Ppm Isoprene Research Articles

Improved isoprene detection performance of Si-doped WO3 films deposited by sputtering and post-annealing.

Si-doped WO3 films were sputtered at room temperature and then annealed in air at 500 °C. The Si doping resulted in structural distortion from space group P21/n to Pc. A high density of pores with a diameter of ∼20 nm was observed in the films, which is ideal for gas sensing applications because of the easy diffusion of gas. Isoprene sensitivity, which is defined as the resistance ratio measured in pure air and in air containing 5 ppm isoprene, was greatly improved by the Si doping. The films containing 6.3 at% Si showed the highest sensitivity of 7.7 at a working temperature of 325 °C. However, despite a lower sensitivity of 6.9 measured at 350 °C, the films exhibited better gas selectivity for isoprene over a range of reference gases, including methanol, ethanol, acetone, CO and CO2. The response and recovery times of the films were very short, being less than 1.5 and 3.0 seconds, respectively. Detailed characterization with a range of techniques verified that the increase in gas sensitivity in the Si-doped films was related to better oxygen adsorbability as a consequence of an increase in positively-charged oxygen vacancies introduced by the aliovalent substitution of W6+ by Si4+.

Photooxidation potential of fine particles from desulfurization flue gas aerosol

In China, desulfurization flue gas from coal-fired power plants (CFPPs) has been the focus of research for many years. In this study, for the first time, we simulated the emission process of flue gas and prepared photocatalysts by deposition. An innovative photocatalytic perspective was applied to study the composition, photocatalytic properties, hygroscopicity, and redox properties of the fine particles from flue gas aerosols. The characterization results of XRD, HRTEM, and XPS of freeze-dried desulfurized flue gas samples indicated that aerosol condensation occurred during the smoke plume transportation process, resulting in the formation of well-crystallized fine particles primarily consisting of soluble salts and metal oxides. The UV–vis and ESR results confirmed that desulfurized flue gas has UV light utilization and photocatalytic potential for producing oxidation groups such as hydroxyl radicals and superoxide radicals in light. The subsequent photocatalyst experiments revealed an 85.4 % reduction of 7 ppm isoprene in 30 min; ozone production (373 μg/m3) was observed under more complicated conditions (NO2 = 80 ppb, VOCs = 7 ppm). As a result of the study, a new research approach was proposed for exploring the photoactive potential of flue gas aerosol produced by CFPPs, as well as its impact on the concentration of VOCs and ozone. The finding provided a new possible pathway for desulfurization flue gas emissions and a reference for futureresearch on the observation and control of atmospheric pollution.

ZIF-8 micro-polyhedron MOF-transformed ZnO/ZnFe2O4 nanosheets for highly selective detection of ppb-level isoprene

Isoprene as a toxic volatile organic compound usually harms human health. Instead, exhaled isoprene may serve as a versatile biomarker in diagnosing blood cholesterol and chronic liver disease. However, such isoprene sensing that is simultaneously required with ppb-level detection limit and excellent selectivity, it is still less than satisfactory. Here, a highly selective and ppb-level isoprene sensing has been developed with ZnO/ZnFe2O4 nanosheets (NSTs), which is transformed from ZIF-8 micro-polyhedron metal-organic framework (MOF). Typically, the ZnO/ZnFe2O4 NSTs are observed of ∼ 60 nm thick and heterojunction between ZnO and ZnFe2O4. Beneficially, the ZnO/ZnFe2O4 NSTs show a higher response to 1 ppm isoprene (Ra/Rg = 19.7) than that of ZnO micro-polyhedrons (Ra/Rg = 3.6) at 120 °C. Remarkably, the ZnO/ZnFe2O4 NSTs display a detection limit as low as 2 ppb and a high selectivity to isoprene even being exposed to multiple interfering gases. Theoretically, a large specific surface of ZnO/ZnFe2O4 NSTs and as-formed heterojunction between ZnO and ZnFe2O4 may widen the electron depletion layer, adsorbing more chemisorbed oxygen species to oxidize isoprene. The approach to ZnO/ZnFe2O4 NSTs might be extended to NSTs of other sensing materials and target gases, which is potential in upcoming intelligent medical diagnosis.

