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Inhalation Exposure (inhalation + exposure)
Selected AbstractsPolicy on Acute Toxic Ingestion or Dermal or Inhalation ExposureJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003ANP-C FAANP, Mary Jo Goolsby EdD ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and fir more practical remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's Clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." SUMMARY The ACEP "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure" includes several helpful resources. In addition to recommending specific clinical actions in response to patient variables, the document includes a table identifying the antidote for many of the most commonly ingested drugs. These include digoxin, iron, opioids, salicylates, acetaminophen, and tricyclic antidepressants. The table also includes both the adult and pediatric dose of each listed antidote. A quick reference is included. This form can be used to guide the history, physical examination, and subsequent actions for treating patients with acute toxic ingestion or dermal or inhalation exposure. Finally, there is a quality assurance form to guide chart reviews. Many of the attributes of a well-developed guideline are identified in the report. The authors clearly identify the situations for which the recommendations are intended as well as those in which they do not apply. For instance, the guidance is not intended for use when patients are unstable and stabilization is the primary focus. It is also not intended for cases of radiation, parenteral, or eye exposure or of food poisoning. The authors describe the process used to develop the recommendations and identify the strength of the evidence on which each recommendation is based. The role of provider judgment in application of the guidance is addressed. Prior to its dissemination, the CPG was subjected to external review by dinical experts. This ACEP policy has applicability for the growing number of NPs working in emergency and urgent cafe settings as well as for those who must provide front line emergency care in remote settings. It provides a framework for responding to acute toxic exposures and provides several useful resources to assist the clinician in responding to situations in which accidental or intentional poisoning is suspected. [source] Policy on Acute Toxic Ingestion or Dermal or Inhalation ExposureJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003ANP-C, FAANP, Mary Jo Goolsby EdD ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and far more practice in remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." [source] Four Weeks' Inhalation Exposure of Long Evans Rats to 4- tert -Butyltoluene: Effect on Evoked Potentials, Behaviour, and Brain NeurochemistryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2000Henrik Rye Lam Long-lasting central nervous system (CNS) neurotoxicity of 4- tert -butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function. [source] DNA damage in mice treated with sulfur dioxide by inhalationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2005Ziqiang Meng Abstract Sulfur dioxide (SO2) is a ubiquitous air pollutant produced by the burning of fossil fuels. In this study, single-cell gel electrophoresis (the Comet assay) was used to evaluate the DNA damage produced by inhalation exposure of mice to SO2. Male and female mice were housed in exposure chambers and treated with 14.00 ± 1.25, 28.00 ± 1.98, 56.00 ± 3.11, and 112.00 ± 3.69 mg/m3 SO2 for 6 hr/day for 7 days, while control groups were exposed to filtered air. Comet assays were performed on blood lymphocytes and cells from the brain, lung, liver, spleen, kidney, intestine, and testicles of the animals. SO2 caused significant, dose-dependent increases in DNA damage, as measured by Olive tail moment, in all the cell types analyzed from both sexes of mice. The results indicate that inhalation exposure to SO2 damages the DNA of multiple organs in addition to the lung, and suggests that this damage could result in mutation, cancer, and other diseases related to DNA damage. Further work will be required to understand the ultimate toxicological significance of this damage. These data also suggest that detecting DNA damage in blood lymphocytes, using the Comet assay, may serve as a useful tool for evaluating the impact of pulmonary SO2 exposure in human biomonitoring studies. