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.

Indoor Air Sources of Outdoor Air Pollution: Health Consequences, Policy, and Recommendations: An Official American Thoracic Society Workshop Report.

Indoor sources of air pollution worsen indoor and outdoor air quality. Thus, identifying and reducing indoor pollutant sources would decrease both indoor and outdoor air pollution, benefit public health, and help address the climate crisis. As outdoor sources come under regulatory control, unregulated indoor sources become a rising percentage of the problem. This American Thoracic Society workshop was convened in 2022 to evaluate this increasing proportion of indoor contributions to outdoor air quality. The workshop was conducted by physicians and scientists, including atmospheric and aerosol scientists, environmental engineers, toxicologists, epidemiologists, regulatory policy experts, and pediatric and adult pulmonologists. Presentations and discussion sessions were centered on 1) the generation and migration of pollutants from indoors to outdoors, 2) the sources and circumstances representing the greatest threat, and 3) effective remedies to reduce the health burden of indoor sources of air pollution. The scope of the workshop was residential and commercial sources of indoor air pollution in the United States. Topics included wood burning, natural gas, cooking, evaporative volatile organic compounds, source apportionment, and regulatory policy. The workshop concluded that indoor sources of air pollution are significant contributors to outdoor air quality and that source control and filtration are the most effective measures to reduce indoor contributions to outdoor air. Interventions should prioritize environmental justice: Households of lower socioeconomic status have higher concentrations of indoor air pollutants from both indoor and outdoor sources. We identify research priorities, potential health benefits, and mitigation actions to consider (e.g., switching from natural gas to electric stoves and transitioning to scent-free consumer products). The workshop committee emphasizes the benefits of combustion-free homes and businesses and recommends economic, legislative, and education strategies aimed at achieving this goal.

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.

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.

The human oxidation field.

Hydroxyl (OH) radicals are highly reactive species that can oxidize most pollutant gases. In this study, high concentrations of OH radicals were found when people were exposed to ozone in a climate-controlled chamber. OH concentrations calculated by two methods using measurements of total OH reactivity, speciated alkenes, and oxidation products were consistent with those obtained from a chemically explicit model. Key to establishing this human-induced oxidation field is 6-methyl-5-hepten-2-one (6-MHO), which forms when ozone reacts with the skin-oil squalene and subsequently generates OH efficiently through gas-phase reaction with ozone. A dynamic model was used to show the spatial extent of the human-generated OH oxidation field and its dependency on ozone influx through ventilation. This finding has implications for the oxidation, lifetime, and perception of chemicals indoors and, ultimately, human health.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Breathing-rate adjusted population exposure to ozone and its oxidation products in 333 cities in China.

While PM2.5 (particles with aerodynamic diameter less than 2.5 µm) concentrations in China are beginning to decline because of pollution abatement measures, ozone (O3) concentrations continue to rise. In this study, we have used a Monte Carlo approach to estimate breathing-rate adjusted (BRA) population exposure to ozone and its oxidation products based on hourly O3 measurements collected in 2017 from monitoring stations in 333 Chinese cities. The median measured outdoor O3 concentration in these cities was 31 ppb, while the median calculated indoor concentrations of ozone and ozone-derived oxidation products were 7.5 ppb and 21 ppb, respectively. The median BRA O3 exposure concentration was 12 ppb, ranging from 2.2 ppb to 18 ppb among the cities. Eastern and central cities had higher exposure concentrations, while northeastern and western cities had lower. On average, the residents of these cities spent 88% of their time indoors. Consequently, even with breathing rate adjustments, indoor O3 exposure averaged 50% of the total O3 exposure nationwide. The median BRA exposure concentration for ozone-derived products was 18 ppb, ranging from 4.5 ppb to 32 ppb among the cities. On average, BRA exposure concentrations were 1.6 times larger for oxidation products than for ozone, while seasonal variations of exposure concentrations were smaller for oxidation products than for ozone. As many of the products of indoor ozone chemistry are toxic, the health consequences of exposure to such products should be further investigated.

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.