A New Perspective towards Diagnosis of Sleep Apnea: Isoprene Detection Using PSSA-g-PANI based SAW Sensor

Cellular metabolic changes triggered by Obstructive Sleep Apnea Syndrome (OSAS) are detected invasively by detecting isoprene as a biomarker of OSAS in the breath. When falling asleep, isoprene level begins to increase above 3 ppm. Therefore, monitoring isoprene levels in exhaled breath under normal conditions may provide a non-invasive method to detect, monitor, and control sleep disorders such as sleep apnea. In this study, PSSA-g-PANI based SAW gas sensors were prepared and tested against isoprene gas. Sensor measurements reveal that PSSA-g-PANI based SAW type sensor detected (1-150) ppm isoprene gas with high sensitivity and thus PSSA-g-PANI based SAW type sensor may enable monitor and control of sleep apnea.

Highly Selective and Sensitive Detection of Breath Isoprene by Tailored Gas Reforming: A Synergistic Combination of Macroporous WO3 Spheres and Au Catalysts.

Precise detection of breath isoprene can provide valuable information for monitoring the physical and physiological status of human beings or for the early diagnosis of cardiovascular diseases. However, the extremely low concentration and low chemical reactivity of breath isoprene hamper the selective and sensitive detection of isoprene using oxide semiconductor chemiresistors. Herein, we report that macroporous WO3 microspheres whose inner macropores are surrounded by Au nanoparticles exhibit a high response (resistance ratio = 11.3) to 0.1 ppm isoprene under highly humid conditions at 275 °C and an extremely low detection limit (0.2 ppb). Furthermore, the sensor showed excellent selectivity to isoprene over five interferants that could be exhaled by humans. Notably, the selectivity to isoprene is critically dependent on the location of Au nanocatalysts and macroporosity. The mechanism underlying the selective isoprene detection is investigated in relation to the reforming of less reactive isoprene into more reactive intermediate species promoted by macroporous catalytic reactors, which is confirmed by the analysis using a proton transfer reaction quadrupole mass spectrometer. The sensor for breath analysis has high potential for simple physical and physiological monitoring as well as disease diagnosis.

Enhanced isoprene gas sensing performance based on p-CaFe2O4/n-ZnFe2O4 heterojunction composites

Isoprene, a toxic volatile organic compound, is harmful to the human body. It is of great application value to develop gas sensing materials for the effective detection of isoprene. In this work, the CaFe2O4, ZnFe2O4 and CaFe2O4/ZnFe2O4 composites are successfully synthesized by hydrothermal approach. Especially, the CaFe2O4/ZnFe2O4-50% presents porous walnut-like structure and exhibits the superior gas sensing properties to isoprene, including a high response to 30 ppm isoprene (S=19.50), low working temperature (200 °C) and fast response-recovery time (~72–35 s). Moreover, the CaFe2O4/ZnFe2O4-50% based sensor also achieves good selectivity, excellent humidity resistance, long-term stability and LOD as low as 0.12 ppb. Further analysis demonstrates that the outstanding gas sensing properties of CaFe2O4/ZnFe2O4-50% can be attributed to the improvement of electron-hole (e--h+) separation rate, the decrease of charge transfer resistance, the high content of OV, large BET surface area, the narrowed band gap and the formation of CaFe2O4/ZnFe2O4 p-n heterojunctions. These results indicate that appropriate CaFe2O4 coupled with ZnFe2O4 to form CaFe2O4/ZnFe2O4 is a promising strategy to achieve a superior isoprene gas sensor.

Hierarchical Pt-decorated In2O3 microspheres with highly enhanced isoprene sensing properties

For advanced fibrosis, isoprene is a typical characteristic marker that could be used to quickly screen the population for chronic liver disease (CLD). To achieve trace detection of isoprene, different mol% Pt-decorated In2O3 and pure In2O3 samples were prepared with the commonly used hydrothermal method. The obtained characterization results show that the prepared Pt-decorated In2O3 (1 mol%) sample had Pt nanoparticles uniformly attached to the surface of porous hierarchical In2O3 nanosheets, and the specific surface area was 62.3 m2/g. Subsequently, these sensors based on Pt–In2O3 and pure In2O3 nanomaterials were prepared, and their response characteristics were studied. The results show that the response of 1 mol% Pt–In2O3 to isoprene gas was significantly enhanced, and the optimal working temperature was 200 °C. The response of 1 mol% Pt–In2O3 to 5 ppb and 5 ppm isoprene was approximately 3.2 times and 25.9 times that of pure In2O3, respectively. Meanwhile, the 1 mol% Pt-modified sample exhibited excellent selectivity for isoprene relative to other biomarkers (carbon monoxide, hydrogen, ethanol, and ammonia). The sensor shows good repeatability and long-term stability. Therefore, the developed 1 mol% Pt-decorated In2O3 was expected to be applied as a gas-sensitive material for breath isoprene, which could be suitable for large-scale CLD rapid breath detection.