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Developmental toxicity evaluation of inhaled tertiary amyl methyl ether in mice and ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2003Frank Welsch Abstract This evaluation was part of a much more comprehensive testing program to characterize the mammalian toxicity potential of the gasoline oxygenator additive tertiary amyl methyl ether (TAME), and was initiated upon a regulatory agency mandate. A developmental toxicity hazard identi,cation study was conducted by TAME vapor inhalation exposure in two pregnant rodent species. Timed-pregnant CD®(Sprague-Dawley) rats and CD-1® mice, 25 animals per group, inhaled TAME vapors containing 0, 250, 1500 or 3500 ppm for 6 h a day on gestational days 6,16 (mice) or 6,19 (rats). The developmental toxicity hazard potential was evaluated following the study design draft guidelines and end points proposed by the United States Environmental Protection Agency. Based on maternal body weight changes during pregnancy, the no-observable-adverse-effect level (NOAEL) was 250 ppm for maternal toxicity in rats and 1500 ppm for developmental toxicity in rats using the criterion of near-term fetal body weights. In mice, more profound developmental toxicity was present than in rats, at both 1500 and 3500 ppm. At the highest concentration, mouse litters revealed more late fetal deaths, signi,cantly reduced fetal body weights per litter and increased incidences of cleft palate (classi,ed as an external malformation), as well as enlarged lateral ventricles of the cerebrum (a visceral variation). At 1500 ppm, mouse fetuses also exhibited an increased incidence of cleft palate and the dam body weights were reduced. Therefore, the NOAEL for the mouse maternal and developmental toxicity was 250 ppm under the conditions of this study. Copyright © 2003 John Wiley & Sons, Ltd. [source] Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic receptorsJOURNAL OF APPLIED TOXICOLOGY, Issue 1 2003Jürgen Pauluhn Abstract The present investigation was conducted to understand better possible confounding factors caused by direct dosing of neonatal mice during the pre-weaning developmental period. By direct dosing, pups might encounter thermal challenges when temporarily removed from their ,natural habitat'. Typically, this leads to a cold environment and food deprivation (impaired lactation) and modulation of the toxic potency of the substance administered. Growth retardation as a consequence of such behavioural changes in pups makes it increasingly difficult to differentiate specific from non-specific mechanisms. Neonatal NMRI mice were dosed daily by gavage (0.7 mg kg,1 body wt.) from postnatal day (PND) 10,16 with S -bioallethrin, deltamethrin or the vehicle. Then the pups, including their non-treated foster dams, were subjected temporarily for 6 h day to a hypo-, normo- or hyperthermic environment, which was followed by normal housing. The measured temperatures in the environmental chambers were ca. 21, 25 and 30°C, respectively. Thus, temperatures in the hypo- and normothermic groups are comparable to the temperatures commonly present in testing laboratories, whereas the hyperthermic condition is that temperature typically present in the ,natural habitat' of pups. A deviation from the normal behaviour of both pups and dams was observed in the hypo- and normothermic groups. In these groups the rectal temperatures of pups were markedly decreased, especially in the early phase of the study (PND 10,12). Neonates that received either test substance displayed changes in body weights and brain weights at terminal sacrifice (PND 17) when subjected temporarily to a non-physiological environment. An enormous influence of environmental temperature on the density of muscarinic receptors in the crude synaptosomal fraction of the cerebral cortex was ascertained. In summary, these results demonstrate that the direct dosing of thermolabile neonatal mice by gavage is subject to significant artefacts that render the interpretation of findings from such studies difficult. It appears that if direct dosing of neonatal pups is mandated, and inhalation is a relevant route of exposure, the combined inhalation exposure of dams with their litters is an alternative procedure that does not cause disruption of the ,natural habitat' of pups. However, owing to their higher ventilation, under such conditions the pups may receive dosages at least double those of the dams. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosolsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2002Joanne D. Kilgour Abstract Acute and repeated inhalation exposures (for 28 days) to polymeric methylene diphenyl diisocyanate (PMDI) were performed in rats. Investigations were made at the end of exposures and after 3, 10 and 30 days of recovery following single acute exposures and after 30 days of recovery following 28 days of exposure. Acute exposures to 10, 30 or 100 mg m,3 PMDI produced clinical signs in all animals that were consistent with exposure to irritant aerosols. An exposure concentration-related body weight loss and increase in lung weight were seen post-exposure, with complete recovery by day 8. The time course