Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Inhalation Exposure”

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

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

At least 1,207 records · Page 67Linked to original sources
PubMed1998

Urinary 2,5-hexanedione increases with potentiation of neurotoxicity in chronic coexposure to n-hexane and methyl ethyl ketone.

OBJECTIVE: MEK (methyl ethyl ketone) is widely and frequently used as an ingredient of mixed solvents together with n-hexane. MEK is known to decrease urinary levels of 2,5-hexanedione dose-dependently in an acute or chronic coexposure with a constant level of n-hexane. This change in urinary 2,5-hexanedione appears to contradict the potentiation effect of MEK on n-hexane-induced neurotoxicity because it is believed that the toxicity of n-hexane is activated through n-hexane metabolism. We aimed to clarify how the urinary level of 2,5-hexanedione changes when MEK modifies the degree of n-hexane-induced neurotoxicity. METHOD: A total of 32 male Wistar rats were divided into 4 groups of 8 each and were then exposed to fresh air only, 2000 ppm n-hexane only, 2000 ppm n-hexane plus 200 ppm MEK, and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Inhalation exposures were performed 12 h/day, 6 days/week, for 20 weeks. Motornerve conduction velocity (MCV), distal latency (DL), and urinary 2,5-hexanedione were measured every 4 weeks. RESULTS: The MCV decreased, the DL increased, and urinary levels of 2,5-hexanedione increased in the 2000-ppm n-hexane plus 200 ppm MEK group in comparison with the 2000-ppm n-hexane only group following 4 weeks' exposure. On the 1st day of exposure, however, coexposure to MEK decreased urinary levels of 2,5-hexanedione dose-dependently. CONCLUSIONS: The present study showed that urinary concentrations of 2,5-hexanedione increased with potentiation of n-hexane neurotoxicity. Urinary 2,5-hexanedione concentration does not necessarily reflect the exposure concentration of n-hexane in coexposure to n-hexane along with MEK or other solvents, but it may be useful as a marker in the assessment of neurotoxicity in coexposure to n-hexane and other solvents.

Animals↗
PubMed2001

Inhalation toxicity of Dioxole and Dioxolane compounds in the rat.

Four chemicals (Dioxole 418, Dioxolane 418, Dioxolane 416 and Dioxolane 456) which are used as stabilizers in highresolution image were tested or both their acute and repeated inhalation toxicity in the rat using nose-only exposures. Acute studies determined the lethal concentrations following a single 4-hour exposure; repeated exposure inhalation studies determined the potency and target tissue(s) following 6-hour/day exposures, 5 days/week for 2 weeks. Each of the chemicals was at least mildly toxic acutely with approximate lethal concentrations of > 1,500 ppm for Dioxole 418, 1,300 ppm for Dioxolane 418, 1,700 ppm for Dioxolane 416, and 4,300 ppm for Dioxolane 456. No specific unusual clinical signs of response were seen in the rats exposed acutely. Repeated exposures with Dioxole 418 and Dioxolane 418 resulted in no evidence of toxicity with NOAEL's being 440 and 500 ppm respectively (the highest concentrations tested). Repeated exposures to 250 ppm Dioxolane 456 were not tolerated with mortalities observed after exposure. Severe bone marrow hypoplasia along with reductions in platelet and neutrophil counts were observed at this concentration with less severe hemopoietic changes seen also at 10 and 51 ppm. The no-effect level for Dioxolane 456 was determined to be 10 ppm in female rats and I ppm in males. The same hemopoietic effects were seen with Dioxolane 416 at exposures of 53 ppm or greater in males but not in females exposed to 53 ppm Dioxolane 416. Hepatocellular hypertrophy and depression of serum alkaline phosphatase activity were seen in male rats exposed to 500 but not 53 ppm Dioxolane 416. Testicular degeneration was also seen in rats exposed to 500 ppm Dioxolane 416. The NOAEL was 5 ppm for the chemical.