Excellent isoprene-sensing performance of In2O3 nanoparticles for breath analyzer applications

We report the sensing performance of In2O3 nanoparticles (NPs) synthesized by a co-precipitation method for the detection of isoprene. The as-synthesized In2O3 NPs exhibited excellent isoprene-sensing performance compared to other previously reported isoprene sensors based on metal-oxide semiconductors. Under an exposure of 1 ppm isoprene at an optimal operating temperature of 350 ℃, the In2O3 NP sensor showed the highest sensing response of ∼231 with a rapid response time of ∼3 s. The low detection limit was approximately 0.001 ppm of isoprene. Furthermore, the In2O3 NP sensor showed a good long-term stability for 90 days by controlling the annealing time. In addition, for the sensor’s practical applications to a breath isoprene analyzer, we tested the sensing ability of the In2O3 NPs by integrating the sensor into a miniaturized gas analyzer based on gas chromatography (GC). The results revealed that the In2O3 NP sensor is sensitive and can distinctly detect 1 ppm isoprene and 10 ppm H2 within ∼100 s in a mixture gas with other breath gases, such as acetone, CO2, CO, and CH4. Our study demonstrated the potential of the In2O3 NP sensor for application in breath isoprene analyzers by controlling the sensor’s annealing time and adopting the GC system.

Selective Breath Isoprene Detection By Filter-Enhanced Sensors

Introduction Breath analysis enables revolutionary, on-demand detection and monitoring of health parameters in a noninvasive and personalized fashion. Breath isoprene is a byproduct of the cholesterol biosynthetic pathway [1] and has been shown to decrease during a cholesterol lowering therapy [2]. However, altered breath isoprene levels can indicate a variety of pathological and physiological states in the human body such as muscle activity, influenza [3], end-stage renal disease, lung cancer or liver disease with advanced fibrosis. Thus, accurate measurement and monitoring of breath isoprene levels by a breath analyzer are promising for non-invasive detection or monitoring of such conditions.Chemical gas sensors are simple to use, offer low cost and high miniaturization potential, and they can detect volatile organic compounds at ppb concentrations [4]. However, they are typically not selective enough to monitor isoprene in a complex gas mixture such as breath. Here, we address this by combining a micromachined gas sensor with a miniaturized separation column of activated alumina [5]. Method The isoprene sensor consists of a compact separation column placed upstream of a chemoresistive microsensor. The separation column is a packed bed of 100 mg activated alumina (50–300 mesh, ~155 m2 g-1) inside a Teflon tube (4 mm inner diameter) and secured on both ends with silanized quartz wool. For the sensor, sensing nanoparticles of Pt-doped SnO2 (0.1 mol% Pt) are produced by flame-spray pyrolysis (FSP) and deposited directly onto micromachined sensor substrates (1.9 x 1.7 mm2) by thermophoresis. Sensing films are heated to 400 °C by providing DC current to the back heater of the sensor substrate. The isoprene sensor is characterized with synthetic gas mixtures using a dynamic mixing setup. Results and Conclusions Figure 1 shows the isoprene sensor consisting of a compact filter placed upstream of a chemoresistive microsensor. The filter contains a polar adsorbent that retains hydrophilic compounds (e.g., ketones, alcohols, ammonia) —representing major interferants in breath and ambient air—while hydrophobic isoprene is not affected and detected selectively by the highly sensitive microsensor. Commercial activated alumina is used as sorbent offering high surface area (~155 m2 g-1) and polarity, resulting in compact (1 cm length) and inexpensive (<1 $) filters. The microsensor is heated by a free-standing membrane-type heater, offering low power requirement (only 85 mW at 400 °C) suitable for battery-driven operation.The filter does not retain isoprene, which is detected by the sensor with fast response and recovery times (5 and 10 s, respectively). The flame-made Pt-doped SnO2 sensor is highly sensitive due to its porous and nanostructured morphology, enabling detection of only 5 ppb of isoprene with high signal-to-noise ratio (>90). When exposing the sensor with filter to 60 s pulses of 1 ppm isoprene, acetone, methanol and ethanol, only isoprene is detected during the exposure, while the hydrophilic analytes are held back (Figure 2). As a result, isoprene is detected without interference (i.e., with very high selectivity). Even when operated continuously for eight days, this sensor showed stable performance with reproducible (regeneration within 10 min) and accurate isoprene detection in simulated breath mixtures composed of breath-relevant concentrations of isoprene, acetone, methanol and ammonia.The filter is modular and, based on its small size and low price, can be readily integrated into inexpensive and portable isoprene detectors. This is promising for non-invasive measurement of blood cholesterol levels from.

