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 289 records · Page 16Linked to original sources
PubMed2002

Characterization of the LOAEL-to-NOAEL uncertainty factor for mild adverse effects from acute inhalation exposures.

This analysis was undertaken to reduce uncertainty in acute inhalation risk assessment for mild acute effects. Applying uncertainty factors (UFs) to the no-observed-adverse-effect level (NOAEL) is the primary approach used in threshold-based risk assessments. When a NOAEL is unavailable, a UF of 10 is often applied to a lowest-observed-adverse-effect level (LOAEL) to estimate the NOAEL. We evaluated the LOAEL-to-NOAEL relationship for mild acute inhalation toxicity for 215 data sets for 36 hazardous air pollutants. The LOAEL-to-NOAEL ratios were 2.0, 5.0, 6.3, and 10.0 for the 50th, 90th, 95th, and 99 th percentile, respectively. The 90% confidence interval for the 95th percentile was 5.0-7.5. Consequently, based on previous dose placement practice, the LOAEL-to-NOAEL UF of 6 would be protective for 95% of the responses, and a value of 10 would be protective of 99% of the responses. The ratio values were not associated with the size of the experimental group. There was little variability among species, particularly at the median. This analysis is reflective only of mild acute inhalation toxicity. For other exposure routes, exposure durations, or more severe toxicity, the distributions are likely to be different.

Air Pollutants↗
PubMed2003

Repeated inhalation exposures to the bioactivated cytotoxicant naphthalene (NA) produce airway-specific Clara cell tolerance in mice.

Repeated exposures to bioactivated cytotoxicants such as naphthalene (NA) render the target population, Clara cells, resistant to further injury through a glutathione-dependent mechanism. The current studies were designed to test the hypothesis that the mechanism for tolerance is localized in Clara cells. We used three approaches to test this hypothesis. First, using airway explants from tolerant mice maintained in culture, we sought to determine if the mechanism of Clara cell tolerance was airway-specific. Second, using inhalation as the route of exposure, we sought to determine if Clara cells at all airways levels become tolerant to repeated inhalation exposures of NA. Third, by measuring gamma-glutamylcysteine synthetase (gamma-GCS) activity and expression we determined if tolerance to inhaled NA resulted from shifts in phase-II metabolism. Our results indicate that Clara cells in explants from tolerant mice remained tolerant to NA injury in culture. When mice were exposed to repeated inhalation exposures of NA (15 ppm), we found that Clara cells at all airway levels became tolerant. Expression and activity analysis revealed that gamma-GCS, the rate-limiting enzyme in glutathione synthesis, is induced in tolerant Clara cells. Buthionine sulfoximine, a gamma-GCS inhibitor, was able to eliminate the resistance of these tolerant cells. We conclude: (1) the mechanism of NA tolerance in Clara cells is airway specific, (2) the specific mechanism allows Clara cells to become tolerant to NA vapor at levels relevant to human exposure, and (3) the mechanism of tolerance to inhaled NA is highly dependent on induction of the catalytic enzyme, gamma-GCS.

Administration, Inhalation↗
PubMed1983

Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure.

One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.

Air↗
PubMed1986

Relative hepatotoxicity of some industrial solvents after intraperitoneal injection or inhalation exposure in rats.

Intraperitoneal LD50 (lethal dose 50% kill) values and minimal liver toxic doses in female Sprague-Dawley rats were determined for the following industrial solvents: toluene, methylene chloride, carbon tetrachloride, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloroethylene, ethanol, methyl ethyl ketone, and dioxane. For the following solvents LC50 values and minimal liver toxic air concentrations were also determined: xylene, styrene, chloroform, tetrachloroethylene, and dimethylformamide (DMF). The serum activity of the enzyme sorbitol dehydrogenase (SDH) was used as an indicator of liver damage. Carbon tetrachloride, chloroform, and DMF were hepatotoxic in low doses compared to LD50 values (TD50 (toxic dose 50%) values approximately 30, 90, and 50 mg/kg). Chloroform and DMF were hepatotoxic in comparatively low concentrations after a 4-hr inhalation exposure (TC50 (toxic concentration 50%) values approximately 590 and 740 mg/m3). Even relatively high doses of the other solvents did not raise the SDH activity. Significant direct (metabolite-mediated) hepatotoxicity seems to be an uncommon feature among commonly used industrial solvents.

