Physiologically based clearance/extraction models for compounds metabolized in the nose: an example with methyl methacrylate.

Abstract:

:Airstream clearance (with units of volume/time) is the volumetric flow from which chemical would have to be completely removed to account for the net loss in the nose. Extraction is the proportion of airflow from which the chemical is completely removed. Over the past several years we have developed physiologically based clearance-extraction (PBCE) models for the nose to assess the physiological, biochemical, and anatomical factors that control airstream clearance. A generic clearance equation was derived for single airway/tissue compartments that had a separate air region and either one, two, or three underlying tissue regions. For all of these structures, airstream clearance (Cl(sys)) has a common form-Equation (1)-related to tissue clearance (Cltot), gas-phase diffusional clearance (PAgas), airflow (Q), and the mucus air partition coefficient (Hmuc:a). Clsys = CltotHm:aPAgasQ/CltotHm:a(Q + PAgas) + PAgasQ. A physiologically based clearance-extraction (PBCE) model for the whole nose combined three separate nasal tissue regions, each with a four-compartment tissue stack (air, mucus, epithelial tissue, and submucosal region). A steady-state solution of the PBCE model successfully described literature results on the steady-state extraction of methyl methacrylate (MMA) and several other metabolized vapors. Model-derived tissue dosimetry estimates, that is, the amount of MMA metabolized in the target epithelial compartment of the olfactory region, for rats and humans provide dosimetric adjustment factors (DAFs) required in calculating a human reference concentration (RfC) from rodent studies. Depending on the assignment of esterase activities to sustentacular and submucosal regions, the DAFs from the PBCE model varied between 1.6 and 8.0, compared to the default value of 0.145. From the experience with MMA, a minimal data set could be defined for building the PBCE model. It consists of mucus:air and blood:air partition coefficients, metabolic constants for enzymatic hydrolysis in nasal tissues from rat and human tissues, immunohistochemistry of the distribution of these activities in rats and human olfactory tissues, and extraction studies in anesthetized rats to assess the total nasal metabolism of the test compound.

journal_name

Inhal Toxicol

journal_title

Inhalation toxicology

authors

Andersen ME,Sarangapani R

doi

10.1080/08958370151126284

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

397-414

issue

5

eissn

0895-8378

issn

1091-7691

journal_volume

13

pub_type

杂志文章
  • Animal models of chronic bronchitis and their relevance to studies of particle-induced disease.

    abstract::Chronic bronchitis is a significant cause of morbidity and mortality. Chronic irritation of the conducting airways by inhaled substances, most importantly cigarette smoke, air pollution, and occupational exposures, is thought to be a key factor in the pathogenesis of chronic bronchitis. Microbial infections have been ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/089583700750019549

    authors: Nikula KJ,Green FH

    更新日期:2000-01-01 00:00:00

  • The temporal profile of cytokines in the bronchoalveolar lavage fluid in mice exposed to the industrial gas phosgene.

    abstract::Diagnosis of an exposure to airborne toxicants can be problematic. Phosgene is used widely in industry for the production of many synthetic products, such as polyfoam rubber, plastics, and dyes. Although nearly 100% of the gas is consumed during processing, there is the potential problem of accidental or even intentio...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370390197254

    authors: Sciuto AM,Clapp DL,Hess ZA,Moran TS

    更新日期:2003-06-01 00:00:00

  • Calibration study on subchronic inhalation toxicity of man-made vitreous fibers in rats.

    abstract::This 3-mo inhalation study investigated the biological effects of a special-purpose glass microfiber (E-glass microfiber), the stone wool fiber MMVF21, and a new high-temperature application fiber (calcium-magnesium-silicate fiber, CMS) in Wistar rats. Rats were exposed 6 h/day, 5 days/wk for 3 mo to fiber aerosol con...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370390229843

    authors: Bellmann B,Muhle H,Creutzenberg O,Ernst H,Müller M,Bernstein DM,Riego Sintes JM

    更新日期:2003-10-01 00:00:00

  • Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs.

    abstract::Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate t...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2013.872212

    authors: Hulet SW,Sommerville DR,Miller DB,Scotto JA,Muse WT,Burnett DC

    更新日期:2014-02-01 00:00:00

  • Negative effect of long-term inhalation of toner on formation of 8-hydroxydeoxyguanosine in DNA in the lungs of rats in vivo.

    abstract::We assessed the effects of long-term inhalation of toner on the pathological changes and formation of 8-hydroxydeoxyguanosine (8-OH-Gua) in DNA in a rat model. Female Wistar rats (10 wk old) were divided evenly into a high concentration exposure group (H: 15.2 mg/m(3)), a low concentration exposure group (L: 5.5 mg/m(...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370500224771

    authors: Morimoto Y,Kim H,Oyabu T,Hirohashi M,Nagatomo H,Ogami A,Yamato H,Obata Y,Kasai H,Higashi T,Tanaka I

