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1.
Environ Sci Technol ; 58(15): 6693-6703, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38577981

RESUMO

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.


Assuntos
Poluição do Ar em Ambientes Fechados , Ozônio , Humanos , Adolescente , Esqualeno/análise , Ozônio/análise , Poluição do Ar em Ambientes Fechados/análise , Pele/química , Oxidantes
2.
Environ Sci Technol ; 57(49): 20678-20688, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38019971

RESUMO

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.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Humanos , Plastificantes , Poluentes Ambientais/análise , Projetos Piloto , Ácidos Ftálicos/metabolismo , Exposição Ambiental/análise , Vestuário
3.
Environ Sci Technol ; 57(40): 15173-15183, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37757488

RESUMO

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-2 and 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.


Assuntos
Poluentes Atmosféricos , Fluorocarbonos , Monitoramento Ambiental , North Carolina , Poluentes Atmosféricos/análise , Fluorocarbonos/análise
4.
Environ Sci Technol ; 56(12): 7820-7829, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35670501

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Humanos , Cinética , Oxirredução , Ozônio/química
5.
Indoor Air ; 32(5): e13022, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35622714

RESUMO

From the thermodynamic perspective, the term temperature is clearly defined for ideal physical systems: A unique temperature can be assigned to each black body via its radiation spectrum, and the temperature of an ideal gas is given by the velocity distribution of the molecules. While the indoor environment is not an ideal system, fundamental physical and chemical processes, such as diffusion, partitioning equilibria, and chemical reactions, are predictably temperature-dependent. For example, the logarithm of reaction rate and equilibria constants are proportional to the reciprocal of the absolute temperature. It is therefore possible to have non-linear, very steep changes in chemical phenomena over a relatively small temperature range. On the contrary, transport processes are more influenced by spatial temperature, momentum, and pressure gradients as well as by the density, porosity, and composition of indoor materials. Consequently, emergent phenomena, such as emission rates or dynamic air concentrations, can be the result of complex temperature-dependent relationships that require a more empirical approach. Indoor environmental conditions are further influenced by the thermal comfort needs of occupants. Not only do occupants have to create thermal conditions that serve to maintain their core body temperature, which is usually accomplished by wearing appropriate clothing, but also the surroundings must be adapted so that they feel comfortable. This includes the interaction of the living space with the ambient environment, which can vary greatly by region and season. Design of houses, apartments, commercial buildings, and schools is generally utility and comfort driven, requiring an appropriate energy balance, sometimes considering ventilation but rarely including the impact of temperature on indoor contaminant levels. In our article, we start with a review of fundamental thermodynamic variables and discuss their influence on typical indoor processes. Then, we describe the heat balance of people in their thermal environment. An extensive literature study is devoted to the thermal conditions in buildings, the temperature-dependent release of indoor pollutants from materials and their distribution in the various interior compartments as well as aspects of indoor chemistry. Finally, we assess the need to consider temperature holistically with regard to the changes to be expected as a result of global emergencies such as climate change.


Assuntos
Poluição do Ar em Ambientes Fechados , Mudança Climática , Temperatura Alta , Humanos , Temperatura , Ventilação
6.
Indoor Air ; 32(1): e12944, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34661313

RESUMO

This research investigates sorption of PCBs to fabrics in a contaminated indoor environment and the effect of laundering on PCB removal from the fabrics. Eight articles of clothing were exposed to the air in a PCB-contaminated building. The background air concentration was 670 ng/m3 PCBtotal with PCB-52 being the main congener. Air and fabric samples were collected for analysis before and periodically throughout the experiment. After 25 weeks, the remaining fabrics were washed and cut into three pieces each. One part was dried in the contaminated building, second in a PCB-free building and third in a mechanical drier. The PCB mass concentration increased during the first 6-10 weeks for all investigated fabrics, after which some fabrics approached equilibrium for more volatile congeners. Mass-normalized cloth-air partition coefficients were quantified for 9 congeners; for PCB-52, these ranged from 106.1 to 107.0 which were consistent with previously reported values. Partition coefficients of PCBs were observed to increase with their respective octanol-air partition coefficients. Washing and drying clothes resulted in the removal between 22% and 84% of PCBs. There was no difference in removal percentage after air-drying in clean or contaminated air. Drying in a mechanical drier removed significantly more PCBs than air-drying.


