Reducing Transdermal Uptake of Semivolatile Plasticizers from Indoor Environments: A Clothing Intervention.

Models and laboratory studies suggest that everyday clothing influences the transdermal uptake of semivolatile organic compounds, including phthalate plasticizers, from indoor environments. However, this effect has not been documented in environmental exposure settings. In this pilot study, we quantified daily excretion of 17 urinary metabolites (µg/day) for phthalates and phthalate alternatives in nine participants during 5 days. On Day 0, baseline daily excretion was determined in participants' urine. Starting on Day 1, participants refrained from eating phthalate-heavy foods and using personal care products. On Days 3 and 4, participants wore precleaned clothing as an exposure intervention. We observed a reduction in the daily excretion of phthalates during the intervention; mono-n-butyl phthalate, monoisobutyl phthalate (MiBP), and monobenzyl phthalate were significantly reduced by 35, 38, and 56%, respectively. Summed metabolites of di(2-ethylhexyl)phthalate (DEHP) were also reduced (27%; not statistically significant). A similar reduction among phthalate alternatives was not observed. The daily excretion of MiBP during the nonintervention period strongly correlated with indoor air concentrations of diisobutyl phthalate (DiBP), suggesting that inhalation and transdermal uptake of DiBP from the air in homes are dominant exposure pathways. The results indicate that precleaned clothing can significantly reduce environmental exposure to phthalates and phthalate alternatives.

Exposure to oxybenzone from sunscreens: daily transdermal uptake estimation.

BACKGROUND: Fugacity, the driving force for transdermal uptake of chemicals, can be difficult to predict based only on the composition of complex, non-ideal mixtures such as personal care products. OBJECTIVE: Compare the predicted transdermal uptake of benzophenone-3 (BP-3) from sunscreen lotions, based on direct measurements of BP-3 fugacity in those products, to results of human subject experiments. METHODS: We measured fugacity relative to pure BP-3, for commercial sunscreens and laboratory mixtures, using a previously developed/solid-phase microextraction (SPME) method. The measured fugacity was combined with a transdermal uptake model to simulate urinary excretion rates of BP-3 resulting from sunscreen use. The model simulations were based on the reported conditions of four previously published human subject studies, accounting for area applied, time applied, showering and other factors. RESULTS: The fugacities of commercial lotions containing 3-6% w/w BP-3 were ~20% of the supercooled liquid vapor pressure. Simulated dermal uptake, based on these fugacities, are within a factor of 3 of the mean results reported from two human-subject studies. However, the model significantly underpredicts total excreted mass from two other human-subject studies. This discrepancy may be due to limitations in model inputs, such as fugacity of BP-3 in lotions used in those studies. SIGNIFICANCE: The results suggest that combining measured fugacity with such a model may provide order-of-magnitude accurate predictions of transdermal uptake of BP-3 from daily application of sunscreen products.

Partitioning of reactive oxygen species from indoor surfaces to indoor aerosols.

Reactive oxygen species (ROS) are among the species thought to be responsible for the adverse health effects of particulate matter (PM) inhalation. Field studies suggest that indoor sources of ROS contribute to measured ROS on PM in indoor air. We hypothesize that ozone reacts on indoor surfaces to form semi-volatile ROS, in particular organic peroxides (OPX), which partition to airborne particles. To test this hypothesis, we modeled ozone-induced formation of OPX, its decay and its partitioning to PM in a residential building and compared the results to field measurements. Simulations indicate that, while ROS of outdoor origin is the primary contributor to indoor ROS (in PM), a substantial fraction of ROS present in indoor PM is from ozone-surface chemistry. At an air change rate equal to 1/h, and an outdoor ozone mixing ratio of 35 ppb, 25% of the ROS concentration in air is due to indoor formation and partitioning of OPX to PM. For the same conditions, but with a modest indoor source of PM (1.5 mg h-1), 44% of indoor ROS on PM is of indoor origin. An indoor source of ozone, such as an electrostatic air cleaner, also increases OPX present in indoor PM. The results of the simulations support the hypothesis that ozone-induced formation of OPX on indoor surfaces, and subsequent partitioning to aerosols, is sufficient to explain field observations. Therefore, indoor sourced ROS could contribute meaningfully to total inhaled PM-ROS.

