Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation Exposure”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources
PubMed2001

An example to illustrate the potential use of probabilistic modelling to estimate operator exposure to pesticides.

To illustrate the potential for probabilistic simulation modelling of operator exposure a probabilistic model was constructed using the draft EUROPOEM II database. The model also incorporated actual pesticide use data. Although the EUROPOEM II database is not complete, and the resulting simulation has to be regarded as only provisional, the data were sufficient to illustrate some of the principles involved. The model was constructed using non-parametric empirical input distributions. Associations were observed in the input exposure data and were reflected in the model. The exposure and usage data were all variable and showed highly negatively skewed distributions and the technique avoided concerns about having to define single representative values for point estimates. Increasing the number of iterations improved the stability of the output, but as expected, resulted in higher exposures being predicted due to a combination of rare events. Analysis of the inputs for individual iterations giving high results indicated that, in this example, these were due to unrepresentatively high input values for inhalation exposure. Simulations that excluded these values were more stable and showed lower exposures, illustrating the need to ensure the validity of the input distributions.

Databases, Factual↗
PubMed2009

Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium.

Previous studies have shown that physiological responses to cigarette smoke can be detected via bronchial airway epithelium gene expression profiling and that heterogeneity in this gene expression response to smoking is associated with lung cancer. In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-specific smoking-related gene expression profiles were validated using independent microarray datasets. Differential expression of select genes was also confirmed by RT-PCR. That smoking induces largely similar gene expression changes in both nasal and bronchial epithelium suggests that the consequences of cigarette smoke exposure can be measured in tissues throughout the respiratory tract. Our findings suggest that nasal epithelial gene expression may serve as a relatively noninvasive surrogate to measure physiological responses to cigarette smoke and/or other inhaled exposures in large-scale epidemiological studies.

Adult↗
PubMed1998

Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.

This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.

Acrylates↗
PubMed1998

Ethylene oxide dosimetry in the mouse.

Ethylene oxide (EO) is a direct-acting mutagen and animal carcinogen used as an industrial intermediate and sterilant with a high potential for human exposure. Understanding the exposure-dose relationship for EO in rodents is critical for developing human EO exposure-dose models. The study reported here examined the dosimetry of EO in male B6C3F1 mice by direct determination of blood EO concentrations. Steady-state blood EO concentrations were measured during a single 4-h nose-only inhalation exposure (0, 50, 100, 200, 300, or 400 ppm EO). In addition, glutathione (GSH) concentrations were measured in liver, lung, kidney, and testis to assess the role of the GSH depletion in the saturable metabolism previously observed in mice (Brown et al., Toxicol. Appl. Pharmacol. 136, 8-19, 1996). Blood EO concentrations were found to increase linearly with exposure concentration up to 200 ppm. Markedly sublinear blood dosimetry was observed at exposure concentrations exceeding 200 ppm. An EO exposure concentration-dependent reduction in tissue GSH levels was observed, with both liver and lung GSH levels significantly depressed at EO exposure concentrations of 100 ppm or greater. Our results also indicate that depletion of GSH is likely responsible for nonlinear dosimetry of EO in mice and that GSH depletion corresponds with reports of dose-rate effects in mice exposed to EO.

Administration, Inhalation↗
PubMed2000

Conservatism in pesticide exposure assessment.

Three important factors are commonly encountered in exposure assessment that when combined could overestimate the exposure to pesticides by as much as two orders of magnitude. The three factors discussed are dermal absorption from laboratory animal studies, daily dose extrapolated from partial day monitoring, and nonbolus dose from dermal or inhalation exposure. Conservatism built into the process by each of these three factors is substantiated with available empirical data. The dose overestimation from these factors varies discriminatively by exposure scenarios and peculiarities of a given chemical. It is for this reason that a generic overestimation factor cannot be ascribed. Following the empirical illustrations, the authors conclude that the most effective approach for dealing with the problem is to generate the most appropriate data possible. This means producing human rather than laboratory animal dermal absorption data, conducting full-day exposure monitoring studies, and whenever feasible generating dermal rather than oral toxicology data (or alternatively data on both oral and dermal pharmacokinetics) in those cases where the dermal route predominates.

Animals↗
PubMed1976

A statistical assessment of the quantitative uptake of vinyl chloride monomer from aqueous solution.

