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PubMed1997

Elimination of 1-hydroxypyrene after human volunteer exposure to polycyclic aromatic hydrocarbons.

The aim of this study was to estimate the kinetics of 1-hydroxypyrene (1-HP) elimination after inhalation exposure to polycyclic aromatic hydrocarbons (PAHs). Samples of inhaled and exhaled air were collected on glass fiber filters backed with tubes filled with Amberlit XAD-2 resin. The filters were extracted by cyclohexane and Amberlit--by acetonitrile. Extracts for the determination of pyrene and benzo[a]pyrene (B[a]P) concentrations were analyzed by high-performance liquid chromatography (HPLC). 1-Hydroxypyrene in urine was determined after its preconcentration on a C-18 column (solid phase extraction method) using the same analytical technique. Five male volunteers were exposed for 6 h (two times, with a 1-month interval) to a PAH mixture at an aluminium plant. The volunteers were breathing at rest through facial mask equipped with a 1000-ml compensation container which allows collection of the exhaled air. Inhaled air samples were collected in the breathing zone of each volunteer. Urine samples were collected until the 71st hour after the onset of exposure. The average respiratory retention of pyrene was found to be 61%. The 1-HP elimination process could be described by one-compartment model with the half-live of 9.8 hour (95% CI 7.9-11.7 h). The simulation of 1-HP elimination in urine during a working week (4 days) indicates that the balance between absorption and elimination is achieved at the end of the second day.

Administration, Inhalation↗
PubMed1993

Predicted infant exposure to tetrachloroethene in human breastmilk.

Based on a variety of maternal occupational and residential inhalation exposure scenarios, estimates of infant exposure to the dry-cleaning solvent tetrachlorothylene (perchloroethylene, PCE) in breastmilk were made. Physiologically based pharmacokinetic (PBPK) modeling indicates that infants may be exposed to elevated levels of PCE in breastmilk due to their mothers' inhalation of PCE. The PBPK-predicted breastmilk PCE concentrations agree very well with measured concentrations, where available. Based on this analysis, infants may be exposed to this workplace chemical via breastmilk at doses corresponding to rather high levels of risk. Predicted breastmilk doses provide the infant with little margin of exposure to doses associated with adverse health effects. In addition, the estimated increased cancer risks associated with these infant exposures are large under certain exposure scenarios. The actual concentrations of PCE in breastmilk of exposed mothers can only be known with certainty if monitoring is conducted. Due to the widespread exposure potential, monitoring studies should be undertaken so that the appropriate risk management alternatives can be better evaluated.

Adult↗
PubMed1997

Age-related changes in ventilatory and heart rate responses to acute ozone exposure in the conscious rat.

To evaluate the effect of age on toxicant-induced pulmonary and extrapulmonary changes, we examined the effect of inhalation exposure to oxone (O3) on the ventilatory and heart rate (HR) responses in 4-6 and 20-22-month-old male rats. The rats, chronically implanted with an electrocardiographic (ECG) electrodes, were placed in a head-out plethysmograph for continuous ventilatory measurements of tidal volume and breathing frequency. Simultaneous measurements of HR were also obtained. A 6-hr exposure of each rat to filtered air was followed 2 days later by a 5-hr exposure to 0.1 ppm O3, 5 days later by a 5-hr exposure to 0.3 ppm O3 and 10 days later by a 5-hr exposure to 0.5 ppm O3. Each of the O3 exposures was preceded by a 1-hr exposure to filtered air. Transient rapid shallow breathing with slightly increased HR appeared 1-2 min after the start of O3 exposure. It was suggested on the basis of the electroencephalographic (EEG) activity of the olfactory bulb that this transient response was mediated through olfactory sensation. Persistent rapid shallow breathing with a progressive decrease in HR occurred with a latent period of 1-2 hr. The last 90-min averaged values for relative minute ventilation tended to decrease with the increase in the level of exposure to O3 and these values for young rats were significantly lower than those for old rats. An exposure of young rats to 0.1 ppm O3 for shorter than 5 hr significantly decreased the tidal volume and HR and increased breathing frequency, but no significant changes were observed in old rats. There were no differences between young and old rats in non-observable-adverse-effect-levels (NOAELs) for the O3-induced persistent ventilatory and HR responses, when the NOAELs were determined by exposure to 0.3 and 0.5 ppm O3. The present results, as well as the reported decrease in body temperature and blood pressure, suggested that the age-related changes in patterns and magnitude of the persistent rapid shallow breathing with a progressive decrease in HR are mediated through some age-related defense mechanism acting against O3 inhalation. The validity of the occupational exposure limit for O3 in workplaces was discussed in the light of the present findings.