Assuntos
Poluição do Ar em Ambientes Fechados , Lavanderia , Bifenilos Policlorados , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Bifenilos Policlorados/análise , Têxteis
7.
Indoor Air ; 32(1): e12932, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34554621

RESUMO

Air exchange is among the most important building parameters influencing indoor air quality and energy use. Over 18-month period we surveyed over 3800 individuals to generate a contemporary, nationwide measure of window- and door-opening behavior. We also identified influences of demographics, climate, and region. For the entire survey, including all seasons and geographic regions, 43.9% of respondents said that at least one window was open the day prior to taking the survey. Greater window-opening frequency was associated with having a lower income, living in attached homes or apartments, renting, lack of air conditioning, or being Asian or Hispanic. People living in the west and north open windows considerably more frequently and longer than those in the southeastern US. Window-opening frequency and duration increases with outdoor temperature until a maximum occurs at 18-21°C. At temperatures greater than this, window frequency decreases. The pattern roughly holds, by region, with the peak occurring at a lower temperature in the NW (12°C), and a higher temperature in the SW and SE. The frequency of door opening is roughly half that of window opening with similar, but not identical, demographic, regional, and climate associations.


Assuntos
Poluição do Ar em Ambientes Fechados , Temperatura , Ventilação , Ar Condicionado , Poluição do Ar em Ambientes Fechados/análise , Habitação , Humanos , Estações do Ano , Estados Unidos
8.
Atmos Environ (1994) ; 2682022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34899026

RESUMO

Per- and polyfluoroalkyl substances (PFASs), with their water- and heat-resistant properties, have been widely used in industrial and consumer products, including floor waxes. Adverse health effects are associated with PFAS exposures (e.g., increased risk of cancer and immunotoxicity); however, exposures resulting from the use of PFAS-containing products are poorly understood. This study examines PFAS emissions during professional floor stripping/waxing and their potential for occupational exposures. We measured PFASs in dust and airborne particulate matter (PM2.0, aerodynamic diameter ≤ 2.0 µm) before, during, and after floor stripping/waxing activities in three rooms in a university building. PM2.0 samples were analyzed for 34 targeted PFASs by ultra-high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometer (UHPLC/ESI-MS/MS). In total, ten PFASs were detected in PM2.0 collected during floor waxing. Five were consistently higher during floor stripping/waxing compared to before (two with 95% confidence interval): perfluoro-2-methoxyacetic acid, perfluorobutanoic acid, perfluorohexanoic acid, perfluoroheptanoic acid, and perfluorooctane sulfonic acid. For these five, estimated exposures during floor stripping were 80.6, 320.5, 83.8, 29.6, and 157.7 pg m-3 per hour of floor stripping, respectively, one order of magnitude greater than typical residential indoor and two orders of magnitude greater than ambient outdoor concentrations. Estimated emission rates were 3.0, 9.6, 3.4, 1.5, and 6.5 ng h-1m-2, respectively (34.6% uncertainty). Inhalation occupational exposures were in the range of 9.42-23.2 pg per kg body weight per hour of floor stripping across the five PFASs.

9.
Environ Sci Technol ; 55(1): 179-187, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33337871

RESUMO

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.


Assuntos
Poluição do Ar em Ambientes Fechados , Ozônio , Poluição do Ar em Ambientes Fechados/análise , Humanos , Lipídeos , Ozônio/análise , Pele/química , Esqualeno
10.
Environ Sci Technol ; 55(20): 13614-13624, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34591444

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Ozônio , Compostos Orgânicos Voláteis , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Vestuário , Monitoramento Ambiental , Humanos , Umidade , Ozônio/análise , Temperatura , Compostos Orgânicos Voláteis/análise
11.
Environ Sci Technol ; 55(15): 10255-10267, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34270218

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , Compostos Orgânicos Voláteis/análise
12.
Environ Sci Technol ; 55(1): 25-43, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33319994

