Charles J. Weschler

The association between asthma and allergic symptoms in children and phthalates in house dust : a nested case-control study

Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case–control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose–response relationships for these associations are supported by trend analyses. This study shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates—BBzP, DEHP, and di-n-butyl phthalate—can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.

Ventilation rates and health: multidisciplinary review of the scientific literature

UNLABELLED The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h(-1)) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. PRACTICAL IMPLICATIONS Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.

Ozone's Impact on Public Health: Contributions from Indoor Exposures to Ozone and Products of Ozone-Initiated Chemistry

Objective The associations between ozone concentrations measured outdoors and both morbidity and mortality may be partially due to indoor exposures to ozone and ozone-initiated oxidation products. In this article I examine the contributions of such indoor exposures to overall ozone-related health effects by extensive review of the literature as well as further analyses of published data. Findings Daily inhalation intakes of indoor ozone (micrograms per day) are estimated to be between 25 and 60% of total daily ozone intake. This is especially noteworthy in light of recent work indicating little, if any, threshold for ozone’s impact on mortality. Additionally, the present study estimates that average daily indoor intakes of ozone oxidation products are roughly one-third to twice the indoor inhalation intake of ozone alone. Some of these oxidation products are known or suspected to adversely affect human health (e.g., formaldehyde, acrolein, hydroperoxides, fine and ultrafine particles). Indirect evidence supports connections between morbidity/mortality and exposures to indoor ozone and its oxidation products. For example, cities with stronger associations between outdoor ozone and mortality tend to have residences that are older and less likely to have central air conditioning, which implies greater transport of ozone from outdoors to indoors. Conclusions Indoor exposures to ozone and its oxidation products can be reduced by filtering ozone from ventilation air and limiting the indoor use of products and materials whose emissions react with ozone. Such steps might be especially valuable in schools, hospitals, and childcare centers in regions that routinely experience elevated outdoor ozone concentrations.

Phthalates in indoor dust and their association with building characteristics

In a recent study of 198 Swedish children with persistent allergic symptoms and 202 controls without such symptoms, we reported associations between the symptoms and the concentrations of n-butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) in dust taken from the childrens’ bedrooms. In the present study we examined associations between the concentrations of different phthalate esters in the dust from these bedrooms and various characteristics of the home. The study focused on BBzP and DEHP because these were the phthalates associated with health complaints. Associations have been examined using parametric and nonparametric tests as well as multiple logistic regression. For both BBzP and DEHP, we found associations between their dust concentrations and the amount of polyvinyl chloride (PVC) used as flooring and wall material in the home. Furthermore, high concentrations of BBzP (above median) were associated with self-reported water leakage in the home, and high concentrations of DEHP were associated with buildings constructed before 1960. Other associations, as well as absence of associations, are reported. Both BBzP and DEHP were found in buildings with neither PVC flooring nor wall covering, consistent with the numerous additional plasticized materials that are anticipated to be present in a typical home. The building characteristics examined in this study cannot serve as complete proxies for these quite varied sources. However, the associations reported here can help identify homes where phthalate concentrations are likely to be elevated and can aid in developing mitigation strategies.

Potential reactions among indoor pollutants

Abstract Reactions among indoor pollutants can produce products that, otherwise, might not be present in an indoor environment. To be relevant in an indoor setting, a chemical reaction must occur within a time interval shorter than or comparable to the residence time for a packet of indoor air. At typical air exchange rates, the reactions that meet this criterion include those of ozone with nitric oxide, nitrogen dioxide, and selected unsaturated hydrocarbons; thermal decomposition of peroxyacyl nitrates; numerous free radical reactions; and selected heterogeneous processes. Stable products include aldehydes, ketones, carboxylic acids and various organic nitrates. These reactions also generate free radicals, starting with the nitrate radical, Criegree biradicals, and peroxyacyl radicals, and leading to the hydroxyl, alkyl, alkylperoxy, hydroperoxy, and alkoxy radicals. Such radicals can react with other indoor species yielding additional aldehydes, ketones, carboxylic acids, dinitrates and peroxyacyl nitrates. Some of the potential products are known or suspected to be irritating (e.g. methacrolein, nonanoic acid, 1,2-propanediol dinitrate, peroxybenzoyl nitrate, and radical anions of the type [Cl… NO2]−) However, some of these same products are difficult to detect using the sampling and analysis techniques currently applied to indoor air.

