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PubMed1998

Comparison of the mutagenic potency of 1,3-butadiene at the hprt locus of T-lymphocytes following inhalation exposure of female B6C3F1 mice and F344 rats.

1,3-Butadiene (BD) is an indirect alkylating agent that has greater cancer potency in the mouse than in the rat. The purpose of the present study was to compare the mutagenic potency of BD at the hprt locus of T-lymphocytes of exposed mice and rats and to determine whether mutations induced in this marker gene can be used as a quantitative indicator for species differences in susceptibility to cancer. To this end, experiments were conducted to define the effects of exposure duration and the time elapsed after exposures on the frequency of hprt mutations (Mf) in T-cells from female B6C3F1 mice and F344 rats of similar age (4-5 weeks) when exposed to BD by inhalation. The accumulation of hprt mutations in T-cells from thymus was assessed in animals necropsied 2 weeks after exposure to 0 or 1250 ppm BD for 1 or 2 weeks, while the time course for the appearance of hprt mutant T-cells (i.e., the phenotypic expression and cell migration) in thymus and spleen was evaluated in animals necropsied at weekly/biweekly intervals up to 10 weeks after exposure for 2 weeks. At necropsy, T-cells were isolated from thymus and spleen and cultured in the presence of IL-2, concanavalin A, and 6-thioguanine (Walker and Skopek, Mutat. Res., 288, 151-162, 1993). BD exposures of 1 and 2 weeks led to mutagenic effects in mouse thymus, with the average Mfs being 3- and 5-fold greater than background values, respectively. In rat thymus, there was only a 1.7-fold increase in Mfs after 2 weeks of BD exposure. In the mutant expression experiment, hprt Mfs in thymus and spleen of both species increased for several weeks post-exposure and then declined. Hprt Mfs in thymus reached maximum levels at 2 weeks post-exposure in mice (Mfs = 11.3 +/- 2.4 x 10(-6)) and at 3 weeks post-exposure in rats (4.9 +/- 1.2 x 10(-6)), while hprt Mfs in spleen reached peak levels at 5 weeks post-exposure in mice (19.7 +/- 1.9 x 10(-6)) and 4 weeks post-exposure in rats (10.1 +/- 1.8 x 10(-6)). Background Mfs for mouse and rat thymus and spleen ranged from 1.6 +/- 0.3 x 10(-6) to 3.0 +/- 1.1 x 10(-6). Statistical analyses of the hprt Mf data for spleen demonstrated that, under these exposure conditions, the mutagenic potency of BD (represented by the difference in the areas under the phenotypic expression curves of treated versus control animals) was 5-fold greater in mice than in rats. The magnitude of the species differences in mutagenic potency, observed after 2 weeks of BD exposure, resembles the species differences in metabolism more closely than the species differences in cancer potency.

Animals↗
PubMed2003

Lethal inhalation exposure during maintenance operation of a hydrogen fluoride liquefying tank.

Calcium sulfate adheres to the inside of liquefying pipes during the production of liquefied hydrogen fluoride. It is regularly washed away with water jets every six months. Two days before the operation, the pipes were experimentally washed down with water and the safety of the operation was confirmed with acidic washing fluid (pH 5). A 65-year-old man was severely sprayed on his face just after the start of the operation. He died half an hour later from acute respiratory failure. High serum concentrations of ionized fluoride indicated massive exposure to hydrofluoric acid (HFA). Pathological findings revealed severe bilateral pulmonary congestion and edema. It was hypothesized that calcium sulfate hardened with the water during the experimental washing and caused some blockages in the pipes. Consequently, choking of the pipes caused the HFA to collect and the washing fluid ran back. Weak HFA is not pungent to skin and mucous membranes. Therefore, it was suggested that a low concentration of HFA was inhaled directly into the peripheral respiratory tracts. No risk management against HFA exposure was in place during the operation. It is especially important to take thorough safety measures against inhalation of HFA. It is also essential that there are no stoppages of the pipes before the operation.

Aged↗
PubMed1995

Local versus systemic immunotoxicity of isobutyl nitrite following subchronic inhalation exposure of female B6C3F1 mice.