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Humanos , Compostos Orgânicos/análise , Compostos Orgânicos Voláteis/análise
13.
Indoor Air ; 31(4): 1199-1216, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33484190

RESUMO

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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Espécies Reativas de Oxigênio/análise
14.
Lancet ; 394(10216): 2243-2254, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31862249

RESUMO

BACKGROUND: 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. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, we enrolled children and young adults with Dravet syndrome. After a 6-week observation period to establish baseline monthly convulsive seizure frequency (MCSF; convulsive seizures were defined as hemiclonic, tonic, clonic, tonic-atonic, generalised tonic-clonic, and focal with clearly observable motor signs), patients were randomly assigned through an interactive web response system in a 1:1:1 ratio to placebo, fenfluramine 0·2 mg/kg per day, or fenfluramine 0·7 mg/kg per day, added to existing antiepileptic agents for 14 weeks. The primary outcome was the change in mean monthly frequency of convulsive seizures during the treatment period compared with baseline in the 0·7 mg/kg per day group versus placebo; 0·2 mg/kg per day versus placebo was assessed as a key secondary outcome. Analysis was by modified intention to treat. Safety analyses included all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov with two identical protocols NCT02682927 and NCT02826863. FINDINGS: Between Jan 15, 2016, and Aug 14, 2017, we assessed 173 patients, of whom 119 patients (mean age 9·0 years, 64 [54%] male) were randomly assigned to receive either fenfluramine 0·2 mg/kg per day (39), fenfluramine 0·7 mg/kg per day (40) or placebo (40). During treatment, the median reduction in seizure frequency was 74·9% in the fenfluramine 0·7 mg/kg group (from median 20·7 seizures per 28 days to 4·7 seizures per 28 days), 42·3% in the fenfluramine 0·2 mg/kg group (from median 17·5 seizures per 28 days to 12·6 per 28 days), and 19·2% in the placebo group (from median 27·3 per 28 days to 22·0 per 28 days). The study met its primary efficacy endpoint, with fenfluramine 0·7 mg/kg per day showing a 62·3% greater reduction in mean MCSF compared with placebo (95% CI 47·7-72·8, p<0·0001); fenfluramine 0·2 mg/kg per day showed a 32·4% reduction in mean MCSF compared with placebo (95% CI 6·2-52·3, p=0·0209). The most common adverse events (occurring in at least 10% of patients and more frequently in the fenfluramine groups) were decreased appetite, diarrhoea, fatigue, lethargy, somnolence, and decreased weight. Echocardiographic examinations revealed valve function within the normal physiological range in all patients during the trial and no signs of pulmonary arterial hypertension. INTERPRETATION: In Dravet syndrome, fenfluramine provided significantly greater reduction in convulsive seizure frequency compared with placebo and was generally well tolerated, with no observed valvular heart disease or pulmonary arterial hypertension. Fenfluramine could be an important new treatment option for patients with Dravet syndrome. FUNDING: Zogenix.


Assuntos
Epilepsias Mioclônicas/tratamento farmacológico , Fenfluramina/uso terapêutico , Convulsões/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Administração Oral , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Fenfluramina/administração & dosagem , Fenfluramina/efeitos adversos , Humanos , Masculino , Estudos Observacionais como Assunto , Placebos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Resultado do Tratamento
15.
Epilepsia ; 61(11): 2396-2404, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33078386