of changes in the lung over the initial days following exposure consisted of a pattern of initial toxicity, rapid and heavy influx of inflammatory cells and soluble markers of inflammation and cell damage, increased lung surfactant, a subsequent recovery and epithelial proliferative phase and, finally, a return to the normal status quo of the lung. During these stages there was evidence for perturbation of lung surfactant homeostasis, demonstrated by increased amounts of crystalline surfactant and increased number and size of lamellar bodies within type II alveolar cells. Repeated exposure over 28 days to the less toxic concentrations of 1, 4 or 10 mg m,3 PMDI produced no clinical signs or body weight changes, but an increase in lung weight was seen in animals exposed to 10 mg m,3, which resolved following the 30-day recovery period. Other effects seen were again consistent with exposure to irritant aerosols, but were less severe than those seen in the acute study. Analysis of bronchoalveolar lavage fluid revealed similar changes to those seen in the acute study. At both 10 and 4 mg m,3 PMDI increased numbers of ,foamy' macrophages in lung lavage cell pellet correlated with the increased phospholipid content of the pellet. Changes in lung lavage parameters and electron microscopic evidence again suggested perturbations in surfactant homeostasis. Histologically, bronchiolitis and thickening of the central acinar regions was seen at 10 and 4 mg m,3, reflecting changes in cell proliferation in the terminal bronchioles and centro-acinar regions. Almost all effects seen had recovered by day 30 post-exposure. Both acute and subacute studies demonstrate rapid recovery of effects in the lung following exposure to PMDI, with no progression of these effects even at concentrations higher than those shown to produce tumours in a chronic study. These findings add weight to the hypothesis that pulmonary tumours seen following chronic exposure to PMDI are most likely due to a combination of the chronic irritant effects of repeated exposure, coupled with the presence of insoluble polyureas formed by polymerization of PMDI (found in studies reported here and previous chronic studies), and therefore acute or short-term exposures to PMDI are likely to be of little concern for long-term pulmonary health. Copyright © 2002 John Wiley & Sons, Ltd. [source] Toxicity of trichloroethylene following inhalation and drinking contaminated waterJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2001Mohammad Waseem Abstract The neurobehavioural effects of trichloroethylene (TCE) were studied in rats following administration of the solvent orally (350, 700 and 1400 ppm in drinking water for 90 days) and through inhalation (376 ppm for 4 h a day, 5 days per week for 180 days). Various aspects of spontaneous locomotor activity were assessed at different periods after exposure through either of the routes. Oral exposure to TCE had no significant effect on spontaneous locomotor activity or cognitive ability, whereas inhalation to the solvent resulted in an increase in the distance travelled and horizontal activity counts at day 30 but a decrease at day 60 of exposure. The time spent in ambulatory and stereotypic movements as well as the number of stereotypic movements were enhanced significantly only at day 30. The resting time was decreased at day 30 but enhanced at day 60 of exposure. The learning ability was not affected significantly up to day 180. The results highlight the neurotoxic potential of inhalation exposure to TCE. Copyright © 2001 John Wiley & Sons, Ltd. [source] Chronic toxicity/oncogenicity study of styrene in cd-1 mice by inhalation exposure for 104 weeksJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2001George Cruzan Abstract Groups of 70 male and 70 female Charles River CD-1 mice were exposed whole body to styrene vapor at 0, 20, 40, 80 or 160 ppm 6 h per day 5 days per week for 98 weeks (females) or 104 weeks (males). The mice were observed daily; body weights, food and water consumption were measured periodically, a battery of hematological and clinical pathology examinations were conducted at weeks 13, 26, 52, 78 and 98 (females)/104 (males). Ten mice of each gender per group were pre-selected for necropsy after 52 and 78 weeks of exposure and the survivors of the remaining 50 of each gender per group were necropsied after 98 or 104 weeks. An extensive set of organs from the control and high-exposure mice were examined histopathologically, whereas target organs, gross lesions and all masses were examined in all other groups. Styrene had no effect on survival in males. Two high-dose females died (acute liver toxicity) during the first 2 weeks; the remaining exposed females had a slightly higher survival than control mice. Levels of styrene and styrene oxide (SO) in the blood at the end of a 6 h exposure during week 74 were proportional to exposure concentration, except that at 20 ppm the SO level was below the limit of detection. There were no changes of toxicological significance in hematology, clinical chemistry, urinalysis or organ weights. Mice exposed to 80 or 160 ppm gained slightly less weight than the controls. Styrene-related non-neoplastic histopathological changes were found only in the nasal passages and lungs. In the nasal passages of males and females at all exposure concentrations, the changes included respiratory metaplasia of the olfactory epithelium with changes in the underlying Bowman's gland; the severity increased with styrene concentration and duration of exposure. Loss of olfactory nerve fibers was seen in mice exposed to 40, 80 or 160 ppm. In the lungs, there was decreased eosinophilia of Clara cells in the terminal bronchioles and bronchiolar epithelial hyperplasia extending into alveolar ducts. Increased tumor incidence occurred only in the lung. The incidence of bronchioloalveolar adenomas was significantly increased in males exposed to 40, 80 or 160 ppm and in females exposed to 20, 40 and 160 ppm. The increase was seen only after 24 months. In females exposed to 160 ppm, the incidence of bronchiolo-alveolar carcinomas after 24 months was significantly greater than in the controls. No difference in lung tumors between control and styrene-exposed mice was seen in the intensity or degree of immunostaining, the location of tumors relative to bronchioles or histological type (papillary, solid or mixed). It appears that styrene induces an increase in the number of lung tumors seen spontaneously in CD-1 mice. Copyright © 2001 John Wiley & Sons, Ltd. [source] Inhalation efficacy of RFI-641 in an African green monkey model of RSV infectionJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2003W.J. Weiss Abstract: Human respiratory syncytial virus (RSV) is a major cause of acute upper and lower respiratory tract infections. RFI-641 is a novel RSV fusion inhibitor with potent in vitro activity. In vivo efficacy of RFI was determined in an African green monkey model of RSV infection involving prophylactic and therapeutic administration by inhalation exposure. Inhalation was with an RFI-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). Efficacy and RFI-641 exposure was determined by collection of throat swabs, nasal washes and bronchial alveolar lavage (BAL) on selected days. The short-exposure group (15 minutes) exhibited no effect on the nasal, throat or BAL samples. The throat and nasal samples for the long-exposure group failed to show a consistent reduction in viral titers. RFI-641 2 hours exposure-treated monkeys showed a statistically significantly log reduction for BAL samples of 0.73,1.34 PFU/ml (P -value 0.003) over all the sampling days. Analysis indicates that the long-exposure group titer was lower than the control titer on day 7 and when averaged across days. The results of this study demonstrate the ability of RFI-641 to reduce the viral load of RSV after inhalation exposure in the primate model of respiratory infection. [source] Withdrawal Severity After Chronic Intermittent Ethanol in Inbred Mouse StrainsALCOHOLISM, Issue 9 2010Pamela Metten Background:, To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. Methods:, Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. Results:, Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 ± 0.02 mg/ml and we restricted the range of this value to 1.00,2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 ± 0.1 mg/ml) and high dose (1.71 ± 0.02 mg/ml). After the third inhalation exposure, ethanol-exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. Conclusion:, The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses. [source] Policy on Acute Toxic Ingestion or Dermal or Inhalation ExposureJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003ANP-C FAANP, Mary Jo Goolsby EdD ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and fir more practical remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's Clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." SUMMARY The ACEP "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure" includes several helpful resources. In addition to recommending specific clinical actions in response to patient variables, the document includes a table identifying the antidote for many of the most commonly ingested drugs. These include digoxin, iron, opioids, salicylates, acetaminophen, and tricyclic antidepressants. The table also includes both the adult and pediatric dose of each listed antidote. A quick reference is included. This form can be used to guide the history, physical examination, and subsequent actions for treating patients with acute toxic ingestion or