Highly sensitive and selective isoprene sensing performance of ZnO quantum dots for a breath analyzer

We report the quantum-size effect on the sensing properties of ZnO nanoparticles for the detection of isoprene. For this purpose, two types of ZnO particles with different sizes, including nanoparticles (NPs, ˜25 nm) and quantum dots (QDs, ˜5 nm), were prepared by a wet chemical method. The ZnO QDs exhibited excellent sensing performance to 1 ppm isoprene compared to NPs. The maximum sensing response and response time were ˜42 and 8 s at 350 °C for the QDs, while ˜5.6 and 40 s at 500 °C for the NPs, respectively. The higher sensing response, rapid response, and lower optimal working temperature of the ZnO QDs can be attributed to an increase in oxygen vacancies, band gap, and specific surface area owing to the small size effect. Both ZnO NPs and QDs showed the lower limit of 0.01 ppm for detecting isoprene. It is noted that the sensing properties of ZnO QDs to 1 ppm isoprene are superior to previously reported isoprene sensors that are based on semiconducting metal oxides. Furthermore, we demonstrated that the low concentration (0.4–6.2 ppm) of isoprene can be selectively detected within ˜83 s using a recently developed miniaturized gas chromatography integrated with the ZnO QD sensor.

Ultra-Low NO2 Detection By Gamma WO3 Synthesized By Reactive Spray Deposition Technology

A porous tungsten oxide (WO3) film based NO2 sensor was developed by a one-step flame based process called Reactive Spray Deposition Technology (RSDT). The RSDT process allows the flexibility to create monoclinic gamma-WO3 with control of the particle size, porosity and thickness of the film. This nano-crystalline WO3 film was deposited directly on gold interdigitated electrodes. The sensor response was measured at the parts per million (ppm) level, (0.17-5 ppm in air at 100% relative humidity) at different operating temperatures (250-350°C) to determine the optimum working temperature. The sensitivity was found to be maximum at 300 °C. The sensors showed a relatively fast response time (∼7s) and recovery time (∼5 min), respectively. The stability of the sensor was evaluated for 300 h in 0.5 ppm NO2 in air at 100% relative humidity (2000 response-recovery cycles). The sensor was stable up to 6 days (~150 h) of continuous operation and degraded between 150 to 300 h. In order to check the selectivity, the sensor was also tested for 10 ppm acetone, 100 ppm ethanol, 10-100 ppm H2, and 10 ppm isoprene. Interference was negligible with 10 ppm acetone, 100 ppm ethanol, 10 ppm H2 and humidity; however, it was significant with 10 ppm isoprene and 100 ppm H2. We have also compared the test data of this gamma WO3 based NO2 sensor prepared by RSDT with the results reported in the literature. The morphology and surface properties of the WO3 film were investigated with XRD, Raman spectroscopy, BET, SEM, TEM, and HRTEM. Here we will provide a brief description of the synthesis, fabrication and testing procedure of the NO2 sensor. The microstructure of the tungsten oxide films, and the effect of the film structure, grain size, and the sensor response to the ppm level concentration of NO2 will be described. The sensing mechanism with emphasis to adsorption and desorption will be explained in details.

