75 results on '"MORRISON, GLENN"'
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2. Reducing Transdermal Uptake of Semivolatile Plasticizers from Indoor Environments: A Clothing Intervention.
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Hammel, Stephanie C., Eftekhari, Azin, Eichler, Clara M. A., Liu, Chih-Wei, Nylander-French, Leena A., Engel, Lawrence S., Lu, Kun, and Morrison, Glenn C.
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- 2023
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3. Cloth–Air Partitioning of Neutral Per- and Polyfluoroalkyl Substances (PFAS) in North Carolina Homes during the Indoor PFAS Assessment (IPA) Campaign.
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Eichler, Clara M. A., Chang, Naomi Y., Cohen Hubal, Elaine A., Amparo, Daniel E., Zhou, Jiaqi, Surratt, Jason D., Morrison, Glenn C., and Turpin, Barbara J.
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- 2023
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4. Ozone-Initiated Yield of Reactive Oxygen Species in a Model Indoor Surface Film.
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Morrison, Glenn, Moravec, Ryan, and Yao, Zhenduo
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- 2023
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5. Cloth–Air Partitioning of Neutral Per- and Polyfluoroalkyl Substances (PFAS) in North Carolina Homes during the Indoor PFAS Assessment (IPA) Campaign
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Eichler, Clara M. A., Chang, Naomi Y., Cohen Hubal, Elaine A., Amparo, Daniel E., Zhou, Jiaqi, Surratt, Jason D., Morrison, Glenn C., and Turpin, Barbara J.
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Partitioning of per- and polyfluoroalkyl substances (PFAS) to indoor materials, including clothing, may prolong the residence time of PFAS indoors and contribute to exposure. During the Indoor PFAS Assessment (IPA) Campaign, we measured concentrations of nine neutral PFAS in air and cotton cloth in 11 homes in North Carolina, for up to 9 months. Fluorotelomer alcohols (i.e., 6:2 FTOH, 8:2 FTOH, and 10:2 FTOH) are the dominant target species in indoor air, with concentrations ranging from 1.8 to 49 ng m–3, 1.2 to 53 ng m–3, and 0.21 to 5.7 ng m–3, respectively. In cloth, perfluorooctane sulfonamidoethanols (i.e., MeFOSE and EtFOSE) accumulated most significantly over time, reaching concentrations of up to 0.26 ng cm–2and 0.24 ng cm–2, respectively. From paired measurements of neutral PFAS in air and suspended cloth, we derived cloth–air partition coefficients (Kca) for 6:2, 8:2, and 10:2 FTOH; ethylperfluorooctane sulfonamide (EtFOSA); MeFOSE; and EtFOSE. Mean log(Kca) values range from 4.7 to 6.6 and are positively correlated with the octanol–air partition coefficient. We investigated the effect of the cloth storage method on PFAS accumulation and the influence of home characteristics on air concentrations. Temperature had the overall greatest effect. This study provides valuable insights into PFAS distribution, fate, and exposure indoors.
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- 2023
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6. Indoor monoterpene emission rates from commercial cannabis cultivation facilities in Colorado
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Urso, Kaitlin, Vizuete, William, Moravec, Ryan, Khlystov, Andrey, Frazier, Alicia, and Morrison, Glenn
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ABSTRACTIn 2019, an air emissions field sampling study was conducted by the Colorado Department of Public Health and Environment’s Air Pollution Control Division (APCD) at four commercial cannabis cultivation facilities. Measurements of ambient biogenic volatile organic compounds (VOC) concentrations were collected from various growing stages of cannabis (vegetative and flowering) and during post-harvest activities (drying and trimming). These data were then used to determine room-specific biogenic VOC emission rates for three of the facilities from the vegetative stage of the life cycle through post-harvest activities. This study shows that the magnitude of biogenic VOC emissions within a cannabis cultivation facility varies widely with the highest emission rates of up to 7.18E–1 kg/hr found during mechanical trimming and up to 2.33E–1 kg/hr in the drying rooms. These were up to an order of magnitude higher than emission rates found in the cultivation rooms. For example, Facility A vegetative room had an emissions rate of 1.46E–2 kg/hr. Normalized by the amount of biomass present, the drying rooms had the highest VOC emissions rates, with a maximum rate of 1.6E–3 kg/hr/kg biomass. The flowering room rates were found to be up to 3.25E–4 kg/hr/kg biomass and drying rooms up to 1.16E–3 kg/hr/kg biomass. When normalized by plant count, emission rates in the flower rooms ranged from 8.11E–6 to 3.62E–4 kg/hr/plant. The dominant monoterpenes from sampling were β-myrcene, terpinolene, and D-limonene. These data suggest that the variability in emission rates across cannabis production will create a challenge in establishing a generalized emission factor for all facilities. Across the industry, cannabis cultivation conditions and strategies can vary widely impacting the amount and type of VOC emissions. Minimizing uncertainties for VOC emission from cannabis facilities requires site-specific information on air exchange rates, plant counts, cannabis strains, biomass, and if hand or mechanical processing is used.Implications: This study found that the magnitude of biogenic VOC emissions within a cannabis cultivation varies widely throughout rooms found in the facility, with the highest emissions found during post-harvest activities (i.e. trimming) and the lowest rates in the vegetative room. These data suggest that the large emission sources of VOCs are found post-harvest and emission inventories based solely on cultivation emissions will underestimate total biogenic VOC emissions from indoor cannabis cultivation facilities. The dominant measured terpenes throughout all facilities from cultivation to post harvest were: β-myrcene, terpinolene, and D-limonene.