dermal or inhalation exposure. Finally, there is a quality assurance form to guide chart reviews. Many of the attributes of a well-developed guideline are identified in the report. The authors clearly identify the situations for which the recommendations are intended as well as those in which they do not apply. For instance, the guidance is not intended for use when patients are unstable and stabilization is the primary focus. It is also not intended for cases of radiation, parenteral, or eye exposure or of food poisoning. The authors describe the process used to develop the recommendations and identify the strength of the evidence on which each recommendation is based. The role of provider judgment in application of the guidance is addressed. Prior to its dissemination, the CPG was subjected to external review by dinical experts. This ACEP policy has applicability for the growing number of NPs working in emergency and urgent cafe settings as well as for those who must provide front line emergency care in remote settings. It provides a framework for responding to acute toxic exposures and provides several useful resources to assist the clinician in responding to situations in which accidental or intentional poisoning is suspected. [source] The Challenge of asthma in adolescencePEDIATRIC PULMONOLOGY, Issue 8 2007Diletta de Benedictis MD Abstract The adolescents with asthma are a distinct group of patients with different problems and needs compared to children and adults. Specific issues of asthma in adolescence are the variability of the clinical spectrum, the presence of particular risk factors for the persistence of symptoms, underdiagnosis and undertreatment of the disease. Refusal of the sick role, denial of symptoms, carelessness about dangerous inhalation exposure, erratic self-medication, overexertion without taking precautions against exercise-induced asthma, and a poor relationship between patients, their families, and often doctors are the main obstacles to successful management of asthma in this critical age. There are also major problems of compliance for these patients. The goal of optimal quality of life will be achieved only if the physician thoroughly understands the adolescent's needs and provides optimal care. Pediatr Pulmonol. 2007, 42:683,692. © 2007 Wiley-Liss, Inc. [source] Characterization of a fatal methyl bromide exposure by analysis of the water coolerAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 7 2009David J. Hewitt MD Abstract Background A suspected inhalation exposure to methyl bromide (MeBr) in the packaging and shipping area of a chemical manufacturer resulted in a worker fatality and several symptomatic cases. However, air testing was negative for MeBr resulting in uncertainty regarding the potential chemical exposure. Methods of quickly confirming the exposure and magnitude were sought. Methods Head space air and water samples were obtained from the breakroom water cooler in the facility and tested for MeBr. Results Increased levels of MeBr were identified in the air and water samples from the cooler and used to calculate the MeBr concentration of air entering the cooler. The MeBr air concentration within the breakroom was estimated as 1,200,2,100,ppm depending on assumptions regarding the amount of water dispensed from the cooler both before and during the incident. Conclusions Estimated MeBr air concentrations in the breakroom were consistent with those known to be associated with reported health effects among the involved workers. The water cooler analysis represented a unique method of retrospectively verifying and quantifying exposure to MeBr. Am. J. Ind. Med. 52:579,586, 2009. © 2009 Wiley-Liss, Inc. [source] Human exposure to phthalates via consumer productsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2006TED SCHETTLER Summary Phthalate exposures in the general population and in subpopulations are ubiquitous and widely variable. Many consumer products contain specific members of this family of chemicals, including building materials, household furnishings, clothing, cosmetics, pharmaceuticals, nutritional supplements, medical devices, dentures, children's toys, glow sticks, modelling clay, food packaging, automobiles, lubricants, waxes, cleaning materials and insecticides. Consumer products containing phthalates can result in human exposures through direct contact and use, indirectly through leaching into other products, or general environmental contamination. Historically, the diet has been considered the major source of phthalate exposure in the general population, but all sources, pathways, and their relative contributions to human exposures are not well understood. Medical devices containing di-(2-ethylhexyl) phthalate are a source of significant exposure in a susceptible subpopulation of