Squalene Depletion in Skin Following Human Exposure to Ozone under Controlled Chamber Conditions.

A major component of human skin oil is squalene, a highly unsaturated hydrocarbon that protects the skin from atmospheric oxidants. Skin oil, and thus squalene, is continuously replenished on the skin surface. Squalene is also quickly consumed through reactions with ozone and other oxidants. This study examined the extent of squalene depletion in the skin oils of the forearm of human volunteers after exposure to ozone in a climate chamber. Temperature, relative humidity (RH), skin coverage by clothing, and participants' age were varied in a controlled manner. Concentrations of squalene were determined in skin wipe samples collected before and after ozone exposure. Exposures to ozone resulted in statistically significant decreases in post-exposure squalene concentrations compared to pre-exposure squalene concentrations in the skin wipes when squalene concentrations were normalized by concentrations of co-occurring cholesterol but not by co-occurring pyroglutamic acid (PGA). The rate of squalene loss due to ozonolysis was lower than its replenishment on the skin surface. Within the ranges examined, temperature and RH did not significantly affect the difference between normalized squalene levels in post-samples versus pre-samples. Although not statistically significant, skin coverage and age of the volunteers (three young adults, three seniors, and three teenagers) did appear to impact squalene depletion on the skin surfaces.

Observing ozone chemistry in an occupied residence.

Outdoor ozone transported indoors initiates oxidative chemistry, forming volatile organic products. The influence of ozone chemistry on indoor air composition has not been directly quantified in normally occupied residences. Here, we explore indoor ozone chemistry in a house in California with two adult inhabitants. We utilize space- and time-resolved measurements of ozone and volatile organic compounds (VOCs) acquired over an 8-wk summer campaign. Despite overall low indoor ozone concentrations (mean value of 4.3 ppb) and a relatively low indoor ozone decay constant (1.3 h-1), we identified multiple VOCs exhibiting clear contributions from ozone-initiated chemistry indoors. These chemicals include 6-methyl-5-hepten-2-one (6-MHO), 4-oxopentanal (4-OPA), nonenal, and C8-C12 saturated aldehydes, which are among the commonly reported products from laboratory studies of ozone interactions with indoor surfaces and with human skin lipids. These VOCs together accounted for ≥12% molecular yield with respect to house-wide consumed ozone, with the highest net product yield for nonanal (≥3.5%), followed by 6-MHO (2.7%) and 4-OPA (2.6%). Although 6-MHO and 4-OPA are prominent ozonolysis products of skin lipids (specifically squalene), ozone reaction with the body envelopes of the two occupants in this house are insufficient to explain the observed yields. Relatedly, we observed that ozone-driven chemistry continued to produce 6-MHO and 4-OPA even after the occupants had been away from the house for 5 d. These observations provide evidence that skin lipids transferred to indoor surfaces made substantial contributions to ozone reactivity in the studied house.

Ozone Loss: A Surrogate for the Indoor Concentration of Ozone-Derived Products.

Ozone concentrations tend to be substantially lower indoors than outdoors, largely because of ozone reactions with indoor surfaces. When there are no indoor sources of ozone, a common condition, the net concentration of gaseous products derived from indoor ozone chemistry scales linearly with the difference between outdoor and indoor ozone concentrations, termed "ozone loss." As such, ozone loss is a metric that might be used by epidemiologists to disentangle the adverse health effects of ozone's oxidation products from those of exposure to ozone itself. The present paper examines the characteristics, potential utility, and limitations of the ozone loss concept. We show that for commonly occurring indoor conditions, the ozone loss concentration is directly proportional to the total rate constant for ozone removal on surfaces (ksum) and inversely proportional to the net removal of ozone by air exchange (λ) plus surface reactions (ksum). It follows that the ratio of indoor ozone to ozone loss is equal to the ratio of λ to ksum. Ozone loss is a promising metric for probing potential adverse health effects resulting from exposures to products of indoor ozone chemistry. Notwithstanding its virtues, practitioners using it should be mindful of the limitations discussed in this paper.