The presence of vinyl chloride monomer (VCM) in foodstuffs and its demonstrated carcinogenic potential when administered by the oral route has raised questions concerning the quantitative estimation of the safety of the use of food packaging fabricated from rigid polyvinyl chloride. A statistical model, which was tested by curve-fitting data obtained from an oral uptake study, has been demonstrated to be of predictive value. Ninety-five percent condifence limits were also calculated, and the data from this study were compared with those from a previous gas phase exposure study. It was concluded that if the total daily liquid intake contained 20 ppm of VCM then the area generated under the blood level-time curve, for rats, would be equivalent to an inhalation exposure of about 2 ppm for 24 hr.

Administration, Oral↗
PubMed1998

[Dichlorvos insect strips indoors: pollution and risk assessment].

Exposure to Danger and Assessing the Hazards: Application of the highly potent pest control agent dichlorvos (DDVP) involves the hazard of effects on the central nervous system and a risk of human cancer. Consumers use dichlorvos in pest strips to protect their rooms from insects. This undifferentiated pest control can lead to chronic exposure. Over several weeks we found an indoor air concentration of dichlorvos between 60 and 1300 micrograms/m3 in 34 m3-experimental-room (chamber). Textiles and foodstuffs in this room were also contaminated. Beside the inhalative intake the oral and dermal intake can also lead to an additional loading of the residents. The ADI-resp. DTA-value of 4 micrograms/kg body-weight and day is exceeded about 10-15 times on the average by inhalative exposure only.

Adolescent↗
PubMed1981

The mammalian toxicity of fluomine dust.

Fluomine is a cobalt chelate compound which complexes molecular oxygen and releases it on heating. This property has led to its use a a regenerable oxygen source in high-altitude aircraft. Investigations into the acute effects of exposure to fluomine by various routes were undertaken as first steps in the toxicological characterization of the material. Single-dose rat and mouse oral administration led to LD50 values of 123 mg/kg for male CF1 mice and 187 mg/kg for male Sprague-Dawley rats. The LC50 values for single four-hour inhalation periods varied from 112 mg/m3 for male rats to 416 mg/m3 for male mice. Fluomine proved to be highly irritating when instilled in the eyes of rabbits and to the lungs of rats on inhalation. Exposure of rabbit skin to the compound demonstrated moderate irritancy particularly in areas of abrasion. Positive reactions to intradermal challenge were demonstrated after both intradermal and inhalation sensitization of guinea pigs.

Animals↗
PubMed2000

Induction of adaptation to inhaled lipopolysaccharide in young and old rats and mice.

Lipopolysaccharide (LPS) is a component of the gram-negative bacterial cell wall that is known to activate inflammatory cells and enhance the production of inflammatory mediators in the lung. As it is a ubiquitous compound, inhalation exposure is highly likely in the human environment. Adaptation is a phenomenon by which a previous exposure results in improved survival or reduced injury as compared to a single exposure alone. We hypothesized that the basic proinflammatory effects of LPS in the lung could result in the development of adaptation in animals. Based on evidence of age- and species-related differences in lung injury, we used an acute lung injury model with inhaled LPS to compare the development of adaptation in young and old Fisher 344 rats and C57Bl/6J mice. Animals were exposed to low-dose (predicted lung deposition approximately 20 ng in rats and approximately 5 ng in mice) LPS aerosols for 10 min on 3 consecutive days; on day 4, a high dose (rats approximately 200 ng; mice approximately 25 ng) was delivered. Another group of animals received only the high LPS dose on day 4, whereas controls were unexposed. Twenty-four hours after the last exposure, cellular and inflammatory parameters in bronchoalveolar lavage (BAL) were determined. An adaptive response was found in both rats and mice. Adapted animals showed significantly fewer BAL neutrophils compared to nonadapted ones; there was also a significantly lower release of oxidants from phorbol methyl ester-stimulated BAL cells from adapted compared to nonadapted animals, which, in turn, showed a greater response than controls. Furthermore, studies in old animals (21 mo of age) showed that adaptation also occurs in this age group. The adaptive response is clear in old mice; in rats, there is greater variability in the response, but an adaptive trend is apparent. Therefore, we have demonstrated that inhaled low-dose LPS can induce adaptation to subsequent higher doses, much as has been shown for other toxicants that induce oxidative lung injury.

Administration, Inhalation↗
PubMed1978

The comparative acute mammalian toxicity of 1-chloroacetophenone (CN) and 2-chlorobenzylidene malononitrile (CS).