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- 2023
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7. Why Indoor Chemistry Matters: A National Academies Consensus Report.
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Habre, Rima, Dorman, David C., Abbatt, Jonathan, Bahnfleth, William P., Carter, Ellison, Farmer, Delphine, Gawne-Mittelstaedt, Gillian, Goldstein, Allen H., Grassian, Vicki H., Morrison, Glenn, Peccia, Jordan, Poppendieck, Dustin, Prather, Kimberly A., Shiraiwa, Manabu, Stapleton, Heather M., Williams, Meredith, and Harries, Megan E.
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- 2022
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8. Quantifying the impact of relative humidity on human exposure to gas phase squalene ozonolysis productsElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2ea00112h
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Lakey, Pascale S. J., Zuend, Andreas, Morrison, Glenn C., Berkemeier, Thomas, Wilson, Jake, Arata, Caleb, Goldstein, Allen H., Wilson, Kevin R., Wang, Nijing, Williams, Jonathan, Abbatt, Jonathan P. D., and Shiraiwa, Manabu
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Squalene is a major skin oil lipid which can react with ozone forming a range of products including carbonyls, carboxylic acids, hydroxy ketones, secondary ozonides and hydroperoxides. Previous experimental studies have shown that the yield of these products depends on relative humidity. A new mechanism is developed which treats the reaction of ozone with carbon–carbon double bonds and the subsequent reactions of the Criegee intermediates forming a range of products in both condensed and gas phases. The mechanism is included in kinetic models for a variety of ozonolysis reaction systems including pure squalene particles, squalene and skin oil films, clothing, and skin covered by clothing. The models reproduce experimental measurements reasonably well using relatively consistent parameters, providing insights into the important reactions and processes controlling the concentrations of different species. In general, gas-phase secondary carbonyl product concentrations increase significantly as a function of relative humidity due to their formation from the reaction of Criegee intermediates with water, while carboxylic acids and hydroxy ketone concentrations decrease. For example, human exposure to gas-phase 6-methyl-5-hepten-2-one can increase by approximately a factor of two as the relative humidity increases from 10% to 95%. The model can also reproduce the decay of carboxylic acids in skin oil due to their reaction with Criegee intermediates. Discrepancies between some of the measurements and model outputs indicate that in addition to impacting chemistry, relative humidity may affect other processes such as partitioning to surfaces and condensed-phase diffusion.
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- 2023
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9. Assessment of aldehyde contributions to PTR-MS m/z69.07 in indoor air measurements
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Ernle, Lisa, Wang, Nijing, Bekö, Gabriel, Morrison, Glenn, Wargocki, Pawel, Weschler, Charles J., and Williams, Jonathan
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Proton transfer reaction-mass spectrometry (PTR-MS) has been widely used for monitoring outdoor and indoor volatile organic compounds. For outdoor air, mass-to-charge-ratio m/z69.07 is usually assigned to isoprene. Isoprene is also a major component of human breath and therefore abundant in occupied indoor environments. Mass 69.07 as an indicator of indoor isoprene can suffer interference resulting from fragmentation of aldehydes [V. Ruzsanyi, et al., Multi-capillary-column proton-transfer-reaction time-of-flight mass spectrometry, J. Chromatogr. A, 2013, 1316, 112–118], which are also abundant indoors, especially when ozone is elevated [C. J. Weschler, Roles of the human occupant in indoor chemistry, Indoor Air, 2016, 26, 6–24]. As part of the Indoor Chemical Human Emission and Reactivity (ICHEAR) campaign we examined this effect in human-occupied chamber studies, in the absence and presence of ozone. We find that such interferences do occur when ozone reacts with both human skin oil and cotton-based clothing. In the presence of humans and 35 ppb ozone, PTR-mass 69.07 was three times higher than the isoprene mixing ratio measured independently by GC-MS. To investigate this effect, we measured the fragmentation patterns of aldehydes and examined the contribution of different aldehydes to m/z69.07 in the ICHEAR experiments. Nonanal, and its contribution to m/z69.07, could be quantified reliably for clothing and human dermal emissions under the experimental conditions. In contrast, decanal is difficult to quantify, since compounds other than decanal fragment to m/z157.16, its MH+peak, which also makes it difficult to estimate decanal's contribution to m/z69.07.
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- 2023
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10. Pastoral Theology and the Little Goodness: Rejoice and Be Glad with the Voice of Song
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Morrison, Glenn
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precis:The essay aims to develop the nature of pastoral theology through orienting the Christian life of faith through a Jewish sense of otherness as the little goodness. In particular, together Pope Francis’s Apostolic Exhortation, Gaudete et exsultate (Rejoice and Be Glad), and Emmanuel Levinas’s ethical metaphysics will be a significant inspiration. Perseverance through adversity in the hope of joy and gladness is both a Jewish and a Christian biblical theme giving light to the mysteries and practice of faith. There is much to reflect about holiness and the mystery of God that Christians can learn from Jewish experience, thought, and writings. In pursuit of care for others, God’s presence in the Other reveals an invincible little goodness evidencing a paschal and maternal character. Here, in the unity of prayer and responsibility, the voice and song of a Good Shepherd comes to mind, with stories of faith that impart hope for a little goodness to stir and bless life with joy and gladness from the heart.
