Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects

Combustion emissions account for over half of the fine particle (PM(2.5)) air pollution and most of the primary particulate organic matter. Human exposure to combustion emissions including the associated airborne fine particles and mutagenic and carcinogenic constituents (e.g., polycyclic aromatic compounds (PAC), nitro-PAC) have been studied in populations in Europe, America, Asia, and increasingly in third-world counties. Bioassay-directed fractionation studies of particulate organic air pollution have identified mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAH), nitrated PAH, nitro-lactones, and lower molecular weight compounds from cooking. A number of these components are significant sources of human exposure to mutagenic and carcinogenic chemicals that may also cause oxidative and DNA damage that can lead to reproductive and cardiovascular effects. Chemical and physical tracers have been used to apportion outdoor and indoor and personal exposures to airborne particles between various combustion emissions and other sources. These sources include vehicles (e.g., diesel and gasoline vehicles), heating and power sources (e.g., including coal, oil, and biomass), indoor sources (e.g., cooking, heating, and tobacco smoke), as well as secondary organic aerosols and pollutants derived from long-range transport. Biomarkers of exposure, dose and susceptibility have been measured in populations exposed to air pollution combustion emissions. Biomarkers have included metabolic genotype, DNA adducts, PAH metabolites, and urinary mutagenic activity. A number of studies have shown a significant correlation of exposure to PM(2.5) with these biomarkers. In addition, stratification by genotype increased this correlation. New multivariate receptor models, recently used to determine the sources of ambient particles, are now being explored in the analysis of human exposure and biomarker data. Human studies of both short- and long-term exposures to combustion emissions and ambient fine particulate air pollution have been associated with measures of genetic damage. Long-term epidemiologic studies have reported an increased risk of all causes of mortality, cardiopulmonary mortality, and lung cancer mortality associated with increasing exposures to air pollution. Adverse reproductive effects (e.g., risk for low birth weight) have also recently been reported in Eastern Europe and North America. Although there is substantial evidence that PAH or substituted PAH may be causative agents in cancer and reproductive effects, an increasing number of studies investigating cardiopulmonary and cardiovascular effects are investigating these and other potential causative agents from air pollution combustion sources.     

Comparison of environmental tobacco smoke concentrations and mutagenicity for several indoor environments

Environmental tobacco smoke (ETS) is a major source for indoor air pollution. Although ETS-caused indoor air pollution has been well studied in the developed countries, few studies have examined ETS indoor air pollution in China, which currently has the largest population of tobacco smokers. In this study, respirable-particulate (RP) from ETS-contaminated (RP-ETS) indoor air was collected and measured in 5 different indoor environments during the winter in the northwestern Liaoning Province, China. The extractable portion of RP-ETS (ERP-ETS) was obtained by dichloromethane extraction and used in the Salmonella mutagenicity assay in the presence of S9 using strains TA98, TA100, and TA1538. The percentage of RP-ETS attributable to ETS (ETS-RP) and the percentage of ERP-ETS attributable to ETS (ETS-ERP) were estimated by measuring the concentration of solanesol, an ETS marker. Comparative results in 5 different indoor environments were: (1) the concentration of RP-ETS ranged from 197.3 to 1227.6 microg/m(3) and approximately 64.7 to 92. 0% of the RP-ETS originated from ETS; (2) the concentration of ERP-ETS ranged 88.8 to 601.5 microg/m(3) and approximately 83.1 to 95.4% of the ERP-ETS originated from ETS; (3) the mutagenic potency (revertants/m(3)) of ERP-ETS ranged from 60.4 to 595.5 for TA98, from 33.7 to 312.8 for TA100, and from 49.7 to 475.2 for TA1538. The data indicate that the extent of ETS pollution and the potential health hazards of ETS to humans in the five indoor environments are in the following increasing order: rural bedrooms, urban living rooms, office rooms, restaurants, and passenger cars in that area.     

GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: a meta-analysis

About half of the world's population is exposed to smoke from heating or cooking with coal, wood, or biomass. These exposures, and fumes from cooking oil use, have been associated with increased lung cancer risk. Glutathione S-transferases play an important role in the detoxification of a wide range of human carcinogens in these exposures. Functional polymorphisms have been identified in the GSTM1, GSTT1, and GSTP1 genes, which may alter the risk of lung cancer among individuals exposed to coal, wood, and biomass smoke, and cooking oil fumes. We performed a meta-analysis of 6 published studies (912 cases; 1063 controls) from regions in Asia where indoor air pollution makes a substantial contribution to lung cancer risk, and evaluated the association between the GSTM1 null, GSTT1 null, and GSTP1 105Val polymorphisms and lung cancer risk. Using a random effects model, we found that carriers of the GSTM1 null genotype had a borderline significant increased lung cancer risk (odds ratio (OR), 1.31; 95% confidence interval (CI), 0.95-1.79; p=0.10), which was particularly evident in the summary risk estimate for the four studies carried out in regions of Asia that use coal for heating and cooking (OR, 1.64; 95% CI, 1.25-2.14; p=0.0003). The GSTT1 null genotype was also associated with an increased lung cancer risk (OR, 1.49; 95% CI, 1.17-1.89; p=0.001), but no association was observed for the GSTP1 105Val allele. Previous meta- and pooled-analyses suggest at most a small association between the GSTM1 null genotype and lung cancer risk in populations where the vast majority of lung cancer is attributed to tobacco, and where indoor air pollution from domestic heating and cooking is much less than in developing Asian countries. Our results suggest that the GSTM1 null genotype may be associated with a more substantial risk of lung cancer in populations with coal exposure.     

Biomonitoring of human genotoxicity induced by complex occupational exposures

Sensitivity, specificity and correlations among several biomarkers for monitoring occupational exposure to complex mixtures of genotoxic agents were assessed in occupational environments in Hungarian study populations. The studies have been focused on DNA adduct formation, urinary metabolites, mutations and micronuclei induced by exposures to complex organic mixtures. In two Hungarian aluminium plants, increased DNA adduct and 1-hydroxypyrene (1-OH-PY) levels were observed in workers as compared to controls. However, no association between the biomarker levels was evident on an individual basis. In Hungarian garage mechanics, DNA adduct determinations did not show increased genotoxic exposure as compared to the controls. However, ambient air measurements, significantly enhanced 1-OH-PY levels, and slightly enhanced frequency of micronuclei indicated increased polycyclic aromatic hydrocarbon (PAH) exposure in the garages, as compared to the general environment. In a Hungarian vulcanizing plant, DNA adduct determinations and 1-OH-PY did not show significantly elevated exposure levels as compared to controls. The glycophorin A (GPA) somatic mutation assay was also negative for this occupational exposure. The results support previous observations of a lack of correlation between DNA adducts detectable by 32P-postlabelling and those measured by the PAH-DNA immunoassay in the same DNA sample. These studies also demonstrate a lack of close correlation between levels of DNA adducts and urinary 1-OH-PY in the same individual.     

Heat and PAHs Emissions in Indoor Kitchen Air and Its Impact on Kidney Dysfunctions among Kitchen Workers in Lucknow,North India

Indoor air quality and heat exposure have become an important occupational health and safety concern in several workplaces including kitchens of hotels. This study investigated the heat, particulate matter (PM), total volatile organic compounds (TVOCs) and polycyclic aromatic hydrocarbons (PAHs) emissions in indoor air of commercial kitchen and its association with kidney dysfunctions among kitchen workers. A cross sectional study was conducted on 94 kitchen workers employed at commercial kitchen in Lucknow city, North India. A questionnaire-based survey was conducted to collect the personal and occupational history of the kitchen workers. The urine analysis for specific gravity and microalbuminuria was conducted among the study subjects. Indoor air temperature, humidity, wet/ dry bulb temperature and humidex heat stress was monitored during cooking activities at the kitchen. Particulate matter (PM) for 1 and 2.5 microns were monitored in kitchen during working hours using Hazdust. PAH_S in indoor air was analysed using UHPLC. Urinary hydroxy-PAHs in kitchen workers were measured using GC/MS-MS. Higher indoor air temperature, relative humidity, PM₁ and PM_2.5 (p<0.001) was observed in the kitchen due to cooking process. Indoor air PAHs identified are Napthalene, fluorine, acenaphthene, phenanthrene, pyrene, chrysene and indeno [1,2,3-cd) pyrene. Concentrations of all PAHs identified in kitchen were above the permissible OSHA norms for indoor air. Specific gravity of urine was significantly higher among the kitchen workers (p<0.001) as compared to the control group. Also, the prevalence of microalbuminuria was higher (p<0.001) among kitchen workers. Urinary PAH metabolites detected among kitchen workers were 1-NAP, 9-HF, 3-HF, 9-PHN and 1-OHP. Continuous heat exposure in kitchens due to cooking can alter kidney functions viz., high specific gravity of urine in kitchen workers. Exposure to PM, VOCs and PAHs in indoor air and presence of urinary PAHs metabolites may lead to inflammation, which can cause microalbuminuria in kitchen workers, as observed in the present study.     

Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002)

Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross-sectional analysis involved data from 454 individuals aged 60 years and older from the 2001–2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1-hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution.     

Thoughts on rationing medical care

The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.     

Evaluation of urinary trans-3'-hydroxycotinine as a biomarker of children's environmental tobacco smoke exposure.

The utility of urinary trans-3'-hydroxy cotinine (3HC) as a biomarker of environmental tobacco smoke (ETS) exposure was investigated in comparison with urinary cotinine (COT), the sum (3HC + COT), and ratio of the two nicotine metabolites (3HC/COT). Participants were 150 ETS exposed children (aged 1-44 months) and their parents. Child urine samples were collected during 3weekly baseline assessments and at interviews administered 3, 6, 12, and 18 months after baseline. Findings indicate that 3HC and COT can be measured reliably (rho = 0.96, 0.88) and show equivalent levels of repeated measures stability (rho = 0.71, 0.75). COT, 3HC, and 3HC + COT showed equally strong associations with air nicotine levels, reported ETS contamination, and reported ETS exposure (r=0.60-0.70). The intraclass correlations of 3HC/COT were lower than those for COT or 3HC. Older children had a higher 3HC/COT ratio than younger children (3.5 versus 2.2), and non-Hispanic White children had a higher ratio than African-American children (3.2 versus 1.9). These findings suggest that COT, 3HC, and 3HC + COT are approximately equivalent and equally strong biomarkers of ETS exposure in children. Moreover, 3HC/COT may provide a useful indicator to investigate age- and race-related differences in the metabolism of COT and 3HC.     

Assessing Exposures to Household Air Pollution in Public Health Research and Program Evaluation

EcoHealth - Exposure to smoke from the use of solid fuels and inefficient stoves for cooking and heating is responsible for approximately 4 million premature deaths yearly. As increasing...     

Evaluation of urinary trans-3′-hydroxycotinine as a biomarker of children's environmental tobacco smoke exposure

Abstract

The utility of urinary trans-3′-hydroxy cotinine (3HC) as a biomarker of environmental tobacco smoke (ETS) exposure was investigated in comparison with urinary cotinine (COT), the sum (3HC?+?COT), and ratio of the two nicotine metabolites (3HC/COT). Participants were 150 ETS exposed children (aged 1–44 months) and their parents. Child urine samples were collected during 3weekly baseline assessments and at interviews administered 3, 6, 12, and 18 months after baseline. Findings indicate that 3HC and COT can be measured reliably (rho?=?0.96, 0.88) and show equivalent levels of repeated measures stability (rho?=?0.71, 0.75). COT, 3HC, and 3HC?+?COT showed equally strong associations with air nicotine levels, reported ETS contamination, and reported ETS exposure (r=0.60–0.70). The intraclass correlations of 3HC/COT were lower than those for COT or 3HC. Older children had a higher 3HC/COT ratio than younger children (3.5 versus 2.2), and non-Hispanic White children had a higher ratio than African-American children (3.2 versus 1.9). These findings suggest that COT, 3HC, and 3HC?+?COT are approximately equivalent and equally strong biomarkers of ETS exposure in children. Moreover, 3HC/COT may provide a useful indicator to investigate age- and race-related differences in the metabolism of COT and 3HC.     

Association between gas cooking and respiratory disease in children.

A four-year longitudinal study of the prevalence of respiratory symptoms and disease in schoolchildren and related environmental and socio-economic factors is in progress. We report results for the first year of this study (1973). A total of 5758 children aged 6 to 11 years from 28 randomly selected areas of England and Scotland were examined. In an analysis of the effects on health of possible indoor pollutants, boys and girls from homes in which gas was used for cooking were found to have more cough, "colds going to the chest", and bronchitis than children from homes where electricity was used. The girls also had more wheeze if their families used gas for cooking. This "cooking effect" appeared to be independent of the effects of age, social class, latitude, population density, family size, overcrowding, outdoor levels of smoke and sulphur dioxide and types of fuel used for heating. It was concluded that elevated levels of oxides of nitrogen arising from the combustion of gas might be the cause of the increased respiratory illness.     