The comparative acute toxicity of two peripheral sensory irritant materials, 1-chloroacetophenone (CN) and 2-chlorobenzylidene malononitrile (CS), has been investigated in several species of small mammal using solutions in polyethylene glycol 300 for intravenous, intraperitoneal and oral administration, and as pure aerosols for inhalation exposure. Additionally, the comparative potency for inducing primary contact dermatitis was studied. CN and CS were found to be about equitoxic by intravenous and intraperitoneal injection, but CS was significantly less toxic by the oral and inhalation routes and less likely to cause non-lethal tissue damage than CN.

Administration, Oral↗
PubMed2005

Determination of age and gender differences in biochemical processes affecting the disposition of 2-butoxyethanol and its metabolites in mice and rats to improve PBPK modeling.

2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BEs major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. [Lee, K.M., Dill, J.A., Chou, B.J., Roycroft, J.H., 1998. Physiologically based pharmacokinetic model for chronic inhalation of 2-butoxyethanol. Toxicol. Appl. Pharmacol. 153, 211-226] to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6 h inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (> or =18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

Administration, Inhalation↗
PubMed1996

Respiratory effects of organic solvent exposure.

Organic solvents are widely used in industrial processes and found in many common household products. Exposures to solvents are common in both idustrialized and industrializing countries. While organic solvents exposure is well known to produce central nervous system toxicity, hepatic, renal and dermatologic injury, the respiratory effects of solvent exposure are poorly documented. Several recent population-based epidemiologic studies have found an independent association of occupational solvent exposure with respiratory symptoms, impaired pulmonary function or respiratory disease, but interpretation of these studies is limited by self-reported exposure data. Animal studies have demonstrated adverse effects in both the conducting and the respiratory airways, although often at very high exposure levels. Human chamber studies have most consistently reported irritation of the eyes, nose and throat without evidence of airway hyper-responsiveness. Case series have observed obstructive and restrictive effects in patients with high level inhalational exposures to solvents, particularly formaldehyde, but occupational epidemiologic studies have not consistently demonstrated changes in pulmonary function. Finally, mortality studied have not found increased mortality rates from respiratory disease in occupations associated with solvent use. In general, solvents have been demonstrated to cause mucosal irritation of the eyes and upper airways, but studies of pulmonary impairment following exposure have been limited and inconsistent. Solvent-mediated respiratory toxicity is biologically plausible, but further research is needed to better characterize exposures and to elucidate the specific mechanisms associated with injury.

Animals↗
PubMed2002

IgE-mediated allergy to phytase -- a new animal feed additive.

BACKGROUND: Although fungal phytase is frequently used as an additive to animal feed few investigations of its allergenic property have been conducted. METHODS: Fifty-three subjects occupationally exposed to powdered phytase from Aspergillus niger were studied. Exposure data and symptoms were registered by the company physician. RESULTS: Thirty-eight subjects complained of work-related respiratory symptoms and 14 of them showed phytase-specific IgE antibodies; only one asymptomatic subject revealed such antibodies. IgE antibodies were significantly more frequently found in the high-exposure group (technical centre) when compared with the low-exposure group (laboratories, experimental animal husbandry). Phytase-specific IgG antibodies were present in 19 symptomatic (50%) and five (33%) asymptomatic subjects. CONCLUSIONS: Our results demonstrate that powdered fungal phytase is a highly sensitizing substance whose inhalation exposure should be avoided. Hypersensitivity symptoms could be prevented by means of extensive hygienic measures and ongoing medical surveillance.

6-Phytase↗
PubMed2003

Physiological modeling of inhalation kinetics of octamethylcyclotetrasiloxane in humans during rest and exercise.

In a recent pharmacokinetic study, six human volunteers were exposed by inhalation to 10 ppm (14)C-D(4) for 1 h during alternating periods of rest and exercise. Octamethylcyclotetrasiloxane (D(4)) concentrations were determined in exhaled breath and blood. Total metabolite concentrations were estimated in blood, while the amounts of individual metabolites were measured in urine. Here, we use these data to develop a physiologically based pharmacokinetic (PBPK) model for D(4) in humans. Consistent with PBPK modeling efforts for D(4) in the rat, a conventional inhalation PBPK model assuming flow-limited tissue uptake failed to adequately describe these data. A refined model with sequestered D(4) in blood, diffusion-limited tissue uptake, and an explicit pathway for D(4) metabolism to short-chain linear siloxanes successfully described all data. Hepatic extraction in these volunteers, calculated from model parameters, was 0.65 to 0.8, i.e., hepatic clearance was nearly flow-limited. The decreased retention of inhaled D(4) seen in humans during periods of exercise was explained by altered ventilation/perfusion characteristics during exercise and a rapid approach to steady-state conditions. The urinary time course excretion of metabolites was consistent with a metabolic scheme in which sequential hydrolysis of linear siloxanes followed oxidative demethylation and ring opening. The unusual properties of D(4) (high lipophilicity coupled with high hepatic and exhalation clearance) lead to rapid decreases in free D(4) in blood. The success of D(4) PBPK models with a similar physiological structure in both humans and rats increases confidence in the utility of the model for predicting human tissue concentrations of D(4) and metabolites during inhalation exposures.