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- 2022
11. Understanding Ozone Transport and Deposition within Indoor Surface Boundary Layers.
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Pei, Gen, Xuan, Yuan, Morrison, Glenn, and Rim, Donghyun
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- 2022
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12. Understanding Ozone Transport and Deposition within Indoor Surface Boundary Layers
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Pei, Gen, Xuan, Yuan, Morrison, Glenn, and Rim, Donghyun
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Ozone-initiated oxidation reactions on indoor surfaces meaningfully alter the chemical composition of indoor air and human exposure to air toxins. Ozone mass transport within the indoor surface boundary layer plays a key role in ozone-surface reaction kinetics. However, limited information is available on detailed ozone transport dynamics near realistic, irregular indoor surfaces. This paper presents a research framework to study the underlying mechanisms of ozone reactions with realistic indoor surfaces based on microscope scanning of surface material and detailed Computational Fluid Dynamics (CFD) simulation. The study results show that indoor surface topography can meaningfully affect ozone mass transport within a surface boundary layer, thereby modulating near-surface ozone concentration gradient and surface uptake. The results also reveal that the effective indoor surface area available for ozone reaction varies with indoor air speed and turbulent air mixing within the boundary layer. The detailed dynamic behaviors of ozone reactions with realistic indoor surfaces provide insights into the implications of pollutant–surface interactions on indoor chemistry and air quality.
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- 2022
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13. Effect of Ozone, Clothing, Temperature, and Humidity on the Total OH Reactivity Emitted from Humans.
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Zannoni, Nora, Li, Mengze, Wang, Nijing, Ernle, Lisa, Bekö, Gabriel, Wargocki, Pawel, Langer, Sarka, Weschler, Charles J., Morrison, Glenn, and Williams, Jonathan
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- 2021
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14. Effect of Ozone, Clothing, Temperature, and Humidity on the Total OH Reactivity Emitted from Humans
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Zannoni, Nora, Li, Mengze, Wang, Nijing, Ernle, Lisa, Bekö, Gabriel, Wargocki, Pawel, Langer, Sarka, Weschler, Charles J., Morrison, Glenn, and Williams, Jonathan
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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.
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- 2021
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15. Evaluating Indoor Air Chemical Diversity, Indoor-to-Outdoor Emissions, and Surface Reservoirs Using High-Resolution Mass Spectrometry
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Sheu, Roger, Fortenberry, Claire F., Walker, Michael J., Eftekhari, Azin, Stönner, Christof, Bakker, Alexa, Peccia, Jordan, Williams, Jonathan, Morrison, Glenn C., Williams, Brent J., and Gentner, Drew R.
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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.
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- 2021
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16. Yields and Variability of Ozone Reaction Products from Human Skin.
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Morrison, Glenn C., Eftekhari, Azin, Majluf, Francesca, and Krechmer, Jordan E.
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- 2021
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17. Assessing Human Exposure to SVOCs in Materials, Products, and Articles: A Modular Mechanistic Framework.
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Eichler, Clara M. A., Hubal, Elaine A. Cohen, Xu, Ying, Cao, Jianping, Bi, Chenyang, Weschler, Charles J., Salthammer, Tunga, Morrison, Glenn C., Koivisto, Antti Joonas, Zhang, Yinping, Mandin, Corinne, Wei, Wenjuan, Blondeau, Patrice, Poppendieck, Dustin, Liu, Xiaoyu, Delmaar, Christiaan J. E., Fantke, Peter, Jolliet, Olivier, Shin, Hyeong-Moo, and Diamond, Miriam L.
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- 2021
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18. Transdermal uptake of benzophenone-3 from clothing: comparison of human participant results to model predictions
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Eftekhari, Azin, Hill, Jonathan T., and Morrison, Glenn C.
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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.
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- 2021
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19. Assessing Human Exposure to SVOCs in Materials, Products, and Articles: A Modular Mechanistic Framework
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Eichler, Clara M. A., Hubal, Elaine A. Cohen, Xu, Ying, Cao, Jianping, Bi, Chenyang, Weschler, Charles J., Salthammer, Tunga, Morrison, Glenn C., Koivisto, Antti Joonas, Zhang, Yinping, Mandin, Corinne, Wei, Wenjuan, Blondeau, Patrice, Poppendieck, Dustin, Liu, Xiaoyu, Delmaar, Christiaan J. E., Fantke, Peter, Jolliet, Olivier, Shin, Hyeong-Moo, Diamond, Miriam L., Shiraiwa, Manabu, Zuend, Andreas, Hopke, Philip K., von Goetz, Natalie, Kulmala, Markku, and Little, John C.
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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.
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- 2021
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20. Yields and Variability of Ozone Reaction Products from Human Skin
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Morrison, Glenn C., Eftekhari, Azin, Majluf, Francesca, and Krechmer, Jordan E.
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The skin of 20 human participants was exposed to ∼110 ppb O3and 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.