    更新日期:2005-12-01 00:00:00

  • Determination of the relative contribution of the non-dissolved fraction of ZnO NP on membrane permeability and cytotoxicity.

    abstract::Background: While the role of lysosomal membrane permeabilization (LMP) in NP-induced inflammatory responses has been recognized, the underlying mechanism of LMP is still unclear. The assumption has been that zinc oxide (ZnO)-induced LMP is due to Zn2+; however, little is known about the role of ZnO nanoparticles (NP)...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958378.2020.1743394

    authors: Ziglari T,Anderson DS,Holian A

    更新日期:2020-02-01 00:00:00

  • Health effects after firing small arms comparing leaded and unleaded ammunition.

    abstract::A number of Norwegian soldiers have reported health problems after live-fire training using the HK416 rifle. The objective of this study was to characterize gaseous and particulate emissions from three different types of ammunition, and record the health effects after exposure to emissions from live-firing. Fifty-five...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2014.970783

    authors: Voie Ø,Borander AK,Sikkeland LI,Grahnstedt S,Johnsen A,Danielsen TE,Longva K,Kongerud J

    更新日期:2014-12-01 00:00:00

  • Lung deposition of droplet aerosols in monkeys.

    abstract::Nonhuman primates are often the animal models of choice to study the infectivity and therapy of inhaled infectious agents. Most animal models for inhaled infectious diseases use aerosol/droplets generated by an atomization technique such as a Collison nebulizer that produces particles in the size range of 1 to 3 micro...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370802105413

    authors: Cheng YS,Irshad H,Kuehl P,Holmes TD,Sherwood R,Hobbs CH

    更新日期:2008-09-01 00:00:00

  • Direct contact with particulate matter increases oxidative stress in different brain structures.

    abstract:INTRODUCTION:Several experimental and epidemiological studies have demonstrated the neurological adverse effects caused by exposure to air pollution, specifically in relation to pollutant particulate matter (PM). The objective of this study was to investigate the direct effect of PM in increased concentrations in diffe...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2015.1060278

    authors: Fagundes LS,Fleck Ada S,Zanchi AC,Saldiva PH,Rhoden CR

    更新日期:2015-01-01 00:00:00

  • Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymers (HDI-IC and HDI-BT): results of subacute and subchronic repeated inhalation exposure studies.

    abstract::This article addresses results of two 13-wk inhalation toxicity studies in Wistar rats with aerosolized 1,6-hexamethylene diisocyanate (HDI) homopolymers using either the isocyanurate (HDI-IC) type or biuret (HDI-BT) type. Groups of 10 rats/sex/level were exposed nose-only to breathing zone concentrations of 0.5, 3.3,...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370118600

    authors: Pauluhn J,Mohr U

    更新日期:2001-06-01 00:00:00

  • The use of biodiesel in a school transportation system: the case of Medford Township, New Jersey.

    abstract::A combination of high fuel prices, bus maintenance costs, and the health and safety of school children, along with a consideration of federal and state regulations, prompted Medford Township school district in southern New Jersey to explore the use of alternative fuels, specifically biodiesel. The school district owns...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370701533467

    authors: Biluck J Jr

    更新日期:2007-09-01 00:00:00

  • Ambient air pollution alters heart rate regulation in aged mice.

    abstract:CONTEXT:Heart rate alterations associated with exposure to particulate matter (PM) and gaseous pollutants have been observed in epidemiological studies and animal experiments. Nevertheless, the time-lag of these associations is still unclear. OBJECTIVE:Determine the association at different time-lags between the compl...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958370903349365

    authors: Ramos-Bonilla JP,Breysse PN,Dominici F,Geyh A,Tankersley CG

    更新日期:2010-03-01 00:00:00

  • Immunotoxicity and hematotoxicity induced by tetrachloroethylene in egyptian dry cleaning workers.

    abstract::The immune and hematological systems can be a target for environmental contaminants with potential adverse effects, so the purpose of this study is to provide documentation on immunotoxicity and hematotoxicity of tetrachloroethylene, which is widely used in dry cleaning in Egypt. This study was carried out on 80 adult...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958370902934894

    authors: Emara AM,Abo El-Noor MM,Hassan NA,Wagih AA

    更新日期:2010-02-01 00:00:00

  • The effects of age and carbon black on airway resistance in mice.