Female B6C3F1 mice were exposed to isobutyl nitrite (IBN) by inhalation at 0, 37.5, 75, or 150 ppm for 6 hr per day, 5 days per week for 15 weeks. The potential of this compound to induce immunotoxicity was assessed during the 3rd, 13th, 14th, and 15th week of exposure and after 2 weeks of recovery following the 15 weeks of exposure. Both systemic and lung immune functions were examined, including body and lymphoid organs weights, pulmonary macrophage function and host defense, expression of splenic lymphocyte cell-surface markers, natural killer cell function, mixed lymphocyte reaction, and induction of specific antibody to a T-cell-dependent antigen. There was a dose-related suppression of T-cell-dependent antibody-forming cell responses in the spleen following IBN exposure; however, other measures of T-cell and nonspecific immunity were not significantly affected. A dose-related increase of H202 production by alveolar macrophages was present after 12 but not after 68 exposures to IBN. In contrast, pulmonary host defense mechanisms against Klebsiella pneumoniae were unaffected. These results suggest that in the absence of changes in host resistance, IBN may have selective and partially reversible effects on the immune system.

Administration, Inhalation↗
PubMed1985

Inhalation exposure in the home to volatile organic contaminants of drinking water.

Our field studies show that indoor air concentrations of volatilized trichloroethylene (TCE) can be substantial when TCE-contaminated water is used domestically. Using a model shower, increases in TCE water concentrations, water temperature and drop path (time) increased the steady-state air TCE concentrations. Volatilization was incomplete and the rates were comparable to predicted ones. Indoor air models show that the inhalation route of exposure for such chemicals has the potential for being much greater than by direct ingestion. This should be considered in developing regulations to limit adverse health impacts from contaminants of potable water.

Administration, Intranasal↗
PubMed1996

Short term inhalation exposure to turpentine: toxicokinetics and acute effects in men.

OBJECTIVES: This study describes the toxicokinetics, pulmonary function, and subjective ratings of discomfort in volunteers experimentally exposed to turpentine vapour (a mixture of monoterpenes). The results were compared with similar exposure to single monoterpenes to look in the toxicokinetics and acute effects for signs of interactions between the monoterpenes. METHODS: Eight male volunteers were exposed to 450 mg/m3 turpentine by inhalation (2 h, 50 W) in an exposure chamber. RESULTS: The mean relative uptakes of alpha-pinene, beta-pinene, and 3-carene were 62%, 66%, and 68% respectively, of the amount supplied. Between 2% and 5% of the net uptake was excreted unchanged in the expired air after the end of exposure. The mean blood clearance 21 hours after exposure (CL21h) of alpha-pinene, beta-pinene and 3-carene, were 0.8, 0.5, and 0.4 l.kg-1.h-1, respectively. The mean half lives (t1/2) of the last phase of alpha-pinene, beta-pinene, and 3-carene averaged 32, 25, and 42 hours, respectively. The t1/2s agreed with previously calculated half lives from single exposures. The total blood clearance CL21h of 3-carene found in this turpentine study was lower, and CL4h of 3-carene was significantly lower than the values obtained from similar exposure to pure 3-carene. The subjects attending both exposure to turpentine and to pure alpha-pinene at 450 mg/m3 had lower CL4h during the exposure to turpentine, when they experienced more discomfort of the throat or the airways (F = 5.7, P = 0.048) than during exposure to control concentrations. After experimental exposure to turpentine an increase in airway resistance was found that differed significantly from results of exposure to 3-carene at 10 mg/m3 (P = 0.021) or 450 mg/m3 (P = 0.047). CONCLUSIONS: Toxicokinetics and acute effects show small, if any, interactions between alpha-pinene, beta-pinene, and 3-carene. The subjects experienced discomfort in the throat and airways during exposure to turpentine and airway resistance was increased after the end of exposure.

Administration, Inhalation↗
PubMed1980

Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor.