Animals↗
PubMed1992

Development of a multicompartmental model of the kinetics of quartz dust in the pulmonary region of the lung during chronic inhalation exposure of rats.

A multicompartmental model for the kinetics of dust retention in the pulmonary region of the lung and in the tracheobronchial lymph nodes has been developed. The model reflects the following ideas concerning the basic features of this process: (1) penetration into the pulmonary interstitium and translocation to the lymph nodes are possible for non-phagocytized particles only; (2) these processes depend on the degree of damage to macrophages by dust and on the extent of compensatory enhancement in the recruitment of neutrophils taking part in the clearance of the pulmonary region free surface; (3) a certain proportion of initially penetrating particles is continuously returned to this surface together with recruited pulmonary macrophages. The model ensures a satisfactory approximation to experimental data on the retention of quartz in the lung and lymph nodes during long term inhalation exposure, and simulation of the kinetic effects associated with both the damage to and the protection of the macrophagal clearance mechanism.

Animals↗
PubMed1987

Effects of protraction of the alpha dose to the lungs of mice by repeated inhalation exposure to aerosols of 239PuO2.

To determine the long-term biological effects of protracted alpha irradiation of the lung, 84-day-old C57BL/6J mice were repeatedly exposed by inhalation to aerosols of 239PuO2 every other month for up to six exposures in 10 months to reestablish lung burdens of 20, 90, or 460 Bq. Other mice were exposed only once when either 84 or 460 days of age to achieve desired initial lung burdens of 20, 90, 460, or 2300 Bq. Suitable control groups were maintained. Groups of mice with similar cumulative alpha doses to the lung had 3.4 to 4.4 times greater incidence of pulmonary tumors (adenomas and adenocarcinomas) when the dose to the lung was protracted by the repeated inhalation exposures compared to mice that received a single inhalation exposure. Excess pulmonary tumors per unit dose to the lung were also greater in groups of repeatedly exposed mice compared to those exposed only once. Repeatedly exposed mice also died earlier with pulmonary tumors than did those exposed once. It appears that protraction of an alpha dose to lungs increases the carcinogenic risk of inhaled 239PuO2 in mice.

Administration, Inhalation↗
PubMed1987

Lysozyme activity in ultrastructurally defined fractions of alveolar macrophages after inhalation exposure to nickel.

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.

Animals↗
PubMed1988

Experimental T-2 toxicosis in swine following inhalation exposure: clinical signs and effects on hematology, serum biochemistry, and immune response.

Nine- to ten-week-old, male castrated, specific pathogen-free derived pigs, weighing 34 to 42 kg, were exposed to a T-2 toxin aerosol (390 micrograms/liter, 1.5 microM mass median aerodynamic diameter) for a time period which allowed an amount equivalent to 8 mg/kg to be nebulized (six pigs). Control animals (five pigs) were exposed to an equivalent amount of the nebulized vehicle. Pigs were immunized subcutaneously with sheep red blood cells on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic studies. Pigs were closely observed, and daily rectal temperatures and weekly weights were measured. The T-2-treated pigs vomited and exhibited cyanosis, anorexia, lethargy, lateral recumbency, slightly elevated rectal temperature, and depressed body weight gain. The lymphocyte count decreased while the neutrophil count increased. The concentrations of total serum protein and hemoglobin declined. There was a marked increase in serum alkaline phosphatase activity on Day 1, followed by a marked and persistent decrease. Mitogen-induced (Con A, PHA, and PWM) blastogenic responses of peripheral blood mononuclear cells and hemagglutination titers to SRBC were also transiently decreased. Thus, inhalation exposure of pigs to a sublethal dose of T-2 toxin caused clinical signs of toxicity and adverse effects on clinical pathologic parameters and immune responses; however, most of these effects were short-lived. The changes described in our study resemble those reported in pigs given T-2 toxin by intravascular injection.