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- 2021
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21. Predicting Transdermal Uptake of Phthalates and a Paraben from Cosmetic Cream Using the Measured Fugacity
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Eftekhari, Azin, Frederiksen, Hanne, Andersson, Anna-Maria, Weschler, Charles J., and Morrison, Glenn
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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.
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- 2020
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22. Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial
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Nabbout, Rima, Mistry, Arun, Zuberi, Sameer, Villeneuve, Nathalie, Gil-Nagel, Antonio, Sanchez-Carpintero, Rocio, Stephani, Ulrich, Laux, Linda, Wirrell, Elaine, Knupp, Kelly, Chiron, Catherine, Farfel, Gail, Galer, Bradley S., Morrison, Glenn, Lock, Michael, Agarwal, Anupam, and Auvin, Stéphane
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IMPORTANCE: Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens. OBJECTIVE: To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens. INTERVENTIONS: Patients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients’ assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline. RESULTS: A total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P < .001) greater reduction in mean monthly convulsive seizure frequency than those receiving the placebo. With fenfluramine, 54% of patients demonstrated a clinically meaningful (≥50%) reduction in monthly convulsive seizure frequency vs 5% with placebo (P < .001). The median (range) longest seizure-free interval was 22 (3.0-105.0) days with fenfluramine and 13 (1.0-40.0) days with placebo (P = .004). The most common adverse events were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Cardiac monitoring demonstrated no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension. CONCLUSIONS AND RELEVANCE: Fenfluramine demonstrated significant improvements in monthly convulsive seizure frequency in patients with Dravet syndrome whose conditions were insufficiently controlled with stiripentol-inclusive antiepileptic drug regimens. Fenfluramine was generally well tolerated. Fenfluramine may represent a new treatment option for Dravet syndrome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02926898
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- 2020
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23. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial
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Lagae, Lieven, Sullivan, Joseph, Knupp, Kelly, Laux, Linda, Polster, Tilman, Nikanorova, Marina, Devinsky, Orrin, Cross, J Helen, Guerrini, Renzo, Talwar, Dinesh, Miller, Ian, Farfel, Gail, Galer, Bradley S, Gammaitoni, Arnold, Mistry, Arun, Morrison, Glenn, Lock, Michael, Agarwal, Anupam, Lai, Wyman W, and Ceulemans, Berten
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Dravet syndrome is a rare, treatment-resistant developmental epileptic encephalopathy characterised by multiple types of frequent, disabling seizures. Fenfluramine has been reported to have antiseizure activity in observational studies of photosensitive epilepsy and Dravet syndrome. The aim of the present study was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome.
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- 2019
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24. Clothing-Mediated Exposures to Chemicals and Particles.
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Licina, Dusan, Morrison, Glenn C., Bekö, Gabriel, Weschler, Charles J., and Nazaroff, William W.
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- 2019
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25. Dynamics of Residential Water-Soluble Organic Gases: Insights into Sources and Sinks.
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Duncan, Sara M., Tomaz, Sophie, Morrison, Glenn, Webb, Marc, Atkin, Joanna, Surratt, Jason D., and Turpin, Barbara J.
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- 2019
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26. Squalene Depletion in Skin Following Human Exposure to Ozone under Controlled Chamber Conditions
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Langer, Sarka, Weschler, Charles J., Bekö, Gabriel, Morrison, Glenn, Sjöblom, Ann, Giovanoulis, Georgios, Wargocki, Pawel, Wang, Nijing, Zannoni, Nora, Yang, Shen, and Williams, Jonathan
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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.
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- 2024
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27. Clothing-Mediated Exposures to Chemicals and Particles
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Licina, Dusan, Morrison, Glenn C., Bekö, Gabriel, Weschler, Charles J., and Nazaroff, William W.
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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.
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- 2019
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28. Dynamics of Residential Water-Soluble Organic Gases: Insights into Sources and Sinks
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Duncan, Sara M., Tomaz, Sophie, Morrison, Glenn, Webb, Marc, Atkin, Joanna, Surratt, Jason D., and Turpin, Barbara J.
- Abstract
Water-soluble organic gas (WSOG) concentrations are elevated in homes. However, WSOG sources, sinks, and concentration dynamics are poorly understood. We observed substantial variations in 23 residential indoor WSOG concentrations measured in real time in a North Carolina, U.S., home over several days with a high-resolution time-of-flight chemical ionization mass spectrometer equipped with iodide reagent ion chemistry (I-HR-ToF-CIMS). Concentrations of acetic, formic, and lactic acids ranged from 30−130, 15−53, and 2.5−360 μg m–3, respectively. Concentrations of several WSOGs, including acetic and formic acids, decreased considerably (∼30–50%) when the air conditioner (AC) cycled on, suggesting that the AC system is an important sink for indoor WSOGs. In contrast to nonpolar organic gases, indoor WSOG loss rate coefficients were substantial for compounds with high oxygen-to-carbon (O/C) ratios (e.g., 1.6–2.2 h–1for compounds with O/C > 0.75 when the AC system was off). Loss rate coefficients in the AC system were more uncertain but were estimated to be 1.5 h–1. Elevated concentrations of lactic acid coincided with increased human occupancy and cooking. We report several WSOGs emitted from cooking and cleaning as well as transported in from outdoors. In addition to indoor air chemistry, these results have implications to exposure and human health.