Administration, Inhalation↗
PubMed2001

A PBPK modeling-based approach to account for interactions in the health risk assessment of chemical mixtures.

The objectives of the present study were: (1) to develop a risk assessment methodology for chemical mixtures that accounts for pharmacokinetic interactions among components, and (2) to apply this methodology to assess the health risk associated with occupational inhalation exposure to airborne mixtures of dichloromethane, benzene, toluene, ethylbenzene, and m-xylene. The basis of the proposed risk assessment methodology relates to the characterization of the change in tissue dose metrics (e.g., area under the concentration-time curve for parent chemical in tissues [AUCtissue], maximal concentration of parent chemical or metabolite [Cmax], quantity metabolized over a period of time) in humans, during mixed exposures using PBPK models. For systemic toxicants, an interaction-based hazard index was calculated using data on tissue dose of mixture constituents. Initially, the AUCtarget tissue (AUCtt) corresponding to guideline values (e.g., threshold limit value [TLV]) of individual chemicals were obtained. Then, the AUCtt for each chemical during mixed exposure was obtained using a mixture PBPK model that accounted for the binary and higher order interactions occurring within the mixture. An interaction-based hazard index was then calculated for each toxic effect by summing the ratio of AUCtt obtained during mixed exposure (predefined mixture) and single exposure (TLV). For the carcinogenic constituents of the mixture, an interaction-based response additivity approach was applied. This method consisted of adding the cancer risk for each constituent, calculated as the product of q*tissue dose and AUCtt. The AUCtt during mixture exposures was obtained using an interaction-based PBPK model. The approaches developed in the present study permit, for the first time, the consideration of the impact of multichemical pharmacokinetic interactions at a quantitative level in mixture risk assessments.

Air Pollutants, Occupational↗
PubMed2002

Effects of aerosols from nontoxic Stachybotrys chartarum on murine airways.

Acute effects on the upper and lower respiratory tract due to inhalation exposure to Stachybotrys chartarum (Sc) extract were investigated in mice. In addition, the capacity of the Sc exposure to activate immune system and cause inflammation in the respiratory tract was studied. The inhalation of Sc extract aerosols was observed to provoke sensory irritation in the airways of both naive and Sc-immunized mice. In contrast, exposure to aerosolized ovalbumin or phosphate buffered saline did not cause this effect. Exposure to Sc twice a week for 3 wk increased significantly the serum total immunoglobulin E (IgE) levels in BALB/c mice immunized with Sc as well as in nonimmunized mice. A slight presence of inflammatory cells was observed in the alveoli 3 days after the last exposure to Sc. In conclusion, Sc extract has the capacity to provoke sensory irritation in the murine airways and to activate the murine immune system.

Aerosols↗
PubMed2006

Influence of particle size distribution on inhalation doses to workers in the Florida phosphate industry.

Previous studies have indicated that inhalation exposures to TENORM aerosols are potentially a major contributor to the annual total effective dose to workers in the Florida phosphate industry. Further research was deemed necessary to characterize the particle size distribution of these aerosols containing various radionuclides of the U decay series. In the present study, individualized assessments of worker committed effective doses are reported in which detailed information is used on the particle size distribution, particle density, particle shape, and radioactivity concentrations from sampled aerosols at 6 different phosphate facilities and at various worker areas within these facilities. Inhalation dose assessments are calculated using the ICRP 66 human respiratory tract model as implemented within the LUDEP and IMBA computer codes. Under the least conservative assumptions of radionuclide-specific lung solubility, the annual total effective doses are shown to be 0.31+/-0.12, 0.27+/-0.07, and 0.22+/-0.02 mSv at granulator, storage, and shipping areas, respectively, and thus all annual doses are below the annual limits to the members of the general public (1 mSv y). In contrast, the most conservative assumptions of lung solubility by radionuclide yield annual total effective doses of 2.24+/-2.53 mSv at granulator areas, 1.26+/-1.19 mSv at storage areas, and 0.56+/-0.36 mSv at shipping areas. In this later case, some 44%, 31%, and 15% of individual dose assessments yield worker doses above the annual dose limit. The study thus demonstrates the importance of facility- and area-specific particle solubility data in dose assessments for regulatory compliance and for making decisions regarding worker respiratory protection.