Aging↗
PubMed2006

Methyl tertiary-butyl ether: studies for potential human health hazards.

When methyl tertiary-butyl ether (MTBE) in gasoline was first introduced to reduce vehicle exhaust emissions and comply with the Clean Air Act, in the United States, a pattern of complaints emerged characterised by seven "key symptoms." Later, carefully controlled volunteer studies did not confirm the existence of the specific key symptoms, although one study of self-reported sensitive (SRS) people did suggest that a threshold at about 11-15% MTBE in gasoline may exist for SRSs in total symptom scores. Neurobehavioral and psychophysiological studies on volunteers, including SRSs, found no adverse responses associated with MTBE at likely exposure levels. MTBE is well and rapidly absorbed following oral and inhalation exposures. Cmax values for MTBE are achieved almost immediately after oral dosing and within 2 h of continuous inhalation. It is rapidly eliminated, either by exhalation as unchanged MTBE or by urinary excretion of its less volatile metabolites. Metabolism is more rapid humans than in rats, for both MTBE and tert-butyl alcohol (TBA), its more persistent primary metabolite. The other primary metabolite, formaldehyde, is detoxified at a rate very much greater than its formation from MTBE. MTBE has no specific effects on reproduction or development, or on genetic material. Neurological effects were observed only at very high concentrations. In carcinogenicity studies of MTBE, TBA, and methanol (included as an endogenous precursor of formaldehyde, without the presence of TBA), some increases in tumor incidence have been observed, but consistency of outcome was lacking and even some degree of replication was observed in only three cases, none of which had human relevance: alpha(2u)-globulin nephropathy-related renal tubule cell adenoma in male rats; Leydig-cell adenoma in male rats, but not in mice, which provide the better model of the human disease; and B-cell-derived lymphoma/leukemia of doubtful pathogenesis that arose mainly in lungs of orally dosed female rats. In addition, hepatocellular adenomas were significantly higher in female CD-1 mice and thyroid follicular-cell adenomas were increased in female B6C3F1 mice treated with TBA, but these results lack any independent confirmation, which would have been possible from a number of other studies.

Air Pollutants↗
PubMed1993

Investigation of the effects of benomyl on rat nasal mucosa.

Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate, CAS Registry No. 17804-35-2] is a widely used agricultural fungicide. Previously, olfactory epithelial lesions were produced following a 45-day inhalation exposure to 50 and 200 mg/m3 benomyl. The present study, part of a range-finding study for a two-generation reproduction study, was conducted to determine if the previously reported effects on the nasal mucosa are the result of systemic toxicity or attributable to the inhalation route of exposure. Groups of 10 7-week-old male Crl:CD BR rats were fed diets containing 0, 5000, 10000, or 15000 ppm benomyl for 32 days. Individual body weights and food consumption were determined weekly and on the last day of the study. After 32 days on test, rats were euthanatized by pentobarbital anesthesia and exsanguination and were examined for gross alterations. The nasal cavity was processed for pathological examination. Mean body weight gain was statistically significantly decreased during the first week of treatment and the overall test period (Days 0-32) at the two highest dose levels. A significant decrease in food consumption also was seen during test interval Days 0-7 for the two highest dose groups. In addition, statistically significant decreases in food consumption were observed at the Day 7-14 interval for the 15,000 ppm dose group and at the 21-28 and 28-32 intervals for the two highest dose groups compared with controls. No histopathological lesions were noted in the nasal epithelium of any of the control or benomyl-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Subacute (28-day) toxicity of furfural in Fischer 344 rats: a comparison of the oral and inhalation route.