Administration, Inhalation↗
PubMed2004

Developmental effects of inhalation exposure to 2-bromopropane in rats.

2-Bromopropane (2-BP), known as a reproductive and hematopoietic toxicant in humans, was assessed for developmental toxicity. Sprague-Dawley rats were exposed by inhalation to 2-BP at a concentration of 0 (control), 125, 250, 500, or 1000 ppm for 6 h per day, 7 days per week during 2 weeks of the pre-mating period, during the mating period until copulation and during the period of gestation days 0-19. After parturition, dams were allowed to breast feed their pups until postnatal day 4. 2-BP exposure resulted in no signs of maternal toxicity as assessed by clinical observations and body weight gain. On the other hand, the inhalation exposure to 1000 ppm markedly decreased the number of pups born, although the number of implantations did not decrease. No effect of 2-BP on pups weights or survival until postnatal day 4 was found. It was found that the repeated inhalation exposure of rats to 1000 ppm 2-BP induced fetal lethality during the post-implantation period.

Abnormalities, Drug-Induced↗
PubMed1995

A new mask filter cartridge used to determine applicator inhalation exposure to an alachlor herbicide (Lasso) during normal spraying operations.

A filter cartridge with a low air-flow resistance was designed for use on a modified half-face respirator worn during the application of alachlor (Lasso) herbicide. The filter trapped large concentrations of alachlor while retaining the ability to trap small respirable droplets. Moreover, alachlor could be recovered from the disassembled cartridge and analyzed by conventional methods. The test cartridges were used in combination with conventional personal air samplers to determine whether the filters trapped more alachlor when compared with personal samplers and to determine accurately the amount of alachlor reaching the breathing zone. Farmers sprayed alachlor in the form of alachlor (N = 7) or alachlor mixed with other herbicides or surfactant (N = 15). An average of 4 x 10(-2) mg or 2 x 10(-4) mg/kg of applied alachlor reached the respirator filters. This concentration was 10-fold higher than the alachlor recovered from the personal samplers. The new filter cartridge is better for determining the amount of alachlor reaching the breathing zone, and there is a low potential for significant inhalation exposure to alachlor during normal spraying operations.

Acetamides↗
PubMed2001

Mixtures of nickel and cobalt chlorides induce synergistic cytotoxic effects: implications for inhalation exposure modeling.

Workers are often simultaneously exposed to two or more chemicals, yet little is known about the toxicity of most chemical mixtures. The traditional assumption, in the absence of further information, has been that the chemical components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show that mixtures of NiCl(2) and CoCl(2) induce a synergistic (that is, greater than additive) toxic response in cell culture. Immortalized alveolar epithelial type II cells were incubated for 4 h with various concentrations of either NiCl(2), CoCl(2), or NiCl(2) and CoCl(2) together, and cell viability assessed 24 h later. The LD(50) for NiCl(2) was 5.7 mM. CoCl(2), with an LD(50) of 1.1 mM, was about five times more potent than NiCl(2). Mixtures of NiCl(2) and CoCl(2) decreased cell viability synergistically. For example, a mixture of 750 microM NiCl(2) and 750 microM CoCl(2) reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data from these studies in a mathematical model; this model describes the equivalent inhalation exposure to an aerosol composed of a mixture of chemicals with different toxicities and also accounts for synergistic responses to these chemicals. Our results along with previous studies using an animal model suggest that these synergisms should be taken into account when conducting future exposure assessments.