Quantifying Ozone-Dependent Emissions of Volatile Organic Compounds from the Human Body.

Ozone reactions on human body surfaces produce volatile organic compounds (VOCs) that influence indoor air quality. However, the dependence of VOC emissions on the ozone concentration has received limited attention. In this study, we conducted 36 sets of single-person chamber experiments with three volunteers exposed to ozone concentrations ranging from 0 to 32 ppb. Emission fluxes from human body surfaces were measured for 11 targeted skin-oil oxidation products. For the majority of these products, the emission fluxes linearly correlated with ozone concentration, indicating a constant surface yield (moles of VOC emitted per mole of ozone deposited). However, for the second-generation oxidation product 4-oxopentanal, a higher surface yield was observed at higher ozone concentrations. Furthermore, many VOCs have substantial emissions in the absence of ozone. Overall, these results suggest that the complex surface reactions and mass transfer processes involved in ozone-dependent VOC emissions from the human body can be represented using a simplified parametrization based on surface yield and baseline emission flux. Values of these two parameters were quantified for targeted products and estimated for other semiquantified VOC signals, facilitating the inclusion of ozone/skin oil chemistry in indoor air quality models and providing new insights on skin oil chemistry.

Indoor ozone: Concentrations and influencing factors.

Because people spend most of their time indoors, much of their exposure to ozone occurs in buildings, which are partially protective against outdoor ozone. Measurements in approximately 2000 indoor environments (residences, schools, and offices) show a central tendency for average indoor ozone concentration of 4-6 ppb and an indoor to outdoor concentration ratio of about 25%. Considerable variability in this ratio exists among buildings, as influenced by seven building-associated factors: ozone removal in mechanical ventilation systems, ozone penetration through the building envelope, air-change rates, ozone loss rate on fixed indoor surfaces, ozone loss rate on human occupants, ozone loss by homogeneous reaction with nitrogen oxides, and ozone loss by reaction with gas-phase organics. Among these, the most important are air-change rates, ozone loss rate on fixed indoor surfaces, and, in densely occupied spaces, ozone loss rate on human occupants. Although most indoor ozone originates outdoors and enters with ventilation air, indoor emission sources can materially increase indoor ozone concentrations. Mitigation technologies to reduce indoor ozone concentrations are available or are being investigated. The most mature of these technologies, activated carbon filtration of mechanical ventilation supply air, shows a high modeled health-benefit to cost ratio when applied in densely occupied spaces.

Effect of Ozone, Clothing, Temperature, and Humidity on the Total OH Reactivity Emitted from Humans.

People influence indoor air chemistry through their chemical emissions via breath and skin. Previous studies showed that direct measurement of total OH reactivity of human emissions matched that calculated from parallel measurements of volatile organic compounds (VOCs) from breath, skin, and the whole body. In this study, we determined, with direct measurements from two independent groups of four adult volunteers, the effect of indoor temperature and humidity, clothing coverage (amount of exposed skin), and indoor ozone concentration on the total OH reactivity of gaseous human emissions. The results show that the measured concentrations of VOCs and ammonia adequately account for the measured total OH reactivity. The total OH reactivity of human emissions was primarily affected by ozone reactions with organic skin-oil constituents and increased with exposed skin surface, higher temperature, and higher humidity. Humans emitted a comparable total mixing ratio of VOCs and ammonia at elevated temperature-low humidity and elevated temperature-high humidity, with relatively low diversity in chemical classes. In contrast, the total OH reactivity increased with higher temperature and higher humidity, with a larger diversity in chemical classes compared to the total mixing ratio. Ozone present, carbonyl compounds were the dominant reactive compounds in all of the reported conditions.

Total OH Reactivity of Emissions from Humans: In Situ Measurement and Budget Analysis.