RESUMO

OBJECTIVE: Fenfluramine has been shown to provide clinically meaningful and statistically significant reductions in convulsive seizure frequency in children and adolescents (aged 2-18 years) with Dravet syndrome in two randomized, placebo-controlled clinical trials. The objective of this analysis was to assess longer-term safety and efficacy of fenfluramine in patients who completed one of the double-blind studies and entered an open-label extension (OLE) study. METHODS: Patients enrolling in the OLE study initiated fenfluramine at 0.2 mg/kg/d regardless of their treatment assignment in the double-blind study. After 4 weeks, the fenfluramine dose could be titrated based on efficacy and tolerability to maximum of 0.7 mg/kg/d (absolute maximum 27 mg/d) or maximum of 0.4 mg/kg/d (absolute maximum 17 mg/d) in patients receiving concomitant stiripentol. The number and type of seizures were recorded daily in an electronic diary, and safety, including echocardiography, was assessed at Months 1, 2, and 3, and at 3-month intervals thereafter. RESULTS: A total of 232 patients were enrolled as of March 13, 2018. During this analysis period, patients were treated for a median 256 days (range = 46-634 days). Over the entire OLE analysis period, the median decrease in convulsive seizure frequency compared to baseline in the double-blind studies was -66.8% (range = -100% to 234.9%; P < .001). The median reduction in seizure frequency was similar in patients <6 (-75.7%) and ≥6 years old (-64.7%). The most commonly reported adverse events included pyrexia (21.6%), nasopharyngitis (19.4%), and decreased appetite (-15.9%). No valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) was observed. SIGNIFICANCE: Study results demonstrate that fenfluramine provides clinically meaningful (≥50%) seizure frequency reduction over an extended period in patients with Dravet syndrome. No patient developed VHD or PAH, and fenfluramine was generally well tolerated.


Assuntos
Epilepsias Mioclônicas/diagnóstico , Epilepsias Mioclônicas/tratamento farmacológico , Fenfluramina/administração & dosagem , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Epilepsias Mioclônicas/epidemiologia , Feminino , Fenfluramina/efeitos adversos , Febre/induzido quimicamente , Humanos , Estudos Longitudinais , Masculino , Convulsões/epidemiologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
16.
Environ Sci Technol ; 54(12): 7471-7484, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32432857

RESUMO

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.


Assuntos
Cosméticos , Ácidos Ftálicos , Dibutilftalato , Exposição Ambiental/análise , Humanos , Compostos Orgânicos , Parabenos/análise
17.
Indoor Air ; 30(6): 1229-1240, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32478932

RESUMO

Ozone has adverse effects on human health. Skin oil on the human surface acts as an ozone sink indoors, producing oxidation products that can cause skin and respiratory irritations. Concentrations of ozone and oxidation products near human surfaces, including the breathing zone, can be modulated by indoor ventilation modes and human surface conditions. The objective of this study is to examine concentrations and spatial heterogeneity of ozone and ozonolysis products under representative ranges of indoor ventilation, clothing, and breathing conditions. Using computational fluid dynamics (CFD) simulation in conjunction with a chemical kinetic model, details of ozone reactions with the human surface and subsequent chemical reactions are examined. The results show that primary ozonolysis products are concentrated near the soiled clothing, while the secondary products are relatively well distributed throughout the room. Increasing indoor air mixing enhances the ozone deposition to the human surface, thereby resulting in higher emission rates of oxidation products in the room. Soiled clothing consumes more ozone than clean clothing and accordingly produces ~ 65% more primary products and ~15% more secondary products. The results also reveal that unsaturated hydrocarbons from the human breath, such as isoprene, contribute to only ~0.5% of ozone removal compared to ozone deposition to the human surface.


Assuntos
Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Ozônio/uso terapêutico , Poluentes Atmosféricos , Humanos , Cinética , Espectrometria de Massas , Modelos Químicos , Oxirredução , Pele , Ventilação
18.
Indoor Air ; 30(6): 1213-1228, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32424858

RESUMO

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.


Assuntos
Poluição do Ar em Ambientes Fechados , Adolescente , Aerossóis , Idoso , Amônia , Butadienos , Monitoramento Ambiental , Expiração , Feminino , Hemiterpenos , Humanos , Masculino , Odorantes , Ozônio , Terpenos , Compostos Orgânicos Voláteis , Adulto Jovem
19.
Environ Sci Technol ; 53(10): 5559-5575, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31034216

RESUMO

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.


Assuntos
Vestuário , Exposição Ambiental , Poluentes Ambientais , Humanos
20.
Environ Sci Technol ; 53(4): 1812-1821, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30633495

RESUMO

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-1 for 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.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Monitoramento Ambiental , Gases , Humanos , North Carolina , Água
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