Aerosols↗
PubMed2003

Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

Short-term increases in ambient air pollution have been associated with an increased incidence of acute cardiac events. We assessed the effect of inhalation exposure to concentrated ambient particles (CAPs) on myocardial ischemia in a canine model of coronary artery occlusion. Six mongrel dogs underwent thoracotomy for implantation of a vascular occluder around the left anterior descending coronary artery and tracheostomy to facilitate particulate exposure. After recovery (5-13 weeks), pairs of subjects were exposed for 6 hr/day on 3 or 4 consecutive days. Within each pair, one subject was randomly assigned to breathe CAPs on the second exposure day and filtered air at other times. The second subject breathed CAPs on the third exposure day and filtered air at other times. Immediately after each exposure, subjects underwent 5-min coronary artery occlusion. We determined ST-segment elevation, a measure of myocardial ischemia heart rate, and arrhythmia incidence during occlusion from continuous electrocardiograms. Exposure to CAPs (median, 285.7; range, 161.3-957.3 microg/m3) significantly (p = 0.007) enhanced occlusion-induced peak ST-segment elevation in precordial leads V4 (9.4 +/- 1.7 vs. 6.2 +/- 0.9 mm, CAPs vs. filtered air, respectively) and V5 (9.2 +/- 1.3 vs. 7.5 +/- 0.9 mm). ST-segment elevation was significantly correlated with the silicon concentration of the particles and other crustal elements possibly associated with urban street dust (p = 0.003 for Si). No associations were found with CAPs mass or number concentrations. Heart rate was not affected by CAPs exposure. These results suggest that exacerbation of myocardial ischemia during coronary artery occlusion may be an important mechanism of environmentally related acute cardiac events.

Air Pollutants↗
PubMedDate not supplied

Deposition and retention of 0.1 micron 67Ga2O3 aggregate aerosols in rats following whole body exposures.

Determinations were made of respiratory tract deposition and gastrointestinal tract burdens following whole body inhalation exposures, typical of those used in many chronic exposures; these were compared to values obtained in nose-only exposures. Fischer-344 rats were exposed in large volume chambers, in a whole body mode, to 0.1 micron volume median diameter (VMD) 67Ga2O3 particles 5 hrs/day. Deposition per unit of exposure time and retention were essentially identical following either 1 or 3 day exposures. The lung deposition of particles was 2.8 units/hr for males and 2.2 units/hr for females if the exposure concentration was expressed as 1 unit/L. These values represent a deposition of approximately 15% of the inhaled particles, similar to values obtained for nose-only exposures. Aerosol deposition per kgm body weight was 24% higher in females than males. Passage of material into the gastrointestinal tract was 1.6-fold greater for these whole body exposures as compared to nose-only exposures to the same aerosol mainly resulting from extra material ingested by grooming of the pelt. Approximately 60% of the pelt burden was calculated to be ingested following whole body exposures.

Aerosols↗
PubMed2003

Effects of inhaled ambient particulate matter on pulmonary antimicrobial immune defense.

Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of <10 microm diameter (PM(10)). These epidemiological findings suggest that PM(10) may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms. To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed. The first examined the effects of a single inhalation exposure to concentrated ambient PM(2.5) (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae. The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 microg/m(3), could exacerbate an ongoing infection. Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S. pneumoniae. Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls. These studies demonstrate that a single exposure to ambient PM(2.5) compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals.

Aging↗
PubMed2005

International Workshop on the Design and Analysis of Experimental Studies using PM Concentrator Technologies, Boston, May 5, 2004.