Humans are a potent, mobile source of various volatile organic compounds (VOCs) in indoor environments. Such direct anthropogenic emissions are gaining importance, as those from furnishings and building materials have become better regulated and energy efficient homes may reduce ventilation. While previous studies have characterized human emissions in indoor environments, the question remains whether VOCs remain unidentified by current measuring techniques. In this study conducted in a climate chamber occupied by four people, the total OH reactivity of air was quantified, together with multiple VOCs measured by proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) and fast gas chromatography-mass spectrometry (fast-GC-MS). Whole-body, breath, and dermal emissions were assessed. The comparison of directly measured OH reactivity and that of the summed reactivity of individually measured species revealed no significant shortfall. Ozone exposure (37 ppb) was found to have little influence on breath OH reactivity but enhanced dermal OH reactivity significantly. Without ozone, the whole-body OH reactivity was dominated by breath emissions, mostly isoprene (76%). With ozone present, OH reactivity nearly doubled, with the increase being mainly caused by dermal emissions of mostly carbonyl compounds (57%). No significant difference in total OH reactivity was observed for different age groups (teenagers/young adults/seniors) without ozone. With ozone present, the total OH reactivity decreased slightly with increasing age.

Ozone Initiates Human-Derived Emission of Nanocluster Aerosols.

Nanocluster aerosols (NCAs, particles <3 nm) are important players in driving climate feedbacks and processes that impact human health. This study reports, for the first time, NCA formation when gas-phase ozone reacts with human surfaces. In an occupied climate-controlled chamber, we detected NCA only when ozone was present. NCA emissions were dependent on clothing coverage, occupant age, air temperature, and humidity. Ozone-initiated chemistry with human skin lipids (particularly their primary surface reaction products) is the key mechanism driving NCA emissions, as evidenced by positive correlations with squalene in human skin wipe samples and known gaseous products from ozonolysis of skin lipids. Oxidation by OH radicals, autoxidation reactions, and human-emitted NH3 may also play a role in NCA formation. Such chemical processes are anticipated to generate aerosols of the smallest size (1.18-1.55 nm), whereas larger clusters result from subsequent growth of the smaller aerosols. This study shows that whenever we encounter ozone indoors, where we spend most of our lives, NCAs will be produced in the air around us.

Assessing Human Exposure to SVOCs in Materials, Products, and Articles: A Modular Mechanistic Framework.

A critical review of the current state of knowledge of chemical emissions from indoor sources, partitioning among indoor compartments, and the ensuing indoor exposure leads to a proposal for a modular mechanistic framework for predicting human exposure to semivolatile organic compounds (SVOCs). Mechanistically consistent source emission categories include solid, soft, frequent contact, applied, sprayed, and high temperature sources. Environmental compartments are the gas phase, airborne particles, settled dust, indoor surfaces, and clothing. Identified research needs are the development of dynamic emission models for several of the source emission categories and of estimation strategies for critical model parameters. The modular structure of the framework facilitates subsequent inclusion of new knowledge, other chemical classes of indoor pollutants, and additional mechanistic processes relevant to human exposure indoors. The framework may serve as the foundation for developing an open-source community model to better support collaborative research and improve access for application by stakeholders. Combining exposure estimates derived using this framework with toxicity data for different end points and toxicokinetic mechanisms will accelerate chemical risk prioritization, advance effective chemical management decisions, and protect public health.

Predicting Transdermal Uptake of Phthalates and a Paraben from Cosmetic Cream Using the Measured Fugacity.

Transdermal uptake models compliment in vitro and in vivo experiments in assessing risk of environmental exposures to semivolatile organic compounds (SVOCs). A key parameter for mechanistic models is the chemical driving force for mass transfer from environmental media to human skin. In this research, we measure this driving force in the form of fugacity for chemicals in cosmetic cream and use it to model uptake from cosmetics as a surrogate for condensed environmental media. A simple cosmetic cream, containing no target analytes, was mixed with diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), and butyl paraben (BP) and diluted to make creams with concentrations ranging from 0.025% to 6%. The fugacity, relative to the pure compound, was measured using solid-phase micro extraction (SPME). We found that the relationship between the concentration and fugacity is highly nonlinear. The relative fugacity of the chemicals for a 2% w/w formulation was used in a diffusion-based model to predict transdermal uptake of each chemical and was compared with excretion data from a prior human subject study with the same formulation. Dynamic simulations of excretion are generally consistent with the results of the human subject experiment but sensitive to the input parameters, especially the time between cream application and showering.