Biochemical Characterization and Homology Modeling of Methylbutenol Synthase and Implications for Understanding Hemiterpene Synthase Evolution in Plants

2-Methyl-3-buten-2-ol (MBO) is a five-carbon alcohol produced and emitted in large quantities by many species of pine native to western North America. MBO is structurally and biosynthetically related to isoprene and can have an important impact on regional atmospheric chemistry. The gene for MBO synthase was identified from Pinus sabiniana, and the protein encoded was functionally characterized. MBO synthase is a bifunctional enzyme that produces both MBO and isoprene in a ratio of ~90:1. Divalent cations are required for activity, whereas monovalent cations are not. MBO production is enhanced by K(+), whereas isoprene production is inhibited by K(+) such that, at physiologically relevant [K(+)], little or no isoprene emission should be detected from MBO-emitting trees. The K(m) of MBO synthase for dimethylallyl diphosphate (20 mm) is comparable with that observed for angiosperm isoprene synthases and 3 orders of magnitude higher than that observed for monoterpene and sesquiterpene synthases. Phylogenetic analysis showed that MBO synthase falls into the TPS-d1 group (gymnosperm monoterpene synthases) and is most closely related to linalool synthase from Picea abies. Structural modeling showed that up to three phenylalanine residues restrict the size of the active site and may be responsible for making this a hemiterpene synthase rather than a monoterpene synthase. One of these residues is homologous to a Phe residue found in the active site of isoprene synthases. The remaining two Phe residues do not have homologs in isoprene synthases but occupy the same space as a second Phe residue that closes off the isoprene synthase active site.

Formation of Strong Airway Irritants in Mixtures of Isoprene/Ozone and Isoprene/Ozone/Nitrogen Dioxide

We evaluated the airway irritation of isoprene, isoprene/ozone, and isoprene/ozone/nitrogen dioxide mixtures using a mouse bioassay, from which we calculated sensory irritation, bronchial constriction, and pulmonary irritation. We observed significant sensory irritation (approximately 50% reduction of mean respiratory rate) by dynamically exposing the mice, over 30 min, to mixtures of isoprene and O3 or isoprene, O3, and NO2. The starting concentrations were approximately 4 ppm O3 and 500 ppm isoprene (+ approximately 4 ppm NO2. The reaction mixtures after approximately 30 sec contained &lt; 0.2 ppm O3. Addition of the effects of the residual reactants and the identified stable irritant products (formaldehyde, formic acid, acetic acid, methacrolein, and methylvinyl ketone) could explain only partially the observed sensory irritation. This suggests that one or more strong airway irritants were formed. It is thus possible that oxidation reactions of common unsaturated compounds may be relevant for indoor air quality.

Formation of strong airway irritants in mixtures of isoprene/ozone and isoprene/ozone/nitrogen dioxide.

We evaluated the airway irritation of isoprene, isoprene/ozone, and isoprene/ozone/nitrogen dioxide mixtures using a mouse bioassay, from which we calculated sensory irritation, bronchial constriction, and pulmonary irritation. We observed significant sensory irritation (approximately 50% reduction of mean respiratory rate) by dynamically exposing the mice, over 30 min, to mixtures of isoprene and O3 or isoprene, O3, and NO2. The starting concentrations were approximately 4 ppm O3 and 500 ppm isoprene (+ approximately 4 ppm NO2. The reaction mixtures after approximately 30 sec contained < 0.2 ppm O3. Addition of the effects of the residual reactants and the identified stable irritant products (formaldehyde, formic acid, acetic acid, methacrolein, and methylvinyl ketone) could explain only partially the observed sensory irritation. This suggests that one or more strong airway irritants were formed. It is thus possible that oxidation reactions of common unsaturated compounds may be relevant for indoor air quality.

Both K-ras and H-ras protooncogene mutations are associated with Harderian gland tumorigenesis in B6C3F1 mice exposed to isoprene for 26 weeks.