A workshop that brought together representatives of most of the laboratories that have conducted animal and/or human inhalation exposure studies with concentrated ambient air particles (CAPs) was convened by the Health Effects Institute in Boston on May 5, 2004. Participants agreed that CAPs researchers need to make serious efforts to harmonize their experimental and analytical protocols to permit the sharing of lessons learned, questions raised, and opportunities for more definitive studies. Standardized outcome measures based on spirometry and response markers in lung bronchoalveolar lavage (BAL) cells and fluids exist, including the appropriate times after exposure to collect samples and measurements. However, for the emerging focus on cardiac system responses, there are many different electrocardiographic (ECG) endpoints being examined, and little standardization on markers that are most informative about adverse effects; on when the measurements need to be made; and on how to make comparable measurements. The workshop focused on two aspects of dealing with these complexities: sorting out influential particulate matter (PM) components responsible for observed effects, and searching for time-varying responses in continuous outcome data. The need for more complete analyses of PM samples from the CAPs studies was also emphasized, as was obtaining a consistent set of parameters characterizing exposure atmospheres and the ambient PM from which the CAPs are sampled. CAPs studies have already had a significant impact within the air pollution health effects community, especially in regard to cardiovascular system effects, and a follow-up meeting with a greater focus on means to harmonize data collection and analysis is needed.

Air Pollutants↗
PubMed2001

Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: a potential interaction between nickel and vanadium sulfate.

Recent epidemiological studies have shown an association between daily morbidity and mortality and ambient particulate matter (PM) air pollution. It has been proposed that bioavailable metal constituents of PM are responsible for many of the reported adverse health effects. Studies of instilled residual oil fly ash (ROFA) demonstrated immediate and delayed responses, consisting of bradycardia, hypothermia, and arrhythmogenesis in conscious, unrestrained rats. Further investigation of instilled ROFA-associated transition metals showed that vanadium (V) induced the immediate responses, while nickel (Ni) was responsible for the delayed effects. Furthermore, Ni potentiated the immediate effects caused by V when administered concomitantly. The present study examined the responses to these metals in a whole-body inhalation exposure. To ensure valid dosimetric comparisons with instillation studies, 4 target exposure concentrations ranging from 0.3-2.4 mg/m(3) were used to incorporate estimates of total inhalation dose derived using different ventilatory parameters. Rats were implanted with radiotelemetry transmitters to continuously acquire heart rate (HR), core temperature (T(CO)), and electrocardiographic data throughout the exposure. Animals were exposed to aerosolized Ni, V, or Ni + V for 6 h per day x 4 days, after which serum and bronchoalveolar lavage samples were taken. Even at the highest concentration, V failed to induce any significant change in HR or T(CO). Ni caused delayed bradycardia, hypothermia, and arrhythmogenesis at concentrations > 1.2 mg/m(3). When combined, Ni and V produced observable delayed effects at 0.5 mg/m(3) and potentiated responses at 1.3 mg/m(3), greater than were produced by the highest concentration of Ni (2.1 mg/m(3)) alone. These results indicate a possible synergistic relationship between inhaled Ni and V, and provide insight into potential interactions regarding the toxicity of PM-associated metals.

Air Pollutants↗
PubMed2000

Skin absorption of some vaporous solvents in volunteers.