    abstract:CONTEXT:Ambient particulate matter (PM) is associated with acute exacerbations of airflow obstruction. Additionally, elderly individuals are more susceptible to increased functional morbidity following acute PM exposure. OBJECTIVE:The purpose of this study is to determine the aging effects of PM exposure on the respon...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2012.731436

    authors: Bennett BA,Mitzner W,Tankersley CG

    更新日期:2012-12-01 00:00:00

  • Toxicity of lunar and martian dust simulants to alveolar macrophages isolated from human volunteers.

    abstract::NASA is planning to build a habitat on the Moon and use the Moon as a stepping stone to Mars. JSC-1, an Arizona volcanic ash that has mineral properties similar to those of lunar soil, is used to produce lunar environments for instrument and equipment testing. NASA is concerned about potential health risks to workers ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370701821219

    authors: Latch JN,Hamilton RF Jr,Holian A,James JT,Lam CW

    更新日期:2008-01-01 00:00:00

  • Incorporation of in vitro metabolism data and physiologically based pharmacokinetic modeling in a risk assessment for chloroprene.

    abstract::Objective: To develop a physiologically based pharmacokinetic (PBPK) model for chloroprene in the mouse, rat and human, relying only on in vitro data to estimate tissue metabolism rates and partitioning, and to apply the model to calculate an inhalation unit risk (IUR) for chloroprene.Materials and methods: Female B6C...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958378.2020.1715513

    authors: Clewell HJ 3rd,Campbell JL,Van Landingham C,Franzen A,Yoon M,Dodd DE,Andersen ME,Gentry PR

    更新日期:2019-01-01 00:00:00

  • Age influence on hypersensitivity pneumonitis induced in mice by exposure to Pantoea agglomerans.

    abstract::Hypersensitivity pneumonitis (HP) represents the immunologically mediated lung disease induced by repeated inhalations of a wide variety of certain finely dispersed organic antigens. In susceptible subjects, these inhalations provoke a hypersensitivity reaction characterized by intense inflammation of the terminal bro...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2013.827284

    authors: Lemieszek MK,Chilosi M,Golec M,Skórska C,Dinnyes A,Mashayekhi K,Vierlinger K,Huaux F,Wielscher M,Hofner M,Yakoub Y,Pastena C,Daniele I,Cholewa G,Sitkowska J,Lisowska W,Zwoliński J,Milanowski J,Mackiewicz B,Góra-Flor

    更新日期:2013-09-01 00:00:00

  • Elementary school absenteeism and air pollution.

    abstract::This study assessed the association between ambient air pollution and daily elementary school absenteeism in Washoe County, NV, between 1996 and 1998. All 57 elementary schools in Washoe County in northern Nevada were included in the data set. There was a total of 27,793 student enrollments during this study period. T...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370050164626

    authors: Chen L,Jennison BL,Yang W,Omaye ST

    更新日期:2000-11-01 00:00:00

  • Blood pressure of rats lowered by sulfur dioxide and its derivatives.

    abstract::This study was designed to investigate effects of sulfur dioxide (SO(2)) and its derivatives (bisulfite and sulfite) on the rat blood pressure. The blood pressures of male Wistar rats exposed to SO(2) and its derivatives at various doses were measured. Findings were that: (1) with acute-one time exposure to SO(2) for ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370390215785

    authors: Meng Z,Geng H,Bai J,Yan G

    更新日期:2003-08-01 00:00:00

  • 3-week inhalation exposure to cigarette smoke and/or lipopolysaccharide in AKR/J mice.

    abstract::AKR/J mice were exposed to cigarette smoke (CS) and/or lipopolysaccharide (LPS) via inhalation for 3 wk and pulmonary responses were evaluated. The objective was to explore the feasibility of coexposing LPS with cigarette smoke under a subacute exposure, as a surrogate for viral or bacterial insults, that would mimic ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370600985784

    authors: Lee KM,Renne RA,Harbo SJ,Clark ML,Johnson RE,Gideon KM

    更新日期:2007-01-01 00:00:00

  • Exposure to ozone induces a systemic inflammatory response: possible source of the neurological alterations induced by this gas.

    abstract::The World Health Organization identified urban outdoor air pollution as the eighth highest mortality risk factor in high-income countries. Exposure to ambient pollutants such as ozone (O3) increases the number of hospital admissions. O3 is a highly reactive gas that reacts with cells lining the airways, producing the ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2014.922648

    authors: González-Guevara E,Martínez-Lazcano JC,Custodio V,Hernández-Cerón M,Rubio C,Paz C

    更新日期:2014-07-01 00:00:00

  • Surfactant protein A, exposure to endotoxin, and asthma in garbage collectors and in wastewater workers.