Air pollutant effects on fetal and early postnatal development

Numerical research on the health effects of air pollution has been published in the last decade. Epidemiological studies have shown that children's exposure to air pollutants during fetal development and early postnatal life is associated with many types of health problems including abnormal development (low birth weight [LBW], very low birth weight [VLBW], preterm birth [PTB], intrauterine growth restriction [IUGR], congenital defects, and intrauterine and infant mortality), decreased lung growth, increased rates of respiratory tract infections, childhood asthma, behavioral problems, and neurocognitive decrements. This review focuses on the health effects of major outdoor air pollutants including particulates, carbon monoxide (CO), sulfur and nitrogen oxides (SO(2), NOx), ozone, and one common indoor air pollutant, environmental tobacco smoke (ETS). Animal data is presented that demonstrate perinatal windows of susceptibility to sidestream smoke, a surrogate for ETS, resulting in altered airway sensitivity and cell type frequency. A study of neonatal monkeys exposed to sidestream smoke during the perinatal period and/or early postnatal period that resulted in an altered balance of Th1-/Th2-cytokine secretion, skewing the immune response toward the allergy-associated Th2 cytokine phenotype, is also discussed.     

High urine 1-hydroxypyrene glucuronide concentrations in Linxian, China, an area of high risk for squamous oesophageal cancer

Most squamous cell carcinomas of the oesophagus in low-risk populations are attributable to alcohol and tobacco consumption, but the aetiologic agents in many high-risk populations have yet to be definitively identified. Linxian, China has some of the highest oesophageal cancer rates in the world. Recent studies suggest that an association exists between high-level exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), and the development of oesophageal cancer. The inhabitants of this high-risk region extensively use coal and wood for cooking and heating in unvented stoves, and thus may be exposed to PAHs produced during the incomplete combustion of these fuel sources. High levels of B[a]P were recently detected in staple food samples from Linxian and histopathologic changes that may be associated with PAH exposure have also been identified in oesophagectomy specimens from the region. In an effort to determine whether this high-risk population is exposed to high levels of PAHs, voided urines from non-smokers (n = 22) without occupational exposure were collected and analysed using immunoaffinity chromatography and synchronous fluorescence spectroscopy for 1-hydroxypyrene glucuronide, a PAH metabolite and index biomarker for mixed PAH exposure. The median urine 1-hydroxypyrene glucuronide concentration (2.06 pmol ml^-1) was equivalent to concentrations detected in current smokers. To the authors' knowledge, this represents the first report of elevated urine 1-hydroxpyrene glucuronide concentrations in Linxian, and the first biologic confirmation that the inhabitants of this rural, non-industrial, high oesophageal cancer risk region are exposed to carcinogenic PAHs.     

Genotoxicity of environmental tobacco smoke: a review

Environmental tobacco smoke (ETS), or second-hand smoke, is a widespread contaminant of indoor air in environments where smoking is not prohibited. It is a significant source of exposure to a large number of substances known to be hazardous to human health. Numerous expert panels have concluded that there is sufficient evidence to classify involuntary smoking (or passive smoking) as carcinogenic to humans. According to the recent evaluation by the International Agency for Research on Cancer, involuntary smoking causes lung cancer in never-smokers with an excess risk in the order of 20% for women and 30% for men. The present paper reviews studies on genotoxicity and related endpoints carried out on ETS since the mid-1980s. The evidence from in vitro studies demonstrates induction of DNA strand breaks, formation of DNA adducts, mutagenicity in bacterial assays and cytogenetic effects. In vivo experiments in rodents have shown that exposure to tobacco smoke, whole-body exposure to mainstream smoke (MS), sidestream smoke (SS), or their mixture, causes DNA single strand breaks, aromatic adducts and oxidative damage to DNA, chromosome aberrations and micronuclei. Genotoxicity of transplacental exposure to ETS has also been reported. Review of human biomarker studies conducted among non-smokers with involuntary exposure to tobacco smoke indicates presence of DNA adducts, urinary metabolites of carcinogens, urinary mutagenicity, SCEs and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutations (in newborns exposed through involuntary smoking of the mother). Studies on human lung cancer from smokers and never-smokers involuntarily exposed to tobacco smoke suggest occurrence of similar kinds of genetic alterations in both groups. In conclusion, these overwhelming data are compatible with the current knowledge on the mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in smokers but with a high biological plausibility also in involuntary smokers.     