- Published
- 2019
- Full Text
- View/download PDF
29. "I Love People So Terribly": Approaching Affectivity with Levinas, Hillesum, and Christian Theology
- Author
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Morrison, Glenn
- Abstract
PRECIS:Through engaging the writings of two Jewish thinkers, Emmanuel Levinas and Etty Hillesum, this essay sets out to develop a Christian theological approach to affectivity. It begins by introducing Levinas and Hillesum to develop a context for dialogue between Jewish thought and Christian theology. Initiating a phenomenological foundation, the essay suggests that affectivity resonates through the human condition of loneliness and otherness. Building on this perspective and aided by Levinas's thought and the practical expression of Hillesum's affectivity of talking to God, the focus turns to introduce and develop the notions of spontaneity, melancholy, and vigilance. Hence, it suggests the central elements of a theological approach to human affectivity in Christian living. Accordingly, by seeking to be poor in spirit and offering friendship to the poor, affectivity becomes a way for the Christian community to live in unity, signifying the resilience to embrace the turbulence of conversion, the shock of encountering the other's suffering, and the joy of loving others "so terribly."
- Published
- 2019
30. Dermal Uptake of Benzophenone-3 from Clothing.
- Author
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Morrison, Glenn C., Bekö, Gabriel, Weschler, Charles J., Schripp, Tobias, Salthammer, Tunga, Hill, Jonathan, Andersson, Anna-Maria, Toftum, Jørn, Clausen, Geo, and Frederiksen, Hanne
- Published
- 2017
- Full Text
- View/download PDF
31. Outcomes Assessment in Clinical Trials of Alzheimer's Disease and its Precursors: Readying for Short-term and Long-term Clinical Trial Needs.
- Author
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POSNER, HOLLY, CURIEL, ROSIE, EDGAR, CHRIS, HENDRIX, SUZANNE, LIU, ENCHI, LOEWENSTEIN, DAVID A., MORRISON, GLENN, SHINOBU, LESLIE, WESNES, KEITH, and HARVEY, PHILIP D.
- Subjects
ALZHEIMER'S disease ,CLINICAL trials ,MEETINGS ,HEALTH outcome assessment ,GROUP process - Abstract
An evolving paradigm shift in the diagnostic conceptualization of Alzheimer's disease is reflected in its recently updated diagnostic criteria from the National Institute on Aging-Alzheimer's Association and the International Working Group. Additionally, it is reflected in the increased focus in this field on conducting prevention trials in addition to improving cognition and function in people with dementia. These developments are making key contributions towards defining new regulatory thinking around Alzheimer's disease treatment earlier in the disease continuum. As a result, the field as a whole is now concentrated on exploring the next-generation of cognitive and functional outcome measures that will support clinical trials focused on treating the slow slide into cognitive and functional impairment. With this backdrop, the International Society for CNS Clinical Trials and Methodology convened semi-annual working group meetings which began in spring of 2012 to address methodological issues in this area. This report presents the most critical issues around primary outcome assessments in Alzheimer's disease clinical trials, and summarizes the presentations, discussions, and recommendations of those meetings, within the context of the evolving landscape of Alzheimer's disease clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2017
32. From the Borderlands Editors.
- Author
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Grimmer, Raelke, Morrison, Glenn, and Sefton-Rowston, Adelle
- Subjects
STORYTELLERS ,BORDERLANDS ,LABOR incentives - Published
- 2019
33. Linking a dermal permeation and an inhalation model to a simple pharmacokinetic model to study airborne exposure to di(n-butyl) phthalate
- Author
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Lorber, Matthew, Weschler, Charles J, Morrison, Glenn, Bekö, Gabriel, Gong, Mengyan, Koch, Holger M, Salthammer, Tunga, Schripp, Tobias, Toftum, Jørn, and Clausen, Geo
- Abstract
Six males clad only in shorts were exposed to high levels of airborne di(n-butyl) phthalate (DnBP) and diethyl phthalate (DEP) in chamber experiments conducted in 2014. In two 6 h sessions, the subjects were exposed only dermally while breathing clean air from a hood, and both dermally and via inhalation when exposed without a hood. Full urine samples were taken before, during, and for 48 h after leaving the chamber and measured for key DnBP and DEP metabolites. The data clearly demonstrated high levels of DnBP and DEP metabolite excretions while in the chamber and during the first 24 h once leaving the chamber under both conditions. The data for DnBP were used in a modeling exercise linking dose models for inhalation and transdermal permeation with a simple pharmacokinetic model that predicted timing and mass of metabolite excretions. These models were developed and calibrated independent of these experiments. Tests included modeling of the “hood-on” (transdermal penetration only), “hood-off” (both inhalation and transdermal) scenarios, and a derived “inhalation-only” scenario. Results showed that the linked model tended to duplicate the pattern of excretion with regard to timing of peaks, decline of concentrations over time, and the ratio of DnBP metabolites. However, the transdermal model tended to overpredict penetration of DnBP such that predictions of metabolite excretions were between 1.1 and 4.5 times higher than the cumulative excretion of DnBP metabolites over the 54 h of the simulation. A similar overprediction was not seen for the “inhalation-only” simulations. Possible explanations and model refinements for these overpredictions are discussed. In a demonstration of the linked model designed to characterize general population exposures to typical airborne indoor concentrations of DnBP in the United States, it was estimated that up to one-quarter of total exposures could be due to inhalation and dermal uptake.