The subacute oral and inhalation toxicity of furfural vapour was studied in Fischer 344 rats to investigate whether route-to-route extrapolation could be employed to derive the limit value for inhalation exposure from oral toxicity data. Groups of 5 rats per sex were treated by gavage daily for 28 days at dose levels of 6-192 mg/kg bw/day, or exposed by inhalation to concentrations of 20-1280 mg/m3 (6 h/day, 5 days/week) or 160-1280 mg/m3 (3 h/day, 5 days/week) for 28 days. Controls received vehicle (corn oil) or were exposed to clean air. Daily oral treatment with the highest dose of furfural (initially 192 mg/kg bw/day, later reduced to 144 mg/kg bw/day and finally to 120 mg/kg bw/day) resulted in mortality, and in increases in absolute and relative kidney and liver weight in surviving females of this group. Exposure of rats by inhalation for 6 h/day, 5 days/week for 28 days induced mortality at concentrations of 640 mg/m3 and above within 1-8 days. At 640 mg/m3 (3 h/day) and at 320 mg/m3 (3 and 6 h/day) and below, however, exposure was tolerated without serious clinical effects. In contrast, histopathological nasal changes were seen even at the lowest concentration of 20 mg/m3. With increasing exposure concentration, the nasal effects increased in incidence and severity and also expanded from the anterior part to the posterior part, including the olfactory epithelium. It was concluded that the no-observed-adverse-effect level (NOAEL) for oral toxicity was 96 mg/kg bw/day. The NOAEL for systemic inhalation toxicity was comparable, i.e. 92 mg/kg bw/day (corresponding to 320 mg/m3 (6 h/day) or 640 mg/m3 (3 h/day)) assuming 100% absorption. The presence of the histopathological nasal changes at the lowest tested concentration of 20 mg/m3 (corresponding to 6 mg/kg bw/day) proves that for locally acting substances like furfural extrapolation from the oral to the inhalation route is not valid.

Administration, Inhalation↗
PubMed1984

Inhalation pharmacokinetics: evaluating systemic extraction, total in vivo metabolism, and the time course of enzyme induction for inhaled styrene in rats based on arterial blood:inhaled air concentration ratios.

A method is described for evaluating systemic extraction of soluble vapors during inhalation exposures. The physiological basis of the method is the inability to achieve complete equilibrium of vapor between arterial blood and inhaled air whenever there is substantial extraction of the soluble vapor during a single pass through the systemic circulation. The technique was applied to estimate styrene extraction ratios at the end of 6-hr exposures in male rats exposed to various concentrations of inhaled styrene. From extraction ratios and several physiological constants, metabolic constants were evaluated for styrene metabolism in vivo. In naive rats, the maximum velocity of metabolism was 10.0 mg/kg/hr, and Km was of the order of 0.2 mg/liter. Pretreatment with pyrazole (320 mg/kg, 1/2 hr before exposure) essentially abolished in vivo styrene metabolism, while pretreatment with phenobarbital (80 mg/kg/day for the 4 days before styrene exposure) increased Vmax about sixfold. Prior exposure to styrene (1000 ppm for 6 hr/day on each of 4 days before experimentation) increased Vmax by a factor of 2. Significant induction of styrene metabolism in vivo was observed in 24-hr continuous exposure to 400, 600, or 1200 ppm. A curve fitting routine was employed with a physiological model of styrene inhalation kinetics to estimate the dynamics of the induction process in the 24-hr exposures. At 400 ppm, induction began after a lag of 15.5 hr, had a half-life of 3.5 hr, and reached 2.7 times the Vmax in naive rats. At 600 ppm, it began after 10.6 hr, proceeded with a half-life of 2.2 hr, and increased Vmax by 3.4 times. At 1200 ppm, induction began earlier, 4.6 hr, and reached a greater value, 4.4 times Vmax, but had a half-life similar to that at 600 ppm. No induction occurred in 48-hr exposure to 200 ppm. Induction complicates kinetic modeling of continuous inhalation with soluble, well-metabolized vapors because it is time and concentration dependent. These methods should prove useful for studying the in vivo metabolism of other soluble, well-metabolized vapors and for examining the time course of induction of the metabolizing enzymes for these chemicals.

Air↗
PubMed2002

What is new in diesel.

We review information from the past 5 years on changes in diesel exhaust (DE) emissions and developments in the study of DE toxicity. New DE technologies have changed the composition of DE considerably, reducing emissions of many of the components of health concern. The increasing similarity of modern diesel and compressed natural-gas engine emissions needs to be reflected in any regulatory analysis. Even for historical DE emissions, considerable study of DE exposure in animals or humans has not produced data useful for risk assessment. DE inhalation exposure in most species (hamsters, guinea pigs, mice) does not produce lung tumors. Inhalation studies of DE in rats found lung tumors only with lung overload, and tumors also occurred when inert dusts were inhaled at overload concentrations. The animal data are reassuring and show that DE is not a concern at ambient exposure levels. Re-analyses of occupational epidemiology have been shown to have serious shortcomings that do not allow the derivation of a quantitative cancer risk. Studies of railroad workers found no dose response; rather cancer risk appeared to decrease for individuals with greater DE exposure. Studies of truck drivers also suffer from serious flaws because of misconceptions about the year that diesel was introduced, lack of an adequate latency period, and the realization that drivers exhibited increased lung cancer risk even prior to the diesel era. Recent industrial hygiene studies of drivers show that DE was not likely to be a primary source of particles or polycyclic aromatic hydrocarbons. Further, there is no dose response across occupations. In fact, the occupation (underground miners) with the highest exposure to DE does not exhibit increased cancer risks. This new information seriously weakens earlier risk characterizations of DE by various regulatory groups. New research and better exposure measurements are needed before a reliable risk assessment of DE can be produced.