Adjuvants, Immunologic↗
PubMed2003

A multicompartment model of carboxyhemoglobin and carboxymyoglobin responses to inhalation of carbon monoxide.

We have developed a model that predicts the distribution of carbon monoxide (CO) in the body resulting from acute inhalation exposures to CO. The model includes a lung compartment, arterial and venous blood compartments, and muscle and nonmuscle soft tissues with both vascular and nonvascular subcompartments. In the model, CO is allowed to diffuse between the vascular and nonvascular subcompartments of the tissues and to combine with myoglobin in the nonvascular subcompartment of muscle tissue. The oxyhemoglobin dissociation curve is represented by a modified Hill equation whose parameters are functions of the carboxyhemoglobin (HbCO) level. Values for skeletal muscle mass and cardiac output are calculated from prediction formulas based on age, weight, and height of individual subjects. We demonstrate that the model fits data from CO rebreathing studies when diffusion of CO into the muscle compartment is considered. The model also fits responses of HbCO to single or multiple exposures to CO lasting for a few minutes each. In addition, the model reproduces reported differences between arterial and venous HbCO levels and replicates predictions from the Coburn-Forster-Kane equation for CO exposures of a 1- to 83-h duration. In contrast to approaches based on the Coburn-Forster-Kane equation, the present model predicts uptake and distribution of CO in both vascular and tissue compartments during inhalation of either constant or variable levels of CO.

Adult↗
PubMed1989

[Reaction of the immune system of the body to combined effects of chemical agents].

A single and chronic inhalation exposure to a complex of chemical substances being part of hydrogen sulphide-containing natural gas (hydrogen sulphide, hydrocarbon, mercaptan, sulphur dioxide) results in a decline in humoral indicators of non-specific body resistance. At the same time the level of inhibition of lysozyme and complement activity along with the bactericidal activity of blood serum have direct dependence on the duration of chemical exposure and can be used as additional tests for early detection of body changes.

Administration, Inhalation↗
PubMed2007

Uncertainties in doses calculated according to ICRP recommendations after inhalation of 239PUO2 and early chest monitoring.

This study estimates uncertainties in Pu biokinetics and effective doses calculated after an acute inhalation exposure to 239PuO2 according to ICRP recommendations (default values for aerosols size and PuO2 dissolution parameters). This was performed using the most recently reported variations in model parameters and simulations after a Monte Carlo approach. Without chest monitoring, uncertainties in thoracic retention and plutonium excretion was 8-10 (95% confidence interval as the ratio between 97.5 and 2.5 percentiles of the lognormal distributions) up to 900 d after exposure. Early chest monitoring reduces significantly the uncertainties in plutonium biokinetics and doses which remain within a 95% confidence interval of 2.3 as compared with 6.6, without monitoring. Analysis of bioassay data previously reported shows that the dose delivered to some individuals can be out of the confidence interval, which was mostly due to an inhibition of the late mechanical clearance of the alveolar interstitium.

Administration, Inhalation↗
PubMed1981

Experimental conditions in GMR chronic inhalation studies of diesel exhaust.

A chronic inhalation exposure study was initiated to study the potential health effects of diesel exhaust on laboratory animals. Test atmospheres of clean air (control) or freshly diluted diesel exhaust at nominal particulate concentrations of 250, 750 and 1500 micrograms m-3 were supplied to four large volume inhalation chambers in which individually housed Fischer 344 albino rats (Rattus norvegicus) and Hartley guinea pigs (Cavia porcellus) were exposed for 20 h per day, 51/2 days per week. The diesel aerosol concentration, chamber temperature and relative humidity were continually monitored and controlled to maintain the exposure dose levels and an environment of 22 +/- 2 degrees C and 50 +/- 20% relative humidity. Animals were randomly sampled from the chambers for physiological, biochemical and pathological studies throughout the exposure period. The study was continued without interruption for 24 months with the mean diesel particle mass concentrations within 6% of the target values. The standard deviation of the mass concentration measurements was approximately 30% of the mean.

Aerosols↗