The influence of personal care products on ozone-skin surface chemistry.

Personal care products are increasingly being marketed to protect skin from the potentially harmful effects of air pollution. Here, we experimentally measure ozone deposition rates to skin and the generation rates and yields of oxidized products from bare skin and skin coated with various lotion formulations. Lotions reduced the ozone flux to the skin surface by 12% to 25%; this may be due to dilution of reactive skin lipids with inert lotion compounds or by reducing ozone diffusivity within the resulting mixture. The yields of volatile squalene oxidation products were 25% to 70% lower for a commercial sunscreen and for a base lotion with an added polymer or with antioxidants. Lower yields are likely due to competitive reactions of ozone with lotion ingredients including some ingredients that are not intended to be ozone sinks. The dynamics of the emissions of squalene ozonation product 6 methyl-2-heptenone (6MHO) suggest that lotions can dramatically reduce the solubility of products in the skin film. While some lotions appear to reduce the rate of oxidation of squalene by ozone, this evidence does not yet demonstrate that the lotions reduce the impact of air pollution on skin health.

Evaluating Indoor Air Chemical Diversity, Indoor-to-Outdoor Emissions, and Surface Reservoirs Using High-Resolution Mass Spectrometry.

Detailed offline speciation of gas- and particle-phase organic compounds was conducted using gas/liquid chromatography with traditional and high-resolution mass spectrometers in a hybrid targeted/nontargeted analysis. Observations were focused on an unoccupied home and were compared to two other indoor sites. Observed gas-phase organic compounds span the volatile to semivolatile range, while functionalized organic aerosols extend from intermediate volatility to ultra-low volatility, including a mix of oxygen, nitrogen, and sulfur-containing species. Total gas-phase abundances of hydrocarbon and oxygenated gas-phase complex mixtures were elevated indoors and strongly correlated in the unoccupied home. While gas-phase concentrations of individual compounds generally decreased slightly with greater ventilation, their elevated ratios relative to controlled emissions of tracer species suggest that the dilution of gas-phase concentrations increases off-gassing from surfaces and other indoor reservoirs, with volatility-dependent responses to dynamically changing environmental factors. Indoor-outdoor emissions of gas-phase intermediate-volatility/semivolatile organic hydrocarbons from the unoccupied home averaged 6-11 mg h-1, doubling with ventilation. While the largest single-compound emissions observed were furfural (61-275 mg h-1) and acetic acid, observations spanned a wide range of individual volatile chemical products (e.g., terpenoids, glycol ethers, phthalates, other oxygenates), highlighting the abundance of long-lived reservoirs resulting from prior indoor use or materials, and their gradual transport outdoors.

Continuous measurement of reactive oxygen species inside and outside of a residential house during summer.

Reactive oxygen species (ROS) are an important contributor to adverse health effects associated with ambient air pollution. Despite infiltration of ROS from outdoors, and possible indoor sources (eg, combustion), there are limited data available on indoor ROS. In this study, part of the second phase of Air Composition and Reactivity from Outdoor aNd Indoor Mixing campaign (ACRONIM-2), we constructed and deployed an online, continuous, system to measure extracellular gas- and particle-phase ROS during summer in an unoccupied residence in St. Louis, MO, USA. Over a period of one week, we observed that the non-denuded outdoor ROS (representing particle-phase ROS and some gas-phase ROS) concentration ranged from 1 to 4 nmol/m3 (as H2 O2 ). Outdoor concentrations were highest in the afternoon, coincident with peak photochemistry periods. The indoor concentrations of particle-phase ROS were nearly equal to outdoor concentrations, regardless of window-opening status or air exchange rates. The indoor/outdoor ratio of non-denuded ROS (I/OROS ) was significantly less than 1 with windows open and even lower with windows closed. Combined, these observations suggest that gas-phase ROS are efficiently removed by interior building surfaces and that there may be an indoor source of particle-phase ROS.

Yields and Variability of Ozone Reaction Products from Human Skin.