Groups of 120 male and 120 female rats were exposed by inhalation to 0, 2, 6, or 15 ppm formaldehyde vapor 6 hr/day, 5 days/week, for 18 months of a 24-month study. The present communication describes interim findings based on data available after 18 months of exposure. Squamous cell carcinomas occurred in the nasal cavities of 36 rats exposed to 15 ppm formaldehyde. The tumors ranged from small early carcinomas of the nasal turbinate to large invasive osteolytic neoplasms which extended into the subcutis of the premaxilla. Similar tumors were not detected in rats exposed for 18 months to 2 or 6 ppm or in mice exposed to 2, 6, or 15 ppm formaldehyde. Rhinitis, epithelial dysplasia, and squamous metaplasia occurred in rats from all exposure levels of formaldehyde; however, the severity and extent of the lesions were dose related. In contrast, papillary hyperplasia and squamous atypia occurred only in animals exposed to 15 ppm formaldehyde.

Animals↗
PubMedDate not supplied

90-day repeated inhalation exposure of surfactant Protein-C/tumor necrosis factor-alpha, (SP-C/TNF-alpha) transgenic mice to air pollutants.

Tumor necrosis factor (TNF)-alpha, a cytokine present in inflammed lungs, is known to mediate some of the adverse effects of ozone and inhaled particles. The authors evaluated transgenic mice with constitutive pulmonary expression of TNF-alpha under transcriptional regulation of the surfactant protein-C promoter as an animal model of biological susceptibility to air pollutants. To simulate a repeated, episodic exposure to air pollutants, wild-type and TNF mice inhaled air or a mixture of ozone (0.4 ppm) and urban particles (EHC-93, 4.8 mg/m3) for 4 h, once per week, for 12 consecutive weeks and were sacrificed 20 h after last exposure. TNF mice exhibited chronic lung inflammation with septal thickening, alveolar enlargement, and elevated protein and cellularity in bronchoalveolar lavage fluid (genotype main effect, p < .001). Repeated exposure to pollutants did not result in measurable inflammatory changes in wild-type mice and did not exacerbate the inflammation in TNF mice. The pollutants decreased recovery of alveolar macrophages in tavage fluid of both wild-type and TNF mice (exposure main effect, p < .001). Exacerbation of the rate of protein nitration reactions specifically in the lungs of TNF mice was revealed by the high ratio of 3-nitrotyrosine to L-DOPA after exposure to the air pollutants (Genotype x Exposure factor interaction, p = .014). Serum creatine kinase-MM isoform increased in TNF mice exposed to pollutants (Genotype X Exposure factor interaction, p = .043). The marked pollutant-related nitration in the lungs of the TNF mice reveals basic differences in free radical generation and scavenging in the inflamed lungs in response to pollutants. Furthermore, elevation of circulating creatine kinase-MM isoform specifically in TNF mice exposed to pollutants suggests systemic adverse impacts from lung inflammatory mediators, possibly on muscles and the cardiovascular system.

Administration, Inhalation↗
PubMed2005

Physiologically based modeling of n-hexane kinetics in humans following inhalation exposure at rest and under physical exertion: impact on free 2,5-hexanedione in urine and on n-hexane in alveolar air.

We used a modified physiologically based pharmacokinetic (PBPK) to describe/predict n-hexane (HEX) alveolar air concentrations and free 2,5-HD urinary concentrations in humans exposed to n-HEX by inhalation during a typical workweek. The effect of an increase in workload intensity on these two exposure indicators was assessed and, using Monte Carlo simulation, the impact of biological variability was investigated. The model predicted HEX alveolar air concentrations at rest of 19.0 ppm (25 ppm exposure) and 38.7 ppm (50 ppm exposure) at the end of the last working day (day 5), while free 2,5-HD urinary concentrations of 3.4 micromol/L (25 ppm) and 6.3 micromol/L (50 ppm) were predicted for the same period (last 4.5 hours of Day 5). Monte Carlo simulations showed that the range of values expected to occur in a group of 1000 individuals exposed to 50 ppm of HEX (95% confidence interval) for free 2,5-HD (1.7-14.7 micromol/L) is much higher compared with alveolar air HEX (33.4-46 ppm). Simulations of exposure at 50 ppm with different workloads predicted that an increase in workload intensity would not greatly affect both indicators studied. However, the alveolar air HEX concentration is more sensitive to modifications of workload intensity and time of sampling, after the end of exposure, compared with 2,5-HD. The PBPK model successfully described the HEX alveolar air concentrations and free 2,5-HD urinary concentrations measured in human volunteers and is the first, to our knowledge, to describe the excretion kinetics of free 2,5-HD in humans over a 5-day period.