OBJECTIVES: To determine the dermal absorption rates of vaporous 1,1,1-trichloroethane (111TRI), trichloroethene (TRI), tetrachloroethene (TETRA), hexane (HEX), toluene (TOL) and m-xylene (XYL) in humans. The determined absorption data were used for the validation of two published models for prediction of non-steady-state skin absorption. METHODS: Five volunteers were dermally exposed on an area of about 1,000 cm2 (forearm and hand) for 20 or 30 min. An inhalation exposure with a known dose rate served as a reference. Using the solvent concentrations in exhaled air, measured after both inhalation and dermal exposure, we calculated the maximum absorption rate into the blood, and the average absorption rates into the skin throughout the exposure, using the linear system dynamics method. RESULTS: The absorption rates into the skin, normalised for exposure concentration, amounted to 0.021 cm/h (111TRI), 0.049 cm/h (TRI), 0.054 cm/h (TETRA), 0.013 cm/h (HEX), 0.14 cm/h (TOL), and 0.12 cm/h (XYL). The maximum absorption rates into the blood ranged from 0.005 nmol/h for 111TRI and HEX to 0.050 nmol/hr for TOL. The ratios between the predicted and experimental values of the absorption rates into the skin ranged, for the model of Cleek and Bunge [4], from 0.3 (HEX) to 1.1 (TRI and TETRA), and for the model of Wilschut and Ten Berge [22], from 1.1 (HEX) to 4.7 (XYL). CONCLUSION: The linear system dynamics method allowed us to calculate not only the total amount absorbed by the skin but also the maximum absorption rate into the blood. The steady-state absorption rate, usually described by a permeability constant, will be below the absorption rate into the skin and above the maximum absorption rate into the blood. The skin absorption rates predicted by the models showed a good agreement with the experimental values. A comparison of the estimated whole-body skin uptake with the inhalatory uptake from the same atmosphere, revealed that the dermal uptake contributed from 0.1% (HEX) to 1% (TOL and XYL) to the total uptake.

Administration, Cutaneous↗
PubMed2002

Pulmonary effects of ultrafine and fine ammonium salts aerosols in healthy and monocrotaline-treated rats following short-term exposure.

In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM). The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals. An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines. Healthy and PH rats were exposed to ultrafine (mass median diameter [MMD] approximate, equals 0.07-0.10 microm; 4 x 10(5) particles/cm(3)) and fine (MMD approximate, equals 0.57-0.64 micro;m; 9 x 10(3) particles/cm(3)) ammonium aerosols during 4 h/day for 3 consecutive days. The mean mass concentrations ranged from 70 to 420 microg/m(3), respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 microg/m(3) for fine-mode aerosols. In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 microm; 2-9 mg/m(3)) and ammonium nitrate (0.4-18 mg/m(3)) was performed. Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure. Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate. Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF). Macrophages were not activated after MCT treatment or the test atmospheres, since no changes were observed in N-acetyl glucosaminidase (NAG). Cell differentiation profiles were inconsistent, partly caused by an already present infection with Haemophilus sp. However, we believe that the test atmospheres did not affect cell differentiation or total cell counts. The results show that at exposure levels of ammonium salts at least one order of magnitude higher than ambient levels, marked adverse health effects were absent in both healthy and PH rats.

Administration, Inhalation↗
PubMed2004

Effects of low sulfur fuel and a catalyzed particle trap on the composition and toxicity of diesel emissions.

In this study we compared a "baseline" condition of uncontrolled diesel engine exhaust (DEE) emissions generated with current (circa 2003) certification fuel to an emissions-reduction (ER) case with low sulfur fuel and a catalyzed particle trap. Lung toxicity assessments (resistance to respiratory viral infection, lung inflammation, and oxidative stress) were performed on mice (C57Bl/6) exposed by inhalation (6 hr/day for 7 days). The engine was operated identically (same engine load) in both cases, and the inhalation exposures were conducted at the same exhaust dilution rate. For baseline DEE, this dilution resulted in a particle mass (PM) concentration of approximately 200 microg/m3 PM, whereas the ER reduced the PM and almost every other measured constituent [except nitrogen oxides (NOx)] to near background levels in the exposure atmospheres. These measurements included PM, PM size distribution, PM composition (carbon, ions, elements), NOx, carbon monoxide, speciated/total volatile hydrocarbons, and several classes of semivolatile organic compounds. After exposure concluded, one group of mice was immediately sacrificed and assessed for inflammation and oxidative stress in lung homogenate. Another group of mice were intratracheally instilled with respiratory syncytial virus (RSV), and RSV lung clearance and inflammation was assessed 4 days later. Baseline DEE produced statistically significant biological effects for all measured parameters. The use of low sulfur fuel and a catalyzed trap either completely or nearly eliminated the effects.