    abstract::Endotoxin causes an inflammation at the bronchial and alveolar level. The inflammation-induced increase in permeability of the bronchoalveolar epithelial barrier is supposed to cause a leakage of pneumoproteins. Therefore, their concentrations are expected to increase in the bloodstream. This study aimed at examining ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370601144456

    authors: Widmeier S,Bernard A,Tschopp A,Jeggli S,Dumont X,Hilfiker S,Oppliger A,Hotz P

    更新日期:2007-04-01 00:00:00

  • Effect of waterpipe tobacco smoking on airway inflammation in murine model of asthma.

    abstract:OBJECTIVE:There has been an increase in the popularity of waterpipe tobacco smoking (WTS) worldwide, especially in the younger population, including asthma patients. In this study, we investigated the effects of waterpipe smoking on airway inflammation, cytokine levels and oxidative stress markers in an antigen-driven ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958378.2017.1280105

    authors: Al-Sawalha NA,Migdadi AM,Alzoubi KH,Khabour OF,Qinna NA

    更新日期:2017-02-01 00:00:00

  • Role of Mitogen-Activated Protein Kinases, Early Response Protooncogenes, and Activator Protein-1 in Cell Signaling by Asbestos.

    abstract::Cell signaling by pathogenic minerals may initiate the transactivation of genes that are critical to carcinogenesis and fibroproliferative diseases of the lung and pleura. We have shown previously that stimulation of the mitogen-activated protein kinase (MAPK) cascade by asbestos fibers leads to phosphorylation events...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958378.2000.11463240

    authors: Mossman B,Hubbard A,Shukla A,Timblin CR

    更新日期:2000-01-01 00:00:00

  • Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

    abstract::Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the br...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370600602116

    authors: Graham JR,Wright BS,Rezk PE,Gordon RK,Sciuto AM,Nambiar MP

    更新日期:2006-06-01 00:00:00

  • Time course for expression of VEGF and its receptor and regulator levels of contraction and relaxation in increased vascular permeability of lung induced by phosgene.

    abstract::Acute lung injury (ALI) induced by phosgene increases risk of serious edema and mortality. Increased permeability of the microvascular endothelium is implicated in the progression of ALI, but the processing interaction and time course activity of the vascular regulators in exudation are still not understood. The main ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370802015091

    authors: Zhang XD,Hai CX,Cai FL,Liang X,Liu R,Chen HL,Qin XJ,Feng AJ

    更新日期:2008-07-01 00:00:00

  • Radiological progression and lung function decrements among silica-exposed ceramic workers: a longitudinal study.

    abstract::Objectives: This follow-up study set out to evaluate the natural course and radiographic progression of silicosis among ceramic workers and describe the risk factors related with disease progression. Materials and methods: We retrospectively analyzed the data of ceramic workers with silicosis who were referred to our ...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958378.2019.1613459

    authors: Karataş M,Gündüzöz M,Büyükşekerci M,Özakıncı OG,Nadir Öziş T

    更新日期:2019-02-01 00:00:00

  • Relative contributions of PM2.5 chemical constituents to acute arterial vasoconstriction in humans.

    abstract::Studies have shown associations between acute ambient particulate matter (PM) levels and increases in morbidity and mortality from cardiovascular diseases. We have previously reported in 24 healthy adults that exposure to concentrated ambient particles plus ozone (CAP + O(3)) caused a mean decrease of 0.09 mm in brach...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370490439489

    authors: Urch B,Brook JR,Wasserstein D,Brook RD,Rajagopalan S,Corey P,Silverman F

    更新日期:2004-06-01 00:00:00

  • NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination.

    abstract::Multi-walled carbon nanotubes (MWCNT) have been reported to cause lung pathologies in multiple studies. However, the mechanism responsible for the bioactivity has not been determined. This study used nine different well-characterized MWCNT and examined the outcomes in vitro and in vivo. MWCNT, from a variety of source...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.3109/08958378.2012.745633

    authors: Hamilton RF Jr,Buford M,Xiang C,Wu N,Holian A

    更新日期:2012-12-01 00:00:00

  • Influence of exhaled air on inhalation exposure delivered through a directed-flow nose-only exposure system.

    abstract::In order to conserve material that is available in limited quantities, "directed-flow" nose-only exposure systems have at times been run at flow rates close to the minute ventilation of the animal. Such low-flow-rate conditions can contribute to a decrease of test substance concentration in inhaled air; near the anima...

    journal_title:Inhalation toxicology

    pub_type: 杂志文章

    doi:10.1080/08958370500282555

    authors: Moss OR,James RA,Asgharian B

    更新日期:2006-01-01 00:00:00