Exercise↗
PubMed1988

Mercapturic acid excretion by rats following inhalation exposure to 1,3-dichloropropene.

Rats were exposed to 1,3-dichloropropene (DCP), a commonly used agricultural nematicide, by inhalation to assess the relationship between DCP concentration and the urinary excretion of the mercapturic acid of cis-DCP (3C-NAC). The nose-only exposure system that was used for simultaneously exposing up to four rodents is described. This apparatus provided for generation and monitoring of relative humidity and test vapor concentration. Animals were exposed for 1 hr to concentrations of up to 789 ppm DCP. Urine was collected for 24 hr after exposure. The quantity of 3C-NAC contained in the urine collections exhibited an exposure concentration-dependent increase from 0 to 284 ppm DCP. However, the amount of 3C-NAC was no greater for animals exposed to 398 or 789 ppm DCP than for animals exposed to 284 ppm DCP.

Acetylcysteine↗
PubMed1988

Genotoxic effects of a sub-acute low-level inhalation exposure to a mixture of carcinogenic chemicals.

A study was conducted using a combined testing protocol (CTP), to determine whether short-term biological end-points, singly or in combination, are sufficiently sensitive to identify damage induced by exposure to ambient levels of industrial chemicals. A small-scale inhalation set-up which is both economical and easy to assemble was designed. Mice were exposed to 4 concentrations of a custom-blend mixture of benzene, chloroprene, epichlorohydrin and xylene in a ratio of 2:2:1:2, respectively. The concentrations for benzene, chloroprene and xylene were 0, 0.1, 1.0 and 10 ppm each. Concentrations for epichlorohydrin were half those for the other components. Groups of 22 males and 22 female mice were exposed to each concentration of the mixture for 3 and 6 weeks. Selected biological end-points including urine mutagenesis, bone marrow cell aberrations and micronuclei, spleen lymphocyte aberrations and liver enzyme induction were monitored. The spleen lymphocyte aberrations and liver enzyme induction were the most sensitive end-points. The lymphocytes showed a significant induction of chromosome aberrations from exposure for 3 weeks to all 3 concentrations of the mixtures. After 6 weeks of exposure, significant induction of aberrations was observed after exposure to low and medium concentrations but not to the high concentration. This lack of response at the high concentration after 6 weeks exposure, appeared to correlate with a significant induction of glutathione S-transferase in the liver. Since this enzyme is known to detoxify 3 of the 4 chemicals in our mixture, it may indicate a detoxification mechanism after enzyme induction. The present study indicates that the CTP is sufficiently sensitive to identify toxicological effects after exposure to ambient levels of a gas mixture.

Administration, Inhalation↗
PubMed1992

Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model.

An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper-reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1984

Kidney structural changes in rats following inhalation exposure to C10-C11 isoparaffinic solvent.

Kidney tissues from Fischer 344 rats exposed by inhalation to either 5.48, 1.83, or 0.0 g/m3 of C10-C11 isoparaffinic solvent vapor for 5, 20 and 40 days (6 h/day, 5 days/week), followed by a 4-week recovery period, were examined by light microscopy (LM) and electron microscopy (EM). At the LM level, an increased incidence of protein droplets was found in the cytoplasm of renal tubular epithelial cells of the exposed male rats relative to controls. Other renal changes observed by LM in the exposed male rats included foci of regenerative epithelium and tubular dilatation with intratubular protein occurring between the inner and outer stripe of the medulla. By EM, the protein droplets were electron dense, angular, crystalline-like structures which were surrounded by acid phosphatase positive reaction product corresponding to remnants of membrane-bound phagolysosomes. After 20 and 40 days of exposure there was focal loss of the brush border, with degeneration and sloughing of necrotic cells. Following a 4-week recovery period reversal of the exposure-related tubular changes was indicated by EM. The kidney changes observed in male rats following exposure to light hydrocarbons have not been observed in female rats or other species and may be unique to the male rat.

