that ETS exposure may pose a hazard for
neuropsychological  development.  With respect to physical development,
while small but consistent effects of active maternal smoking during
pregnancy have been observed on height growth, there is no evidence that
postnatal ETS exposure has a significant impact in otherwise healthy
children.  As discussed in greater detail below, developmental effects of
ETS exposure on the respiratory system include lung growth and development,
childhood asthma exacerbation, and, in children, acute low respiratory tract
illness, middle ear infection and chronic respiratory symptoms.

Female and Male Reproductive Toxicity

Though active smoking by women has been found to be associated with
decreased fertility in a number of studies, and tobacco smoke appears to be
anti-estrogenic, the epidemiological data on ETS exposure and fertility are
not extensive and show mixed results, and it is not possible to determine
whether ETS affects fecundability or fertility.  Regarding other female
reproductive effects, while studies indicate a possible association of ETS
exposure with early menopause, the analytic methods of these studies could
not be thoroughly evaluated, and therefore at present, there is not firm
evidence that ETS exposure affects age at menopause.  Although associations
have been seen epidemiologically between active smoking and sperm
parameters, conclusions can not be made regarding ETS exposure and male
reproduction, as there is very limited information available on this topic.

Respiratory Effects

ETS exposure produces a variety of acute effects involving the upper and
lower respiratory tract.  In children, ETS exposure can exacerbate asthma,
and increases the risk of lower respiratory tract illness, and acute and
chronic middle ear infection.  ETS may also exacerbate asthma in adults.
Eye and nasal irritation are the most commonly reported symptoms among adult
nonsmokers exposed to ETS.  Odor annoyance has been demonstrated in several
studies.

Regarding chronic health effects, there is compelling evidence that ETS is a
risk factor for induction of new cases of asthma as well as for increasing
the severity of disease among children with established asthma.  In
addition, chronic respiratory symptoms in children, such as cough, phlegm,
and wheezing, are associated with parental smoking.  While the results from
all studies are not wholly consistent, there is evidence that childhood
exposure to ETS affects lung growth and development, as measured by small,
but statistically significant decrements in pulmonary function tests;
associated reductions may persist into adulthood.  The effect of chronic ETS
exposure on pulmonary function in otherwise healthy adults is likely to be
small, and unlikely by itself to result in clinically significant chronic
disease.  However, in combination with other insults (e.g., prior smoking
history, exposure to occupational irritants or ambient air pollutants), ETS
exposure could contribute to chronic respiratory impairment in adults.  In
addition, regular ETS exposure in adults has been reported to increase the
risk of occurrence of a variety of lower respiratory symptoms.  

Children are especially sensitive to the respiratory effects of ETS
exposure. Children with cystic fibrosis are likely to be more sensitive than
healthy individuals.  Several studies of patients with cystic fibrosis, a
disease characterized by recurrent and chronic pulmonary infections, suggest
that ETS can exacerbate the condition.  Several studies have shown an
increased risk of atopy (a predisposition to develop IgE antibodies against
common allergens, which can then be manifested as a variety of allergic
conditions) in children of smoking mothers, though the evidence regarding
this issue is mixed.  

Carcinogenic Effects

The role of ETS in the etiology of cancers in nonsmokers was explored, as
smoking is an established cause of a number of cancers (lung, larnyx, oral
cavity, esophagus and bladder), and a probable cause of several others
(cervical, kidney, pancreas, and stomach).  Also, ETS contains a number of
constituents which have been identified as carcinogens.  

Reviews published in the 1986 Report of the Surgeon General, by the National
Research Council in 1986, and by the U.S. EPA in 1992 concluded that ETS
exposure causes lung cancer.  Three large U.S. population-based studies and
a smaller hospital-based case control study have been published since the
completion of the U.S. EPA review.  The population-based studies were
designed to and have successfully addressed many of the weaknesses for which
the previous studies on ETS and lung cancer have been criticized.  Results
from these studies are compatible with the causal association between ETS
exposure and lung cancer already reported by the U.S. EPA, Surgeon General,
and National Research Council.  Of  the studies examining the effect of ETS
exposure on nasal sinus cancers, all three show consistent associations,
presenting strong evidence that ETS exposure increases the risk of nasal
sinus cancers in nonsmoking adults.  Further study is needed to characterize
the magnitude of the risk of nasal sinus cancer from ETS exposure.  