Reactions of ozone with human skin lipids: Sources of carbonyls, dicarbonyls, and hydroxycarbonyls in indoor air

This study has used proton transfer reaction-mass spectrometry (PTR-MS) for direct air analyses of volatile products resulting from the reactions of ozone with human skin lipids. An initial series of small-scale in vitro and in vivo experiments were followed by experiments conducted with human subjects in a simulated office. The latter were conducted using realistic ozone mixing ratios (≈15 ppb with occupants present). Detected products included mono- and bifunctional compounds that contain carbonyl, carboxyl, or α-hydroxy ketone groups. Among these, three previously unreported dicarbonyls have been identified, and two previously unreported α-hydroxy ketones have been tentatively identified. The compounds detected in this study (excepting acetone) have been overlooked in surveys of indoor pollutants, reflecting the limitations of the analytical methods routinely used to monitor indoor air. The results are fully consistent with the Criegee mechanism for ozone reacting with squalene, the single most abundant unsaturated constituent of skin lipids, and several unsaturated fatty acid moieties in their free or esterified forms. Quantitative product analysis confirms that squalene is the major scavenger of ozone at the interface between room air and the human envelope. Reactions between ozone and human skin lipids reduce the mixing ratio of ozone in indoor air, but concomitantly increase the mixing ratios of volatile products and, presumably, skin surface concentrations of less volatile products. Some of the volatile products, especially the dicarbonyls, may be respiratory irritants. Some of the less volatile products may be skin irritants.

SVOC exposure indoors: fresh look at dermal pathways

UNLABELLED This paper critically examines indoor exposure to semivolatile organic compounds (SVOCs) via dermal pathways. First, it demonstrates that--in central tendency--an SVOCs abundance on indoor surfaces and in handwipes can be predicted reasonably well from gas-phase concentrations, assuming that thermodynamic equilibrium prevails. Then, equations are developed, based upon idealized mass-transport considerations, to estimate transdermal penetration of an SVOC either from its concentration in skin-surface lipids or its concentration in air. Kinetic constraints limit air-to-skin transport in the case of SVOCs that strongly sorb to skin-surface lipids. Air-to-skin transdermal uptake is estimated to be comparable to or larger than inhalation intake for many SVOCs of current or potential interest indoors, including butylated hydroxytoluene, chlordane, chlorpyrifos, diethyl phthalate, Galaxolide, geranyl acetone, nicotine (in free-base form), PCB28, PCB52, Phantolide, Texanol and Tonalide. Although air-to-skin transdermal uptake is anticipated to be slow for bisphenol A, we find that transdermal permeation may nevertheless be substantial following its transfer to skin via contact with contaminated surfaces. The paper concludes with explorations of the influence of particles and dust on dermal exposure, the role of clothing and bedding as transport vectors, and the potential significance of hair follicles as transport shunts through the epidermis. PRACTICAL IMPLICATIONS Human exposure to indoor pollutants can occur through dietary and nondietary ingestion, inhalation, and dermal absorption. Many factors influence the relative importance of these pathways, including physical and chemical properties of the pollutants. This paper argues that exposure to indoor semivolatile organic compounds (SVOCs) through the dermal pathway has often been underestimated. Transdermal permeation of SVOCs can be substantially greater than is commonly assumed. Transport of SVOCs from the air to and through the skin is typically not taken into account in exposure assessments. Yet, for certain SVOCs, intake through skin is estimated to be substantially larger than intake through inhalation. Exposure scientists, risk assessors, and public health officials should be mindful of the dermal pathway when estimating exposures to indoor SVOCs. Also, they should recognize that health consequences vary with exposure pathway. For example, an SVOC that enters the blood through the skin does not encounter the same detoxifying enzymes that an ingested SVOC would experience in the stomach, intestines, and liver before it enters the blood.