Acid Phosphatase↗
PubMed1987

Single inhalation exposure to 90SrCl2 in the beagle dog: hematological effects.

The toxicity of 90Sr administered by the inhalation route was studied in young adult Beagle dogs exposed once to aerosols containing 90SrCl2. Due to its relatively soluble chemical form, 90Sr was rapidly translocated from lung to bone where a substantial portion was retained for a long period of time. This resulted in only a brief radiation exposure of the respiratory tract and a protracted exposure of the skeleton. The long-term retained burdens ranged from 0.037 to 4.4 MBq 90Sr/kg body wt. Dogs were subsequently observed throughout their life span. Six dogs with long-term retained burdens of 1.7 to 4.1 MBq 90Sr/kg died at less than 32 days after exposure from radiation-induced bone marrow hypoplasia. Review of hematological parameters of all dogs showed a similar, consistent, and dose-related pancytopenia in those animals having a long-term retained burden of greater than 0.37 MBq 90Sr/kg. Thrombocytopenia and neutropenia persisted in all exposed dogs through 1000 days after exposure. For reference purposes, a burden of 0.37 MBq 90Sr/kg is calculated to deliver an average radiation dose to the skeleton over 30, 100, and 1000 days after intake of 1.0, 2.8, and 17 Gy, respectively. The hematologic changes were similar to those seen in people exposed to high doses of whole-body external radiation.

Administration, Inhalation↗
PubMed1991

Vestibular-oculomotor, opto-oculomotor and visual function in the rat after long-term inhalation exposure to toluene.

Pigmented rats were exposed to toluene (1000 ppm, 21 h/day) for 6 or 11 weeks. The function of the vestibulo- and opto-oculomotor systems was tested one month after the end of the exposure by recording of nystagmus, induced by vestibular or optokinetic stimuli. The eye movements were recorded by a magnetic search coil technique. The optokinetic gain in the exposed animals was reduced compared to a control group. There was also a slight reduction in gain during sinusoidal oscillatory vestibular stimulation. No effect of the toluene exposure on the gain or duration of nystagmus during acceleratory or deceleratory rotatory stimulation was demonstrated, nor was there any change in the duration of the optokinetic after-nystagmus. The function of the visual system was tested 2 to 5 days after exposure by recording the electroretinogram and the visual evoked response. The conduction velocity in peripheral nerve was also measured. No effect of the toluene exposure on these variables was seen. The results indicate that long-term inhalation of toluene causes a long-lasting, possibly permanent, lesion within the vestibulo-cerebellum. They gave no evidence that such exposure affects peripheral vestibular or visual function.

Administration, Inhalation↗
PubMed1989

Effect of four-week repeated inhalation exposure to unconjugated azodicarbonamide on specific and non-specific airway sensitivity of the guinea pig.

Reports of respiratory problems among industrial workers exposed repeatedly by inhalation to azodicarbonamide (ADA) raised concern that ADA might be a pulmonary sensitizer. We used a non-invasive method for measuring specific airway conductance to evaluate the potential for repeated inhalation of unconjugated ADA to cause specific or non-specific pulmonary sensitization in the guinea pig. Two groups of male Hartley guinea pigs were exposed 6 h/day, 5 days/week for 4 weeks to aerosolized ADA at 51 or 200 mg/m3, or to filtered air as controls. One group was tested for specific sensitization to ADA by measuring specific airway conductance during inhalation challenge with ADA before and on the third day after the 4-week ADA exposure. The ADA concentrations for the challenges were identical to the repeated exposure concentrations (51 or 200 mg/m3, 200 mg/m3 for controls). The other group was tested for non-specific airway sensitization by inhalation challenge with aerosolized histamine before and after the 4-week ADA exposure. Histamine was administered in stepwise increasing concentrations to elicit an airway response in each guinea pig. Skin tests for immunological responses to ADA, body weight and histopathology of the respiratory tract and skin test sites were also evaluated. The 4-week exposure to ADA did not result in either specific or non-specific airway sensitization. The ADA exposure did not induce positive skin reactions, influence body weight or cause histopathological responses. These results indicate that ADA, acting alone (i.e. not conjugated to a protein), is not a pulmonary sensitizer in the guinea pig exposed repeatedly for 4 weeks and challenged to simulate a 'Monday morning' exposure.