Environmental tobacco smoke and sudden infant death syndrome: a review

Environmental tobacco smoke (ETS), containing the developmental neurotoxicant, nicotine, is a prevalent component of indoor air pollution. Despite a strong association with active maternal smoking and sudden infant death syndrome (SIDS), information on the risk of SIDS due to prenatal and postnatal ETS exposure is relatively inconsistent. This literature review begins with a discussion and critique of existing epidemiologic data pertaining to ETS and SIDS. It then explores the biologic plausibility of this association, with comparison of the known association between active maternal smoking and SIDS, by examining metabolic and placental transfer issues associated with nicotine, and the biologic responses and mechanisms that may follow exposure to nicotine. Evidence indicates that prenatal and postnatal exposures to nicotine do occur from ETS exposure, but that the level of exposure is often substantially less than levels induced by active maternal smoking. Nicotine also has the capacity to concentrate in the fetus, regardless of exposure source. Experimental animal studies show that various doses of nicotine are capable of affecting a neonate's response to hypoxic conditions, a process thought to be related to SIDS outcomes. Mechanisms contributing to deficient hypoxia response include the ability of nicotine to act as a cholinergic stimulant through nicotinic acetylcholine receptor (nAChR) binding. The need for future research to investigate nicotine exposure and effects from non-maternal tobacco smoke sources in mid to late gestation is emphasized, along with a need to discourage smoking around both pregnant women and infants.     

High urine 1-hydroxypyrene glucuronide concentrations in Linxian,China, an area of high risk for squamous oesophageal cancer

Most squamous cell carcinomas of the oesophagus in low-risk populations are attributable to alcohol and tobacco consumption, but the aetiologic agents in many high-risk populations have yet to be definitively identified. Linxian, China has some of the highest oesophageal cancer rates in the world. Recent studies suggest that an association exists between high-level exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), and the development of oesophageal cancer. The inhabitants of this high-risk region extensively use coal and wood for cooking and heating in unvented stoves, and thus may be exposed to PAHs produced during the incomplete combustion of these fuel sources. High levels of B[a]P were recently detected in staple food samples from Linxian and histopathologic changes that may be associated with PAH exposure have also been identified in oesophagectomy specimens from the region. In an effort to determine whether this high-risk population is exposed to high levels of PAHs, voided urines from non-smokers (n = 22) without occupational exposure were collected and analysed using immunoaffinity chromatography and synchronous fluorescence spectroscopy for 1-hydroxypyrene glucuronide, a PAH metabolite and index biomarker for mixed PAH exposure. The median urine 1-hydroxypyrene glucuronide concentration (2.06 pmol ml^-1) was equivalent to concentrations detected in current smokers. To the authors' knowledge, this represents the first report of elevated urine 1-hydroxpyrene glucuronide concentrations in Linxian, and the first biologic confirmation that the inhabitants of this rural, non-industrial, high oesophageal cancer risk region are exposed to carcinogenic PAHs.     

Non-cancer effects of chemical agents on children's health

This paper provides an overview about the non-cancer health effects for children from relevant chemical agents in our environment. In addition, a meta-analysis was conducted on the association between sudden infant death syndrome (SIDS) and maternal smoking during pregnancy as well as postnatal exposure to environmental tobacco smoke (ETS).In children, birth deformities, neurodevelopment, reproductive outcomes and respiratory system are mainly affected by chemical exposures. According to recent systematic reviews, evidence is sufficient for cognitive impairments caused by low lead exposure levels. Evidence for neurotoxicity from prenatal methylmercury exposure is sufficient for high exposure levels and limited for low levels. Prenatal exposure to polychlorinated biphenyls (PCB) and related toxicants results in cognitive and motor deficits.Maternal smoking during pregnancy is a risk factor for preterm birth, foetal growth deficit and SIDS. The meta-analytic pooled risk estimate for SIDS based on 15 studies is 2.94 (95% confidence interval: 2.43–3.57). Postnatal exposure to ETS was found to increase the SIDS risk by a factor of 1.72 (95% CI: 1.28–2.30) based on six studies which took into account maternal smoking during pregnancy. Additionally, postnatal ETS exposure causes acute respiratory infections, ear problems, respiratory symptoms, more severe asthma, and it slows lung growth. These health effects are also of concern for postnatal exposure to ambient and indoor air pollution.Children differ from adults with respect to several aspects which are relevant for assessing their health risk. Thus, independent evaluation of toxicity in childhood populations is essential.     