Indoor Ozone Exposures

Indoor and outdoor ozone concentrations were measured from late May through October at three office buildings with very different ventilation rates. The indoor values closely tracked the outdoor values, and, depending on the ventilation rate, were 20 to 80 percent of those outdoors. The indoor/outdoor data are adequately described with a mass balance model. The model can also be coupled with reported air exchange rates to estimate indoor/outdoor ratios for other structures. The results from this and previous studies indicate that indoor concentrations are frequently a significant fraction of outdoor values. These observations, and the fact that most people spend greater than 90 percent of their time indoors, indicate that indoor ozone exposure (concentration X time) is greater than outdoor exposure for many people. Relatively inexpensive strategies exist to reduce indoor ozone levels, and these could be implemented to reduce the publics total ozone exposure.

Children's Phthalate Intakes and Resultant Cumulative Exposures Estimated from Urine Compared with Estimates from Dust Ingestion, Inhalation and Dermal Absorption in Their Homes and Daycare Centers

Total daily intakes of diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), di(isobutyl) phthalate (DiBP), butyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) were calculated from phthalate metabolite levels measured in the urine of 431 Danish children between 3 and 6 years of age. For each child the intake attributable to exposures in the indoor environment via dust ingestion, inhalation and dermal absorption were estimated from the phthalate levels in the dust collected from the child’s home and daycare center. Based on the urine samples, DEHP had the highest total daily intake (median: 4.42 µg/d/kg-bw) and BBzP the lowest (median: 0.49 µg/d/kg-bw). For DEP, DnBP and DiBP, exposures to air and dust in the indoor environment accounted for approximately 100%, 15% and 50% of the total intake, respectively, with dermal absorption from the gas-phase being the major exposure pathway. More than 90% of the total intake of BBzP and DEHP came from sources other than indoor air and dust. Daily intake of DnBP and DiBP from all exposure pathways, based on levels of metabolites in urine samples, exceeded the Tolerable Daily Intake (TDI) for 22 and 23 children, respectively. Indoor exposures resulted in an average daily DiBP intake that exceeded the TDI for 14 children. Using the concept of relative cumulative Tolerable Daily Intake (TDIcum), which is applicable for phthalates that have established TDIs based on the same health endpoint, we examined the cumulative total exposure to DnBP, DiBP and DEHP from all pathways; it exceeded the tolerable levels for 30% of the children. From the three indoor pathways alone, several children had a cumulative intake that exceeded TDIcum. Exposures to phthalates present in the air and dust indoors meaningfully contribute to a child’s total intake of certain phthalates. Such exposures, by themselves, may lead to intakes exceeding current limit values.

Generation and Quantification of Ultrafine Particles through Terpene/Ozone Reaction in a Chamber Setting

Terpene/ozone reactions produce gas- and condensed-phase products and thus contribute to both indoor and outdoor aerosol. These reactions may be important in indoor settings, where terpenes are generated from indoor sources and ambient ozone can reach significant levels. Moreover, airway irritation has been observed in mice exposed to terpene oxidation products (OPs). The aim of this study was to characterize a system for generating and quantifying ultrafine particles formed through terpene/ozone reactions in preparation for inhalation toxicology experiments. Two common monoterpenes, f -pinene and d -limonene, and a hemiterpene, isoprene, were investigated. Ozone and gas-phase terpene were introduced continuously into a reaction flow tube, from which reaction products entered a plexiglass chamber. Particle number, mass, and size distribution (∼15-750 nm) were monitored in the chamber for various reactant concentrations and air exchange rates (AERs). In all experiments, ozone was the limiting reagent and the reaction rate was much more rapid than the AER. Particles formed rapidly and in high concentrations in the pinene and limonene systems. Particle formation was slower in the isoprene system and fewer particles were formed; moreover, particle diameters were smaller. In all 3 systems, progressive growth of particles was observed due to condensation and coagulation processes. The isoprene system displayed instability with respect to aerosol characteristics and did not reach steady-state conditions. In the pinene system, ozone concentration was a strong predictor of steady-state particle number and mass concentration and particle diameter. The particle number was greater at higher AERs, but particles were smaller. This study is the first to incorporate measurement of ultrafine particles formed from terpene/ozone reactions into a controlled exposure chamber setting. Following system characterization, we will conduct mouse exposures to further investigate the respiratory effects of gas- and particle-phase terpene OPs.