Isoprene is the 2-methyl analog of 1,3-butadiene, a genotoxic and carcinogenic compound in rats and mice. Male B6C3F1 mice were exposed to 0, 2200 or 7000 ppm isoprene by inhalation (6 h/day; 5 days/week) for 26 weeks. Following a 26-week recovery period, an increased incidence of Harderian gland (HG) neoplasms was observed at both concentrations. The present study was designed to characterize genetic alterations in the K-ras and H-ras protooncogenes in HG neoplasms. Mutations in K-ras and H-ras were identified by single-strand conformational analysis and direct sequencing of polymerase chain reaction (PCR) amplified DNA, isolated from paraffin-embedded sections of HG neoplasms. A higher frequency of ras mutations, in particular K-ras mutations, was detected in isoprene-induced neoplasms than in 1,3-butadiene-induced or control HG neoplasms. All of the isoprene-induced HG neoplasms exhibited activated K-ras (60%) or H-ras (40%) mutations. In contrast, ras mutations were detected in 69% of HG neoplasms from 1,3-butadiene exposed mice (14% K-ras and 55% H-ras) and in 56% of HG neoplasms obtained from control B6C3F1 mice (8% K-ras and 48% H-ras). The predominant mutations in isoprene-induced HG neoplasms, but not in previously or newly analysed 1,3-butadiene-induced HG neoplasms, consisted of A-->T transversions (CAA-->CTA) at K-ras codon 61 (15/30) and C-->A transversions (CAA-->AAA) at H-ras codon 61 (8/30). Two-thirds of the K-ras CTA mutations were detected in HG neoplasms from the 2200 ppm exposure group while one-third was present in the 7000 ppm group. Isoprene-induced HG neoplasms with K-ras or H-ras mutations had an elevated proliferating cell nuclear antigen (PCNA) index, compared to spontaneous HG neoplasms without ras mutations. The high frequency and specificity of the ras mutation profile suggest that ras protooncogene activation contributes to isoprene-induced HG tumorigenesis.

Inhalation toxicity and carcinogenicity of isoprene in rats and mice: comparisons with 1,3-butadiene

As with 1,3-butadiene (BD), inhalation exposure of B6C3F 1 mice to isoprene (2-methyl-1,3-butadiene) caused a macrocytic anemia; induced increases in sister chromatid exchanges in bone marrow cells and in levels of micronucleated erythrocytes in peripheral blood; and produced degeneration of the olfactory epithelium, forestomach epithelial hyperplasia, and testicular atrophy. Most notable was the finding that like BD, isoprene induced neoplasms in the liver, lung, Harderian gland, and forestomach of mice. The carcinogenic effects of isoprene were observed after a 26-week exposure (6 h/day, 5 days/week) of male mice to 700 ppm or higher concentrations of isoprene followed by a 26-week recovery period. Unlike BD, isoprene did not induce lymphomas or hemangiosarcomas of the heart in mice under these conditions nor did it induce chromosomal aberrations in mouse bone marrow cells. No toxicological effects were evident in rats exposed for 13 weeks to either isoprene or BD at concentrations up to 7000 ppm or 8000 ppm, respectively. Interstitial cell hyperplasia of the testis was observed in male F344 rats exposed to 7000 ppm isoprene for 26 weeks, and following a 26-week recovery period, there was a marginal increase in benign testicular interstitial cell tumors.

Disposition of inhaled isoprene in B6C3F 1 mice

Isoprene (2-methyl-1,3-butadiene) is the monomeric unit of widely occurring natural products called terpenes. Isoprene is widely used in industry with nearly 1.1 million pounds produced in the United States in 1987. The purpose of this investigation was to determine the toxicokinetics of inhaled isoprene in B6C3F 1 mice and to compare the data to previously published toxicokinetic data in F344 rats (A. R. Dahl, L. S. Birnbaum, J. A. Bond, P. G. Gervasi, and R. F. Henderson, 1987, Toxicol. Appl. Pharmacol. 89, 237–248). The comparative toxicokinetics in the two species will be useful for extrapolation of rodent toxicity data to humans. Male B6C3F 1 mice were exposed to nominal concentrations of 20, 200, and 2000 ppm isoprene or [ 14C]isoprene for up to 6 hr. For all exposures, steady-state levels of isoprene were reached rapidly (i.e., within 15 to 30 min) after the onset of exposure. The mean (±SE) steady-state blood levels of isoprene (identified by headspace analysis) for the 20, 200, and 2000 ppm exposures were 24.8 ± 3.3, 830 ± 51, and 6800 ± 400 ng isoprene/ml blood, respectively. At the two higher exposure concentrations, the increases in blood levels of isoprene were proportional to the increases in air concentrations of isoprene. There was approximately a 2.3-fold decrease in the retained 14C/inhaled 14C ratio with increasing exposure concentration. Depending on the exposure concentration, from 52% (20 ppm isoprene) to 73% (2000 ppm isoprene) of the metabolite-associated (nonisoprene) radioactivity was excreted in the urine over a 64-hr postexposure period. 14CO 2 exhalation after the end of the 6-hr exposure was minimal (2%) at the 20 ppm exposure and increased up to 18% at the higher isoprene exposure concentrations. These data suggest that metabolism of isoprene in mice is nonlinear within the range of exposure concentrations used in this study. Hemoglobin adduct formation reached near-maximum between 200 and 2000 ppm isoprene exposure concentration, consistent with our conclusion that pathways for metabolism of isoprene were saturated. Isoprene metabolites were present in blood after inhalation of isoprene at all concentrations studied. There were substantial differences in the toxicokinetics of inhaled isoprene in mice compared to rats. In mice, fractional retention of inhaled isoprene, which reflects, in part, metabolism of isoprene, was linearly related to exposure concentrations up to 200 ppm but decreased at 2000 ppm; in rats, fractional retention of inhaled isoprene decreased with increasing exposure concentration over a range of exposures from 8 to 1500 ppm. Rats metabolized a greater fraction of the inhaled isoprene than did mice at all exposure concentrations. The differences in uptake and disposition between the two species should be considered in extrapolation of rodent data to humans.