Biomonitoring of environmental tobacco smoke (ETS)-related exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

The exposure of non-smokers to the tobacco-specific N-nitrosamine 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a rodent lung carcinogen, was determined in the air of various indoor environments as well as by biomonitoring of non-smokers exposed to environmental tobacco smoke (ETS) under real-life conditions using the urinary NNK metabolites 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-(N-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). NNK was not detectable (&lt;0.5 ng m^-3) in 11 rooms in which smoking did not occur. The mean NNK concentration in 19 rooms in which smoking took place was 17.5 (2.4-50.0) ng m^-3. The NNK levels significantly correlated with the nicotine levels (r=0.856; p&lt; 0.0001). Of the 29 non-smokers investigated, 12 exhibited no detectable NNAL and NNAL-Gluc excretion (&lt;3 pmol day) in their urine. The mean urinary excretion of NNAL and NNAL-Gluc of the 17 remaining non-smokers was 20.3 (&lt;3-63.2) and 22.9 (&lt;3-90.0) pmol day^-1, respectively. Total NNAL excretion (NNAL+NNAL-Gluc) in all non-smokers investigated significantly correlated with the amount of nicotine on personal samplers worn during the week prior to urine collection (r=0.88; &lt;0.0001) and with the urinary cotinine levels (r=0.40; p=0.038). No correlation was found between NNAL excretion and the reported extent of ETS exposure. Average total NNAL excretion in the non-smokers with detectable NNAL levels was 74 times less than in 20 smokers who were also investigated. The cotinine/total NNAL ratios in urine of smokers (9900) and non-smokers (9300) were similar. This appears to be at variance with the ratios of the corresponding precursors (nicotine/NNK) in mainstream smoke (16400) and ETS (1000). Possible reasons for this discrepancy are discussed. The possible role of NNK as a lung carcinogen in non-smokers is unclear, especially since NNK exposure in non-smokers is several orders of magnitude lower than the ordinary exposure to exogenous and endogenous N-nitrosamines and the role of NNK as a human lung carcinogen is not fully understood.     

Urinary mutagenicity in nonsmokers following exposure to fresh diluted sidestream cigarette smoke

Ten healthy male and 10 healthy female 'never-smoking' subjects (ages 21-50) participated in a 5-day environmental room study to determine if an acute exposure to a high level of fresh diluted sidestream smoke (FDSS) would alter urinary mutagenicity. On Monday, Tuesday, Thursday and Friday, the 20 subjects sat in environmental rooms for 7.33h and were exposed to filtered and humidified air. On Wednesday, the 20 subjects were exposed in the environmental rooms for 7.33h to an average respirable suspended particle (RSP) concentration of 179 microg/m(3) of FDSS generated by machine smoking 1R4F Kentucky reference cigarettes. This level of FDSS is approximately three times the ETS level seen in the top 5% of US workplaces which allow smoking. A cumulative 7.33h air sample from each environmental room was collected and determined to be mutagenic by Ames Salmonella assay. Subjects' urinary mutagenicity was measured on Wednesday as compared with Tuesday or Thursday by assaying concentrates of 24h urine samples in Ames Salmonella bacterial strains TA98 and YG1024. Diet was strictly controlled on all study days, with broiled and pan-fried meat not served to minimize ingestion of mutagenic protein pyrolysis products. Although all the urinary mutagenicity values were within the range reported for minor changes in diet, the subjects experienced a small but statistically significant increase (p<0.05) in urinary mutagenicity in strain YG1024, but not in the less sensitive strain TA98 on the day of FDSS exposure.     

Analysis of Intervention Strategies for Inhalation Exposure to Polycyclic Aromatic Hydrocarbons and Associated Lung Cancer Risk Based on a Monte Carlo Population Exposure Assessment Model

It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs), a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF) and potential impact fraction (PIF) of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making.