Air Pollutants↗
PubMed1990

The immunotoxicity of three nickel compounds following 13-week inhalation exposure in the mouse.

Groups of B6C3F1 mice were exposed to aerosols of nickel subsulfide (Ni3S2), nickel oxide (NiO), or nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day, 5 days per week for 65 days to determine the immunotoxicity of these compounds. Exposure concentrations were 0.11, 0.45, and 1.8 mg Ni/m3 for Ni3S2, 0.47, 2.0, and 7.9 mg Ni/m3 for NiO; and 0.027, 0.11, and 0.45 mg Ni/m3 for NiSO4. Thymic weights were decreased only in mice exposed to 1.8 mg Ni/m3 Ni3S2. Increased numbers of lung-associated lymph nodes (LALN), but not spleen nucleated cells, were seen with all compounds. Nucleated cells in lavage samples were increased in mice exposed to the highest concentrations of NiSO4 and NiO and to 0.45 and 1.8 mg Ni/m3 Ni3S2. Increased antibody-forming cells (AFC) were seen in LALN of mice exposed to 2.0 and 7.9 mg Ni/m3 NiO and 1.8 mg Ni/m3 Ni3S2. Decreased AFC/10(6) spleen cells were observed in mice exposed to NiO, and decreased AFC/spleen were seen for mice exposed to 1.8 mg Ni/m3 Ni3S2. Only mice exposed to 1.8 mg Ni/m3 Ni3S2 had a decrease in mixed lymphocyte response. All concentrations of NiO resulted in decreases in alveolar macrophage phagocytic activity, as did 0.45 and 1.8 mg Ni/m3 Ni3S2. None of the nickel compounds affected the phagocytic activity of peritoneal macrophages. Only 1.8 mg Ni/m3 Ni3S2 caused a decrease in spleen natural killer cell activity. Results indicate that inhalation exposure of mice to nickel can result in varying effects on the immune system, depending on dose and physicochemical form of the nickel compound. These nickel-induced changes may contribute to significant immunodysfunction.

Aerosols↗
PubMed1998

A subacute inhalation exposure evaluation of a scrubbing solution used in petroleum refineries.

The potential for subacute toxicity and neurotoxicity of a potassium carbonate-based scrubbing solution used in petroleum refineries was evaluated in Sprague-Dawley Crl:CD BR rats. Exposures were to aerosols of a "used" scrubbing solution by wholebody inhalation, 6 h/d, for 21 consecutive days at target concentrations of 0 (filtered air-control), 0.1, 0.2, or 0.4 mg/L (30 animals/sex/group). A functional observation battery (FOB) and locomotor activities tests were conducted and monitored. No apparent adverse effects were noted at any exposure level as determined by clinical observations, food consumption, hematology, serum chemistry, ophthalmologic observations, and gross pathology. Statistically significant increases in lung weights were noted at all treatment levels but returned to control values upon cessation of exposure except for the 0.4 mg/L female group. There were no significant changes in other organ weights. Histopathologic findings were restricted to the respiratory tract and characterized by minimal to moderate epithelial hyperplasia, epithelial necrosis, and cytoplasmic vacuolation at levels I and II of the nasal cavities. Lung bronchiolization and alveolar macrophage infiltration were also observed. The respiratory-tract findings were considered a local response to the high alkalinity of the test material as substantiated by the return to normal upon cessation of exposure. Exposure to scrubbing solution had no adverse effect on FOB endpoints and locomotor activity evaluations, brain weight and size, and neuropathologic examinations. In conclusion, inhalation exposure to a used scrubbing solution aerosol for 21 d did not result in any persistent systemic toxicity or neurotoxicity in either male or female rats.

Animals↗
PubMed1985

Uptake, distribution and behavioral effects of inhalation exposure to manganese (MnO2) in the adult mouse.