individuals. Cosmetics, personal care products, pharmaceuticals, nutritional supplements, herbal remedies and insecticides, may result in significant but poorly quantified human exposures to dibutyl phthalate, diethyl phthalate, or dimethyl phthalate. Oven baking of polymer clays may cause short-term, high-level inhalation exposures to higher molecular weight phthalates. [source] Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosolsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2002Joanne D. Kilgour Abstract Acute and repeated inhalation exposures (for 28 days) to polymeric methylene diphenyl diisocyanate (PMDI) were performed in rats. Investigations were made at the end of exposures and after 3, 10 and 30 days of recovery following single acute exposures and after 30 days of recovery following 28 days of exposure. Acute exposures to 10, 30 or 100 mg m,3 PMDI produced clinical signs in all animals that were consistent with exposure to irritant aerosols. An exposure concentration-related body weight loss and increase in lung weight were seen post-exposure, with complete recovery by day 8. The time course of changes in the lung over the initial days following exposure consisted of a pattern of initial toxicity, rapid and heavy influx of inflammatory cells and soluble markers of inflammation and cell damage, increased lung surfactant, a subsequent recovery and epithelial proliferative phase and, finally, a return to the normal status quo of the lung. During these stages there was evidence for perturbation of lung surfactant homeostasis, demonstrated by increased amounts of crystalline surfactant and increased number and size of lamellar bodies within type II alveolar cells. Repeated exposure over 28 days to the less toxic concentrations of 1, 4 or 10 mg m,3 PMDI produced no clinical signs or body weight changes, but an increase in lung weight was seen in animals exposed to 10 mg m,3, which resolved following the 30-day recovery period. Other effects seen were again consistent with exposure to irritant aerosols, but were less severe than those seen in the acute study. Analysis of bronchoalveolar lavage fluid revealed similar changes to those seen in the acute study. At both 10 and 4 mg m,3 PMDI increased numbers of ,foamy' macrophages in lung lavage cell pellet correlated with the increased phospholipid content of the pellet. Changes in lung lavage parameters and electron microscopic evidence again suggested perturbations in surfactant homeostasis. Histologically, bronchiolitis and thickening of the central acinar regions was seen at 10 and 4 mg m,3, reflecting changes in cell proliferation in the terminal bronchioles and centro-acinar regions. Almost all effects seen had recovered by day 30 post-exposure. Both acute and subacute studies demonstrate rapid recovery of effects in the lung following exposure to PMDI, with no progression of these effects even at concentrations higher than those shown to produce tumours in a chronic study. These findings add weight to the hypothesis that pulmonary tumours seen following chronic exposure to PMDI are most likely due to a combination of the chronic irritant effects of repeated exposure, coupled with the presence of insoluble polyureas formed by polymerization of PMDI (found in studies reported here and previous chronic studies), and therefore acute or short-term exposures to PMDI are likely to be of little concern for long-term pulmonary health. Copyright © 2002 John Wiley & Sons, Ltd. [source] Respiratory hypersensitivity to trimellitic anhydride in Brown Norway Rats: a comparison of endpointsJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2002Jürgen Pauluhn Abstract A rat bioassay has been developed to provide an objective approach for the identification and classification of respiratory allergy using trimellitic anhydride (TMA), which is a known respiratory tract irritant and asthmagen. Particular emphasis was placed on the study of route-of-induction-dependent effects and their progression upon inhalation challenge with TMA (,23 mg m,3 for a duration of 30 min), which included analysis of specific and non-specific airway hyperreactivity and pulmonary inflammation initiated and sustained by immunological processes. Refinement of the bioassay focused on procedures to probe changes occurring upon challenge with TMA or methacholine aerosols using physiological, biochemical and immunological procedures. Following challenge with TMA, the rats sensitized to TMA showed marked changes in peak inspiratory and expiratory air flows and respiratory minute volume. In these animals, a sustained pulmonary inflammation occurred, characterized by specific endpoints determined in bronchoalveolar lavage (lactate dehydrogenase, protein, nitrite, eosinophil peroxidase, myeloperoxidase). When compared with the naive controls, lung