Human Ammonia Emission Rates under Various Indoor Environmental Conditions.

Ammonia (NH3) is typically present at higher concentrations in indoor air (∼10-70 ppb) than in outdoor air (∼50 ppt to 5 ppb). It is the dominant neutralizer of acidic species in indoor environments, strongly influencing the partitioning of gaseous acidic and basic species to aerosols, surface films, and bulk water. We have measured NH3 emissions from humans in an environmentally controlled chamber. A series of experiments, each with four volunteers, quantified NH3 emissions as a function of temperature (25.1-32.6 °C), clothing (long-sleeved shirts/pants or T-shirts/shorts), age (teenagers, adults, and seniors), relative humidity (low or high), and ozone (<2 ppb or ∼35 ppb). Higher temperature and more skin exposure (T-shirts/shorts) significantly increased emission rates. For adults and seniors (long clothing), NH3 emissions are estimated to be 0.4 mg h-1 person-1 at 25 °C, 0.8 mg h-1 person-1 at 27 °C, and 1.4 mg h-1 person-1 at 29 °C, based on the temperature relationship observed in this study. Human NH3 emissions are sufficient to neutralize the acidifying impacts of human CO2 emissions. Results from this study can be used to more accurately model indoor and inner-city outdoor NH3 concentrations and associated chemistry.

Indoor acids and bases.

Numerous acids and bases influence indoor air quality. The most abundant of these species are CO2 (acidic) and NH3 (basic), both emitted by building occupants. Other prominent inorganic acids are HNO3 , HONO, SO2 , H2 SO4 , HCl, and HOCl. Prominent organic acids include formic, acetic, and lactic; nicotine is a noteworthy organic base. Sources of N-, S-, and Cl-containing acids can include ventilation from outdoors, indoor combustion, consumer product use, and chemical reactions. Organic acids are commonly more abundant indoors than outdoors, with indoor sources including occupants, wood, and cooking. Beyond NH3 and nicotine, other noteworthy bases include inorganic and organic amines. Acids and bases partition indoors among the gas-phase, airborne particles, bulk water, and surfaces; relevant thermodynamic parameters governing the partitioning are the acid-dissociation constant (Ka ), Henry's law constant (KH ), and the octanol-air partition coefficient (Koa ). Condensed-phase water strongly influences the fate of indoor acids and bases and is also a medium for chemical interactions. Indoor surfaces can be large reservoirs of acids and bases. This extensive review of the state of knowledge establishes a foundation for future inquiry to better understand how acids and bases influence the suitability of indoor environments for occupants, cultural artifacts, and sensitive equipment.

The Indoor Chemical Human Emissions and Reactivity (ICHEAR) project: Overview of experimental methodology and preliminary results.

With the gradual reduction of emissions from building products, emissions from human occupants become more dominant indoors. The impact of human emissions on indoor air quality is inadequately understood. The aim of the Indoor Chemical Human Emissions and Reactivity (ICHEAR) project was to examine the impact on indoor air chemistry of whole-body, exhaled, and dermally emitted human bioeffluents under different conditions comprising human factors (t-shirts/shorts vs long-sleeve shirts/pants; age: teenagers, young adults, and seniors) and a variety of environmental factors (moderate vs high air temperature; low vs high relative humidity; presence vs absence of ozone). A series of human subject experiments were performed in a well-controlled stainless steel climate chamber. State-of-the-art measurement technologies were used to quantify the volatile organic compounds emitted by humans and their total OH reactivity; ammonia, nanoparticle, fluorescent biological aerosol particle (FBAP), and microbial emissions; and skin surface chemistry. This paper presents the design of the project, its methodologies, and preliminary results, comparing identical measurements performed with five groups, each composed of 4 volunteers (2 males and 2 females). The volunteers wore identical laundered new clothes and were asked to use the same set of fragrance-free personal care products. They occupied the ozone-free (<2 ppb) chamber for 3 hours (morning) and then left for a 10-min lunch break. Ozone (target concentration in occupied chamber ~35 ppb) was introduced 10 minutes after the volunteers returned to the chamber, and the measurements continued for another 2.5 hours. Under a given ozone condition, relatively small differences were observed in the steady-state concentrations of geranyl acetone, 6MHO, and 4OPA between the five groups. Larger variability was observed for acetone and isoprene. The absence or presence of ozone significantly influenced the steady-state concentrations of acetone, geranyl acetone, 6MHO, and 4OPA. Results of replicate experiments demonstrate the robustness of the experiments. Higher repeatability was achieved for dermally emitted compounds and their reaction products than for constituents of exhaled breath.