Air Pollutants↗
PubMed2006

Types and patterns of response in the larynx following inhalation.

The laryngeal mucosa responds to insult similarly to other epithelial tissues but the response depends on location within the larynx since important anatomic differences exist, even within rodent species. Although dogs and nonhuman primates are also utilized for inhalation toxicology studies, little published information is available regarding sites of injury from inhaled toxicants in these species. Accurate and consistent fixation, trimming, and microtomy of laryngeal sections allow the pathologist to compare the morphology of laryngeal mucosa from exposed and control animals and detect and interpret subtle differences resulting from inhalation exposure. There are anatomic landmarks that are keys to providing consistent sections through important areas of the laryngeal mucosa. Repeated inhalation of toxic concentrations of chemicals, drugs, or environmental contaminants induces a wide range of responses, depending on the physical properties and concentration of the toxic substance and duration of exposure. Responses include edema, acute to chronic inflammation, fibrosis, mucosal ulceration, degeneration, and necrosis. Attempts at repair include regeneration, hyperplasia, squamous metaplasia, hyperkeratosis, and neoplasia. Awareness of normal histology and zones of transition from squamous to respiratory epithelium in different areas of the larynx in different species is critical to avoid confusing normal epithelium with metaplasia or hyperplasia. Microscopic examination of laryngeal mucosa from animals exposed via inhalation and necropsied following a recovery period provides the opportunity to determine the degree of regression or progression of exposure-induced laryngeal lesions.

Animals↗
PubMedDate not supplied

Association of particulate air pollution and acute mortality: involvement of ultrafine particles?

Recent epidemiological studies show an association between particulate air pollution and acute mortality and morbidity down to ambient particle concentrations below 100 micrograms/m3. Whether this association also implies a causality between acute health effects and particle exposure at these low levels is unclear at this time; no mechanism is known that would explain such dramatic effects of low ambient particle concentrations. Based on results of our past and most recent inhalation studies with ultrafine particles in rats, we propose that such particles, that is, particles below approximately 50 nm in diameter, may contribute to the observed increased mortality and morbidity In the past we demonstrated that inhalation of highly insoluble particles of low intrinsic toxicity, such as TiO2, results in significantly increased pulmonary inflammatory responses when their size is in the ultrafine particle range, approximately 20 nm in diameter. However, these effects were not of an acute nature and occurred only after prolonged inhalation exposure of the aggregated ultrafine particles at concentrations in the milligrams per cubic meter range. In contrast, in the course of our most recent studies with thermodegradation products of polytetrafluoroethylene (PTFE) we found that freshly generated PTFE fumes containing singlet ultrafine particles (median diameter 26 nm) were highly toxic to rats at inhaled concentrations of 0.7-1.0 x 10(6) particles/cm3, resulting in acute hemorrhagic pulmonary inflammation and death after 10-30 min of exposure. We also found that work performance of the rats in a running wheel was severely affected by PTFE fume exposure. These results confirm reports from other laboratories of the highly toxic nature of PTFE fumes, which cannot be attributed to gas-phase components of these fumes such as HF, carbonylfluoride, or perfluoroisobutylene, or to reactive radicals. The calculated mass concentration of the inhaled ultrafine PTFE particles in our studies was less than 60 micrograms/m3, a very low value to cause mortality in healthy rats. Aging of the fumes with concomitant aggregation of the ultrafine particles significantly decreases their toxicity. Since ultrafine particles are always present in the urban atmosphere, we suggest that they play a role in causing acute lung injury in sensitive parts of the population.

Aerosols↗
PubMed1978

Biochemical and toxicological effects of combined exposure to 1,1,1-trichloroethane and trichloroethylene on rat liver and brain.