- Published
- 2017
- Full Text
- View/download PDF
34. Passive removal materials for indoor ozone control.
- Author
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Darling, Erin, Morrison, Glenn C., and Corsi, Richard L.
- Subjects
OZONE & the environment ,BUILDING materials & the environment ,GAS phase reactions ,HEALTH impact assessment ,INORGANIC compounds ,INDOOR air quality - Abstract
The indoor environment can contribute significantly to population exposure to ozone. This paper reviews the state of knowledge on building materials and coatings that are intended to passively remove ozone from indoor air. These passive removal materials, or PRMs, should have high ozone removal potential without significant and harmful reaction product formation. Ozone interactions with indoor environments, including surface and gas-phase reactions, known byproducts of these reactions, and health impacts of ozone and its byproducts are described. Research that has targeted PRMs for ozone removal is then summarized, and the materials in question are assessed in terms of their ability to reduce indoor ozone concentrations; ozone deposition velocities, reaction probabilities, as well as byproduct molar yields are presented and compared. This evaluation of the literature suggests that the most promising PRMs for ozone control are inorganic materials, including clay-based bricks and plasters, calcareous stone, and ceiling tile made of mineral fibers or volcanic perlite. Simple model equations are presented and used to highlight the potential for PRMs as a means for reducing indoor ozone concentrations. The removal effectiveness for ozone and reaction-derived formaldehyde is predicted for a commercially-available wall coating (clay paint) applied in a residential building. Removal effectiveness is also discussed in the context of required surface area and application costs for clay paint. A list of conclusions, limitations and research needs based on the existing knowledge base is also presented. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
35. Assessing cognition and function in Alzheimer's disease clinical trials: Do we have the right tools?
- Author
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Snyder, Peter J., Kahle-Wrobleski, Kristin, Brannan, Stephen, Miller, David S., Schindler, Rachel J., DeSanti, Susan, Ryan, J. Michael, Morrison, Glenn, Grundman, Michael, Chandler, Julie, Caselli, Richard J., Isaac, Maria, Bain, Lisa, and Carrillo, Maria C.
- Abstract
Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging—Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28–29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
36. Reducing Transdermal Uptake of Semivolatile Plasticizers from Indoor Environments: A Clothing Intervention
- Author
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Hammel, Stephanie C., Eftekhari, Azin, Eichler, Clara M. A., Liu, Chih-Wei, Nylander-French, Leena A., Engel, Lawrence S., Lu, Kun, and Morrison, Glenn C.
- Abstract
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.
- Published
- 2023
- Full Text
- View/download PDF
37. Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs
- Author
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Morrison, Glenn C, Weschler, Charles J, Bekö, Gabriel, Koch, Holger M, Salthammer, Tunga, Schripp, Tobias, Toftum, Jørn, and Clausen, Geo
- Abstract
To assess the influence of clothing on dermal uptake of semi-volatile organic compounds (SVOCs), we measured uptake of selected airborne phthalates for an individual wearing clean clothes or air-exposed clothes and compared these results with dermal uptake for bare-skinned individuals under otherwise identical experimental conditions. Using a breathing hood to isolate dermal from inhalation uptake, we measured urinary metabolites of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) from an individual exposed to known concentrations of these compounds for 6?h in an experimental chamber. The individual wore either clean (fresh) cotton clothes or cotton clothes that had been exposed to the same chamber air concentrations for 9 days. For a 6-h exposure, the net amounts of DEP and DnBP absorbed when wearing fresh clothes were, respectively, 0.017 and 0.007?µg/kg/(µg/m3); for exposed clothes the results were 0.178 and 0.261?µg/kg/(µg/m3), respectively (values normalized by air concentration and body mass). When compared against the average results for bare-skinned participants, clean clothes were protective, whereas exposed clothes increased dermal uptake for DEP and DnBP by factors of 3.3 and 6.5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.
- Published
- 2016
- Full Text
- View/download PDF
38. Fibrous Dysplasia: Management of the Optic Canal
- Author
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Satterwhite, Thomas S., Morrison, Glenn, Ragheb, John, Bhatia, Sanjib, Perlyn, Chad, and Wolfe, S. Anthony
- Published
- 2015
- Full Text
- View/download PDF
39. Surgical treatment of refractory status epilepticus in children.
- Author
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BHATIA, SANJIV, AHMAD, FAIZ, MILLER, IAN, RAGHEB, JOHN, MORRISON, GLENN, JAYAKAR, PRASANNA, and DUCHOWNY, MICHAEL
- Published
- 2013
- Full Text
- View/download PDF
40. Impacts of a clay plaster on indoor air quality assessed using chemical and sensory measurements.
- Author
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Darling, Erin K., Cros, Clement J., Wargocki, Pawel, Kolarik, Jakub, Morrison, Glenn C., and Corsi, Richard L.