Clothing-Mediated Exposures to Chemicals and Particles.

A growing body of evidence identifies clothing as an important mediator of human exposure to chemicals and particles, which may have public health significance. This paper reviews and critically assesses the state of knowledge regarding how clothing, during wear, influences exposure to molecular chemicals, abiotic particles, and biotic particles, including microbes and allergens. The underlying processes that govern the acquisition, retention, and transmission of clothing-associated contaminants and the consequences of these for subsequent exposures are explored. Chemicals of concern have been identified in clothing, including byproducts of their manufacture and chemicals that adhere to clothing during use and care. Analogously, clothing acts as a reservoir for biotic and abiotic particles acquired from occupational and environmental sources. Evidence suggests that while clothing can be protective by acting as a physical or chemical barrier, clothing-mediated exposures can be substantial in certain circumstances and may have adverse health consequences. This complex process is influenced by the type and history of the clothing; the nature of the contaminant; and by wear, care, and storage practices. Future research efforts are warranted to better quantify, predict, and control clothing-related exposures.

Reducing Indoor Levels of "Outdoor PM2.5" in Urban China: Impact on Mortalities.

This study estimates adult mortalities attributed to PM2.5 across urban China in 2015 and the corresponding mortalities that might be avoided by meeting the yearly averaged indoor PM2.5 threshold in the newly established Assessment Standard for Healthy Building (ASHB) and seven other potential thresholds. We use outdoor PM2.5 concentrations from ∼1500 monitoring sites in 339 Chinese cities, coupled with a detailed exposure model, to estimate outdoor and indoor exposures to PM2.5 originating outdoors. We proceed to calculate premature mortality attributable to PM2.5 exposure using an integrated exposure-response model. Results indicate that indoor exposures accounted for 66%-87% of total exposure to PM2.5 of outdoor origin and 81% (95% confidence interval (CI), 71%-87%), i.e., 316 000 (95% CI, 176 000-435 000), of the 389 000 (95% CI, 245 000-501 000) mortalities attributable to "outdoor PM2.5" for the urban population ≥25 years of age in China in 2015. Potentially 14 000 (95% CI, 8000-20 000) deaths might be avoided if indoor PM2.5 of outdoor origin met the ASHB guideline of 35 µg/m3 for annual mean indoor PM2.5, and 162 000 (95% CI, 79 000-237 000) deaths might be avoided by meeting a 10 µg/m3 threshold. The analysis in this work should be helpful in formulating indoor air quality policies.

Ozone in urban China: Impact on mortalities and approaches for establishing indoor guideline concentrations.

Reducing indoor ozone levels may be an effective strategy to reduce total exposure and associated mortality. Here we estimate (a) premature mortalities attributable to ozone for China's urban population ≥25 years of age; (b) the fraction of total exposure occurring indoors; and (c) mortalities that can be potentially avoided through meeting current and more stringent indoor ozone standards/guidelines based on 1-hour daily maxima. To estimate ozone-attributable premature mortalities, we used hourly outdoor ozone concentrations measured at 1497 monitoring stations located in 339 Chinese cities and a published concentration-response model. We proceeded to estimate province-specific infiltration factors and co-occurring hourly indoor ozone concentrations. For the year 2015, we estimated that indoor exposures accounted for 59% (95% confidence interval (CI): 26%-79%) of the total ozone exposure that resulted in 70800 (95% CI: 35 900-137 700) premature all-cause mortalities in urban China. If the current Chinese indoor ozone standards (80 ppbv (160 µg/m3 ); 56 ppbv (112 µg/m3 )) were met, the mean estimates of reduction in mortalities would be indistinguishable from zero. With stricter 1-hour indoor ozone guidelines, the expected mortality reductions increase exponentially per unit decrease in indoor ozone. The analysis in this paper should help facilitate formulating present and future indoor ozone guidelines.