Administration, Inhalation↗
PubMed1995

Studies on the prenatal toxicity of 3-methyl-1-butanol and 2-methyl-1-propanol in rats and rabbits following inhalation exposure.

3-Methyl-1-butanol (MEB) and 2-methyl-1-propanol (MEP) were tested for their prenatal inhalation toxicity in pregnant Wistar rats or Himalayan rabbits. Twenty-five female rats and 15 female rabbits per group were exposed to MEB and MEP vapors at concentrations of 10, 2.5, or 0.5 mg/liter, 6 hr/day. The rats were exposed on Days 6-15 postcoitum (pc) and the rabbits were exposed on Days 7-19 postinsemination (pi). Control groups were exposed to clean air. The body weights of the animals of either species were determined several times throughout the studies. All rats and all rabbits were killed on Day 20 pc and Day 29 pi, respectively. The fetuses were removed from the uterus and examined for compound-related effects. The high concentration of 10 mg/liter caused a slight retardation of body weight gain in the dams of either species exposed to MEB and in the dams of rabbits exposed to MEP during the first days of the exposure period. Eye irritation was observed only in the MEB-treated rabbits during the period of exposure to 10 mg/liter. The fetuses of either species exhibited no signs of embryo-/fetotoxicity or teratogenic effects caused by MEP or MEB. Under the experimental conditions, 2.5 mg/liter was found to be a no-observable-adverse-effect level (NOAEL) for the dams of either species exposed to MEB and for the does exposed to MEP, whereas 10 mg/liter MEP was the NOAEL for the maternal rats. For both substances 10 mg/liter was defined as the NOAEL for the conceptuses of either species.

Abnormalities, Drug-Induced↗
PubMed1993

Enhanced hepatic expression of P450IIE1 following inhalation exposure to pyridine.

Previous research has shown that intraperitoneal injection of the solvent pyridine results in a dose- and time-dependent induction of hepatic P450IIE1 in rats, with a twofold increase observed at 6 hr post-treatment. However, inhalation is the primary route of exposure expected for humans exposed to pyridine in laboratory and industrial settings or in tobacco smoke. In view of the potency and rapidity of induction associated with pyridine treatment, research was initiated to examine whether inhalation of the solvent at the current threshold limit value level of 5 ppm or at an elevated level of 440 ppm resulted in sufficient nasal and pulmonary uptake and systemic redistribution to cause increased hepatic expression of rat cytochrome P450IIE1. Rats were exposed, 6 hr/day, to 5 ppm pyridine for 4 days; to 440 ppm pyridine for 1 or 4 days; or to filtered air for 1 or 4 days. Rats were sacrificed 18 hr after the last exposure. Liver samples were taken from the air- and pyridine-exposed rats. Expression of immunoreactive P450IIE1 was examined in tissue sections using immunohistochemistry and in microsomal preparations using Western blot analyses. Hepatic tissue obtained from rats exposed to 5 ppm pyridine for 4 days or to 440 ppm pyridine for 1 or 4 days displayed significantly elevated levels of immunoreactive P450IIE1. Immunohistochemical analyses of liver sections showed that inhalation of pyridine at 5 ppm resulted in an elevated expression of P450IIE1 in hepatocytes surrounding terminal hepatic venules (THVs). Exposure to 440 ppm pyridine caused both increased expression of IIE1 in hepatocytes surrounding THVs after a single 6-hr exposure and an approximately three- to fourfold increase in the total number of cells expressing IIE1 after 4 days of exposure. Dilution analysis of immunohistochemically stained tissue revealed a significant difference between air-exposed controls and pyridine-exposed rats, at all exposure levels. P450IIE1 levels in microsomes isolated from rats receiving 5 and 440 ppm pyridine for 4 days were increased 2.5- and 10-fold as judged from scanning laser densitometry. This study reveals that inhalation of pyridine vapors at levels equal to or greater than the current threshold limit value of 5 ppm results in significant hepatic induction of P450IIE1 in rats.

Administration, Inhalation↗