The skin of 20 human participants was exposed to ∼110 ppb O3 and volatile products of the resulting chemistry were quantified in real time. Yields (ppb product emitted/ppb ozone consumed) for 40 products were quantified. Major products of the primary reaction of ozone-squalene included 6-methyl 5-hepten-2-one (6-MHO) and geranyl acetone (GA) with average yields of 0.22 and 0.16, respectively. Other major products included decanal, methacrolein (or methyl vinyl ketone), nonanal, and butanal. Yields varied widely among participants; summed yields ranged from 0.33 to 0.93. The dynamic increase in emission rates during ozone exposure also varied among participants, possibly indicative of differences in the thickness of the skin lipid layer. Factor analysis indicates that much of the variability among participants is due to factors associated with the relative abundance of (1) "fresh" skin lipid constituents (such as squalene and fatty acids), (2) oxidized skin lipids, and (3) exogenous compounds. This last factor appears to be associated with the presence of oleic and linoleic acids and could be accounted for by uptake of cooking oils or personal care products to skin lipids.

Transdermal uptake of benzophenone-3 from clothing: comparison of human participant results to model predictions.

BACKGROUND: Models of transdermal uptake of chemicals from clothing have been developed, but not compared with recent human subject experiments. In a well-characterized experiment, participants wore t-shirts pre-dosed with benzophenone-3 (BP-3) and BP-3 and a metabolite were monitored in urine voids. OBJECTIVE: Compare a dynamic model of transdermal uptake from clothing to results of the human subject experiment. METHODS: The model simulating dynamic transdermal uptake from clothing was coupled with direct measurements of the gas phase concentration of benzophenone-3 (BP-3) near the surface of clothing to simulate the conditions of the human subject experiment. RESULTS: The base-case model results were consistent with the those reported for human subjects. The results were moderately sensitive to parameters such as the diffusivity in the stratum corneum (SC), the SC thickness, and SC-air partition coefficient. The model predictions were most sensitive to the clothing fit. Tighter clothing worn during exposure period significantly increased excretion rates but tighter fit "clean" clothing during post-exposure period acts as a sink that reduces transdermal absorption by transferring BP-3 from skin surface lipids to clothing. The shape of the excretion curve was most sensitive to the diffusivity in the SC and clothing fit. SIGNIFICANCE: This research provides further support for clothing as an important mediator of dermal exposure to environmental chemicals.

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.

A high throughput method for measuring cloth-air equilibrium distribution ratios for SVOCs present in indoor environments.

Accumulation of chemicals from the environment to clothing and other textiles can influence human uptake by several exposure routes. In this research, we demonstrate that the cloth-air equilibrium distribution ratio for species i, KCA_i, can be measured relatively easily and quickly using headspace analysis of cloth dosed with two common indoor air SVOCs, diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP). A known mass of a phthalate was applied to the cloth in a volatile solvent carrier. After evaporation of the solvent, the cloth was placed in a vial and allowed to equilibrate with the air in the vial. Since the volume of headspace air is small, the total mass required to transfer from cloth to air is small and also the time required for air equilibration with the fabric surface is very short (minutes). Distribution ratios for the two phthalate esters sorbed to cotton jean material, reported as the concentration in the bulk cloth divided by the air concentration, were measured at 20, 25, 32, and 40 °C. The volume-normalized distribution ratio, Kvol [(µg/m3)/(µg/m3)], ranged from (0.75 ± 0.01)× 105 to (5.6 ± 0.2) × 105 for DEP and (5 ± 0.3)× 105 to (57 ± 1) × 105 for DnBP. Mass-normalized distribution ratio, Kmass [m3/g], ranged from (0.25 ± 0.01) to (1.8 ± 0.1) for DEP and (1.6 ± 0.1) to (18.5 ± 0.5) for DnBP. The cloth-air distribution ratios obtained from this study compare favorably with previously published results using other methods. Although equilibration with air in the headspace can be rapid, diffusion into the textile fibers is a slower equilibration process. Overall, this simple method has the potential to rapidly generate distribution ratios for a large number of chemical-textile pairs.