- Subjects
ENVIRONMENTAL impact analysis ,CLAY ,PLASTER ,INDOOR air quality ,CHEMICAL detectors ,INDOOR air pollution ,CHEMICAL reactions - Abstract
Abstract: Passive removal materials (PRMs) are building materials or furnishings that effectively control indoor pollution without substantial formation of chemical byproducts and without an energy penalty. Recent studies have suggested that clay might be an effective PRM for ozone. To assess clay wall plaster as a PRM for improving air quality by controlling ozone, perceived air quality (PAQ) was determined in the presence of eight combinations of an emitting and reactive pollutant source (new carpet), clay plaster applied to gypsum wallboard, and chamber air with and without ozone. A panel of 24 human subjects assessed air quality in twin 30m
3 chambers using a continuous acceptability scale. Air samples were collected immediately prior to panel assessment to quantify concentrations of C5 –C10 saturated n-aldehydes and two aromatic aldehydes that are commonly produced by reaction of ozone with carpet. Perceived air quality was most acceptable and concentrations of aldehydes were lowest when only clay plaster or both clay plaster and carpet were present in the chambers without ozone. The least acceptable PAQ and the highest concentrations of aldehydes were observed when carpet and ozone were present together; addition of clay plaster for this condition improved PAQ and considerably decreased aldehyde concentrations. [Copyright &y& Elsevier]- Published
- 2012
- Full Text
- View/download PDF
41. Investigation of volatile organic compounds in office buildings in Bangkok, Thailand: Concentrations, sources, and occupant symptoms.
- Author
-
Ongwandee, Maneerat, Moonrinta, Rathakheth, Panyametheekul, Sirima, Tangbanluekal, Chalongkwan, and Morrison, Glenn
- Subjects
VOLATILE organic compounds ,OFFICE building air conditioning ,VENTILATION ,INDOOR air quality ,BENZENE ,PRINCIPAL components analysis - Abstract
Abstract: To conserve energy, office buildings with air-conditioning systems in Thailand are operated with a tight thermal envelope. This leads to low fresh-air ventilation rates and is thought to be partly responsible for the sick building syndrome symptoms reported by occupants. The objectives of this study are to measure concentrations and to determine sources of 13 volatile organic compounds (VOCs) in office buildings with air-conditioning systems in the business area of Bangkok. Indoor and outdoor air samples from 17 buildings were collected on Tenax-TA
™ sorbent tubes and analyzed for individual VOCs by thermal desorption-gas chromatography/mass spectrometry (TD–GC/MS). Building ventilation was measured with a constant injection technique using hexafluorobenzene as a tracer gas. The results show that the VOC concentrations varied significantly among the studied buildings. The two most dominant VOCs were toluene and limonene with average concentrations of 110 and 60.5 μg m−3 , respectively. A Wilcoxon sum rank test indicated that the indoor concentrations of aromatic compounds and limonene were statistically higher than outdoor concentrations at the 0.05 level, while the indoor concentrations of chlorinated compounds were not. Indoor emission factors of toluene and limonene were found to be highest with the average values of 80.9 and 18.9 μg m−2 h−1 , respectively. Principal component analysis was applied to the emission factors of 13 VOCs, producing three components based on source similarities. Furthermore, a questionnaire survey investigation and field measurements of building air exchange pointed to indoor air complaints related to inadequate ventilation. [Copyright &y& Elsevier]- Published
- 2011
- Full Text
- View/download PDF
42. Surface Reaction Rate and Probability of Ozone and Alpha-Terpineol on Glass, Polyvinyl Chloride, and Latex Paint Surfaces.
- Author
-
Shi Shu and Morrison, Glenn C.
- Published
- 2011
- Full Text
- View/download PDF
43. Passive reduction of human exposure to indoor ozone.
- Author
-
Kunkel, Donna A., Gall, Elliott T., Siegel, Jeffrey A., Novoselac, Atila, Morrison, Glenn C., and Corsi, Richard L.
- Subjects
CHEMICAL reduction ,OZONE ,CONSTRUCTION materials ,DRYWALL ,ACTIVATED carbon ,HUMIDITY ,ENERGY consumption - Abstract
Abstract: Reactive building materials offer an opportunity to provide indoor air cleaning with minimal energy use. Laboratory and test house experiments provide evidence that indoor ozone concentrations can be diminished by activated carbon (AC) and unpainted gypsum wallboard (GWB) panels. These two materials are highly reactive with ozone and produce few byproducts. When measured in a 14.2m
3 stainless-steel chamber, the mean deposition velocities to the materials were 5.3m h-1 for AC and 2.4mh−1 for GWB for a variety of airflow and relative humidity conditions. The ozone decay rates for both the materials were also measured in an unoccupied 34.5m3 bedroom under various mixing conditions. In this case, ozone removal increased relative to background by 27–100% with a 4.4m2 panel of a reactive material placed on one wall of the bedroom. The ozone decay rate for the bedroom increased over background by approximately 2–3h−1 for GWB and 2–7h−1 for AC. Application of a mass balance model for a typical home demonstrates that effectiveness for ozone removal depends weakly on the air exchange rate and strongly on the panel material, panel area, and mixing conditions. An ozone removal effectiveness of over 80% is possible with sufficient panel area and positioning that provides elevated air speeds near the panels. [Copyright &y& Elsevier]- Published
- 2010
- Full Text
- View/download PDF
44. INVOKE‐2: A phase 2 randomized, double‐blind, placebo‐controlled study to evaluate the efficacy and safety of AL002 in participants with early Alzheimer's disease.