Inhalation Pharmacokinetics of Isoprene in Rats and Mice

Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.

Inhalation pharmacokinetics of isoprene in rats and mice.

Studies on inhalation pharmacokinetics of isoprene were conducted in rats (Wistar) and mice (B6C3F1) to investigate possible species differences in metabolism of this compound. Pharmacokinetic analysis of isoprene inhaled by rats and mice revealed saturation kinetics of isoprene metabolism in both species. For rats and mice, linear pharmacokinetics apply at exposure concentrations below 300 ppm isoprene. Saturation of isoprene metabolism is practically complete at atmospheric concentrations of about 1000 ppm in rats and about 2000 ppm in mice. In the lower concentration range where first-order metabolism applies, metabolic clearance (related to the concentration in the atmosphere) of inhaled isoprene per kilogram body weight was 6200 mL/hr for rats and 12,000 mL/hr for mice. The estimated maximal metabolic elimination rates were 130 mumole/hr/kg for rats and 400 mumole/hr/kg for mice. This shows that the rate of isoprene metabolism in mice is about two or three times that in rats. When the untreated animals are kept in a closed all-glass exposure system, the exhalation of isoprene into the system can be measured. This shows that the isoprene endogenously produced by the animals is systemically available within the animal organism. From such experiments the endogenous production rate of isoprene was calculated to be 1.9 mumole/hr/kg for rats and 0.4 mumole/hr/kg for mice. Our data indicate that the endogenous production of isoprene should be accounted for when discussing a possible carcinogenic or mutagenic risk of this compound.

Mechanisms of cigarette smoke toxicity: the inactivation of human α-1-proteinase inhibitor by nitric oxide/isoprene mixtures in air

A mixture of nitric oxide (NO) and isoprene in air has been studied as a model for gas-phase cigarette smoke. We have shown that this model system duplicates many of the properties of cigarette smoke including the inactivation of human alpha-1-proteinase inhibitor (a1PI). In this study, buffered solutions of a1PI were exposed to puffs of air containing 300 ppm NO and 400 ppm isoprene. Bubbling of the NO/air/isoprene gas stream directly through buffered protein solutions causes a1PI to undergo a fast loss of inhibitory capacity. This fast inactivation is not observed when a1PI is exposed to aqueous extracts of the NO/air/isoprene mixture. Both direct exposure and exposure to aqueous extracts, however, cause a1PI to undergo a slow loss of activity that continues for several days as the protein is incubated in the buffer solutions. Gas-phase cigarette smoke has already been shown to cause this same two-phase inactivation of a1PI. The inactivation of a1PI by the model system is dependent on the presence of oxygen in the gas stream, suggesting that the oxidation of nitric oxide to nitrogen dioxide in air is involved in the formation of the inactivating species. The nature of these species remains to be determined; however, small alkoxyl or peroxyl radicals (such as are spin-trappable from gas-phase smoke as well as from the NO/air/isoprene system) do not appear to inactivate a1PI. One possibility is that the inactivating species are metastable compounds formed by radical processes in the gas phase of both cigarette smoke and our model system. Our data suggest that one possible class of species is peroxynitrates.