Animals↗
PubMed2002

Characterization of emissions from burning incense.

The primary objective of this study was to improve the characterization of particulate matter emissions from burning incense. Emissions of particulate matter were measured for 23 different types of incense using a cyclone/filter method. Emission rates for PM2.5 (particulate matter less than 2.5 microm in aerodynamic diameter) ranged from 7 to 202 mg/h, and PM2.5 emission factors ranged from 5 to 56 mg/g of incense burned. Emission rates were also determined using an electrical low pressure impactor (ELPI) and a small electrostatic precipitator (ESP), and emission rates were compared to those determined using the cyclone/filter method. Emission rates determined by the ELPI method were consistently lower than those determined by the cyclone/filter method, and a linear regression correlation was found between emission rates determined by the two methods. Emission rates determined by the ESP method were consistently higher than those determined by the cyclone/filter method, indicating that the ESP may be a more effective method for measuring semivolatile particle emissions. A linear regression correlation was also found between emission rates determined by the ESP and cyclone/filter methods. Particle size distributions were measured with the ELPI, and distributions were found to be similar for most types of incense that were tested. Size distributions by mass typically ranged from approximately 0.06 to 2.5 microm in aerodynamic diameter, with peak values between 0.26 and 0.65 microm. Results indicated that burning incense emits fine particulate matter in large quantities compared to other indoor sources. An indoor air quality model showed that indoor concentrations of PM25 can far exceed the outdoor concentrations specified by the US EPA's National Ambient Air Quality Standards (NAAQS), so incense smoke can pose a health risk to people due to inhalation exposure of particulate matter. Emissions of carbon monoxide (CO), nitric oxide (NO), and sulfur dioxide (SO2) were also measured for seven types of incense. Emission rates of the gaseous pollutants were sufficient to cause indoor concentrations, estimated using the indoor air quality model, to exceed the outdoor concentrations specified by the NAAQS under certain conditions. However, the incense samples that were tested would fill a room with thick smoke under these conditions.

Air Pollutants↗
PubMedDate not supplied

Modeling aggregate exposures to glycol ethers from use of commercial floor products.

Computer modeling of aggregate exposure provides the capability to estimate the range of doses that can occur from product use and to understand the relative importance of different routes of exposure. This paper presents an assessment of aggregate occupational exposure to two glycol ethers used as solvents in floor maintenance products for industrial and institutional facilities, using a simulation tool named PROMISE. Three commercial floor-care products were assumed to be applied in sequence--a floor stripper, then a floor cleaner, and lastly a protective coating. The glycol ethers modeled were ethylene glycol butyl ether (EGBE) in the floor stripper and in the floor cleaner, and dipropylene glycol methyl ether (DPGME) in the coating. Modeling uncertainty was assessed through a comparison of the PROMISE inhalation exposure estimates with those from an independent model (MCCEM), and parameter uncertainty was investigated using PROMISE software's Monte Carlo simulation capabilities. Modeling results indicated that inhalation is the dominant exposure route. The predicted average air concentration and inhalation dose from PROMISE agreed with the second model (MCCEM) within 10%. Monte Carlo simulation indicated that the upper end of the aggregate-dose distribution for the scenario was more than 50% higher than the value of the point estimate. The modeled 8-h TWA concentrations for EGBE and DPGME were lower than the corresponding permissible exposure limits American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLV) by at least a factor of 20, indicating that under the assumed conditions workplace exposures to glycol ethers are below levels of concern.

Adult↗
PubMed2003

Risk assessment dosimetry model for inhaled particulate matter: II. Laboratory surrogates (rat).