1. Inhalation exposure of adult male rats to a mixture of 1,1,1-trichloroethane (500 p.p.m.) and trichloroethylene (200 p.p.m.) for four days 6 h daily resulted in an accumulation of 1,1,1-trichloroethane in perirenal fat. Further exposure on the fifth day caused a rapid increase in various organ contents of both solvents with secondary depression of brain RNA. 2. The four-day exposure doubled the RNA content of liver and caused a slight decline in the concentrations of glutathione in liver. 3. The amount of cytochrome P-450 in liver was increased, as well as the overall mono-oxygenase activity, measured with styrene as substrate. During continuing treatment on the fifth day, styrene mono-oxygenase activity decreased, the activity after 6 h being only about 50% of that at the beginning of the fifth day of exposure. 4. UDP-glucuronosyl transferase activity (measured in digitonin-activated microsomes) was doubled by the four-day combined exposure to 1,1,1-trichloroethane and trichloroethylene. 5. The changes during the fifth day of exposure, e.g. rapid increase in the concentrations of solvents in organs, the detection of trichloroethylene in tissues and depression of mono-oxygenase activity, obviously also occurred during the exposures on days 1 to 4 and reverted during each post-exposure period.

Animals↗
PubMed1983

Chronic exposure to trichloroethylene: lipid and acyl group composition in gerbil cerebral cortex and hippocampus.

Inhalation exposure of Mongolian gerbils to trichloroethylene (50 and 150 ppm) for 12 months caused only small changes in the lipid composition of their cerebral cortex and hippocampus. Total protein content and lipid class distribution were almost unaffected. However, the cholesterol to phospholipid ratio decreased in the cortex of animals exposed to trichloroethylene. This might be due to changes in the relative proportions of different membranes or cellular types. The finding of most interest was among the long-chain polyunsaturated fatty acids where changed ratios were found between long-chain derivatives of the linoleic and the linolenic acid series and a decrease in two minor fatty acids, 20:5 (n-3) and 22:5 (n-3). We think it is likely that such changes occur as a result of peroxidation of polyunsaturated fatty acids or in order to withstand the fluidizing properties of trichloroethylene.

Animals↗
PubMed1987

Prenatal toxicity of 2-methoxypropylacetate-1 in rats and rabbits.

2-Methoxypropylacetate-1 was investigated in Wistar rats and Himalayan rabbits for embryotoxic potential. Rats after inhalation exposure to 0, 0.6, 3.0, or 14.9 mg/liter (approximately 0, 110, 550, or 2700 ppm, respectively) for 6 hr per day from gestation Days 6 through 15 exhibited some degree of maternal toxicity at 2700 and 550 ppm. At 2700 ppm an increase of skeletal anomalies of the thoracic vertebrae among the fetuses was observed and interpreted as an exposure-related slight teratogenic effect. In Himalayan rabbits exposed via inhalation to 0, 0.2, 0.8, or 3.0 mg/liter (approximately 0, 36, 145, or 550 ppm, respectively) for 6 hr per day from gestation Days 6 through 18 teratogenicity was much more pronounced: at 550 ppm, in the absence of clear maternal toxicity, the fetuses of all litters showed severe malformations. No maternal or fetal effects were observed at 145 and 36 ppm. Dermal application of 1000 and 2000 mg/kg to Himalayan rabbits from gestation Days 6 through 18 failed to produce maternal or fetal toxicity.

Abnormalities, Drug-Induced↗
PubMed2004

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

Animals↗
PubMedDate not supplied

Two-year and lifetime toxicity and carcinogenicity studies of ozone in B6C3F1 mice.

To evaluate the toxicity and carcinogenic potential of long-term exposure to ozone, B6C3F1 mice were exposed by whole-body inhalation to 0, 0.12, 0.5, or 1.0 ppm and 0, 0.5, or 1.0 ppm ozone for 24 or 30 mo (lifetime), respectively. The incidence of alveolar/ bronchiolar adenomas and carcinomas (combined) increased (p < 0.05) in female mice exposed to 1.0 ppm for 24 or 30 mo and marginally increased (p > 0.05) in male mice exposed to concentrations of 0.5 or 1.0 ppm. An increased incidence of nonneoplastic lesions were observed in the nasal cavities and in the centriacinar region of the lung of mice exposed to 0.5 or 1.0 ppm for 24 and 30 mo. Nasal cavity lesions were mild and included hyaline degeneration, hyperplasia, squamous metaplasia, fibrosis and suppurative inflammation of the transitional and respiratory epithelium of the lateral wall, and atrophy of the olfactory epithelium. Lung lesions included replacement of the epithelium of the alveolar ducts and adjacent alveolar septa with epithelium similar to that normally found in terminal bronchioles (metaplasia) and associated alveolar histiocytosis. Based on the results of these studies, we conclude that inhalation exposure of B6C3F1 mice to ozone for 24 or 30 mo (a) is carcinogenic in female B6C3F1 mice exposed to 1.0 ppm of ozone based on an increased incidence of alveolar/bronchiolar adenoma or carcinoma and (b) results in mild, site-specific, nonneoplastic lesions in the nasal cavity and centriacinar lung of male and female mice exposed to 0.5 or 1.0 ppm of ozone for 2 yrs, which persist with continued exposure to 30 mo. It is uncertain whether or not the marginal increase (p > 0.05) of alveolar/bronchiolar neoplasms in male B6C3F1 mice resulted from exposure to ozone.