weights were increased significantly, as were the weights of lung-associated lymph nodes following inhalation induction and auricular lymph nodes following topical induction. The extent of changes observed was equal or more pronounced in animals sensitized epicutaneously (day 0 : 150 µl vehicle/50% TMA on each flank, day 7; booster administration to the skin of the dorsum of both ears using half the concentration and volume used on day 0) when compared with rats sensitized by 5 × 3 h day,1 inhalation exposures (low dose: 25 mg TMA m,3, high dose: 120 mg TMA m,3). In summary, the findings support the conclusion that the Brown Norway rat model is suitable for identifying TMA as an agent that causes both an immediate-type change of breathing patterns and a delayed-type sustained pulmonary inflammatory response. However, it remains unresolved whether the marked effects observed in the topically sensitized rats are more related to a route-of-induction or dose-dependent phenomenon. Copyright © 2002 John Wiley & Sons, Ltd. [source] Noninvasive in vivo electron paramagnetic resonance study to estimate pulmonary reducing ability in mice exposed to NiO or C60 nanoparticlesJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Hidekatsu Yokoyama MD Abstract Purpose To develop new methods that can estimate the influences of manufactured nanomaterials on biological systems, the in vivo pulmonary reducing ability of mice that had received inhalation exposures to NiO or C60 nanoparticles was investigated using a 700 MHz electron paramagnetic resonance (EPR) spectrometer. Materials and Methods NiO or C60 suspensions were atomized and mice in exposure chambers inhaled the resulting aerosol particles for 3 hours. The exposure conditions, number-based geometric average diameters, and the average number concentration were precisely controlled at almost the same levels for both NiO and C60 nanoparticles. Two days or 2 weeks after exposure, an EPR study was conducted noninvasively. Temporal changes in EPR signal intensity at the target area (ie, lung field) were obtained by the region-selected intensity determination (RSID) method. Results NiO nanoparticles significantly suppressed pulmonary reducing ability 2 days and 2 weeks after exposure, but C60 nanoparticles had no such effect. Conclusion This is the first in vivo estimation of the reducing ability in experimental animals exposed to manufactured nanoparticles. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [source] Upper and lower respiratory diseases after occupational and environmental disastersMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2008David J. Prezant MD Abstract Respiratory consequences from occupational and environmental disasters are the result of inhalation exposures to chemicals, particulate matter (dusts and fibers) and/or the incomplete products of combusion that are often liberated during disasters such as fires, building collapses, explosions and volcanoes. Unfortunately, experience has shown that environmental controls and effective respiratory protection are often unavailable during the first days to week after a large-scale disaster. The English literature was reviewed using the key words,disaster and any of the following: respiratory disease, pulmonary, asthma, bronchitis, sinusitis, pulmonary fibrosis, or sarcoidosis. Respiratory health consequences after aerosolized exposures to high-concentrations of particulates and chemicals can be grouped into 4 major caterogies: 1) upper respiratory disease (chronic rhinosinusitis and reactive upper airways dysfunction syndrome), 2) lower respiratory diseases (reactive [lower] airways dysfunction syndrome, irritant-induced asthma, and chronic obstructive airways diseases), 3) parenchymal or interstitial lung diseases (sarcoidosis, pulmonary fibrosis, and bronchiolitis obliterans, and 4) cancers of the lung and pleura. This review describes several respiratory consequences of occupational and environmental disasters and uses the World Trade Center disaster to illustrate in detail the consequences of chronic upper and lower respiratory inflammation. Mt Sinai J Med 75:89,100, 2008. © 2008 Mount Sinai School of Medicine [source] Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responsesCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009K. Kulhankova Summary Background Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. Objective We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. Methods C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. Results Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG1, and IgG2a production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG1, lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. Conclusions Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures. [source] | ||||||||||