Inhalation toxicology investigations are often performed with laboratory animals to address the potential health effects of inhaled air pollutants on human beings. In Part II of this risk assessment study we have considered the deposition of inhaled particulate matter in the laboratory rat as the surrogate of choice. Calculations were performed in an analogous manner to those conducted in Part I for human subjects. To simulate a wide range of human respiratory intensities associated with different levels of physical activities that must be recognized in the determination of air pollution standards, the CO(2) concentrations within animal inhalation exposure chambers may be controlled. Accordingly, we have regulated rat breathing parameters to correspond to a range of human activities, from rest to work. The results of this interspecies modeling study have been presented in a variety of graphical formats to ease comparisons with findings from experiments and to facilitate integration of the results into risk assessment analyses. The findings of our work clearly demonstrate that interspecies simulations can be employed to design animal tests a priori so that the results can be effectively and efficiently extrapolated to human conditions in a meaningful manner.

Administration, Inhalation↗
PubMedDate not supplied

Review of studies concerning the tumorigenicity of 2-butoxyethanol in B6C3F1 mice and its relevance for human risk assessment.

The U.S. National Toxicology Program (NTP) has completed 2-yr inhalation exposures in rats and mice with 2-butoxyethanol (BE). This review concerns the most significant findings from those studies and describes recent research into the mechanistic aspects of BE-mediated tumorigenesis in the mouse and the relevance of such effects to humans. Two tumor types were increased in B6C3F1 mice leading to the classification of "some evidence" of carcinogenicity: liver hemangiosarcomas in male mice and forestomach tumors in female mice (primarily benign papillomas). The results of research collected to date indicate that the tumorigenesis noted for BE was produced by indirect mechanisms. In particular, the occurrence of liver hemangiosarcomas in male mice has been linked to oxidative damage subsequent to red blood cell hemolysis and iron deposition in this organ. Oral administration of BE in mice up to 600 mg/kg/d for up to 90 d produces a dose-related increase in iron (Perl's staining) in Kupffer cells and hepatocytes, increased DNA synthesis in endothelial cells, and enhanced oxidative damage. Further, iron alone, and not BE or BAA, is responsible for producing oxidative damage in cultured hepatocytes from rats or mice. Forestomach neoplasms in female mice were most likely a result of prolonged exposure-induced irritation with compensatory hyperplasia and subsequent tumor promotion. This mechanism is supported by studies indicating elevated levels of BE and BAA in the mouse forestomach tissues and stomach contents following multiple routes of exposure, forestomach epithelial cell cytotoxicity and cell proliferation following administration of BE and BAA, and the increased capacity of forestomach tissues from female mice to metabolize BE to the more irritating metabolite, BAA. The current article summarizes the results of a number of in vivo and in vitro studies designed to elucidate the underlying mechanisms of tumorigenesis by BE in the mouse and discusses the relevance of these for human risk.

Administration, Oral↗
PubMedDate not supplied

Measurement of benzene in human breath associated with an environmental exposure.

The concentration of benzene in breath was measured after exposure to environmental benzene. Five volunteers were exposed to environmental tobacco smoke at different exposure levels and for different exposure durations. The breath samples were collected before, during, and postexposure for up to three hours. Benzene in breath was confirmed as a short-term biomarker of environmental benzene exposure at the sub-ppm level. Less than 10% of the inhaled benzene was expired within three hours following two-hour inhalation exposures, with a greater percentage expired following shorter exposures. An average of 64% percent of the inhaled benzene was absorbed through the lung barrier, with the percentage absorbed decreasing with continued exposure. Benzene biological half-lives of 7.6 and 68 minutes were calculated empirically using a two-compartment model based on the exponential benzene decay curve after correcting the breath concentrations for background breath concentrations. The breath concentration calculated at the end of the exposure by extrapolation of the postexposure breath samples demonstrates a discontinuity with the breath concentration collected during exposure, consistent with equilibrium exchange between blood and breath.

Adult↗