- Author
-
Paul, Robert, Jackson, Sam, Ward, Michael, Joshi, Aashka, Castro, Abraham, Yeh, Felix L, Liao, Yijie, and Morrison, Glenn
- Abstract
Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in the brain predominantly by microglia. Mutations in TREM2 cause an increased risk of developing Alzheimer's Disease (AD). E.g., the R47H coding variant confers similar risk for AD as does one copy of APOE4. AL002 is a humanized monoclonal IgG1 antibody (mAb) that activates the TREM2 signaling pathway to increase the ability of microglia to clear pathology and protect neurons. AL002 is believed to be the first anti‐TREM2 mAb in clinical development for the treatment of AD. AL002 was generally well tolerated in a Phase 1 study (INVOKE) and has demonstrated proof of target engagement and proof of mechanism. These results have supported progressing AL002 to the INVOKE‐2 Phase 2 study of AL002 in patients with early AD. Method: INVOKE‐2 is a randomized, double‐blind, dose‐ranging, placebo‐controlled study to evaluate the efficacy and safety of AL002 in participants with early AD (NCT04592874). This is a global study that will enroll approximately 265 participants in North America, Australia, New Zealand, Europe, and South America. Participants will be randomized to receive one of 3 doses of AL002 or placebo, administered via IV infusion every 4 weeks, for up to 96 weeks. The objectives of this Phase 2 study are to assess the efficacy and safety of AL002. Result: All participants must have a diagnosis of early AD with evidence of cerebral amyloidosis and a clinical severity consistent with Stage 2 to early Stage 4 (2018 Research Framework), including a CDR‐GS of 0.5 or 1, MMSE from 22 to 30, and RBANS DMI of 85 or lower. Efficacy will be assessed with clinical outcome assessments (including CDR‐SB and ADAS‐Cog13), and fluid and imaging biomarkers. Safety will be assessed through monitoring of AEs, suicidality assessments, changes in laboratory and vital signs, ECG and MRI. PK in serum and CSF will be assessed. Conclusion: INVOKE‐2 is designed to investigate the efficacy and safety of AL002, representing a novel, first‐in‐class neuro‐immunological approach for treating AD. Enrollment is ongoing. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Influence of Ammonia and Carbon Dioxide on the Sorption of a Basic Organic Pollutant to Carpet and Latex-Painted Gypsum Board.
- Author
-
ONGWANDEE, MANEERAT and MORRISON, GLENN C.
- Published
- 2008
- Full Text
- View/download PDF
46. Interfacial Chemistry in INDOOR ENVIRONMENTS.
- Author
-
Morrison, Glenn
- Published
- 2008
- Full Text
- View/download PDF
47. Ozone-Initiated Secondary Emission Rates of Aldehydes from Indoor Surfaces in Four Homes.
- Author
-
Hong Wang and Morrison, Glenn C.
- Published
- 2006
- Full Text
- View/download PDF
48. Ozone Interactions with Carpet: Secondary Emissions of Aldehydes.
- Author
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Morrison, Glenn c. and Nazaroff, William W.
- Published
- 2002
- Full Text
- View/download PDF
49. The Rate of Ozone Uptake on Carpets: Experimental Studies.
- Author
-
Morrison, Glenn C. and Nazaroff, William W.
- Published
- 2000
- Full Text
- View/download PDF
50. A Single Dose Mass Balance Study of the Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Humans Using Accelerator Mass Spectrometry
- Author
-
Graham, Richard A., Lum, Bert L., Morrison, Glenn, Chang, Ilsung, Jorga, Karin, Dean, Brian, Shin, Young G., Yue, Qin, Mulder, Teresa, Malhi, Vikram, Xie, Minli, Low, Jennifer A., and Hop, Cornelis E. C. A.
- Abstract
Vismodegib (GDC-0449), a small-molecule Hedgehog pathway inhibitor, was well tolerated in patients with solid tumors and showed promising efficacy in advanced basal cell carcinoma in a Phase I trial. The purpose of the study presented here was to determine routes of elimination and the extent of vismodegib metabolism, including assessment and identification of metabolites in plasma, urine, and feces. Six healthy female subjects of nonchildbearing potential were enrolled; each received a single 30-ml oral suspension containing 150 mg of vismodegib with 6.5 µg of [14C]vismodegib to yield a radioactivity dose of approximately 37 kBq (1000 nCi). Plasma, urine, and feces samples were collected over 56 days to permit sample collection for up to 5 elimination half-lives. Nonradioactive vismodegib was measured in plasma using liquid chromatographic-tandem mass spectrometry, and total radioactivity in plasma, urine, and feces was measured using accelerator mass spectrometry. Vismodegib was slowly eliminated by a combination of metabolism and excretion of parent drug, most of which was recovered in feces. The estimated excretion of the administered dose was 86.6% on average, with 82.2 and 4.43% recovered in feces and urine, respectively. Vismodegib was predominant in plasma, with concentrations representing >98% of the total circulating drug-related components. Metabolic pathways of vismodegib in humans included oxidation, glucuronidation, and uncommon pyridine ring cleavage. We conclude that vismodegib and any associated metabolic products are mainly eliminated through feces after oral administration in healthy volunteers.
- Published
- 2011
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