Indoor ozone/human chemistry and ventilation strategies.

This study aimed to better understand and quantify the influence of ventilation strategies on occupant-related indoor air chemistry. The oxidation of human skin oil constituents was studied in a continuously ventilated climate chamber at two air exchange rates (1 h-1 and 3 h-1 ) and two initial ozone mixing ratios (30 and 60 ppb). Additional measurements were performed to investigate the effect of intermittent ventilation ("off" followed by "on"). Soiled t-shirts were used to simulate the presence of occupants. A time-of-flight-chemical ionization mass spectrometer (ToF-CIMS) in positive mode using protonated water clusters was used to measure the oxygenated reaction products geranyl acetone, 6-methyl-5-hepten-2-one (6-MHO) and 4-oxopentanal (4-OPA). The measurement data were used in a series of mass balance models accounting for formation and removal processes. Reactions of ozone with squalene occurring on the surface of the t-shirts are mass transport limited; ventilation rate has only a small effect on this surface chemistry. Ozone-squalene reactions on the t-shirts produced gas-phase geranyl acetone, which was subsequently removed almost equally by ventilation and further reaction with ozone. About 70% of gas-phase 6-MHO was produced in surface reactions on the t-shirts, the remainder in secondary gas-phase reactions of ozone with geranyl acetone. 6-MHO was primarily removed by ventilation, while further reaction with ozone was responsible for about a third of its removal. 4-OPA was formed primarily on the surfaces of the shirts (~60%); gas-phase reactions of ozone with geranyl acetone and 6-MHO accounted for ~30% and ~10%, respectively. 4-OPA was removed entirely by ventilation. The results from the intermittent ventilation scenarios showed delayed formation of the reaction products and lower product concentrations compared to continuous ventilation.

Indoor Chemistry.

This review aims to encapsulate the importance, ubiquity, and complexity of indoor chemistry. We discuss the many sources of indoor air pollutants and summarize their chemical reactions in the air and on surfaces. We also summarize some of the known impacts of human occupants, who act as sources and sinks of indoor chemicals, and whose activities (e.g., cooking, cleaning, smoking) can lead to extremely high pollutant concentrations. As we begin to use increasingly sensitive and selective instrumentation indoors, we are learning more about chemistry in this relatively understudied environment.

Assessing Human Exposure to Organic Pollutants in the Indoor Environment.

There is an ongoing probing of the role of chemicals in the indoor environment. The majority of potential target substances are so-called very volatile, volatile, and semi-volatile organic compounds (VVOCs, VOCs, and SVOCs). Depending on their physical properties and the mass transfer conditions, they are distributed in or between the gas phase, particle phase, settled house dust, surface films, clothing, and other fabrics as well as the exposed skin and hair of the occupants themselves. Therefore, inhalation, ingestion, and dermal uptake all must be considered as relevant pathways for exposure assessment in human habitats. Exposure to VVOCs, VOCs, and SVOCs can be estimated by measuring their concentrations in relevant indoor compartments or by determining the amounts of the target compounds and/or their metabolites in urine and blood. Assessing the various routes of exposure often requires a combination of sophisticated and interdisciplinary theoretical background and experimental techniques. Consequently, close communication and collaboration between chemical and exposure scientists are needed to achieve a better understanding of human exposure to chemical substances in various indoor environments. Embedded in the toxicological context, this is the basis for assessing the corresponding health risks and for determining control strategies or approaches to limit such risks.