The epidemiological and biochemical evidence suggest that exposure to ETS
may increase the risk of cervical cancer.  Positive associations were
observed in two of three case-control studies and a statistically
nonsignificant positive association was observed in the only cohort study
conducted.  Findings of DNA adducts in the cervical epithelium as well as
nicotine and cotinine in the cervical mucus of ETS-exposed nonsmokers
provides biological plausibility.   

For other cancer sites in adults, there has been limited ETS-related
epidemiological research in general:  there is currently insufficient
evidence to draw any conclusion regarding the relationship between ETS
exposure and the risk of occurrence. A review of the available literature
clearly indicates the need for more research.  For example, although
compounds established as important in the etiology of stomach cancer are
present in tobacco smoke, only a single cohort study has been performed for
this site.  Precursors of endogenously formed N-nitroso compounds suspected
of causing brain tumors are present in high concentrations in ETS, and the
one cohort and two case-control studies available suggest a positive
association, but the results are based on small numbers and may be
confounded by active smoking.  In biochemical studies of nonsmokers, higher
levels of hemoglobin adducts of the established bladder carcinogen,
4-aminobiphenyl, have been found in those exposed to ETS.  However, no
significant increases in bladder cancer were seen in the two epidemiological
studies (case-control) conducted to date, although both studies were limited
in their ability to detect an effect.  Several compounds in tobacco smoke
are associated with increased risk of leukemia, but only one small
case-control study in adults, reporting an increased risk with ETS exposure
during childhood, has been performed. Finally, all four studies on ETS
exposure and breast cancer suggest an association, but in two of the studies
the associations were present only in select groups, and in three studies
there is either no association between active smoking and the risk of breast
cancer or the association for active smoking is weaker than for passive
smoking.  Moreover, there is no indication of increasing risk with
increasing intensity of ETS exposure.  Still, results from a recent study
suggest that tobacco smoke may influence the risk of breast cancer in
certain susceptible groups of women, and this requires further investigation.

Regarding childhood cancers, it is unclear whether parental smoking
increases risk overall, or for specific cancers such as acute lymphoblastic
leukemia and brain tumors, the two most common cancers in children.  The
lack of clarity is due to the conflicting results reported and the
limitations of studies finding no association.  The epidemiological data on
ETS exposure and rare childhood cancers also provide an inadequate
foundation for making conclusions regarding causality.  Some studies found
small increased risks in children in relation to parental smoking for
neuroblastoma, Wilm's tumor, bone and soft-tissue sarcomas, but not for germ
cell tumors.  Studies to date on these rare cancers have been limited in
their power to detect effects.  The impact of ETS exposure on childhood
cancer would benefit from far greater attention than it has received to date.

Cardiovascular Effects

The epidemiological data, from prospective and case-control studies
conducted in diverse populations, in males and females and in western and
eastern countries, are supportive of a causal association between ETS
exposure from spousal smoking and coronary heart disease (CHD) mortality in
nonsmokers.  To the extent possible, estimates of risk were determined with
adjustment for demographic factors, and often for other factors related to
heart disease, such as blood pressure, serum cholesterol level and obesity
index.  Risks associated with ETS exposure were almost always strengthened
by adjustment for other cofactors.  For nonsmokers exposed to spousal ETS
compared to nonsmokers not exposed, the risk of CHD mortality is increased
by a factor of 1.3.  The association between CHD and risk is stronger for
mortality than for non-fatal outcomes, including angina.

Data from clinical studies suggest various mechanisms by which ETS causes
heart disease.  In a number of studies in which nonsmokers were exposed to
ETS, carotid wall thickening and compromise of endothelial function were
similar to, but less extensive than those experienced by active smokers.
Other effects observed include impaired exercise performance, altered
lipoprotein profiles, enhanced platelet aggregation, and increased
endothelial cell counts.  These findings may account for both the short- and
long-term effects of ETS exposure on the heart.