Administration, Inhalation↗
PubMed1987

Mucus protection and airway peroxidation following nitrogen dioxide exposure in the rat.

In the current study, biochemical measures of lipid peroxidation following 4-h inhalation exposure to 76 mg/m3 (40 ppm) nitrogen dioxide were correlated with measures of deposition and tissue antioxidant levels in the nasal cavity and the trachea of the Fischer rat. In addition, respiratory-tract mucus samples were collected via esophageal cannulation and nasopharyngeal lavage over known time periods, and were analyzed for phospholipid (PL) content to provide an index of the unsaturated lipids (UL) that they may contain. UL are thought to be important in the scavenging of oxidants by the mucous lining layer. Nasal deposition efficiency, as measured in the surgically isolated upper respiratory tract under unidirectional flow conditions, averaged 25%, corresponding to an absolute deposition rate of 41 nmol/min. Vitamin E levels averaged 1.7, 5.9, and 0.7 nmol/mumol PL in nasal, tracheal, and pulmonary tissues, respectively. The level in the trachea was significantly (p less than 0.005) higher than in the other tissues. As estimated from the increase in lavage PL content over 1 h, the overall mucous PL transport rate was less than 0.013 nmol/min, suggesting the PL of the mucous lining layer could not offer significant protection against the inhaled NO2. Conjugated dienes were detected in two of four pooled nasal tissue samples. Thiobarbituric acid-reactive material levels in tracheal tissues were significantly elevated over control levels by NO2 (p less than 0.05). Thus, despite the relatively high vitamin E levels, 4-h NO2 exposure appeared to result in lipid peroxidation in the trachea and, perhaps, in the nasal airways of the rat, a result that correlated with the apparent lack of oxidant-scavenging species in the mucus lining these airways.

Animals↗
PubMed1994

Induction of respiratory hypersensitivity to diphenylmethane-4,4'-diisocyanate (MDI) in guinea pigs. Influence of route of exposure.

The induction of respiratory sensitization in guinea pigs to diphenylmethane-4,4'-diisocyanate (MDI), a known human respiratory allergen, has been investigated and different routes of exposure compared. Guinea pigs were exposed to MDI by i.d. injection, by topical application or by inhalation. Pulmonary hypersensitivity was measured subsequently as a function of changes in respiratory rate following challenge with atmospheres containing MDI. In addition, contact hypersensitivity was measured by topical challenge and antibody responses evaluated by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). Attempts to sensitize guinea pigs by inhalation exposure to MDI were unsuccessful. Antibody responses and contact sensitization were both infrequent and low grade, and no animals exhibited pulmonary responses following challenge with atmospheric MDI. In contrast, sensitization by either i.d. injection or topical application of MDI induced antibody responses in the majority of animals. Moreover, a proportion of animals in each case exhibited pulmonary responses following subsequent inhalation challenge. These data indicate that the route of exposure influences markedly the effectiveness of sensitization to respiratory allergens such as MDI and that skin contact may be an important cause of occupational respiratory allergy.

Administration, Inhalation↗
PubMed1993

Acute toluene exposure increases extracellular GABA in the cerebellum of rat: a microdialysis study.

Effect of acute inhalation exposure of toluene or halothane anaesthesia on extracellular levels of gamma-aminobutyric acid (GABA) was monitored within the cerebellum of rats by microdialysis. GABA increased during and after exposure to toluene (2000 p.p.m., 2 hr) in contrast, halothane had no noticeable effect on GABA levels. When tetrodotoxin was added to the perfusion medium basal concentrations of GABA decreased to about 74% of control concentrations. Extracellular GABA levels did not increase during exposure to toluene when tetrodotoxin was added to the perfusion medium. The results indicate that toluene increase GABA within the cerebellum by sodium dependent mechanisms, possibly by modulating the neuronal input from the mossy fibers to the cerebellar cortex.

Animals↗