Adult male mice were exposed either to sublethal levels of MnO2 dust or filtered air (control group) 7 hours/day, 5 days/week for 16 to 32 weeks. Following a 16 week initial exposure period, randomly selected samples (8 animals) from both the control and Mn-exposed groups were observed for behavioral performance (ambulations and rearings in the open-field, "hole-in-board" explorations, rotarod) and learning (passive avoidance) and tissue Mn levels were determined via atomic absorption spectrometry. Exposure continued for the remaining animals and the sampling procedure was repeated biweekly for an additional 8 time points. At week 32, Mn exposure was terminated. However, biweekly testing of the remaining animals continued for an additional 3 time points. Mn-exposed animals had significantly higher blood, liver, kidney, lung, cerebrum, cerebellum plus brainstem, and testis Mn levels than control animals. With the exception of the liver, these levels declined with increasing exposure time. No histopathologic effects attributable to Mn-exposure were observed. However, significant overall effects on growth and behavior were obtained. Specifically, Mn-exposed subjects weighed more, executed more rearings in the open-field, and tended to exhibit longer latencies to enter the open-field. When the post-exposure data were analyzed separately, no significant effects were obtained. While no general relationship was obtained between tissue Mn levels and behavior, selected behavioral measures did correlate with tissue Mn levels. Animals exposed via feeding to comparable Mn levels across the same length of exposure employed in the inhalation study did not demonstrate any significant behavioral alterations.

Air Pollutants↗
PubMed2000

Characterization of a microprocessor-controlled tubular multiple metered dose inhaler aerosol generator for inhalation exposures of pharmaceuticals.

A microprocessor-controlled tubular multiple metered dose inhaler (MDI) aerosol generator was constructed for the delivery of pharmaceutical aerosols to inhalation chambers. The MDIs were mounted in four cassettes containing one to four MDIs on a stepped end plate. The MDIs in each cassette were pneumatically activated at intervals that were controlled by the microprocessor. The cassettes permitted easy replacement of each set of MDIs with a fresh set of MDIs whenever necessary. Aerosol concentration was controlled by varying the number of active MDIs in each cassette and the frequency of activations per minute of each row. Aerosol from the MDIs flowed along the long axis of the tube, which provided a path length sufficient to diminish impaction losses. Using a light-scattering device to monitor the aerosol concentration, the pulsatile output from the MDIs in the cassettes was demonstrated to be adequately damped out provided that the dilution/mixing/aging chamber exceeded 3 ft in length. The tube diameter selected was the minimum compatible with mounting the required number of MDIs so that the linear velocity of the aerosol was adequate to efficiently transport the aerosol out of the dilution chamber. Aerosol concentration and particle size data were recorded for a nose-only rodent exposure chamber. Reproducible aerosol concentrations ranging from 0.03 to 0.6 mg/L were generated. Particle sizes ranged from 2- to 3-microm mass median aerodynamic diameter. Thus, the aerosol generated was within the size range suitable for inhalation exposures.

Aerosols↗
PubMed1996

PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure.

During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice while decreases in glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day and 1-month exposed mice. Within exposure groups, the apparent Vmaxc maintained significant increases in the 1-month and 2-year control groups. Although the same initial increase exists in the exposed group, the 2-year Vmaxc is significantly smaller than the 1-month group (p < 0.001). Within group differences in median Kfc values show a significant decrease in both 1-month and 2-year groups among control and exposed mice (p < 0.001). Although no changes in methylene chloride solubility as a result of prior exposure were observed in blood, muscle, liver, or lung, a marginal decrease in the fat:air partition coefficient was found in the exposed mice at p = 0.053. Age related solubility differences were found in muscle:air, liver:air, lung:air, and fat:air partition coefficients at p < 0.001, while the solubility of methylene chloride in blood was not affected by age (p = 0.461). As a result of this study, we conclude that age and prior exposure to methylene chloride can produce notable changes in disposition and metabolism and may represent important factors in the interpretation for toxicologic data and its application to risk assessment.

Administration, Inhalation↗